4G/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study

In Caucasian patients with severe sepsis due to pneumonia carriers of the 4G allele of PAI-1 polymorphism have higher risk for multiple organ dysfunction syndrome and septic shock and in agreement they showed more fulminant disease progression based on continuous clinical variables

Phaeochromocytomás krízisben végzett acut laparoscopos adrenalectomia [Urgent laparoscopic adrenalectomy in acute crisis caused by pheochromocytoma]

Esetismertetés: A szerzők egy 30 éves nőbeteg esetét mutatják be, akinek intenzív osztályos felvételére hypertoniás krízist kísérő mellkasi panaszok, cardialis decompensatio, progrediáló acut légzési elégtelenség és tudatzavar miatt került sor. A gyors kivizsgálás mellett azonnal megkezdett intenzív terápia ellenére a felvételt követő harmadik napra többszervi elégtelenség képe alakult ki. Miután a kórkép kialakulása a bal oldali mellékvese térfoglaló folyamatára volt visszavezethető, a multidiszciplináris konzílium acut laparoscopos adrenalectomia végzése mellett foglalt állást. Az eltávolított képlet szövettani diagnózisa phaeochromocytoma volt. A postoperativ időszakban a beteg állapota fokozatosan javult, tünetei, panaszai regrediáltak, majd gyógyultan távozott. Megbeszélés: A phaeochromocytoma diagnózisa nehéz feladat, az általa kiváltott tünetek és panaszok sok egyéb kórképre is utalhatnak. Az acut phaeochromocytomás krízis általában belgyógyászati, intenzív terápiás eszközökkel uralható. A súlyos, többszervi elégtelenséghez vezető esetekben indokolt az acut műtéti beavatkozás. Az ilyen beavatkozások rizikója igen magas, de korrekt intra- és postoperativ észleléssel, megfelelő intenzív terápiával a laparoscopos műtét ezekben az esetekben választható megoldás lehet

Elevated serum 70 kDa heat shock protein level reflects tissue damage and disease severity in the syndrome of hemolysis, elevated liver enzymes, and low platelet count

Objective: We have recently demonstrated that serum 70 kDa heat shock protein (Hsp70) levels are increased in the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome). The aim of the present study was to investigate in an independent, larger cohort of patients whether serum Hsp70 levels are related to laboratory markers of HELLP syndrome. Study design: The study population included 14 patients with HELLP syndrome. Serum Hsp70 levels were measured by enzyme- linked immunosorbent assay. The relationship between serum Hsp70 levels and laboratory markers of hemolysis, hepatocellular damage, renal insufficiency, inflammation or disseminated intravascular coagulation (DIC), as well as platelet count was investigated by calculating correlation coefficients, standardized regression coefficients and by principal component analysis. Results: Serum Hsp70 levels showed a very strong correlation to the markers of hemolysis (plasma free hemoglobin level, serum lactate dehydrogenase activity, and total bilirubin level) and of hepatocellular injury (serum aminotransferase activities), supported also by principal component analysis. Furthermore, circulating Hsp70 concentration reflected the severity of HELLP syndrome as expressed by the significant inverse correlation to the lowest platelet count. By contrast, there was no relationship between serum Hsp70 levels and markers of inflammation, coagulation, fibrinolysis or renal insufficiency. Conclusion: Elevated serum 70 kDa heat shock protein level seems to reflect tissue damage (hemolysis and hepatocellular injury) and disease severity in patients with HELLP syndrome. However, further investigations are needed to determine the clinical relevance of these findings. ? 2007 Elsevier Ireland Ltd. All rights reserved

Analysis of the 8.1 ancestral MHC haplotype in severe, pneumonia-related sepsis.

The most frequent Caucasian MHC haplotype, AH8.1 - associated with numerous immunopathological differences and certain autoimmune diseases - was recently linked to the delayed onset of bacterial colonization in cystic fibrosis. Based on this observation, we hypothesized that the carriers of AH8.1 have lower risk for a worse outcome in sepsis. AH8.1 carrier state was determined in 207 Caucasian patients with severe, pneumonia-related sepsis. Our data showed that in patients without chronic obstructive pulmonary disease (COPD), septic shock - a serious consequence of the bacterial infection - occurred significantly less frequently (OR=0.3383; 95% CI=0.1141-0.995; p=0.043) in carriers of AH8.1, than in non-carriers. According to the multivariate logistic regression analysis, this haplotype had an independent protective role against septic shock in all patients (OR=0.315; 95% CI=0.100-0.992; p=0.048), particularly in COPD-free patients (OR=0.117; 95% CI=0.025-0.554; p=0.007). These results indicate that AH8.1 may confer protection against the progression of bacterial infection, and this could explain, at least partially, its high frequency in the Caucasian population

Complement activation, inflammation and relative ADAMTS13 deficiency in secondary thrombotic microangiopathies

BACKGROUND: The secondary forms of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (secondary TMA) emerge as complications of coexisting diseases. OBJECTIVES: We hypothesized that secondary TMA could be characterized by the presence of relative ADAMTS13 deficiency and complement activation, and this relationship may have a prognostic value for outcome. PATIENTS AND METHODS: Fifty-three patients with thrombotic microangiopathy (TMA) and coexisting disease (such as malignancies, sepsis, heart surgery with extracorporeal circulation, solid organ transplantation, systemic autoimmune disorders), 41 patient controls, and 34 healthy controls were enrolled in our case-control study with 30days follow-up. Complement profile (from serum) and activation products, von Willebrand factor (VWF, from EDTA plasma), and ADAMTS13 activity were determined. RESULTS: ADAMTS13 activity was reduced, while VWF level was elevated in secondary TMA patients. The activity of the classical, lectin and alternative pathways, as well as the levels of C3, C4, and Factor H were significantly lower in secondary TMA patients, and were accompanied by high activation product levels (C3a and sC5b-9). Factor H concentration correlated to relative ADAMTS13 deficiency (i.e. VWF/ADAMTS13 ratio (r=-0.368, p=0.019)). 28/53 patients (53%) died during the follow-up period. Increased sC5b-9, C3a, and C reactive protein levels were all associated with a poor patient outcome. CONCLUSIONS: Our results indicate that the secondary TMA syndrome and its poor outcome is characterized by relative ADAMTS13 deficiency, inflammation, and complement activation with consumption via the classical and alternative pathways. It is yet to be determined whether complement inhibition could be a possible therapeutic option for patients with secondary TMA