Histopathological growth patterns of resected non-colorectal,non-neuroendocrine liver metastases: a retrospective multicenter study

Background

Distinct Histopathological Growth Patterns can be identified in liver metastases from melanoma, breast and colorectal cancers. For each of these distinct liver metastasis types the HGP has proven a biomarker for survival after partial hepatectomy, with the desmoplastic type marking favourable prognosis. Whether HGPs can be considered a pan-cancer phenomenon remains unknown. This study therefore evaluates the presence of HGPs and their prognostic value across non-colorectal non-neuroendocrine liver metastases.

Methods

A retrospective multicentre cohort study was performed in patients who underwent curative intent resection of non-colorectal non-neuroendocrine liver metastasis. HGPs were assessed on Haematoxylin and Eosin slides according to consensus guidelines and classified as desmoplastic or non-desmoplastic. Overall- and recurrence-free survival were evaluated using Kaplan–Meier and multivariable Cox regression analysis.

Results

In total, 132 patients with liver metastasis from 25 different tumour types were eligible for analysis, of which 26 (20%) had a desmoplastic HGP. Five-year OS and RFS (95%CI) were 53% (36–78%) versus 40% (30–53%), and 33% (19–61%) versus 15% (9–27%) for patients with desmoplastic compared to non-desmoplastic metastases, respectively (p?=?0.031 & p?=?0.004). On multivariable analysis (adjusted HR [95%CI]) a desmoplastic HGP was prognostic for both OS (0.46 [0.25–0.86]) and RFS (0.38 [0.21–0.69]).

Conclusions

This study demonstrates that HGPs apply to liver metastases across a wide variety of primary tumour origins. They hold a prognostic value in these cases, suggesting that HGPs could represent a pan-cancer biomarker for survival after surgical resection of liver metastases.

     

Sex differences in cardiac and autonomic response to clinical and experimental pain in LBP patients.

Rehabilitation professionals are currently using heart rate (HR) in order to assess the sincerity of effort in certain evaluations. It has been shown that a relation exists between HR and pain but no study has measured cardiac response during both clinical and experimental pain among a patient population using an intra-subject design. Thirty patients with low back pain (LBP) participated in this study including 16 men. Clinical pain was induced by applying a postero-anterior pressure (PA) on a painful lumbar segment for 15 and 30s in order to reproduce the patient's typical LBP at an intensity ranging between 50 and 70/100. Experimental pain was induced with a 15s thermal stimulus at a temperature which reproduced the same pain intensity as the 15s PA. For both reproduced clinical pain durations, we observed a rise in HR ranging between 8.5% and 12.67%. However, unlike men, women's cardiac response failed to show a constant rise in HR during the 30s PA. For all subjects, the rise in HR was much lower during the experimental pain condition (p<0.001), reaching only 5%. On the other hand, galvanic skin responses were significantly higher during the experimental pain condition (p<0.001). During this same condition, women also had a greater rise in galvanic skin responses than men (p=0.04). Finally, a significant correlation was found between both types of pain. These results suggest that pain induced during a clinical evaluation will produce a significant HR augmentation. However, heart rate variability analysis showed greater sympathetic cardiac regulation for men. The sex differences observed in this study call for caution when interpreting HR during pain assessment.     

Speckle tracking analysis allows sensitive detection of stress cardiomyopathy in severe aneurysmal subarachnoid hemorrhage patients

Purpose

Stress cardiomyopathy is a common life-threatening complication after aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that left ventricular (LV) longitudinal strain alterations assessed with speckle tracking could identify early systolic function impairment.

Methods

This was an observational single-center prospective pilot controlled study conducted in a neuro-intensive care unit. Forty-six patients with severe SAH with a World Federation of Neurological Surgeons grade (WFNS) ≥III were included. Transthoracic echocardiography (TTE) was performed on day 1, day 3, and day 7 after the patient’s admission. A cardiologist blinded to the patient’s management analyzed the LV global longitudinal strain (GLS). The control group comprised normal subjects matched according to gender and age.

Results

On day 1 median (25th–75th percentile) GLS was clearly impaired in SAH patients compared to controls [?16.7 (?18.7/?13.7) % versus ?20 (?22/?19) %, p < 0.0001], whereas LVEF was preserved [65 (59?70) %]. GLS was severely impaired in patients with a WFNS score of V versus III–IV [?15.6 (?16.9/?12.3) % versus ?17.8 (?20.6/?15.8) %, p = 0.008]. Seventeen (37 %) patients had a severe GLS alteration (>?16 %). In these patients, GLS improved from day 1 [?12.4 (?14.8/?10.9) %] to last evaluation [?16.2 (?19/?14.6) %, p = 0.0007] in agreement with the natural evolution of stress cardiomyopathy.

