Clinical Manifestations and Genetic Analysis of 5 Korean Choroideremia Patients Initially Diagnosed With Retinitis Pigmentosa.

BACKGROUND: To investigate the clinical findings of choroideremia patients and perform genetic analysis by whole-exome sequencing (WES). METHODS: A total of 94 patients initially diagnosed with retinitis pigmentosa (RP) at another hospital, and who visited our hospital for genetic analysis by WES, were included in the study, along with 64 family members. All subjects underwent comprehensive ophthalmic evaluation, including best-corrected visual acuity, slit lamp examination, fundus photography, fundus autofluorescence (FAF), fluorescein angiography (FAG), visual field (VF), electroretinogram (ERG), and optical coherence tomography (OCT). RESULTS: In six male patients with suspected choroideremia, extensive retinal pigment epithelium (RPE) and severe loss of choroid were observed in the fundus, but not in the macula. CHM gene mutation was confirmed in five patients. A novel single nucleotide variant at a splice site was observed in one patient. OCT showed marked thinning of the outernuclear layer and choroid, except in the macula. FAF showed a small area of hyperfluorescence in the posterior pole. In addition, characteristic interlaminar bridges were observed in four patients. On FAG, hypofluorescence was seen up to the far-peripheral retina in five patients. CONCLUSION: Of the 94 patients initially diagnosed with RP, CHM mutation was identified in five (5.3%) by WES. Choroideremia should be considered as a differential diagnosis of RP. WES would be useful for identifying the causes of hereditary retinal disease.

Renal infarction associated with low dose intravenous immunoglobulin in a kidney transplant recipient with sepsis: a case report and literature review.

BACKGROUND: The use of human intravenous immunoglobulin gamma (IVIG) is associated with thromboembolic events as a complication. There are few reported cases of renal infarction during IVIG use in the general population, but transplant kidney may be more susceptible to thromboembolic events following IVIG use. CASE PRESENTATION: A 41-year-old woman visited with fever and pain at the transplant kidney. Six years ago, she underwent kidney transplantation from a deceased donor. Laboratory and radiologic findings were compatible to septic condition, secondary to acute pyelonephritis. We started antibiotics, inotropics, and IVIG. The patient abruptly developed gross hematuria and urine output decreased to 100 cc/day during IVIG administration. Renal doppler and pathologic findings revealed renal infarction. Oliguria and azotemia persisted and she is undergoing maintenance hemodialysis. CONCLUSION: Our case shows that infarction of transplant kidney can be caused by IVIG use in a patient with severe infection. Thus, when using IVIG for kidney transplant patients with high risk of thromboembolic events, we may be careful to prevent the thromboembolic events.

Botulinum Toxin A Injection for the Treatment of Intractable Dry Eye Disease.

Background and Objectives: To evaluate the clinical efficacy of periocular botulinum toxin A (BTA) injection in patients with intractable dry eye disease (DED). Materials and Methods: Medical records of patients with intractable DED who underwent periocular BTA injection from December 2019 to March 2020 were reviewed retrospectively. Patients were injected with 2.5 units of BTA in the medial part of the lower eyelids. The clinical data collected included age, sex, ocular surface disease index (OSDI) score, tear film break up time (TBUT), Schirmer test results, tear osmolarity (I-PEN), and tear meniscus height (TMH) measured by anterior segment optical coherence tomography. All subjective and objective data were collected before treatment and at 1 month after treatment. Results: Twenty-eight consecutive patients were eligible for chart review and analysis. Significant improvements in OSDI, tear osmolarity, and TMH were observed at 1 month after periorbital BTA injection. At the baseline and 1-month follow-up examinations, OSDI scores were 62.22 ± 21.30 and 47.98 ± 17.23, respectively (p < 0.001). TMH increased significantly after treatment (82.25 ± 40.50 at baseline vs. 138.02 ± 66.62 1-month after treatment; p < 0.001). Tear osmolarity using I-PEN showed a significant decrease after treatment (320.82 ± 24.66 at baseline vs. 302.75 ± 22.33 at 1 month after treatment; p < 0.001). No significant differences were found in TBUT or Schirmer test results before and after BTA injection. Conclusions: BTA injection into the medial part of the eyelid improves dry eye symptoms, the amount of tear retention, and tear osmolarity. Based on the objective parameters of the tear condition, this study supports the idea of BTA use as a potential treatment option for patients with intractable DED.

Visceral Fat Area Determined Using Bioimpedance Analysis Is Associated with Hearing Loss.

