Testicular germ cell tumors arise in the absence of sex-specific differentiation.

In response to signals from the embryonic testis, the germ cell intrinsic factor NANOS2 coordinates a transcriptional program necessary for the differentiation of pluripotent-like primordial germ cells toward a unipotent spermatogonial stem cell fate. Emerging evidence indicates that genetic risk factors contribute to testicular germ cell tumor initiation by disrupting sex-specific differentiation. Here, using the 129.MOLF-Chr19 mouse model of testicular teratomas and a NANOS2 reporter allele, we report that the developmental phenotypes required for tumorigenesis, including failure to enter mitotic arrest, retention of pluripotency and delayed sex-specific differentiation, were exclusive to a subpopulation of germ cells failing to express NANOS2. Single-cell RNA sequencing revealed that embryonic day 15.5 NANOS2-deficient germ cells and embryonal carcinoma cells developed a transcriptional profile enriched for MYC signaling, NODAL signaling and primed pluripotency. Moreover, lineage-tracing experiments demonstrated that embryonal carcinoma cells arose exclusively from germ cells failing to express NANOS2. Our results indicate that NANOS2 is the nexus through which several genetic risk factors influence tumor susceptibility. We propose that, in the absence of sex specification, signals native to the developing testis drive germ cell transformation.

In vitro gametogenesis (IVG): reflections from a workshop.

Key ideas from a workshop convened by the National Academies of Sciences, Engineering, and Medicine to discuss developments in IVG (National Academies of Sciences, Engineering, and Medicine 2023) chaired by Dr Eli Y. Adashi (former Dean of Medicine and Biological Sciences at Brown University). The authors are solely responsible for the content of this paper, which does not necessarily represent the views of the National Academies of Sciences, Engineering, and Medicine.

Patient perspectives on the use of indwelling pleural catheters in malignant pleural effusions.

BACKGROUND: Indwelling pleural catheters are an effective treatment option for patients with malignant pleural effusions. Despite their popularity, there remains a paucity of data on the patient experience and key patient-centred outcomes. OBJECTIVE: To investigate the experience of patients receiving an indwelling pleural catheter to better inform and identify potential areas for improvement in care. METHODS: This was a multicentre survey study at three academic, tertiary-care centres in Canada. Patients with a diagnosis of malignant pleural effusion who had an indwelling pleural catheter inserted were included. An adapted questionnaire specific to indwelling pleural catheters was used with responses recorded on a 4-point Likert scale. Patients completed the questionnaire in-person or by phone at 2-week and 3-month follow-up appointments. RESULTS: A total of 105 patients were enrolled in the study with 84 patients included in the final analysis. At the 2-week follow-up, patient-reported improvements in dyspnoea and quality of life from indwelling pleural catheter were high at 93% and 87%, respectively. The predominant issues identified were discomfort at time of insertion (58%), itching (49%), difficulty with sleeping (39%), discomfort with home drainage (36%) and the pleural catheter reminding patients of their disease (63%). Avoiding hospitalisation for the management of dyspnoea was important to 95% of patients. Findings were similar at 3 months. CONCLUSIONS: Indwelling pleural catheters are an effective intervention to directly improve dyspnoea and quality of life but have important disadvantages for some; clinicians and patients should be aware of these when making an informed decision regarding treatment.

Delayed male germ cell sex-specification permits transition into embryonal carcinoma cells with features of primed pluripotency.

