Complications after breast augmentation with dermal fillers containing copolyamide: A systematic review.

Background: Dermal fillers containing copolyamide are used for breast augmentation and are marketed under different labels, such as Aquafilling, Los Deline, Aqualift, and Activegel. In recent years, the number of publications reporting complications after use of these fillers has increased. Methods: Through a computerized search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of published studies on complications, treatment options, and radiological findings related to breast augmentation with dermal fillers containing copolyamide was performed. Publications between January 1, 2007, and January 23, 2023, were included. Retrieved studies were screened for inclusion and quality assessment. The Joanna Briggs checklist for case reports and the Strengthening the Reporting of Observational Studies in Epidemiology checklist for cross-sectional studies were used. Results: Sixteen studies met the inclusion criteria: 14 case reports and 2 retrospective cohort studies, including 196 women and 333 complications. Long-term complications (≥30 days after surgery) were described in 15 studies. The most commonly reported complications were nodules in the breast (130 patients), pain (92 patients), inflammation and/or infection (43 patients), breast deformities (35 patients), and migration of the filler to the pectoralis muscle, abdominal wall, thoracic wall, pubic area, back, or upper extremity (27 patients). The median time between injection of the dermal filler and any complication was 18 months, and the majority of patients with complications required surgical intervention. Conclusion: Given the reports of severe complications months to years after injection of dermal fillers containing copolyamide and the lack of studies evaluating long-term safety, our interpretation is that dermal fillers containing copolyamide should not be used for breast augmentation.

Treatment of orbital fractures - a critical analysis of ophthalmic outcomes and scenarios for re-intervention.

BACKGROUND: Malplaced implants in orbital reconstruction may lead to serious complications and necessitate re-intervention. The aim of this study was to describe outcomes, complications and scenarios of re-intervention in a historical case series of orbital fractures treated with free-hand orbital wall reconstruction. The main hypothesis was that early re-interventions are mainly because of malplaced implants in the posterior orbit. METHODS: Retrospective review of 90 patients with facial fractures involving the orbit, reconstructed with radiopaque orbital wall implants, from 2011 to 2016. Data were obtained from medical records and computed tomography images. Recorded parameters were fracture type, ocular injury, ocular motility, diplopia, eye position, complications and re-interventions. Secondary reconstructions because of enophthalmos were volumetrically evaluated. RESULTS: Early complications requiring re-intervention within 1 month were seen in 12 (13%) patients, where all except two were because of malplaced implants. The implant incongruence was without exception found in the posterior orbit. Late complications consisted of four (4%) cases of ectropion and five (5%) cases of entropion that needed corrective surgery. The majority of the patients with eye-lid complications had undergone repeated surgeries. Secondary orbital surgeries were performed in nine (10%) patients. Five of these patients had secondary reconstruction for enophthalmos and associated diplopia. None of these patients became completely free from either enophthalmos or diplopia after the secondary surgery. CONCLUSION: Re-intervention after orbital reconstruction is mainly related to malplaced implants in the posterior orbit. Incomplete results in patients requiring secondary surgery for enophthalmos infer the importance of accurate restoration of the orbit at primary surgery. Abstract presented at: Swedish surgery Week 2021 and SCAPLAS 2022.

Patient Reported Outcome Following the Skoog Unilateral Cleft Lip Repair among Adults- a Long-Term Cohort Study and Comparison to a Non-cleft Population.

OBJECTIVE: The study primarily aimed to compare satisfaction with lip appearance among adults treated for unilateral cleft lip and palate (UCLP) with Skoog's primary lip repair procedure to those without clefts. The secondary aim was to determine whether satisfaction with lip appearance and the desire to change the lip/face appearance correlated with the number of secondary lip revisions performed. DESIGN: Long-term follow-up. PATIENTS/SETTINGS: All UCLP patients treated at the Uppsala University Hospital born between 1960- and 1987 (n = 109) were invited. At an average of 37 years following the primary lip repair, the participation rate was 76% (n = 83). A control group of adults without cleft (n = 67) completed the same study protocol for comparison. MAIN OUTCOME MEASURES: Satisfaction with appearance was measured with The Satisfaction with Appearance Questionnaire (SWA) and a modified version of the Body Cathexis -Scale was used to assess the desire to change the lip and facial appearance. RESULTS: UCLP patients were less satisfied with their lip, face, and overall appearance and reported a greater desire to change the appearance of their lips and face than non-cleft controls (p < 0.001). Dissatisfaction with lip appearance correlated to a greater willingness to change the appearance of the lip and face. No correlation was found between satisfaction with appearance and the number of the previously performed secondary lip revisions. CONCLUSION: Adults treated for UCLP are less satisfied with the appearance of their lips compared to the non-cleft population. The number of secondary revisions does not necessarily correlate to greater satisfaction with lip appearance.

