Development of an algorithm combining blood-based biomarkers, fecal immunochemical test, and age for population-based colorectal cancer screening.

BACKGROUND AND AIMS: Implementation of screening modalities have reduced the burden of colorectal cancer (CRC), but high false positive rates pose a major problem for colonoscopy capacity. We aimed to create a tailored screening algorithm that expands the fecal immunochemical test (FIT) with a blood specimen and current age to improve selection of individuals for diagnostic colonoscopy. METHODS: In this prospective multi-center study, eight blood-based biomarkers (CEA, Ferritin, hsCRP, HE4, Cyfra21-1, Hepsin, IL-8 and OPG) were investigated in 1,977 FIT positive individuals from the Danish national CRC screening program undergoing follow-up colonoscopy. Specimens were analyzed on ARCHITECT i2000®, ARCHITECT c8000® or Luminex xMAP® machines. FIT analyses and blood-based biomarker data were combined with clinical data (i.e., age and colonoscopy findings) in a cross-validated logistic regression model (algorithm) benchmarked against a model solely using the FIT result (FIT model) applying different cutoffs for FIT positivity. RESULTS: The cohort included individuals with CRC (n = 240), adenomas (n = 938) or no neoplastic lesions (n = 799). The cross-validated algorithm combining the eight biomarkers, quantitative FIT result and age performed superior to the FIT model in discriminating CRC versus non-CRC individuals (AUC 0.77 versus 0.67, p < 0.001). When discriminating individuals with either CRC or high- or medium-risk adenomas versus low-risk adenomas or clean colorectum, the AUCs were 0.68 versus 0.64 for the algorithm and FIT model, respectively. CONCLUSIONS: The algorithm presented here can improve patient allocation to colonoscopy, reducing colonoscopy burden without compromising cancer and adenomas detection rates or vice versa.

Social media as a new source of medical information and support: analysis of scoliosis-specific information.

BACKGROUND CONTEXT: It has never been easier for patients to obtain information about and to connect with others with a given health issue. Frequently, patients turn to social media. There, more information and emotional support from individuals with similar experiences should empower patients, contributing to a better functional and overall outcome. Unfortunately, social media often contains biased reports and misinformation. PURPOSE: This study aimed to assess the footprint of AIS (adolescent idiopathic scoliosis) on the top four social media platforms. STUDY DESIGN: Cross-sectional analysis. METHODS: Independent searches were conducted across four major social media platforms (Facebook, Instagram, YouTube, and LinkedIn) using the keywords "scoliosis" and "#scoliosis" for Instagram. The top 50 posts from each platform were evaluated based on the overall tone of the post (positive, negative, neutral); who made the post (business, patient, family/friend, hospital/physician); the intent of the postcy (advertisement, educate the viewer about scoliosis/disease process/treatments, raise awareness, provide support to patients and their family/friends, promote research); the credentials of the poster [MD, clinician (non-MD), non-clinician, unknown]; the type of media used in the post (text only, picture, video, multiple) and if the post had an external link and what content the link provided (academic, hospital/physician, health news outlet, alternative treatment, personal blog, business, other). RESULTS: 196 unique postings were analyzed for the various content criteria. Across all four platforms, the majority of posts were made by a non-clinician (42.8%) representing a business (49.3%), with the intent to educate (32.3%) using a neutral tone (52.5%). Pictures (61%) were the most common media, and 56.3% of all posts contained external links. Often, those links lead to sites promoting alternative treatments (28.8%). In comparison to the overall analysis, Instagram deviated from the patterns the most. Instagram was the only platform with a predominantly positive tone (62%). Here, 71% of the postings came from an actual patient with the intent to describe their experience or daily life with scoliosis (36%). Instagram had the lowest rate of external links (39%) and most of those lead to another person's Instagram account or a personal blog (47%). Hospital and physician groups had the highest presence on YouTube (35%), but the highest MD authorship was on Facebook (28%). CONCLUSION: Social media can be a powerful tool to disseminate information and create supportive communities for patients with chronic conditions. Healthcare providers and educators are underutilizing these outlets to reach our patients and help provide them the information and support networks they need.

Cross sectional analysis of scoliosis-specific information on the internet: potential for patient confusion and misinformation.

