Ophthalmologic Phenotype-Genotype Correlations in Patients With Oculocutaneous Albinism Followed in a Reference Center.

Purpose: Albinism is a group of genetic disorders that includes several conditions related to a defect in melanin production. There is a broad phenotypic and genotypic variability between the different forms. The aim of this study was to assess the ophthalmologic characteristics according to patients' genotypes in a cohort followed in the Reference Center for oculocutaneous albinism (OCA) of Bordeaux University Hospital, France. Methods: A retrospective observational study was conducted in a cohort of patients with OCA seen in consultation in the ophthalmology department between 2017 and 2021 in whom a genetic analysis was performed. Results: In total, 127 patients with OCA were included in this study and matched with the results of the genetic analysis. In the population aged over 6 years, there was no statistical difference in binocular visual acuity between the OCA1, OCA2, and OCA4 forms (P = 0.27). There was difference in ametropia between the three forms (P = 0.003). A two-by-two comparison using the Bonferroni correction showed a significant difference in ametropia between the OCA2 and OCA4 forms (P = 0.007) and between the OCA1 and OCA2 forms (P = 0.0075). Regardless of the form, most patients (75.4%) had grade 4 foveal hypoplasia. There was no association between the grade of foveal hypoplasia and the gene involved (P = 0.87). Conclusions: We described a genotype-phenotype correlation for the three most represented forms of albinism in our cohort. This study allowed assessing the degree of visual deficiency in young children with OCA.

Early non-invasive ventilation and high-flow nasal oxygen therapy for preventing endotracheal intubation in hypoxemic blunt chest trauma patients: the OptiTHO randomized trial.

BACKGROUND: The benefit-risk ratio of prophylactic non-invasive ventilation (NIV) and high-flow nasal oxygen therapy (HFNC-O2) during the early stage of blunt chest trauma remains controversial because of limited data. The main objective of this study was to compare the rate of endotracheal intubation between two NIV strategies in high-risk blunt chest trauma patients. METHODS: The OptiTHO trial was a randomized, open-label, multicenter trial over a two-year period. Every adult patients admitted in intensive care unit within 48 h after a high-risk blunt chest trauma (Thoracic Trauma Severity Score ≥ 8), an estimated PaO2/FiO2 ratio < 300 and no evidence of acute respiratory failure were eligible for study enrollment (Clinical Trial Registration: NCT03943914). The primary objective was to compare the rate of endotracheal intubation for delayed respiratory failure between two NIV strategies: i) a prompt association of HFNC-O2 and "early" NIV in every patient for at least 48 h with vs. ii) the standard of care associating COT and "late" NIV, indicated in patients with respiratory deterioration and/or PaO2/FiO2 ratio ≤ 200 mmHg. Secondary outcomes were the occurrence of chest trauma-related complications (pulmonary infection, delayed hemothorax or moderate-to-severe ARDS). RESULTS: Study enrollment was stopped for futility after a 2-year study period and randomization of 141 patients. Overall, 11 patients (7.8%) required endotracheal intubation for delayed respiratory failure. The rate of endotracheal intubation was not significantly lower in patients treated with the experimental strategy (7% [5/71]) when compared to the control group (8.6% [6/70]), with an adjusted OR = 0.72 (95%IC: 0.20-2.43), p = 0.60. The occurrence of pulmonary infection, delayed hemothorax or delayed ARDS was not significantly lower in patients treated by the experimental strategy (adjusted OR = 1.99 [95%IC: 0.73-5.89], p = 0.18, 0.85 [95%IC: 0.33-2.20], p = 0.74 and 2.14 [95%IC: 0.36-20.77], p = 0.41, respectively). CONCLUSION: A prompt association of HFNC-O2 with preventive NIV did not reduce the rate of endotracheal intubation or secondary respiratory complications when compared to COT and late NIV in high-risk blunt chest trauma patients with non-severe hypoxemia and no sign of acute respiratory failure. CLINICAL TRIAL REGISTRATION: NCT03943914, Registered 7 May 2019.

Second-degree burn induced by high-concentration topical capsaicin with mobility sequelae: A case report.

High-concentration topical capsaicin is used as a second-line treatment for neuropathic pain. Transient, mild burning sensation and erythema are expected adverse drug reactions. Here, we report the first case of second degree burn after the application of a high-concentration topical capsaicin patch with secondary mobility sequelae. Nine months after the application, neuropathic pain still remained and the patient described mobility difficulties in daily activities, preventing her from returning to work. This report aims to raise the question of the benefit/risk ratio of high concentration topical capsaicin.

