Postoperative Proliferation Detection in Eyes Treated for Rhegmatogenous Retinal Detachment by WideField OCT Angiography.

Purpose: Proliferative retinal changes may occur postsurgery for rhegmatogenous retinal detachment (RRD), possibly preceding recurrent detachment. This study aims to establish the groundwork for an imaging system capable of discerning changes in retinal vessel tortuosity after RRD repair, analyzing widefield optical coherence tomography angiography (WF-OCTA) images. Methods: Eighty-eight eyes of 86 patients with RRD who underwent surgical procedures and had repeated imaging with clear widefield optical coherence tomography (WF-OCT) and WF-OCTA on different postoperative days were enrolled in this retrospective study. We compared WF-OCTA images over time to identify alterations in retinal vessel tortuosity and observed regional changes in retinal morphology. Results: After image processing, changes in retinal vessel tortuosity were detected in 66 quadrants. These changes, attributed to retinal traction from proliferative membranes, were observed in 56 quadrants, among which retinal thickness remained unchanged in seven sectors (12.5%) according to the WF-OCT map. In nine quadrants, changes in retinal vessel tortuosity were attributed to changes in subretinal fluid, aligning with observable variations in retinal thickness. Conclusions: Observation of vessel tortuosity changes using WF-OCTA can help detect early postoperative proliferative changes in eyes with RRD. Translational Relevance: Because WF-OCTA can detect minute vessel tortuosity changes, it can offer a noninvasive alternative for the detection of early postoperative proliferative changes.

Three-month outcomes of treatment with faricimab or aflibercept for neovascular age-related macular degeneration: a propensity score matching study in a Japanese population.

PURPOSE: This study aimed to compare the treatment outcomes of patients with neovascular age-related macular degeneration (nAMD) who initially received faricimab or aflibercept treatment using propensity score matching (PSM) to align patient backgrounds. METHODS: Patients with treatment-naïve nAMD who received either faricimab or aflibercept for three consecutive monthly injections as the loading phase were enrolled in this study. In the 1:1 PSM, sex, age, best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and AMD subtypes in the pre-treatment state were selected as covariates. We examined the BCVA, CMT, CCT, and remaining fluid at 1-, 2-, and 3-month after the first injection. RESULTS: After PSM, 43 eyes were included in the faricimab and aflibercept group each. Both groups showed significant improvements in BCVA, CMT, and CCT at 1-, 2-, and 3-month after the initial injection compared with baseline. Meanwhile, no significant differences were observed between the two groups at any time point regarding BCVA, CMT, and CCT. At 1-month, 18.6% of patients in the faricimab group and 41.9% in the aflibercept group demonstrated residual subretinal fluid or intraretinal fluid, with a significant difference between the groups (P = 0.03). CONCLUSION: The BCVA improved after three loading injections of both faricimab and aflibercept. Faricimab may provide a favorable early treatment response in reducing subretinal fluid in a Japanese cohort.

Increased levels of circulating cell-free DNA in COVID-19 patients with respiratory failure.

Cell-free DNA (cfDNA) is released from injured cells and aggravates inflammation. Patients with coronavirus disease (COVID-19) often develop pneumonia and respiratory failure, and require oxygen therapy (OT), including mechanical ventilation (MV). It remains unclear whether cfDNA predicts the risk of receiving OT or MV in COVID-19 patients. Therefore, we hypothesized that circulating cfDNA levels could reflect the severity of respiratory failure and determine a therapeutic approach for oxygenation in patients with COVID-19. We analyzed cfDNA levels in serum samples from 95 hospitalized patients with COVID-19 at Showa University Hospital (Tokyo, Japan). cfDNA levels were assessed by measuring the copy numbers of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) using quantitative real-time PCR (qPCR). Both cf-nDNA and cf-mtDNA levels were negatively correlated with adjusted SpO2 for FiO2 (SpO2/FiO2 ratio). Elevated cf-nDNA and cf-mtDNA levels were associated with the requirement for OT or MV during patient admission. Multivariate logistic regression analysis revealed that cf-nDNA and cf-mtDNA levels were independent risk factors for OT and MV. These results suggest that both serum cf-nDNA and cf-mtDNA could serve as useful early biomarkers to indicate the necessity of OT or MV in patients with COVID-19.

