Spinal or general anaesthesia for lower-limb amputation in peripheral artery disease - a retrospective cohort study.

BACKGROUND: The present study aimed to determine which method of anaesthesia (spinal anaesthesia or general anaesthesia) is better in reducing post-operative analgesic requirements in patients undergoing major limb amputation for lower-limb ischaemia. Another aim was to find out if anaesthesiologists use neuraxial anaesthesia in high-risk patients despite abnormal coagulation profile or use of anticoagulation. METHODS: The study was a retrospective cohort study. All patients undergone above-the-knee amputation or below-the-knee amputation due to peripheral artery disease between 1996 and 2010 were reviewed to evaluate post-operative opioid consumption and complications. RESULTS: A total of 434 amputations in 323 patients were included in the study. The number of surgical complications, the need for surgical revision and the number of intensive care unit admissions were significantly higher in the general anaesthesia group. The need for post-operative opioid medication was significantly lower in patients with above-the-knee amputation and spinal anaesthesia. The use of post-operative epidural analgesia did not reduce analgesic requirements. In the present study, there were patients who received neuraxial anaesthesia despite abnormal coagulation profile or uninterrupted warfarin or clopidogrel. There were no reported cases of spinal or epidural haematoma. CONCLUSION: Patients with spinal anaesthesia had a lower rate of surgical complications, re-operations and intensive care unit admissions. Patients with above-the-knee amputation and spinal anaesthesia had a lesser need for opioid medication in the post-operative period than patients with general anaesthesia. Anaesthesiologists performed neuraxial anaesthesia and/or analgesia in high-risk patients despite abnormal coagulation profile or ongoing anticoagulation, but no adverse outcomes were reported.

Histological damage of colonic epithelium is associated with clinical severity and outcome in colectomized critically Ill patients.

BACKGROUND: Severe intestinal mucosal damage and organ failure has been associated in experimental models. Our purpose was to determine whether there is any association between histopathological findings and postoperative mortality among ICU patients undergoing emergency colectomies for various illnesses. METHODS: In a retrospective case control study, total colectomy specimens from 50 patients in a mixed ICU were analysed: 18 had sepsis, 11 vascular operations, and 21 Clostridium difficile colitis. Overall thickness, the width of epithelial defects, and presence of cryptal damage were assessed. Extent of necrosis and amount of neutrophils were separately evaluated in the layers of the colonic wall. Clinical features, including sequential organ failure assessment (SOFA) scores and survival, were registered. RESULTS: The histopathological findings for the three clinical entities were similar, except for the abundance of characteristic pseudomembranes in the Clostridium group. Mucosal height (maximum) showed a negative correlation with SOFA score on admission (ρ = -0.296, P = 0.037), and with preoperative blood lactate level (ρ = -0.316; P = 0.027). The nonsurvivors had wider enterocyte defects (60 vs. 40.8, P = 0.002) and more severe crypt damage (61 vs. 27 %; P = 0.024) than the survivors. CONCLUSIONS: The histopathological damage involves all layers of the colon wall among ICU patients being largely similar in sepsis, C. difficile infection, and ischemia after vascular operations. Mucosal epithelial damage is associated with clinical severity of the illness and mortality.

Factors associated with discrepancy between prescribed and administered enteral nutrition in general ICU.

BACKGROUND: Discrepancy between prescribed and administered enteral nutrition (EN) is a common problem during intensive care. The aim of this study was to find out the success rate and factors associated with inadequacy of enteral nutrition in a mixed general intensive care unit (ICU). METHODS: This was a retrospective single-center study of 892 patients with ICU length of stay (LOS) ≥4 days. The factors associated with adequacy of enteral nutrition on day 4 were analyzed. These included disease-specific factors, patient-related factors, severity of illness, and procedural factors. RESULTS: Of the 892 patients, 349 (39.1%) had an EN success rate of ≥70%, which was associated with a lower amount of prescribed enteral energy (500 kcal [500-800] vs. 800 kcal [500-1200], p < 0.001) and bolus administration of enteral nutrition (41 of 349 vs. 27 of 543, p < 0.001). Other factors impairing successful EN were severe inflammation, surgery, and GI-related admission diagnosis. CONCLUSIONS: On the fourth day during ICU stay discrepancy between prescribed and administered enteral nutrition was associated to severe inflammation, GI-related diagnosis, and prescribing policy.

