No Transfer of Pressure to Adjacent Discs During Human Low-Pressure Controlled Discography: A Prospective Clinical Study.

Background: A substantial part of low back pain (LBP) originates from degeneration of the intervertebral disc. To confirm the diagnosis of discogenic pain, provocation discography seems the best available tool. However, provocation discography is also considered to be a controversial and subjective test because the patient's personal pain response is the most crucial for the result of the test. Recently, an in vivo porcine study and a study in nine human subjects showed passing of pressure to the adjacent discs during discography. This could mean that the concordant pain the patient describes originates from an adjacent disc. The object of this study is to assess if during human lumbar pressure-controlled provocation discography there is pressure transmission to adjacent discs. Methods: Consecutive patients between age 18 and 65 years with intractable low back pain and at least 50% preserved height of the suspected painful disc were included. Exclusion criteria were prior lumbar surgery of the suspected level, use of anticoagulants, pregnancy, local infection, and iodine allergy. An arterial blood pressure monitoring system simultaneously assessed the pressure in the adjacent discs while low-speed flow, pressure-controlled discography was performed. Results: In 50 patients with a positive discography, the average intradiscal peak pressure was 15.1 psi (SD = 11.1). In 48 procedures, no pressure rise in the adjacent discs was found. A small pressure rise (1.1 psi) in the adjacent disc during discography was recorded in two patients. Conclusions: Pressure rise in adjacent discs does not seem to occur during low-speed flow pressure-controlled lumbar provocation discography. False-positive pain reactions caused by potentially painful adjacent discs are therefore unlikely during pressure-controlled discography.

Whole liver CT texture analysis to predict the development of colorectal liver metastases-A multicentre study.

OBJECTIVES: CT texture analysis has shown promise to differentiate colorectal cancer patients with/without hepatic metastases. AIM: To investigate whether whole-liver CT texture analysis can also predict the development of colorectal liver metastases. MATERIAL AND METHODS: Retrospective multicentre study (n=165). Three subgroups were assessed: patients [A] without metastases (n=57), [B] with synchronous metastases (n=54) and [C] who developed metastases within ≤24 months (n=54). Whole-liver texture analysis was performed on primary staging CT. Mean grey-level intensity, entropy and uniformity were derived with different filters (σ0.5-2.5). Univariable logistic regression (group A vs. B) identified potentially predictive parameters, which were tested in multivariable analyses to predict development of metastases (group A vs. C), including subgroup analyses for early (≤6 months), intermediate (7-12 months) and late (13-24 months) metastases. RESULTS: Univariable analysis identified uniformity (σ0.5), sex, tumour site, nodal stage and carcinoembryonic antigen as potential predictors. Uniformity remained a significant predictor in multivariable analysis to predict early metastases (OR 0.56). None of the parameters could predict intermediate/late metastases. CONCLUSIONS: Whole-liver CT-texture analysis has potential to predict patients at risk of developing early liver metastases ≤6 months, but is not robust enough to identify patients at risk of developing metastases at later stage.

Vagus Nerve Stimulation in children: A focus on intellectual disability.

INTRODUCTION: Vagus Nerve Stimulation (VNS) can be an efficacious add-on treatment in patients with drug-resistant epilepsy, who are not eligible for surgery. Evidence of VNS efficacy in children with intellectual disability (ID) is scarce. OBJECTIVES: The purpose of this study was to review all available VNS data in the pediatric population (≤18 years old) and focus on the subpopulation with ID since appropriate treatment of these children is often challenging and complex. METHODS: Cochrane, EMBASE, PubMed and MEDLINE were used to collect all research associated to VNS and ID (or synonyms) leading to a total of 37 studies. Seven studies showed the results of patients with ID and those without separately; thereby only these studies were included in the VNS meta-analysis. RESULTS: Our meta-analysis showed that VNS was less effective in pediatric epilepsy patients with ID compared to those without ID (Mantel-Haenszel meta-analysis; p = 0.028, OR 0.18 (CI 95% 0.039-0.84)). However, there were no prospective controlled studies. Numerous studies reported quality of life (QoL) improvements in this subpopulation. The most common adverse events were transient and well tolerated. Side effects on cognition and behavior were not reported. DISCUSSION: These results might be a reason to consider VNS early on in the treatment of this subgroup. The significantly greater amount of retrospective studies, differences in follow-up (FU), lack of control data, heterogeneous series and limited number of patients could have biased the outcome measurements. Hence, current data do not exclude VNS for children with drug-resistant epilepsy and ID but should be interpreted with caution.