Conclusions

On the basis of LV GLS assessment, we demonstrated for the first time that myocardial alteration compatible with a stress cardiomyopathy is detectable in up to 37 % of patients with severe SAH while LVEF is preserved. GLS could be used for sensitive detection of stress cardiomyopathy. This is critical because cardiac impairment remains a major cause of morbidity and mortality after SAH.

     

Usefulness of B-type natriuretic peptide in elderly patients with acute dyspnea

Objective Differentiating cardiogenic pulmonary edema (CPE) from respiratory causes of dyspnea is particularly difficult in elderly patients. The aim of our study was to evaluate B-type natriuretic peptide (BNP) in patients older than 65 years presenting with acute dyspnea.Design Prospective study.Setting Medical emergency department of a 2000-bed urban teaching hospital.Patients Patients aged over 65 years presenting with acute dyspnea and a respiratory rate more than 25/min or a PaO₂ below 70 mmHg, SpO₂ less than 92%, PaCO₂ higher than 45 mmHg with pH less than 7.35, were included. BNP levels, measured blind at admission were compared with the final diagnosis (CPE or no CPE) as defined by experts.Intervention None.Measurements and results Three hundred eight patients (mean age of 80 years) were enrolled in the study. The median BNP was 575 pg/ml [95% confidence interval (CI): 410–898] in the CPE group (n=141) versus 75 pg/ml (95% CI: 59–98) in the no CPE group (n=167) (p<0.001). The best threshold value of BNP was 250 pg/ml, with a sensitivity and specificity for CPE of 0.78 (95% CI: 0.71–0.84) and 0.90 (95% CI: 0.84–0.93), respectively. The area under the ROC curve was 0.874±0.081 (p<0.001). The accuracy of BNP-assisted diagnosis was higher than that of the emergency physician (0.84 versus 0.77, p<0.05).Conclusion Analysis of BNP is useful in elderly patients with acute dyspnea, but the threshold value is higher than that previously determined.Presented, in part, at the 30^th annual congress of the Société de Réanimation de Langue Française, Paris, January 2002 (abstract no. SP 94).     

Establishing a link between heart rate and pain in healthy subjects: a gender effect.

Heart rate (HR) is currently used by rehabilitation clinicians as a complementary objective measure of pain. The premise is that, as pain increases, HR should also increase. However, this relationship is not clearly established. The goal of this study was to verify the relationship between HR and pain perception. Thirty-nine healthy volunteers participated in this experimental study. Painful stimuli were induced by a 2-minute immersion of the hand in hot water (47 degrees C). HR was recorded before and during the stimulation and was matched to a pain rating. We observed a rise of 11% in HR after 2 minutes of immersion. There was a significant intrasubject correlation between HR and pain intensity (r = 0.50, P < .001) and pain unpleasantness (r = 0.55, P < .001). Furthermore, there was a strong gender effect in the intersubject correlations. Men presented a strong correlation between mean HR and mean pain perception (intensity: r = 0.77, unpleasantness: r = 0.86), whereas this relationship was absent in women (intensity: r = -0.2, unpleasantness: r = 0.001). In conclusion, results show that, for healthy volunteers, experimental pain can elicit a rise in HR up to 11%. Moreover, the relationship between HR response and pain is gender related. Considering that a positive relationship between HR and pain perception was only found in men, these results do not support a clinical significance of the use of HR for pain evaluation in women. Clinical implications need to be further evaluated with patients before clinicians can use HR as a complementary tool in pain assessment. PERSPECTIVE: A positive correlation between HR and pain was observed for men but not for women. These differences underline the importance of taking into account gender differences in the development of complementary pain assessment. Further research should be conducted to verify the role of sex hormones on heart rate and pain.     

Combined measurements of N-terminal pro-brain natriuretic peptide and cardiac troponins in potential organ donors

Objective Brain death may induce cardiac dysfunction. In potential organ donors measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP) and circulating cardiac troponins T and I (cTnT and cTnI), alone or in combination, are performed to investigate the accuracy of these biomarkers for early diagnosis of left ventricular systolic dysfunction. Design and setting Prospective study in a multidisciplinary intensive care unit of an university hospital. Patients 63 brain-dead patients scheduled for multiple organ harvesting. Measurements and results We measured NT-proBNP, cTnT, and cTnI and determined fractional area change (FAC) using transesophageal echocardiography. Forty-five patients had normal FAC, 9 a moderate decrease in FAC (30–50), and 9 a severe decrease in FAC (≤ 30%). NT-proBNP and cTnT concentrations were significantly higher in patients with a severe decrease in FAC than in those with a moderate decrease. Combining measurements of these two biomarkers, the sensitivity of the test to predict severe decrease in FAC increased significantly to reach 1.00 compared with the sensitivities of individual measurements. The ROC curve area of combined measurements of NT-proBNP and cTnT was significantly higher than single measurements: 0.87 vs. 0.82 for NT-proBNP, 0.78 for cTnT, and 0.72 for cTnI. Conclusions In potential organ donors the combined measurement of NT-proBNP and cTnT concentrations is more accurate than individual measurement of NT-proBNP, cTnT, and cTnI in the early diagnosis of severe left ventricular systolic dysfunction. These findings may lead to improve the quality of cardiac care of the potential organ donors.     

