Background: We evaluated severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-specific humoral and cellular responses for up to 6 months after the 3rd dose of ancestral coronavirus disease 2019 (COVID-19) vaccination in people living with HIV (PLWH) and healthy controls (HCs) who were not infected with COVID-19. Methods: Anti-spike receptor-binding domain IgG (anti-RBD IgG) concentrations using chemiluminescence immunoassay and neutralizing antibodies using focus reduction neutralization test (FRNT) were assessed at 1 week after each dose of vaccination, and 3 and 6 months after the 3rd dose in 62 PLWH and 25 HCs. T-cell responses using intracellular cytokine stain were evaluated at 1 week before, and 1 week and 6 months after the 3rd dose. Results: At 1 week after the 3rd dose, adequate anti-RBD IgG (> 300 binding antibody unit /mL) was elicited in all PLWH except for one patient with 36 CD4 T-cell count/mm3 . The geometric mean titers of 50% FRNT against wild type (WT) and omicron BA.5 strains of SARS-CoV-2 in PLWH with CD4 T-cell count ≥ 500 cells/mm3(high CD4 recovery, HCDR) were comparable to HC, but they were significantly decreased in PLWH with CD4 T-cell count < 500/mm3 (low CD4 recovery, LCDR). After adjusting for age, gender, viral suppression, and number of preexisting comorbidities, CD4 T-cell counts < 500/mm3 significantly predicted a poor magnitude of neutralizing antibodies against WT, omicron BA.5, and XBB 1.5 strains among PLWH. Multivariable linear regression adjusting for age and gender revealed that LCDR was associated with reduced neutralizing activity (P = 0.017) and interferon-γ-producing T-cell responses (P = 0.049 for CD T-cell; P = 0.014 for CD8 T-cell) against WT, and strongly associated with more decreased cross-neutralization against omicron BA.5 strains (P < 0.001). Conclusion HCDR demonstrated robust humoral and cell-mediated immune responses after a booster dose of ancestral SARS-CoV-2 vaccine, whereas LCDR showed diminished immune responses against WT virus and more impaired cross-neutralization against omicron BA.5 strain.

Background: Currently, little is known about the relationship between the temporal radiographic latent trajectories, which are based on the extent of coronavirus disease 2019 (COVID-19) pneumonia and clinical outcomes. This study aimed to elucidate the differences in the temporal trends of critical laboratory biomarkers, utilization of critical care support, and clinical outcomes according to temporal radiographic latent trajectories. Methods: We enrolled 2,385 patients who were hospitalized with COVID-19 and underwent serial chest radiographs from December 2019 to March 2022. The extent of radiographic pneumonia was quantified as a percentage using a previously developed deep-learning algorithm. A latent class growth model was used to identify the trajectories of the longitudinal changes of COVID-19 pneumonia extents during hospitalization. We investigated the differences in the temporal trends of critical laboratory biomarkers among the temporal radiographic trajectory groups. Cox regression analyses were conducted to investigate differences in the utilization of critical care supports and clinical outcomes among the temporal radiographic trajectory groups. Results: The mean age of the enrolled patients was 58.0 ± 16.9 years old, with 1,149 (48.2%) being male. Radiographic pneumonia trajectories were classified into three groups: The steady group (n = 1,925, 80.7%) exhibited stable minimal pneumonia, the downhill group (n = 135, 5.7%) exhibited initial worsening followed by improving pneumonia, and the uphill group (n = 325, 13.6%) exhibited progressive deterioration of pneumonia. There were distinct differences in the patterns of temporal blood urea nitrogen (BUN) and C-reactive protein (CRP) levels between the uphill group and the other two groups. Cox regression analyses revealed that the hazard ratios (HRs) for the need for critical care support and the risk of intensive care unit admission were significantly higher in both the downhill and uphill groups compared to the steady group. However, regarding in-hospital mortality, only the uphill group demonstrated a significantly higher risk than the steady group (HR, 8.2; 95% confidence interval, 3.08–21.98). Conclusion Stratified pneumonia trajectories, identified through serial chest radiographs, are linked to different patterns of temporal changes in BUN and CRP levels. These changes can predict the need for critical care support and clinical outcomes in COVID-19 pneumonia.Appropriate therapeutic strategies should be tailored based on these disease trajectories.

Background: Tinnitus is a bothersome condition associated with various mechanisms of action. Although treatment methods vary according to these mechanisms, standardized guidelines would benefit both patients and clinicians. We conducted a Delphi study, a method that collects expert opinions through multiple rounds of questionnaires, to reach a consensus on tinnitus treatment with professional experts. Methods: A two-round modified Delphi survey was conducted to develop a clinical consensus on tinnitus treatment. The experts scored each statement on a scale of 1 (highest disagreement) to 9 (highest agreement) for their level of agreement on tinnitus treatment.Consensus was defined when 75% or more of the participants scored 7–9, and 15% or less scored 1–3. To ensure reliability of the responses, the content validity ratio and Kendall’s coefficient of concordance were evaluated. Results: Approximately 19 of 31 statements reached a consensus. All 3 statements reached a consensus regarding the candidates for treatment. Regarding treatment, 3 of 8 statements on medication, 2 of 2 statements on tinnitus retraining therapy/cognitive behavioral therapy, and 5 of 7 statements on auditory rehabilitation reached a positive consensus. Although all 6 statements regarding miscellaneous treatment reached a consensus, most were negatively agreed. For treatment with neuromodulation, none of the 5 statements reached a consensus. Conclusion The experts reached a high level of consensus on treatment candidates, tinnitus retraining therapy/cognitive behavioral therapy, and auditory rehabilitation in this modified Delphi study. The results of this study can provide beneficial and practical information for clinicians regarding the treatment of tinnitus.

