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Background: Painful vaso-occlusive episodes (VOEs) are the hallmark of sickle cell disease (SCD) and account for frequent visits to the emergency department (ED) or urgent care (UC). Currently, the early administration of analgesics is recommended as initial management; however, there is a need for further understanding of the effect of prompt analgesics and hydration during VOEs. The objective of this study is to analyze the factors associated with the rate of hospital admission in the setting of time to intravenous (IV) analgesics and hydration. Method: This retrospective single-institution study reviewed adult and pediatric patients with SCD who presented with VOEs from January 2018 to August 2023. Results: Of 303 patient encounters, the rates of admission for the overall group, the subgroup which received IV hydration within 60 min of arrival, and the subgroup which received both IV analgesics and hydration within 60 min were 51.8%, 25.6% (RR = 0.46), and 18.2% (RR = 0.33), respectively. Further, factors such as gender and the use of hydroxyurea were found to be significantly associated with the rate of admission. Conclusions: This signifies the importance of standardizing the management of VOEs through the timely administration of IV analgesics and hydration in both adult and pediatric ED/UC.
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BACKGROUND: A phase I clinical study for patients with locally advanced H&N cancer with a new class of botanical drug APG-157 provided hints of potential synergy with immunotherapy. We sought to evaluate the efficacy of the combination of APG-157 and immune checkpoint inhibitors. METHODS: CCL23, UM-SCC1 (human), and SCCVII (HPV-), MEER (HPV+) (murine) H&N cancer cell lines were utilized for in vitro and in vivo studies. We measured tumor growth by treating the mice with APG-157, anti-PD-1, and anti-CTLA-4 antibody combinations (8 groups). The tumor microenvironments were assessed by multi-color flow cytometry, immunohistochemistry, and RNA-seq analysis. Fecal microbiome was analyzed by 16S rRNA sequence. RESULTS: Among the eight treatment groups, APG-157 + anti-CTLA-4 demonstrated the best tumor growth suppression (p = 0.0065 compared to the control), followed by anti-PD-1 + anti-CTLA-4 treatment group (p = 0.48 compared to the control). Immunophenotype showed over 30% of CD8+ T cells in APG-157 + anti-CTLA-4 group compared to 4%-5% of CD8+ T cells for the control group. Differential gene expression analysis revealed that APG-157 + anti-CTLA-4 group showed an enriched set of genes for inflammatory response and apoptotic signaling pathways. The fecal microbiome analysis showed a substantial difference of lactobacillus genus among groups, highest for APG-157 + anti-CTLA-4 treatment group. We were unable to perform correlative studies for MEER model as there was tumor growth suppression with all treatment conditions, except for the untreated control group. CONCLUSIONS: The results indicate that APG-157 and immune checkpoint inhibitor combination treatment could potentially lead to improved tumor control.
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Antígeno CTLA-4 , Neoplasias de Cabeza y Cuello , Inhibidores de Puntos de Control Inmunológico , Microambiente Tumoral , Animales , Ratones , Antígeno CTLA-4/antagonistas & inhibidores , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Línea Celular Tumoral , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de los fármacos , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/patología , Humanos , Femenino , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: This study aimed to assess the impact of periodontitis (PD) on the health related quality of life (HRQoL) and oral health related QoL (OHRQoL) of subjects with rheumatoid arthritis (RA) and PD. METHODS: Subjects from dental and RA clinics were screened. Complete periodontal examinations were performed. Subjects were divided into 4 groups: RA-PD, RA, PD and healthy controls (HC). Questionnaires on characteristics and Malaysian versions of Oral Health Impact Profile (OHIP-14(M)) and Health Assessment Questionnaire (HAQ-DI)) were answered. RESULTS: A total of 187 subjects were included (29 RA-PD, 58 RA, 43 PD and 57 HC). OHIP-14(M) severity score was highest in the PD group (17.23 ± 10.36) but only significantly higher than the HC group (p < 0.05). The HAQ-DI scores of the RA group was significantly higher than the PD and HC groups (p < 0.05). The interaction between the effects of PD and RA on the OHRQoL and HRQoL was statistically significant (p < 0.05). CONCLUSION: PD and RA subjects both suffer impacts on their OHRQoL and HRQoL respectively. The interaction effect of both diseases significantly conferred impacts on their OHRQoL and HRQoL as measured by the OHIP-14(M) and HAQ-DI.
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Artritis Reumatoide , Periodontitis , Estudios Transversales , Humanos , Salud Bucal , Calidad de Vida , Encuestas y CuestionariosRESUMEN
Usher syndrome is the most prevalent cause of hereditary deaf-blindness, characterized by congenital sensorineural hearing impairment and progressive photoreceptor degeneration beginning in childhood or adolescence. Diagnosis and management of this disease are complex, and the molecular changes underlying sensory cell impairment remain poorly understood. Here we characterize two zebrafish models for a severe form of Usher syndrome, Usher syndrome type 1C (USH1C): one model is a mutant with a newly identified ush1c nonsense mutation, and the other is a morpholino knockdown of ush1c. Both have defects in hearing, balance and visual function from the first week of life. Histological analyses reveal specific defects in sensory cell structure that are consistent with these behavioral phenotypes and could implicate Müller glia in the retinal pathology of Usher syndrome. This study shows that visual defects associated with loss of ush1c function in zebrafish can be detected from the onset of vision, and thus could be applicable to early diagnosis for USH1C patients.