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Mutations in the RPE65 gene, associated with Leber congenital amaurosis, early-onset severe retinal dystrophy, and retinitis pigmentosa, gained growing attention since gene therapy for patients with RPE65-associated retinal dystrophy is available in clinical practice. RPE65 gene accounts for a very small proportion of patients with inherited retinal degeneration, especially Asian patients. Because RPE65-associated retinal dystrophy shares common clinical characteristics, such as early-onset severe nyctalopia, nystagmus, low vision, and progressive visual field constriction, with retinitis pigmentosa by other genetic mutations, appropriate genetic testing is essential to make a correct diagnosis. Also, fundus abnormalities can be minimal in early childhood, and the phenotype is highly variable depending on the type of mutations in RPE65-associated retinal dystrophy, which makes a diagnostic difficulty. The aim of this paper is to review the epidemiology of RPE65-associated retinal dystrophy, mutation spectrum, genetic diagnosis, clinical characteristics, and voretigene neparvovec, a gene therapy product for the treatment of RPE65-related retinal dystrophy.
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Purpose@#This study aimed to establish and validate optical coherence tomography (OCT) based diagnostic criteria of high myopia. @*Methods@#This was a cross-sectional study including 100 eyes of high myopia with axial length larger than 26.5 mm and 100 control eyes, which were examined by spectral-domain OCT. Vertical and horizontal OCT of 9 mm scanning across fovea were analyzed. OCT characteristics including mirror artifact, scleral sink due to steep inclination of posterior sclera, scleral visibility, abnormality of outer retinal layer, foveoschisis, and dome-shaped macula were assessed in each group. @*Results@#The mean axial length was 28.65 ± 2.07 mm (range, 26.51–34.59 mm) in high myopia group and 23.79 ± 0.99 mm (range, 21.26–25.94 mm) in control group. Among the OCT characteristics noted at high frequency in the eyes with high myopia, three criteria achieving high sensitivity and specificity were determined: scleral sink over 500 μm, scleral visibility over 100 μm, and dome-shaped macula. Under conditions of presence of any of three criteria in either horizontal or vertical OCT scanning, the diagnostic sensitivity, specificity, positive predictive value, and negative predictive value for high myopia were found to be 95.0%, 98.0%, 98.0%, and 95.1%, respectively. In a new set of OCT images from 50 eyes with high myopia and 50 eyes of nonhigh myopia cases, the OCT-based criteria also proved similar level of diagnostic validity. @*Conclusions@#The OCT-based criteria, which directly addressed posterior scleral contour changes, may lead to an intuitive and accurate diagnosis of high myopia. Also, the criteria may contribute to early detection and monitoring of eyes that cannot be defined as high myopia but can progress. OCT may be useful for monitoring high myopia patients as OCT can detect myopia-associated retinal pathologies as well as scleral contour changes.
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Lewy bodies (LBs) and Lewy neurites (LNs) are pathological hallmarks of Parkinson’s disease (PD) or dementia with LBs (DLB). Incidental Lewy body disease (iLBD) is defined when LBs and LNs are found in the brain of normal elderly individuals. A 65-year-old man presented with autopsy-proven Lewy body pathology (LBP). He had never complained of cognitive impairments or parkinsonian motor symptoms, and he had always maintained independence in activities of daily living. Hypopigmentations in the locus coeruleus and substantia nigra were discovered during the autopsy. The patient showed severe-to-extremely severe LBs in the neocortex and limbic areas, except in the nucleus basalis of Meynert, amygdala, and brainstem, according to microscopic findings. Hence, using several of the previously known staging systems, it was difficult to classify the patient’s LBP type. Furthermore, these findings were unique because they had never been observed before in iLBD.
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Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) overlap clinically with parkinsonism or extrapyramidal signs and pathologically with tauopathy. Asymmetric parkinsonism and cortical dysfunctions are classical features of CBD. However, symmetric parkinsonism, frequent falls, and supranuclear gaze palsy are key features of PSP. Despite biochemically classified as 4R tauopathies, tufted astrocytes of PSP and astrocytic plaque of CBD show pathologically important differences. Herein, we report a 68-year-old man with pathologically confirmed CBD. He was clinically suspected to have PSP because of progressive gait disturbances, frequent falls, and vertical saccade limitation. Neurological examination performed at age 71 revealed symmetrical bradykinesia, axial rigidity, and postural instability with worsening of early existing symptoms. Magnetic resonance imaging of the brain taken at age 70 detected midbrain and left frontotemporal atrophy and right middle cerebral artery infarction. Left frontotemporoparietal hypometabolism and asymmetrically decreased fluoro-propyl-carbomethoxy-iodophenyl-tropane uptake in the basal ganglia were observed. The autopsy was performed at the time of his death (at age 72), which revealed severe pallor of the substantia nigra and mildly hypopigmented locus ceruleus.AT8 immunohistochemistry and Gallyas staining revealed tau-positive neuronal and glial inclusions, astrocytic plaques, ballooned neurons, and numerous threads in both gray and white matter. No abnormal inclusions were revealed by beta-amyloid, α-synuclein and TDP-43 immunohistochemistry. In our case, cerebral infarction, periventricular and deep white matter ischemic changes, and midbrain atrophy were likely to produce PSP–CBD overlapping symptoms. However, our patient was finally confirmed to have CBD based on pathological findings such as astrocytic plaques.
