Operating Room Extubation for Patients Undergoing Cardiac Surgery: A National Society of Thoracic Surgeons Database Analysis.

BACKGROUND: The utility of operating room extubation (ORE) after cardiac surgery over fast-track extubation (FTE) within 6 hours remains contested. We hypothesized ORE would be associated with equivalent rates of morbidity and mortality, relative to FTE. METHODS: Patients undergoing nonemergent cardiac surgery were identified in The Society of Thoracic Surgeons Adult Cardiac Surgery Database between July 2017 and December 2022. Only procedures with The Society of Thoracic Surgeons risk models were included. Risk-adjusted outcomes of ORE and FTE were compared by observed-to-expected ratios with 95% CIs aggregated over all procedure types, and ORE vs FTE adjusted odds ratios (ORs) specific to each procedure type using multivariable logistic regression. Analyzed outcomes were operative mortality, prolonged length of stay, composite reoperation for bleeding and reintubation, and composite morbidity and mortality. RESULTS: The study population of 669,099 patients across 1069 hospitals included 36,298 ORE patients in 296 hospitals. Risk-adjusted analyses found that ORE was associated with statistically similar or better results across each of the 4 outcomes and procedure subtypes. Notably, rates of postoperative mortality were significantly lower in ORE patients undergoing coronary artery bypass grafting (OR, 0.54; 95% CI, 0.46-0.65), aortic valve replacement (OR, 0.43; 95% CI, 0.24-0.77), and mitral valve replacement (OR, 0.48; 95% CI, 0.26-0.89). CONCLUSIONS: Extubation in the OR was safe and effective in a selected patient population and may be associated with superior outcomes in coronary artery bypass, aortic valve replacement, and mitral valve replacement. These national data appear to confirm institutional experiences regarding the potential benefit of OR extubation. Further refinement of optimal populations may justify randomized investigation.

Development and Characterization of a Photocrosslinkable, Chitosan-Based, Nerve Growth Factor-Eluting Hydrogel for the Ocular Surface.

Purpose: Recombinant human nerve growth factor (rhNGF; cenegermin-bkbj, OXERVATE) is the first and only U.S. Food and Drug Administration-approved treatment for moderate to severe neurotrophic keratopathy. The aim of this study was to determine the feasibility of incorporating a version of rhNGF in a mucoadhesive hydrogel capable of sustained drug release to the ocular surface. Methods: Hydrogels loaded with rhNGF were synthesized by conjugating chitosan with azidobenzoic acid (Az-Ch), adding rhNGF, and exposing the solution to ultraviolet (UV) radiation to induce photocrosslinking. Az-Ch hydrogels were evaluated for physical properties and rhNGF release profiles. Cytocompatbility of Az-Ch was assessed using immortalized human corneal limbal epithelial (HCLE) cells. TF1 erythroleukemic cell proliferation and HCLE cell proliferation and migration were used to assess the bioactivity of rhNGF released from Az-Ch hydrogels. Results: Az-Ch formed hydrogels in <10 seconds of UV exposure and demonstrated high optical transparency (75-85 T%). Az-Ch hydrogels exhibited good cytocompatibility with no demonstratable effect on HCLE cell morphology or viability. rhNGF was released gradually over 24 hours from Az-Ch hydrogels and retained its ability to induce TF1 cell proliferation. No significant difference was observed between rhNGF released from Az-Ch and freshly prepared rhNGF solutions on HCLE cell proliferation or percent wound closure after 12 hours; however, both were significantly better than control (P < 0.01). Conclusions: rhNGF-loaded Az-Ch hydrogels exhibited favorable physical, optical, and drug-release properties, as well as retained drug bioactivity. This drug delivery system has the potential to be further developed for in vivo and translational clinical applications. Translational Relevance: Az-Ch hydrogels may be used to enhance rhNGF therapy in patients with NK.

Existential distress and meaning making among female breast cancer patients with cancer-related fertility concerns.

