OX40 shapes an inflamed tumor immune microenvironment and predicts response to immunochemotherapy in diffuse large B-cell lymphoma.

OX40 enhances the T-cell activation via costimulatory signaling. However, its molecular characteristics and value in predicting response to immunochemotherapy in DLBCL remain largely unexplored. Here, we performed an integrative analysis of sequencing and multiplex immunofluorescence staining, and discovered abnormally higher expression of OX40 in DLBCL patients. Elevated OX40 could activate T cells leading to a higher immune score for tumor immune microenvironment (TiME). OX40 upregulation simultaneously happened with immune-related genes including PD-1, CTLA4 and TIGIT et,al. Patients with high OX40 expression exhibited a lower Ann Arbor stage and IPI score and more easily achieved a complete response/partial response. The analysis of infiltrated T-cell subset revealed that patients with a greater number of CD4+/OX40+ or CD8+/OX40+ T cells had a longer OS. Our findings indicated that OX40 shapes an inflamed tumor immune microenvironment and predicts response to immunochemotherapy, providing insights for the application of OX40 agonist in DLBCL patients.

Lenalidomide maintenance following high-dose therapy and autologous haematopoietic stem cell transplantation in chemo-resistant or high-risk non-Hodgkin lymphoma: A phase I/II study.

Improved maintenance treatments are needed for patients with relapsed/refractory aggressive lymphomas after autologous haematopoietic stem cell transplantation (ASCT). Several studies with lenalidomide have been found to have activity in the treatment of relapsed/refractory aggressive lymphomas. In the present phase I/II, single-arm, open-label study, 59 patients with high-risk relapsed non-Hodgkin lymphoma received pretransplant BEAM chemotherapy and ASCT followed by 12 months of maintenance lenalidomide once daily on Days 1-21 (28-day cycles) beginning at post-transplantation Day 100. The most common histologies were mantle cell lymphoma (56%) and diffuse large B-cell lymphoma (24%). The maximum tolerated dose in the dose-finding part of the study was 15 mg, but cytopenias led to the subsequent adoption of a 10 mg dose in the final study. Sixteen patients (27%) completed 12 cycles of lenalidomide maintenance. The most common reason for discontinuation was adverse events (31%). These were primarily haematologic, and 56% of patients experienced Grade 3-4 events. Two-year PFS rates (95% CIs) were 70% (56%-80%), 45% (19%-68%) and 81% (66%-90%); 2-year OS rates (95% CIs) were 91% (80%-96%), 93% (61%-99%) and 90% (76%-96%) in all patients, patients completing and patients not completing 12-month maintenance respectively. These results do not support the use of lenalidomide maintenance in this setting.

Myopia and Its Association with Near Work, Outdoor Time, and Housing Type among Schoolchildren in South India.

SIGNIFICANCE: In this comprehensive assessment of environmental associations with refractive status among schoolchildren in India, outdoor time was the key modifiable risk factor associated with myopia rather than time spent on near work. PURPOSE: This study aimed to investigate the environmental risk factors associated with myopia among adolescent schoolchildren in South India. METHODS: Children in grades 8 to 10 from 11 schools in Tamil Nadu, South India, underwent eye examination and risk factor assessments through a modified version of the Sydney myopia questionnaire. Time spent on near work and outdoors was analyzed after division into three groups based on tertiles. Mixed-effects logistic regression was performed to assess the factors associated with myopia. RESULTS: A total of 3429 children (response rate, 78.4%) provided both questionnaire and refraction data. The mean (standard deviation) age was 14 (0.93) years with an equal distribution of sexes. Myopia was present among 867 children (noncycloplegic spherical equivalent refraction, ≤-0.75 D). Refraction was not associated with near work tertiles ( P = .22), whereas less time outdoors was associated with higher myopic refractions ( P = .01). Refraction shifted toward increased myopia with an increase in the near-work/outdoor time ratio ( P = .005). Children living in apartment housing had a higher prevalence of myopia compared with other types of housing ( P < .001). In multivariate analysis, increased time outdoors was a protective factor against myopia (odds ratio, 0.79; 95% confidence interval, 0.63 to 0.99; P = .04), whereas living in apartment housing (odds ratio, 1.27; 95% confidence interval, 1.04 to 1.55; P = .02) was a significant risk factor. CONCLUSIONS: In this cohort of Indian children, outdoor time, increased near-work/outdoor time ratio, and type of housing were the factors associated with myopia. Policies should target implementing a balance between near-work and outdoor time among children.