Utility of pneumonia severity assessment tools for mortality prediction in healthcare-associated pneumonia: a systematic review and meta-analysis.

Accurate prognostic tools for mortality in patients with healthcare-associated pneumonia (HCAP) are needed to provide appropriate medical care, but the efficacy for mortality prediction of tools like PSI, A-DROP, I-ROAD, and CURB-65, widely used for predicting mortality in community-acquired and hospital-acquired pneumonia cases, remains controversial. In this study, we conducted a systematic review and meta-analysis using PubMed, Cochrane Library (trials), and Ichushi web database (accessed on August 22, 2022). We identified articles evaluating either PSI, A-DROP, I-ROAD, or CURB-65 and the mortality outcome in patients with HCAP, and calculated the pooled sensitivities, specificities, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the summary area under the curves (AUCs) for mortality prediction. Additionally, the differences in predicting prognosis among these four assessment tools were evaluated using overall AUCs pooled from AUC values reported in included studies. Eventually, 21 articles were included and these quality assessments were evaluated by QUADAS-2. Using a cut-off value of moderate in patients with HCAP, the range of pooled sensitivity, specificity, PLR, NLR, and DOR were found to be 0.91-0.97, 0.15-0.44, 1.14-1.66, 0.18-0.33, and 3.86-9.32, respectively. Upon using a cut-off value of severe in those patients, the range of pooled sensitivity, specificity, PLR, NLR, and DOR were 0.63-0.70, 0.54-0.66, 1.50-2.03, 0.47-0.58, and 2.66-4.32, respectively. Overall AUCs were 0.70 (0.68-0.72), 0.70 (0.63-0.76), 0.68 (0.64-0.73), and 0.67 (0.63-0.71), respectively, for PSI, A-DROP, I-ROAD, and CURB-65 (p = 0.66). In conclusion, these severity assessment tools do not have enough ability to predict mortality in HCAP patients. Furthermore, there are no significant differences in predictive performance among these four severity assessment tools.

The factors associated with retinal pigment epithelium tear development in the early phase after treatment initiation for age-related macular degeneration.

PURPOSE: This study aimed to evaluate the factors associated with retinal pigment epithelium (RPE) tear development in the early phase after anti-vascular endothelial growth factor (VEGF) drug initiation in eyes with neovascular age-related macular degeneration (nAMD) and retinal pigment epithelial detachment (PED). METHODS: Treatment-naive eyes with nAMD and PED for which anti-VEGF drug injections had been initiated and followed up for at least 3 months after the 1st anti-VEGF drug injection, were retrospectively investigated. Baseline characteristics of the PEDs, including type, height, and area, were evaluated using fundus photographs, fluorescein angiography, and optical coherence tomography images. The association between patient age, sex, medical history, PED characteristics, and the development of RPE tears within 3 months of starting anti-VEGF therapy was examined. RESULTS: This study included 244 eyes (230 patients; mean age 75.0 years, 159 males and 71 females). RPE tears occurred in 13 eyes (5.3%) within 3 months of the start of anti-VEGF therapy. Multivariate analysis showed an association of the development of RPE tears with PED height (every 100 µm, odds ratio [OR]: 1.50, 95% confidence interval [CI]: 1.07-2.12, p = 0.019), PED area (every 10 mm2, OR: 3.02, CI: 1.22-7.46, p = 0.016), and the presence of fibrovascular PED (OR: 59.22, CI: 4.12-850.59, p = 0.002). Eyes with cleft (the hypo-reflective space beneath the fibrovascular PED) were more likely to develop an RPE tear (p = 0.01, χ-square test). CONCLUSIONS: Fibrovascular PED, large PED area, high PED height, and the cleft finding are independent risk factors for the development of RPE tears early after the administration of anti-VEGF drugs.

Risk factors for interstitial lung disease in patients with non-small cell lung cancer with epidermal growth factor receptor-tyrosine kinase inhibitors: A systematic review and meta-analysis.