Use of the Cephalic Vein in DIEP Breast Reconstruction Does Not Increase Risk of Lymphedema of the Ipsilateral Arm.

SUMMARY: Flap failure is a rare but devastating complication in deep inferior epigastric perforator (DIEP) flap reconstructions. Common causes of partial or complete flap failure are related to venous congestion. Although the cephalic vein is usually a safe and reliable recipient vein for additional venous outflow, there is a hypothesized risk of donor-arm lymphedema secondary to lymphatic vessel damage in the vicinity of the cephalic vein or related to scarring and reduced venous backflow of the arm. The aim was to assess whether the cephalic vein as an additional recipient vessel, by means of the superficial inferior epigastric vein in DIEP flap breast reconstruction, was associated with long-term volume changes of the arm and/or symptoms of lymphedema. Arm volume was assessed preoperatively in patients scheduled to undergo unilateral delayed DIEP flap breast reconstruction at Uppsala University Hospital, Sweden, between 2001 and 2007. Long-term postoperative assessments were performed in 2015 to 2016. Water displacement and circumferential measurement were assessed preoperatively and postoperatively by the same lymphedema therapists. Patients were divided into two groups: DIEP reconstruction with the cephalic vein or without. Fifty-four patients fulfilled the inclusion criteria and completed the study, with a mean follow-up time of 136 months. There was no increased occurrence of lymphedema in the group undergoing DIEP flap reconstruction with the cephalic vein as extra venous drainage, based on an analysis of change from baseline in arm volume difference.This study shows that the cephalic vein can be used for secondary venous outflow in DIEP breast reconstruction without long-term risk of ipsilateral arm volume increase or symptoms of lymphedema. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

"Location of cutaneous malignant melanoma in Sweden 2004-2018 - mortality and sex differences".

BACKGROUND: Cutaneous malignant melanoma (CMM) is one of the most common causes of cancer-related death in Sweden. There is increasing evidence that localisation of the primary CMM lesion differs between sexes and is associated with different outcomes. However, definitive convincing data is lacking. AIMS: To describe changes in the distribution of CMM anatomical location over time according to sex and determine differences in mortality by location. METHOD: This is a retrospective nation-wide cohort study of all patients diagnosed with CMM in Sweden between 2004 and 2018. Hazard ratios (HRs) were calculated using a multivariate cox regression model adjusting for age, sex, T-stage, multiple melanomas and comorbidities. RESULTS: A total of 68,666 patients were included. In males, trunk CMM was the most common location (51% of all male CMM), with an increasing proportion over time. In females, lower extremity CMM had the largest proportion in 2004 (33%) followed by trunk CMM (27%). By 2018, trunk CMM became more common than lower extremity CMM in females. Upper and lower extremity CMMs had lower HR for all-cause mortality compared with trunk CMM (0.896 and 0.887, respectively, p<0.001), while head and neck CMM had higher HR compared with trunk CMM (1.090, p<0.001). Males had greater risk than females (HR 1.352, p<0.001). CONCLUSIONS: Head and neck CMMs were associated with increased risk of all-cause mortality, while both upper and lower extremity CMMs were associated with decreased risk. Both sexes had increasing proportions of trunk and upper extremity CMM over time, with corresponding decreases in lower extremity and, head and neck CMM.

[Filler injection for breast augmentation - potentially harmful injections]. / Bröstförstoring med fillers kan ge allvarliga komplikationer.