Virtual simulated international placements as an innovation for internationalisation in undergraduate programs: a mixed methods study.

BACKGROUND: Inherent features in virtual simulation could be utilised to deliver collaborative global education that is inclusive, accessible, and valued by students and facilitators. The aim of this study was to evaluate the impact of the International Eyecare Community (IEC) platform's virtual simulated international placements (VSIP) in optometric education. METHODS: An international, multi-center, cross-sectional mixed methods study with Deakin University, Australia, and the Elite School of Optometry, India, was used to evaluate the impact of VSIP in the IEC using pre-existing deidentified data collected from teaching and learning activities within the optometry course curriculum. Data on students and facilitators perceptions of the VSIP were collected through deidentified transcripts from focus group discussions. The data were interpreted using descriptive statistics and qualitative analysis using constant comparison for thematic analysis. RESULTS: A total of 64 out of 167 student participants completed survey responses (39%) and 46 out of 167 (28%) completed self-reflective inventories. Focus groups with 6 student participants and 6 facilitator participants were recorded and analysed. Student participants reported the IEC was relevant (98% agreement) and motivated them to apply theoretical knowledge to a clinical context (97% agreement). The themes identified through qualitative analysis were: factors inherent to the virtual simulation that enabled learning through VSIP, the VSIP supported cognitive apprenticeship, VSIP enabled clinical learning for optometric education, VSIP' role in cross-cultural professional identity development in optometry students. CONCLUSION: The study found that the VSIP platform helped to motivate students to learn and improve their clinical skills. The VSIP was considered a potential supplement to physical clinical placements and could revolutionize global optometric education by offering co-learning across cultures.

Lean in one way, in obesity another: effects of moderate exercise in brown adipose tissue of early overfed male Wistar rats.

BACKGROUND: Early postnatal overfeeding (PO) induces long-term overweight and reduces brown adipose tissue (BAT) thermogenesis. Exercise has been suggested as a possible intervention to increase BAT function. In this study, we investigated chronical effects of moderate-intensity exercise in BAT function in postnatal overfed male Wistar rats METHODS: Litters' delivery was on postnatal-day 0 - PN0. At PN2, litters were adjusted to nine (normal litter - NL) or three pups (small litter - SL) per dam. Animals were weaned on PN21 and in PN30 randomly divided into sedentary (NL-Sed and SL-Sed) or exercised (NL-Exe and SL-Exe), N of 14 litters per group. Exercise protocol started (PN30) with an effort test; training sessions were performed three times weekly at 60% of the VO2max achieved in effort test, until PN80. On PN81, a temperature transponder was implanted beneath the interscapular BAT, whose temperature was assessed in periods of lights-on and -off from PN87 to PN90. Sympathetic nerve activation of BAT was registered at PN90. Animals were euthanized at PN91 and tissues collected RESULTS: PO impaired BAT thermogenesis in lights-on (pPO < 0.0001) and -off (pPO < 0.01). Exercise increased BAT temperature in lights-on (pExe < 0.0001). In NL-Exe, increased BAT activity was associated with higher sympathetic activity (pExe < 0.05), ß3-AR (pExe < 0.001), and UCP1 (pExe < 0.001) content. In SL-Exe, increasing BAT thermogenesis is driven by a combination of tissue morphology remodeling (pExe < 0.0001) with greater effect in increasing UCP1 (pExe < 0.001) and increased ß3-AR (pExe < 0.001) content. CONCLUSION: Moderate exercise chronically increased BAT thermogenesis in both, NL and SL groups. In NL-Exe by increasing Sympathetic activity, and in SL-Exe by a combination of increased ß3-AR and UCP1 content with morphologic remodeling of BAT. Chronically increasing BAT thermogenesis in obese subjects may lead to higher overall energy expenditure, favoring the reduction of obesity and related comorbidities.

