Primary hemiarthroplasty versus conservative treatment for comminuted fractures of the proximal humerus in the elderly (ProCon): A Multicenter Randomized Controlled trial

Background. Fractures of the proximal humerus are associated with a profound temporary and sometimes permanent, impairment of function and quality of life. The treatment of comminuted fractures of the proximal humerus like selected three-or four-part fractures and split fractures of the humeral head is a demanding and unresolved problem, especially in the elderly. Locking plates appear to offer improved fixation; however, screw cut-out rates ranges due to fracture collapse are high. As this may lead to higher rates of revision surgery, it may be preferable to treat comminuted fractures in the elderly primarily with a prosthesis or non-operatively. Results from case series and a small-sample randomized controlled trial (RCT) suggest improved function and less pain after primary hemiarthroplasty (HA); however these studies had some limitations and a RCT is needed. The primary aim of this study is to compare the Constant scores (reflecting functional outcome and pain) at one year after primary HA versus non-operative treatment in elderly patients who sustained a comminuted proximal humeral fracture. Secondary aims include effects on functional outcome, pain, complications, quality of life, and cost-effectiveness. Methods/Design. A prospective, multi-center RCT will be conducted in nine centers in the Netherlands and Belgium. Eighty patients over 65 years of age, who have sustained a three-or four part, or split head proximal humeral fracture will be randomized between primary hemiarthroplasty and conservative treatment. The primary outcome is the Constant score, which indicates pain and function. Secondary outcomes include the Disability of the Arm and Shoulder (DASH) score, Visual Analogue Scale (VAS) for pain, radiographic healing, health-related quality of life (Short-form-36, EuroQol-5D) and healthcare consumption. Cost-effectiveness ratios wi

The role of ADAMTS13 in acute myocardial infarction:cause or consequence?

ADAMTS13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, is a metalloprotease that cleaves von Willebrand factor (VWF). There is considerable evidence that VWF levels increase and ADAMTS13 levels decrease in ST-elevation myocardial infarction (STEMI) patients. It is unclear whether this contributes to no reflow, infarct size, and intramyocardial haemorrhage (IMH). We aimed to determine the role of ADAMTS13 in STEMI patients and to investigate the benefits of recombinant ADAMTS13 (rADAMTS13) in a porcine model of myocardial ischaemia-reperfusion. In 49 consecutive percutaneous coronary intervention (PCI)-treated STEMI patients, blood samples were collected directly after through 7 days following PCI. Cardiac magnetic resonance was performed 4-6 days after PCI to determine infarct size and IMH. In 23 Yorkshire swine, the circumflex coronary artery was occluded for 75 min. rADAMTS13 or vehicle was administered intracoronary following reperfusion. Myocardial injury and infarct characteristics were assessed using cardiac enzymes, ECG, and histopathology. In patients with IMH, VWF activity and VWF antigen were significantly elevated directly after PCI and for all subsequent measurements, and ADAMTS13 activity significantly decreased at 4 and 7 days following PCI, in comparison with patients without IMH. VWF activity and ADAMTS13 activity were not related to infarct size. In rADAMTS13-treated animals, no differences in infarct size, IMH, or formation of microthrombi were witnessed compared with controls. No correlation was found between VWF/ADAMTS13 and infarct size in patients. However, patients suffering from IMH had significantly higher VWF activity and lower ADAMTS13 activity. Intracoronary administration of rADAMTS13 did not decrease infarct size or IMH in a porcine model of myocardial ischaemia-reperfusion. These data dispute the imbalance in ADAMTS13 and VWF as the cause of no reflow

Residual disease at the bronchial stump after curative resection for lung cancer

The most important surgical goal during potentially curative surgery for non-small cell lung cancer (NSCLC) is a macroscopic and microscopic radical resection (R0-resection). Studies reporting on recurrence and long-term survival mainly comprise patients with completely resected NSCLC (R0-resection). However, there is limited data on incidence, treatment and prognosis of patients with microscopic residual tumour tissue at the bronchial resection margin (R1-resection). Furthermore, the definition of an R1-resection of the bronchial resection margin is not uniform in literature. Based on 19 studies published between 1945 and 2003 with a substantial number of included patients with resected NSCLC, the incidence of an R1-resection of the bronchial resection margin is approximately 4-5% (range 1.2-17%) of all lung resections. Divided into the localisation of the microscopic residual disease, survival of patients with carcinoma in situ (CIS) at the bronchial resection margin is comparable to the survival after a radical resection. The prognosis is negatively influenced in case of microscopic mucosal residual disease. Survival is even worse in patients with peribronchial residual disease; 1- and 5-year survivals range between 20-50% and 0-20%, respectively. This poor prognosis is because peribronchial residual disease, in 75-85% of the patients, is associated with mediastinal lymph node metastasis. According to the stage, survival of patients with stage I and II NSCLC and an R1-resection of the bronchial resection margin is significantly worse as compared to stage-corrected survival after a radical resection. In these patients, survival is limited due to local recurrence. The negative effect of an R1-resection of the bronchial margin in stage III NSCLC is limited, as these patients die due to disseminated disease (distant metastasis) before local recurrence occurs. A conservative approach with frequent bronchoscopic surveillance is justified for CIS. For patients with microscopic residual disease at the bronchial margin and stage I and II NSCLC, further treatment has to be considered. Adjuvant treatment in patients with stage III NSCLC has no proven benefit in terms of surviva

