Continuous arteriovenous hemofiltration: in vivo functional characteristics and its dependence on vascular access and filter design

The in vivo functional characteristics of continuous arteriovenous hemofiltration (CAVH) were studied in 21 intensive-care patients with acute renal failure. FH-66 hemofilters were applied. The relationships between prefilter blood pressure (BP), blood flow (QB) and filtration rate (QF) were evaluated by stepwise clamping of the arterial access and simultaneous measurements of these parameters. The correlations between BP and QB, and between QB and QF, were linear (p less than 0.001). The total pressure drop across the extracorporeal circuit was 90 +/- 12 mmHg with Scribner shunt and 70 +/- 13 mmHg with femoral catheters as vascular access. The relative pressure drops across arterial access, hemofilter and venous access for Scribner shunt and for femoral catheter were 30%, 43% and 27% and 12%, 74% and 14%, respectively. At a given BP, QB was lower and transmembrane filtration pressure (TMP) higher in CAVH with Scribner shunt. QB was 102 +/- 38 ml/min; QF was 20 +/- 7 ml/min. The effects of hemofilter geometry and membrane material on functional parameters of CAVH were evaluated by applying four hemofilters (Amicon D-20 HP, D-30 HP, Gambro FH-66, Fresenius AV-400) consecutively in the same patient. The filters were different with respect to hollow fiber length, its internal diameter, number of fibers and membrane material. BP, hematocrit (Hct) and plasma protein remained constant during measurements. QB increased with decreasing filter resistance. QF did not increase with increasing QB. QF was also not closely related to membrane surface area. The hydraulic permeability (Lp) had a major impact on QF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lupusnephritis

During the course of systemic lupus erythematosus (SLE) 30?C90% of patients develop a renal manifestation which has proven to be decisive for morbidity and mortality. Histologically six different classes have been described leading to different treatment strategies. In mesangial proliferative lupus nephritis (class II) extrarenal manifestations determine the immunosuppressive treatment. However, in class III and IV (focal or diffuse proliferative manifestation) cyclophosphamide or possibly mycophenolate mofetil (MMF) as an alternative is necessary. In membranous lupus nephritis (class V) dual renin-angiotensin aldosterone (RAAS) blockade is most important. With class I (minimal mesangial lupus nephritis) and class VI (sclerosis) no immunosuppressive therapy is needed. New treatment options concentrate on B-cell depletion, inhibition of cytokines and co-stimulatory molecules. Recently, for the first time in SLE, a monoclonal antibody (belimumab) against B lymphocyte-stimulating factor (Blys) has been approved for treatment in combination with standard therapy.     

Effect of hyperglycaemia on inflammatory and stress responses and clinical outcome of pneumonia in non-critical-care inpatients: results from an observational cohort study

Aims/hypothesis

Despite the condition’s high prevalence, the influence of hyperglycaemia on clinical outcomes in non-critical-care inpatients with infections remains ill defined. In this study, we analysed associations of glucose levels at admission and during initial inpatient treatment with the inflammatory response and clinical outcome in community-acquired pneumonia (CAP) patients.

Methods

This secondary observational analysis included 880 confirmed CAP patients. We used severity-adjusted multivariate regression models to investigate associations of initial and 96 h mean glucose levels with serially measured biomarker levels over 7 days (C-reactive protein [CRP], procalcitonin, white blood cell count [WBC], pro-adrenomedullin [ProADM]) and adverse clinical course (death and intensive-care unit admission).

Results

In the 724 non-diabetic patients (82.3% of the study population), moderate or severe hyperglycaemia (glucose 6–11 mmol/l and >11 mmol/l, respectively) was associated with increased risk for adverse clinical course (adjusted OR [95% CI] 1.4 [0.8, 2.4] and 3.0 [1.1, 8.0], respectively) and with higher CRP, WBC and ProADM levels over 7 days (p?<?0.05, ANOVA, all days). In diabetic patients (n?=?156), no similar associations were found for initial hyperglycaemia, although mean 96 h glucose levels ?≥?9 mmol/l were associated with adverse clinical course (adjusted OR 5.4 [1.1, 25.8]; p?=?0.03). No effect modification by insulin treatment was detected (interaction terms p?>?0.2 for all analyses).

Conclusions/interpretation

Initial hyperglycaemia in non-diabetic CAP patients, and prolonged hyperglycaemia in diabetic or non-diabetic CAP patients, are associated with a more pronounced inflammatory response and CAP-related adverse clinical outcome. Optimal glucose targets for insulin treatment of hyperglycaemia in non-critical-care settings should be defined.     