Phase 1 trial of carfilzomib in relapsed/refractory peripheral T-cell lymphoma.

Peripheral T-cell lymphomas (PTCL) are a unique subset of lymphomas with a poor prognosis due to limited treatment options. We performed a phase 1 study of carfilzomib in patients with relapsed/refractory PTCL to determine the safety profile and the maximum tolerated dose (MTD) of this agent. The study was a classical 3 + 3 phase 1 design with intra-patient dose escalation allowed beginning on day 8 of cycle 1 and subsequently. Dose-limiting toxicity (DLT) was defined as the occurrence of any grade 3/4 adverse event. Carfilzomib was given on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Fifteen patients were enrolled from 3 centers. The median age of patients was 62. The median number of prior therapies for subjects on this trial was five. The MTD of carfilzomib was 36 mg/m2. Dose-limiting toxicities included anemia and sepsis. Serious adverse events were seen in 45% of patients. Single-agent carfilzomib leads to a complete response in one patient and a partial response in one patient. Overall, the drug was reasonably tolerated for a heavily pretreated population, but the limited response rate and short duration of response demonstrate a lack of promise for carfilzomib as a single agent in this patient population.

Dynamic biomarker and imaging changes from a phase II study of pre- and post-surgical sunitinib.

OBJECTIVE: To explore translational biological and imaging biomarkers for sunitinib treatment before and after debulking nephrectomy in the NeoSun (European Union Drug Regulating Authorities Clinical Trials Database [EudraCT] number: 2005-004502-82) single-centre, single-arm, single-agent, Phase II trial. PATIENTS AND METHODS: Treatment-naïve patients with metastatic renal cell carcinoma (mRCC) received 50 mg once daily sunitinib for 12 days pre-surgically, then post-surgery on 4 week-on, 2 week-off, repeating 6-week cycles until disease progression in a single arm phase II trial. Structural and dynamic contrast-enhanced magnet resonance imaging (DCE-MRI) and research blood sampling were performed at baseline and after 12 days. Computed tomography imaging was performed at baseline and post-surgery then every two cycles. The primary endpoint was objective response rate (Response Evaluation Criteria In Solid Tumors [RECIST]) excluding the resected kidney. Secondary endpoints included changes in DCE-MRI of the tumour following pre-surgery sunitinib, overall survival (OS), progression-free survival (PFS), response duration, surgical morbidity/mortality, and toxicity. Translational and imaging endpoints were exploratory. RESULTS: A total of 14 patients received pre-surgery sunitinib, 71% (10/14) took the planned 12 doses. All underwent nephrectomy, and 13 recommenced sunitinib postoperatively. In all, 58.3% (seven of 12) of patients achieved partial or complete response (PR or CR) (95% confidence interval 27.7-84.8%). The median OS was 33.7 months and median PFS was 15.7 months. Amongst those achieving a PR or CR, the median response duration was 8.7 months. No unexpected surgical complications, sunitinib-related toxicities, or surgical delays occurred. Within the translational endpoints, pre-surgical sunitinib significantly increased necrosis, and reduced cluster of differentiation-31 (CD31), Ki67, circulating vascular endothelial growth factor-C (VEGF-C), and transfer constant (KTrans , measured using DCE-MRI; all P < 0.05). There was a trend for improved OS in patients with high baseline plasma VEGF-C expression (P = 0.02). Reduction in radiological tumour volume after pre-surgical sunitinib correlated with high percentage of solid tumour components at baseline (Spearman's coefficient ρ = 0.69, P = 0.02). Conversely, the percentage tumour volume reduction correlated with lower baseline percentage necrosis (coefficient = -0.51, P = 0.03). CONCLUSION: Neoadjuvant studies such as the NeoSun can safely and effectively explore translational biological and imaging endpoints.

In Vivo Bioconcentration of 10 Anionic Surfactants in Rainbow Trout Explained by In Vitro Data on Partitioning and S9 Clearance.