The Influence of Pre- and Postoperative Fear Avoidance Beliefs on Postoperative Pain and Disability in Patients With Lumbar Spinal Stenosis: Analysis of the Lumbar Spinal Outcome Study (LSOS) Data.

STUDY DESIGN: Prospective multicenter cohort study. OBJECTIVE: To evaluate the effect of pre- and postoperatively assessed fear avoidance beliefs (FAB) on pain and disability in patients with degenerative lumbar spinal stenosis (LSS) after decompression surgery. SUMMARY OF BACKGROUND DATA: To the present, the influence of pre- and postoperative FAB on the prognosis after surgery for LLS is still unclear. METHODS: Patients of the Swiss Lumbar Stenosis Outcome Study (LSOS) with confirmed LSS undergoing first-time decompression without fusion were enrolled in this study. The main outcome of this study was minimal clinically important difference (MCID) in spinal stenosis measure symptoms (pain) and function (disability) after 12 months. To analyze the influence of pre- and postoperatively assessed FAB on pain and disability we built simple and multiple logistic regression models. RESULTS: In this analysis of 234 patients undergoing decompression surgery for symptomatic degenerative LSS we found baseline FAB measured by the FAB physical activity subscale (FABQ-P) not to be associated with pain (OR 0.95; 95% CI: 0.55-1.67) and disability (OR 1.11; 95% CI: 0.64-1.92) at 12 months' follow-up. In the final multiple logistic regression models patients with high FABQ-P at 6 months (OR 0.46; 95% CI: 0.24-0.91) and high persistent FABQ-P at baseline and 6 months (OR 0.34, 95% CI: 0.16-0.73) were less likely to report a MCID for spinal stenosis measure symptoms at 12 months. Our analysis found a similar trend for disability; however, the results were not statistically significant. CONCLUSION: In elderly patients undergoing decompression surgery for symptomatic degenerative LSS preoperative fear avoidance beliefs were not a prognostic indicator for the outcome. Patients with FAB at 6 months and persistent FAB were less likely to experience clinically relevant improvement in pain at 12 months. Studies should address the importance of persistent postoperative FAB. LEVEL OF EVIDENCE: 3.

Predictive Factors for Successful Outcome of Pulsed Radiofrequency Treatment in Patients with Intractable Lumbosacral Radicular Pain.

BACKGROUND: In a previous prospective study on pulsed radiofrequency (PRF) treatment adjacent to the lumbar dorsal root ganglion (DRG) for patients with chronic lumbosacral radicular pain, we reported success in 55.4% of the patients at 6 months. Identification of predictors for success after PRF may improve outcome. We assessed the predictors of PRF in patients with chronic intractable lumbosacral radicular pain. METHODS: Patients with monosegmental chronic lumbosacral radicular pain of L5 or S1 first received a selective nerve root block at the corresponding level. Independent of the result of this block a PRF treatment at the same level was performed. At 6 weeks, 3 months, and 6 months after the procedure the outcome was evaluated. RESULTS: A positive diagnostic nerve root block and age ≥ 55 were predictive factors for successful outcome at 6 months, while disability was a negative predictor.The use of failed back surgery syndrome, gender, duration of pain, Numerical Rating Scale, level and side of treatment, DN4, and RAND-36 as predictors for success was not supported. CONCLUSIONS: Successful outcome after PRF adjacent to the DRG, in patients with intractable chronic lumbosacral radicular pain, is more likely in patients ≥ 55 years, with limited disability and after a positive diagnostic nerve root block. A combination of all these factors creates a fair predictive value (AUC: 0.73).

