Statin-induced necrotizing autoimmune myopathy (SINAM): case report and review of the literature.

Statins are a well-known and highly effective treatment for hypercholesterolemia in order to prevent cardiovascular disease. Occasionally, patients may experience muscle-related events such as myalgia or muscle cramps. Recently, SINAM (statin-induced necrotizing autoimmune myopathy) has been described in patients using statins. Although very uncommon, it may cause a life-threatening situation associated with rhabdomyolysis. We present a case concerning a 71-year-old woman who presented with muscle fatigue for several weeks. Statin therapy was discontinued but symptoms did not resolve. Further workup led to a diagnosis of SINAM for which treatment with immunosuppressants was started.

Aseptic meningitis after SARS-CoV-2 Pfizer/BioNTech vaccination.

OBJECTIVE: Aseptic meningitis is a rare, but possible severe side effect after SARS-CoV-2 Pfizer/BioNTech vaccination. CASE PRESENTATION: Recently, a first case of aseptic meningitis after the first shot of mRNA-BNT162b2 SARS-CoV-2 (Pfizer/BioNTech) vaccine was reported. We present the first case of a 34-year-old woman without relevant medical history developing aseptic meningitis after her 2nd Pfizer/BioNTech vaccination. She was admitted with severe headache and fever for 5 days prior to her presentation at the emergency department. An extensive work-up of the clinical problem could narrow the differential diagnosis. Symptoms resolved after methylprednisolone therapy. CONCLUSION: This case highlights a rare but important side effect after vaccination that primary physicians and neurologists should be aware of in order to identify and efficiently manage these patients.

To treat or not to treat? Managing comorbidities in cancer patients under immune checkpoint inhibition.

Objectives: Assessing the safety and efficacy of immune checkpoint inhibition in risky cancer patient subgroups: pre-existing organ failure, elderly, presence of auto-immune disease, transplanted patients and brain metastasis treated with immune checkpoint inhibitors. Methods: PubMed, Web of Science and Google scholar databases were searched for English articles published prior to February 2019. Search terms used were organ failure, dialysis, elderly, organ transplant, liver disease, auto-immune disease, immunosuppression, and brain metastasis. Results: Our literature data indicate that immune checkpoint inhibition in the majority of these subpopulations can be administered safely without any loss of efficacy. These data are mostly based on case-reports as only a minority of high-risk patients were included in (the earliest) clinical trials. Validation of these results is necessary on a larger scale. Conclusion: Future trials should not automatically exclude aforementioned patient groups but alter the study design and make their inclusion possible, since more data are needed to answer several remaining questions in these populations. Especially since ICI appears to be safe to administer in these patients.

Comparison of different equations to assess glomerular filtration in critically ill patients.

PURPOSE: To evaluate equations for estimation of glomerular filtration rate (GFR) and measured urinary creatinine clearance, compared to measured GFR in critically ill patients. METHODS: GFR was measured using inulin clearance. Multiple blood samples were collected per patient for determination of serum creatinine, cystatin C and inulin. GFR was estimated by the use of the following estimation equations (eGFR): four commonly used creatinine-based equations [Cockcroft-Gault, Modification of Diet in Renal Disease (both the short and long formula) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)], five cystatin C based estimation equations (Hoek, Larsson, Filler, Le Bricon, CKD-EPIcys) and one equation combining cystatin C and serum creatinine (CKD-EPIcr-cys). In addition we measured urinary creatinine clearance. Bias, precision and accuracy of all estimates were compared to those of the inulin clearance. RESULTS: Data were collected from 83 patients, of whom 68 were considered evaluable. The median age was 58 years [interquartile range (IQR) 39-68]. The median inulin clearance was 80 mL/min/1.73 m(2) (IQR 31-114). Equations based on creatinine had much bias and poor precision and accuracy. Measured urinary creatinine clearances overestimated GFR. Equations based on cystatin C were free of bias, but also had limited precision and accuracy. CONCLUSIONS: In this cohort of patients, estimates of GFR had low accuracy and precision. Cystatin C based formulas, especially CKD-EPIcr-cys, showed limited bias; however, the accuracy and precision of these estimates were still insufficient. Measured urinary creatinine clearance overestimates GFR, but may provide a cheap alternative, when this is taken into account.

Two-tier approach for the detection of alpha-galactosidase A deficiency in kidney transplant recipients.

