Very Long-term Survivorship in Pediatric DIPG: Case Report and Review of the Literature.

Diffuse intrinsic pontine gliomas are lethal tumors with a prognosis generally less than 1 year. Few cases of survivors of 5 years or more have been reported. This case report highlights the journey of a 9.5-year survivor who underwent 3 rounds of focal radiotherapy; she experienced 6 years of progression-free survival following the first round but ultimately succumbed to her disease. An autopsy revealed a favorable IDH1 mutation and the absence of H3K27M. This case reiterates the importance of extensive molecular analyses in diffuse intrinsic pontine gliomas and explores the potential benefit of re-irradiation in patients with positive responses and long periods of remission.

Recurrent primary intracranial sarcoma, DICER1-mutant in a pediatric patient with DICER1 syndrome: the importance of molecular testing.

Pediatric intracranial sarcomas are rare, aggressive tumors with a poor prognosis in general. Here we report the case of a child who was initially diagnosed with a primary intracranial sarcoma, DICER1-mutant; subsequent genetic analyses confirmed a pathogenic germline DICER1 mutation. She received multimodal standard treatments consisting of surgery, radiotherapy and chemotherapy. The tumor recurred 2.5 years later within the surgical cavity. Following the gross tumor resection of this new lesion, the same multimodal standard approach was used. From a molecular perspective, evidence of hyperactivation of the MAPK-kinase pathway with a pathogenic KRAS mutation at both diagnosis and recurrence was present. The patient is currently in remission, 18 months post-end of treatment.

Bevacizumab in the Treatment of Refractory Brain Edema in High-grade Glioma.

We report the case of a 14-year-old boy with a steroid-dependent refractory tumor whose longstanding dexamethasone treatment was successfully discontinued after a course of bevacizumab. The use of bevacizumab despite the absence of clear evidence of radionecrosis allowed a significant decrease in the amount of the brain edema.

Prognostic Factors for Visual Outcomes in Closed Idiopathic Macular Holes after Vitrectomy: Outcomes at 4 Years in a Monocentric Study.

Purpose: To identify predictive factors of visual outcomes in the eyes after successful macular hole (MH) surgery. Methods: It is a retrospective monocentric study of the eyes that underwent successful vitrectomy for full-thickness MH in an academic, tertiary care center (CHU de Québec-Université Laval, Québec, Canada) between 2014 and 2018. We included a single eye per patient and excluded the eyes with ocular comorbidities. Clinical and anatomical features of patients were collected, including demographics, MH duration, baseline MH size, baseline visual acuity (VA), and final VA. Multiple logistic regressions were performed to determine predictive factors of VA ≥70 ETDRS letters (Snellen equivalent: 20/40) and VA gain ≥15 ETDRS letters at final follow-up. Areas under the receiver operating characteristic curve (AUC) were used to determine the performance of each model and identify the Youden index maximizing performance at a given threshold. Results: A total of 460 eyes were included in this study; 274/460 eyes (60%) achieved final VA ≥70 ETDRS letters and 304/460 eyes (66%) had a VA gain ≥15 ETDRS letters at 24 months follow-up. Multiple logistic regression analyses showed that the main predictive factors for final VA ≥70 ETDRS letters (model AUC = 0.716) were baseline VA (OR = 1.064; p < 0.001), MH duration (OR = 0.950; p=0.005), and age (OR = 0.954; p=0.004). Predictors of VA gain ≥15 ETDRS letters at final follow-up (model AUC = 0.615) were baseline VA (OR = 0.878; p < 0.001), MH duration (OR = 0.940; p < 0.001), and MH size (OR = 0.998; p=0.036). Thresholds for the final VA ≥70 ETDRS letters model and the VA gain ≥15 ETDRS letters model were VA ≥55.5 ETDRS letters (Snellen equivalent: 6/30) and MH size of 237 µm, respectively. Conclusion: The eyes with shorter MH duration, smaller MH size, and higher preoperative VA achieved better visual outcomes after successful MH surgery.

DELAYED FOLLOW-UP IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TREATED UNDER UNIVERSAL HEALTH COVERAGE: Risk Factors and Visual Outcomes.