BACKGROUND: The use of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) can potentially result in interstitial lung disease (ILD), which can substantially impact a patient's quality of life, subsequently leading to the interruption or discontinuation of EGRF-TKI treatment. Clinicians, therefore, need to thoroughly assess patients to determine if they are at risk for ILD. METHODS: We searched for observational study in the following databases: MEDLINE via the PubMed, CENTRAL, and IchushiWeb. The primary outcome was risk factors for the development of ILD, while the secondary outcome was risk factors for the severity of ILD. Of the 1602 studies returned, we selected 11 for meta-analysis, performed using a random-effects model. RESULTS: Risk factors for developing ILD were sex (odds ratio (OR), 1.87; 95% confidence interval (CI), 1.08-3.22; I2 = 0%; P = 0.02), smoking history (OR, 2.13; 95% CI, 1.51-3.00; I2 = 3 4%; P = 0.0001), and history of ILD (OR = 5.95; 95% CI, 3.34-10.59; I2 = 67%; P = 0.0009). Age, previous thoracic surgery or radiotherapy, performance status, histological type of lung cancer, and treatment line were not statistically significant risk factors for ILD. Risk factors identified in one study were serum albumin level, history of nivolumab use, radiographic residual lung volume, and history of pulmonary infection. CONCLUSIONS: We identified risk factors for developing ILD in patients with non-small cell lung cancer treated with EGFR-TKIs.

Wide-Field Choroidal Thickness Analysis after Half-Fluence Photodynamic Therapy Combined with Intravitreal Aflibercept Injection in Pachychoroid Neovasculopathy.

Background: Pachychoroid neovasculopathy (PNV) is a pachychoroid-spectrum disease. As blood circulation throughout the choroid may be involved in PNV pathogenesis, analysis using ultra-wide-field (UWF) fundus imaging is crucial. We evaluated choroidal thickness after half-fluence photodynamic therapy (PDT) combined with intravitreal aflibercept injection for PNV using UWF swept-source optical coherence tomography. Methods: Seventeen eyes with PNV that underwent half-fluence PDT with an adjuvant single intravitreal aflibercept injection were analyzed. To compare choroidal thicknesses in the central and peripheral choroids, we set subfields <3, <9, and 9-18 mm from the fovea. The <9 and 9-18 mm subfields were divided into four quadrants. Results: Choroidal thickness in each subfield decreased significantly after half-fluence PDT (p < 0.001); this reduction was more pronounced in the central area. We also investigated the relationship between the dominant side of the deep choroidal veins that harbor choroidal vein efflux from the macula. When choroidal thickness in the supratemporal and infratemporal 9 mm subfields were evaluated, the ratio of choroidal thickness reduction was not significantly different between the dominant and non-dominant sides. The dominant side was not associated with the extent of choroidal thickness reduction in PNV. Conclusions: Half-fluence PDT caused thinning of the entire choroid, especially in the central area, in PNV.

Portal Vein Thrombosis With Hypoplasia in the Left Lobe of the Liver: A Case Report.

Portal vein thrombosis (PVT) is an acute-onset, emergent thrombotic disease that is difficult to diagnose without an apparent underlying disease unless the clinician actively suspects its presence. We present a case of acute PVT with underlying left lobe hypoplasia of the liver, a previously undescribed condition. A 79-year-old male patient presented to the emergency department with the chief complaint of anorexia. His medical history included hypertension and an old brain infarction. The patient had no history of surgery. Contrast-enhanced CT revealed the disappearance of the left lobe of the liver and defects in the contrast effect in the left portal vein. The diagnosis reached was PVT with left lobe hypoplasia of the liver. Hypoplasia of the liver manifests few symptoms and may be identified incidentally. Clinicians need to be aware that PVT can develop from various underlying conditions, including hypoplasia of the liver, and we recommend aggressive imaging studies to help detect the presence of PVT when encountering similar cases.

Efficacy and safety of macrolide therapy for adult asthma: A systematic review and meta-analysis.

