Prognostic value of the Geneva prediction rule in patients with pulmonary embolism

Background

Assessment of pre-test probability of pulmonary embolism (PE) and prognostic stratification are two widely recommended steps in the management of patients with suspected PE. Some items of the Geneva prediction rule may have a prognostic value.We analyzed whether the initial probability assessed by the Geneva rule was associated with the outcome of patients with PE.

Methods

In a post-hoc analysis of a multicenter trial including 1,693 patients with suspected PE, the all-cause death or readmission rates during the 3-month follow-up of patients with confirmed PE were analyzed. PE probability group was prospectively assessed by the revised Geneva score (RGS). Similar analyses were made with the a posteriori-calculated simplified Geneva score (SGS).

Results

PE was confirmed in 357 patients and 21 (5.9%) died during the 3-month follow-up. The mortality rate differed significantly with the initial RGS group, as with the SGS group. For the RGS, the mortality increased from 0% (95% Confidence Interval: [0–5.4%]) in the low-probability group to 14.3% (95% CI: [6.3-28.2%]) in the high-probability group, and for the SGS, from 0% (95% CI: [0–5.4%] to 17.9% (95% CI: [7.4-36%]). Readmission occurred in 58 out of the 352 patients with complete information on readmission (16.5%). No significant change of readmission rate was found among the RGS or SGS groups.

Conclusions

Returning to the initial PE probability evaluation may help clinicians predict 3-month mortality in patients with confirmed PE.(ClinicalTrials.gov: NCT00117169)     

Robotic Partial Nephrectomy with Superselective Versus Main Artery Clamping: A Retrospective Comparison

Background

Concerns have been raised regarding partial nephrectomy (PN) techniques that do not occlude the main renal artery.

Objective

Compare the perioperative outcomes of superselective versus main renal artery control during robotic PN.

Design, setting, and participants

A retrospective analysis of 121 consecutive patients undergoing robotic PN using superselective control (group 1, n = 58) or main artery clamping (group 2, n = 63).

Intervention

Group 1 underwent tumor-specific devascularization, maintaining ongoing arterial perfusion to the renal remnant at all times. Group 2 underwent main renal artery clamping, creating global renal ischemia.

Outcome measurements and statistical analysis

Perioperative and functional data were evaluated. The Pearson chi-square or Fisher exact and Wilcoxon rank sum tests were used.

Results and limitations

All robotic procedures were successful, all surgical margins were negative, and no kidneys were lost. Compared with group 2 tumors, group 1 tumors were larger (3.4 vs 2.6 cm, p = 0.004), more commonly hilar (24% vs 6%, p = 0.009), and more complex (PADUA 10 vs 8, p = 0.009). Group 1 patients had longer median operative time (p < 0.001) and transfusion rates (24% vs 6%, p < 0.01) but similar estimated blood loss (200 vs 150 ml), perioperative complications (15% vs 13%), and hospital stay. Group 1 patients had less decrease in estimated glomerular filtration rate at discharge (0% vs 11%, p = 0.01) and at last follow-up (11% vs 17%, p = 0.03). On computed tomography volumetrics, group 1 patients trended toward greater parenchymal preservation (95% vs 90%, p = 0.07) despite larger tumor size and volume (19 vs 8 ml, p = 0.002). Main limitations are the retrospective study design, small cohort, and short follow-up.

Conclusions

Robotic PN with superselective vascular control enables tumor excision without any global renal ischemia. Blood loss, complications, and positive margin rates were low and similar to main artery clamping. In this initial developmental phase, limitations included more perioperative transfusions and longer operative time. The advantage of superselective clamping for better renal function preservation requires validation by prospective randomized studies.

Patient summary

Preserving global blood flow to the kidney during robotic partial nephrectomy (PN) does not lead to a higher complication rate and may lead to better postoperative renal function compared with clamped PN techniques.     

