Blinatumomab in Relapsed/Refractory Burkitt Lymphoma.

In patients with relapsed/refractory Burkitt lymphoma (r/r BL), overall survival (OS) is poor, and effective therapies and evidence for the best therapy are lacking. The monoclonal antibody blinatumomab may represent a novel option. However, only limited data on the use of blinatumomab in r/r BL are so far available.

Haploinsufficiency due to a novel ACO2 deletion causes mitochondrial dysfunction in fibroblasts from a patient with dominant optic nerve atrophy.

ACO2 is a mitochondrial protein, which is critically involved in the function of the tricarboxylic acid cycle (TCA), the maintenance of iron homeostasis, oxidative stress defense and the integrity of mitochondrial DNA (mtDNA). Mutations in the ACO2 gene were identified in patients suffering from a broad range of symptoms, including optic nerve atrophy, cortical atrophy, cerebellar atrophy, hypotonia, seizures and intellectual disabilities. In the present study, we identified a heterozygous 51 bp deletion (c.

A patient-based model of RNA mis-splicing uncovers treatment targets in Parkinson's disease.

Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder with monogenic forms representing prototypes of the underlying molecular pathology and reproducing to variable degrees the sporadic forms of the disease. Using a patient-based in vitro model of -linked PD, we identified a U1-dependent splicing defect causing a drastic reduction in DJ-1 protein and, consequently, mitochondrial dysfunction. Targeting defective exon skipping with genetically engineered U1-snRNA recovered DJ-1 protein expression in neuronal precursor cells and differentiated neurons.

Ideal timing of indwelling catheter removal after robot-assisted radical prostatectomy with a running barbed suture technique: a prospective analysis of 425 consecutive patients.

Objective: To compare prospectively early outcome and complications of catheter removal after robot-assisted radical prostatectomy (RARP) on the 4th or 7th day with a standardized running barbed suture technique.

Introduction: The time point of removing the indwelling catheter after RARP mainly depends on institute's/surgeon's preferences. Removal should be late enough to avoid urinary leakage and complications such as acute urinary retention (AUR) but early enough to avoid unnecessary catheter indwelling.

Mutations in Disrupt Endoplasmic Reticulum-Mitochondria Contact Sites Interfering with Calcium Homeostasis and Mitochondrial Dynamics in Parkinson's Disease.

The outer mitochondrial membrane protein Miro1 is a crucial player in mitochondrial dynamics and calcium homeostasis. Recent evidence indicated that Miro1 mediates calcium-induced mitochondrial shape transition, which is a prerequisite for the initiation of mitophagy. Moreover, altered Miro1 protein levels have emerged as a shared feature of monogenic and sporadic Parkinson's disease (PD), but, so far, no disease-associated variants in have been identified.

Regulation of hypoxia-induced autophagy in glioblastoma involves ATG9A.

Background: Hypoxia is negatively associated with glioblastoma (GBM) patient survival and contributes to tumour resistance. Anti-angiogenic therapy in GBM further increases hypoxia and activates survival pathways. The aim of this study was to determine the role of hypoxia-induced autophagy in GBM.

Iatrogenic perforation of the left heart during placement of a chest drain.

Chest drain placement is a standard procedure for treating pneumothorax and pleural effusions and has a low complication rate. It is a safe and efficient procedure if image guidance is used. If the anatomic orientation is hampered and neither air nor fluids can be initially aspirated, more complex imaging than a chest x-ray is indicated to avoid major complications.

Citrate pharmacokinetics and calcium levels during high-flux dialysis with regional citrate anticoagulation.

Background: Regional citrate anticoagulation is a very effective anticoagulation method for haemodialysis. However, it is not widely used, primarily due to the risk of hypocalcaemia. We studied citrate and calcium kinetics to better understand safety aspects of this anticoagulation method.

Hemofiltration of recombinant hirudin by different hemodialyzer membranes: implications for clinical use.

Recombinant hirudin (lepirudin) is a potent direct thrombin inhibitor that is used particularly for treatment of immune-mediated heparin-induced thrombocytopenia. Because hirudin is almost exclusively eliminated by the kidneys, its half-life is markedly prolonged in patients with severe renal insufficiency. Therefore, these patients are at risk for bleeding, particularly because no antidote is available.

Reduction of hypotensive side effects during online-haemodiafiltration and low temperature haemodialysis.

Background: This study compares the effect of online-haemodiafiltration (o-HDF, post-dilution mode) with conventional haemodialysis (HD) and 'temperature-controlled' HD (Temp-HD) on the haemodynamic stability of hypotension-prone patients.

Methods: Seventeen patients with a history of frequent hypotensive episodes during dialysis sessions were studied, each patient serving as his or her own control. The first 25 HD treatments in comparison with 25 o-HDF sessions were evaluated using identical dialysate temperature.

Rationale for the use of blood volume and temperature control devices during hemodialysis.

Despite substantial progress in blood purification techniques over the last three decades, treatment-related hypotensive episodes remain one of the major problems in hemodialysis therapy. There are two main reasons for hypotension occurring during dialysis treatments. First, hypovolemia is frequently induced by rapid fluid removal from the blood compartment which is in excess of refilling of fluids from the interstitial space.