Bioconcentration factors (BCFs) in rainbow trout were measured for 10 anionic surfactants with a range of alkyl chain lengths and different polar head groups. The BCFs ranged from 0.04 L kg-1 ww (for C10SO3) to 1370 L kg-1 ww (C16SO3). There was a strong correlation between the log BCF and log membrane lipid-water distribution ratio (DMLW, r2 = 0.96), and biotransformation was identified as the dominant elimination mechanism. The strong positive influence of DMLW on BCF was attributed to two phenomena: (i) increased partitioning from water into the epithelial membrane of the gill, leading to more rapid diffusion across this barrier and more rapid uptake, and (ii) increased sequestration of the surfactant body burden into membranes and other body tissues, resulting in lower freely dissolved concentrations available for biotransformation. Estimated whole-body in vivo biotransformation rate constants kB-BCF are within a factor three of rate constants estimated from S9 in vitro assays for six of the eight test chemicals for which kB-BCF could be determined. A model-based assessment indicated that the hepatic clearance rate of freely dissolved chemicals was similar for the studied surfactants. The dataset will be useful for evaluation of in silico and in vitro methods to assess bioaccumulation.

Prevalence of myopia among urban and suburban school children in Tamil Nadu, South India: findings from the Sankara Nethralaya Tamil Nadu Essilor Myopia (STEM) Study.

PURPOSE: To report the baseline prevalence of myopia among school children in Tamil Nadu, South India from a prospective cohort study. METHODS: Children between the ages of 5 and 16 years from 11 schools in two districts of Tamil Nadu underwent vision screening. All children underwent visual acuity assessment using a Pocket Vision Screener followed by non-cycloplegic open-field autorefraction (Grand Seiko WAM-5500). Myopia was defined as a spherical equivalent (SE) refraction of ≤-0.75 D and high myopia was defined as SE ≤ -6.00 D. Distribution of refraction, biometry and factors associated with prevalence of myopia were the outcome measures. RESULTS: A total of 14,699 children completed vision screening, with 2% (357) of them having ocular abnormalities other than refractive errors or poor vision despite spectacle correction. The remaining 14,342 children (7557 boys; 52.69%) had a mean age of 10.2 (Standard Deviation [SD] 2.8) years. A total of 2502 had myopia in at least one eye, a prevalence of 17.5% (95% CI: 14.7-20.5%), and 74 (0.5%; 95% CI: 0.3-0.9%) had high myopia. Myopia prevalence increased with age (p < 0.001), but sex was not associated with myopia prevalence (p = 0.24). Mean axial length (AL; 23.08 (SD = 0.91) mm) and mean anterior chamber depth (ACD; 3.45 (SD = 0.27) mm) positively correlated with age (p < 0.001). The mean flat (K1; 43.37 (SD = 1.49) D) and steep (K2; 44.50 (SD = 1.58) D) corneal curvatures showed negative correlation with age (p = 0.02 and p < 0.001, respectively). In the multivariable logistic regression, older age and urban school location had higher odds for prevalence of myopia. CONCLUSION: The baseline prevalence of myopia among 5- to 16-year-old children in South India is larger than that found in previous studies, indicating that myopia is becoming a major public health problem in this country.

Enhanced hepatic respiratory capacity and altered lipid metabolism support metabolic homeostasis during short-term hypoxic stress.

BACKGROUND: Tissue hypoxia is a key feature of several endemic hepatic diseases, including alcoholic and non-alcoholic fatty liver disease, and organ failure. Hypoxia imposes a severe metabolic challenge on the liver, potentially disrupting its capacity to carry out essential functions including fuel storage and the integration of lipid metabolism at the whole-body level. Mitochondrial respiratory function is understood to be critical in mediating the hepatic hypoxic response, yet the time-dependent nature of this response and the role of the respiratory chain in this remain unclear. RESULTS: Here, we report that hepatic respiratory capacity is enhanced following short-term exposure to hypoxia (2 days, 10% O2) and is associated with increased abundance of the respiratory chain supercomplex III2+IV and increased cardiolipin levels. Suppression of this enhanced respiratory capacity, achieved via mild inhibition of mitochondrial complex III, disrupted metabolic homeostasis. Hypoxic exposure for 2 days led to accumulation of plasma and hepatic long chain acyl-carnitines. This was observed alongside depletion of hepatic triacylglycerol species with total chain lengths of 39-53 carbons, containing palmitic, palmitoleic, stearic, and oleic acids, which are associated with de novo lipogenesis. The changes to hepatic respiratory capacity and lipid metabolism following 2 days hypoxic exposure were transient, becoming resolved after 14 days in line with systemic acclimation to hypoxia and elevated circulating haemoglobin concentrations. CONCLUSIONS: The liver maintains metabolic homeostasis in response to shorter term hypoxic exposure through transient enhancement of respiratory chain capacity and alterations to lipid metabolism. These findings may have implications in understanding and treating hepatic pathologies associated with hypoxia.