OBJECTIVES: The current study explored the impact of cancer-related fertility concerns on existential distress and meaning making among female breast cancer (BC) patients of childbearing age and assessed support needs. METHODS: The current study was embedded within a larger study. A seven-question online survey was administered to female BC participants to explore meaning and identity in their lives. Applied thematic analysis was used to analyze participants' written responses. RESULTS: A total of 98 participants completed the survey, the majority of whom identified as white, married or partnered, and employed full time and with stage I or II BC. More than 50% of the participants expressed a need for support from a counselor or support group during their cancer experience. Three subthemes emerged related to existential distress and cancer-related fertility concerns: (1) loss of womanhood: treatment-related physical changes impact on gender identity; (2) existential distress due to treatment decisions impacting fertility; and (3) shattered vision: cancer-related infertility impact on meaning and purpose. Four subthemes emerged related to meaning making with fertility-related existential concerns: (1) coping with loss of meaning, (2) re-evaluating priorities in life; (3) resilience to loss, and (4) persistent loss of meaning. SIGNIFICANCE OF RESULTS: Study results offer valuable insights into the experiences of female BC survivors' cancer-related fertility on existential distress and meaning making. Development of psychological interventions targeted to support this population to cope with existential distress due to cancer-related fertility concerns and meaning making are needed to improve the quality of life of this population.

The U-shaped association of post-lung transplant mortality with pretransplant eGFR underscores possible limitations of creatinine-based estimation equations for risk stratification.

BACKGROUND: Pre-existing chronic kidney disease (CKD) may have an impact on post-lung transplant survival and the development of end stage kidney disease (ESKD). METHODS: We analyzed the US transplant database from 2006 to 2020. Adult patients who received their first lung transplant and were not on dialysis were included. Multivariable Cox regression was used to assess the effect of pretransplant eGFR on mortality and cumulative incidence competing risk was used to explore the effect on ESKD. RESULTS: The adjusted hazard ratio (aHR) for mortality showed a "U" shaped association with eGFR with a rising mortality at <60 and >100 ml/min/1.73m2. The increase in mortality with higher eGFR was only seen in those <30 year and were primarily in whites with a lower body mass index and in patients with cystic fibrosis (CF). The aHR for ESKD increased below an eGFR of 100 rising to 1.74 at an eGFR of 60. Any decrease in eGFR between listing and transplant >10% was associated with higher risk of ESKD. CONCLUSIONS: The U-shaped association of pretransplant eGFR with post-transplant mortality correlated with younger age, lower BMI and a diagnosis of CF. The aHR for ESKD following lung transplantation increased exponentially with worsening eGFR pretransplant.

Early Trajectories of Patient Reported Outcomes in Breast Cancer Patients Undergoing Lumpectomy Versus Mastectomy.

PURPOSE: This study was designed to: (1) characterize longitudinal patient-reported outcomes (PROs) between breast cancer patients undergoing lumpectomy and mastectomy and (2) compare return to baseline scores at 3 months and 6 months postoperatively. METHODS: Newly diagnosed breast cancer patients seen at an academic breast center between June 2019 and February 2021 were invited to participate in longitudinal PRO surveys at their initial clinic visit. If willing to participate, patients were emailed the validated BREAST-Q™ questionnaire at the initial clinic visit (baseline), 2 weeks after surgery, and then every 3 months for the first year. We used linear mixed models to estimate the differences in slopes over time between lumpectomy and mastectomy for each PRO measure. Pearson's Chi-square tests with Yates' continuity correction were used to compare proportions of patients who return to baseline PRO scores. P < 0.05 was considered significant. RESULTS: Of 164 patients invited to participate, 100 (61%) completed a baseline survey and were included in analyses. Mastectomy patients had significantly greater decreases in breast satisfaction (P = 0.002), psychosocial well-being (P < 0.0001), and sexual well-being (P < 0.0001) over time compared with lumpectomy patients. Both surgical groups reported a decrease in physical well-being, although the decline was more significant in lumpectomy patients (P = 0.005). At 3 months and 6 months after surgery, significantly larger proportions of lumpectomy patients returned to their baseline breast satisfaction, psychosocial well-being, and physical well-being compared with mastectomy patients. CONCLUSIONS: Understanding how outcomes important to patients change over the care continuum can provide opportunities for early intervention and may prevent debilitating long-term morbidities of treatment.