Testicular teratomas result from anomalies in embryonic germ cell development. In 129 inbred mice, teratoma initiation coincides with germ cell sex-specific differentiation and the mitotic-meiotic switch: XX and XY germ cells repress pluripotency, XX germ cells initiate meiosis, and XY germ cells activate male-specific differentiation and mitotic arrest. Here, we report that expression of Nanos2, a gene that is crucial to male sex specification, is delayed in teratoma-susceptible germ cells. Decreased expression of Nanos2 was found to be due, in part, to the Nanos2 allele present in 129 mice. In teratoma-susceptible germ cells, diminished expression of genes downstream of Nanos2 disrupted processes that were crucial to male germ cell differentiation. Deficiency for Nanos2 increased teratoma incidence in 129 mice and induced developmental abnormalities associated with tumor initiation in teratoma-resistant germ cells. Finally, in the absence of commitment to the male germ cell fate, we discovered that a subpopulation of teratoma-susceptible germ cells transition into embryonal carcinoma (EC) cells with primed pluripotent features. We conclude that delayed male germ cell sex-specification facilitates the transformation of germ cells with naïve pluripotent features into primed pluripotent EC cells.

Using an eLearning Module to Facilitate Sepsis Knowledge Acquisition Across Multiple Institutions and Learner Disciplines.

OBJECTIVE: Guidelines exist for care of pediatric sepsis, but no study has assessed the benefit of electronic learning (eLearning) in this topic area. The objective of this multicenter study was to assess knowledge acquisition and retention for pediatric sepsis across multiple health care provider roles, using an adaptive and interactive eLearning module. METHODS: The study used pretest, posttest, and 90-day delayed test scores to evaluate provider knowledge after an adaptive and interactive eLearning module intervention. The eLearning module contained conditional logic-based assessments that allowed real-time adjustments of the displayed content according to each participant's demonstrated knowledge. Physicians, nurses, and advanced practice providers, primarily emergency department based, at 9 pediatric institutions were included. Changes in test scores were stratified by provider role. RESULTS: A total of 574 participants completed the posttest, and 296 (51.6%) of those completed the delayed test. Across all providers, there was an increase in test scores of 15.7% between the pretest and posttest (P < 0.001) with a large effect size as measured by Cramer's V. Across all providers, there was an overall test score increase of 5.2% (P < 0.001) between the pretest and delayed test, with a small effect size. CONCLUSIONS: An eLearning module improved immediate and delayed pediatric sepsis knowledge in pediatric health care providers across multiple institutions and provider roles. Immediate knowledge gain was meaningful as indicated by effect sizes, although by the time of the delayed test, the effect was smaller. This module fills an important gap in currently available pediatric sepsis education.

IL-33 activates tumor stroma to promote intestinal polyposis.

Tumor epithelial cells develop within a microenvironment consisting of extracellular matrix, growth factors, and cytokines produced by nonepithelial stromal cells. In response to paracrine signals from tumor epithelia, stromal cells modify the microenvironment to promote tumor growth and metastasis. Here, we identify interleukin 33 (IL-33) as a regulator of tumor stromal cell activation and mediator of intestinal polyposis. In human colorectal cancer, IL-33 expression was induced in the tumor epithelium of adenomas and carcinomas, and expression of the IL-33 receptor, IL1RL1 (also referred to as IL1-R4 or ST2), localized predominantly to the stroma of adenoma and both the stroma and epithelium of carcinoma. Genetic and antibody abrogation of responsiveness to IL-33 in the Apc(Min/+) mouse model of intestinal tumorigenesis inhibited proliferation, induced apoptosis, and suppressed angiogenesis in adenomatous polyps, which reduced both tumor number and size. Similar to human adenomas, IL-33 expression localized to tumor epithelial cells and expression of IL1RL1 associated with two stromal cell types, subepithelial myofibroblasts and mast cells, in Apc(Min/+) polyps. In vitro, IL-33 stimulation of human subepithelial myofibroblasts induced the expression of extracellular matrix components and growth factors associated with intestinal tumor progression. IL-33 deficiency reduced mast cell accumulation in Apc(Min/+) polyps and suppressed the expression of mast cell-derived proteases and cytokines known to promote polyposis. Based on these findings, we propose that IL-33 derived from the tumor epithelium promotes polyposis through the coordinated activation of stromal cells and the formation of a protumorigenic microenvironment.

Germ cell tumors: Insights from the Drosophila ovary and the mouse testis.