Do associated auto-antibodies influence the outcome of myasthenia gravis after thymectomy?

Myasthenia gravis (MG) is a neuromuscular autoimmune disease, where antibodies against the acetylcholine receptor destroy this receptor. The role of thymectomy in the treatment of MG remains controversial. Because of the frequent association with other autoimmune diseases, we hypothesized that patients with multiple autoantibodies (autoAbs) might have a lower chance of reaching complete stable remission after thymectomy. We analyzed sera of 85 MG patients who underwent a thymectomy between April 2004 and December 2012. We used four different immunodot kits (D-Tek, Mons, Belgium): ANA25 Quantrix, Synthetase 10 Diver, Myositis 7 Diver and Liver 10 profile Diver, all automatized on the BlueDiver Instrument (D-Tek). The Myasthenia Gravis Foundation of America (MGFA) postintervention status was used to determine the outcome after thymectomy. AutoAbs other than anti-acetylcholine receptor (AChR) antibodies were detected in 29.4% of the patients of whom 16.5% clinically had a second autoimmune disease. In none of the seronegative patients other autoAbs were detected. No significant difference was observed in the 3-years remission rate after thymectomy in patients with or without antibodies other than anti-AChR antibodies. Although these autoAbs do not predict outcome in our MG patient cohort, screening for multiple autoAbs in MG patients might be warranted to identify patients with additional autoimmune diseases.

Prevalence and Predictive Factors of Chronic Postsurgical Pain and Poor Global Recovery 1 Year After Outpatient Surgery.

OBJECTIVES: To prospectively describe the prevalence and predictive factors of chronic postsurgical pain (CPSP) and poor global recovery in a large outpatient population at a university hospital, 1 year after outpatient surgery. MATERIALS AND METHODS: A prospective longitudinal cohort study was performed. During 18 months, patients presenting for preoperative assessment were invited to participate. Outcome parameters were measured by using questionnaires at 3 timepoints: 1 week preoperatively, 4 days postoperatively, and 1 year postoperatively. A value of >3 on an 11-point numeric rating scale was considered to indicate moderate to severe pain. A score of ≤80% on the Global Surgical Recovery Index was defined as poor global recovery. RESULTS: A total of 908 patients were included. The prevalence of moderate to severe preoperative pain was 37.7%, acute postsurgical pain 26.7%, and CPSP 15.3%. Risk factors for the development of CPSP were surgical specialty, preoperative pain, preoperative analgesic use, acute postoperative pain, surgical fear, lack of optimism, and poor preoperative quality of life. The prevalence of poor global recovery was 22.3%. Risk factors for poor global recovery were recurrent surgery because of the same pathology, preoperative pain, preoperative analgesic use, surgical fear, lack of optimism, poor preoperative and acute postoperative quality of life, and follow-up surgery during the first postoperative year. DISCUSSION: Moderate to severe CPSP after outpatient surgery is common, and should not be underestimated. Patients at risk for developing CPSP can be identified during the preoperative phase.

Efficacy and adverse events of aflibercept, ranibizumab and bevacizumab in age-related macular degeneration: a trade-off analysis.