Reproducible Derivation and Expansion of Corneal Mesenchymal Stromal Cells for Therapeutic Applications.

Purpose: A reproducible protocol for the production of corneal mesenchymal stem/stromal cells (cMSCs) is necessary for potential clinical applications. We aimed to describe successful generation and expansion of cMSCs using an explant method. Methods: Corneoscleral rims of human cadaveric eyes were divided into four pieces and used as explants to allow outgrowth of cMSCs (passage 0, or P0). The cells were subcultured at a 1:10 ratio until passage 5 (P5). The characteristics as well as therapeutic effects of expanded cMSCs were evaluated both in vitro, using a scratch assay, and in vivo using epithelial debridement and chemical injury mouse models. Results: All explants demonstrated outgrowth of cells by 7 days. Although the initial outgrowth included mixed mesenchymal and epithelial cells, by P1 only cMSCs remained. By subculturing each flask at a ratio of 1:10, the potential yield from each cornea was approximately 12 to 16 × 1010 P5 cells. P5 cMSCs demonstrated the cell surface markers of MSCs. The secretome of P5 cMSCs induced faster closure of wounds in an in vitro scratch assay. Subconjunctival injection of P5 cMSCs in mouse models of mechanical corneal epithelial debridement or ethanol injury led to significantly faster wound healing and decreased inflammation, relative to control. Conclusions: cMSCs can be reproducibly derived from human cadaveric corneas using an explant method and expanded with preservation of characteristics and corneal wound healing effects. Translational Relevance: The results of our study showed that cMSCs produced using this scheme can be potentially used for clinical applications.

Patients' Experience With Opioid Pain Medication After Discharge From Surgery: A Mixed-Methods Study.

BACKGROUND: Decreasing the number of prescription opioids has been a leading strategy in combating the opioid epidemic. In Vermont, statewide and institutional policies have affected prescribing practices, resulting in a 40% decrease in postoperative opioid prescribing. The optimal approach to postoperative opioid prescribing remains unknown. In this study, we describe patients' experience with pain control 1 wk after discharge from surgery. MATERIALS AND METHODS: We assessed patients' experience using a telephone questionnaire, 1-wk after discharge after undergoing common surgical procedures between 2017 and 2019 at an academic medical center (n = 1027). Scaled responses regarding pain control, opioids prescribed, and opioids used (response rate 96%) were analyzed using a mixed-methods approach; open-ended patient responses to questions regarding whether the number of opioids prescribed was "correct" were analyzed using qualitative content analysis. RESULTS: One week after discharge, 96% of patients reported that their pain was well controlled. When asked whether they received the correct number of opioid pills postoperatively, qualitative analysis of patient responses yielded the following six themes: (1) I had more than I needed, but not more than I wanted; (2) Rationed medication; (3) Medication was not effective; (4) Caution regarding risks of opioids; (5) Awareness of the public health concerns; and (6) Used opioids from a prior prescription. CONCLUSIONS: Patient-reported pain control after common surgical procedures was excellent. However, patients are supportive of receiving more pain medications than they actually use, and they fear that further restrictions may prevent them or others from managing pain adequately. Understanding the patients' perspective is important for surgical education and improving discharge protocols.

A Machine Learning Approach to Identification of Unhealthy Drinking.

