[The unconscious child]. / Das bewusstlose Kind.

Acute disturbance of consciousness in a child is a potentially life-threatening condition. There are a variety of possible causes - traumatic, infectious, toxic, metabolic/endocrine, cardio-circulatory - to name a few. The history often provides important clues to narrow down the differential diagnoses. The recognition of reversible causes and a structured diagnostic process are life-saving in an emergency.

Mucha-Habermann disease: a pediatric case report and proposal of a risk score.

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a rare inflammatory dermatological disease. A case of a 13-year-old boy with FUMHD possibly triggered by mycoplasma infection is presented. Based on FUMHD cases identified in a MEDLINE literature search, demographic, treatment, and outcome data were analyzed. An FUMHD mortality risk score is proposed based on the likelihood ratios of risk factors for a fatal outcome. Our FUMHD case had marked leukopenia and thrombocytopenia at admission. He recovered without systemic immunosuppressive treatment. Literature review revealed 119 FUMHD cases. Overall lethality was 14/119 (12%, CI 6-17%), and lethality in children was lower (1/54, 2%, CI 0-6%) compared to adults (13/65, 20%, CI 11-31%). Risk factors for a fatal outcome (likelihood ratio; P) were sepsis (24.97, P < 0.001), adult vs. pediatric patient age (11.19; P = 0.001), systemic involvement (19.97, P < 0.001), and mucosal involvement (4.58; P = 0.032). The proposed FUMHD mortality risk score = Age/10 + 4 + 4 (if systemic involvement) + 1 (if mucosal involvement) was discriminative (sensitivity 93%, specificity 77%). In FUMHD, immune-suppressive treatment intensity should be balanced against the mortality risk, as infectious complications are a frequent cause of death.

Rotationally Stable Screw-Anchor With Locked Trochanteric Stabilizing Plate Versus Proximal Femoral Nail Antirotation in the Treatment of AO/OTA 31A2.2 Fracture: A Biomechanical Evaluation.

OBJECTIVES: Third-generation cephalomedullary nails currently represent the gold standard in the treatment of unstable trochanteric femur fractures. Recently, an extramedullary rotationally stable screw-anchor system (RoSA) has been developed. It was designed to combine the benefits of screw and blade and to improve stability using a locked trochanteric stabilizing plate (TSP). The purpose of this study was to compare the biomechanical behavior of RoSA/TSP and the proximal femoral nail antirotation (PFNA). METHODS: Standardized AO/OTA 31A2.2 fractures were induced by an oscillating saw in 10 paired human specimens (n = 20; mean age = 85 years; range: 71-96 years). The fractures were stabilized by either the RoSA/TSP (Koenigsee Implants, Allendorf, Germany) or the PFNA (DePuy Synthes, Zuchwil, Switzerland). Femurs were positioned in 25 degrees of adduction and 10 degrees of posterior flexion and were cyclically loaded with axial sinusoidal pattern at 0.5 Hz, starting at 300 N, with stepwise increase by 300 N every 500 cycles until bone-implant failure occurred. After every load step, the samples were measured visually and radiographically. Femoral head migration was assessed. RESULTS: The stiffness at the load up to the clinically relevant load step of 1800 N (639 ± 378 N/mm (RoSA/TSP) vs. 673 ± 227 N/mm (PFNA); P = 0.542) was comparable, as was the failure load (3000 ± 787 N vs. 3780 ± 874 N; P = 0.059). Up to 1800 N, no femoral head rotation, head migration, or femoral neck shortening were observed either for RoSA/TSP or PFNA. Whereas failure of the PFNA subsumed fractures of the greater trochanter and the lateral wall, a posterior femoral neck fracture with a significantly increased femoral neck shortening (1.7 mm vs. 0 mm; P = 0.012) was the cause of failure with RoSA/TSP. This specific kind of failure was induced by a femoral neck weakening caused by the posterior TSP stabilizing screw. CONCLUSIONS: There was no significant difference in biomechanical properties between the RoSA/TSP and the PFNA for the fracture pattern tested. However, failure modes differed between the 2 implants with greater femoral neck shortening observed in the RoSA/TSP group.

GOT1/AST1 expression status as a prognostic biomarker in pancreatic ductal adenocarcinoma.