Ovarian and testicular germ cell tumors of young adults are thought to arise from defects in germ cell development, but the molecular mechanisms underlying malignant transformation are poorly understood. In this review, we focus on the biology of germ cell tumor formation in the Drosophila ovary and the mouse testis, for which evidence supports common underlying mechanisms, such as blocking initiation into the differentiation pathway, impaired lineage progression, and sexual identity instability. We then discuss how these concepts inform our understanding of the disease in humans. Mol. Reprod. Dev. 84: 200-211, 2017. © 2017 Wiley Periodicals, Inc.

Developing a clinically feasible personalized medicine approach to pediatric septic shock.

RATIONALE: Using microarray data, we previously identified gene expression-based subclasses of septic shock with important phenotypic differences. The subclass-defining genes correspond to adaptive immunity and glucocorticoid receptor signaling. Identifying the subclasses in real time has theranostic implications, given the potential for immune-enhancing therapies and controversies surrounding adjunctive corticosteroids for septic shock. OBJECTIVES: To develop and validate a real-time subclassification method for septic shock. METHODS: Gene expression data for the 100 subclass-defining genes were generated using a multiplex messenger RNA quantification platform (NanoString nCounter) and visualized using gene expression mosaics. Study subjects (n = 168) were allocated to the subclasses using computer-assisted image analysis and microarray-based reference mosaics. A gene expression score was calculated to reduce the gene expression patterns to a single metric. The method was tested prospectively in a separate cohort (n = 132). MEASUREMENTS AND MAIN RESULTS: The NanoString-based data reproduced two septic shock subclasses. As previously, one subclass had decreased expression of the subclass-defining genes. The gene expression score identified this subclass with an area under the curve of 0.98 (95% confidence interval [CI95] = 0.96-0.99). Prospective testing of the subclassification method corroborated these findings. Allocation to this subclass was independently associated with mortality (odds ratio = 2.7; CI95 = 1.2-6.0; P = 0.016), and adjunctive corticosteroids prescribed at physician discretion were independently associated with mortality in this subclass (odds ratio = 4.1; CI95 = 1.4-12.0; P = 0.011). CONCLUSIONS: We developed and tested a gene expression-based classification method for pediatric septic shock that meets the time constraints of the critical care environment, and can potentially inform therapeutic decisions.

A Multibiomarker-Based Model for Estimating the Risk of Septic Acute Kidney Injury.

OBJECTIVE: The development of acute kidney injury in patients with sepsis is associated with worse outcomes. Identifying those at risk for septic acute kidney injury could help to inform clinical decision making. We derived and tested a multibiomarker-based model to estimate the risk of septic acute kidney injury in children with septic shock. DESIGN: Candidate serum protein septic acute kidney injury biomarkers were identified from previous transcriptomic studies. Model derivation involved measuring these biomarkers in serum samples from 241 subjects with septic shock obtained during the first 24 hours of admission and then using a Classification and Regression Tree approach to estimate the probability of septic acute kidney injury 3 days after the onset of septic shock, defined as at least two-fold increase from baseline serum creatinine. The model was then tested in a separate cohort of 200 subjects. SETTING: Multiple PICUs in the United States. INTERVENTIONS: None other than standard care. MEASUREMENTS AND MAIN RESULTS: The decision tree included a first-level decision node based on day 1 septic acute kidney injury status and five subsequent biomarker-based decision nodes. The area under the curve for the tree was 0.95 (CI95, 0.91-0.99), with a sensitivity of 93% and a specificity of 88%. The tree was superior to day 1 septic acute kidney injury status alone for estimating day 3 septic acute kidney injury risk. In the test cohort, the tree had an area under the curve of 0.83 (0.72-0.95), with a sensitivity of 85% and a specificity of 77% and was also superior to day 1 septic acute kidney injury status alone for estimating day 3 septic acute kidney injury risk. CONCLUSIONS: We have derived and tested a model to estimate the risk of septic acute kidney injury on day 3 of septic shock using a novel panel of biomarkers. The model had very good performance in a test cohort and has test characteristics supporting clinical utility and further prospective evaluation.