INTRODUCTION: Unhealthy drinking is prevalent in the United States, and yet it is underidentified and undertreated. Identifying unhealthy drinkers can be time-consuming and uncomfortable for primary care providers. An automated rule for identification would focus attention on patients most likely to need care and, therefore, increase efficiency and effectiveness. The objective of this study was to build a clinical prediction tool for unhealthy drinking based on routinely available demographic and laboratory data. METHODS: We obtained 38 demographic and laboratory variables from the National Health and Nutrition Examination Survey (1999 to 2016) on 43,545 nationally representative adults who had information on alcohol use available as a reference standard. Logistic regression, support vector machines, k-nearest neighbor, neural networks, decision trees, and random forests were used to build clinical prediction models. The model with the largest area under the receiver operator curve was selected to build the prediction tool. RESULTS: A random forest model with 15 variables produced the largest area under the receiver operator curve (0.78) in the test set. The most influential predictors were age, current smoker, hemoglobin, sex, and high-density lipoprotein. The optimum operating point had a sensitivity of 0.50, specificity of 0.86, positive predictive value of 0.55, and negative predictive value of 0.83. Application of the tool resulted in a much smaller target sample (75% reduced). CONCLUSION: Using commonly available data, a decision tool can identify a subset of patients who seem to warrant clinical attention for unhealthy drinking, potentially increasing the efficiency and reach of screening.

Therapeutic Effects of Lyophilized Conditioned-Medium Derived from Corneal Mesenchymal Stromal Cells on Corneal Epithelial Wound Healing.

Objectives: The conditioned-medium derived from corneal mesenchymal stromal cells (cMSCs) has been shown to have wound healing and immunomodulatory effects in corneal injury models. Here, the therapeutic effects of lyophilized cMSC conditioned-medium were compared with fresh conditioned-medium. Methods: The epithelial wound healing effects of fresh and lyophilized cMSC conditioned-medium were compared with conditioned-medium from non-MSC cells (corneal epithelial cells) using scratch assay. To evaluate the anti-inflammatory effects of fresh and lyophilized cMSC conditioned-media, macrophages were stimulated by a Toll-Like Receptor (TLR) ligand followed by treatment with the conditioned-media and measuring the expression of inflammatory genes. In vivo wound healing effects of fresh and lyophilized cMSC conditioned-media were assessed in a murine model of cornea epithelial injury. Results: Both fresh and lyophilized cMSCs-derived conditioned-medium induced significantly faster closure of in vitro epithelial wounds compared to conditioned-medium from non-MSC cells (P < .0001). Treating stimulated macrophages with fresh or lyophilized cMSCs-derived conditioned-media significantly decreased the expression of inflammatory genes compared to control (P < .0001). Murine corneal epithelial wounds were healed by 87.6 ± 2.7% and 86.2 ± 4.6% following treatment with fresh and lyophilized cMSC conditioned-media, respectively, while the control was healed by 64.7 ± 16.8% (P < .05). Conclusion: Lyophilized cMSC-derived conditioned-medium is as effective as fresh conditioned-medium in promoting wound healing and modulating inflammation. The results of this study support the application of lyophilized cMSCs-derived conditioned-medium, which allows for more extended storage, as a promising non-invasive option in the treatment of corneal wounds.

Glaucoma Care of Prison Inmates at an Academic Hospital.

Importance: Glaucoma care for prison inmates is underrepresented in the literature even though managing the treatment of such patients may provide unique challenges. Objectives: To evaluate the glaucoma profile of prison inmates treated at an academic ophthalmology center and to report on the medical and surgical management and follow-up metrics. Design, Setting, and Participants: This retrospective cohort study assessed data from 82 incarcerated patients treated at the glaucoma clinic, an academic referral center at the University of Illinois at Chicago, between January 2013 and December 2017. Main Outcomes and Measures: Diagnosis, glaucoma severity, medical and surgical interventions, and patient-reported medication adherence were recorded for each visit. Recommended and actual follow-up times were recorded and compared. Data analyses were conducted from January 2013 to December 2018. Results: In total, 82 patients (161 eyes) had 375 visits during the study period. All patients were male and ranged from 20 to 75 years of age (mean [SD] age, 50.8 [11.9] years). Most participants were black patients (65 [79.3%]). The most common diagnoses were primary open-angle glaucoma (POAG; 53 eyes [32.9%]) and POAG suspect (52 eyes [32.3%]). Glaucoma severity ranged from mild (25 of 77 eyes [32.5%]) to advanced (41 of 77 eyes [53.2%]). Overall, 59 patients (73.2%) were treated medically with up to 4 topical agents (40.0%). Of those treated, 70.0% of patients (95% CI, 57.7%-81.2%) reported medication nonadherence during at least 1 visit. Medication nonadherence was more common among those taking 4 different topical medications (21 of 24 [87.5%]) compared with others taking fewer medications (20 of 35 [57.1%]), for a difference of 30.4% (95% CI, 7.0%-53.6%; P = .02), and among those with advanced disease (22 of 26 [84.6%]) compared with glaucoma suspect (6 of 13 [46.2%]), for a difference of 38.4% (95% CI, 9.3%-67.5%; P = .02). Nineteen office procedures, including laser peripheral iridotomy and laser trabeculoplasty, were performed on 14 eyes. Seventeen incisional glaucoma procedures were performed on 15 eyes, including glaucoma drainage device implant (11 procedures [64.7%]) and trabeculectomy (3 procedures [17.6%]). Only 26.6% of return office visits (95% CI, 21.3%-32.3%) occurred within the recommended follow-up time frame. Furthermore, 93 patients (34.8%; 95% CI, 28.2%-40.0%) were seen more than 1 month after the recommended follow-up. Conclusions and Relevance: Despite incarceration in prison, where medication administration and appointment attendance are theoretically controlled, the results of this study suggested that substantial medication and follow-up nonadherence exists among inmates.