BACKGROUND: Visceral fat area (VFA) using bioimpedance analysis (BIA) as a simple analyzer can be used to assess VFA, which may be associated with HL. The aim of the present study was to evaluate the clinical relevance and usefulness of VFA using BIA as a predictor of HL. PATIENTS AND METHODS: In total, 18,415 patients were recruited into our study. VFAs were measured using multi-frequency BIA. VFAs were normalized by body mass index (BMI). Participants were divided into 3 tertiles based on their VFA/BMI for both sexes. For both ears of each participant, the low-frequency (Low-Freq), mid-frequency (Mid-Freq), and high-frequency (High-Freq) values were obtained calculating the pure tone averages at 0.5 and 1 kHz, 2 and 3 kHz, and 4 and 6 kHz, respectively. The average hearing threshold (AHT) was calculated as the pure tone average at the 4 frequencies (i.e., 0.5, 1, 2, and 3 kHz). HL was defined as AHT >40 dB. RESULTS: The VFA/BMI had the greatest AUROC among VFA, BMI, and VFA/BMI in both sexes in this study. In both univariate and multivariate analyses, VFA/BMI tertiles were associated with all 4 hearing thresholds (i.e., Low-Freq, Mid-Freq, High-Freq, and AHT). The 4 hearing thresholds were positively correlated with VFA/BMI as a continuous variable. The odds ratio for HL increased as the VFA/BMI tertile increased. CONCLUSION: VFA/BMI was associated with hearing impairment in the Asian population. The participants with high VFA/BMI should be closely monitored for hearing impairment.

Correction of Involutional Entropion by Excising Redundant Skin and Pretarsal Orbicularis Muscle without Vertical and Horizontal Tarsal Fixation.

PURPOSE: This study evaluated the effect of the excision of redundant skin and pretarsal orbicularis muscle, without vertical or horizontal tarsal fixation, on the correction of involutional entropion. METHODS: This retrospective interventional case series recruited patients with involutional entropion who underwent excision of redundant skin and pretarsal orbicularis muscle, without vertical or horizontal tarsal fixation, from May 2018 to December 2021. Preoperative clinical characteristics and surgical outcomes, including recurrence at 1, 3, and 6 months, were determined by reviewing the medical charts. Surgical treatment included the excision of redundant skin and pretarsal orbicularis muscle, without any tarsal fixation, and simple skin suture. RESULTS: All 52 patients (58 eyelids) attended every follow-up visit and were thus included in the analysis. Among 58 eyelids, 55 (94.8%) had satisfactory results. The recurrence rate was 3.45% (two eyelids) and the overcorrection rate was 1.7% (one eyelid). CONCLUSIONS: Excision of only redundant skin and the pretarsal orbicularis muscle, without capsulopalpebral fascia reattachment or horizontal lid laxity correction, is a simple surgery for correcting involutional entropion.

Modified Charlson comorbidity index as a survival prediction tool for older patients after liver transplantation.

Purpose: An increasing number of older patients now undergo liver transplantation (LT). Although the overall outcomes in older patients are not different from those of younger patients, there is no tool to predict LT prognosis in older patients. We hypothesized that a modified Charlson comorbidity index (mCCI) and 5-factor modified frailty index (mFI-5) can predict outcomes in older patients after LT. Methods: This retrospective study included 155 patients (aged >65 years) who underwent LT at Seoul National University Hospital. The recipients were subcategorized into 2 groups based on the mCCI score and mFI-5: the low (0-1) and high (2-5) mCCI groups, and low (≤0.4) and high (>0.4) mFI-5 groups. The independent effect of each variable on post-LT survival was determined using the mCCI subgroup, age at transplantation, sex, Child-Turcotte-Pugh score, model for end-stage liver disease (MELD) score, and mFI-5 subgroup. Results: The high-mCCI group (41 patients) showed significantly lower 1- and 3-month and 1-, 3-, and 5-year survival than the low-mCCI group. Using the Cox regression model, the mCCI, sex, and MELD score remained significant. The mFI-5 was not a significant factor to predict patients' survival. Conclusion: The mCCI and MELD scores could be used to predict post-LT survival in older patients.

MicroRNA-155 acts as an anti-inflammatory factor in orbital fibroblasts from Graves' orbitopathy by repressing interleukin-2-inducible T-cell kinase.

