Uwe Kuhlmann

Best supportive care and therapeutic plasma exchange with or without eculizumab in Shiga-toxin-producing E. coli O104:H4 induced haemolytic–uraemic syndrome: an analysis of the German STEC-HUS registry

BACKGROUND May 22nd marks the beginning of a Shiga-toxin-producing Escherichia coli (STEC) O104:H4 outbreak in Northern Germany. By its end on 27 July, it had claimed 53 deaths among 2987 STEC and 855 confirmed haemolytic-uraemic syndrome (HUS) cases. METHODS To describe short-term effectiveness of best supportive care (BSC), therapeutic plasma exchange (TPE) and TPE with eculizumab (TPE-Ecu) in 631 patients with suspected HUS treated in 84 hospitals in Germany, Sweden and the Netherlands using the web-based registry of the DGfN (online since 27 May). RESULTS Of 631 entries, 491 fulfilled the definition of HUS (median age 46 years; 71% females). The median (inter-quartile range) hospital stay was 22 (14-31) days. Two hundred and eighty-one (57%) patients underwent dialysis and 114 (23%) mechanical ventilation. Fifty-seven patients received BSC, 241 TPE and 193 TPE-Ecu. Treatment strategy was dependent on disease severity (laboratory signs of haemolysis, thrombocytopenia, peak creatinine level, need for dialysis, neurological symptoms, frequency of seizures) which was lower in BSC than in TPE and TPE-Ecu patients. At study endpoint (hospital discharge or death), the median creatinine was lower in BSC [1.1 mg/dL (0.9-1.3)] than in TPE [1.2 mg/dL (1.0-1.5), P < 0.05] and TPE-Ecu [1.4 mg/dL (1.0-2.2), P < 0.001], while need for dialysis was not different between BSC (0.0%, n = 0), TPE (3.7%; n = 9) and TPE-Ecu (4.7%, n = 9). Seizures were absent in BSC and rare in TPE (0.4%; n = 1) and TPE-Ecu (2.6%; n = 5) patients. Total hospital mortality in HUS patients was 4.1% (n = 20) and did not differ significantly between the TPE and TPE-Ecu groups. CONCLUSIONS Despite frequent renal impairment, advanced neurological disorders and severe respiratory failure, short-term outcome was better than expected when compared with previous reports. Within the limitations of a retrospective registry analysis, our data do not support the notion of a short-term benefit of Ecu in comparison to TPE alone in the treatment of STEC-HUS. A randomized trial comparing BSC, TPE and Ecu seems to be prudent and necessary prior to establishing new treatment guidelines for STEC-HUS.

Clinical and Immunological Follow-Up of Pemphigus Patients on Adjuvant Treatment with Immunoadsorption or Rituximab

Background: Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering skin disease which is associated with pathogenic IgG autoantibodies against desmogleins (Dsg) 1 and 3. Novel therapeutic strategies such as immunoadsorption (IA) or the anti-CD20 antibody rituximab (Rtx) hold promise to be effective in severe or recalcitrant PV. Patients and Methods: In the present retrospective study, 6 patients with extensive cutaneous PV were subjected to adjuvant IA treatment while 5 patients with severe mucosal PV received adjuvant Rtx treatment. Results: Within 6 months, IA and Rtx induced excellent clinical responses which were associated with a significant reduction of prednisolone doses and a decrease in anti-Dsg-specific IgG. Over a 12-month period, 3 IA-treated patients required additional adjuvant drugs while all of the PV patients on Rtx had no or only minimal residual symptoms. Conclusion: The relative therapeutic (long-term) efficacy of IA and Rtx in cutaneous versus mucosal PV needs to be evaluated in a prospective study.

Macrophage activation is associated with poorer long-term outcomes in renal transplant patients

Grebe SO, Kuhlmann U, Fogl D, Luyckx VA, Mueller TF. Macrophage activation is associated with poorer long‐term outcomes in renal transplant patients.
Clin Transplant 2011: 25: 744–754.

Effects of Two Immunosuppressive Treatment Protocols for IgA Nephropathy

The role of immunosuppression in IgA nephropathy (IgAN) is controversial. In the Supportive Versus Immunosuppressive Therapy for the Treatment of Progressive IgA Nephropathy (STOP-IgAN) Trial, 162 patients with IgAN and proteinuria >0.75 g/d after 6 months of optimized supportive care were randomized into two groups: continued supportive care or additional immunosuppression (GFR≥60 ml/min per 1.73 m2: 6-month corticosteroid monotherapy; GFR=30-59 ml/min per 1.73 m2: cyclophosphamide for 3 months followed by azathioprine plus oral prednisolone). Coprimary end points were full clinical remission and GFR loss ≥15 ml/min per 1.73 m2 during the 3-year trial phase. In this secondary intention to treat analysis, we separately analyzed data from each immunosuppression subgroup and the corresponding patients on supportive care. Full clinical remission occurred in 11 (20%) patients receiving corticosteroid monotherapy and three (6%) patients on supportive care (odds ratio, 5.31; 95% confidence interval, 1.07 to 26.36; P=0.02), but the rate did not differ between patients receiving immunosuppressive combination and controls on supportive care (11% versus 4%, respectively; P=0.30). The end point of GFR loss ≥15 ml/min per 1.73 m2 did not differ between groups. Only corticosteroid monotherapy transiently reduced proteinuria at 12 months. Severe infections, impaired glucose tolerance, and/or weight gain in the first year were more frequent with either immunosuppressive regimen than with supportive care. In conclusion, only corticosteroid monotherapy induced disease remission in a minority of patients who had IgAN with relatively well preserved GFR and persistent proteinuria. Neither immunosuppressive regimen prevented GFR loss, and both associated with substantial adverse events.

Obstructive sleep apnoea: clinical signs, diagnosis and treatment

Humans spend one-third of their lifetime sleeping. It has only been ∼50 years since it was recognized that sleep is not simply a passive state characterized by the absence of wakefulness, but rather a condition that has a typical structure with electrophysiologically, clearly distinguishable phases that follow one another according to a characteristic pattern in healthy subjects. Using electroencephalogram (EEG), electrooculogram (EOG) and electromyogram (EMG), sleep is classified as rapid eye movement (REM) sleep or one of four different non-REM sleep stages. Altogether, one spends ∼20–25% of the total sleep time in deep sleep and REM sleep, respectively, and ∼50% in light sleep. After the age of 50, the percentage of deep and REM sleep decreases, whereas light sleep and periods of wakefulness during the night increases. During the night, 4–6 sleep cycles are completed lasting 70–90 min and consisting of an initial period of light sleep, followed by deep sleep and finally REM sleep. Whereas deep sleep is predominantly present during the first hours of sleep, there is an increase in REM sleep in the second half of the night, often accompanied by dreaming.

Wie weit muss der Blutdruck runter

ZusammenfassungDer hypertensive Notfall ist ein relativ häufiges Problem in der internis tischen Notfallmedizin und bedarf eines gut stratifizierten Nebeneinanders von diagnostischen und therapeutischen Maßnahmen. Unsere Autoren haben die wesentlichen Punkte, die Sie beachten müssen, zusammengefasst.