Clinical utility of emerging biomarkers in prostate cancer liquid biopsies.

Introduction: Prostate cancer (PCa) is one of the most common malignancies in men and a major cause of cancer deaths among men worldwide. Prostate specific antigen (PSA) monitoring and histopathological examination of tumor biopsies remain gold standards in PCa diagnostics. These clinical parameters are not well suited for patient stratification, predicting and monitoring treatment response. On the other hand, liquid biopsies offer a unique opportunity to easily isolate tumor-derived material for longitudinal clinical assessment.Areas covered: In this review we focus on the clinical application of novel liquid biomarkers that have the potential to monitor and stratify patients in order to achieve better therapeutic effects and improve clinical outcomes. Enumeration and characterization of circulating tumor cells (CTCs), tumor-educated platelets, exosomes, and cell-free nucleic acids have been studied for their clinical utility in PCa diagnostics, prognostics, monitoring treatment response and guiding treatment choice.Expert opinion: Liquid biomarkers have high potential to be used for prognosis, monitoring treatment response and guiding treatment selection. Although there is a remarkable progress in PCa biomarker discovery, their clinical validation is very limited. Research should be focused on biomarker validation and the incorporation of these biomarkers in clinical practice.

Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia.

The MUSASHI (MSI) family of RNA binding proteins (MSI1 and MSI2) contribute to a wide spectrum of cancers including acute myeloid leukemia. We find that the small molecule Ro 08-2750 (Ro) binds directly and selectively to MSI2 and competes for its RNA binding in biochemical assays. Ro treatment in mouse and human myeloid leukemia cells results in an increase in differentiation and apoptosis, inhibition of known MSI-targets, and a shared global gene expression signature similar to shRNA depletion of MSI2. Ro demonstrates in vivo inhibition of c-MYC and reduces disease burden in a murine AML leukemia model. Thus, we identify a small molecule that targets MSI's oncogenic activity. Our study provides a framework for targeting RNA binding proteins in cancer.

Self-insertion of foreign bodies into the orbit and periocular tissue.

We describe six patients with 12 separate episodes of self-inflicted periocular foreign body injuries, which presented to our institution recently. All patients were male, relatively young (mean 28.5 years old), incarcerated, and had significant underlying psychiatric conditions. The subjects had inserted staples (6), paperclips (2), or other small metallic wire segments (4) into the periocular region. Most cases (9/12) involved concurrent self-inflicted injury to other body parts. Ten cases involved foreign bodies inserted through the palpebral conjunctiva into the upper eyelid, while two cases involved insertion into the orbit. Identification and surgical retrieval of foreign bodies was successful in most cases (9/11) but was not attempted in one case. Self-inflicted periocular injuries, while rare, are challenging cases for which the ophthalmologist should be prepared. A multidisciplinary approach, including psychiatric assessment and treatment, is important for optimal care.

