Longitudinal Comparison of Orbital Volumes from Enucleated Eyes with Hydroxyapatite Orbital Implant in Unilateral Retinoblastoma Patients.

PURPOSE: To compare the orbital volume between enucleated and contralateral, uninvolved orbits over a 5-year period in patients with unilateral retinoblastoma who underwent enucleation with hydroxyapatite (HA) implant placement by a single surgeon. METHODS: A retrospective review was performed on the clinical records and radiographic images of unilateral retinoblastoma patients who underwent enucleation with primary HA implantation from 2003 to 2020 at a single institution. Bilateral orbital volume measurements were taken from the initial postoperative MRI scan and again at 1- and 5-years postenucleation. The main outcome measure was the longitudinal change in volume difference (∆𝑉). The implant size, age at enucleation, and sex were also evaluated. A linear mixed-effect model was used for analysis. RESULTS: A total of 124 patients (73 males) with HA implants following enucleation were included. Overall, the unaffected orbit trended toward having a greater volume compared with the enucleated orbit, but this was not statistically significant (ß = 0.003; p = 0.122). The mean age at enucleation was 2.4 years. The median time between enucleation and the initial, 1-year, and 5-year postoperative MRIs was 6 months, 17 months, and 55 months, respectively. There was no statistical correlation between age at enucleation, gender, implant size, or orbital volume at any time points (p > 0.05). CONCLUSIONS: Patients treated with enucleation and primary HA implant placement for unilateral retinoblastoma did not display significant asymmetry in orbital volume on 5-year postenucleation MRIs, suggesting that HA implants promote orbital growth comparable to a nonenucleated orbit in the pediatric population.

Testosterone-Induced Central Serous Chorioretinopathy Mimicking a Choroidal Mass.

PURPOSE: To describe a case of supplemental testosterone-induced central serous chorioretinopathy (CSCR) mimicking a choroidal mass in a 63-year-old male. METHODS: Case report. PATIENT: A 63-year-old male patient on self-prescribed supplemental testosterone with CSCR mimicking a choroidal mass. RESULTS: A 63-year-old male presented with new onset vision loss, subretinal fluid, and choroidal mass in his left eye. Intravenous fluorescein angiography showed an enhancing choroidal mass involving the fovea. B scan ultrasonography revealed diffuse choroidal thickening. Given concern for a diffuse uveal melanoma, the lesion was biopsied showing non-diagnostic rare, atypical melanocytes. Four months after initial presentation, the patient was diagnosed with polycythemia vera. Fourteen months after diagnosis, he admitted to testosterone supplementation. Upon cessation of the testosterone supplement, the lesion progressively flattened to a chorioretinal scar with subretinal fluid resolution, and the return of normal choroidal thickness over the next 14 months. DISCUSSION: Testosterone supplementation has been linked to erythrocytosis and polycythemia vera. In the retina, testosterone supplementation has been linked to CSCR and both central and branch retinal artery and vein occlusions. This case demonstrates the importance of inquiring about all prescribed and over the counter medications in patients presenting with retinal lesions of unknown origin.

Retinopathy, Optic Neuropathy, and Cataract in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review.

PURPOSE: Few reports describe the risks of late ocular toxicities after radiation therapy (RT) for childhood cancers despite their effect on quality of life. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) ocular task force aims to quantify the radiation dose dependence of select late ocular adverse effects. Here, we report results concerning retinopathy, optic neuropathy, and cataract in childhood cancer survivors who received cranial RT. METHODS AND MATERIALS: A systematic literature search was performed using the PubMed, MEDLINE, and Cochrane Library databases for peer-reviewed studies published from 1980 to 2021 related to childhood cancer, RT, and ocular endpoints including dry eye, keratitis/corneal injury, conjunctival injury, cataract, retinopathy, and optic neuropathy. This initial search yielded abstracts for 2947 references, 269 of which were selected as potentially having useful outcomes and RT data. Data permitting, treatment and outcome data were used to generate normal tissue complication probability models. RESULTS: We identified sufficient RT data to generate normal tissue complication probability models for 3 endpoints: retinopathy, optic neuropathy, and cataract formation. Based on limited data, the model for development of retinopathy suggests 5% and 50% risk of toxicity at 42 and 62 Gy, respectively. The model for development of optic neuropathy suggests 5% and 50% risk of toxicity at 57 and 64 Gy, respectively. More extensive data were available to evaluate the risk of cataract, separated into self-reported versus ophthalmologist-diagnosed cataract. The models suggest 5% and 50% risk of self-reported cataract at 12 and >40 Gy, respectively, and 50% risk of ophthalmologist-diagnosed cataract at 9 Gy (>5% long-term risk at 0 Gy in patients treated with chemotherapy only). CONCLUSIONS: Radiation dose effects in the eye are inadequately studied in the pediatric population. Based on limited published data, this PENTEC comprehensive review establishes relationships between RT dose and subsequent risks of retinopathy, optic neuropathy, and cataract formation.