Apoptosis during breast carcinoma progression.

The purpose of this study was to investigate apoptosis, proliferation, and the expression of apoptosis-influencing proteins bcl-2 and bax and estrogen and progesterone receptors during breast carcinoma progression. The material consisted of 53 paired breast carcinoma samples representing primary and recurrent tumors and 24 control samples. The recurrent sample was located either in the breast scar tissue or at a distant metastatic site. Apoptosis was detected both morphologically and by 3' end labeling of fragmented DNA. Cell proliferation was evaluated immunohistochemically by the MIB index. The expressions of bcl-2, bax, and estrogen and progesterone receptors were studied immunohistochemically. There was a significant increase in the extent of apoptosis and proliferation in recurrent tumors compared to the primary lesions (P = 0.015 and P = 0.038, respectively). In primary tumors with an apoptotic index of >0.50%, the survival of the patients was significantly shorter (P = 0.015). In cases with a significant increase in apoptosis or proliferation in the recurrent tumor, the survival of the patients was significantly shorter (P = 0.009 and P = 0.003, respectively). Of the variables analyzed, bcl-2 expression and a positive estrogen receptor status were significantly associated with a low extent of apoptosis (P = 0.010 and P = 0.042, respectively). Their changes were parallel to the changes in apoptosis during tumor progression, although the associations did not reach statistical significance. The results show that increased apoptosis is associated with a worse prognosis in breast carcinoma. A significant increase in apoptosis in recurrent breast carcinoma lesions predicts a worse clinical outcome.

Inducible nitric oxide synthase expression, apoptosis, and angiogenesis in in situ and invasive breast carcinomas.

In this investigation, we studied the expression of inducible nitric oxide synthase (iNOS) and its association to apoptosis and angiogenesis in 43 in situ and 68 invasive breast carcinomas. Its expression was studied immunohistochemically using a polyclonal iNOS antibody, and the staining was evaluated both in tumor and stromal cells. Apoptosis was detected by 3' end labeling of fragmented DNA (terminal deoxynucleotidyl transferase-mediated nick end labeling method). Vascularization was detected immunohistochemically using an antibody to the FVIII-related antigen, and calculated microvessel densities were determined. In addition to strong iNOS expression in stromal cells, iNOS positivity was observed in tumor cells in 46.5% of in situ and 58.8% of invasive carcinomas. In invasive carcinomas, there were more cases with iNOS positivity both in tumor and stromal cells compared to in situ carcinomas (0.007). The proportion of cases with iNOS-positive tumor cells increased in in situ carcinomas from grade I to III (20.0%, 46.2%, and 73.3%). In invasive ductal carcinomas, there were more cases with iNOS-positive tumor cells than with in situ carcinomas (P = 0.04). Carcinomas with both iNOS-positive tumor and stromal cells had a higher apoptotic index (P = 0.02) and a higher calculated microvessel densities index (P = 0.02). A high number of iNOS-positive stromal cells associated with metastatic disease (P = 0.05). The results show that breast carcinoma cells, in addition to stromal cells, express iNOS and are capable of producing NO. Carcinomas with iNOS-positive tumor and stromal cells have a higher apoptotic indices and increased vascularization, suggesting that iNOS contributes to promotion of apoptosis and angiogenesis in breast carcinoma. The association of the number of iNOS-positive stromal cells with metastatic disease might be attributable to stimulation of angiogenesis, resulting in a higher vascular density and consequently a higher probability for tumor cells to invade.

eNOS expression is associated with the estrogen and progesterone receptor status in invasive breast carcinoma.

