Meta-analysis Of Retrospective Studies Research Articles

Hypomagnesemia and clinical benefits of anti-EGFR monoclonal antibodies in wild-type KRAS metastatic colorectal cancer: a systematic review and meta-analysis

Hypomagnesemia is a recognized side-effect of cetuximab- or panitumumab-based chemotherapy for metastatic colorectal cancer (mCRC). The clinical relevance of hypomagnesemia is under debate. Thus, a systematic review and meta-analysis of retrospective studies and randomized clinical trials (RCTs) comparing hypomagnesemia with normal magnesium levels in wild-type KRAS mCRC was performed. One RCT, two retrospective studies, and two American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) conference presentations from phase III RCTs involving 1723 patients were included in this study. Patients with hypomagnesemia demonstrated better progression-free survival (PFS) (Hazard ratio [HR]: 0.64; 95% confidence interval [CI]: 0.47–0.88), overall survival (OS) (HR: 0.72; 95% CI: 0.53–0.92), and objective response rate (ORR) (Risk ratio [RR]: 1.81; 95% confidence interval [CI]: 1.30–2.52). By subgroup analysis, frontline, later lines or combination therapy with hypomagnesemia were associated with PFS benefits (HR: 0.78; 95% CI: 0.62–0.98; HR: 0.60; 95% CI: 0.40–0.90; HR: 0.62; 95% CI: 0.41–0.94, respectively). In patients with wild-type KRAS mCRC, hypomagnesemia is associated with better clinical benefits of PFS, OS and ORR when treated with cetuximab- or panitumumab-based chemotherapy. Future clinical trials should corroborate its predictive role.

196 Meta-Analysis of the Effect of Intracranial Infections on Morbidity and Mortality of Civilian Craniocerebral Gunshot Injuries

Abstract INTRODUCTION Civilian gunshot wounds to the head (GSWH) are a significant cause of traumatic brain injury-related mortality in the US. Intracranial infections are feared delayed complications in civilian GSWH and the benefit of prophylactic antibiotics has not been thoroughly studied. METHODS We conducted a meta-analysis of retrospective studies. A database search was conducted in PubMed, EMBASE, Scopus, Web of Science and Cochrane Library for articles after 2000 for intracranial infections (meningitis, cerebritis, ventriculitis and cerebral abscess) after civilian GSWH. We compared the intracranial infection rate in patients who received antibiotic prophylaxis with those who did not. We also compared the mortality of postoperative patients developing intracranial infections with the rest, and their morbidity, as evidenced by their Glasgow Outcome Scale (GOS), and grouped as favorable (GOS 4–5) or unfavorable (GOS 2–3). RESULTS >We identified 64 relevant articles, 7 of which had extractable information. Two articles compared intracranial infection rates with and without antibiotic prophylaxis in 219 GSWH patients. Prophylactic antibiotics did not decrease the risk of developing intracranial infections (OR 1.84; 95% CI 0.93–3.62; P = 0.08). Five articles reported 509 patients admitted with GSWH, 91.9% male, mean age 26.6 years old. 224 patients survived resuscitation and surgery. Postoperative intracranial infections did not significantly increase mortality (OR 0.67; CI 0.19–2.43; P = 0.55), but led to more unfavorable outcomes (OR 4.86; CI 1.19–19.79; P = 0.03). Of note, 160 out of the 224 initial survivors (71.4%) were reported to have received prophylactic antibiotics. CONCLUSION Prophylactic antibiotics are routinely given to GSWH patients to prevent infections. This meta-analysis of retrospective studies suggests that 1. prophylactic antibiotics did not decrease the risk of intracranial infections; 2. the presence of intracranial infections in a GSWH setting did not affect mortality and 3. patients developing intracranial infections had worse neurological outcomes.

The Clinical Effect of Metformin on the Survival of Lung Cancer Patients with Diabetes: A Comprehensive Systematic Review and Meta-analysis of Retrospective Studies.