UVEAL MELANOMA PRESENTING AS HEPATIC METASTASIS IN A PATIENT WITH OCULODERMAL MELANOCYTOSIS.

PURPOSE: To report an atypical case of occult uveal melanoma in a patient with oculodermal melanocytosis that first presented with symptoms of hepatic metastasis. METHODS: A previously healthy 16-year-old boy with noted ocular hyperpigmentation developed abdominal pain and vomiting and was found to have a hepatic mass consistent with a metastatic lesion from an occult uveal melanoma. RESULTS: On examination, the patient's visual acuity was 20/20, and pupils were reactive without an afferent pupillary defect in both eyes. Examination of the left eye revealed normal findings. In the right eye, conjunctiva was freely moving over hyperpigmented sclera. Dilated fundus examination demonstrated a hyperpigmented, minimally elevated, choroidal mass in the right eye. Results of fundus autofluorescence, IV fluorescein angiography, spectral-domain optical coherence tomography, and ultrasonography were suspicious for uveal melanoma. Genetic testing of the hepatic mass was positive for BAP1, confirming that the metastasis originated as uveal melanoma rather than cutaneous or intracranial melanoma. Magnetic resonance imaging of the brain and orbits showed negative impression for intracranial lesions. A PET scan revealed numerous additional metastatic lesions, and the patient was referred to palliative care. CONCLUSION: Patients with oculodermal melanocytosis are at an increased risk for both uveal melanoma and subsequent metastasis, and frequent monitoring should be performed because treatment options for metastatic uveal melanoma are limited.

Metastasis of Conjunctival Melanoma to the Cardiac Atrium: A Case Report.

The authors present an unreported case of malignant conjunctival melanoma with metastasis to the right cardiac atrium. A 67-year-old woman with history of conjunctival melanoma of the OS presented with asymptomatic recurrence with new extension to the fornix. Surgical management was planned; however, the patient was admitted to the hospital with symptoms of heart and respiratory failure. She was found to have a large mass in the right atrium. The mass was resected and was found to be metastatic conjunctival melanoma. The patient received chemotherapy and her symptoms have improved. This case highlights the high recurrence rate of conjunctival melanoma and the importance of tumor surveillance.

An unusual case of a pigment epithelial cyst masquerading as a uveal melanoma after zoster ophthalmicus-related iris atrophy.

Purpose: To report the case of a 69-year-old male who was referred for a previously unidentified pigmented iris lesion with surrounding iris atrophy masquerading as an iris melanoma. Observations: A sharply demarcated pigmented lesion extending from the trabecular meshwork to the pupillary margin was identified in the left eye. There was adjacent iris stromal atrophy. Testing was consistent with a cyst-like lesion. The patient later described a prior episode of ipsilateral herpes zoster involving the ophthalmic division of cranial nerve five. Conclusions and Importance: Iris cysts present an uncommon iris tumor, often going unrecognized especially if located on the posterior iris surface. When they present acutely, as in this case where a previously unidentified cyst was revealed following zoster-induced sectoral iris atrophy, these pigmented lesions can be concerning for malignancy. Accurately identifying iris melanomas and differentiating them from benign iris lesions is imperative.

An exploratory study of sleep habits in school-aged survivors of retinoblastoma.