TOPIC: To quantify the gain in visual acuity and serious side effects of ranibizumab, bevacizumab and aflibercept in age-related macular degeneration (AMD). CLINICAL RELEVANCE: There is an ongoing debate about the optimal treatment of AMD with these three antivascular endothelial growth factor (anti-VEGF) treatments. METHODS: Network meta-analyses. (Pre)Medline, EMBASE, SCOPUS, Cochrane Library (until April 2013), Science Citation Index and reference lists were searched for placebo-controlled randomised trials or head-to-head comparisons. Outcomes were 1-year follow-up data of visual acuity (letters gained) and serious (vascular death, any death, stroke, myocardial infarction, transient ischaemic attack) and thrombotic events. Two investigators independently assessed eligibility and quality of included studies and extracted data. RESULTS: 11 trials (enrolling 8341 patients) assessing five active treatments were included. Compared with placebo, all anti-VEGF treatments had a significantly higher percentage of letters gained: ranibizumab 0.3 mg 2.39% (95% CI 1.59 to 3.19; p<0.001), ranibizumab 0.5 mg 3.56% (95% CI 2.58 to 4.13; p<0.001), bevacizumab 1.25 mg 2.14% (95% CI 0.47 to 3.82; p=0.012), aflibercept 0.5 mg 2.91% (95% CI 0.99 to 4.82; p=0.003) and aflibercept 2 mg 3.44% (95% CI 1.73 to 5.14; p<0.001). Compared with placebo, serious side effects were higher in all other treatments: ranibizumab 0.3 mg 4.41% (95% CI 3.42 to 5.40; p<0.001), ranibizumab 0.5 mg 5.33% (95% CI 4.37 to 6.30; p<0.001), bevacizumab 1.25 mg 5.58% (95% CI 3.567 to 7.60; p<0.001), aflibercept 0.5 mg 5.65% (95% CI (3.28 to 8.02; p<0.001) and aflibercept 2 mg 5.29% (95% CI 3.18 to 7.39; p<0.001). Compared with placebo, systemic thrombotic events also occurred more often in all other treatments. CONCLUSIONS: The study revealed only a modest superiority of aflibercept 2 mg and ranibizumab 0.5 mg over other formulations and dosages.

Controlled-release oxycodone versus naproxen at home after ambulatory surgery: a randomized controlled trial.

BACKGROUND: Strong opioids in the home setting after ambulatory surgery have rarely been studied for fear of hazardous adverse effects such as respiratory depression. OBJECTIVES: We compared the efficacy of paracetamol/controlled-release (CR) oxycodone and paracetamol/naproxen for treatment of acute postoperative pain at home after ambulatory surgery. Secondary outcomes were adverse effects of study medication, treatment satisfaction, and postoperative analgesic compliance. METHODS: Patients undergoing ambulatory knee arthroscopy or inguinal hernia repair surgery (n = 105) were randomized into 3 groups: Group1 paracetamol/naproxen (n = 35), Group 2 paracetamol/CR oxycodone for 24 hours (n = 35), and Group 3 paracetamol/CR oxycodone for 48 hours (n = 35). Pain intensity at movement and at rest using a visual analog scale as well as satisfaction with postoperative analgesia and side effects were recorded for up to 48 hours postoperatively. Compliance with study medication was also assessed. RESULTS: For pain at movement and at rest, no significant differences were found between the paracetamol/naproxen group and either the paracetamol/CR oxycodone for 24 hours group (ß = 2.6 [4.9]; P = 0.597) or the paracetamol/CR oxycodone for 48 hours (ß = -1.7 [5.1]; P = 0.736). No major adverse effects of study medication were registered and satisfaction with postoperative pain treatment was high in all groups. Compliance was comparable across the groups. Despite clear instructions, 8 patients with the lowest pain scores did not use any of the prescribed pain medication. CONCLUSIONS: Paracetamol/CR oxycodone and paracetamol/naproxen are equally effective in treatment of acute postoperative pain at home after ambulatory surgery with comparable patient satisfaction level. We suggest paracetamol/CR oxycodone to be a valuable alternative for the current paracetamol/naproxen gold standard, particularly in patients with a contraindication for nonsteroidal anti-inflammatory drugs. ClinicalTrials.gov identifier: NCT02152592.

Continuous paravertebral block for postoperative pain compared to general anaesthesia and wound infiltration for major oncological breast surgery.