Preclinical investigations have revealed an anti-cancer effect of metformin. Several studies of metformin treatment have demonstrated the improved clinical outcomes of lung cancer patients with diabetes; however, the results have been inconsistent among studies. Our systematic review and meta-analysis aimed to summarize the up-to-date effects of metformin on diabetic lung cancer patients.A systematic search was performed for studies published. Then, these studies were evaluated for inclusion, and relevant data was extracted. The summary risk estimates for the associations of metformin treatment with overall survival (OS) and progression-free survival (PFS) were analyzed using random/fixed-effects models. Analyses stratified by histological type were also conducted. Based on the 10 studies included in our analysis, metformin treatment was found to significantly improve survival, corresponding to reductions of 23% and 47% in OS [hazard ratio (HR)=0.77, 95% confidence interval (95%CI)=0.66-0.9, p=0.001] and PFS (HR=0.53, 95%CI=0.41-0.68, p<0.001), respectively. In addition, significant improvements in the OS for non-small cell lung cancer (NSCLC) (HR=0.77, 95%CI=0.71-0.84, p=0.002) and small cell lung cancer (SCLC) (HR=0.52, 95%CI=0.29-0.91, p=0.022) were observed in association with metformin treatment in analysis stratified by histological type. This stratified analysis also revealed a significant improvement in PFS for both NSCLC (HR=0.53, 95%CI=0.39-0.71, p<0.001) and SCLC (HR=0.54, 95%CI=0.34-0.84, p=0.007). We found that metformin treatment significantly improved the OS and PFS of diabetic lung cancer patients, and our findings suggest that metformin might be an effective treatment option for diabetic patients with lung cancer.

John Kwoka's Mergers, Merger Control, and Remedies: A Critical Review

John Kwoka’s recently published Mergers, Merger Control, and Remedies (2015) has received considerable attention from both antitrust practitioners and academics. The book features a meta-analysis of retrospective studies of consummated mergers, joint ventures, and other horizontal arrangements. Based on summary statistics derived from these studies, Kwoka concludes that domestic antitrust agencies are excessively tolerant in their merger enforcement; that merger remedies are ineffective at mitigating market power; and that merger enforcement has become increasingly lax over time. We review both his evidence and his empirical methods, and conclude that serious deficiencies in both undermine the basis for these conclusions.

Incidence of Lymph Node Metastases in Apparent Early-Stage Low-Grade Epithelial Ovarian Cancer: A Comprehensive Review.

This study aimed to determine the incidence of lymph node (LN) metastases in presumed stage I-II low-grade epithelial ovarian cancer (EOC). Eligible studies were identified from MEDLINE and EMBASE (time frame, 2015-1975), that analyzed patients with clinical or radiologic presumed early-stage EOC who underwent a complete pelvic and para-aortic lymphadenectomy as part of their surgical staging. The number and site of dissected and involved LNs and the correlation with overall outcome are analyzed. The term low grade and also the older term well differentiated were used. Thirteen of 978 identified studies were selected, and 13 of 75 studies were identified as eligible. A total of 1403 patients were analyzed in these 13 retrospective studies. The final International Federation of Gynecology and Obstetrics staging after completed surgical staging was I to II in 912 patients (65%). A total of 338 patients (24%) had grade 1 tumors whereas 473 patients (34%) had grade 2, and 502 patients (36%) had grade 3 tumors. Systematic lymphadenectomy was performed in 1159 patients (83%), whereof 1142 (82%) were pelvic and para-aortic LN dissections.In 185 patients (13%), an upstaging from an apparent clinical stage I-II to IIIC occurred because of LN involvement: 64 (35%) of the patients had only pelvic LNs metastases, 69 (37%) had only para-aortic LNs metastasis, and 51 (28%) had both a pelvic and para-aortic LN involvement. When analyzing only the patients with low-grade (grade 1 as the old classification) presumed early-stage disease (n = 273), only 8 patients (2.9%; range, 0-6.2) were identified with LNs metastases present. The incidence of occult LN metastases in apparent early-stage low-grade EOC is 2.9% in a metaanalysis of retrospective studies. Future larger-scale prospectively assessed studies with established surgical quality of the LN dissection are warranted to establish the true incidence of LN metastasis in presumed early low-grade disease.