OBJECTIVE/BACKGROUND: Retinoblastoma is an ocular cancer diagnosed in early childhood. Previous research has indicated the impact of cancer treatment on sleep, but little is known about how sleep is impacted among survivors of retinoblastoma. The current study aimed to describe sleep habits of school-age survivors of retinoblastoma, to examine associations between sleep and quality of life, and to examine concordance between parent and child reports of sleep habits. PATIENTS/METHODS: Sixty-nine survivors of retinoblastoma (Mage = 10.89, SD = 1.07, 50.7% female; 56.5% unilateral disease) and their caregivers participated, providing information on both self- and parent-reported sleep habits, quality of life, and demographic data. RESULTS: Greater sleep concerns than national norms were reported by parents (bedtime resistance (t(58) = 2.69, p = .009), greater sleep onset delay (t(66) = 2.46, p = .017), shorter sleep duration (t(57) = 2.12, p = .038), increased daytime sleepiness (t(53) = 6.45, p= <.001)) and children (sleep location (t(61) = 2.39, p = .02), restless legs syndrome (t(62) = -2.21, p = .03), parasomnias (t(64) = 19.19, p=<.001)) . Both children and parents of children who received enucleation endorsed greater sleep concerns across several domains (e.g., electronic use before bed, sleep-disordered breathing). Child- and parent-reported sleep concerns were generally associated with decreased quality of life. Finally, child- and parent-report of sleep habits appeared generally consistent. CONCLUSIONS: Survivors of retinoblastoma experience sleep difficulties. As such, assessment and targeted intervention is important to mitigate any effects on quality of life. Future research should examine sleep habits of survivors of retinoblastoma across cultures and developmental periods.

Intravitreal Carboplatin as Salvage Treatment for Progressive Vitreous Disease in Retinoblastoma: A Phase I Clinical Trial.

PURPOSE: To determine the safety and toxicity profile of intravitreal carboplatin as salvage treatment for retinoblastoma with vitreous disease. DESIGN: Single-institution, interventional prospective clinical trial. PARTICIPANTS: Patients with progressive or recurrent vitreous seeds after completion of primary treatment for intraocular retinoblastoma. METHODS: Eligible eyes received an intravitreal injection of carboplatin every 14 to 21 days with simultaneous focal therapy (laser, thermotherapy, and brachytherapy) provided at the discretion of the ocular oncologist. The evaluation with examination under anesthesia, ultrasound biomicroscopy, and electroretinography (ERG) were performed before each injection to assess for tumor response and drug-related toxicity. A serious adverse event resulted in dose recalculation and ultimately early closure of the study. MAIN OUTCOME MEASURES: Regression pattern of vitreous disease and incidence of dose-limiting toxicities. RESULTS: Four patients were enrolled at an initial dose of 0.3 mg. Complete regression of vitreous seeds was noted in all patients after 5, 2, 2, and 1 injections (respectively). Two patients developed recurrent vitreous disease at 3 and 25 months after complete regression and ultimately required enucleation. A serious adverse event occurred in 1 patient who developed acute vision loss with extinguished ERG response 72 hours after the second injection; ultimately, this eye developed a cataract and required enucleation. After temporary suspension and dose modification, 3 patients were enrolled at an injection dose of 3 µg and treated with a total of 5, 2, and 1 injections, respectively. Complete regression of vitreous disease was not achieved in any patient though ERG amplitudes remained stable. After removal from protocol, all 3 patients had a complete response to intravitreal melphalan. Concern for dose escalation and further toxicity in the setting of an effective and safe alternative (melphalan) led to the termination of the study. CONCLUSIONS: Intravitreal carboplatin may be effective in treating progressive vitreous seeding at higher doses, but permanent retinal toxicity was observed. Other alternative agents should be considered. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Psychosocial outcomes and quality of life among school-age survivors of retinoblastoma.