BACKGROUND: The evidence for macrolide therapy in adult asthma is not properly established and remains controversial. We conducted a systematic review and meta-analysis to examine the efficacy and safety of macrolide therapy for adult asthma. METHODS: We searched randomized controlled trials from MEDLINE via the PubMed, CENTRAL, and Ichushi Web databases. The primary outcome was asthma exacerbation. The secondary outcomes were serious adverse events (including mortality), asthma-related quality of life (symptom scales, Asthma Control Questionnaire, and Asthma Quality of Life Questionnaire), rescue medication (puffs/day), respiratory function (morning peak expiratory flow, evening peak flow, and forced expiratory volume in 1 s), bronchial hyperresponsiveness, and minimum oral corticosteroid dose. Of the 805 studies, we selected seven studies for the meta-analysis, which was conducted using a random-effects model. SYSTEMATIC REVIEW REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN000050824). RESULTS: No significant difference between macrolide and placebo for asthma exacerbations was observed (risk ratio 0.71, 95 % confidence interval [CI] 0.46-1.09; p = 0.12). Macrolide therapy for adult asthma showed a significant improvement in rescue medication with short-acting beta-agonists (mean difference -0.41, 95 % CI -0.78 to -0.04; p = 0.03). Macrolide therapy did not show more serious adverse events (odd ratio 0.61, 95 % CI 0.34-1.10; p = 0.10) than those with placebo. The other secondary outcomes were not significantly different between the macrolide and placebo groups. CONCLUSIONS: Macrolide therapy for adult asthma may be more effective than placebo and could be a treatment option.

Clinical Features of Pediatric Uveitis at a Tertiary Referral Center in the Western Region of Japan.

PURPOSE: This study aimed to assess the clinical features of pediatric uveitis at a tertiary referral center in Western Japan. METHODS: One hundred forty eyes of 80 patients aged <20 years at the time of uveitis onset, who visited Kyushu University Hospital between January 2010 and December 2019 were included in this study. Clinical records were retrospectively reviewed. Demographics, clinical findings, treatments, and visual prognoses were compared between the disease groups. RESULTS: Of 80 patients, 32 were males and 48 were females. The average age of onset was 12.5 ± 4.8 (0-19) years. Tubulointerstitial nephritis and uveitis (TINU) and juvenile idiopathic arthritis (JIA) were the most frequent causes, accounting for 11.3% and 10% of cases, respectively, followed by sarcoidosis (5%), Behçet's disease, acute anterior uveitis, Vogt-Koyanagi-Harada disease, and juvenile chronic iridocyclitis (3.8% each). Infectious uveitis accounted for 7.6% of the cases: cytomegalovirus was the most frequent agent. Of these cases, 43.8% were unclassified. Systemic therapies were administered to 87.5% of the patients with JIA, 33.3% of those with TINU, and 28.6% of the other diagnostic groups. In the unclassified group, 80% of the patients were followed up with only topical corticosteroids. LogMAR visual acuity of 0 or less accounted for more than 80% in the final examination. CONCLUSION: TINU and JIA were the most common causes of pediatric uveitis. Although each required systemic therapy, most unclassified cases of pediatric uveitis were managed by topical corticosteroids alone with good visual prognosis. Accurate diagnosis is important for pediatric uveitis management.

Clinical inertia in asthma.

Despite advances in pharmaceutical treatment in recent years, a relatively high proportion of patients with asthma do not have adequate asthma control, causing chronic disability, poor quality of life, and multiple emergency department visits and hospitalizations. A multifaceted approach is needed to overcome the problems with managing asthma, and clinical inertia (CI) is a crucial concept to assist with this approach. It divides clinical inertia into three main categories, which include healthcare provider-related, patient-related, and healthcare system-related CI. The strategies to overcome these CI are complex, and the M-GAP approach, which combines a multidisciplinary approach, dissemination of guidelines, utilization of applications, and development and promotion of low-cost prescriptions, will help clinicians.

Efficacy of Additional Corticosteroids After Dexamethasone Treatment for Moderate to Severe COVID-19: An Observational Study.