A cohort study for the development and validation of a reflective inventory to quantify diagnostic reasoning skills in optometry practice.

BACKGROUND: Diagnostic reasoning is an essential skill for optometry practice and a vital part of the curriculum for optometry trainees but there is limited understanding of how diagnostic reasoning is performed in optometry or how this skill is best developed. A validated and reliable self-reflective inventory for diagnostic reasoning in optometry, would enable trainees and registered practitioners to benchmark their diagnostic reasoning skills, identify areas of strength and areas for improvement. METHODS: A 41 item self-reflective inventory, the Diagnostic Thinking Inventory, used extensively in the medical field was adapted for use in optometry and called the Diagnostic Thinking Inventory for Optometry (DTI-O). The inventory measures two subdomains of diagnostic reasoning, flexibility in thinking and structured memory. Context based changes were made to the original inventory and assessed for face and content validity by a panel of experts. The inventory was administered to two groups, experienced (qualified) optometrists and second-year optometry students to establish validity and reliability of the self-reflective tool in optometry. RESULTS: Exploratory Factor Analysis uncovered 13 domain specific items were measuring a single construct, diagnostic reasoning. One misfitting item was removed following Rasch analysis. Two unidimensional subdomains were confirmed in the remaining 12 items: Flexibility in Thinking (χ2 = 12.98, P = 0.37) and Structured Memory (χ2 = 8.74, P = 0.72). The 'Diagnostic Thinking Inventory for Optometry Short' (DTI-OS) tool was formed from these items with the total and subdomain scores exhibiting strong internal reliability; Total score Cα = 0.92. External reliability was established by test-retest methodology (ICC 0.92, 95% CI 0.83-0.96, P < .001) and stacked Rasch analysis (one-way ANOVA, F = 0.07, P = 0.80). Qualified optometrists scored significantly higher (P < .001) than students, demonstrating construct validity. CONCLUSION: This study showed that the DTI-O and DTI-OS are valid and reliable self-reflective inventories to quantify diagnostic reasoning ability in optometry. With no other validated tool to measure this metacognitive skill underpinning diagnostic reasoning a self-reflective inventory could support the development of diagnostic reasoning in practitioners and guide curriculum design in optometry education.

Supervisor experiences of extended clinical placements in optometry: a mixed methods study.

BACKGROUND: In Australia, optometry students have traditionally undertaken their clinical training in short-block rotations at University-led teaching clinics in metropolitan locations. Demand for clinical placements is growing as the number of optometry students steadily increases. As such, universities and clinical education providers must look for more diverse methods of student placement. Extended clinical placements in community-based settings are one alternative: a model similar to the longitudinal clerkships in medicine. This study aimed to explore the experience of extended clinical placements from the perspective of the optometrists who supervised students. It also sought to determine whether there were differences in views between metropolitan and rural practitioners. METHODS: This mixed methods study included a survey and interviews with optometrists who had previously supervised Deakin University optometry students on an extended 26-week (2 x 13-weeks) clinical placement. Lines of enquiry focused on; the benefits and challenges associated with extended placements; areas for improvement; duration of the placement; and willingness to supervise further students. Interviews were transcribed verbatim and analysed using Braun and Clarke's 6 step method of thematic analysis with a qualitative descriptive approach. RESULTS: Supervisors felt that hosting a student prompted greater reflective practice and critical appraisal of clinical decisions. The extended nature of the placement was thought to foster greater immersion in the clinical setting and community for the students and establish a stronger relationship between supervisor and student. Supervisors recognised the importance of role-modelling and mentoring the next generation of optometrists however noted that taking on a student was a sizeable commitment. Willingness to host a student was not dependent on the supervisor's location (rural vs metropolitan) p = 0.57. However, interviews uncovered motivations that were unique to supervisors residing in rural locations, such as succession planning. CONCLUSION: Overall, supervisors were positive about the value of student extended clinical placement in optometry and felt that it was a fulfilling and professionally beneficial experience. Lack of time and financial remuneration were the key downsides highlighted. Schools of optometry might carefully consider engaging in discussion about the duration of such placements, but 26 weeks was considered appropriate by supervisors.