BACKGROUND: Retinoblastoma is the most common intraocular childhood cancer and is typically diagnosed in young children. With increasing number of survivors and improved medical outcomes, long-term psychosocial impacts need to be explored. Thus, the current study sought to assess functioning in school-aged survivors of retinoblastoma. PROCEDURE: Sixty-nine survivors of retinoblastoma underwent a one-time evaluation of psychosocial functioning. Survivors (Mage = 10.89 years, SD = 1.07 years; 49.3% male; 56.5% unilateral disease) and parents completed measures of quality of life (QoL; PedsQL) and emotional, behavioral, and social functioning (PROMIS [patient-reported outcome measurement information system] Pediatric Profile, BASC-2 parent report). Demographic and medical variables were also obtained. RESULTS: On the whole, both survivors and caregivers indicated QoL and behavioral and emotional health within the typical range of functioning. Survivors reported better physical QoL compared to both parent report and a national healthy comparison sample, whereas caregivers reported that survivors experienced lower social, school, and physical QoL than a healthy comparison. Regarding behavioral and emotional health, survivors indicated more anxiety than a nationally representative sample. Parents of female survivors endorsed lower adaptive scores than parents of male survivors. CONCLUSIONS: Results indicated that survivors of retinoblastoma reported QoL and behavioral and emotional health within normal limits, although parents appear to perceive greater impairment across several assessed domains. Understanding both survivor and parent reports remains important for this population. Future research should explore psychosocial functioning of these survivors as they transition to adolescence and early adulthood, given the increased independence and behavioral and emotional concerns during these developmental periods.

Delayed recurrence of an iridociliary malignant melanoma 180° from the primary tumor.

Purpose: We report the case of a 66-year-old female who returned with a rare recurrence of iridociliary melanoma 180° from the original lesion. Observations: Upon initial presentation eleven years prior, a pigmented iris lesion suspicious for primary uveal melanoma was noted in the right eye at 9 o'clock. After one year of observation, inferior growth of the iris lesion prompted treatment via primary iridectomy with excisional biopsy and pupilloplasty. Postoperative biopsy confirmed spindle B type melanoma with epithelial foci, and adjuvant brachytherapy was performed to treat the reported positive anterior ciliary body involvement. Ten years after initial plaque brachytherapy treatment, the patient returned with a pigmented iris lesion in the right eye at 3:30-5 o'clock, which was treated with enucleation. On pathology, the new melanoma was predominantly epithelioid, consistent with a transformed recurrent iridociliary melanoma. The patient remains metastasis free 13 years after initial diagnosis. Conclusions and importance: This case describes a rare, late recurrence of an iridociliary melanoma 180° away eleven years after initial presentation, emphasizing the importance of lifelong follow-up for patients with iridociliary melanoma. This rare form of recurrence has not been previously reported in the literature. We hypothesize the original lesion contained radiotherapy resistant epithelioid cells which grew superficially on the posterior iris and anterior ciliary body, ultimately breaking back through the anterior iris 180° away.

Metastatic Death Based on Presenting Features and Treatment for Advanced Intraocular Retinoblastoma: A Multicenter Registry-Based Study.

