Major elective surgery for vascular disease in patients aged 80 or more: perioperative (30-day) outcomes

Although major vascular surgery is performed with increasing frequency in elderly people, the impact of age on outcomes is uncertain. We evaluated the perioperative (30-day) outcomes for patients who underwent major elective vascular operations under general or peripheral anesthesia in their eighties and nineties in a 14-year period. Data for all consecutive 3,060 patients (456 of them > or years old) who underwent 3,314 elective vascular surgery procedures were prospectively entered into a computerized vascular registry. Detailed information was collected on patients' preoperative status, type of procedure and anesthesia, perioperative outcomes, and predictors of perioperative outcomes. The end points of the study were perioperative death and main surgical complications. Perioperative all-cause mortality rates varied across operations and were higher in elderly than in younger patients (1.4% vs. 0.2%, P = 0.014) after abdominal surgery (2.4% vs. 0.1%, P = 0.006) and especially after abdominal aortic aneurysm repair (2.8% vs. 0%, P = 0.035). In the elderly cohort, the mortality rate was <1% for almost 60% of all operations. In logistic regression analysis, only preoperative hypertension (odds ratio [OR] = 72.5, 95% confidence interval [CI] 9.4-557.6), congestive heart failure (OR = 16.5, 95% CI 2.3-115.9), and perioperative cardiac (OR = 20.7, 95% CI 1.6-273.8) and pulmonary (OR = 41.7, 95% CI 7.9-218.9) complications were associated with a higher 30-day death risk. In this series, perioperative outcomes were not influenced by the type of elective surgical procedure. Though overall mortality after major vascular surgery was higher in patients > or 80 years old, age per se was not an independent factor of a higher perioperative mortality risk or fatal and nonfatal complications.     

Unique sleep‐stage transitions determined by obstructive sleep apnea severity,age and gender

In obstructive sleep apnea, patients’ sleep is fragmented leading to excessive daytime sleepiness and co‐morbidities like arterial hypertension. However, traditional metrics are not always directly correlated with daytime sleepiness, and the association between traditional sleep quality metrics like sleep duration and arterial hypertension is still ambiguous. In a development cohort, we analysed hypnograms from mild (n = 209), moderate (n = 222) and severe (n = 272) obstructive sleep apnea patients as well as healthy controls (n = 105) from the European Sleep Apnea Database. We assessed sleep by the analysis of two‐step transitions depending on obstructive sleep apnea severity and anthropometric factors. Two‐step transition patterns were examined for an association to arterial hypertension or daytime sleepiness. We also tested cumulative distributions of wake as well as sleep‐states for power‐laws (exponent α) and exponential distributions (decay time τ) in dependency on obstructive sleep apnea severity and potential confounders. Independent of obstructive sleep apnea severity and potential confounders, wake‐state durations followed a power‐law distribution, while sleep‐state durations were characterized by an exponential distribution. Sleep‐stage transitions are influenced by obstructive sleep apnea severity, age and gender. N2 → N3 → wake transitions were associated with high diastolic blood pressure. We observed higher frequencies of alternating (symmetric) patterns (e.g. N2 → N1 → N2, N2 → wake → N2) in sleepy patients both in the development cohort and in a validation cohort (n = 425). In conclusion, effects of obstructive sleep apnea severity and potential confounders on sleep architecture are small, but transition patterns still link sleep fragmentation directly to obstructive sleep apnea‐related clinical outcomes like arterial hypertension and daytime sleepiness.     

Breast Osteoblast-like Cells: A Reliable Early Marker for Bone Metastases From Breast Cancer

Background

The development of bone metastasis from breast cancer results from a functional interaction between tumor cells and osteoclasts or osteoblasts. The main aim of this study was therefore to test the hypothesis that the appearance of breast osteoblast-like cells (BOLCs) in primary mammary lesions is a precursor (and hence an early predictor) of the formation of breast cancer metastases to bone.

Long-term response to interferon alpha is unrelated to“interferon sensitivity determining region” variability in patients with chronic hepatitis C virus-1b infection

Background/Aims: Contradictory data have been reported about the predictive value of the variability in interferon sensitivity determining region (ISDR) of hepatitis C virus (HCV) genotype-1b on response to interferon-alpha (IFN-α) therapy. The aim of this study was to examine this issue in a series of patients with long-term response to IFN treatment.Methods: We retrospectively analyzed 24 patients with chronic HCV genotype-1b infection treated with IFN-α (total dose median 677, range 216–1350 MU) selected in 6 Italian Liver Units. These patients were defined as true long-term responders (LTR) since they showed persisting biochemical and virological responses to IFN treatment (mean follow-up 38 months). HCV genomes from pretreatment serum samples were amplified and directly sequenced. The ISDR amino-acid sequences obtained were aligned and compared with the published sequence of HCV-J.Results: Amino-acid substitutions were found in 23 of the 24 patients, and 22 of them showed an H to R amino-acid change at codon 2218. Fourteen patients showed only one mutation (at codon 2218), two had 2, five had 3, one had 4 and one had 5 mutations. When we compared the ISDR sequences from the 24 LTR with those of non-responders (NR), we found no significant correlation between the number of mutations and the response to therapy.Conclusions: Our results demonstrate that the persisting efficacy of IFN treatment in patients with chronic HCV is not related to the number of ISDR amino acid susbstitutions of the infecting viruses. Further studies are needed to verify whether other NS5A sequences outside the ISDR might be involved in the mechanisms of IFN resistance.     

CD28 affects the earliest signaling events generated by TCR engagement

The efficiency and magnitude of T cell responses are influenced by ligation of the co-stimulatory receptor CD28 by B7 molecules expressed on antigen-presenting cells (APC). In contrast to most previous studies in which agonistic anti-TCR/CD3 and anti-CD28 antibodies were employed, here we have investigated the contribution of CD28 to T cell activation under physiological conditions of antigen presentation. Jurkat T cells and primary T cells from TCR-transgenic mice stimulated with superantigen and antigen, respectively, presented by B7-expressing APC were utilized. In both systems we show that inhibiting CD28/B7 interaction resulted in impaired TCR-induced tyrosine phosphorylation of the signal-transducing ζ chain and ZAP-70. Consistent with a blockade of TCR-proximal signaling events, Jurkat cells stimulated in the absence of CD28 ligation were found to have strongly diminished tyrosine phosphorylation of cellular substrates and downstream signaling pathways such as Ca²⁺ /calcineurin, ERK/MAPK and JNK. Our results provide evidence for a role of CD28 in enhancing TCR signaling capacity during the earliest stages of T cell : APC interaction.