MP75-18 PARTIAL NEPHRECTOMY VERSUS RADICAL NEPHRECTOMY FOR CLINICAL T1B AND T2 RENAL MASS: A META-ANALYSIS OF OVER 9000 CASES

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy V1 Apr 2016MP75-18 PARTIAL NEPHRECTOMY VERSUS RADICAL NEPHRECTOMY FOR CLINICAL T1B AND T2 RENAL MASS: A META-ANALYSIS OF OVER 9000 CASES Maria Carmen Mir, Ithaar Derweesh, Francesco Porpiglia, Alessandro Volpe, Giacomo Novara, Vincenzo Ficarra, Nicola Pavan, Humberto Laydner, Jihad Kaouk, Homi Zargar, and Riccardo Autorino Maria Carmen MirMaria Carmen Mir More articles by this author , Ithaar DerweeshIthaar Derweesh More articles by this author , Francesco PorpigliaFrancesco Porpiglia More articles by this author , Alessandro VolpeAlessandro Volpe More articles by this author , Giacomo NovaraGiacomo Novara More articles by this author , Vincenzo FicarraVincenzo Ficarra More articles by this author , Nicola PavanNicola Pavan More articles by this author , Humberto LaydnerHumberto Laydner More articles by this author , Jihad KaoukJihad Kaouk More articles by this author , Homi ZargarHomi Zargar More articles by this author , and Riccardo AutorinoRiccardo Autorino More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1736AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Partial nephrectomy (PN) is the reference standard of management for cT1a (<4 cm) renal mass. However, its role in the management of larger tumors is still debated. We performed a meta-analysis of studies comparing radical nephrectomy (RN) to PN for cT1b and T2 renal mass. METHODS A systematic literature review was performed to identify pertinent studies published up to October 2015. PRISMA criteria were followed for article selection. Odds ratio (OR) was used for all binary variables, and weight mean difference (WMD) was used for the continuous parameters. Pooled estimates were calculated with fixed-effect model, if no significant heterogeneity was identified; alternatively, the random-effect model was used when significant heterogeneity was detected. Demographics, surgical, functional and oncological outcomes were compared between RN and PN. Sensitivity analysis was performed for studies related to cT2 (> 7 cm) tumors. RESULTS Twenty-two retrospective case-control studies including 9525 patients (RN=7269; PN=2256) were deemed eligible and included in the analysis. Patients undergoing PN were younger (WMD: 2.3 years; p<0.001), and with smaller masses (WMD: -0.65 cm, p<0.001), whereas there was no difference for the baseline renal function. RN was favored for shorter operative time (WMD: 17.7 min; p<0.001), lower estimated blood loss (WMD: -102.6; p<0.001), and lower odds of postoperative complications (OR: 1.74; p<0.001). PN was associated with improved preservation of renal function, as shown by higher postoperative eGFR (WMD: 12.4 ml/min; p<0.001) and lower postoperative onset of CKD (OR: 0.36; p<0.001). Likelihood of tumor recurrence was lower for PN (OR: 0.6; p<0.001), as well as cancer-specific (OR: 0.58; p=0.001) and all-cause mortality (OR: 0.67; p=0.005). A sensitivity analysis was performed for 4 available studies on T2 (> 7 cm) tumors (n=2004). Also in this subgroup, tumor size was smaller for PN (WMD: 1.8 cm; p=0.02). Also, higher estimated blood loss was found for PN (WMD: 107.6 m; p<0.001), as well as a higher likelihood of complications (OR: 2.5; p<0.001). Higher recurrence rate (OR: 0.52; p=0.003), and a higher cancer specific mortality (OR: 0.59; p=0.03) was recorded for RN group for cT2 only. Difference in tumor size between the study group is indicative of a selection bias in this metaanalysis of retrospective studies. CONCLUSIONS Current evidence suggests that PN does not compromise oncologic outcomes in larger tumors, and it may be associated with improved renal functional preservation, despite a higher risk of surgery-related complications. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e985-e986 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Maria Carmen Mir More articles by this author Ithaar Derweesh More articles by this author Francesco Porpiglia More articles by this author Alessandro Volpe More articles by this author Giacomo Novara More articles by this author Vincenzo Ficarra More articles by this author Nicola Pavan More articles by this author Humberto Laydner More articles by this author Jihad Kaouk More articles by this author Homi Zargar More articles by this author Riccardo Autorino More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Brachytherapy for prostate cancer: feasible but oncological equivalence unproven.