Breast augmentation using implants is one of the most frequently performed aesthetic surgical procedures worldwide. It is considered to be a safe procedure, but requires general anesthesia and recovery can take time. The global aesthetic industry has been searching for a less invasive procedure to increase breast volume. Since 2018 a filler, Los Deline, is being used for breast augmentation. Surgeons at breast units in Stockholm have encountered and treated patients with complications after injections with this filler. The filler can cause breast deformities, infections and also has the ability to migrate. These complications can be severe and require several surgical treatments. We do not consider Los Deline to be a safe product for breast augmentation.

Radiological evaluation in patients with clinical suspicion of cerebral venous sinus thrombosis presenting with nontraumatic headache - a retrospective observational study with a validation cohort.

BACKGROUND: Clinical suspicion of cerebral venous sinus thrombosis (CVST) is imprecise due to non-specific symptoms such as headache. The aim was to retrospectively assess the diagnostic value of nonenhanced CT (neCT) in patients with nontraumatic headache and clinically suspected CVST. METHODS: A retrospective consecutive series of patients referred 2013-2015 for radiology were evaluated. Eligible patients had nontraumatic headache and suspicion of CVST stated in the referral, investigated with CT venography (CTV) and nonenhanced CT (neCT). neCT scans were re-evaluated for the presence of CVST or other pathology. All CTVs were checked for the presence of CVST. The validation cohort consisted of 10 patients with nontraumatic CVT (2017-2019). RESULTS: Less than 1% (1/104) had a suspected thrombus on neCT, confirmed by subsequent CTV. The remaining 99% had a CTV excluding CVST. Eleven percent had other imaging findings explaining their symptoms. In the patient with CVST, the thrombosed dural sinus was high attenuating (maximum HU 89) leading to the suspicion of CVST confirmed by CTV. The validation cohort (n = 10) confirmed the presence of a high attenuating (HU > 65) venous structure in the presence of a confirmed thrombus in all patients presenting within 10 days (suspicion written in referral, 10%). CONCLUSIONS: Despite clinical suspicion, imaging findings of CVST in nontraumatic headache are uncommon. Evaluating neCT for high attenuation in dural sinuses, followed by CTV for confirmation in selected cases seems reasonable. CVST should be recognized by all radiologists and requires a high level of awareness when reading neCT for other indications.

Diagnostic value of alternative techniques to gadolinium-based contrast agents in MR neuroimaging-a comprehensive overview.

Gadolinium-based contrast agents (GBCAs) increase lesion detection and improve disease characterization for many cerebral pathologies investigated with MRI. These agents, introduced in the late 1980s, are in wide use today. However, some non-ionic linear GBCAs have been associated with the development of nephrogenic systemic fibrosis in patients with kidney failure. Gadolinium deposition has also been found in deep brain structures, although it is of unclear clinical relevance. Hence, new guidelines from the International Society for Magnetic Resonance in Medicine advocate cautious use of GBCA in clinical and research practice. Some linear GBCAs were restricted from use by the European Medicines Agency (EMA) in 2017.This review focuses on non-contrast-enhanced MRI techniques that can serve as alternatives for the use of GBCAs. Clinical studies on the diagnostic performance of non-contrast-enhanced as well as contrast-enhanced MRI methods, both well established and newly proposed, were included. Advantages and disadvantages together with the diagnostic performance of each method are detailed. Non-contrast-enhanced MRIs discussed in this review are arterial spin labeling (ASL), time of flight (TOF), phase contrast (PC), diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS), susceptibility weighted imaging (SWI), and amide proton transfer (APT) imaging.Ten common diseases were identified for which studies reported comparisons of non-contrast-enhanced and contrast-enhanced MRI. These specific diseases include primary brain tumors, metastases, abscess, multiple sclerosis, and vascular conditions such as aneurysm, arteriovenous malformation, arteriovenous fistula, intracranial carotid artery occlusive disease, hemorrhagic, and ischemic stroke.In general, non-contrast-enhanced techniques showed comparable diagnostic performance to contrast-enhanced MRI for specific diagnostic questions. However, some diagnoses still require contrast-enhanced imaging for a complete examination.

Sentinel Lymph Node Biopsy and Complete Lymph Node Dissection for Melanoma.