In this study we investigated the immunohistochemical expression of eNOS and nNOS in 80 invasive breast carcinomas. Since NO is known to influence apoptosis and angiogenesis we also determined the apoptotic index of the tumor cells by the TUNEL method and tumor angiogenesis by immunostaining the sections with FVIII-related antigen and assessing the number of positively stained vessels. Respectively, 65% and 11% of the cases expressed cytoplasmic positivity for eNOS and nNOS. The mean apoptotic index of the tumors was 0.60%. eNOS or nNOS expression did not associate with the apoptotic index (p=0.36 and p=0.58, respectively). Cases with a positive estrogen or progesterone receptor status were significantly more often eNOS positive than receptor negative cases (p=0.012 and p=0.015, respectively). No association was found between the estrogen or progesterone receptor status and nNOS expression. Neither eNOS nor nNOS expression was associated with vascular density, tumor grade or the TNM status of the tumors. The results show that eNOS and nNOS are expressed in breast carcinomas possibly contributing to their NO synthesis. No association with apoptosis or angiogenesis was detected. eNOS expression was, however, associated with the positive estrogen and progesterone receptors status suggesting that its synthesis might be regulated by hormonal stimulation.

Expression of caspases 3, 6 and 8 is increased in parallel with apoptosis and histological aggressiveness of the breast lesion.

The aim of this investigation was to study the expression of caspases 3, 6 and 8 and their association to apoptosis in preneoplastic and neoplastic lesions of the breast. The material consisted of nine benign breast epithelial hyperplasias, 15 atypical hyperplasias, 74 in situ and 82 invasive carcinomas. The extent of apoptosis was assessed by the TUNEL method and caspase 3, 6 and 8 expression by immunohistochemistry with specific antibodies. Increased caspase 3 immunopositivity, as compared to staining of normal breast ductal epithelium, was seen in 22% of benign epithelial hyperplasias, 25% of atypical hyperplasias, 58% of in situ carcinomas and 90% of invasive carcinomas. The corresponding percentages for caspase 6 and 8 were 11%, 25%, 60%, 87% and 22%, 57%, 84%, 83% respectively. In high-grade in situ lesions there were significantly more cases with strong caspase 3, 6 and 8 immunoreactivity than in low- and intermediate-grade lesions (P = 0.0045, P = 0.049 and P = 0.0001 respectively). In invasive carcinomas, however, no association between a high tumour grade and caspase 3, 6 or 8 expression was found (P = 0.27, P = 0.26 and P = 0.69 respectively). The mean apoptotic index was 0.14 +/- 0.14% in benign epithelial hyperplasias, 0.17 +/- 0.12% in atypical hyperplasias, 0.61 +/- 0.88% in in situ carcinomas and 0.94 +/- 1.21% in invasive carcinomas. In all cases strong caspase 3, 6 and 8 positivity was significantly associated with the extent of apoptosis (P < 0.001, P = 0.015 and P = 0.050 respectively). The results show that synthesis of caspases 3, 6 and 8 is up-regulated in neoplastic breast epithelial cells in parallel to the increase in the apoptotic index and progression of the breast lesions.

MnSOD expression is less frequent in tumour cells of invasive breast carcinomas than in in situ carcinomas or non-neoplastic breast epithelial cells.

Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme capable of neutralizing superoxide anion molecules. In previous studies it has been suggested to suppress both tumour proliferation and apoptosis. This study investigated 65 invasive, 50 in situ and 19 benign hyperplastic breast lesions for its immunohistochemical expression. MnSOD expression was also tested with in situ hybridization. To study cell proliferation, apoptosis and their association with MnSOD expression the neoplastic breast lesions were immunostained with a monoclonal antibody to Ki-67 and the extent of apoptosis in them was determined by the TUNEL method. 32/65 (49%) of the invasive ductal carcinomas, 41/50 (82%) of the in situ and 15/19 (79%) of the benign hyperplasias expressed the MnSOD protein. There were significantly more MnSOD positive cases in in situ carcinoma and in benign hyperplasia than in invasive carcinoma (p=0.00016 and p=0.022, respectively). Positivity was also more frequently found in non-neoplastic ductal and acinar epithelial cells than in invasive carcinoma. On the other hand, neoplastic epithelial cells of invasive and in situ carcinoma showed strong positivity more often than the epithelial cells of benign hyperplasia or non-neoplastic epithelium. In breast lesions, MnSOD positivity did not associate with proliferation or apoptosis. The lower frequency of MnSOD positive cases in invasive breast carcinoma suggests that the lack of its expression might contribute to the development of an invasive breast carcinoma phenotype and that it could in this way operate as a tumour suppressor gene, as previously suggested.