Student perspectives of extended clinical placements in optometry: a qualitative study.

BACKGROUND: The number of students enrolled in health courses at Australian universities is rising, increasing demand for clinical placements. Optometry students have historically undertaken clinical training in short-block rotations at university-led teaching clinics in metropolitan locations. This is changing, with some optometry programs adopting extended placements. These placements are conducted in community-based practices, with many incorporating a rural component to the training. This study explored factors which influence placement success and satisfaction from the perspective of optometry students. METHODS: Nine focus groups were undertaken with 42 final year optometry students upon completion of a 26-week placement (of which at least half was undertaken in a non-metropolitan area, or area where a shortage of optometrists has been identified). Focus groups were audio recorded and transcribed verbatim. Thematic analysis was conducted according to Braun and Clarke's 6 step method. RESULTS: Four key themes were identified during analysis. 'Changing identity', related to how the students grew both personally and professionally, with the extended placement being considered the vital component that allowed students to begin thinking of themselves as clinicians. The theme 'Dealing with complex dynamics and circumstances' predominantly described instances where the student-supervisor relationship was strained, resulting in high levels of anxiety made worse by a perceived lack of university support. 'Optometrist under instruction', related to students feeling that the placement was an ideal opportunity to trial the everyday reality of work without the obligation of an ongoing commitment or employment contract. Finally, the theme 'Rural practice is more rewarding', was about a chance to seek different experiences, meet new people and challenge themselves professionally. CONCLUSION: While the majority of students enjoyed their placement and felt that it was the key component of their training that equipped them for future practice, it is clear that universities and placement providers must provide both students and supervisors thorough and explicit guidance covering placement expectations. Furthermore, student support systems should be embedded into placement programs to ensure where issues arise, they are dealt with promptly and successfully. It is vital that ongoing professional development and pedagogical training for supervisors underpins continued accreditation.

The perceived value and impact of virtual simulation-based education on students' learning: a mixed methods study.

BACKGROUND: Virtual simulations are used throughout healthcare training programs to enable development of clinical skills, however the potential for virtual simulation to enhance cognitive and affective skills is less well understood. This study explored pre-clinical optometry students' perceptions of the impact of virtual simulation on the development of core competency skills including patient-centred care, communication, scientific literacy, and evidence-based practice. METHODS: A mixed methods study was conducted using pre-existing anonymized data from an electronic survey distributed to pre-clinical optometry students enrolled in the double degree Bachelor of Vision Science/Master of Optometry at Deakin University, Australia. The data were interpreted using descriptive statistics and qualitative analysis using constant comparison for thematic analysis. RESULTS: A total of 51 responses were analyzed. Students reported that virtual simulation motivated them to become an optometrist (93%) and to learn beyond the course material (77%). Students reported that after participating in the virtual simulation, their core competency skills improved: patient-centered care (100%) evidence-based practice (93%) and clinical reasoning (93%). The themes identified through qualitative analysis were: enablers to cognitive experience in virtual simulation in optometry education, realism of the virtual simulation design, dimensions of fidelity in virtual simulations design replicated the complexity of the optometric environment, virtual simulation as an enabler for learning and assessment in optometry education, a place to develop cognitive and affective skills and application of learning in the virtual simulation developed an appreciation of future roles and professional identity. CONCLUSION: Optometry students perceived virtual simulation in optometric education as a valuable training and assessment strategy enabled by qualities that generate contextual, cognitive, functional, task and psychological fidelity. The data provide insight to inform how optometry educators can incorporate simulation into the curriculum.