To investigate the role of microRNA (miR)-155 in inflammation in an in-vitro model of Graves' orbitopathy (GO). The expression levels of miR-155 were compared between GO and non-GO orbital tissues. The effects of inflammatory stimulation of interleukin (IL)-1ß and tumour necrosis factor alpha (TNF-α) on miR-155 expression on GO and non-GO orbital fibroblasts (OFs) were investigated. The effects of miR-155 mimics and inhibitors of inflammatory proteins and IL-2-inducible T-cell kinase (ITK) expression were examined, along with those related to the knockdown of ITK with siITK transfection on inflammatory proteins. We also examined how ITK inhibitors affect miR-155 expression in GO and non-GO OFs. The expression levels of miR-155 were higher in GO orbital tissues than in non-GO tissue. The overexpression of miR-155 was induced by IL-1ß and TNF-α in OFs from GO and non-GO patients. IL-1ß-induced IL-6 (ICAM1) protein production was significantly reduced (increased) by miR-155 mimics and inhibitors. The mRNA and protein levels of ITK were downregulated by overexpressed miR-155 via miR-155 mimics. Knockdown of ITK via siITK transfection induced a decrease in the expression levels of ITK, IL-17, IL-6, IL-1ß, and TNF-α protein. The expression of miR-155 was significantly downregulated by treatment with ITK inhibitors and Bruton's tyrosine kinase (BTK)/ITK dual inhibitors in a time-dependent manner. Our results indicated a potential relationship between miR-155 and ITK in the context of GO OFs. The overexpression of miR-155 repressed ITK expression and relieved inflammation. Thus, miR-155 appears to have anti-inflammatory effects in GO OFs. This discovery provides a new concept for developing GO treatment therapeutics.

Clinical Significance of the Edema Index in Incident Peritoneal Dialysis Patients.

BACKGROUND: Proper monitoring for volume overload is important to improve prognosis in peritoneal dialysis (PD) patients. The association between volume status and residual renal function (RRF) remains an unresolved issue. The aim of the present study was to evaluate the association between the edema index and survival or RRF in incident PD patients. PATIENTS AND METHODS: We identified all adults who underwent PD. The edema index was defined as the ratio of extracellular fluid to total body fluid. Participants with available data regarding survivorship or non-survivorship during the first year after PD initiation were included in the area under the receiver operating characteristic curve analysis. The cutoff value of the edema index for 1-year mortality was >0.371 in men and >0.372 in women. Participants were divided into two groups according to the cutoff value of their baseline edema indices: High (>cutoff value) and Low (≤ cutoff value). Survivors during the first year after PD initiation were divided into two groups according to the initial and 1-year edema index: Non-improvement (maintenance of criteria in the initial Low group during the year) and Other (all participants except those in the Non-improvement group). RESULTS: In total, 631 patients were enrolled in the present study. The cutoff value of the edema index for 1-year mortality was >0.371 in men and >0.372 in women. The respective mean initial RRF values (mL · min(-1) · 1.73 m(-2)) in the Low and High groups, respectively, were 4.88 ± 4.09 and 4.21 ± 3.28 in men (P = 0.108), and 3.19 ± 2.57 and 2.98 ± 2.70 in women (P = 0.531). There were no significant differences between groups in either sex. The respective mean RRF values at 1 year after PD initiation in the Low and High groups, respectively, were 3.56 ± 4.35 and 2.73 ± 2.53 in men, and 2.80 ± 2.36 and 1.85 ± 1.51 in women. RRF at 1 year after PD initiation was higher in the Low group than in the High group (men: P = 0.027; women: P = 0.001). In men, the cumulative 5-year survival rates were 78.7% and 46.2% in the Low and High groups, respectively, whereas in women, rates were 77.2% and 58.8% in the Low and High groups, respectively. For survivors during the first year after PD initiation, the Non-improvement group was associated with a poor survival rate compared with the Other group for both sexes. CONCLUSION: A high edema index was associated with mortality in incident PD patients at baseline and follow-up. The edema index may be used as a new marker for predicting mortality in PD patients.

Comparison of Various Anthropometric Indices as Risk Factors for Hearing Impairment in Asian Women.

BACKGROUND: The objective of the present study was to examine the associations between various anthropometric measures and metabolic syndrome and hearing impairment in Asian women. METHODS: We identified 11,755 women who underwent voluntary routine health checkups at Yeungnam University Hospital between June 2008 and April 2014. Among these patients, 2,485 participants were <40 years old, and 1,072 participants lacked information regarding their laboratory findings or hearing and were therefore excluded. In total 8,198 participants were recruited into our study. RESULTS: The AUROC value for metabolic syndrome was 0.790 for the waist to hip ratio (WHR). The cutoff value was 0.939. The sensitivity and specificity for predicting metabolic syndrome were 72.7% and 71.7%, respectively. The AUROC value for hearing loss was 0.758 for WHR. The cutoff value was 0.932. The sensitivity and specificity for predicting hearing loss were 65.8% and 73.4%, respectively. The WHR had the highest AUC and was the best predictor of metabolic syndrome and hearing loss. Univariate and multivariate linear regression analyses showed that WHR levels were positively associated with four hearing thresholds including averaged hearing threshold and low, middle, and high frequency thresholds. In addition, multivariate logistic analysis revealed that those with a high WHR had a 1.347-fold increased risk of hearing loss compared with the participants with a low WHR. CONCLUSION: Our results demonstrated that WHR may be a surrogate marker for predicting the risk of hearing loss resulting from metabolic syndrome.