We hypothesized that improved acute postoperative pain relief will be achieved using general anaesthesia (GA) either in combination with continuous thoracic paravertebral block (GA-cPVB) or single shot (GA-sPVB) as compared to GA supplemented by local wound infiltration (GA-LWI) after unilateral major breast cancer surgery. A randomised controlled trial was conducted in 46 adult women in a day-care or short-stay hospital setting after major breast cancer surgery. Pain-intensity was measured using an 11-point visual analogue scale (VAS) until postoperative day 2. GA-sPVB was stopped due to slow inclusion. No significant difference in VAS score was noted between GA-LWI (VAS median 0.5 (interquartile range 0.18-2.00)) and GA-cPVB, (VAS 0.3 (0.00-1.55, p = 0.195)) 24 hours after surgery or at any point postoperatively until postoperative day 2. We conclude that both GA-LWI and GA-cPVB anaesthetic techniques are equally effective in treatment of acute postoperative pain after major oncological breast surgery. As GA-LWI is easily to perform with fewer complications and it is more cost-effective it should be preferred over GA-cPVB.

Intraoperative magnetic resonance imaging versus standard neuronavigation for the neurosurgical treatment of glioblastoma: A randomized controlled trial.

BACKGROUND: Although the added value of increasing extent of glioblastoma resection is still debated, multiple technologies can assist neurosurgeons in attempting to achieve this goal. Intraoperative magnetic resonance imaging (iMRI) might be helpful in this context, but to date only one randomized trial exists. METHODS: We included 14 adults with a supratentorial tumor suspect for glioblastoma and an indication for gross total resection in this randomized controlled trial of which the interim analysis is presented here. Participants were assigned to either ultra-low-field strength iMRI-guided surgery (0.15 Tesla) or to conventional neuronavigation-guided surgery (cNN). Primary endpoint was residual tumor volume (RTV) percentage. Secondary endpoints were clinical performance, health-related quality of life (HRQOL) and survival. RESULTS: Median RTV in the cNN group is 6.5% with an interquartile range of 2.5-14.75%. Median RTV in the iMRI group is 13% with an interquartile range of 3.75-27.75%. A Mann-Whitney test showed no statistically significant difference between these groups (P =0.28). Median survival in the cNN group is 472 days, with an interquartile range of 244-619 days. Median survival in the iMRI group is 396 days, with an interquartile range of 191-599 days (P =0.81). Clinical performance did not differ either. For HRQOL only descriptive statistics were applied due to a limited sample size. CONCLUSION: This interim analysis of a randomized trial on iMRI-guided glioblastoma resection compared with cNN-guided glioblastoma resection does not show an advantage with respect to extent of resection, clinical performance, and survival for the iMRI group. Ultra-low-field strength iMRI does not seem to be cost-effective compared with cNN, although the lack of a valid endpoint for neurosurgical studies evaluating extent of glioblastoma resection is a limitation of our study and previous volumetry-based studies on this topic.

Application of an electronic nose in the diagnosis of head and neck cancer.

OBJECTIVES/HYPOTHESIS: Electronic nose (E-nose) technology has various applications such as the monitoring of air quality and the detection of explosive and chemical agents. We studied the diagnostic accuracy of volatile organic compounds (VOC) pattern analysis in exhaled breath by means of an E-nose in patients with head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Cohort study. Exhaled breath samples from patients with HNSCC were analyzed by using an E-Nose. METHODS: Thirty-six patients diagnosed with HNSCC exhaled into a 5-litre Tedlar bag. The control group consisted of 23 patients visiting the outpatient clinic for other (benign) conditions. Air samples were analyzed using an E-nose. RESULTS: Logistic regression showed a significant difference (P < 0.05) in VOC resistance patterns between patients diagnosed with HNSCC and the control group, with a sensitivity of 90% and a corresponding specificity of 80%. CONCLUSIONS: E-nose application holds a promising potential for application in the diagnosis of HNSCC due to its rapid, simple, and noninvasive nature. LEVEL OF EVIDENCE: 3b.