Effects of tracker location on the accuracy and precision of the Gazepoint GP3 HD for spectacle wearers.

Remote view eye-tracking systems are prone to errors when used on spectacle wearers due to reflections from the lenses and frame that result in inaccurate tracking. Traditionally, these trackers are situated below a computer monitor and the viewer's eye moments are recorded while they view the screen. Reflections may be influenced by the pantoscopic tilt of the spectacles, whereby the tilt angle causes incident light to be reflected to the camera. To overcome this problem, we propose mounting the tracker above the monitor to avoid these reflections and test the accuracy and precision of subjects with single vision spectacles, multifocals, and no correction, using both mounting positions. Experimental results showed that this alternate position had overall worse accuracy (4.06° ± 0.13) and precision (0.67° ± 0.05) compared to the standard configuration (2.15° ± 0.06 vs. 0.50° ± 0.03), with more invalid readings (5.91 vs. 19.19%) for single vision lens wearers. Multifocals performed better for the top-mounting position for the top portion of the monitor, suggesting higher-order aberrations from the bottom portion of the lens negatively impact data quality. Higher pantoscopic tilt angles displayed an improved accuracy for this alternate position (r(9) = - 0.69, p = 0.02), with superior accuracy for tilt angles greater than 14° compared to the standard configuration. This study quantifies the impact of spectacle wear on eye-tracking performance and suggests other alternate mounting positions may be viable in certain situations.

Podocyte endowment and the impact of adult body size on kidney health.

Low birth weight is a risk factor for chronic kidney disease, whereas adult podocyte depletion is a key event in the pathogenesis of glomerulosclerosis. However, whether low birth weight due to poor maternal nutrition is associated with low podocyte endowment and glomerulosclerosis in later life is not known. Female Sprague-Dawley rats were fed a normal-protein diet (NPD; 20%) or low-protein diet (LPD; 8%), to induce low birth weight, from 3 wk before mating until postnatal day 21 (PN21), when kidneys from some male offspring were taken for quantitation of podocyte number and density in whole glomeruli using immunolabeling, tissue clearing, and confocal microscopy. The remaining offspring were fed a normal- or high-fat diet until 6 mo to induce catch-up growth and excessive weight gain, respectively. At PN21, podocyte number per glomerulus was 15% lower in low birth weight (LPD) than normal birth weight (NPD) offspring, with this deficit greater in outer glomeruli. Surprisingly, podocyte number in LPD offspring increased in outer glomeruli between PN21 and 6 mo, although an overall 9% podocyte deficit persisted. Postnatal fat feeding to LPD offspring did not alter podometric indexes or result in glomerular pathology at 6 mo, whereas fat feeding in NPD offspring was associated with far greater body and fat mass as well as podocyte loss, reduced podocyte density, albuminuria, and glomerulosclerosis. This is the first report that maternal diet can influence podocyte endowment. Our findings provide new insights into the impact of low birth weight, podocyte endowment, and postnatal weight on podometrics and kidney health in adulthood.NEW & NOTEWORTHY The present study shows, for the first time, that low birth weight as a result of maternal nutrition is associated with low podocyte endowment. However, a mild podocyte deficit at birth did not result in glomerular pathology in adulthood. In contrast, postnatal podocyte loss in combination with excessive body weight led to albuminuria and glomerulosclerosis. Taken together, these findings provide new insights into the associations between birth weight, podocyte indexes, postnatal weight, and glomerular pathology.

Emergency response to radiological and nuclear accidents and incidents.

Bone marrow damage is an important consequence of exposure to acute high-dose whole-body radiation. As such, haematologists can play an important role in managing this complication. However, these accident and incident scenarios are complex and often involve injuries to other organs and tissues from heat, projectiles and chemicals. In the case of a large-scale event there will likely be severe infrastructure disruptions and injury or death to medical personnel. Accurate estimates of dose and uniformity of exposure are needed to intelligently direct appropriate interventions, which range from antibiotics, antifungals and anti-virus drugs, molecularly-cloned haematopoietic growth factors and, in rare instances, haematopoietic cell transplants. These therapies are ones that haematologists often use in the context of anti-cancer therapy, especially therapy of haematological cancers like leukaemia. However, most haematologists have little knowledge of radiation biology and should consider updating this aspect of their expertise in continuing medical education. As in other areas of medicine, prevention is better than cure and haematologists should be active in decreasing risks of a nuclear war.