Field evaluation of a new antibody-based diagnostic for Schistosoma haematobium and S. mansoni at the point-of-care in northeast Zimbabwe.

BACKGROUND: Rapid diagnostic tests (RDTs) for use at the point-of-care (POC) are likely to become increasingly useful as large-scale control programmes for schistosomiasis get underway. Given the low sensitivity of the reference standard egg count methods in detecting light infections, more sensitive tests will be required to monitor efforts aimed at eliminating schistosomiasis as advocated by the World Health Assembly Resolution 65.21 passed in 2012. METHODS: A recently developed RDT incorporating Schistosoma mansoni cercarial transformation fluid (SmCTF) for detection of anti-schistosome antibodies in human blood was here evaluated in children (mean age: 7.65 years; age range: 1-12 years) carrying light S. mansoni and S. haematobium infections in a schistosome-endemic area of Zimbabwe by comparison to standard parasitological techniques (i.e. the Kato-Katz faecal smear and urine filtration). Enzyme-linked immunosorbent assays (ELISAs) incorporating S. haematobium antigen preparations were also employed for additional comparison. RESULTS: The sensitivity of the SmCTF-RDT compared to standard parasitological methods was 100% while the specificity was 39.5%. It was found that the sera from RDT "false-positive" children showed significantly higher antibody titres in IgM-cercarial antigen preparation (CAP) and IgM-soluble egg antigen (SEA) ELISA assays than children identified by parasitology as "true-negatives". CONCLUSIONS: Although further evaluations are necessary using more accurate reference standard tests, these results indicate that the RDT could be a useful tool for the rapid prevalence-mapping of both S. mansoni and S. haematobium in schistosome-endemic areas. It is affordable, user-friendly and allows for diagnosis of both schistosome species at the POC.

'It really has made me think': Exploring how informal STEM learning practitioners developed critical reflective practice for social justice using the Equity Compass tool.

Critical reflective practice is a foundation of socially just pedagogy. This paper focuses on the informal STEM (science, technology, engineering, and maths) learning sector, where there is an acute shortage of support for critical reflective practice despite long-standing, entrenched issues of inequity. We analyse how practitioners used a new reflective tool, the Equity Compass, co-developed by researchers and practitioners through a five-year partnership. We report on multimodal qualitative data (interviews, ethnographic observations, group discussions, partner site visits, and workshops) from 12 practitioners in four settings in the UK: a community zoo, regional science centre, digital arts centre and an initiative supporting girls and non-binary young people into STEM. We discuss how using the Equity Compass: (i) increased and deepened practitioners' knowledge and understanding of equity issues; (ii) supported personal and institutional critical reflection, helping practitioners move beyond 'gut instinct' to interrogate their own positionality, ask new questions, and critically evaluate the effectiveness of attempts at inclusive practice; and (iii) fostered more intentional equitable planning and practice, such as participatory approaches that shared authority with learners and introduced more inclusive forms of representation. We conclude by discussing the challenges, limitations, and implications for supporting critical reflective practice among educators.

From Botox Party to Botulism: A Case Report and Public Health Warning on Adulterated Botulinum Toxin Injection.

Botulinum toxin (BoNT) is a potent neurotoxin with broad applications in medicine and cosmetics. Cases of botulism toxicity from aesthetic injections have been spiking in recent months across the United States. Here, we present a patient who presented with bulbar paralysis and increasing respiratory distress following BoNT injections performed at her home by an unlicensed aesthetician. The patient presented with ptosis, dysphagia, dysarthria, shortness of breath, and proximal muscle weakness. The patient was given botulism antitoxin and showed marked improvement in the following days. The pathophysiology of iatrogenic botulism is unknown but may be due to improper injections with large doses or direct injection into the bloodstream. Counterfeit BoNT injections have been reported and may include unsafe components or dangerous levels of BoNT that surpass the therapeutic dose.