RECIST measurements in cancer treatment: is there a role for physician assistants? - A pilot study.

BACKGROUND: Decision making in cancer treatment is influenced by standardized RECIST measurements which are subjective to interobserver variability. Aim of this pilot study was to evaluate whether it is feasible to transfer the radiologist's task of RECIST measurements to a trained radiology physician assistant and whether this influences diagnostic performance. METHODS: 177 lesions in twenty patients were measured on baseline and two follow-up CTs using RECIST 1.1: Arm A according to routine clinical practice where various radiologists read scans of the referred patients. Arm B according to the experimental setting where a radiology physician assistant performed RECIST measurements of target lesions defined by the radiologists on baseline scans. Performance and agreement were compared between groups. RESULTS: Standard deviation between lesion measurements of arm A and B was four millimeters. Interobserver agreement comparing response category classification was substantial, ĸ = 0.77 (95% CI: 0.66 - 0.87). Sensitivity and specificity for the radiology physician assistant for assessing progressive disease were 100% (95% CI: 61% - 100%) and 94% (95% CI: 81% - 98%) respectively. CONCLUSION: RECIST measurements performed by a paramedic are a feasible alternative to standard practice. This could impact the workflow of radiological units, opening ways to re-assigning radiologists' important, standardized but time consuming tasks to paramedics.

Diagnostic radiation exposure in children with spinal dysraphism: an estimation of the cumulative effective dose in a cohort of 135 children from The Netherlands.

OBJECTIVE: Based on the assumption that children with spinal dysraphism are exposed to a large amount of ionising radiation for diagnostic purposes, our objective was to estimate this exposure, expressed in cumulative effective dose. DESIGN: Retrospective cohort study. SETTINGS: The Netherlands. PATIENTS: 135 patients with spinal dysraphism and under 18 years of age treated at our institution between 1991 and 2010. RESULTS: A total of 5874 radiological procedures were assessed of which 2916 (49.6%) involved ionising radiation. Mean cumulative effective dose of a child with spinal dysraphism during childhood was 23 mSv, while the individual cumulative effective dose ranged from 0.1 to 103 mSv. Although direct radiography accounted for 81.7% of examinations, the largest contributors to the cumulative effective dose were fluoroscopic examinations (40.4% of total cumulative effective dose). CONCLUSIONS: Exposure to ionising radiation and associated cancer risk were lower than expected. Nevertheless, the use of ionising radiation should always be justified and the medical benefits should outweigh the risk of health detriment, especially in children.

Prediction of proliferative vitreoretinopathy after retinal detachment surgery: potential of biomarker profiling.

PURPOSE: To investigate the potential of a combined assessment of clinical risk factors and biomarker profiling in the prediction of proliferative vitreoretinopathy (PVR) after retinal detachment surgery. DESIGN: Retrospective case-control study. METHODS: Multiplex bead-based immunoassays were used for the simultaneous measurement of 50 biomarkers in subretinal fluid samples obtained from patients who underwent scleral buckling surgery for primary rhegmatogenous retinal detachment (RRD). Of 306 samples that were collected and stored in our BioBank, we selected 21 samples from patients in whom a redetachment developed as a result of PVR within 3 months after reattachment surgery for primary RRD (PVR group). These were compared with age-, sex-, and storage time-matched RRD samples from 54 patients with an uncomplicated postoperative course after primary RRD repair (RRD group). RESULTS: Preoperative PVR was the only clinical variable that was an independent predictor of postoperative PVR development (P = .035) and resulted in an area under the receiver operating characteristic curve of 0.67 (95% confidence interval, 0.51 to 0.83). The addition of the biomarkers chemokine (C-C motif) ligand 22, interleukin-3, and macrophage migration inhibitory factor improved the model significantly (P < .001) and resulted in an area under the receiver operating characteristic curve of 0.93 (95% confidence interval, 0.82 to 1.04). A sensitivity of 94.1% and a specificity of 94.2% were reached, using a cutoff value of 5%. CONCLUSIONS: In combination with preoperative PVR grade, the measurement of a single biomarker or a small multibiomarker panel shows great potential and may predict postoperative PVR development after primary RRD in a highly sensitive and specific manner.