Background: We evaluated severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-specific humoral and cellular responses for up to 6 months after the 3rd dose of ancestral coronavirus disease 2019 (COVID-19) vaccination in people living with HIV (PLWH) and healthy controls (HCs) who were not infected with COVID-19. Methods: Anti-spike receptor-binding domain IgG (anti-RBD IgG) concentrations using chemiluminescence immunoassay and neutralizing antibodies using focus reduction neutralization test (FRNT) were assessed at 1 week after each dose of vaccination, and 3 and 6 months after the 3rd dose in 62 PLWH and 25 HCs. T-cell responses using intracellular cytokine stain were evaluated at 1 week before, and 1 week and 6 months after the 3rd dose. Results: At 1 week after the 3rd dose, adequate anti-RBD IgG (> 300 binding antibody unit /mL) was elicited in all PLWH except for one patient with 36 CD4 T-cell count/mm3 . The geometric mean titers of 50% FRNT against wild type (WT) and omicron BA.5 strains of SARS-CoV-2 in PLWH with CD4 T-cell count ≥ 500 cells/mm3(high CD4 recovery, HCDR) were comparable to HC, but they were significantly decreased in PLWH with CD4 T-cell count < 500/mm3 (low CD4 recovery, LCDR). After adjusting for age, gender, viral suppression, and number of preexisting comorbidities, CD4 T-cell counts < 500/mm3 significantly predicted a poor magnitude of neutralizing antibodies against WT, omicron BA.5, and XBB 1.5 strains among PLWH. Multivariable linear regression adjusting for age and gender revealed that LCDR was associated with reduced neutralizing activity (P = 0.017) and interferon-γ-producing T-cell responses (P = 0.049 for CD T-cell; P = 0.014 for CD8 T-cell) against WT, and strongly associated with more decreased cross-neutralization against omicron BA.5 strains (P < 0.001). Conclusion HCDR demonstrated robust humoral and cell-mediated immune responses after a booster dose of ancestral SARS-CoV-2 vaccine, whereas LCDR showed diminished immune responses against WT virus and more impaired cross-neutralization against omicron BA.5 strain.

Background: Currently, little is known about the relationship between the temporal radiographic latent trajectories, which are based on the extent of coronavirus disease 2019 (COVID-19) pneumonia and clinical outcomes. This study aimed to elucidate the differences in the temporal trends of critical laboratory biomarkers, utilization of critical care support, and clinical outcomes according to temporal radiographic latent trajectories. Methods: We enrolled 2,385 patients who were hospitalized with COVID-19 and underwent serial chest radiographs from December 2019 to March 2022. The extent of radiographic pneumonia was quantified as a percentage using a previously developed deep-learning algorithm. A latent class growth model was used to identify the trajectories of the longitudinal changes of COVID-19 pneumonia extents during hospitalization. We investigated the differences in the temporal trends of critical laboratory biomarkers among the temporal radiographic trajectory groups. Cox regression analyses were conducted to investigate differences in the utilization of critical care supports and clinical outcomes among the temporal radiographic trajectory groups. Results: The mean age of the enrolled patients was 58.0 ± 16.9 years old, with 1,149 (48.2%) being male. Radiographic pneumonia trajectories were classified into three groups: The steady group (n = 1,925, 80.7%) exhibited stable minimal pneumonia, the downhill group (n = 135, 5.7%) exhibited initial worsening followed by improving pneumonia, and the uphill group (n = 325, 13.6%) exhibited progressive deterioration of pneumonia. There were distinct differences in the patterns of temporal blood urea nitrogen (BUN) and C-reactive protein (CRP) levels between the uphill group and the other two groups. Cox regression analyses revealed that the hazard ratios (HRs) for the need for critical care support and the risk of intensive care unit admission were significantly higher in both the downhill and uphill groups compared to the steady group. However, regarding in-hospital mortality, only the uphill group demonstrated a significantly higher risk than the steady group (HR, 8.2; 95% confidence interval, 3.08–21.98). Conclusion Stratified pneumonia trajectories, identified through serial chest radiographs, are linked to different patterns of temporal changes in BUN and CRP levels. These changes can predict the need for critical care support and clinical outcomes in COVID-19 pneumonia.Appropriate therapeutic strategies should be tailored based on these disease trajectories.

Background: Tinnitus is a bothersome condition associated with various mechanisms of action. Although treatment methods vary according to these mechanisms, standardized guidelines would benefit both patients and clinicians. We conducted a Delphi study, a method that collects expert opinions through multiple rounds of questionnaires, to reach a consensus on tinnitus treatment with professional experts. Methods: A two-round modified Delphi survey was conducted to develop a clinical consensus on tinnitus treatment. The experts scored each statement on a scale of 1 (highest disagreement) to 9 (highest agreement) for their level of agreement on tinnitus treatment.Consensus was defined when 75% or more of the participants scored 7–9, and 15% or less scored 1–3. To ensure reliability of the responses, the content validity ratio and Kendall’s coefficient of concordance were evaluated. Results: Approximately 19 of 31 statements reached a consensus. All 3 statements reached a consensus regarding the candidates for treatment. Regarding treatment, 3 of 8 statements on medication, 2 of 2 statements on tinnitus retraining therapy/cognitive behavioral therapy, and 5 of 7 statements on auditory rehabilitation reached a positive consensus. Although all 6 statements regarding miscellaneous treatment reached a consensus, most were negatively agreed. For treatment with neuromodulation, none of the 5 statements reached a consensus. Conclusion The experts reached a high level of consensus on treatment candidates, tinnitus retraining therapy/cognitive behavioral therapy, and auditory rehabilitation in this modified Delphi study. The results of this study can provide beneficial and practical information for clinicians regarding the treatment of tinnitus.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.