Brachytherapy for prostate cancer: feasible but oncological equivalence unproven.

Somatostatin analogues do not prevent carcinoid crisis.

Carcinoid crisis is a life-threatening syndrome of neuroendocrine tumors (NETs) characterized by dramatic blood pressure fluctuation, arrhythmias, and bronchospasm. In the era of booming anti-tumor therapeutics, this has become more important since associated stresses can trigger carcinoid crisis. Somatostatin analogues (SSTA) have been recommended for prophylactic administration before intervention procedures for functioning NETs. However, the efficacy is still controversial. The aim of this article is to review efficacy of SSTA for preventing carcinoid crisis. PubMed, Cochrane Controlled trials Register, and EMBASE were searched using 'carcinoid crisis' as a search term combining terms with 'somatostatin'; 'octreotide'; 'lanreotide' and 'pasireotide' until December 2013. Twenty-eight articles were retrieved with a total of fifty-three unique patients identified for carcinoid crisis. The most common primary sites of NETs were the small intestine and respiratory tract. The triggering factors for carcinoid crisis included anesthesia/ surgery (63.5%), interventional therapy (11.5%), radionuclide therapy (9.6%), examination (7.7%), medication (3.8%), biopsy (2%) and spontaneous (2%). No randomized controlled trials (RCTs) were identified and two case-control studies were included to assess the efficacy of SSTA for preventing carcinoid crisis by meta-analysis. The overall pooled risk of perioperative carcinoid crisis was similar despite the prophylactic administration of SSTA (OR 0.44, 95% CI: 0.14 to 1.35, p=0.15). SSTA was not helpful for preventing carcinoid crisis based on a meta-analysis of retrospective studies. Attentive monitoring and careful intervention are essential. Future studies with better quality are needed to clarify any effect of SSTA for preventing carcinoid crisis.

Does minimally-invasive pancreaticoduodenectomy have advantages over its open method? A meta-analysis of retrospective studies.

BackgroundWhile more and more open procedures now routinely performed using laparoscopy, minimally invasive pancreaticoduodenectomy (MIPD) remains one of the most challenging abdominal procedures. Therefore, we carried out this meta-analysis to evaluate whether MIPD is safe, feasible and worthwhile.MethodsPubMed, EMBASE, and Cochrane Library were searched to identify studies published between January 1994 and November 2013 comparing MIPD with open pancreaticoduodenectomy (OPD). Intraoperative outcomes, oncologic safety, postoperative complications, and postoperative recovery were evaluated.Results11 retrospective studies representing 869 patients (327 MIPDs, 542 OPDs) were included. MIPD was associated with a reduction in estimated blood loss (MD −361.93 ml, 95% CI −519.22 to −204.63 ml, p<0.001, I2 = 94%), wound infection (OR 0.41, 95% CI 0.22 to 0.78, p = 0.007, I2 = 0%), and hospital stay (MD −2.64 d, 95% CI −4.23 to −1.05 d, p = 0.001, I2 = 78%). However, it brings longer operative time (MD 105 min, 95% CI 49.73 to 160.26 min, p<0.001, I2 = 93%). There were no significant differences between the two procedures in likelihood of overall complications (p = 0.05), pancreatic fistula (PF) (p = 0.86), delayed gastric empting (DGE) (p = 0.96), positive surgical margins (p = 0.07), retrieval of lymph nodes (p = 0.48), reoperation (p = 0.16) and mortality (p = 0.64).ConclusionsOur results suggest that MIPD is currently safe, feasible and worthwhile. But considering the selection bias, complexity of MIPD and lack of long-term oncologic outcomes, we suggest it be performed in a high-volume pancreatic surgery center in selected patients.