PURPOSE: To evaluate presenting features, tumor size, and treatment methods for risk of metastatic death due to advanced intraocular retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 1841 patients with advanced RB. METHODS: Advanced RB was defined by 8th edition American Joint Committee on Cancer (AJCC) categories cT2 and cT3 and new AJCC-Ophthalmic Oncology Task Force (OOTF) Size Groups (1: < 50% of globe volume, 2: > 50% but < 2/3, 3: > 2/3, and 4: diffuse infiltrating RB). Treatments were primary enucleation, systemic chemotherapy with secondary enucleation, and systemic chemotherapy with eye salvage. MAIN OUTCOME MEASURES: Metastatic death. RESULTS: The 5-year Kaplan-Meier cumulative survival estimates by patient-level AJCC clinical subcategories were 98% for cT2a, 96% for cT2b, 88% for cT3a, 95% for cT3b, 92% for cT3c, 84% for cT3d, and 75% for cT3e RB. Survival estimates by treatment modality were 96% for primary enucleation, 89% for systemic chemotherapy and secondary enucleation, and 90% for systemic chemotherapy with eye salvage. Risk of metastatic mortality increased with increasing cT subcategory (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastatic mortality in categories cT3c (glaucoma, hazard ratio [HR], 4.9; P = 0.011), cT3d (intraocular hemorrhage, HR, 14.0; P < 0.001), and cT3e (orbital cellulitis, HR, 19.6; P < 0.001) than in category cT2a and with systemic chemotherapy with secondary enucleation (HR, 3.3; P < 0.001) and eye salvage (HR, 4.9; P < 0.001) than with primary enucleation. The 5-year Kaplan-Meier cumulative survival estimates by AJCC-OOTF Size Groups 1 to 4 were 99%, 96%, 94%, and 83%, respectively. Mortality from metastatic RB increased with increasing Size Group (P < 0.001). Cox proportional hazards regression analysis revealed that patients with Size Group 3 (HR, 10.0; P = 0.002) and 4 (HR, 41.1; P < 0.001) had a greater risk of metastatic mortality than Size Group 1. CONCLUSIONS: The AJCC-RB cT2 and cT3 subcategories and size-based AJCC-OOTF Groups 3 (> 2/3 globe volume) and 4 (diffuse infiltrating RB) provided a robust stratification of clinical risk for metastatic death in advanced intraocular RB. Primary enucleation offered the highest survival rates for patients with advanced intraocular RB.

High-risk Pathologic Features Based on Presenting Findings in Advanced Intraocular Retinoblastoma: A Multicenter, International Data-Sharing American Joint Committee on Cancer Study.

PURPOSE: To determine the value of clinical features for advanced intraocular retinoblastoma as defined by the eighth edition of the American Joint Committee on Cancer (AJCC) cT3 category and AJCC Ophthalmic Oncology Task Force (OOTF) Size Groups to predict the high-risk pathologic features. DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: Eighteen ophthalmic oncology centers from 13 countries over 6 continents shared evaluations of 942 eyes enucleated as primary treatment for AJCC cT3 and, for comparison, cT2 retinoblastoma. METHODS: International, multicenter, registry-based data were pooled from patients enrolled between 2001 and 2013. High-risk pathologic features were defined as AJCC categories pT3 and pT4. In addition, AJCC OOTF Size Groups were defined as follows: (1) less than half, (2) more than half but less than two thirds, (3) more than two thirds of globe volume involved, and (4) diffuse infiltrating retinoblastoma. MAIN OUTCOME MEASURES: Statistical risk of high-risk pathologic features corresponding to AJCC cT3 subcategories and AJCC OOTF Size Groups. RESULTS: Of 942 retinoblastoma eyes treated by primary enucleation, 282 (30%) showed high-risk pathologic features. Both cT subcategories and AJCC OOTF Size Groups (P < 0.001 for both) were associated with high-risk pathologic features. On logistic regression analysis, cT3c (iris neovascularization with glaucoma), cT3d (intraocular hemorrhage), and cT3e (aseptic orbital cellulitis) were predictive factors for high-risk pathologic features when compared with cT2a with an odds ratio of 2.3 (P = 0.002), 2.5 (P = 0.002), and 3.3 (P = 0.019), respectively. Size Group 3 (more than two-thirds globe volume) and 4 (diffuse infiltrative retinoblastoma) were the best predictive factors with an odds ratio of 3.3 and 4.1 (P < 0.001 for both), respectively, for high-risk pathologic features when compared with Size Groups 1 (i.e., < 50% of globe volume). CONCLUSIONS: The AJCC retinoblastoma staging clinical cT3c-e subcategories (glaucoma, intraocular hemorrhage, and aseptic orbital cellulitis, respectively) as well as the AJCC OOTF Size Groups 3 (tumor more than two thirds of globe volume) and 4 (diffuse infiltrative retinoblastoma) both allowed stratification of clinical risk factors that can be used to predict the presence of high-risk pathologic features and thus facilitate treatment decisions.

Light Therapy for QoL/Depression in AYA With Cancer: A Randomized Trial.