Prognostication in pancreatic ductal adenocarcinoma (PDAC) remains a challenge. Recently, a link between mutated KRAS and glutamic-oxaloacetic transaminase (GOT1/AST1) has been described as part of the metabolic reprogramming in PDAC. The clinical relevance of this novel metabolic KRAS-GOT1 link has not been determined in primary human patient samples. Here we studied the GOT1 expression status as a prognostic biomarker in PDAC. We employed three independent PDAC cohorts with clinicopathological- and follow-up data: a) ICGC, comprising 57 patients with whole-exome sequencing and genome-wide expression profiling; b) ULM, composed of 122 surgically-treated patients with tissue-samples and KRAS status; c) a validation cohort of 140 primary diagnostic biopsy samples. GOT1 expression was assessed by RNA level (ICGC) or immunolabeling (ULM/validation cohort). GOT1 expression varied (ICGC) and correlation with the KRAS mutation- and expression status was imperfect (P = 0.2, ICGC; P = 0.8, ULM). Clinicopathological characteristics did not differ when patients were separated based on GOT1 high vs. low (P = 0.08-1.0); however, overall survival was longer in patients with GOT1-expressing tumors (P = 0.093, ICGC; P = 0.049, ULM). Multivariate analysis confirmed GOT1 as an independent prognostic marker (P = 0.009). Assessment in univariate (P = 0.002) and multivariate models in the validation cohort (P = 0.019), containing 66% stage IV patients, confirmed the independency of GOT1. We propose the GOT1 expression status as a simple and reliable prognostic biomarker in pancreatic ductal adenocarcinoma.

Contribution of protein Z and protein Z-dependent protease inhibitor in generalized Shwartzman reaction.

OBJECTIVE: Sepsis, a leading cause of mortality in critically ill patients, is closely linked to the excessive activation of coagulation and inflammation. Protein Z, a cofactor for the protein Z-dependent protease inhibitor, enhances the inhibition of coagulation factor Xa, and protein Z-dependent protease inhibitor inhibits factor XIa in a protein Z-independent fashion. The functions of protein Z and protein Z-dependent protease inhibitor in the inflammatory and coagulant responses to septic illness have not been evaluated. DESIGN: For induction of generalized Shwartzman reaction, dorsal skinfold chamber-equipped mice were challenged twice with lipopolysaccharide (0.05 mg/kg on day -1 and 5 mg/kg body weight 24 hr later). Time-matched control animals received equal volumes of saline. SETTING: University research laboratory. SUBJECTS, INTERVENTIONS, AND MEASUREMENTS: Using intravital fluorescence microscopy in protein Z-dependent protease inhibitor deficient (ZPI) and protein Z deficient (PZ) mice, as well as their wild-type littermates (ZPI, PZ), kinetics of light/dye-induced thrombus formation and microhemodynamics were assessed in randomly chosen venules. Plasma concentrations of chemokine (C-X-C motif) ligand 1, interleukin-6, and interleukin-10 were measured. Liver and lung were harvested for quantitative analysis of leukocytic tissue infiltration and thrombus formation. MAIN RESULTS: After induction of generalized Shwartzman reaction, all mice showed significant impairment of microhemodynamics, including blood flow velocity, volumetric blood flow, and functional capillary density, as well as leukocytopenia and thrombocytopenia. Thrombus formation time was markedly prolonged after induction of generalized Shwartzman reaction in all mice, except of ZPI mice, which also had a significantly higher fraction of occluded vessels in liver sections. PZ mice developed the highest concentrations of interleukin-6 and interleukin-10 in response to generalized Shwartzman reaction and showed greater leukocytic tissue infiltration than their wild-type littermates. CONCLUSIONS: In this murine model of generalized Shwartzman reaction, protein Z-dependent protease inhibitor deficiency enhanced the thrombotic response to vascular injury, whereas protein Z deficiency increased inflammatory response.

Denaturing gradient gel electrophoresis (DGGE)-based monitoring of intestinal lactobacilli and bifidobacteria of pigs during a feeding trial.

The aim of this study was to determine the influence of different feeding strategies on the gut microbiota of organic growing-finishing pigs. A total of 76 pigs were allocated to four different dietary treatments (control, probiotics, maize silage and grass silage). Effects of the applied probiotic preparation on the composition of the intestinal and faecal microbiota were monitored. By using a DGGE (denaturing gradient gel electrophoresis)-based methodology, fingerprints of the intestinal microbiota were obtained. The total microbial DNA was isolated from faecal and colon samples and amplified with PCR using different primer sets to detect bifidobacteria and lactobacilli. PCR products were separated using DGGE and the resulting profiles were compared with the findings of the other dietary treatments. Bands were excised from the gels and sequenced for further identification. Particularly two different DGGE profiles of bifidobacteria were observed, while lactobacilli showed larger variety within the dietary treatments.