BACKGROUND/PURPOSE: To report the rate of delayed follow-up visits (DFU), to identify risk factors of DFU, and to assess the impact of DFU on outcomes in neovascular age-related macular degeneration. METHODS: This retrospective study included all patients with neovascular age-related macular degeneration (n = 1,291) treated with antivascular endothelial growth factor injections between January 2013 and December 2020 in 2 centers in Quebec, Canada. A DFU was defined as a delay of ≥4 weeks than scheduled. Visual outcomes, especially ≥15 letters loss, were reported. RESULTS: A total of 351 patients (27.2%) experienced ≥1 DFU. Odds were greater among older patients ( P = 0.005), patients treated at the hospital rather than the clinic ( P < 0.001), and patients with worse initial visual acuity ( P = 0.024). A DFU was associated with a mean visual acuity loss of 4.2 ± 13.4 letters ( P < 0.001) and an increased incidence of intraretinal fluid and subretinal fluid ( P = 0.001, P = 0.005) at 6 months despite resumption of injections. Central foveal thickness increased after DFU but returned to pre-DFU visit at 6 months. CONCLUSION: The DFU rate in patients with neovascular age-related macular degeneration treated under a universal health care system was around 27%. Delayed follow-up visits caused significant decreases in visual acuity and increases in intraretinal fluid and subretinal fluid on optical coherence tomography that did not recover after injections resumption despite normalization of central foveal thickness.

Predicting Visual Improvement After Macular Hole Surgery: A Combined Model Using Deep Learning and Clinical Features.

Purpose: The purpose of this study was to assess the feasibility of deep learning (DL) methods to enhance the prediction of visual acuity (VA) improvement after macular hole (MH) surgery from a combined model using DL on high-definition optical coherence tomography (HD-OCT) B-scans and clinical features. Methods: We trained a DL convolutional neural network (CNN) using pre-operative HD-OCT B-scans of the macula and combined with a logistic regression model of pre-operative clinical features to predict VA increase ≥15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 6 months post-vitrectomy in closed MHs. A total of 121 MHs with 242 HD-OCT B-scans and 484 clinical data points were used to train, validate, and test the model. Prediction of VA increase was evaluated using the area under the receiver operating characteristic curve (AUROC) and F1 scores. We also extracted the weight of each input feature in the hybrid model. Results: All performances are reported on the held-out test set, matching results obtained with cross-validation. Using a regression on clinical features, the AUROC was 80.6, with an F1 score of 79.7. For the CNN, relying solely on the HD-OCT B-scans, the AUROC was 72.8 ± 14.6, with a F1 score of 61.5 ± 23.7. For our hybrid regression model using clinical features and CNN prediction, the AUROC was 81.9 ± 5.2, with an F1 score of 80.4 ± 7.7. In the hybrid model, the baseline VA was the most important feature (weight = 59.1 ± 6.9%), while the weight of HD-OCT prediction was 9.6 ± 4.2%. Conclusions: Both the clinical data and HD-OCT models can predict postoperative VA improvement in patients undergoing vitrectomy for a MH with good discriminative performances. Combining them into a hybrid model did not significantly improve performance. Translational Relevance: OCT-based DL models can predict postoperative VA improvement following vitrectomy for MH but fusing those models with clinical data might not provide improved predictive performance.

Outcomes of surgical repair of Retinoschisis-associated retinal detachment compared to Rhegmatogenous retinal detachment.

