Kosuke Kawai

Key Points: Standard-of-care therapy for IgA nephropathy has historically relied on renin–angiotensin–aldosterone system inhibitors. Current treatment goals aim to slow eGFR decline to reduce the risk of ESKD. Analysis of renin–angiotensin–aldosterone system inhibitor therapy alone found an eGFR decline of −4.5 ml/min per 1.73 m ² per year, which may not limit ESKD risk. Background: IgA nephropathy is a chronic autoimmune kidney disease characterized by deposition of immune complexes in the glomeruli, leading to inflammation and progressive, irreversible, kidney damage. Patients with IgA nephropathy face a lifetime risk of ESKD, and an associated increase in mortality unless their annual eGFR decline is generally maintained at or below 1 ml/min per 1.73 m ² . The current standard of care in IgA nephropathy involves supportive CKD therapies, notably renin–angiotensin–aldosterone system inhibitors (RAASi). Importantly, the long-term effectiveness of RAASi in slowing IgA nephropathy disease progression remains uncertain. Meta-analyses of randomized controlled trials with comparable designs offer an opportunity to assess the impact of RAASi therapy on kidney function. Such analyses facilitate outcome comparisons across studies and may generate important evidence and contribute to informed clinical decision making. Methods: A meta-analysis was conducted using randomized controlled trials that reported the slope of eGFR decline and included one arm receiving maximally tolerated doses of RAASi. The analysis aimed to evaluate the impact of RAASi therapy on kidney function in high-risk patients with IgA nephropathy. Results: A systematic literature review of four databases returned 171 studies published between January 2006 and November 2024. Of these, ten included a control arm of participants with IgA nephropathy receiving maximized RAASi treatment ( N =1366) and reported eGFR annualized slope decline. Meta-analysis of the pooled data demonstrated a mean annual eGFR slope decline of −4.5 ml/min per 1.73 m ² (95% confidence interval, −5.3 to −3.8) among participants treated with RAASi therapy alone. Conclusions: Treatment with maximally tolerated RAASi alone does not sufficiently slow the rate of eGFR decline in high-risk patients with IgA nephropathy, leaving patients at risk of ESKD. These findings underscore the need for disease-modifying therapies capable of effectively preserving kidney function, particularly in this predominantly young patient population.

Background: We conducted a systematic review and meta‐analysis of studies examining the association of viral infections with the risk of cardiovascular disease, including coronary heart disease (CHD) and stroke. Methods: MEDLINE, Embase, Web of Science, African‐Wide Information, and the Cochrane Library database were searched from inception to July 2024. Results: We included 155 studies. HIV infection was consistently associated with an elevated risk of CHD (pooled adjusted risk ratio [RR], 1.60 [95% CI, 1.38–1.85]) and stroke (RR, 1.45 [95% CI, 1.26–1.67]). SARS‐CoV‐2 infection was associated with an increased risk of CHD (RR, 1.74 [95% CI, 1.44–2.11]) and stroke (RR, 1.69 [95% CI, 1.23–2.31]). In self‐controlled case series studies, laboratory‐confirmed influenza infection was associated with an elevated risk of acute myocardial infarction (pooled incidence rate ratio, 4.01 [95% CI, 2.66–6.05]) and stroke during the first 1 month (incidence rate ratio, 5.01 [95% CI, 3.41–7.37]). In cohort studies, hepatitis C virus infection was associated with a higher risk of CHD (RR, 1.27 [95% CI, 1.13–1.42]) and stroke (RR, 1.23 [95% CI, 1.04–1.46]). Herpes zoster was also associated with an elevated risk of CHD (RR, 1.12 [95% CI, 1.08–1.15]) and stroke (RR, 1.18 [95% CI, 1.09–1.27]). There is insufficient evidence to determine the effect of cytomegalovirus on cardiovascular disease. Although on a limited basis, hepatitis A virus, herpes simplex virus type 1, respiratory syncytial virus, human papillomavirus, dengue, and chikungunya have been linked to an increased risk of cardiovascular disease. Conclusions: Influenza, SARS‐CoV‐2, HIV, hepatitis C virus, and herpes zoster were associated with an increased risk of major cardiovascular events. Vaccines may play an important role in preventing the risk of cardiovascular disease.