OBJECTIVE: Secondary outcomes from a published feasibility and acceptability trial were examined to explore the effect of bright white light (BWL) on quality of life (QoL) and depressive symptoms compared to dim red light (DRL) control in adolescents and young adults (AYAs) receiving cancer-directed therapy. METHODS: Fifty-one AYAs (12-22 years, 51% male) newly diagnosed with cancer were randomized to receive 8 weeks of BWL (n = 26) or DRL (n = 25). The CDI-2 (total score, negative mood/physical symptoms, interpersonal problems, ineffectiveness, and negative self-esteem) and parent- and self-report PedsQL (total score and subscales of physical, emotional, social, and school QoL) were completed at multiple timepoints. RESULTS: BWL produced improvements in self-reported total depression (d = -.64; 95% confidence interval [CI] = -1.26, -0.01), negative self-esteem (d = -.80; 95% CI = -1.43, -.14), negative mood/physical symptoms (d = -.73; 95% CI = -1.36, -0.08), ineffectiveness (d = -.43; 95% CI = -1.04, .19), total self-reported QoL (d = .41; 95% CI = -.16, .96), emotional (d = .78; 95% CI = .19, 1.37), school functioning (d = .48; 95% CI = -.09, 1.04), and parent-reported school functioning (d = .66; 95% CI = 0.02, 1.33). BWL reported a greater rate of improvement than DRL for total depression (ß = .49, p < .05) and self-esteem (ß = .44, p < .05), and parent-reported school functioning (ß = -1.68, p < .05). CONCLUSIONS: BWL improved QoL and depressive symptoms for AYAs with cancer. These findings will inform larger randomized controlled trials.

Long-acting opioid prescribing patterns of ophthalmic plastic surgeons in the medicare Part D database.

PURPOSE: To assess extended release/long acting (ER/LA) opioid prescribing patterns among ophthalmic plastic surgeons in the Centers for Medicare and Medicaid Services (CMS) Part D database. METHODS: A retrospective observational cohort study was conducted on oculoplastic surgeons in the CMS Part D database who prescribed ER/LA opioids from 2013 to 2017. American Society of Ophthalmic Plastics and Reconstructive Surgery (ASOPRS) and non-ASOPRS surgeons were analyzed as groups. Prescribers were also analyzed based on gender and practice experience. RESULTS: Oculoplastic surgeons (64 ASOPRS and 78 non-ASOPRS) were responsible for 1,177 ER/LA opioid prescriptions from 2013 to 2017. ASOPRS members accounted for 4.6% and non-ASOPRS members accounted for 7.5% of all ER/LA opioids prescribed by ophthalmologists over the study period (p= .02). The total number of ASOPRS and non-ASOPRS members prescribing ER/LA opioids decreased by 52% (p= .10) and 58% (p= .07) from 2013 to 2017 respectively. CONCLUSION: ER/LA opioids are indicated for treatment of chronic pain and may be appropriately prescribed by the oculoplastic surgeon in certain circumstances, however due to the higher risk of overdose injury, those circumstances must be defined and justified. While a relatively small number of oculoplastic surgeons (10.6% ASOPRS and 19.6% non-ASOPRS) prescribed ER/LA opioids from 2013 to 2017, non-ASOPRS oculoplastic surgeons wrote 23.5% more ER/LA opioid prescriptions over the study period. Over the 5-year study period there was a general decline in the prescribing of ER/LA opioids by oculoplastic surgeons. Reviewing the prescribing practices of oculoplastic specialists, regardless of professional affiliation, is necessary to understand the role of ER/LA opioids for all of ophthalmology.