Adipokine levels in subretinal fluid from patients with rhegmatogenous retinal detachment.

Adipokines have recently emerged as a novel group of mediators with important roles in inflammatory and immune responses and in the process of wound healing. This study investigated the involvement of several adipokines in the future development of proliferative vitreoretinopathy (PVR) following reattachment surgery for rhegmatogenous retinal detachment (RRD). A multiplex immunoassay was used to measure 6 different adipokines in 75 subretinal fluid samples collected during reattachment surgery for primary RRD. Twenty-one patients who developed a redetachment due to postoperative PVR after scleral buckling surgery (PVR group) were compared with age-, sex-, and storage-time-matched RRD samples from 54 patients with an uncomplicated postoperative course (RRD group). Levels of adiponectin (P = 0.006), cathepsin S (P = 0.001), and leptin (P = 0.041) were significantly elevated in the PVR group as compared to the RRD group. Levels of tissue inhibitor of metalloproteinase (TIMP)-1 were significantly lower in the PVR group than in the RRD group (P = 0.044). After correction for diabetes, body mass index (BMI), macular involvement, and preoperative PVR, the association between postoperative PVR development and adiponectin, cathepsin S, and TIMP-1 remained statistically significant (P < 0.05), whereas the significant correlation between PVR and elevated leptin levels was lost (P = 0.068). There were no significant differences in levels of chemerin (P = 0.351) and adipsin (P = 0.915). Of all adipokines investigated, multivariate logistic regression analysis showed that adiponectin was the exclusive predictor of the development of postoperative PVR after scleral buckling surgery (P = 0.003). Our findings indicate that, at the time of surgery for primary RRD, an altered expression of certain adipokines is associated with the future development of postoperative PVR.

Antiangiogenic isoforms of vascular endothelial growth factor predominate in subretinal fluid of patients with rhegmatogenous retinal detachment and proliferative vitreoretinopathy.

BACKGROUND: In proliferative vitreoretinopathy (PVR), a nonangiogenic eye disease that is characterized by the formation of mainly avascular membranes, vascular endothelial growth factor (VEGF) levels are found to be upregulated. Recently, it was discovered that VEGF is alternatively spliced to form the angiogenic (VEGF xxx) and antiangiogenic (VEGF xxx b) family of isoforms. Previous studies on expression of VEGF in PVR samples have not distinguished between the two families of isoforms. METHODS: We measured total VEGF and VEGF xxx b levels in subretinal fluid of patients with PVR (n = 10) and in patients with uncomplicated rhegmatogenous retinal detachment (n = 27) using enzyme-linked immunosorbent assay. RESULTS: : We found total VEGF levels to be 2- to 3-fold elevated in the PVR group as compared with the rhegmatogenous retinal detachment group (P = 0.047). Antiangiogenic VEGF xxx b isoforms predominated (>60% of total VEGF) in the majority of rhegmatogenous retinal detachment and PVR samples investigated, although a wide variability of isoform ratios was observed within both groups. CONCLUSION: The absence of an increased ratio of VEGF xxx to VEGF xxx b in patients with PVR as compared with patients with uncomplicated rhegmatogenous retinal detachment may explain a lack of blood vessels in PVR membranes. Elevated VEGF levels indicate that this cytokine may play a role in the pathogenesis of PVR that is not related to angiogenesis.

Tumour ADC measurements in rectal cancer: effect of ROI methods on ADC values and interobserver variability.