Comparative Evolution of an Archetypal Adaptive Radiation: Innovation and Opportunity in Anolis Lizards.

Adaptive radiation is a widely recognized pattern of evolution wherein substantial phenotypic change accompanies rapid speciation. Adaptive radiation may be triggered by environmental opportunities resulting from dispersal to new areas or via the evolution of traits, called key innovations, that allow for invasion of new niches. Species sampling is a known source of bias in many comparative analyses, yet classic adaptive radiations have not been studied comparatively with comprehensively sampled phylogenies. In this study, we use unprecedented comprehensive phylogenetic sampling of Anolis lizard species to examine comparative evolution in this well-studied adaptive radiation. We compare adaptive radiation models within Anolis and in the Anolis clade and a potential sister lineage, the Corytophanidae. We find evidence for island (i.e., opportunity) effects and no evidence for trait (i.e., key innovation) effects causing accelerated body size evolution within Anolis. However, island effects are scale dependent: when Anolis and Corytophanidae are analyzed together, no island effect is evident. We find no evidence for an island effect on speciation rate and tenuous evidence for greater speciation rate due to trait effects. These results suggest the need for precision in treatments of classic adaptive radiations such as Anolis and further refinement of the concept of adaptive radiation.

Refractive outcomes of phacoemulsification cataract surgery in glaucoma patients.

PURPOSE: To evaluate refractive outcomes after phacoemulsification cataract surgery in patients with glaucoma. SETTING: University of Colorado Health Eye Center, Aurora, Colorado, USA. DESIGN: Retrospective case series. METHODS: The incidence of refractive surprise was evaluated in patients with and without glaucoma after phacoemulsification cataract surgery. Refractive surprise was defined as the difference in spherical equivalent of the refractive target and postoperative refraction in diopters (D). RESULTS: The study comprised 206 eyes in the glaucoma group and 1162 control eyes. The refractive surprise greater than ±0.5 D and ±1.0 D was 29.9% and 4.9% in the control group and 40.3% (P = .0061) and 11.2% (P = .0011) in the glaucoma group. Primary open-angle glaucoma (POAG) (n = 154 eyes), chronic angle-closure glaucoma (n = 18 eyes), and pseudoexfoliation glaucoma (n = 23 eyes) had odds ratios of 1.90 (P = .1760), 14.54 (P = .0006), and 7.27 (P = .0138), respectively, of refractive surprise greater than ±1.0 D compared with patients without glaucoma. Refractive surprise was noted more often in POAG eyes with axial lengths longer than 25.0 mm (P = .0298). Glaucoma eyes had worse mean postoperative corrected distance visual acuity than control eyes (glaucoma: 0.1088 logarithm of the minimum angle of resolution [logMAR]; controls: 0.0358 logMAR; P = .01). CONCLUSION: Patients with a diagnosis of glaucoma were more likely to have a refractive surprise and/or worse visual outcome after phacoemulsification cataract surgery.

One-day postoperative intraocular pressure spikes after phacoemulsification cataract surgery in patients taking tamsulosin.

PURPOSE: To evaluate the relationship between 1-day postoperative intraocular pressure (IOP) after phacoemulsification cataract surgery and tamsulosin use. SETTING: University of Colorado Health Eye Center, Aurora, Colorado, USA. DESIGN: Retrospective cohort study. METHODS: Registry data from men who had cataract surgery were used. Patients taking tamsulosin at the time of surgery were included as cases, while patients with no history of tamsulosin use were used as controls. The primary outcome was a 1-day postoperative IOP spike defined as an IOP increase greater than 10 mm Hg compared with baseline or a 1-day postoperative IOP of 30 mm Hg or higher. General estimating equations were used for analysis. RESULTS: The study comprised 584 men (864 eyes). An IOP increase greater than 10 mm Hg or IOP 30 mm Hg or higher after cataract surgery occurred in 12.4% and 9.3%, respectively, of eyes in the tamsulosin group versus 4.4% and 2.1%, respectively, in the control group (all P = .001). After adjusting for significant covariates, patients on tamsulosin were 2.6 times (95% confidence interval [CI], 1.2-5.7; P = .01] and 3.8 (95% CI, 1.3-10.9; P = .01) more likely to have a 1-day postoperative IOP increase greater than 10 mm Hg or a 1-day postoperative IOP of 30 mm Hg or higher. CONCLUSION: Patients on tamsulosin had an increased risk of a 1-day postoperative IOP spike after cataract surgery, showing the importance of identifying patients on tamsulosin preoperatively to better manage and potentially mitigate IOP spikes. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