PURPOSE OF REVIEW: The main surgical treatment for invasive malignant melanoma consists of wide surgical and examination of the sentinel node and in selected cases complete lymph node dissection. The aim of this review is to present data for the optimal surgical management of patients with malignant melanoma. RECENT FINDINGS: A surgical excision margin of 1-2 cm is recommended for invasive melanoma depending on the thickness of the melanoma. Sentinel node biopsy may be considered for patients with at least T1b melanomas thickness 0.8 to 1.0 mm or less than 0.8 mm Breslow thickness with ulceration, classified as T1b lesion, per recent AJCC guidelines. Two randomized controlled trials have been published-DeCOG (German Dermatologic Cooperative Oncology Group Selective Lymphadenectomy) and MSLT-2 (Multicenter Selective Lymphadenectomy Trial) comparing the complete lymph node dissection (CLND) with observation after positive sentinel node biopsy. In the MSLT-2 study, the disease control rate was improved in the immediate CLND group compared with observation but there was no difference in 3-year melanoma specific survival (86% ± 1.3% and 86% ± 1.2%, respectively; p = 0.42). Isolated limb perfusion (ILP) or isolated limb infusion (ILI) with melphalan and actinomycin D is recommended for large and multiple in-transit metastases and satellite metastases in the extremities when local excision is considered ineffective or too extensive. In light of new adjuvant treatment options and new indications for checkpoint inhibitors, and the lack of survival benefit after CLND, we can expect open surgery to decrease in melanoma disease.

Arterial spin labeling MR imaging for differentiation between high- and low-grade glioma-a meta-analysis.

Background: Arterial spin labeling is an MR imaging technique that measures cerebral blood flow (CBF) non-invasively. The aim of the study is to assess the diagnostic performance of arterial spin labeling (ASL) MR imaging for differentiation between high-grade glioma and low-grade glioma. Methods: Cochrane Library, Embase, Medline, and Web of Science Core Collection were searched. Study selection ended November 2017. This study was prospectively registered in PROSPERO (CRD42017080885). Two authors screened all titles and abstracts for possible inclusion. Data were extracted independently by 2 authors. Bivariate random effects meta-analysis was used to describe summary receiver operating characteristics. Trial sequential analysis (TSA) was performed. Results: In total, 15 studies with 505 patients were included. The diagnostic performance of ASL CBF for glioma grading was 0.90 with summary sensitivity 0.89 (0.79-0.90) and specificity 0.80 (0.72-0.89). The diagnostic performance was similar between pulsed ASL (AUC 0.90) with a sensitivity 0.85 (0.71-0.91) and specificity 0.83 (0.69-0.92) and pseudocontinuous ASL (AUC 0.88) with a sensitivity 0.86 (0.79-0.91) and specificity 0.80 (0.65-0.87). In astrocytomas, the diagnostic performance was 0.89 with sensitivity 0.86 (0.79 to 0.91) and specificity 0.79 (0.63 to 0.89). Sensitivity analysis confirmed the robustness of the findings. TSA revealed that the meta-analysis was adequately powered. Conclusion: Arterial spin labeling MR imaging had an excellent diagnostic accuracy for differentiation between high-grade and low-grade glioma. Given its low cost, non-invasiveness, and efficacy, ASL MR imaging should be considered for implementation in the routine workup of patients with glioma.

The Skoog Lip Repair for Unilateral Cleft Lip Deformity: The Uppsala Experience.

BACKGROUND: The Uppsala Craniofacial Center has been treating patients with unilateral cleft lip deformity using the lip repair technique described by Tord Skoog. The aim of this study was to determine complications after lip surgery and the incidence and indications for lip revisions in all patients born with unilateral cleft lip from 1960 to 2004. METHODS: All patients who were born from 1960 to 2004 with unilateral cleft lip, cleft lip and alveolus, or cleft lip and palate and underwent lip repair were studied retrospectively. The timing, indication, complications of the primary procedure, and type of secondary surgery were recorded. Kruskal-Wallis and Fisher's exact tests were used, with Bonferroni correction. RESULTS: The study included 443 patients. The total rate of early surgical complications was 6 percent (n = 26). Secondary surgery for short upper lip was performed in 3.8 percent (n = 17), 8.4 percent (n = 37) underwent reduction of excess vermillion, 8.6 percent (n = 38) underwent scar revision, 11 percent (n = 51) underwent revision for incongruent vermillion-cutaneous border, and 10 percent (n = 45) underwent revision for other indications. Altogether, 45 percent had no secondary revisions. CONCLUSION: In conclusion, the Skoog lip repair is associated with a low total revision rate, and a short-lip deformity is rare. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Home institution bias in the New England Journal of Medicine? A noninferiority study on citation rates.