Background: Loss of nuclear BRCA1‐associated protein 1 (nBAP1) expression is strongly linked to monosomy 3 in uveal melanoma. While fine‐needle aspiration (FNA) aids diagnosis, the prognostic value of nBAP1 immunocytochemistry (ICC) is still being investigated. This study examines the correlation between nBAP1 loss on ICC and fluorescence in situ hybridization (FISH) findings, as well as its clinical impact.Methods: Intraocular FNA cytology specimens with clinical concern for uveal melanoma from April 2015 to March 2023 with available nBAP1 ICC, FISH results, and clinical follow‐up were examined. Two independent reviewers, blinded to the cytogenetic results, interpreted the nBAP1 ICC as either loss or retained. Statistical analysis using Fisher's exact test was utilized to evaluate the relationship between nBAP1 loss on ICC and FISH findings. Kaplan–Meier survival plots were constructed to examine the metastasis‐free survival.Results: Among the 79 cases included in the study, 86.1% (68/79) showed nBAP1 loss. Approximately 63.2% of patients with nBAP1 loss had monosomy 3, whereas none with nBAP1 retained had monosomy 3 (p < 0.001). Of the nBAP1 loss cases, 41.2% (28/68) had monosomy 3 alone, while 22.1% (15/68) had both monosomy 3 and 6p gain. Patients with nBAP1 loss had a significantly higher risk of metastasis (p ≤ 0.04), with a 5‐year metastasis‐free survival of 57.1% versus 100% in nBAP1 retained cases.Conclusion: BAP1 ICC is a cost‐effective prognostic tool in uveal melanoma FNAs, strongly correlating with monosomy 3 and poor outcomes. Integrating BAP1 ICC with FISH enhances risk stratification, enabling earlier identification of high‐risk patients and guiding treatment decisions.

The nested frailty model, a random effects survival model that can accommodate data clustered at two hierarchical levels, has been rarely used in practice. We aimed to evaluate the utility of the Bayesian nested frailty modeling approach in the context of a study to examine the effects of various surgical procedures for patients with patulous Eustachian tube dysfunction (PETD). A nested frailty model was employed to account for the correlation between each pair of ears within patients and the correlation between multiple event times within each ear. Some patients underwent multiple different surgical treatments in their affected ears. We incorporated two nested lognormal frailties into the Cox proportional hazards model. The Bayesian Monte Carlo Markov Chain approach was utilized. We examined the consequences of ignoring a multilevel structure of the data. The variances of patient-level and ear-level random effects were both found to be significant in the nested frailty model. Shim insertion and patulous Eustachian tube reconstruction using Alloderm or cartilage were associated with a lower risk of recurrence of PETD symptoms than calcium hydroxyapatite injection. Bayesian nested frailty models provide flexibility in modeling hierarchical survival data and effectively account for multiple levels of clustering. Our study highlights the importance of accounting for all levels of hierarchical clustering for valid inference.