The Effect of Dumping on Weight Loss in Conversion of Failed Restrictive Surgery: a Cross-Sectional Pilot Study

Purpose

Dumping is currently seen as a negative side effect of Roux-en-Y gastric bypass (RYGB). However, it may help patients to comply with their prescribed diet. In this study, we assess the role of dumping on weight loss in patients who have undergone conversion of failed restrictive surgery into RYGB.

Methods

An analysis was performed of 100 consecutive patients who underwent revisional RYGB (rRYGB) between 2006 and 2011 due to inadequate weight loss or band intolerance after laparoscopic adjustable gastric banding (LAGB). The percentage of excess weight loss (%EWL) was used to evaluate weight reduction. The Sigstad clinical diagnostic index was used to detect dumping symptoms.

Results

Fifty-five patients (59.1%) suffered from dumping. Overall, dumpers showed a greater %EWL than non-dumpers (83.8 ± 48.0 vs 66.9 ± 44.1%, respectively, p = 0.0725). When rRYGB was performed because of inadequate weight loss following LAGB, dumping played a crucial role in weight loss (88.0 ± 21.2 vs 68.9 ± 34.5%, p = 0.0137). This effect positively correlates to post-LAGB body mass index (BMI) with a statistically significant result at BMI >?35 kg/m² (82.4 ± 15.7 vs 58.4 ± 32.4%, p = 0.00341). A regression analysis of the Sigstad dumping score and %EWL shows that dumping tends to increase the %EWL.

Conclusions

This study provides new insights into the effect of dumping on weight loss in patients who underwent conversion of failed restrictive surgery into RYGB. Based on the findings in our patient group, we suggest that dumping helps patients achieve sustainable weight loss. Therefore, dumping can be regarded as a positive side effect rather than a complication.

     

Cost-effectiveness of activated protein C in real-life clinical practice

Background

Recombinant human activated protein C (rhAPC) has been reported to be cost-effective in severely ill septic patients in studies using data from a pivotal randomized trial. We evaluated the cost-effectiveness of rhAPC in patients with severe sepsis and multiple organ failure in real-life intensive care practice.

Methods

We conducted a prospective observational study involving adult patients recruited before and after licensure of rhAPC in France. Inclusion criteria were applied according to the label approved in Europe. The expected recruitment bias was controlled by building a sample of patients matched for propensity score. Complete hospitalization costs were quantified using a regression equation involving intensive care units variables. rhAPC acquisition costs were added, assuming that all costs associated with rhAPC were already included in the equation. Cost comparisons were conducted using the nonparametric bootstrap method. Cost-effectiveness quadrants and acceptability curves were used to assess uncertainty of the cost-effectiveness ratio.

Results

In the initial cohort (n = 1096), post-license patients were younger, had less co-morbid conditions and had failure of more organs than did pre-license patients (for all: P < 0.0001). In the matched sample (n = 840) the mean age was 62.4 ± 14.9 years, Simplified Acute Physiology Score II was 56.7 ± 18.5, and the number of organ failures was 3.20 ± 0.83. When rhAPC was used, 28-day mortality tended to be reduced (34.1% post-license versus 37.4% pre-license, P = 0.34), bleeding events were more frequent (21.7% versus 13.6%, P = 0.002) and hospital costs were higher (€47,870 versus €36,717, P < 0.05). The incremental cost-effectiveness ratios gained were as follows: €20,278 per life-year gained and €33,797 per quality-adjusted life-year gained. There was a 74.5% probability that rhAPC would be cost-effective if there were willingness to pay €50,000 per life-year gained. The probability was 64.3% if there were willingness to pay €50,000 per quality-adjusted life-year gained.

Conclusion

This study, conducted in matched patient populations, demonstrated that in real-life clinical practice the probability that rhAPC will be cost-effective if one is willing to pay €50,000 per life-year gained is 74.5%.     

Anti-citrullinated peptides antibodies in systemic sclerosis: Meta-analysis of frequency and meaning

Objectives

Diagnosis of systemic sclerosis (SSc) is partially determined by the presence of specific autoantibodies often associated with specific clinical features. Recent studies report the presence of ACPA in SSc. We aimed to evaluate the prevalence of ACPA in SSc and to assess their influence on clinical presentation of SSc.