Phase 3 study comparing tigecycline and ertapenem in patients with diabetic foot infections with and without osteomyelitis.

A phase 3, randomized, double-blind trial was conducted in subjects with diabetic foot infections without osteomyelitis (primary study) or with osteomyelitis (substudy) to determine the efficacy and safety of parenteral (intravenous [iv]) tigecycline (150 mg once-daily) versus 1 g once-daily iv ertapenem ± vancomycin. Among 944 subjects in the primary study who received ≥1 dose of study drug, >85% had type 2 diabetes; ~90% had Perfusion, Extent, Depth/tissue loss, Infection, and Sensation infection grade 2 or 3; and ~20% reported prior antibiotic failure. For the clinically evaluable population at test-of-cure, 77.5% of tigecycline- and 82.5% of ertapenem ± vancomycin-treated subjects were cured. Corresponding rates for the clinical modified intent-to-treat population were 71.4% and 77.9%, respectively. Clinical cure rates in the substudy were low (<36%) for a subset of tigecycline-treated subjects with osteomyelitis. Nausea and vomiting occurred significantly more often after tigecycline treatment (P = 0.003 and P < 0.001, respectively), resulting in significantly higher discontinuation rates in the primary study (nausea P = 0.007, vomiting P < 0.001). In the primary study, tigecycline did not meet criteria for noninferiority compared with ertapenem ± vancomycin in the treatment of subjects with diabetic foot infections.

Prolonged intestinal mucosal acidosis is associated with multiple organ failure in human acute pancreatitis: gastric tonometry revisited.

AIM: To evaluate whether multiple determinations of intramucosal pH (pHi) in acute pancreatitis (AP) patients could provide additional information of the disease severity during early hospitalization. METHODS: Twenty-one patients suffering from acute pancreatitis were monitored by gastric tonometry in the first 72 h after hospital admission. RESULTS: In the survivor group (n = 15) the initially low pHi values returned to normal level (pHi > or = 7.32) within 48 h (median pHi: d 1: 7.21; d 2: 7.32; d 3: 7.33). In contrast, pHi values in the non-survivor group n = 6) were persistently either below or in the low normal range (median pHi 7.12; 7.12; 7.07 respectively), but pHi differences between the two groups reached significance only after 24 h (P<0.01). Mucosal acidosis detected at any time during the monitored period was associated with the emergence of single or multiple organ dysfunction (P<0.01). CONCLUSION: Prolonged gastric mucosal acidosis was associated with remote organ dysfunction and failure in Acute Pancreatitis, however, correlation with the fatal outcome became significant only 24 h after admission. Due to its non-invasive nature gastric tonometry may supplement the pro-inflammatory markers to achieve a multi-faceted monitoring of the disease.

Alpha-fetoprotein expression is a potential prognostic marker in hepatocellular carcinoma.

AIM: To characterize the alpha-fetoprotein (AFP) positive and negative hepatocellular carcinoma (HCC) samples. METHODS: Thirty-seven paraffin-embedded human HCC samples were analyzed by immunohistochemistry for the following antigens: AFP, beta-catenin, p53, CD44, MSH-2, MLH-1, and HNF-4. The tumors were divided into two groups based on the AFP expression. The immunophenotypic data and important clinical parameters were studied between the two groups. RESULTS: Twenty-one of the thirty-seven examined HCCs were AFP positive. Seven with nuclear p53 staining were AFP positive, while seven tumors with nuclear beta-catenin staining were AFP negative. CD44 staining and high histological tumor grade were more frequent among the AFP-positive HCCs. The other immunophenotypical and clinical parameters did not show statistically significant difference in their distribution between the AFP positive and negative samples. CONCLUSION: AFP expression in HCC correlates with unfavorable prognostic factors, while nuclear beta-catenin positivity is more common among the AFP-negative liver tumors. This observation supports the microarray data on in vivo human tumors.

[Surgical alternatives in the treatment of liver tumors]. / Sebészeti alternatívák a májdaganatok kezelésében.