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Traditionally, liver transplantation for hepatocellular carcinoma with portal vein tumor thrombosis is not recommended. However, with recent developments in locoregional therapies for hepatocellular carcinoma, more aggressive treatments have been attempted for advanced hepatocellular carcinoma. Recently, various studies on locoregional therapies for downstaging followed by living donor liver transplantation reported inspiring overall survival and recurrence-free survival of patients. These downstaging procedures included three-dimensional conformal radiation therapy, trans-arterial chemoembolization, stereotactic body radiation therapy, trans-arterial radioembolization, hepatic arterial infusion chemotherapy and combinations of these therapies. Selection of the optimal downstaging protocol should depend on tumor location, biology and background liver status. The risk factors affecting outcome include pre-downstaging alpha-fetoprotein values, delta alpha-fetoprotein values, disappearance of portal vein tumor thrombosis on imaging and meeting the Milan criteria or not after downstaging. For hepatocellular carcinoma with portal vein tumor thrombosis, downstaging procedure with liver transplantation in mind would be helpful. If the reaction of the downstaged tumor is good, liver transplantation may be performed.
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Hepatocellular adenoma is a benign tumor of the liver occurring predominantly in young women taking oral contraceptives. The malignant transformation of hepatocellular adenoma into hepatocellular carcinoma has rarely been reported. Herein, we report the case of an elderly male patient with hepatocellular carcinoma that developed from hepatocellular adenoma. The patient’s high risk for surgery and conflicting biopsy and imaging results made it difficult to determine the treatment direction. Eventually, the mass was completely removed by laparoscopic left hemi-hepatectomy without complications.
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Traditionally, liver transplantation for hepatocellular carcinoma with portal vein tumor thrombosis is not recommended. However, with recent developments in locoregional therapies for hepatocellular carcinoma, more aggressive treatments have been attempted for advanced hepatocellular carcinoma. Recently, various studies on locoregional therapies for downstaging followed by living donor liver transplantation reported inspiring overall survival and recurrence-free survival of patients. These downstaging procedures included three-dimensional conformal radiation therapy, trans-arterial chemoembolization, stereotactic body radiation therapy, trans-arterial radioembolization, hepatic arterial infusion chemotherapy and combinations of these therapies. Selection of the optimal downstaging protocol should depend on tumor location, biology and background liver status. The risk factors affecting outcome include pre-downstaging alpha-fetoprotein values, delta alpha-fetoprotein values, disappearance of portal vein tumor thrombosis on imaging and meeting the Milan criteria or not after downstaging. For hepatocellular carcinoma with portal vein tumor thrombosis, downstaging procedure with liver transplantation in mind would be helpful. If the reaction of the downstaged tumor is good, liver transplantation may be performed.
ABSTRACT
Hepatocellular adenoma is a benign tumor of the liver occurring predominantly in young women taking oral contraceptives. The malignant transformation of hepatocellular adenoma into hepatocellular carcinoma has rarely been reported. Herein, we report the case of an elderly male patient with hepatocellular carcinoma that developed from hepatocellular adenoma. The patient’s high risk for surgery and conflicting biopsy and imaging results made it difficult to determine the treatment direction. Eventually, the mass was completely removed by laparoscopic left hemi-hepatectomy without complications.
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Purpose@#To investigate whether estramustine phosphate (EMP) monotherapy is applicable to castration-resistantprostate cancer (CRPC) patients who cannot receive cytotoxic chemotherapy. @*Materials and Methods@#This retrospective single-arm study was conducted in CRPC patients who had notexperienced cytotoxic chemotherapy and received EMP monotherapy (560 mg/day) at 2 institutions from 2008to 2017. We analyzed prostate-specific antigen (PSA) responses, overall survival, and adverse effects of EMPtreatment. @*Results@#A total of 28 patients were analyzed. A reduction in serum PSA was observed in 11 patients (39.3%).Seven cases (25.9%) achieved more than 25% reduction of PSA, and 5 of them (18.5%) experienced more than50% reduction. Median overall survival was 23 months (interquartile range, 10–60 months). Multivariable analysesdemonstrated that low level of PSA at diagnosis of CRPC and long duration of prior androgen deprivation therapywere independent favorable factors predicting long-term overall survival. Adverse effects were edema (n=2; grade2), nausea/vomiting (n=1; grade 2), gynecomastia (n=1; grade 2), and dyspnea (n=1; grade 1). Neither thromboembolicevent nor grade 3–5 toxicity was observed. There was no discontinuation caused by side effects ofEMP. @*Conclusions@#EMP monotherapy could be considered as a safe treatment option with some effectiveness for CRPCpatients who did not undergo cytotoxic chemotherapy. EMP is not generally recommended anticancer drug in thecurrent guidelines for CRPC, but EMP monotherapy is thought to have an alternative role when a standard treatmentcannot be selected due to patient's age, health condition, or comorbidity.