Soy intake and endometrial cancer risk varies according to study population.

The plethora of often contradictory results published on the effect of soy on cancer risk point to both positive and negative effects in gynaecological cancer. Both a meta-analysis of retrospective studies by Myung et al. (BJOG 2009 116: 1697–705) and the single other prospective study examining the effect of soy and isoflavones (Ollberding et al. J Natl Cancer Inst. 2012 104:67–76) conclude that higher soy intake reduces the risk of endometrial cancer (OR 0.70 95% CI 0.57–0.86 and RR = 0.66, 95% CI 0.47–0.91, respectively). In the current study, Budhathoki et al. find a lack of association between endometrial cancer and soy food intake in Japanese women. Although this is in keeping with the findings of the subanalyses of Ollberding et al.'s multi-ethnic US cohort, the lack of association observed may have resulted from a loss of statistical power during stratification rather than a true effect. Notably, the consumption of soy products is much higher in the Japanese cohort than in the American cohort, making comparisons difficult. In the US study, the inverse association of intake with risk is seen in women with consumptions of total isoflavone of greater than 7.82 mg/1000 kcal per day. In comparison, in this study the median intake of the women even in the lowest tertile was 9.46 mg/1000 kcal per day. The opposing findings clearly highlight the dangers of extrapolating findings between different populations. Although not without its limitations, this large prospective population study with a high response rate to a validated questionnaire and a low loss to follow up, goes a long way towards answering whether any association with long-term soy intake and endometrial cancer risk exists within the Japanese population. Caution should be exercised when interpreting these findings, as the incidence of endometrial cancer was low and it is unclear whether follow up even beyond 12 years is sufficient to witness a true difference in cancer incidence. Budhathoki et al. use baseline food questionnaires upon which to base their associations. This presupposes that there will be no change in diet during the entire follow-up period. Although validation studies of this and other nutritional questionnaires have since confirmed that soy consumption was relatively stable over the study period, this should not be assumed at the start of a prospective study. Furthermore, although Budhathoki et al. adjust for a number of potential confounders, unaccounted variables and combinations of variables between the groups may have attenuated true associations. Indeed, the authors note reductions in risk were only seen in other published studies in overweight women. In the UK, the market for soy-based health products is relatively low, except as an alternative to traditional HRT. While it might be tempting to extrapolate the findings of this and other studies to validate the safety of isoflavone/soy supplementation and even its use in endometrial protection, the RCOG in their Scientific Impact Paper No. 6 Alternatives to HRT for the management of symptoms of the menopause still advise caution in recommending soy supplementation due to the danger of increasing endometrial cancer risk. We have no conflicts of interest to declare.

Prevalence of self-reported childhood abuse in psychosis: A meta-analysis of retrospective studies

There is extensive clinical literature reporting traumatic childhood experiences in patients with psychosis. A quantitative meta-analysis addressing the prevalence of self-reported childhood sexual (CSA), physical (CPA) and emotional abuse (CEA) in psychotic patients has yet to be done. We conducted, a systematic literature search to identify retrospective studies addressing self-reported childhood abuse in patients with DSM/ICD psychosis. Demographic, clinical, and methodological variables were extracted from each publication, or obtained directly from its authors. Quantitative meta-analysis of CSA, CPA, CEA in the sample of patients was performed. Statistical heterogeneity and publication bias were assessed and meta-regressions performed to control for different moderators.Twenty-three studies were retrieved and included a total of 2017 psychotic patients. The prevalence of self-reported CSA, CPA, CEA were respectively of 26%, 39% and 34%. Age, publication year, gender and substance abuse moderated CSA, while age, clinical setting and substance abuse moderated CPA. Results indicated that CEA was moderated by gender and publication year of the study. According to our meta-analysis, psychotic patients have a consistently high self-report of childhood traumatic events which are sexual, physical and emotional in nature. It is our opinion that clinicians should be trained and skilled to carefully investigate childhood abuse in psychosis.