Association of Peri-ictal MRI Abnormalities With Mortality, Antiseizure Medication Refractoriness, and Morbidity in Status Epilepticus.

BACKGROUND AND OBJECTIVES: Status epilepticus (SE) is a life-threatening emergency requiring a prompt assessment of patient prognosis to guide management. MRI allows the identification of peri-ictal MRI abnormalities (PMAs) and provides insight into brain structural modifications induced by SE. However, little is known about the significance of PMA in SE prognosis. The aim of this study was to determine whether PMAs are associated with an increased mortality in SE and to establish the association between PMA and refractoriness to antiseizure medications, complications encountered, and induced morbidity. METHODS: We conducted a retrospective observational cohort study including all eligible consecutive patients over 15 years old and hospitalized with SE at Bordeaux University Hospital (France) between January 2015 and December 2019. The primary end point was in-hospital mortality. A dedicated neuroradiologic reassessment was performed, together with a comprehensive medical review assessing baseline characteristics, in-hospital death, SE characterization, drug refractoriness, and following outcome in survivors. RESULTS: Of 307 patients included, 79 (26%) showed PMA related to SE. Demographic, functional status at baseline and median delay between SE onset and MRI examination were similar in the PMA-positive and PMA-negative groups. In-hospital death occurred in 15% (45/307) patients and was significantly higher in the PMA-positive group (27%, 21/79 vs 11%, 24/228; p < 0.001). In multivariate analysis, the presence of PMA (odds ratio [OR] 2.86, 95% CI 1.02-8.18; p = 0.045), together with SE duration (OR 1.01, 95% CI 1.01-1.02; p = 0.007), older age at SE onset (OR 1.05, 95% CI 1.01-1.09; p = 0.013), preexisting ultimately fatal comorbidity (OR 4.01, 95% CI 1.56-10.6; p = 0.004), and acute lesional SE etiology (OR 3.74, 95% CI 1.45-10.2; p = 0.007) were independent predictors associated with in-hospital death. Patients with PMA had a higher risk of refractory SE (71 vs 33%, p < 0.001). Among survivors, delayed-onset epilepsy (40% vs 21%, p = 0.009) occurred more frequently in the PMA-positive group. DISCUSSION: PMA-positive cases had a higher mortality rate in the largest cohort so far to assess the prognosis value of PMA in SE. As a noninvasive and easily available tool, PMA represents a promising structural biomarker for developing a personalized approach to prognostication in patients with SE receiving MRI.

Antiparkinson Drug Benztropine Suppresses Tumor Growth, Circulating Tumor Cells, and Metastasis by Acting on SLC6A3/DAT and Reducing STAT3.

Tumor growth, progression, and therapy resistance are crucial factors in the prognosis of cancer. The properties of three-dimensional (3D) tumor-like organoids (tumoroids) more closely resemble in vivo tumors compared to two-dimensionally cultured cells and are therefore effectively used for assays and drug screening. We here established a repurposed drug for novel anticancer research and therapeutics using a 3D tumoroid-based screening system. We screened six pharmacologically active compounds by using an original tumoroid-based multiplex phenotypic screening system with a matrix metalloproteinase 9 (MMP9) promoter-driven fluorescence reporter for the evaluation of both tumoroid formation and progression. The antiparkinson drug benztropine was the most effective compound uncovered by the screen. Benztropine significantly inhibited in vitro tumoroid formation, cancer cell survival, and MMP9 promoter activity. Benztropine also reduced the activity of oncogenic signaling transducers and trans-activators for MMP9, including STAT3, NF-κB, and ß-catenin, and the properties of cancer stem cells/cancer-initiating cells. Benztropine and GBR-12935 directly targeted the dopamine transporter DAT/SLC6A3, whose genetic alterations such as amplification were correlated with poor prognosis for cancer patients. Benztropine also inhibited the tumor growth, circulating tumor cell (CTC) number, and rate of metastasis in a tumor allograft model in mice. In conclusion, we propose the repurposing of benztropine for anticancer research and therapeutics that can suppress tumor progression, CTC, and metastasis of aggressive cancers by reducing key pro-tumorigenic factors.