Background Previous studies have demonstrated dexamethasone (DEX)'s efficacy for coronavirus disease 2019 (COVID-19). In contrast, patients with residual lung field shading and symptoms after DEX treatment have been observed, and the efficacy of additional corticosteroids (AC) is unknown. Objectives We aimed to investigate the efficacy of AC in patients with COVID-19 with residual respiratory symptoms or who required oxygen therapy or invasive mechanical ventilation after DEX treatment. Methods This was a single-center, retrospective observational study including 261 patients with community-onset COVID-19, aged ≥ 18 years, admitted to our hospital between March 1, 2020, and May 31, 2021. Finally, 34 patients were included in the study who met all four of the following criteria: (1) required oxygen therapy or invasive ventilation, (2) were treated with DEX, (3) had residual shading on chest imaging after DEX treatment, or (4) had unimproved respiratory symptoms or oxygen saturation < 90%. We reviewed the medical records and clinical courses of 14 patients who received AC therapy (AC group) and 20 patients who did not (non-additional corticosteroids or NC group). Results The 90-day mortality rate was 35.7% in the AC group and 25.0% in the NC group. There was no statistically significant difference between the two groups (p = 0.797). In addition, there was no difference between groups in the proportion of patients who required oxygen therapy at discharge (64% vs. 35%, p = 0.162). The time from the end of DEX therapy to discharge was significantly longer in the AC group (median 7.5 vs. 33 days, p = 0.019). Regarding serious adverse events, infection was statistically more common in the AC group than in the NC group (p = 0.005). Conclusions AC after DEX treatment does not improve clinical outcomes and may prolong hospital stay.

Clinical Utility of SARS-CoV-2 Antibody Titer Multiplied by Binding Avidity of Receptor-Binding Domain (RBD) in Monitoring Protective Immunity and Clinical Severity.

Conventional serum antibody titer, which expresses antibody level, does not provide antigen binding avidity of the variable region of the antibody, which is essential for the defense response to infection. Here, we quantified anti-SARS-CoV-2 antibody binding avidity to the receptor-binding domain (RBD) by competitive binding-inhibition activity (IC50) between SARS-CoV-2 S1 antigen immobilized on the DCP microarray and various RBD doses added to serum and expressed as 1/IC50 nM. The binding avidity analyzed under equilibrium conditions of antigen-antibody binding reaction is different from the avidity index measured with the chaotropic agent, such as urea, under nonequilibrium and short-time conditions. Quantitative determination of the infection-protection potential of antibodies was assessed by ABAT (antigen binding avidity antibody titer), which was calculated by the quantity (level) × quality (binding avidity) of antibodies. The binding avidity correlated strongly (r = 0.811) with cell-based virus-neutralizing activity. Maturation of the protective antibody induced by repeated vaccinations or SARS-CoV-2 infection was classified into three categories of ABAT, such as an initial, low, and high ABAT. Antibody maturity correlated with the clinical severity of COVID-19. Once a mature high binding avidity was achieved, it was maintained for at least 6-8 months regardless of the subsequent change in the antibody levels.

Differences in Central and Peripheral Choroidal Thickness among the Subtypes of Age-Related Macular Degeneration in an Asian Population.

Age-related macular degeneration (AMD) causes visual impairment in individuals who are >50 years of age. However, no study has investigated AMD when using ultra-wide-field swept-source optical coherence tomography (UWF SS-OCT). We aimed to evaluate central and peripheral choroidal thicknesses using UWF SS-OCT, and to compare these across the AMD subtypes. We included 75 eyes of patients with typical AMD (tAMD), 56 with polypoidal choroidal vasculopathy (PCV), 29 with pachychoroid neovasculopathy (PNV), and 12 with retinal angiomatous proliferation (RAP). To compare choroidal thicknesses in the central and peripheral choroids, we established subfields of <3 mm, <9 mm, and 9-18 mm from the fovea. PNV patients were significantly younger than those with tAMD (p = 0.01). The choroidal thicknesses of PNV were significantly greater than that of tAMD in all subfields (p < 0.01), and choroidal thickness significantly correlated with age and axial length in all subfields (p < 0.05). Even after adjusting for age and axial length, the choroidal thickness in PNV was significantly greater than that in tAMD (p < 0.05). In addition, the ratio of the posterior <9 mm to a peripheral 9-18 mm choroidal thickness in PNV was significantly greater than that in tAMD (p < 0.01). A thickened choroid in PNV was more pronounced in the posterior choroid than in the periphery.

COVID-19-Induced Eosinophilic Lower Airway Inflammation in Those With Multiple COVID-19 Vaccinations.