Because of development in diagnostics and treatment modalities of focal liver diseases liver tumors are subject of general interest, but in Hungary the number of surgical intervention indicated by liver tumor is smaller than required. The aim of author to review the modern surgical and alternative procedures. He summarizes the natural history of different type of focal lesions particularly the primary and metastatic liver tumors. He gives an overview about the surgical procedures and their risk factors, complications and contraindications. The role of percutaneous and minimal-invasive interventions are discussed as well, and the combined therapeutic strategy is stressed.

[Transfusion problems in surgery and anesthesiology. The causes, consequences, prevention and treatment of perioperative anemia]. / A sebészet és az aneszteziológia transzfúziológiai problémái. A perioperatív anaemia okai, következményei, megelózése és kezelése.

INTRODUCTION: The classical indication for blood transfusion is the correction of oxygen delivery failure, and the elimination of tissue ischaemia. Such indications in the surgical and anesthesiological practice are the acute haemorrhagic states (trauma, acute gastrointestinal bleeding, intraoperative hemorrhage), as well as diseases associated with chronic blood loss (occult bleeding caused by malignancies, and ulcerating processes etc.). The traditional surgical and anesthesiological viewpoint has adopted a remarkably liberal approach to the indication of blood transfusion, and a whole range of its subtle, medium-long term adverse effects has been taken into account only recently. The purpose of this review was to analyze the causes and pathophysiological consequences of perioperative anemia and blood loss, as well as to reconsider the proper indications of blood transfusion in the view of immunological sequela. The most recent data on the transfusion related immuno-depression and immunomodulation are summarized. The authors wish to provide clues for the definition of "transfusion trigger", in addition, methods available for the clinical practice to reduce blood demand and to restore oxygen transport capacity during surgical and anesthesiological interventions are revisited. Based on the review of the literature and the personal experience of the authors the practical recommendations concerning the administration of blood and blood products should be summarized as follows: 1. Blood transfusion is rarely indicated if the hemoglobin level is above 10 g/dl, and in fact always necessary if it is less than 6 g/dl, especially, if the anemia developed acutely. 2. The "transfusion trigger" is subject to continued debate, and whether a particular patient with intermediary (6-10 g/dl) Hb levels should be transfused or not must be assessed in the perspective of the potential complications initiated by the inadequate oxygenation. 3. If major co-morbidity (e.g. emphysema, ischaemic heart disease) is present, 10 g/dl Hb, in case of respirator dependency 12 g/dl Hb levels justify the administration of transfusion. If feasible, the beneficial effects of allogenous blood sparing methodologies should be utilized. CONCLUSIONS: Although the National Blood Supply Service is excellently organized in Hungary, the current clinical practice is not satisfactory. The use of up-to-date methods at the average surgical departments is suboptimal, and due to the lack of knowledge concerning the recent advances in immunology the clinicians are far too liberal in the indication of blood transfusion. The objective is to establish a modern surgical and anesthesiological transfusion practice based on the solid understanding of immunological facts, and to modernize the continued education, as well as to improve the financing of costly blood saving methodologies.

[Current diagnostics and therapy of focal liver lesions]. / A gócos májbetegségek korszerú diagnosztikája és terápiája.

Increasing number of tumorous diseases, the extension of Hepatitis B and C infection, and growing frequency of cirrhotic patients have emphasized the importance of treatment of primary and secondary liver tumors. On the other hand the development in imaging procedures have been resulted in diagnosis of different focal liver lesion with unknown origin, and had to decide whether the patient should be treated or only observation is indicated. First the author gives a review about the most frequent focal liver lesions and their therapeutic consequence. He discusses in detail the indication, risk factors, technics, contraindications and complications of surgical interventions. The possibilities and results of ablative and minimal invasive procedures are analysed, and the author underlines the necessity of combined therapy. The results of different therapeutic modalities are presented according to literary data, and the author summarizes the therapeutic tactics accepted today.