Transcutaneous CO2 monitoring as indication for inpatient non-invasive ventilation initiation in patients with amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) is characterized by profound muscle weakness, including diaphragmatic weakness resulting in hypercapnic respiratory failure. While non-invasive ventilation (NIV) is usually initiated in the home, patients presenting with hypercapnic respiratory failure may be at high risk of adverse outcomes with delays in treatment. We aim to describe the clinical utility of transcutaneous CO2 (TCO2 ) to assess the need for inpatient initiation of NIV. METHODS: Eight patients from the University of Michigan Pranger ALS clinic were directly admitted to the hospital for urgent initiation of NIV between May 2020-May 2021. A retrospective review of electronic medical records, including pre-hospital pulmonary function assessments, hospitalization blood gases, and NIV use metrics was performed. RESULTS: All eight patients had symptoms of respiratory insufficiency at time of admission, although not all patients had forced vital capacity (FVC) measurements that would identify need for NIV. All patients had measured TCO2 > 45 mmHg. Seven of eight patients had worsening hypercapnia after admission, indicating advanced respiratory failure. All patients were titrated to tolerance of continuous nocturnal NIV while in the hospital, with an average length of stay of 6.5 days (range, 3-8). All patients demonstrated compliance with NIV, >4 h, at post-hospital follow-up. DISCUSSION: Many current ambulatory measurements underestimate, or incompletely evaluate, respiratory dysfunction, and arterial blood gases are not typically readily available. Outpatient TCO2 measurements can serve as a useful screening tool to identify ALS patients who would benefit from inpatient initiation and titration of NIV.

The Sex Differences in Uveal Melanoma: Potential Roles of EIF1AX, Immune Response and Redox Regulation.

BACKGROUND: Uveal melanoma (UVM) is a rare cancer that shows sex difference in incidence and survival, with little previous report for the underlying mechanism. METHODS: This study used the SEER data (1974-2016) for an age-dependent analysis on sex difference in UVM, and further used the TCGA-UVM genomics dataset for analyzing the differential gene expression profiles in tumors from men and women. RESULTS: Our results demonstrate a sex difference in older age (≥40 years) but not in younger patients, with men exhibiting a higher incidence rate than women. However, younger women have shown a continuous increasing trend since 1974. Examining the 11 major oncogenes and tumor suppressors in UVM revealed that EIF1AX showed a significant sex difference in mRNA accumulation and copy number variation, with female tumors expressing higher levels of EIF1AX and exhibiting more variations in copy numbers. EIF1AX mRNA levels were significantly inversely correlated with EIF1AX copy numbers in female tumors only, but not in male tumors. Differential gene expression analysis at the whole genomic level identified a set of 92 protein-coding and 16 RNA-coding genes which exhibited differential expression in men and women (fold of change cutoff at 1.7, adjusted p value < 0.05, FDR < 0.05). Network analysis showed significant difference in immune response and in disulfide bond formation, with EGR1/EGR2 and PDIA2 genes as regulators for immune response and disulfide bond formation, respectively. The melanocortin pathway which is linked to both melanin synthesis and obesity seems to be altered with unclear significance, as the sex difference in POMC, DCT/TYRP2, and MRAP2 was observed but with no clear direction. CONCLUSION: This study reveals possible mechanisms for the sex difference in tumorigenesis of UVM which has potentials for better understanding and prevention of UVM.

Noninvasive ventilation: An important option in the management of hemidiaphragm paralysis.

Hemidiaphragm paralysis (HP) is a potential complication of cardiac surgery. While most patients are either asymptomatic or have mild symptoms, some are at risk of developing life-threatening hypercapnia. We present a case of a patient who developed HP after tricuspid valve replacement. Diaphragm plication was deferred due to underlying comorbidities, but over time she developed severe hypercapnic respiratory failure requiring intensive care unit admission. Chronic noninvasive ventilation therapy (NIV) was initiated, which improved her symptoms and hypercapnia and prevented further hospitalizations. For patients with iatrogenic HP unable to undergo diaphragm plication, Pulmonology referral for initiation of NIV should be strongly considered.

Mortality and Healthcare Use of Patients with Compensated Hypercapnia.