Prediction of long-term mortality following hip fracture surgery: evaluation of three risk models

Introduction: Several prognostic models have been developed for mortality in hip fracture patients, but their accuracy for long-term prediction is unclear. This study evaluates the performance of three models assessing 30-day, 1-year and 8-year mortality after hip fracture surgery: the Nottingham Hip Fracture Score (NHFS), the model developed by Holt et al. and the Hip fracture Estimator of Mortality Amsterdam (HEMA). Materials and methods: Patients admitted with a fractured hip between January 2012 and June 2013 were included in this retrospective cohort study. Relevant variables used by the three models were collected, as were mortality data. Predictive performance was assessed in terms of discrimination with the area under the receiver operating characteristic curve and calibration with the Hosmer–Lemeshow goodness-of-fit test. Clinical usefulness was evaluated by determining risk groups for each model, comparing differences in mortality using Kaplan–Meier curves, and by assessing positive and negative predictive values. Results: A total of 344 patients were included for analysis. Observed mortality rates were 6.1% after 30 days, 19.1% after 1 year and 68.6% after 8 years. The NHFS and the model by Holt et al. demonstrated good to excellent discrimination and adequate calibration for both short- and long-term mortality prediction, with similar clinical usefulness measures. The HEMA demonstrated inferior prediction of 30-day and 8-year mortality, with worse discriminative abilities and a significant lack of fit. Conclusions: The NHFS and the model by Holt et al. allowed for accurate identification of low- and high-risk patients for both short- and long-term mortality after a fracture of the hip. The HEMA performed poorly. When considering predictive performance and ease of use, the NHFS seems most suitable for implementation in daily clinical practice

Mortality Prediction in Hip Fracture Patients: Physician Assessment Versus Prognostic Models

Objectives:To evaluate 2 prognostic models for mortality after a fracture of the hip, the Nottingham Hip Fracture Score and Hip Fracture Estimator of Mortality Amsterdam and to compare their predictive performance to physician assessment of mortality risk in hip fracture patients.Design:Prospective cohort study.Setting:Two level-2 trauma centers located in the Netherlands.Patients:Two hundred forty-four patients admitted to the Emergency Departments of both hospitals with a fractured hip.Intervention:Data used in both prediction models were collected at the time of admission for each individual patient, as well as predictions of mortality by treating physicians.Main Outcome Measures:Predictive performances were evaluated for 30-day, 1-year, and 5-year mortality. Discrimination was assessed with the area under the curve (AUC); calibration with the Hosmer-Lemeshow goodness-of-fit test and calibration plots; clinical usefulness in terms of accuracy, sensitivity, and specificity.Results:Mortality was 7.4% after 30 days, 22.1% after 1 year, and 59.4% after 5 years. There were no statistically significant differences in discrimination between the prediction methods (AUC 0.73-0.80). The Nottingham Hip Fracture Score demonstrated underfitting for 30-day mortality and failed to identify the majority of high-risk patients (sensitivity 33%). The Hip fracture Estimator of Mortality Amsterdam showed systematic overestimation and overfitting. Physicians were able to identify most high-risk patients for 30-day mortality (sensitivity 78%) but with some overestimation. Both risk models demonstrated a lack of fit when used for 1-year and 5-year mortality predictions.Conclusions:In this study, prognostic models and physicians demonstrated similar discriminating abilities when predicting mortality in hip fracture patients. Although physicians overestimated mortality, they were better at identifying high-risk patients and at predicting long-term mortality.Level of Evidence:Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence

Mitotic index does not predict prognosis in stage IA non-small cell lung cancer

Despite radical resection, many patients with stage IA non-small cell lung cancer (NSCLC) die of metastatic disease, showing that apparently there were already micrometastases at the time of surgery. To identify patients at risk for metastatic disease, accurate prognostic factors are needed. Because the mitotic activity index (MAI) is of good prognostic value in several other cancers, we assessed its value in stage IA NSCLC. We assessed the MAI in the sections of 133 patients with radically resected stage IA NSCLC. MAI, histologic subtype, age, sex, location of tumor, type of surgery and tumor diameter were correlated with survival. The mean MAI was 29, ranging from 0 to 89. MAI was not correlated to histologic tumor type or lymph node sample procedure, or any of the other clinicopathologic features. No correlation was found between MAI and survival. Univariate analysis showed that only age was a significant predictor of survival (P = 0.0007). This was confirmed by multivariate analysis. The mitotic index is not a predictor of prognosis in stage IA NSCLC. Therefore other prognostic factors have to be investigated

Initial bronchoscopic treatment for patients with intraluminal bronchial carcinoids

OBJECTIVE: Carcinoid of the lung is considered low-grade malignancy, and less invasive treatment may therefore be considered. We analyzed the long-term outcome of initial bronchoscopic treatment in patients with intraluminal bronchial carcinoids. METHODS: Initial bronchoscopic treatment was applied to improve presurgical condition, to obtain tissue samples for proper histologic classification, and to enable less extensive parenchymal resection. For intraluminal bronchial carcinoid, complete tumor eradication with initial bronchoscopic treatment was attempted. High-resolution computed tomography in addition to bronchoscopy was used to determine intraluminal versus extraluminal tumor growth. Surgery followed in cases of atypical carcinoid, residue, or recurrence. RESULTS: Seventy-two patients, 43 of them female, have been treated (median age 47 years, range 16-80 years). Median follow-up has been 65 months (range 2-180 months). Fifty-seven (79%) had typical carcinoids and 15 (21%) had atypical carcinoids. Initial bronchoscopic treatment resulted in complete tumor eradication in 33 of 72 cases (46%), 30 typical and 3 atypical. Thirty-seven of 72 cases (51%), 11 atypical, required surgery (2 for late detected recurrences). Two patients had metastatic atypical carcinoid, 1 already at referral. Of the 6 deaths, 1 was tumor related. CONCLUSIONS: Initial bronchoscopic treatment is a potentially more tissue-sparing alternative than immediate surgical resection in patients with intraluminal bronchial carcinoids. For successful tumor eradication with initial bronchoscopic treatment in central carcinoids, assessment of intraluminal versus extraluminal growth may be of much more importance than histologic division between typical and atypical carcinoid. Disease-specific mortality is low, and long-term outcome has been excellent. Implementation of initial bronchoscopic treatment had no negative impact on surgical treatment outcom

Changes in Coronary Blood Flow After Acute Myocardial Infarction Insights From a Patient Study and an Experimental Porcine Model

The aim of this study was to determine the effects of an acute myocardial infarction (AMI) on baseline and hyperemic flow in both culprit and nonculprit arteries. An impaired coronary flow reserve (CFR) after AMI is related to worse outcomes. The individual contribution of resting and hyperemic flow to the reduction of CFR is unknown. Furthermore, it is unclear whether currently used experimental models of AMI resemble the clinical situation with respect to coronary flow parameters. Intracoronary Doppler flow velocity measurements were obtained in culprit and nonculprit arteries immediately after successfully revascularized ST-segment elevation myocardial infarction (n = 40). Stable patients without obstructive coronary artery disease served as control subjects and were selected by propensity-score matching (n = 40). Similar measurements in an AMI porcine model were taken both before and immediately after 75-min balloon occlusion of the left circumflex artery (n = 11). In the culprit artery, CFR was 36% lower than in matched control subjects (Δ = -0.9; 1.8 ± 0.9 vs. 2.8 ± 0.7; p < 0.001) with consistent observations in swine (Δ = -0.9; 1.5 ± 0.4 vs. 2.4 ± 0.9 for after and before AMI, respectively; p = 0.04). An increased baseline and a decreased hyperemic flow contributed to the reduction in CFR in both patients (baseline flow: Δ = +5 and hyperemic flow: Δ = -7 cm/s) and swine (baseline flow: Δ = +8 and hyperemic flow: Δ = -6 cm/s). Similar changes were observed in nonculprit arteries (CFR: 2.8 ± 0.7 vs. 2.0 ± 0.7 for STEMI patients and control subjects; p < 0.001). CFR significantly correlated with infarct size as a percentage of the left ventricle in both patients (r = -0.48; p = 0.001) and swine (r = -0.61; p = 0.047). CFR in both culprit and nonculprit coronary arteries decreases after AMI with contributions from both an increased baseline flow and a decreased hyperemic flow. The decreased CFR after AMI in culprit and nonculprit vessels is not a result of pre-existing microvascular dysfunction, but represents a combination of post-occlusive hyperemia, myocardial necrosis, hemorrhagic microvascular injury, compensatory hyperkinesis, and neurohumoral vasoconstrictio