Recently, in the four top journals of humanities, an institutional bias towards publication of authors from Harvard and Yale was shown. The New England Journal of Medicine (NEJM) is today the highest ranked general medical journal. It is unknown if there exists institutional bias favoring publication of articles originating from Harvard University, since the NEJM is produced by the Massachusetts Medical Society with close connections to the Harvard University. We examined if studies originating from the Harvard University published in the NEJM were noninferior in terms of citation rates compared to articles with an origin outside Harvard University. We evaluated original research articles published in the NEJM in 2000 up until June 2001. A two-sample noninferiority test based on the primary endpoint of citations was performed. Twenty-two studies were affiliated to the Harvard University and 280 studies were not affiliated to the Harvard University. The mean number of citations for Harvard affiliated studies was 625 (95% CI 358-952, median 354) and for non-Harvard affiliated studies 493 (95% CI 421-569, median 303). The mean difference was not statistically different between affiliations, but fulfilled the requirements for noninferiority [132 (95% CI - 138-402, P = 0.343), Δ 200]. In summary, citation rates were comparable between studies origination from the Harvard University compared to non-Harvard Institutions. Based on these results there appears to be low risk of institutional bias in the publishing process of original studies in the NEJM.

Discrimination between primary low-grade and high-grade glioma with 11C-methionine PET: a bivariate diagnostic test accuracy meta-analysis.

OBJECTIVE: To perform a meta-analysis evaluating the diagnostic accuracy of 11C-methionine (MET) positron emission tomography (PET) to discriminate between primary low-grade glioma (LGG) and high-grade glioma (HGG). METHODS: A systematic database search was performed by a librarian in relevant databases with the latest search on 07 November 2016. Hits were assessed for inclusion independently by two authors. Individual patient data on relative MET uptake was extracted on patients examined pre-operatively with MET PET and subsequent neuropathological diagnosis of astrocytoma or oligodendroglioma. Individual patient data were analysed for diagnostic accuracy using a bivariate diagnostic random-effects meta-analysis model with restricted maximum likelihood estimation method. Bivariate meta-regression and subgroup analyses assessed study heterogeneity and validity. This study is registered with PROSPERO, number CRD42016050747. RESULTS: Out of 1828 hits, 13 studies comprising of 241 individuals were included in the quantitative and qualitative analysis. MET PET had an area under the bivariate summary receiver operating characteristics curve of 0.78 to discriminate between LGG and HGG and a summary sensitivity of 0.80 with 95% confidence interval (CI) (0.66-0.88) and a summary false positive rate of 0.28, 95% CI (0.19-0.38). Heterogeneity was described by; bias in patient inclusion, study quality, and ratio method. Optimal cutoff for relative MET uptake was 2.21. CONCLUSION: MET PET had a moderately high diagnostic accuracy for the discrimination between primary LGG and HGG. Advances in knowledge: MET PET can be used as a clinical tool for the non-invasive discrimination between LGG and HGG with a moderately high accuracy at cut-off 2.21.

Glioma Grade Discrimination with MR Diffusion Kurtosis Imaging: A Meta-Analysis of Diagnostic Accuracy.

Purpose To assess the diagnostic test accuracy and sources of heterogeneity for the discriminative potential of diffusion kurtosis imaging (DKI) to differentiate low-grade glioma (LGG) (World Health Organization [WHO] grade II) from high-grade glioma (HGG) (WHO grade III or IV). Materials and Methods The Cochrane Library, Embase, Medline, and the Web of Science Core Collection were systematically searched by two librarians. Retrieved hits were screened for inclusion and were evaluated with the revised tool for quality assessment for diagnostic accuracy studies (commonly known as QUADAS-2) by two researchers. Statistical analysis comprised a random-effects model with associated heterogeneity analysis for mean differences in mean kurtosis (MK) in patients with LGG or HGG. A bivariate restricted maximum likelihood estimation method was used to describe the summary receiver operating characteristics curve and bivariate meta-regression. Results Ten studies involving 430 patients were included. The mean difference in MK between LGG and HGG was 0.17 (95% confidence interval [CI]: 0.11, 0.22) with a z score equal to 5.86 (P < .001). The statistical heterogeneity was explained by glioma subtype, echo time, and the proportion of recurrent glioma versus primary glioma. The pooled area under the curve was 0.94 for discrimination of HGG from LGG, with 0.85 (95% CI: 0.74, 0.92) sensitivity and 0.92 (95% CI: 0.81, 0.96) specificity. Heterogeneity was driven by neuropathologic subtype and DKI technique. Conclusion MK shows high diagnostic accuracy in the discrimination of LGG from HGG. © RSNA, 2017 Online supplemental material is available for this article.