AMD-like retinopathy associated with intravenous iron.

Iron accumulation in the retina is associated with the development of age-related macular degeneration (AMD). IV iron is a common method to treat iron deficiency anemia in adults, and its retinal manifestations have not hitherto been identified. To assess whether IV iron formulations can be retina-toxic, we generated a mouse model for iron-induced retinal damage. Male C57BL/6J mice were randomized into groups receiving IV iron-sucrose (+Fe) or 30% sucrose (-Fe). Iron levels in neurosensory retina (NSR), retinal pigment epithelium (RPE), and choroid were assessed using immunofluorescence, quantitative PCR, and the Perls' iron stain. Iron levels were most increased in the RPE and choroid while levels in the NSR did not differ significantly in +Fe mice compared to controls. Eyes from +Fe mice shared histological features with AMD, including Bruch's membrane (BrM) thickening with complement C3 deposition, as well as RPE hypertrophy and vacuolization. This focal degeneration correlated with areas of high choroidal iron levels. Ultrastructural analysis provided further detail of the RPE/photoreceptor outer segment vacuolization and Bruch's membrane thickening. Findings were correlated with a clinical case of a 43-year-old patient who developed numerous retinal drusen, the hallmark of AMD, within 11 months of IV iron therapy. Our results suggest that IV iron therapy may have the potential to induce or exacerbate a form of retinal degeneration. This retinal degeneration shares features with AMD, indicating the need for further study of AMD risk in patients receiving IV iron treatment.

Synchrotron radiation Mössbauer spectra of a rotating absorber with implications for testing velocity and acceleration time dilation.

Many Mössbauer spectroscopy (MS) experiments have used a rotating absorber in order to measure the second-order transverse Doppler (TD) shift, and to test the validity of the Einstein time dilation theory. From these experiments, one may also test the clock hypothesis (CH) and the time dilation caused by acceleration. In such experiments the absorption curves must be obtained, since it cannot be assumed that there is no broadening of the curve during the rotation. For technical reasons, it is very complicated to keep the balance of a fast rotating disk if there are moving parts on it. Thus, the Mössbauer source on a transducer should be outside the disk. Friedman and Nowik have already predicted that the X-ray beam finite size dramatically affects the MS absorption line and causes its broadening. We provide here explicit formulas to evaluate this broadening for a synchrotron Mössbauer source (SMS) beam. The broadening is linearly proportional to the rotation frequency and to the SMS beam width at the rotation axis. In addition, it is shown that the TD shift and the MS line broadening are affected by an additional factor assigned as the alignment shift which is proportional to the frequency of rotation and to the distance between the X-ray beam center and the rotation axis. This new shift helps to align the disk's axis of rotation to the X-ray beam's center. To minimize the broadening, one must focus the X-ray on the axis of the rotating disk and/or to add a slit positioned at the center, to block the rays distant from the rotation axis of the disk. Our experiment, using the (57)Fe SMS, currently available at the Nuclear Resonance beamline (ID18) at the ESRF, with a rotating stainless steel foil, confirmed our predictions. With a slit installed at the rotation axis (reducing the effective beam width from 15.6 µm to 5.4 µm), one can measure a statistically meaningful absorption spectrum up to 300 Hz, while, without a slit, such spectra could be obtained up to 100 Hz only. Thus, both the broadening and the alignment shift are very significant and must be taken into consideration in any rotating absorber experiment. Here a method is offered to measure accurately the TD shift and to test the CH.