Age-related macular degeneration and coronary heart disease: Evaluation of genetic and environmental associations

An association between coronary heart disease (CHD) and age-related macular degeneration (AMD) has long been postulated but results from epidemiological case-control studies, and genetic analyses have been ambiguous. In this study we illuminate the association between AMD and CHD with respect to genetic and environmental risk factors, age of disease onset and AMD subgroups. AMD patients (n = 1036) and age-matched control subjects (n = 412) between 68 and 95 years of age were included in the case-control study. A medical history of CHD, cerebral stroke and arterial hypertension was determined for each individual. The assessment of interacting factors included the current use of systemic medications and smoking habits. Analysis of AMD associated genetic variants included frequent polymorphisms at the complement factor H (CFH, MIM 134370) gene (rs1061170 [p.Y402H], rs800292 [p.I62V]), the complement factor H-related 3 (CFHR3, MIM 605336)/complement factor H-related 1 (CFHR1, MIM 134371) locus (rs6677604; proxy for ΔCFHR3/CFHR1; r² = 0.97) as well as the age-related maculopathy susceptibility 2 (ARMS2, MIM 611313) gene (rs10490924 [p.A69S]).Logistic regression identified a significant positive association of AMD with AMD-risk variants in CFH, ARMS2, and smoking ≥20 packs/year. A history of CHD and the current use of antihyperuricemic agents were inversely associated with the disease. Significantly fewer patients with rs6677604 nonrisk genotype A/A regularly used statins. ARMS2:p.A69S risk variant was significantly associated with exsudative AMD. AMD patients with risk variants at rs1061170 (CFH:p.Y402H) and ARMS2 and smokers (≥20 packs/year) were significantly earlier affected by AMD than those carrying the non-risk variants at each locus.Our data support three major conclusions. First, the age of AMD onset is significantly influenced by genetic and environmental risk factors. Second, in support of previous reports we also show that the ARMS2 rs10490924:T allele is significantly linked to exsudative AMD. And finally, a self-reported history of CHD was inversely associated with AMD in this study. Novel therapeutic strategies aiming at preventing the development of AMD may considerably differ from those that have been developed to treat cardiovascular disorders as both common disorders likely underlie different pathomechanisms.     

M?gliche Ans?tze f��r eine gute Transition

The goals of the transition from pediatrics to adult medicine are to achieve the best possible health status and the greatest potential for the patients, but also to encourage their self-determination, decision-making ability, and capacity to communicate to ensure the highest degree of autonomy and joie de vivre possible. The process of transition must be initiated early and take into consideration chronological age, health status, physical maturity, and psychosocial aspects. To accomplish this, a transition team, an individually tailored transition plan, joint consultations as well as discussions and training concepts are necessary. An assessment of the transition success is important. Several promising approaches already exist, e.g., the transfer program ??Endlich Erwachsen?? (??Finally a Grown-up??) or computer-assisted training models such as??OTIS.?? Successful transition with a team consisting of pediatricians, internists, psychologists, social workers, and nurses is only sustainable when financing for these efforts is assured by the health insurance providers. For example, after kidney transplantation this strategy contributes to improved graft survival with longer independence from continuous renal replacement therapy.     

Is survival following post-operative radiotherapy in pN1-non-small cell lung cancer reduced? Results of a multivariate analysis

Prognostic factors and the role of post-operative radiotherapy (PORT) in patients with pN1 nodal stage following surgery for NSCLC were identified. The clinical course of 211 patients with pN1 nodal involvement following thoracic surgery were reviewed, 97 of them received PORT. Multi-variate survival analysis with respect to prognostic factors (including treatment) was performed. The most frequent site of recurrence was the ipsilateral bronchus-stump or hilus (63% of recurrences). The 5-year rate of intercurrent deaths for PORT was 1% vs 6% in the group without PORT. The 5-year rate of locoregional recurrence was similar (24% vs 19%) for PORT vs no PORT (p=0.97). PORT patients had a higher rate of distant metastases (p=0.04). The 5-year rate of overall survival was 45% without PORT and 25% with PORT (p=0.003). Multivariate survival analysis identified 4 prognostic factors associated with decreased survival rate: age, extended pneumectomy, number of involved nodes and PORT dose. A PORT dose of 50 Gy corresponds to an increase in relative risk of death in the range of 1.5. Patients with PORT do not have an increased rate of intercurrent deaths. However in this cohort, PORT in pN1 patients was associated with a decreased survival rate due to distant metastases. Even after correction with respect to accepted prognostic factors in multivariate survival analysis, PORT was not able to improve or equalize prognosis of these negatively selected patients. The main site of recurrence is the bronchial stump and hilus. If PORT is applied in pN1 patients, a reduction of the target volume should be discussed since local control in high-risk patients may be of relevance.     

Combined orbito-frontal injuries

Our experiences in 55 patients suffering from orbitofrontal injuries are discussed. The prognosis is determined by the severity of the brain injuries and the cerebral complications. The relation of fronto-basal, orbital, and maxillofacial fractures to lesions of the brain tissue and contents of the orbita is best demonstrated in high-resolution CT scan. Surgery is usually possible in one interdisciplinary operating session. Penetrating injuries with CSF leakage primarily require operative therapy; indirect, open, frontobasal fractures should be covered secondarily within two weeks following trauma. A debridement of the paranasal sinuses is necessary if drainage is obstructed or infection is imminent. We found no improvement of visual function in eight patients following transethmoidal optic nerve decompression; the visus recovered only in one patient after removal of a bone fragment impressing on the eyeball. Typical complications are systematic or central nervous system infections; less frequent are traumatic cavernoussinus fistulas and pneumato- or encephaloceles.