BACKGROUND: The aim of this study is to compare outcomes of primary retinal detachment (RD) repair in retinoschisis-associated RD (RSRD) and rhegmatogenous RD (RRD). METHODS: This is a retrospective observational cohort study. Charts of 2247 consecutive patients operated for RD repair at the Centre hospitalier universitaire de Québec - Université Laval between 2014 and 2018 were reviewed. Patients with RSRD and RRD were included to compare the visual and anatomical outcomes of both groups. RESULTS: There were 41 patients (1.8%) with RSRD and 1661 patients (74%) with RRD. RSRD patients had more primary repair failures (n = 9, 22%, vs. n = 166, 10%; p = 0.013). The primary anatomical success rates for pars plana vitrectomy with and without scleral buckle (PPV-SB vs. PPV) as primary repair method were similar in both RSRD patients (n = 11/14, 79% vs. n = 20/25, 80%; p = 0.92) and RRD patients (n = 751/827, 91% vs. n = 641/721, 89%; p = 0.21). At final follow-up, best corrected visual acuity (VA) in logarithm of the minimum angle of resolution (logMAR) was 0.30 [0.10, 0.88] and 0.18 [0.10, 0.40] (p = 0.03) in RSRD patients and RRD patients, respectively. Presence of retinoschisis was associated with worse final VA (ß 0.082, p < 0.001). Other predictive variables included female sex, macula-off presentation, number of RD quadrants involved, longer symptoms duration, worse baseline VA, and primary repair failure. The greatest predictors were worse baseline VA, primary repair failure, and macula-off status at presentation. Presence of retinoschisis did not significantly increase risk of primary repair failure in multivariable analysis (OR 1.45, 95% CI: 0.50-4.17; p = 0.49). Symptoms duration was the greatest effect factor associated with for primary repair failure (OR 1.37, 95% CI: 1.12-1.69; p = 0.003). CONCLUSIONS: RSRD is associated with more primary repair failure in univariate analysis, but not in multivariate analysis after adjusting for symptoms duration. It is however associated with worse final VA even after adjusting for primary repair failure. Both PPV and PPV-SB are valid repair methods for RSRD. However, RSRD remains a challenge to treat.

Revision Surgery for Idiopathic Macular Hole after Failed Primary Vitrectomy.

PURPOSE: To investigate the anatomical and functional outcomes of revision surgery after failed primary surgery for idiopathic macular hole (MH). METHODS: All consecutive patients with MH were identified from a cohort of patients operated between 2014 and 2018 at the CHU de Québec-Université Laval (Québec). The clinical and anatomical features of patients with unclosed MH after primary surgery were retrospectively collected. Our primary outcome was MH nonclosure rate after revision surgery. Our secondary outcomes were best-corrected visual acuity (BCVA) with ETDRS scale and MH size of eyes with revision surgery preoperatively and at 3 and 12 months after revision surgery. RESULTS: In our cohort of 1085 eyes, 926 eyes met inclusion criteria and were analyzed in the study. We identified 22 eyes with failed primary surgery (2.4%), of which 20 underwent revision surgery. We had no bilateral MH in these 22 eyes. The nonclosure rate of MH after revision surgery was 15%. The mean final BCVA for closed MH after revision surgery was 55 ± 19 letters. Compared to the initial presentation, the mean change in visual acuity (VA) for closed MH was +4 ± 31 letters and +16 ± 17 letters at 3 and 12 months after the revision surgery, respectively. At initial presentation, patients with failed primary surgery had a baseline MH size of 665 ± 226 µm. The mean MH size after failed primary surgery was 607 ± 162 µm and 546 ± 156 µm for the three unclosed MHs one month after revision surgery. CONCLUSION: The success rate of revision surgery in eyes with unclosed MH is 85%. After successful revision surgery, eyes demonstrated an improvement in VA and closure of the MH.

Case Reports of Aripiprazole and Problematic Gambling in Schizophrenia: A Critical Review of the Evidence.

BACKGROUND: Pharmacovigilance studies have reported a higher risk of problematic gambling (PG) in people receiving aripiprazole (ARI), a partial dopamine agonist. This association needs to be specifically assessed in schizophrenia (SZ) given the high prevalence of risk factors for PG in this population (eg, comorbid substance use) and given the nature of the dopamine dysfunction in this disorder. At the present stage, case studies may shed light on such an association. METHODS: All published cases involving SZ patients with PG while on ARI were systematically identified. Two instruments were used to assess causality. RESULTS: We identified 16 published SZ cases exposed to ARI experiencing PG. Half of whom had a gambling history before ARI exposition. Naranjo scores led to the estimation of a possible link between ARI exposition and PG in 15 of 16 cases (average score of 3) and probable (score of 5) in 1 case. More than 50% of items were left unknown owing to the lack of information or scale limitations. Using the Liverpool algorithm, causality estimation was raised to probable in 13 of 16 cases, definite in 1 case, and nonassessable in 2 cases. CONCLUSIONS: The present review confirms that ARI may be involved in the occurrence of PG in some SZ patients. However, important information to assess causality was frequently missing, and the 2 scales used did not yield the same degree of certainty. The current article calls for including more details in future case reports and for well-powered studies carefully assessing factors such as comorbid diagnoses.