BACKGROUND CONTEXT: Patients and their families are increasingly turning to the internet for medical information. Most of these patients believe the information to be accurate and reliable. However, the quality and accuracy of that information on the internet is variable and unregulated. Accurate and applicable information may align patients' expectations and improve satisfaction and overall outcomes. PURPOSE: This study aimed to evaluate the quality and accuracy of scoliosis-related information available on the internet. STUDY DESIGN: Cross-sectional analysis. METHODS: Independent searches were conducted on the three most commonly accessed search engines (Google, Yahoo and Bing) using the keyword "scoliosis". The top 30 sites from each search engine were reviewed. Each website was categorized as per its authorship and sourcing. Each site was then evaluated for accuracy, readability and with quality-assurance markers such as Health on the Net code (HONcode), DISCERN, Journal of American Medical Association (JAMA) systems. The accuracy of the website was assessed by two fellowship-trained spine specialists. Website accuracy was rated on a scale of 1-4 based on the level of agreement with the information presented. Websites with greater than 75% agreement were rated 4. Finally, the sites were evaluated with a validated website distraction index and assessed for mobile friendliness. RESULTS: 42 unique websites were analyzed. 31% of the sites were categorized as academic (13 academic, 9 healthcare system, 12 health news outlets and 8 unspecified) and had the highest rate of physician authorship (54%). Accuracy ranged from less than 25% to more than 75% were recorded with a mean accuracy of 3 signifying 50-75% agreement. Academic sites had the highest scoliosis specific accuracy score (P < 0.05). Overall, average readability was at a 12th grade reading level. More than 90% of the sites were mobile friendly. Approximately 71% of the websites did not have HONcode certification, although health news outlets had the highest rate of certification (67%). There was a significant effect of HONcode certification on DISCERN, JAMA, grade level and reading ease. On average, HONcode certified websites had lower grade level readability with greater reading ease and higher DISCERN and JAMA scores than un-certified sites (p < 0.05). On average, health news outlets had the highest DISCERN, JAMA, and reading ease scores and were written at the lowest grade reading level but had the highest level of distraction (p < 0.05). CONCLUSION: For the iGeneration and their care-givers, the internet remains the most popular source of health-related and medical information. Despite the wide number of sources available, the quality, accuracy, pertinence and intelligibility of the information remains highly variable. As clinicians, we should direct patients to verifiable sites with regulated information and, where possible, contribute high quality information to those sites.

Return to Sport After Hip Arthroscopy for Femoroacetabular Impingement Syndrome in NCAA Division I Athletes: Experience at a Single Institution.

BACKGROUND: The rate of return to sport after surgical treatment of femoroacetabular impingement (FAI) syndrome (FAIS) has been studied in high-level athletes. However, few studies examining this rate have focused exclusively on National Collegiate Athletic Association (NCAA) Division I athletes. PURPOSE: To evaluate the return-to-sport rate after hip arthroscopy for FAIS and to examine the influence of sport type on the clinical presentation of FAIS in collegiate athletes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Included in this study were NCAA Division I student-athletes who underwent hip arthroscopy for FAIS at our institution between 2010 and 2017. Exclusion criteria were history of previous hip pathology, pediatric hip disease, radiographic evidence of osteoarthritis (Tönnis grade >0), prior lower extremity procedure, history of chronic pain, osteoporosis, or history of systemic inflammatory disease. Athletes were categorized into 6 subgroups based on the type of sport (cutting, contact, endurance, impingement, asymmetric/overhead, and flexibility) by using a previously reported classification system. Patient characteristics and preoperative, intraoperative, and return-to-sport variables were compared among sport types. RESULTS: A total of 49 hip arthroscopies for FAIS were performed in 39 collegiate athletes (10 females, 29 males; mean age, 19.5 ± 1.3 years). A total of 1 (2.6%) cutting athlete, 15 (38.5%) contact athletes, 8 (20.5%) impingement athletes, 6 (15.4%) asymmetric/overhead athletes, and 9 (23.1%) endurance athletes were included in the study. There were no differences among sports groups with respect to the FAI type. Endurance athletes had lower rates of femoral osteochondroplasty (45.5%) and labral debridement (0.0%) (P < .0001). Contact sport athletes had higher rates of labral debridement (50.0%; P < .0001). Patients were evaluated for return to sport at an average of 1.96 ± 0.94 years. Overall, the return-to-sport rate was 89.7%. There were no differences in return-to-sport rates based on the sport type except for endurance athletes, who returned at a lower rate (66.6%; P < .001). No differences in return-to-sport rate (P = .411), duration after return (P = .265), or highest attempted level of sport resumed (P = .625) were found between patients who underwent labral repair versus debridement. CONCLUSION: Collegiate-level athletes who underwent hip arthroscopy for FAIS returned to sport at high and predictable rates, with endurance athletes possibly returning to sport at lower rates than all other sport types. Surgical procedures may be influenced by sport type, but the rate of return to sport between athletes who underwent labral debridement versus labral repair was similar.