Biological heterogeneity of er-positive breast cancers in the post-menopausal population

In the natural history of post-menopausal patients with primary breast cancer, high estrogen receptor levels (ER) have been associated with a poor recurrence-free survival. The purpose of this study was to investigate whether there are any biological intratumoral characteristics to support this puzzling clinical observation. In a population of 542 post-menopausal, primary-breast-cancer patients, 3 normal distributions fitted into the frequency distribution curve of the logarithmically transformed ER-EIA values. The biological profiles of the low ER group, and of the intermediate and high ER groups identified in the ER-positive population were compared. Parameters correlated with ER functional aspect (progesterone receptors and PS2), receptors of epidermal growth factor (EGFR), protease cathepsin D and tumor proliferation (deduced from thymidine kinase activity) were analyzed. As previously reported, the levels of progesterone receptors and PS2 increased significantly from the low to the high ER groups. The highest levels of cathepsin D and thymidine kinase which have been previously related to a poor prognosis in breast cancer were found in the low ER group, but high levels were, surprisingly, also found in the high ER group. This study indicates that the ER-positive post-menopausal population is biologically heterogeneous. The high levels of thymidine kinase found in the high ER group suggest that overexpression of ER may be associated with proliferation enhancement, partly explaining the poor spontaneous prognosis related to this subset.     

Cysticercosis as a major risk factor for epilepsy in Burundi,east Africa

PURPOSE: Human cysticercosis is a direct consequence of infection by Taenia solium larvae (Cysticercus cellulosae). Results of studies on the impact of neurocysticercosis on epilepsy in Africa are inconsistent. The objective was to evaluate the role of cysticercosis in epilepsy in Burundi. METHODS: A prevalent matched case-control design was used in the Kiremba area, Burundi, between March and April 2001. One case with epilepsy was matched to two control subjects, according to their age. Cases were subjects who had shown at least two unprovoked epileptic seizures within a 24-h time range and who lived in the Kiremba area. The control subjects also lived in Kiremba and had neither neurologic illness nor kinship with the people with epilepsy. Seropositivity for cysticercosis was the exposure variable. Three hundred twenty-four prevalent cases, with onset of epilepsy between 1950 and 2000, and 648 age-matched controls were included. RESULTS: This study found a link between cysticercosis infestation and the occurrence of epilepsy (odds ratio, 3.8; 95% confidence interval, 2.5-5.1). CONCLUSIONS: The study highlighted the importance of cysticercosis in the area of Kiremba, as 31.5% of the control subjects screened positive for this parasite. The attributable risk for cysticercosis was 50% (95% confidence interval, 42-57) in this population.     

Short-term survival of newborn neurons in the adult olfactory bulb after exposure to a complex odor environment

In the olfactory bulb of adult mice, new neurons are continually integrated into existing neuronal networks. Previous studies have demonstrated that exposure to a complex odor environment increases the incorporation of newborn bulbar neurons without modifying the proliferation rate. Whether this incorporation is transient or leads to the long-lasting presence of new neurons has not yet been answered. Because a transient increase of new neurons impacts olfactory information processing differently than a long-lasting increase, we conducted experiments to investigate the time course of survival and cell death of newly generated bulbar neurons following exposure to an enriched olfactory environment. Dividing cells were labeled with bromodeoxyuridine (BrdU) and were counted at several survival time points thereafter. Interestingly, whereas the number of surviving BrdU-labeled cells was elevated at the time when animals were withdrawn from their enriched housing, this number returned to control level 1 month later. Similarly, when olfactory memory was investigated, we found that the improvement of short-term memory, induced by enriched odor exposure, lasted less than 1 month. These findings indicate not only that the recruitment of newborn neurons closely followed the degree of environment complexity, but also that olfactory memory is tightly associated with the level of ongoing neurogenesis in the adult olfactory bulb.     

Hypogonadism in a patient with a mutation in the luteinizing hormone beta-subunit gene

A 30-year-old man who presented with delayed puberty and infertility was found to have hypogonadism associated with an absence of circulating luteinizing hormone. The patient had a homozygous missense mutation in the gene that encodes the beta subunit of luteinizing hormone (Gly36Asp), a mutation that disrupted a vital cystine knot motif and abrogated the heterodimerization and secretion of luteinizing hormone. Treatment with human chorionic gonadotropin increased circulating testosterone, promoted virilization, and was associated with the appearance of normal spermatozoa in low concentrations. This case illustrates the important physiological role that luteinizing hormone plays in male sexual maturation and fertility.     