Juvenile hormones direct primordial germ cell migration to the embryonic gonad.

Germ cells are essential to sexual reproduction. Across the animal kingdom, extracellular signaling isoprenoids, such as retinoic acids (RAs) in vertebrates and juvenile hormones (JHs) in invertebrates, facilitate multiple processes in reproduction. Here we investigated the role of these potent signaling molecules in embryonic germ cell development, using JHs in Drosophila melanogaster as a model system. In contrast to their established endocrine roles during larval and adult germline development, we found that JH signaling acts locally during embryonic development. Using an in vivo biosensor, we observed active JH signaling first within and near primordial germ cells (PGCs) as they migrate to the developing gonad. Through in vivo and in vitro assays, we determined that JHs are both necessary and sufficient for PGC migration. Analysis into the mechanisms of this newly uncovered paracrine JH function revealed that PGC migration was compromised when JHs were decreased or increased, suggesting that specific titers or spatiotemporal JH dynamics are required for robust PGC colonization of the gonad. Compromised PGC migration can impair fertility and cause germ cell tumors in many species, including humans. In mammals, retinoids have many roles in development and reproduction. We found that like JHs in Drosophila, RA was sufficient to impact mouse PGC migration in vitro. Together, our study reveals a previously unanticipated role of isoprenoids as local effectors of pre-gonadal PGC development and suggests a broadly shared mechanism in PGC migration.

The Price of Foods, Beverages, and Diets in Australia: An Updated Systematic Review.

CONTEXT: The price and affordability of food are priorities for public health and health equity; however, Australia lacks a consistent method to evaluate healthy versus unhealthy diets, creating a gap in routine food price reporting. OBJECTIVE: This review aimed to identify and summarize recent methods used to assess and monitor the price and/or affordability of food and beverages in Australia using a health lens. DATA SOURCES: Four academic databases (MEDLINE Complete, Global Health, CINAHL Complete, and Business Source Complete) were searched in English from 2016 to 2022. Relevant gray literature was searched through Google Scholar and government websites. DATA EXTRACTION: Five reviewers screened titles and abstracts, and full-text screening was conducted by 1 reviewer, with eligibility confirmed by a second reviewer. The quality of studies was assessed using the Joanna Briggs Institute "Checklist for Analytical Cross-Sectional Studies." DATA ANALYSIS: Twenty-five eligible studies were identified. Eleven studies used a version of the Healthy Diets Australian Standardized Affordability and Pricing protocol to collect prices for a "healthy" diet modelled on dietary guidelines and an "unhealthy" diet based on a habitual Australian diet. These studies consistently found unhealthy diets to be more expensive than healthy diets. Other identified methods included assessing the price of household diets across healthy baskets (n = 6), store types (n = 5), a planetary health diet (n = 1), packaged foods according to their Health Star Rating (n = 1), a fruit and vegetable basket (n = 1), school canteen foods against a traffic light system (n = 1), and weekly healthy meal plans (n = 1). Healthy diets tended to be less costly than less healthy diets, but both diets were often unaffordable in regional areas, for people on low incomes, and for First Nations peoples. CONCLUSION: Consistent country-wide application of methods for monitoring the price and affordability of foods and diets in Australia is needed-including tailored approaches for priority groups. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022333531.

Malnutrition risk, outcomes, and costs among older adults undergoing elective surgical procedures: A retrospective cohort study.