HbA1c Levels Are Associated with Chronic Kidney Disease in a Non-Diabetic Adult Population: A Nationwide Survey (KNHANES 2011-2013).

BACKGROUND: Many studies have reported an association between glycated hemoglobin A1c (HbA1c) and metabolic syndrome (MetS) in non-diabetes patients. Each component of MetS is in fact related to chronic kidney disease (CKD) incidence and progression. Therefore, HbA1c in non-diabetic mellitus (DM) may be intrinsically associated with the prevalence of CKD. The hypothesis of the present study was that high HbA1c in non-DM patients is associated with CKD. PATIENTS AND METHODS: The total number of participants in this study was 24,594. The participants were divided into three groups according to their HbA1c levels: a Low group (<5.7% or <39 mmol/mol), a Middle group (5.7-6.0% or 39-42 mmol/mol), and a High group (>6.0% or >42 mmol/mol). The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: The number of participants allocated to the Low, Middle, and High groups was 8,651, 4,634, and 1,387, respectively. Linear regression analyses were performed to evaluate the association between variables. Standardized ß ± standard error was 0.25 ± 0.22 for waist circumference, 0.44 ± 0.20 for fasting glucose, -0.14 ± 0.30 for high-density lipoprotein cholesterol levels, 0.15 ± 2.31 for triglyceride levels, 0.21 ± 0.00 for systolic blood pressure, 0.10 ± 0.00 for diastolic blood pressure, and -0.22 ± 0.42 for eGFR (P < 0.001 for all variables). eGFR in non-diabetes participants was inversely associated with the HbA1c level, where eGFR decreased as HbA1c levels increased. Standardized ßs were -0.04 ± 0.42 in multivariable analysis (P < 0.001). The proportion of participants with only MetS, only CKD, or both MetS and CKD was higher in the High group than in the Low and Middle groups. CONCLUSION: High HbA1c in non-DM patients may be associated with CKD. Renal function in patients with high HbA1c levels may need to be monitored.

Association between low-grade albuminuria and hearing impairment in a non-diabetic Korean population: The Korea National Health and Nutrition Examination Survey (2011-2013).

INTRODUCTION: The objective of the present study was to examine the association between low-grade albuminuria and hearing impairment in the non-diabetic population. MATERIALS AND METHODS: Data from the Korean National Health and Nutrition Examination Survey 2011-2013 were used in the analyses. Participants were excluded from this study if they were younger than 19 years old, or had urine albumin/creatinine ratio (UACR) ≥ 30 mg/g or diabetes mellitus. There were 10,608 participants included in this study. The participants were divided into three groups according to their UACR tertiles. RESULTS: There were 1560; 1561; and 1552 male and 1982; 1975; and 1978, female participants in the low, middle, and high tertile groups, respectively. The results indicated the association between low-grade albuminuria and the numbers of metabolic syndrome (MetS) components or Framingham risk score, and the presence of MetS or the proportions of participants at high cardiovascular risk. Univariate and multivariate linear regression analyses demonstrated an association between the UACR and average hearing threshold (AHT) that was observed in both sexes. Multivariate analyses showed that mean AHTs in the low, middle, and high tertile groups were, respectively, 16.127 dB, 17.139 dB, and 18.604 dB for men, and 14.842 dB, 15.100 dB, and 16.353 dB, respectively, for women. Low-frequency, mid-frequency, and high-frequency hearing thresholds according to UACR tertiles showed similar trends. In both sexes, multivariate logistic regression analyses revealed that participants in the low and middle tertile groups had a decreased risk for hearing loss compared to participants in the high tertile group. CONCLUSION: Low-grade albuminuria was associated with hearing impairment in the non-diabetic participants of this study.

Immunoglobulin E-mediated hypersensitivity reaction after intraperitoneal administration of vancomycin.

Intraperitoneal (IP) vancomycin is widely used to treat Gram-positive peritonitis associated with peritoneal dialysis. There have been two cases of red man syndrome (RMS), a vancomycin-specific nonimmunologic reaction, associated with IP vancomycin. However, immune-mediated hypersensitivity reaction to IP vancomycin has not yet been reported. A 49 year old woman on continuous ambulatory peritoneal dialysis developed her first peritonitis episode. The patient was treated with IP vancomycin once/wk for 4 weeks. She experienced mild itching and flushing throughout her body for 1 day after the second treatment. Whenever vancomycin was administered, generalized urticaria and a prickling sensation developed, and the intensity increased gradually; however, these symptoms improved after vancomycin was discontinued. An allergic skin test was performed 6 weeks after the previous urticarial episode, and an intradermal skin test revealed a positive response to vancomycin. To our knowledge, this is the first case report of immunoglobulin E-mediated hypersensitivity reaction to IP vancomycin administration.