Anatomic Evaluation of the Interportal Capsulotomy Made with the Modified Anterior Portal versus Standard Anterior Portal: Comparable Utility with Decreased Capsule Morbidity.

PURPOSE: To identify potential differences in interportal capsulotomy size and cross-sectional area (CSA) using the anterolateral portal (ALP) and either the: (i) standard anterior portal (SAP) or (ii) modified anterior portal (MAP). MATERIALS AND METHODS: Ten cadaveric hemi pelvis specimens were included. A standard arthroscopic ALP was created. Hips were randomized to SAP (n=5) or MAP (n=5) groups. The spinal needle was placed at the center of the anterior triangle or directly adjacent to the ALP in the SAP and MAP groups, respectively. A capsulotomy was created by inserting the knife through the SAP or MAP. The length and width of each capsulotomy was measured using digital calipers under direct visualization. The CSA and length of the capsulotomy as a percentage of total iliofemoral ligament (IFL) side-to-side width were calculated. RESULTS: There were no differences in mean cadaveric age, weight or IFL dimensions between the groups. Capsulotomy CSA was significantly larger in the SAP group compared with the MAP group (SAP 2.16±0.64 cm2 vs. MAP 0.65±0.17 cm2, P=0.008). Capsulotomy length as a percentage of total IFL width was significantly longer in the SAP group compared with the MAP group (SAP 74.2±14.1% vs. MAP 32.4±3.7%, P=0.008). CONCLUSION: The CSA of the capsulotomy and the percentage of the total IFL width disrupted are significantly smaller when the interportal capsulotomy is performed between the ALP and MAP portals, compared to the one created between the ALP and SAP. Surgeons should be aware of this fact when performing hip arthroscopy.

Does Bone Plug and Graft Orientation (Inferior Versus Posterior) Alter Native Femoral Footprint Coverage in Bone Patellar Tendon Bone Anterior Cruciate Ligament Reconstruction?

PURPOSE: The purpose of this study was to compare the percentage of native femoral anterior cruciate ligament (ACL) footprint covered by the 2 most clinically relevant bone plug/graft orientations used with interference screw fixation in ACL reconstruction. A secondary purpose was to assess whether a transtibial or tibia-independent drilling technique would affect this outcome. METHODS: Five matched pairs of cadaver knees were used. Each matched pair had 1 knee assigned to a 10-mm femoral socket prepared via a transtibial (TT) drilling technique and the other via an anteromedial (AM) drilling technique. The bone plug of each graft was press-fitted into the femoral socket with the graft collagen in 2 distinct clinically relevant orientations (collagen inferior or posterior). The digitized graft collagen cross-sectional area (CSA) in each orientation was overlaid onto the native femoral ACL footprint CSA to generate a percentage of native ACL footprint covered by graft collagen. RESULTS: The average native ACL femoral footprint CSA was 110.5 ± 9.1 mm2, with no difference between knees assigned to TT or AM drilling (112.6 ± 2.7 vs 108.4 ± 13.0 mm2, P = .49). The average femoral socket CSA was 95.4 ± 8.7 mm2, with no difference between TT and AM tunnels (95.5 ± 9.9 vs 95.3 ± 8.4 mm2, P = .96). There was no difference between the percentage of native footprint covered between TT and AM sockets (76.8% ± 7.8% vs 82.2% ± 13.7%, P = .47). Irrespective of drilling technique, there was significantly greater native ACL footprint covered by graft collagen when the bone plug was oriented with graft collagen inferior rather than posterior (75.6% ± 6.3% vs 65.4% ± 11.4%, P = .02). CONCLUSION: Orienting the femoral bone plug such that the graft collagen is inferior rather than posterior significantly increases native ACL femoral footprint coverage in bone-patellar tendon-bone ACL reconstruction. This effect is consistent across AM and TT drilling techniques. CLINICAL RELEVANCE: Surgeons attempting to restore an anatomic ACL footprint should consider bone plug-graft orientation when performing ACL reconstruction. STUDY DESIGN: Controlled laboratory study.