OBJECTIVES: To assess the influence of region of interest (ROI) size and positioning on tumour ADC measurements and interobserver variability in patients with locally advanced rectal cancer (LARC). METHODS: Forty-six LARC patients were retrospectively included. Patients underwent MRI including DWI (b0,500,1000) before and 6-8 weeks after chemoradiation (CRT). Two readers measured mean tumour ADCs (pre- and post-CRT) according to three ROI protocols: whole-volume, single-slice or small solid samples. The three protocols were compared for differences in ADC, SD and interobserver variability (measured as the intraclass correlation coefficient; ICC). RESULTS: ICC for the whole-volume ROIs was excellent (0.91) pre-CRT versus good (0.66) post-CRT. ICCs were 0.53 and 0.42 for the single-slice ROIs versus 0.60 and 0.65 for the sample ROIs. Pre-CRT ADCs for the sample ROIs were significantly lower than for the whole-volume or single-slice ROIs. Post-CRT there were no significant differences between the whole-volume ROIs and the single-slice or sample ROIs, respectively. The SDs for the whole-volume and single-slice ROIs were significantly larger than for the sample ROIs. CONCLUSIONS: ROI size and positioning have a considerable influence on tumour ADC values and interobserver variability. Interobserver variability is worse after CRT. ADCs obtained from the whole tumour volume provide the most reproducible results. Key Points • ROI size and positioning influence tumour ADC measurements in rectal cancer • ROI size and positioning influence interobserver variability of tumour ADC measurements • ADC measurements of the whole tumour volume provide the most reproducible results • Tumour ADC measurements are more reproducible before, rather than after, chemoradiation treatment • Variations caused by ROI size and positioning should be taken into account when using ADC as a biomarker for tumour response.

Interleukin and growth factor levels in subretinal fluid in rhegmatogenous retinal detachment: a case-control study.

BACKGROUND: Rhegmatogenous retinal detachment (RRD) is a major cause of visual loss in developed countries. Proliferative vitreoretinopathy (PVR), an eye-sight threatening complication of RRD surgery, resembles a wound-healing process with inflammation, scar tissue formation, and membrane contraction. This study was performed to determine the possible involvement of a wide range of cytokines in the future development of PVR, and to identify predictors of PVR and visual outcome. METHODOLOGY: A multiplex immunoassay was used for the simultaneous detection of 29 different cytokines in subretinal fluid samples from patients with primary RRD. Of 306 samples that were collected and stored in our BioBank between 2001 and 2008, 21 samples from patients who developed postoperative PVR were compared with 54 age-, sex-, and storage-time-matched RRD control patients who had an uncomplicated postoperative course during the overall follow-up period. FINDINGS: Levels of IL-1α, IL-2, IL-3, IL-6, VEGF, and ICAM-1 were significantly higher (P<0.05) in patients who developed postoperative PVR after reattachment surgery than in patients with an uncomplicated postoperative course, whereas levels of IL-1ß, IL-4, IL-5, IL-7, IL-9, IL-10, IL-11, IL-12p70, IL-13, IL-15, IL-17, IL-18, IL-21, IL-22, IL-23, IL-25, IL-33, TNF-α, IFN-γ, IGF-1, bFGF, HGF, and NGF were not (P>0.05). Multivariate logistic regression analysis revealed that IL-3 (P = 0.001), IL-6 (P = 0.047), ICAM-1 (P = 0.010), and preoperative visual acuity (P = 0.026) were independent predictors of postoperative PVR. Linear regression analysis showed that ICAM-1 (P = 0.005) and preoperative logMAR visual acuity (P = 0.001) were predictive of final visual outcome after primary RRD repair. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that after RRD onset an exaggerated response of certain cytokines may predispose to PVR. Sampling at a time close to the onset of primary RRD may thus provide clues as to which biological events may initiate the development of PVR and, most importantly, may provide a means for therapeutic control.