Effectiveness of antiviral prophylaxis coupled with contact tracing in reducing the transmission of the influenza A (H1N1-2009): a systematic review

BackgroundDuring the very early stage of the 2009 pandemic, mass chemoprophylaxis was implemented as part of containment measure. The purposes of the present study were to systematically review the retrospective studies that investigated the effectiveness of antiviral prophylaxis during the 2009 pandemic, and to explicitly estimate the effectiveness by employing a mathematical model.MethodsA systematic review identified 17 articles that clearly defined the cases and identified exposed individuals based on contact tracing. Analysing a specific school-driven outbreak, we estimated the effectiveness of antiviral prophylaxis using a renewal equation model. Other parameters, including the reproduction number and the effectiveness of antiviral treatment and school closure, were jointly estimated.ResultsBased on the systematic review, median secondary infection risks (SIRs) among exposed individuals with and without prophylaxis were estimated at 2.1% (quartile: 0, 12.2) and 16.6% (quartile: 8.4, 32.4), respectively. A very high heterogeneity in the SIR was identified with an estimated I2 statistic at 71.8%. From the outbreak data in Madagascar, the effectiveness of mass chemoprophylaxis in reducing secondary transmissions was estimated to range from 92.8% to 95.4% according to different model assumptions and likelihood functions, not varying substantially as compared to other parameters.ConclusionsOnly based on the meta-analysis of retrospective studies with different study designs and exposure settings, it was not feasible to estimate the effectiveness of antiviral prophylaxis in reducing transmission. However, modelling analysis of a single outbreak successfully yielded an estimate of the effectiveness that appeared to be robust to model assumptions. Future studies should fill the data gap that has existed in observational studies and allow mathematical models to be used for the analysis of meta-data.

Reply to Head et al.

We thank Dr Kappetein’s group for their comments [1] regarding our manuscript [2] and we appreciate the opportunity to provide clarification. The first comment raises the concern that our article does not adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [3]. On a thorough review of the 27-point checklist, we have to admit that we have not provided the time frame in which the search for relevant articles was completed. All articles that appear in the MEDLINE database up to 12/1/2009 were searched for inclusion. We also did not provide registration information for our meta-analysis, as the registration process remains optional. Nevertheless, our study addresses all other relevant items from this extensive checklist to various degrees. The point of including other sources to identify relevant articles remains valid. However, the PRISMA guidelines do not require inclusion of other database sources such as Cochrane and Embase, as the authors of the letter seem to imply. In fact, as stated in the PRISMA document, the MEDLINE database remains one of the most comprehensive sources of healthcare information [3]. Dr Kappetein et al. note that in Fig. 2 of the manuscript, there is an outlying odds ratio (OR) of 17.241 from the Al-Radi et al. article [4]. They question how this was calculated when the reported hospital mortality was 1.5% for repair and 21% for replacement, and note that this would yield an OR of 21/1.5 = 14. Actually, what the authors of the comment have calculated is not an OR but a relative risk. The OR calculation in our manuscript was correct: 1/65 patients in the repair group and 29/137 in the replacement group died, yielding an OR of 17.18 (64 × 29/1 × 108). The slight discrepancy from the reported OR of 17.241 stems from the fact that we initially calculated the OR in the opposite direction to reflect survival for replacement compared to repair which was 0.058. Subsequently, we took the reciprocal that was rounded off for ease of presentation, since repair did show superiority compared to replacement. Our method for evaluating log-term survival has been well described and we refer the reader to the well-written article by Parmar et al. for greater insight into understanding the calculation and application of this method for obtaining summary statistics from time-to-event studies [5]. We examined the survival curves from each of the included studies and calculated log hazard ratios (and variances) using non-overlapping 6-month time intervals. This approach allows the investigator to calculate an overall log hazard ratio for each study. All of the included studies provided follow-up of at least 5 years with the exception of the study by Hickey et al. [6]. We are in agreement and have explicitly stated in our article that a meta-analysis of retrospective studies has inherent limitations which need to be considered. Unfortunately, upon searching the literature, we only found studies of retrospective nature. Short of a prospective randomized trial, patient characteristics, surgeon preference and technical ability will continue to play a role in mitral procedure selection. In trying to provide an evidence-based meta-analysis of clinically relevant studies, we selected for inclusion only those articles that would not obviously bias treatment strategy. For example, we excluded patients with hemodynamic instability, who would be more likely to undergo replacement. Therefore, our study provides a useful source of additional information to guide decision making in patients with ischemic mitral regurgitation.