Outcome switching in randomized controlled oncology trials reporting on surrogate endpoints: a cross-sectional analysis.

Inconsistent reporting of clinical trials is well-known in the literature. Despite this, factors associated with poor practice such as outcome switching in clinical trials are poorly understood. We performed a cross-sectional analysis to evaluate the prevalence of, and the factors associated with outcome switching. PubMed and Embase were searched for pharmaceutical randomized controlled trials (RCTs) in oncology reporting on a surrogate primary outcome published in 2015. Outcome switching was present in 18% (39/216). First-author male sex was significantly more likely associated with outcome switching compared to female sex with an OR of 3.05 (95% CI 1.07-8.64, p = 0.04) after multivariable adjustment. For-profit funded RCTs were less likely associated with outcome switching compared to non-profit funded research with an OR of 0.22 (95% CI 0.07-0.74, p = 0.01). First author male sex was more likely associated with outcome switching compared to female sex in drug oncology RCTs reporting on a primary surrogate endpoint. For-profit funded research was less likely associated with outcome switching compared to research funded by non-profit organizations. Furthermore, 18 percent of drug oncology trials reporting on a surrogate endpoint could have a higher risk of false positive results due to primary outcome switching.

Self-declared stock ownership and association with positive trial outcome in randomized controlled trials with binary outcomes published in general medical journals: a cross-sectional study.

BACKGROUND: Describe the prevalence and types of conflicts of interest (COI) in published randomized controlled trials (RCTs) in general medical journals with a binary primary outcome and assess the association between conflicts of interest and favorable outcome. METHODS: Parallel-group RCTs with a binary primary outcome published in three general medical journals during 2013-2015 were identified. COI type, funding source, and outcome were extracted. Binomial logistic regression model was performed to assess association between COI and funding source with outcome. RESULTS: A total of 509 consecutive parallel-group RCTs were included in the study. COI was reported in 74% in mixed funded RCTs and in 99% in for-profit funded RCTs. Stock ownership was reported in none of the non-profit RCTs, in 7% of mixed funded RCTs, and in 50% of for-profit funded RCTs. Mixed-funded RCTs had employees from the funding company in 11% and for-profit RCTs in 76%. Multivariable logistic regression revealed that stock ownership in the funding company among any of the authors was associated with a favorable outcome (odds ratio = 3.53; 95% confidence interval = 1.59-7.86; p < 0.01). CONCLUSION: COI in for-profit funded RCTs is extensive, because the factors related to COI are not fully independent, a multivariable analysis should be cautiously interpreted. However, after multivariable adjustment only stock ownership from the funding company among authors is associated with a favorable outcome.

Ruptured carotid-ophthalmic aneurysm treatment: a non-inferiority meta-analysis comparing endovascular coiling and surgical clipping.