Renal systems biology of patients with systemic inflammatory response syndrome.

A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on patient response during critical illness. To achieve this, we examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Quantification of plasma metabolites indicated greater change as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular-weight proteins and acute-phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among patients on HD. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and N-acetylaspartate were inversely correlated with the majority of significantly downregulated genes. Thus, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness; changes were not effectively mitigated by hemodialysis. These studies allude to several novel mechanisms whereby renal dysfunction contributes to critical illness.

Lumbar microdiscectomy and lumbar decompression improve functional outcomes and depression scores.

STUDY DESIGN: Retrospective review. INTRODUCTION: Lumbar radiculopathy and claudicant leg pain are common degenerative spinal conditions often treated by elective microdiscectomy or decompression. Published outcome data for these procedures have focused on improvement in pain scores, and not on grounded functional outcome or depression scores.1,2,3 Moreover, depression is considered by many surgeons to be a red flag for poor outcome for surgical treatment. We asked what effect lumbar microdiscectomy and laminectomy procedures had on functional outcome and depression scores in our clinical population. METHODS: Beginning in January 2010, the following outcome data were prospectively gathered before and after surgery from all patients at the Cleveland Clinic undergoing either lumbar microdiscectomy or lumbar decompression: EQ-5D (EuroQOL, quality-of-life measure), PHQ-9 (measure of depressive symptoms), PDQ (pain disability questionnaire), and Rankin scores (disability or dependence in daily activities). RESULTS: The mean EuroQOL scores improved by 35% (from 0.4-0.75 of a maximum of 1.0) for both microdiscectomy and lumbar laminectomies. The mean PHQ-9 scores (measure of depressive symptoms) significantly improved for most patients undergoing either procedure. In line with previously published reports, we also found improvement in Rankin scores and Pain Disability Questionnaire scores. CONCLUSIONS: Our outcome data indicate that microdiscectomy and lumbar decompression not only reduce disability and pain but also improve depressive symptoms and overall quality of life for patients. These findings support operative treatment of lumbar radiculopathy and neurogenic claudication including treatment performed in the depressed population.

Microglia derived IL-6 suppresses neurosphere generation from adult human retinal cell suspensions.

Following retinal degeneration or inflammation that disrupts tissue architecture, there is limited evidence of tissue regeneration, despite evidence of cells with progenitor properties in the adult human retina at all ages. With the prospect of tissue/cell transplantation, redressing homeostasis whilst overcoming glial barrier or gliosis remains key to successful graft versus host integration and functional recovery. Activated human retinal microglia (MG) secrete cytokines, including IL-6, which may suppress neurogenesis or cellular (photoreceptor) replacement. To investigate this hypothesis, adult human retinal explants were cultured in cytokine-conditioned media (TNFalpha, TGFbeta, LPS/IFNgamma) to activate microglia in situ. Following culture of retinal explants for 4 days, supernatant conditioned by resulting migrated microglia was collected after a further 3 days and fed to retinal cell suspensions (RCS). Neurosphere (NS) generation and survival analysis was performed after 7 and 14 days in culture, with or without addition of conditioned media and with or without concomitant IL-6 neutralisation. Neurosphere phenotype was analysed by immunohistochemistry and cell morphology. Migratory MG from retinal explants were activated (iNOS-positive) and expressed CD45, CD11b, and CD11c. LPS/IFNgamma-activated MG conditioned media (MG-CM) contained significant levels of IL-6 (1265 +/- 143) pg/ml, which inhibited neurosphere generation within RCS in the presence of optimal neurosphere generating N2-FGF2 culture medium. Neutralising IL-6 activity reinstated NS generation and the differentiation capacity was maintained in the spheres that formed. Even in the presence of high levels of IL-6, those few NS that did form demonstrated a capacity to differentiate. The data supports activated MG-derived IL-6 influence retinal cell turnover.

CD133+ adult human retinal cells remain undifferentiated in Leukaemia Inhibitory Factor (LIF).