BACKGROUND: We examine here the association between malnutrition risk and adverse health outcomes among older adult patients undergoing elective surgical procedures. METHODS: We conducted a retrospective study using linked clinical and administrative databases. Malnutrition risk was assessed prior to surgery, defined by unintentional weight loss and decreased food intake. We performed a logistic regression analysis of the primary outcome, a composite adverse outcome measure, including death, bleeding, pneumonia, and other surgical complications. We conducted Fine-Gray proportional hazard regression analysis of hospital length of stay (LOS). We performed a generalized linear regression analysis of in-hospital cost data. All regression analyses controlled for frailty, age, sex, surgical category, and comorbidities. RESULTS: Of a total of 3457 older adult elective surgical patients (65-102 years), 310 (9.0%) screened positive for malnutrition risk. In multivariable regression analyses, malnutrition risk was associated with an increased risk of the composite adverse outcome (odds ratio [OR] = 1.74; 95% CI = 1.25-2.39), higher hospitalization costs (relative cost = 1.84; 95% CI = 1.59-2.13), and a decreased risk of discharge from the hospital (hazard ratio = 0.67; 95% CI = 0.59-0.77) compared with those who screened negative. CONCLUSION: Older adult patients with malnutrition risk were at an increased risk of adverse surgical outcomes, had longer LOS in the hospital, and incurred higher costs of care. It is important to screen for malnutrition risk and refer older adults for dietetic consults prior to elective surgery.

Neurologic Complications of Patients With COVID-19 Requiring Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.

In COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO), our primary objective was to determine the frequency of intracranial hemorrhage (ICH). Secondary objectives were to estimate the frequency of ischemic stroke, to explore association between higher anticoagulation targets and ICH, and to estimate the association between neurologic complications and in-hospital mortality. DATA SOURCES: We searched MEDLINE, Embase, PsycINFO, Cochrane, and MedRxiv databases from inception to March 15, 2022. STUDY SELECTION: We identified studies that described acute neurological complications in adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring ECMO. DATA EXTRACTION: Two authors independently performed study selection and data extraction. Studies with 95% or more of its patients on venovenous or venoarterial ECMO were pooled for meta-analysis, which was calculated using a random-effects model. DATA SYNTHESIS: Fifty-four studies (n = 3,347) were included in the systematic review. Venovenous ECMO was used in 97% of patients. Meta-analysis of ICH and ischemic stroke on venovenous ECMO included 18 and 11 studies, respectively. The frequency of ICH was 11% (95% CI, 8-15%), with intraparenchymal hemorrhage being the most common subtype (73%), while the frequency of ischemic strokes was 2% (95% CI, 1-3%). Higher anticoagulation targets were not associated with increased frequency of ICH (p = 0.06). In-hospital mortality was 37% (95% CI, 34-40%) and neurologic causes ranked as the third most common cause of death. The risk ratio of mortality in COVID-19 patients with neurologic complications on venovenous ECMO compared with patients without neurologic complications was 2.24 (95% CI, 1.46-3.46). There were insufficient studies for meta-analysis of COVID-19 patients on venoarterial ECMO. CONCLUSIONS: COVID-19 patients requiring venovenous ECMO have a high frequency of ICH, and the development of neurologic complications more than doubled the risk of death. Healthcare providers should be aware of these increased risks and maintain a high index of suspicion for ICH.

Is repeat head computed tomography necessary in children admitted with mild head injury and normal neurological exam?

BACKGROUND: Children admitted following mild head injury (MHI) often undergo repeat head computed tomography (HCT) to identify progression of injury, although there is little evidence to support this practice. METHODS: From January 2007 to December 2009, we retrospectively reviewed the medical records of patients aged 2 months to 18 years admitted with a diagnosis of MHI to a Level I Pediatric Trauma Center. Data including Glasgow Coma Scale, loss of consciousness, length of stay (LOS), and number and results of HCTs were analyzed. RESULTS: A total of 507 patients were admitted with MHI and normal neurological exam; 389 had a normal and 118 had an abnormal initial HCT. The median LOS in the normal HCT group was 17.68 h (5.47-109.68) and in the abnormal HCT group 36.63 h (10.15-192.40). The median number of HCTs in the normal HCT group was 1 (1-2) and in the abnormal HCT group 2 (1-5). CONCLUSIONS: Children admitted with MHI, abnormal initial HCT and normal neurological exam had longer LOS and more HCTs compared with children with normal initial HCTs. No patient in either group had any change in their management based on HCT. Therefore, repeat HCT may be unnecessary for patients with MHI and normal neurological exam.