The First 2 Years of Biosimilar Epoetin for Cancer and Chemotherapy-Induced Anemia in the U.S.: A Review from the Southern Network on Adverse Reactions.

Biosimilars are biologic drug products that are highly similar to reference products in analytic features, pharmacokinetics and pharmacodynamics, immunogenicity, safety, and efficacy. Biosimilar epoetin received Food and Drug Administration (FDA) approval in 2018. The manufacturer received an FDA nonapproval letter in 2017, despite receiving a favorable review by FDA's Oncologic Drugs Advisory Committee (ODAC) and an FDA nonapproval letter in 2015 for an earlier formulation. We discuss the 2018 FDA approval, the 2017 FDA ODAC Committee review, and the FDA complete response letters in 2015 and 2017; review concepts of litigation, naming, labeling, substitution, interchangeability, and pharmacovigilance; review European and U.S. oncology experiences with biosimilar epoetin; and review the safety of erythropoiesis-stimulating agents. In 2020, policy statements from AETNA, United Health Care, and Humana indicated that new epoetin oncology starts must be for biosimilar epoetin unless medical need for other epoetins is documented. Empirical studies report that as of 2012, reference epoetin use decreased from 40%-60% of all patients with cancer with chemotherapy-induced anemia to <5% of such patients because of safety concerns. Between 2018 and 2020, biosimilar epoetin use varied, increasing to 81% among one private insurer's patients covered by Medicare whose cancer care is administered with Oncology Analytics and to 41% with the same private insurer's patients with cancer covered by commercial health insurance and administered by the private insurer, to 0% in several Veterans Administration Hospitals, increasing to 100% in one large county hospital in California, and with yet-to-be-reported data from most oncology settings. We conclude that biosimilar epoetin appears to have overcome some barriers since 2015, although current uptake in the U.S. is variable. Pricing and safety considerations for all erythropoiesis-stimulating agents are primary determinants of biosimilar epoetin oncology uptake. IMPLICATIONS FOR PRACTICE: Few oncologists understand substitution and interchangeability of biosimilars with reference drugs. Epoetin biosimilar is new to the market, and physician and patient understanding is limited. The development of epoetin biosimilar is not familiar to oncologists.

A call for HoLEP: AEEP for mega-prostates (≥ 200 cc).

PURPOSE: To evaluate the efficiency and efficacy of HoLEP, and methods of tissue retrieval, in patients with prostate volume (PV) ≥ 200 cc (Group 1) and to compare these to patients with PV 80-199 cc (Group 2). METHODS: A database of all cases performed under the care of two surgeons at a tertiary HoLEP centre was reviewed. RESULTS: 157 patients with PV ≥ 200 cc were compared to 157 of the most recent consecutive cases with PV 80-199 cc. Median (IQR) enucleation efficiency was greater in Group 1 [2.8 g/min (2.2-3.5)] than Group 2 [2.1 g/min (1.6-2.5), p < 0.001]. Morcellation efficiency did not differ significantly. Cystotomy was required for tissue retrieval in Group 1 only (5.7%). Decrease in serum haemoglobin (Hb) was greater in Group 1 (19 g/l (30-8) vs 12 (18-3.5), p < 0.001) with a transfusion rate of 4.5% vs 1.3%, respectively (p = 0.104). Length of stay was longer in Group 1 than Group 2 (1 day (1-2) vs 1 (1-1), p < 0.001). There were no significant differences between groups in: time to and success of first trial without catheter, pre- and post-operative IPSS, Qmax and PVR, and 3 month catheter-free and urinary incontinence rates. CONCLUSION: HoLEP outcomes are largely PV-independent even when PV is ≥ 200 cc, although length of stay and reduction in Hb are greater in this group. Alternatives to pure morcellation, such as cystotomy and resection of nodules, are more likely to be necessary with PV ≥ 200 cc.