BACKGROUND: CD133 is a cell surface marker of haematopoietic stem and progenitor cells. Leukaemia inhibitory factor (LIF), sustains proliferation and not differentiation of embryonic stem cells. We used CD133 to purify adult human retinal cells and aimed to determine what effect LIF had on these cultures and whether they still had the ability to generate neurospheres. METHODS: Retinal cell suspensions were derived from adult human post-mortem tissue with ethical approval. With magnetic automated cell sorting (MACS) CD133+ retinal cells were enriched from post mortem adult human retina. CD133+ retinal cell phenotype was analysed by flow cytometry and cultured cells were observed for proliferative capacity, neuropshere generation and differentiation with or without LIF supplementation. RESULTS: We demonstrated purification (to 95%) of CD133+ cells from adult human postmortem retina. Proliferating cells were identified through BrdU incorporation and expression of the proliferation markers Ki67 and Cyclin D1. CD133+ retinal cells differentiated whilst forming neurospheres containing appropriate lineage markers including glia, neurons and photoreceptors. LIF maintained CD133+ retinal cells in a proliferative and relatively undifferentiated state (Ki67, Cyclin D1 expression) without significant neurosphere generation. Differentiation whilst forming neurospheres was re-established on LIF withdrawal. CONCLUSION: These data support the evidence that CD133 expression characterises a population of cells within the resident adult human retina which have progenitor cell properties and that their turnover and differentiation is influenced by LIF. This may explain differences in retinal responses observed following disease or injury.

Prescription opioid dependence is associated with poorer outcomes in disabling spinal disorders.

STUDY DESIGN: Prospective outcomes study involving patients with chronic disabling occupational spinal disorders (CDOSD) diagnosed with (n = 199) or without (n = 1124) postinjury opioid-dependence disorder (ODD), based on the Diagnostic and Statistical Manual of Mental Disorders-fourth edition cirteria. OBJECTIVE: To determine whether prescription opioid dependence, assessed at the beginning of rehabilitation treatment, is associated with poorer treatment outcomes in patients with CDOSDs attending an interdisciplinary rehabilitation program. SUMMARY OF BACKGROUND DATA: Controversy exists regarding the risk of iatrogenic ODD and treatment outcomes when long-term opioid therapy is used in the treatment of chronic nonmalignant pain conditions. METHODS: A consecutive sample of patients with CDOSDs [n = 1323; mean (SD) length of disability = 18.8 (20.7) months] attending a tertiary referral center received intensive physical reactivation and pain/disability management interventions, based on a functional restoration model, including detoxification from opioids. One-year outcomes included return to work, work retention, healthcare utilization, new surgeries, recurrent injuries, and disability claim settlement. RESULTS: Prevalence of ODD in this CDOSD population on entering the rehabilitation program was 15%. Even after adjusting for relevant demographic factors and comorbid psychiatric disorders, opioid-dependent patients were 1.7 times [95% confidence interval (CI): 1.0, 2.7] less likely to return to work, 2 times (95% CI: 1.3, 3.0) less likely to retain work at the 1-year interview, and 1.7 times (95% CI: 1.2, 2.5) more likely to engage in healthcare utilization from new providers, compared with nonopioid-dependent patients. CONCLUSIONS: Iatrogenic prescription opioid dependence may be a risk factor for less successful long-term work and health outcomes, even after detoxification from opioids as part of an interdisciplinary functional rehabilitation program. Chronic prescription opioid dependence in this patient population is also associated with a significantly higher prevalence of comorbid psychiatric conditions, both axis I and II.

Five-year retrospective review of guideline-based management of fungal endophthalmitis.

PURPOSE: Guidelines were introduced in 2000 at the Bristol Eye Hospital (BEH) for the management of fungal endophthalmitis. A 5-year retrospective audit re-evaluated the guidelines and monitored the management of this rare condition. Clinical effectiveness and management costs were considered in light of visual outcome. METHODS: Cases were identified through a 5-year retrospective review of theatre logbooks, Patient Administration System coded admissions with primary diagnosis of purulent endophthalmitis and pharmacy logbooks of patients receiving antifungal therapy. Data correlation and review of patient management were carried out in light of the findings. RESULTS: Twenty-three cases were included, based on clinical disease and/or positive smears or cultures. Age range was 13-74 years, with a male : female ratio of 16 : 7 and right eye : left eye ratio of 14 : 9. Risk factors for fungal endophthalmitis included septicaemia caused by intravenous drug use (78%), presence of indwelling lines (9%), postocular surgery (9%) and post-trauma (4%). Guidelines were rigidly followed in 56% of cases, with improved visual acuity in 9/13 patients compared to 4/10 where management deviated from guidelines. Deviation from guidelines occurred with incomplete use of the recommended drug regimen for the disease severity or use of drugs that were alternative to the suggested guidelines. Treatment was initiated on clinical judgement in 91% of cases and laboratory diagnosis in 9%. CONCLUSION: The BEH guidelines provided a useful reference when managing this uncommon condition. Voriconazole, a newer broad-spectrum agent with good ocular penetration (used in 9%), has been added to the revised guidelines. Monitoring rare conditions over prolonged time frames supports evidence-based medicine