Predictive value of initial histology and effect of plasmapheresis on long-term prognosis of rapidly progressive glomerulonephritis.

Intensive immunosuppressive therapy has improved the outcome of patients with rapidly progressive glomerulonephritis (RPGN), which progresses to end-stage renal failure in 90% of patients without intervention. However, it remains unclear which patients benefit most from immunosuppressive therapy and whether plasmapheresis improves long-term outcome. This prospective multicenter study randomized 39 patients with biopsy-proven RPGN (Couser type II, n = 6; pauci-immune type III, n = 33) to undergo either immunosuppressive therapy with prednisone and cyclophosphamide (n = 18) or plasmapheresis in addition to immunosuppression (n = 21).

Determination of Cremophor EL in plasma after sample preparation with solid phase extraction and plasma protein precipitation.

The non-ionic emulsifier Cremophor EL can be quantified using a special potentiometric titration technique with barium chloride activation and precipitation with sodium tetraphenylborate. The end point of the titration is indicated by an ionsensitive coated wire electrode which responds to an excess of tetraphenylborate ions. Sample preparation is necessary to quantify the excipient in plasma of patients receiving ciclosporin formulations with Cremophor EL (Sandimmun), since plasma proteins cause disturbances of the titration.

Ultrafiltration profiling and measurement of relative blood volume as strategies to reduce hemodialysis-related side effects.

Hemodialysis (HD) side effects, such as hypotension and muscle cramps, may be related to excessive ultrafiltration (UF) in relation to refilling of fluids from the extravascular space, resulting in hemoconcentration and reduction of relative blood volume (RBV). This study examines the suitability of RBV measurements and UF modeling to reduce the incidence of dialysis side effects. We followed up 188 dialysis sessions in 53 patients.

Titrimetric determination of Cremophor EL in aqueous solutions and biofluids: part 2: ruggedness of the method with respect to biofluids.

A titration method for Cremophor EL, as a multicomponent mixture commonly used as non-ionic emulgent for manufacturing certain parenteralia, was developed for quantitative routine analysis in biofluids. A coated wire electrode is used as the end-point indicator in potentiometric titrations of Cremophor EL with sodium tetraphenylborate. The method tolerates a broad pH range, addition of alkanols and components of drug formulations and is sufficiently rugged.

Recombinant hirudin (lepirudin) as anticoagulant in intensive care patients treated with continuous hemodialysis.

Background: Recombinant hirudin (lepirudin) is a potent direct thrombin inhibitor, which has been approved for the treatment of heparin-induced thrombocytopenia type II (HIT). Because the drug is mainly eliminated by the kidneys, a single loading dose of hirudin may induce therapeutic anticoagulation for up to one week in patients with renal insufficiency. Thus, the use of hirudin in critically ill patients with renal failure could markedly increase their bleeding risk.

Individualized drug dosage in patients treated with continuous hemofiltration.

Background: Subtherapeutic drug dosing may be even more dangerous than overdosage, especially for intensive care patients requiring hemofiltration.

Proposal: According to Dettli's fundamental equation, body clearance of any drug (Cl) is a linear function of creatinine clearance (Cl = Cl anur + a x C(Cr)), with [a = (Cl norm - Cl anur)/C(Cr), norm]. We propose to individualize drug dosage during high-flux hemofiltration by basing it on Dettli's equation and on total C(Cr) (C(Cr) tot = C(Cr) ren + C(Cr) filt).

Pharmacokinetic principles during continuous renal replacement therapy: drugs and dosage.

Some drugs are removed significantly by continuous renal replacement therapies (CRRTs), and a substitutional dose is required to prevent underdosing of the substance. This review outlines the basic pharmacokinetic principles that determine whether a dose adjustment is required. Only the free non-protein-bound fraction of a drug can pass through the dialyzer membrane.

Evaluation and optimisation of separation buffers for the determination of corticosteroids with micellar electrokinetic capillary chromatography (MECC).

Separation buffers for the determination of the corticosteroids cortisone, hydrocortisone, prednisone and prednisolone with micellar electrokinetic chromatography were developed with respect to separation efficacy and the migration times, depending on the type and the concentration of the organic modifier acetonitrile as well as on the addition of gamma-cyclodextrin. The buffer containing 50 mM SDS and 16% (v/v) acetonitrile enables the rapid profiling of prednisolone together with cortisone and prednisone. Addition of gamma-cyclodextrin alters the elution sequence, but does not further enhance resolution of the corticosteroids.

Efficiency of haemoperfusion materials at removing the fungal toxin orellanine from human plasma.

Orellanine is the main toxin of various Cortinarius mushrooms and responsible for their nephrotoxicity. The present study was undertaken to estimate the value of haemoperfusion in Cortinarius intoxications. The efficiency of the haemoperfusion materials activated charcoal (DHP-1) and Amberlite XAD 4 resin at removing orellanine from plasma was tested in an in vitro model.