Rationale: Acute hypercapnic respiratory failure has been shown to be associated with worse outcomes for various disease states, but less is known about patients with compensated hypercapnic respiratory failure. Although these patients have a normal pH, it remains unknown whether chronically elevated carbon dioxide partial pressure (Pco2), irrespective of etiology, puts patients at risk of adverse events. Objectives: To understand the burden of and clinical factors associated with morbidity and mortality in patients with compensated hypercapnic respiratory failure. Methods: We performed a query of the electronic medical record to identify patients hospitalized at the University of Michigan from January 1 to December 31, 2018, who had compensated hypercapnia, by using a Pco2 ⩾ 50 mm Hg and a pH of 7.35-7.45 on arterial blood gas . We obtained demographic and clinical data from the electronic medical record. Survival probabilities for Pco2 subgroups (50.0-54.9, 55.0-64.9, and ⩾65.0 mm Hg) were determined by using the Kaplan-Meier product limit estimator. Cox proportional hazard models were constructed to test the association between Pco2 and all-cause mortality. Results: We identified 491 patients with compensated hypercapnia. The mean age was 60.5 ± 16.2 years. Patients were 57.4% male and 86.2% white. The mean pH and Pco2 were 7.38 ± 0.03 and 58.8 ± 9.7 mm Hg, respectively. There was a total of 1,030 hospitalizations, with 44.4% of patients having two or more admissions. The median numbers of cumulative hospital and intensive care unit days were 21.0 (interquartile range [IQR], 11.0-38.0) and 7.0 (IQR, 3.0-14.0) days, respectively. Two hundred seventeen patients (44.2%) died over a median of 592 days. In univariate analysis, every 5-mm Hg increase in Pco2 was associated with a higher risk of all-cause death (hazard ratio, 1.09; 95% confidence interval [CI]: 1.03-1.16; P = 0.004). This association was maintained after adjusting for the age, sex, body mass index (BMI), and Charlson comorbidity index (hazard ratio of 1.09 for every 5-mm Hg increase in Pco2; 95% CI: 1.02-1.16; P = 0.009). There was a statistically significant interaction between the Pco2 and the BMI in relation to mortality (P = 0.01 for the interaction term). Conclusions: Patients with compensated hypercapnic respiratory failure have high mortality and healthcare use, with higher Pco2 being associated with worse survival. Hypercapnic patients with obesity have a higher risk of death with increases in Pco2.

Cognitive and Adaptive Functioning in Youth With Retinoblastoma: A Longitudinal Investigation Through 10 Years of Age.

PURPOSE: To describe the trajectory of cognitive and adaptive functioning in pediatric patients with retinoblastoma from diagnosis through age 10. This is an extension of a previous report that discussed findings from diagnosis through age 5. PATIENTS AND METHODS: Ninety-eight participants with retinoblastoma completed psychological assessments as part of their enrollment on an institutional treatment protocol, with 73 completing an additional assessment at age 10. Trajectories of adaptive and cognitive functioning were determined, with data analyzed by treatment strata, and patients with 13q- analyzed separately. RESULTS: Longitudinal trajectories identified a significant change point in trends at age 5, with functioning declining from diagnosis through age 5 and then increasing from age 5 to age 10. This pattern was observed for all strata for adaptive functioning, but only for enucleation-only patients (strata C low) for cognitive functioning. Cognitive trajectories were also influenced by laterality and enucleation status. At age 10, overall functioning was generally within the average range, although estimated intelligence quotient was significantly below the normative mean for enucleation-only (C low) patients. Patients with 13q- demonstrated very low functioning, but few analyses were significant because of small sample size. CONCLUSION: The results generally indicate that previously demonstrated declines in functioning from diagnosis through age 5 improve by age 10. However, these early declines, as well as the continuous difficulties observed in patients treated with enucleation only, suggest the need for early intervention services for young patients with retinoblastoma. Continuous monitoring of the psychological functioning of patients with retinoblastoma, increased awareness of risk factors such as unilateral disease, enucleation, race, and surgery-only treatment plans, and referral to Early Intervention for all patients are indicated.

Response criteria for intraocular retinoblastoma: RB-RECIST.

Standardized guidelines for assessing tumor response to therapy are essential for designing and conducting clinical trials. The Response Evaluation Criteria In Solid Tumors (RECIST) provide radiological standards for assessment of solid tumors. However, no such guidelines exist for the evaluation of intraocular cancer, and ocular oncology clinical trials have largely relied on indirect measures of therapeutic response-such as progression-free survival-to evaluate the efficacy of treatment agents. Herein, we propose specific criteria for evaluating treatment response of retinoblastoma, the most common pediatric intraocular cancer, and emphasize a multimodal imaging approach for comprehensive assessment of retinoblastoma tumors in clinical trials.