INTRODUCTION: Aneurysms of the carotid-ophthalmic segment are relatively rare, comprising only five percent of all intracranial aneurysms. There is no consensus regarding the optimal management for ruptured carotid-ophthalmic aneurysms, whether endovascular coiling or surgical clipping provide the most favourable patient outcome. The aim of this meta-analysis is to analyse these two treatment modalities for ruptured carotid-ophthalmic aneurysms with respect to independent clinical outcome. METHODS: We performed a systematic literature search in PubMed, Cochrane Central Registry of Controlled Trials and Clinicaltrials.gov for treatment of ruptured carotid-ophthalmic aneurysms, comparing endovascular coiling and surgical clipping. Primary outcome in the study was independent clinical patient outcome at follow up (defined as Glasgow Outcome Scale four-five). Secondary outcomes were poor clinical patient outcome, mortality and total angiographic occlusion. The meta-analysis was performed using the Mantel-Haenszel method for dichotomous outcome. RESULTS: Four studies met the inclusion criteria and were included in the meta-analysis. In total, 152 patients were included. Sixty-seven of these patients were treated with endovascular coiling and 85 patients were treated with microsurgical clipping. The proportion of patients with an independent clinical outcome after coiling and clipping was comparable, OR 1.04 (95% CI: 0.40, 2.71). The proportion of patients with an independent outcome in the endovascular group was 76% and in the surgical group 71%. Mortality between the two treatment arms was equal. CONCLUSION: Clinical outcome after endovascular coiling and surgical clipping for ruptured carotid-ophthalmic aneurysms was comparable between surgical clipping and endovascular coiling. There was no proven difference in clinical outcome after endovascular coiling and surgical clipping for ruptured carotid-ophthalmic aneurysms but the evidence was based on few studies of moderate to low quality and we cannot rule out the possibility of a difference in clinical outcome between the two treatment modalities.

The association of funding source on effect size in randomized controlled trials: 2013-2015 - a cross-sectional survey and meta-analysis.

BACKGROUND: Trials financed by for-profit organizations have been associated with favorable outcomes of new treatments, although the effect size of funding source impact on outcome is unknown. The aim of this study was to estimate the effect size for a favorable outcome in randomized controlled trials (RCTs), stratified by funding source, that have been published in general medical journals. METHODS: Parallel-group RCTs published in The Lancet, New England Journal of Medicine, and JAMA between 2013 and 2015 were identified. RCTs with binary primary endpoints were included. The primary outcome was the OR of patients' having a favorable outcome in the intervention group compared with the control group. The OR of a favorable outcome in each trial was calculated by the number of positive events that occurred in the intervention and control groups. A meta-analytic technique with random effects model was used to calculate summary OR. Data were stratified by funding source as for-profit, mixed, and nonprofit. Prespecified sensitivity, subgroup, and metaregression analyses were performed. RESULTS: Five hundred nine trials were included. The OR for a favorable outcome in for-profit-funded RCTs was 1.92 (95% CI 1.72-2.14), which was higher than mixed source-funded RCTs (OR 1.34, 95% CI 1.25-1.43) and nonprofit-funded RCTs (OR 1.32, 95% CI 1.26-1.39). The OR for a favorable outcome was higher for both clinical and surrogate endpoints in for-profit-funded trials than in RCTs with other funding sources. Excluding drug trials lowered the OR for a favorable outcome in for-profit-funded RCTs. The OR for a favorable surrogate outcome in drug trials was higher in for-profit-funded trials than in nonprofit-funded trials. CONCLUSIONS: For-profit-funded RCTs have a higher OR for a favorable outcome than nonprofit- and mixed source-funded RCTs. This difference is associated mainly with the use of surrogate endpoints in for-profit-financed drug trials.

Global DNA Methylation Analysis Identifies Two Discrete clusters of Pheochromocytoma with Distinct Genomic and Genetic Alterations.

Pheochromocytomas and paragangliomas (PPGLs) are rare and frequently heritable neural-crest derived tumours arising from the adrenal medulla or extra-adrenal chromaffin cells respectively. The majority of PPGL tumours are benign and do not recur with distant metastases. However, a sizeable fraction of these tumours secrete vasoactive catecholamines into the circulation causing a variety of symptoms including hypertension, palpitations and diaphoresis. The genetic landscape of PPGL has been well characterized and more than a dozen genes have been described as recurrently mutated. Recent studies of DNA-methylation have revealed distinct clusters of PPGL that share DNA methylation patterns and driver mutations, as well as identified potential biomarkers for malignancy. However, these findings have not been adequately validated in independent cohorts. In this study we use an array-based genome-wide approach to study the methylome of 39 PPGL and 4 normal adrenal medullae. We identified two distinct clusters of tumours characterized by different methylation patterns and different driver mutations. Moreover, we identify genes that are differentially methylated between tumour subcategories, and between tumours and normal tissue.