BACKGROUND: Anderson-Fabry disease (AFD) is an X-linked condition originating from a deficiency in alpha-galactosidase, a lysosomal enzyme. Multi-organ involvement ensues in early adulthood and vital organs are affected: the kidneys, brain, heart. Several reports however suggest that AFD is underdiagnosed. METHODS: We screened a kidney transplant population using a two-tier approach. The first tier was the determination of alpha-galactosidase A (AGALA) activity using a dried blood spot on filter paper (DBFP); in the second tier, patients with the lowest alpha-galactosidase levels were further subjected to mutation analysis of the GLA gene. RESULTS: From the database of 2328 patients, 1233 subjects met the inclusion criteria. Finally, after informed consent, 673 patients were screened (54.5%-395 women and 278 men). DBFP analysis resulted in a mean AGALA of 2.63 +/- 2.48 micromol/L/h (2.5 and 97.5 percentile were 0.0001 and 5.07 micromol/L/h, respectively). Eleven patients were subjected to further genetic analysis. In a male patient a pathogenic missense mutation p.Ala143Thr (c.427A>G) was identified. CONCLUSIONS: Our results show that the proposed approach can detect AFD patients in a until now seldomly screened high-risk group: kidney transplant patients. We conclude that screening for AFD in high-risk populations is a cost-effective, technically feasible and clinically valuable objective.

Two-tier approach for the detection of alpha-galactosidase A deficiency in a predominantly female haemodialysis population.

INTRODUCTION: Fabry's disease (AFD) is an X-linked lysosomal storage disease, resulting from a deficiency in alpha-galactosidase A (AGALA). Untreated, this leads to precocious failure of vital organ function and death. As enzyme replacement therapy is available, it is of vital importance that affected individuals can be traced. MATERIALS AND METHODS: We set up a screening in the Flemish haemodialysis population using a two-tier approach. The first tier was a determination of alpha-galactosidase A activity using a dried blood spot on filter paper, in the second tier, patients with the lowest alpha-galactosidase levels were further subjected to mutation analysis of the GLA gene. RESULTS: 1284 patients (1047 women, 237 men) were evaluated for inclusion, eliminating patients with definite renal diagnoses. Total 922 patients (71.8 %) were screened (742 women, 180 men). Fifty seven patients were subjected to further genetic analysis. Three GLA mutation carriers were identified: two apparently nonrelated female patients carry the missense mutation p.Ala143Thr (c.427G > A), a missense mutation p.Trp236Arg (c.706T > C) was identified in a man. While the male patient had been clinically diagnosed with AFD, the female patients had remained unrecognized. Additional family based screening resulted in the identification of nine mutation carriers (four males and five females). DISCUSSION: We demonstrated that the prevalence of GLA mutation carriers in our haemodialysis population is 0.3%. Our results show that the proposed approach accurately detects AFD patients. We conclude that screening for AFD in high risk populations is a cost-effective, technically feasible and clinically valuable objective.

Phenytoin intoxication in critically ill patients.

Phenytoin intoxication can result in major and possibly life-threatening disorders. Furthermore, the hepatic clearance can become saturated, thus, shifting the elimination from first- to zero-order kinetics. This results in a slow elimination of the compound in case of intoxication. The treatment modalities for phenytoin overdose are limited. Taking into account the high level of protein binding, the molecule is not easily eliminated from the body by means of extracorporal epuration. Although reports exist on the use of MARS (molecular adsorbents recirculating system) dialysis, peritoneal dialysis, and standard dialysis for the elimination, in practice, hemoperfusion, is the most often applied technique. The authors report the case of a hypoalbuminemic patient with severe neurologic signs of phenytoin intoxication (total concentration moderately elevated, free fraction high). A combination of high-flux dialysis and hemoperfusion resulted in a considerable extraction of the drug, accelerating the natural clearance from the body and ameliorating clinical signs of intoxication. In selected patients (with a high free fraction of phenytoin), high-flux dialysis may be a valuable alternative or adjuvant to hemoperfusion.

Enzyme replacement therapy in Anderson-Fabry's disease: beneficial clinical effect on vital organ function.

Two recent randomized trials pointed out the beneficial effect of enzyme replacement therapy on biochemical parameters in patients with Anderson-Fabry's disease. Clinical end-points, such as amelioration or stabilization of renal function deterioration, or improvement of left ventricular hypertrophy have not been evaluated in depth. We report the case of a patient whose moderately impaired renal function was stabilized with the start of enzyme treatment. In addition, left ventricular hypertrophy tended to regress. To our knowledge this is the first observation of clinical efficacy of the enzyme replacement therapy in Anderson-Fabry's disease in patients with moderately impaired renal function.