Use of a genomic test (MammaPrint™) in daily clinical practice to assist in risk stratification of young breast cancer patients

Breast cancer as a heterogeneous disease demands reliable tools in order to identify those patients who most likely will benefit from receiving adjuvant treatment, such as chemotherapy. The MammaPrint test was established on the basis of a 70-gene expression profile. In this prospective study, the adaptation of MammaPrint™ into clinical work-up procedures was investigated in 56 patients with an average age of 45 years treated at a general hospital in Germany between 2004 and 2008. To assess the accuracy of MammaPrint in this younger patient group, a meta-analysis was performed on a subgroup from previously described retrospective studies (n = 689). 44 patients had MammaPrint results and were eligible for the analysis. The results revealed a low risk result in 29 patients and a high risk result in 15 patients. Using St. Gallen 2007 guidelines for risk assessment, the numbers were 4 for low risk and 6 for high risk, respectively, while 34 patients were classified as intermediate risk. In the group of women with intermediate risk, MammaPrint assigned 23 patients to low risk and 11 to the high risk group. In the meta-analysis of retrospective studies, 10 year overall survival for the low and high MammaPrint groups was 90.2 and 65.2%, respectively. Using gene expression analysis as additional tool, patients with an intermediate clinical risk can be accurately separated into low and high risk groups. The gene expression analysis provides more accurate information on recurrence risk compared to conventional clinicopathological criteria and thus may provide additional guidance in daily clinical practice in future. Results of further prospectively designed studies like the MINDACT trial will confirm the retrospective analysis and will determine how both low and high risk patients can best be treated.

September 10 Highlights

Bruno et al. studied patients with acute cerebral infarction. Admission hyperglycemia was associated with worse clinical outcomes, including a greater chance for intracerebral hemorrhage. This association was independent of rt-PA use or other factors that contribute to stroke outcomes, such as age, stroke severity, and history of diabetes mellitus. see page 669 by Roger Simon, MD In 1977 Meyers and Yamaguchi reported that glucose administration prior to experimental global cerebral ischemia in primates worsened neurologic outcome. A meta-analysis of retrospective studies has supported a correlation to this observation in clinical stroke morbidity and mortality.1 Large prospective trials now provide additional insight into this association. From the 1,259 patients in the TOAST trial of heparinoid treatment, admission hyperglycemia was associated with worse outcome in nonlacunar stroke but was not associated with hemorrhagic transformation.2 The Bruno et al. study analyzes data from the NINDS rt-PA trial, which again shows an association between admission hyperglycemia and stroke outcome, with hypertension as a covariable. Importantly, in this study hyperglycemic patients were at higher risk for symptomatic hemorrhage. Thus, normalization of glucose might be a reasonable component of acute stroke management if the risks of treatment induced hypoglycemia could be avoided.3 Curiously, 25 years after …