A 29-year-old woman was admitted with a diagnosis of ischemic enteritis. She had a coronavirus disease 2019 (COVID-19) infection four weeks before this visit and continued to experience a cough. Four months before, she received the third COVID-19 vaccine. Chest computer tomography revealed scattered ground-glass opacities in both upper lobes. Based on abnormalities in chest imaging, eosinophilia, and a high level of fractional exhaled nitric oxide, she was diagnosed with eosinophilic lower airway inflammation due to COVID-19. Since the visit, the patient had an intermittent fever and no radiological improvement, so systemic corticosteroid treatment was initiated, and the symptoms and clinical findings improved. Clinicians should know the potential association between COVID-19 and eosinophilic lower airway inflammation, which may still occur despite multiple vaccinations.

Persistence of vascular empty sleeves in choroidal neovascularization after VEGF therapy in both animal models and humans.

PURPOSE: Choroidal neovascularization (CNV) often recurs during anti-vascular endothelial growth factor (VEGF) therapy; however, little is known about the mechanism of vascular regrowth. Vascular regrowth along the empty sleeves of basement membranes was proposed as a mechanism for recurrence after the reversal of VEGF inhibition in tumors. This study investigated whether the proposed mechanism is involved in CNV during VEGF therapy. METHODS: We made two observations using a mice model, as well as patients with CNV. Laser-induced CNV mice were used to examine the vascular empty sleeves of the basement membrane and CNV with the immunohistochemistry of type IV collagen and CD31, respectively. A retrospective cohort study included 17 eyes from 17 patients with CNV treated with anti-VEGF treatment. Vascular regrowth during anti-VEGF treatment was assessed using optical coherence tomography angiography (OCTA). RESULTS: In the CNV mouse model, the CD31+ vascular endothelium area was decreased during anti-VEGF treatment compared with the IgG control (33516.7 ± 10864.7 vs. 10745.9 ± 5755.9 µm2, P < 0.05), whereas a significant difference was not observed in the area of type IV collagen+ vascular empty sleeve after the treatment compared with the control (29135.0 ± 7432.9 vs. 24592.0 ± 5935.3 µm2, P = 0.7). The proportions of CD31+ to type IV collagen+ areas were significantly decreased after the treatment (38.7 ± 7.4% vs. 17.1 ± 5.4%, P < 0.05). In the OCTA observations, the follow-up period in the retrospective cohort study was 58.2 ± 23.4 months. CNV regrowth was observed in 682 neovessels of the 17 eyes. In group 1, CNV regression and regrowth are in the same form (129 neovessels, 18.9%). In group 2, CNV regression and regrowth are in a different form (170 neovessels, 24.9%). In group 3, CNV regrowth is with a different form without the regression (383 neovessels, 56.2%). CONCLUSIONS: Parts of CNV regrowth may occur along the vascular empty sleeve, which remain after anti-VEGF treatment.

Complications of a lung biopsy for severe respiratory failure: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to evaluate the complications of lung biopsy in patients with acute respiratory failure (ARF), including acute respiratory distress syndrome (ARDS). METHODS: We searched the MEDLINE and Cochrane Central Register of Controlled Trials. The primary outcomes were biopsy-related death, respiratory failure, cardiac complications, bleeding, and other major complications. We used the McMaster Quality Assessment Scale of Harms (McHarm) to evaluate the risk of bias. A random-effects model was used to calculate the pooled frequencies. RESULTS: Thirteen studies (consisting of 574 patients) were included in the meta-analysis. Furthermore, most of the included studies had a high or unclear risk of bias in half of the items in McHarm. All included studies evaluated surgical lung biopsies. The median overall hospital mortality was 53% (range: 17%-90%). The pooled frequencies of biopsy-related death, respiratory failure, cardiac complication, bleeding, and other major complications were 0.00% (95% confidence interval [CI]: 0.00%-0.21%), 1.30% (95% CI: 0.00%-5.69%), 1.03% (95% CI: 0.00%-3.73%), 1.46% (95% CI: 0.16%-3.56%), and 4.26% (95% CI: 0.00%-13.0%), respectively. CONCLUSIONS: The results of this study will be valuable information in considering the indications of lung biopsy in patients with ARF, including ARDS. TRIAL REGISTRATION: The protocol was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN 000040650).