Objective: Clinicians increasingly perform balloon dilation of the Eustachian tube (BDET) to treat obstructive Eustachian tube dysfunction (OETD) refractory to medical management. Reported complications have been limited and include patulous Eustachian tube dysfunction (PETD). This multicenter study investigates the incidence of PETD and associated factors.Methods: Consecutive patients at three academic centers undergoing BDET (January 2014–November 2019) for OETD refractory to medical therapy were included. PETD was diagnosed by patient‐reported symptoms of autophony of voice and/or breathing. Associated factors studied include age, sex, comorbidities, balloon size, duration of inflation, repeat BDET, and adjunctive procedures.Results: BDET procedures (n = 295 Eustachian tubes) were performed on 182 patients. Mean age was 38.4 years (SD 21.0; range 7–78) and 41.2% were female. Twenty cases of PETD (6.8% of procedures; 9.3% of patients) occurred following BDET. Risk of PETD did not vary by institution, comorbidities, or adjunctive procedure. Age ≤18 years (adjusted risk ratio [RR] = 3.26; 95% confidence interval [CI]: 1.24, 8.54; p = 0.02), repeat BDET (RR = 3.26; 95% CI: 2.15, 4.96; p < 0.001), and severe preoperative Eustachian tube inflammation (RR = 2.83; 95% CI: 1.10, 7.28; p = 0.03) were associated with increased risk of developing PETD in the multivariable model. Most symptoms were reported as mild or intermittent.Conclusion: BDET caused PETD symptoms in approximately 7% of dilated Eustachian tubes in this study with increased risk for younger patients and those with severe inflammation or undergoing repeat dilations. Although most cases were self‐limited, symptoms can persist. Awareness of risk factors may aid clinicians in limiting this complication.Level of Evidence: 4 Laryngoscope, 133:3152–3157, 2023

Objective: To evaluate the management of juvenile nasopharyngeal angiofibroma (JNA) from a national perspective with outcomes comparison based on hospital volume.Study Design: Ten‐year Pediatric Health Information Systems (PHIS) data analysis.Methods: The PHIS database was queried for the diagnosis of JNA. Data regarding demographics, surgical approach, embolization, length of stay, charges, readmission, and revision surgery was collected and analyzed. Hospitals were classified as low volume if fewer than 10 cases and high volume if greater than or equal to 10 cases during the study period. A random effects model compared outcomes based on hospital volume.Results: A total of 287 JNA patients were identified with a mean age of 13.8 (± 2.7) years. Nine hospitals were classified as high volume, accounting for a total of 121 patients. The mean length of hospitalization, blood transfusion rate, and 30‐day readmissions did not differ significantly by hospital volume. Patients cared for at high‐volume institutions were less likely to require postoperative mechanical ventilation (8.3% vs. 25.0%; adjusted RR = 0.32; 95% CI 0.14–0.73; p < 0.01) or return to the operating room for residual disease than patients admitted to low‐volume hospitals (7.4% vs. 20.5%; adjusted RR = 0.38; 95% CI 0.18–0.79; p = 0.01).Conclusions: The management of JNA is complex from both an operative and perioperative management standpoint. Over the past decade, nearly half (42.2%) of JNA patients have been managed at nine institutions in the United States. These centers have significantly lower rates of postoperative mechanical ventilation and the need for revision surgery.Level of Evidence: 3 Laryngoscope, 133:3216–3220, 2023

Objectives: Enlarged vestibular aqueduct (EVA) is the most common anatomic abnormality contributing to permanent hearing loss (HL) in children. Although the association between EVA and HL is well‐documented, the pass rate for the newborn hearing screening (NBHS) for patients with EVA‐related HL is not. Our objective was to investigate the association between NBHS results and audiologic and clinical outcomes in a large cohort of pediatric patients with EVA.Methods: This was a retrospective chart review of patients seen in the Boston Children's Hospital (BCH) Department of Otolaryngology and Communication Enhancement with confirmed HL, known NBHS results, and confirmed EVA. Demographic, clinical, audiologic, and imaging data were collected from the medical record. Frequency‐specific data points from pure‐tone audiograms and/or automated auditory brainstem response tests were recorded, and four‐frequency pure tone average was calculated using air conduction thresholds at 500, 1000, 2000, and 4000 Hz.Results: Of the 183 patients included in the study, 84 (45.9%) passed their NBHS, whereas 99 (54.1%) did not pass. Compared with patients who did not pass, patients who passed were more likely to have unilateral EVA and unilateral HL, whereas they were less likely to undergo cochlear implantation and to have causative SLC26A4 variants.Conclusions: EVA‐associated HL may be identified at birth or during childhood, with nearly half the patients in this cohort passing their NBHS. Our results provide prognostic information for patients with EVA who pass their NBHS and highlight the importance of regular hearing monitoring for children not initially suspected of having HL.Level of Evidence: 4 Laryngoscope, 133:2786–2791, 2023