High variability of plasma drug concentrations in dual protease inhibitor regimens

Ritonavir (RTV) strongly increases the concentrations of protease inhibitors (PIs) in plasma in patients given a combination of RTV and another PI. This pharmacological interaction is complex and poorly characterized and shows marked inter- and intraindividual variations. In addition, RTV interacts differently with saquinavir (SQV), indinavir (IDV), amprenavir (APV), and lopinavir (LPV). In this retrospective study on 542 human immunodeficiency virus-infected patients, we compared inter- and intraindividual variability of plasma PI concentrations and correlations between the C(min) (minimum concentration of drug in plasma) values for RTV and the coadministered PI C(min) values. Mean RTV C(min)s are significantly lower in patients receiving combinations containing APV or LPV than in combinations with SQV or IDV. With the most common PI dose regimens (600 mg of IDV twice a day [BID], 800 mg of SQV BID, and 400 mg of LPV BID), the interindividual C(min) variability of patients treated with a PI and RTV seemed to be lower with APV and LPV than with IDV and SQV. As regards intraindividual variability, APV also differed from the other PIs, exhibiting lower C(min) variability than with the other combinations. Significant positive correlations between RTV C(min) and boosted PI C(min) were observed with IDV, SQV, and LPV, but not with APV. Individual dose adjustments must take into account the specificity the pharmacological interaction of each RTV/PI combination and the large inter- and intraindividual variability of plasma PI levels to avoid suboptimal plasma drug concentrations which may lead to treatment failure and too high concentrations which may induce toxicity and therefore reduce patient compliance.     

Apoptosis and proliferation kinetics of T cells in patients having experienced antiretroviral treatment interruptions

Multiple failures of antiretroviral treatments, as a result of multidrug-resistant virus, have led to a proposal for structured therapeutic interruptions (STI). However, a significant decrease in CD4+ T cells may occur. The aim of our study was to determine the kinetics of T cell subpopulation changes, T cell apoptosis and peripheral blood mononuclear cell proliferation after STI. The impact of resistance mutation disappearance on T cell apoptosis was also studied. Ten patients were enrolled prospectively, and blood sampling was performed at weeks 0, 2, 4, 6, 8 and 12. The mean increase in viral load was 1.3 log(10) copies/ml, ranging from 0.1 to 3.2. CD4+ T cell count decreased to a mean of 80 cells/mm(3) from baseline to week 12. In the same period, CD8+ T cells decreased to a mean of 139 cells/mm(3). A significant increase in both T cell apoptosis and proliferation of mononuclear cells was observed. However, proliferation was an early and brief event. The increase in CD4+ T cell apoptosis was obvious in patients exhibiting complete reversion of resistance mutations to antiviral drugs. Our results suggest that during STI, apoptosis is an overwhelming phenomenon compared with proliferation, and may explain the limited immunological impact of this therapeutic option.     

Comparison of two clinical prediction rules and implicit assessment among patients with suspected pulmonary embolism

PURPOSE: Two prediction rules for pulmonary embolism have been described recently: the Wells' rule, which was derived from both outpatients and inpatients, and which includes a subjective element; and the Geneva rule, which is entirely standardized and is suitable only for emergency department patients. We compared the predictive accuracy and the concordance of the two methods, as well as the Geneva score overridden by implicit clinical judgment. SUBJECTS AND METHODS: We studied 277 consecutive patients admitted to the emergency departments of three teaching hospitals. Clinical probability was assessed prospectively with the Geneva score and the Geneva score overridden by implicit clinical judgment in case of a disagreement. The Wells' score was calculated retrospectively. RESULTS: The three methods classified similar proportions of patients as having a low (53% to 58% of patients), intermediate (37% to 41% of patients), or high (4% to 10% of patients) probability of pulmonary embolism. The actual frequencies of pulmonary embolism in each category were also similar (5% to 13% in the low, 38% to 40% in the intermediate, and 67% to 91% in the high clinical probability categories). Receiver operating characteristic curve analysis showed no difference between the two prediction rules, but the Geneva score overridden by implicit evaluation had a marginally higher accuracy. Concordance between the two prediction rules was fair (kappa coefficient = 0.43). Clinicians disagreed with the Geneva score in 21% of patients (n = 57). CONCLUSIONS: The two prediction rules had a similar predictive accuracy for pulmonary embolism among emergency department patients. The Geneva rule appears to be more accurate when combined with clinical judgment, although it does not apply to inpatients.