Fun moments or consequential experiences? A model for conceptualising and researching equitable youth outcomes from informal STEM learning.

While there are many different frameworks seeking to identify what benefits young people might derive from participation in informal STEM (Science, Technology, Engineering and Mathematics) learning (ISL), this paper argues that the sector would benefit from an approach that foregrounds equity and social justice outcomes. We propose a new model for reflecting on equitable youth outcomes from ISL that identifies five key areas: (1) Grounded fun; (2) STEM capital; (3) STEM trajectories; (4) STEM identity work; and (5) Agency+ . The model is applied to empirical data (interviews, observations and youth portfolios) collected over one year in four UK-based ISL settings with 33 young people (aged 11-14), largely from communities that are traditionally under-represented in STEM. Analysis considers the extent to which participating youth experienced equitable outcomes, or not, in relation to the five areas. The paper concludes with a discussion of implications for ISL and how the model might support ongoing efforts to reimagine ISL as vehicle for social justice.

Changing the field: A Bourdieusian analysis of educational practices that support equitable outcomes among minoritized youth on two informal science learning programs.

Supporting more equitable participation in science, technology, engineering, and mathematics (STEM) remains a key, persistent educational challenge. This paper employs a sociological Bourdieusian lens to explore how equitable youth outcomes might be supported through informal science learning (ISL). Drawing on multimodal, ethnographic data from four case study youth aged 11-14 from two ISL programs, we identify four areas of practice that were enacted to a greater or lesser extent in the programs in support of equitable youth outcomes. We identify how the equitable potential of these practices was realized through a disruption of dominant power relations. It is argued that ISL should focus on changing the field, rather than young people. Affordances and limitations of the Bourdieusian lens are discussed.

Comparison of Outcomes of Glaucoma Drainage Implant Surgery With or Without Prior Failed Trabeculectomy.

PRECIS: A comparison of 186 glaucoma patients with mixed diagnoses who underwent nonvalved glaucoma drainage device (GDD) implant surgery showed similar long-term intraocular pressure (IOP), medication, and visual acuity (VA) outcomes between those with prior failed trabeculectomy surgery versus those without. PURPOSE: The purpose of this study was to evaluate whether prior failed trabeculectomy adversely affects the outcome of glaucoma tube surgery. PATIENTS AND METHODS: A total of 186 eyes of 186 patients who underwent a nonvalved GDD implant surgery by a single surgeon between 1996 and 2015 at a University practice were included. Patients were of mixed diagnoses and over 18 years old. Before the GDD surgery, 65 had a previous failed glaucoma filtering surgery and 121 had no prior glaucoma surgery. Demographic information, preoperative and postoperative IOP, medication, VA, and complications were collected from chart review. RESULTS: No significant difference was noted in mean IOP and mean medication use (13.0 and 12.6 mm Hg on 2.0 and 1.7 medication classes at 5 y postoperatively, respectively), mean VA and change in VA from baseline, or numbers of complications (P>0.05), between eyes that had a prior failed filtration surgery and those that had not. Kaplan-Meier plots for failure over 5 years using a lower limit of <5 mm Hg and an upper limit of ≥18, ≥15, or ≥12 mm Hg did not show a significant difference between groups. Subanalyses were performed to examine only primary glaucoma eyes and results were similar. Further group subanalyses comparing those with baseline IOP ≥25 or <25 mm Hg, age 65 and above or below 65 years and those specifically with Baerveldt 350 mm2 implants also did not show significant differences. CONCLUSION: Prior failed filtration surgery does not appear to affect the outcome of future GDD surgery.