Background: We investigated the longitudinal association of herpes zoster (HZ), commonly known as “shingles,” and long‐term risk of stroke or coronary heart disease (CHD) among participants in 3 large US cohorts, the NHS (Nurses' Health Study), NHS II (Nurses' Health Study II), and HPFS (Health Professionals Follow‐Up Study). Methods and Results: Participants were 79 658 women in the NHS (2000–2016), 93 932 women in the NHS II (2001–2017), and 31 440 men in the HPFS (2004–2016), without prior stroke or CHD. Information on HZ, stroke, and CHD was collected on biennial questionnaires and confirmed by medical record review. Cox proportional hazards regression models were used to estimate multivariable‐adjusted hazard ratios for stroke and for CHD according to years since HZ compared with never HZ. During >2 million person‐years of follow‐up, 3603 incident stroke and 8620 incident CHD cases were documented. History of HZ was significantly and independently associated with higher long‐term risk of stroke and CHD. In pooled analyses, compared with individuals with no history of HZ, the multivariable‐adjusted hazard ratios (95% CIs) for stroke were 1.05 (0.88–1.25) among those with 1 to 4 years since HZ, 1.38 (1.10–1.74) for among those with 5 to 8 years since HZ, 1.28 (1.03–1.59) among those with for 9 to 12 years since HZ, and 1.19 (0.90–1.56) among those with ≥13 years since HZ. For CHD, the corresponding multivariable‐adjusted hazard ratios (95% CIs) were 1.13 (1.01–1.27) for 1 to 4 years, 1.16 (1.02–1.32) for 5 to 8 years, 1.25 (1.07–1.46) for 9 to 12 years, and 1.00 (0.83–1.21) for ≥13 years. Conclusions: HZ is associated with higher long‐term risk of a major cardiovascular event. These findings suggest there are long‐term implications of HZ and underscore the importance of prevention.

Objectives: Telemedicine can improve access to pediatric otolaryngology care by decreasing travel time and cost, and lowering the risk of viral transmission during the SARS‐CoV‐2 (COVID‐19) pandemic. This study aims to identify the clinical role and outcomes of telemedicine for tracheostomy‐dependent children before and during the COVID‐19 pandemic.Methods: Retrospective chart review of 42 tracheostomy‐dependent pediatric patients who utilized telemedicine between October 2013 and April 2020 (pre‐COVID‐19), and 111 patients who utilized telemedicine between May 2020 and July 2021 (during COVID‐19) at a tertiary free‐standing children's hospital outpatient clinic.Results: The majority of pre‐COVID‐19 telecommunication solely addressed tracheostomy stomal concerns as compared with during COVID‐19 (99% vs. 3%, p < .001), while telecommunication during COVID‐19 was mainly used for routine follow‐up as compared with pre‐COVID‐19 (99% vs. 0%, p < .001). Telemedicine visits during COVID‐19 were significantly less likely to result in the need for in‐person office visits as compared with those pre‐COVID‐19 (4% vs. 22%; p < .001). There was no significant difference in urgent emergency department (ED) evaluation following telemedicine pre‐ and during COVID‐19 (16% vs. 11%). The most common reasons for ED presentation both pre‐ and during COVID‐19 following telemedicine visit included respiratory distress, dislodged tracheostomy tube, and tracheostomy bleeding.Conclusion: The clinical role of telemedicine has evolved from problem‐based evaluation to routine follow‐up during the COVID‐19 pandemic. Although telemedicine can decrease the need for in‐person office evaluation of routine tracheostomy concerns, respiratory complications and tracheostomy bleeding still require urgent in‐person ED evaluation.Level of evidence: Level 4.