Lens reabsorption following self-induced needling and subsequent intracapsular secondary intraocular lens placement.

We present the case of a young man who inadvertently penetrated his cornea and lens with a needle used for injecting heroin. Three years later, the lens had completely reabsorbed leaving a fibrosed capsular bag. We describe the surgical techniques used to insert a secondary intraocular lens into the capsular bag with excellent visual outcome.

Patterned growth of neuronal cells on modified diamond-like carbon substrates.

Diamond-like carbon (DLC) has been explored as a biomaterial with potential use for coating implantable devices and surgical instruments. In this study the interaction of DLC with mammalian neuronal cells has been studied along with its modifications to improve its function as a biomaterial. We describe the use of DLC, oxidised DLC and phosphorus-doped DLC to support the growth and survival of primary central nervous system neurones and neuroblastoma cells. None of these substrates were cytotoxic and primary neurones adhered better to phosphorus-doped DLC than unmodified DLC. This property was used to culture cortical neurones in a predetermined micropattern. This raises the potential of DLC as a biomaterial for central nervous system (CNS) implantation. Furthermore, patterned DLC and phosphorus-doped DLC can direct neuronal growth, generating a powerful tool to study neuronal networks in a spatially distinct way. This study reports the generation of nerve cell patterns via patterned deposition of DLC.

Subperiosteal orbital hemorrhage following self-strangulation.

Subperiosteal orbital hematomas are uncommon. The delayed presentation of such an event is described in an anticoagulated patient who attempted self-strangulation. Despite the initial presence of a relative afferent pupillary defect, excellent visual recovery occurred, demonstrating the importance of prompt recognition and treatment. The causes, mechanism of visual loss, radiographic diagnosis, and treatment of subperiosteal hemorrhages are discussed.

Turnover of resident retinal microglia in the normal adult mouse.

The retina contains two distinct populations of monocyte-derived cells: perivascular cells (macrophages) and parenchymal cells (microglia), important in homeostasis, neuroinflammation, degeneration, and injury. The turnover of these cells in the retina and their repopulation in normal physiological conditions have not been clarified. Bone marrow (BM) cells from EGFP-transgenic mice were adoptively transferred into lethally irradiated normal adult C57BL/6 mice. Eight, 14, and 26 weeks later mice were sacrificed and retinal flatmounts were prepared. Retinal microglia were identified by F4/80, CD45, and Iba-1 immunostaining. BrdU was injected into normal mice for 3-14 days and cell proliferation was examined by confocal microscopy of retinal flatmounts. Few (6.15 +/- 2.02 cells/retina) BrdU(+) cells were detected and of these some coexpressed CD11b (1.67 +/- 0.62 cells/retina) or F4/80 (0.57 +/- 0.30 cells/retina). BM-derived EGFP(+) cells were detected by 8-weeks post-transplantation. By 6 months, all retinal myeloid cells were EGFP(+). Consecutively, donor BM-EGFP(+) cells were demonstrated within the: (1) peripheral and juxtapapillary retina, (2) ganglion cell layer, (3) inner and outer plexiform layers, and (4) photoreceptor layer. EGFP(+) cells within the ganglion layer were amoeboid in shape and F4/80(high)CD45(high)Iba-1(high), whereas cells in the inner and outer plexiform layers were ramified and F4/80(low) CD45(low)Iba-1(low). Perivascular macrophages expressed less F4/80, CD45, and Iba-1 compared with parenchymal microglia. Our results suggest that BM-derived monocyte precursor cells are able to migrate across the BRB and replace retinal microglia/macrophages. The complete replacement of retinal microglia/macrophages takes about 6 months. In situ proliferation was predominantly of nonhemopoetic retinal cells.

Therapy insight: prophylaxis, monitoring and treatment of perioperative myocardial ischemia with emphasis on urological surgery.

Unrecognized or silent perioperative myocardial ischemia is common in patients who undergo high-risk surgery, including cystectomy, and could predict cardiac morbidity and mortality in postoperative patients. This disorder is not merely a marker of extensive coronary disease but has a close association with perioperative myocardial infarction (PMI). In a review of published data, including meta-analyses, in the context of high-risk urological surgery, up to 50% of PMIs were found to go unrecognized if only clinical signs and symptoms are considered. Prevention and treatment of these previously unrecognized cardiac events might significantly reduce long-term morbidity and mortality. The emergence of reliable markers of PMI, such as increased levels of troponin I, could help in the detection of events that would have otherwise remained unnoticed. In this Review we examine the effect of these developments in the context of high-risk urological surgery. Changes to preoperative assessment, perioperative management, and prophylaxis of PMI are critically assessed. We performed a prospective audit using postoperative troponin I levels to assess the rate of silent perioperative myocardial ischemia and infarction. An increasingly proactive attitude towards perioperative monitoring for myocardial ischemia and infarction has evolved, and postoperative serial screening with troponin I might be beneficial in high-risk patients undergoing major urological surgery.

The effect of postmortem time, donor age and sex on the generation of neurospheres from adult human retina.

BACKGROUND/AIM: Postmortem adult human retina contains pluripotent progenitor cells capable of forming neurospheres with different retinal cell types. The authors examine whether this is the case at all ages and at different postmortem times. METHODS: Adult human postmortem retina-derived cell suspensions generated neurospheres in fibroblast growth factor 2 and N2 supplement. The yield of neurospheres from limited dilution or single cell cultures is very low so the authors studied cells generated per 10(5) viable cells from a cell suspension derived from whole retina. Retinal tissue from donors aged 18-91 at various postmortem times (between 23-44 h) was studied in the context of generation rate and time for neurospheres. RESULTS: The potential to generate neurospheres from adult human retina remains throughout life. Neurosphere cellular components were not affected by donor age or postmortem time (they contained nestin(+), glial fibrillary acidic protein(+) and neurofilament(+) cells). An average of 34.36 neurospheres were generated per 10(5) viable cells. After a few days in culture neurospheres begin to form. The time for this to occur was independent of donor age but prolonged at longer postmortem times. No significant effect of donor sex was found. CONCLUSION: Neurosphere-forming retinal progenitor cells are found in adult human retina throughout life. This cell population is a potential target for therapeutic intervention to influence repair and regeneration of the retina.

Recovery from macular phototoxicity after corneal triple procedure.

PURPOSE: Visual recovery from macular phototoxicity in 2 cases after prolonged exposure to operating microscope light from uncomplicated corneal triple-procedure surgery. Recovery is discussed in the context of repair and regeneration. METHODS: Retrospective case reports. RESULTS: Immediately postoperatively, both patients reported positive scotomata and were found to have macular retinal pigment epithelial depigmentation. In 1 case, the fovea was involved. By 6 to 12 months, the scotomata had disappeared despite large areas of retinal pigment epithelial hyperpigmentation remaining. CONCLUSION: Recovery from macular phototoxicity occurs, although the mechanism remains unclear. Positive scotomata in these cases resolved over several months. The time scale of recovery was consistent with the time required for cellular replacement and possible differentiation from neural progenitor cells.

Ultrastructural evaluation of explanted opacified Hydroview (H60M) intraocular lenses.

AIM: To describe the ultrastructural appearance of explanted opacified Hydroview H60M intraocular lenses. METHODS: 14 explanted lenses were examined by scanning electron microscopy, and their appearance compared with a non-implanted H60M lens from the same time period. Wavelength-dispersive x ray spectroscopy (WDX) was performed on two opacified lenses. RESULTS: Subsurface deposits were seen in all explanted opacified lenses. These deposits broke only onto the surface of more densely opacified lenses. WDX confirmed that the deposits contained both calcium and phosphorous, consistent with their being calcium apatite. CONCLUSION: These findings challenge the widely accepted opinion that H60M intraocular lens opacification begins on the surface of the optic.