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Background@#and Purpose: The Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) is widely used for estimating the symptoms of Parkinson’s disease. Translation and validation of the MDS-UPDRS is necessary for non-English speaking countries and regions. The aim of this study was to validate the Korean version of the MDS-UPDRS. @*Methods@#Altogether, 362 patients in 19 centers were recruited for this study. We translated the MDS-UPDRS to Korean using the translation-back translation method and cognitive pretesting. We performed both confirmatory and exploratory factor analyses to validate the scale.We calculated the comparative fit index (CFI) for confirmatory factor analysis, and used unweighted least squares for exploratory factor analysis. @*Results@#The CFI was higher than 0.90 for all parts of the scale. Exploratory factor analysis also showed that the Korean MDS-UPDRS has the same number of factors in each part as the English version. @*Conclusions@#The Korean MDS-UPDRS has the same overall structure as the English MDSUPDRS. Our translated scale can be designated as the official Korean MDS-UPDRS.
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Background@#and PurposeImpulse-control disorder is an important nonmotor symptom of Parkinson's disease (PD) that can lead to financial and social problems, and be related to a poor quality of life. A nationwide multicenter prospective study was performed with the aim of validating the Korean Version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (K-QUIP-RS). @*Methods@#The K-QUIP-RS was constructed using forward and backward translation, and pretesting of the prefinal version. PD patients on stable medical condition were recruited from 27 movement-disorder clinics. Participants were assessed using the K-QUIP-RS and evaluated for parkinsonian motor and nonmotor statuses and for PD-related quality of life using a predefined evaluation battery. The test–retest reliability of the K-QUIP-RS was assessed over an interval of 10–14 days, and correlations between the KQUIP-RS and other clinical scales were analyzed. @*Results@#This study enrolled 136 patients. The internal consistency of the K-QUIP-RS was indicated by a Cronbach's α coefficient of 0.846, as was the test–retest reliability by a Guttman split-half coefficient of 0.808. The total K-QUIP-RS score was positively correlated with the scores for depression and motivation items on the Unified PD Rating Scale (UPDRS), Montgomery-Asberg Depression Scale, and Rapid-Eye-Movement Sleep-Behavior-Disorders Questionnaire. The total K-QUIP-RS score was also correlated with the scores on part II of the UPDRS and the PD Quality of Life-39 questionnaire, and the dopaminergic medication dose. @*Conclusions@#The K-QUIP-RS appears to be a reliable assessment tool for impulse-control and related behavioral disturbances in the Korean PD population.
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Purpose@#Tenofovir disoproxil fumarate is accepted as an effective and tolerable drug for treatment of HBV, similar to entecavir. However, there are some concerns about the nephrotoxicity of tenofovir. The aim of this study is to compare the renal-function change of liver recipients who received tenofovir or entecavir for HBV. @*Methods@#Among 468 patients with HBV who underwent liver transplantation at Samsung Medical Center between January 2008 and December 2015, the patients treated with tenofovir (n = 39) or entecavir (n = 429) were reviewed retrospectively.Baseline characteristics and renal-function change after 1 month, 1 year, and 2 years were compared. Propensity-score matching was performed for 37 patients using tenofovir and 132 patients using entecavir. We also analyzed risk factors of renal dysfunction. @*Results@#Age, preoperative creatinine, estimated glomerular filtration rate (e-GFR), and hepatic encephalopathy score showed statistical difference between the tenofovir and entecavir groups. The proportion of patients with ‘decreased renal function (e-GFR < 60 mL/min/1.73 m 2 )’ was higher in the tenofovir group than in the entecavir group (33.3% vs. 12.4% at postoperative one year, p < 0.005). After propensity-score matching, there was no statistical difference in preoperative characteristics. Postoperative 1-, 2-, and 3-year e-GFR and creatinine showed no statistical difference in either group. On multivariate analysis, only preoperative high e-GFR showed a protective effect on renal-function change (odds ratio, 0.97; p < 0.001), and there was no aggravating factor. @*Conclusion@#Tenofovir disoproxil fumarate does not induce renal dysfunction in liver-transplanted patients with HBV more than does entecavir.
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Subject(s)
Humans , Follow-Up Studies , Parkinson Disease , Quality of Life , Weights and MeasuresABSTRACT
Purpose@#The purpose of this study was to describe the health care experiences among patients with Parkinson’s disease. @*Methods@#Of the qualitative research methods, Colaizzi’s phenomenological method was used in this study. A total of nine patients, who were diagnosed with Parkinson’s disease and receiving outpatient treatment, were selected as the subjects of this study. Subsequently, data were collected through individual in-depth interview. @*Results@#The four categories obtained as a result were ‘strenuous efforts to control my own body,’ ‘subject of health that no one can replace,’ ‘focus on the current while expecting a breakthrough in health management,’ and ‘human dignity that cannot be lost to the end.’ @*Conclusion@#The study results are expected to help health care providers deeply understand the experiences in health care among patients with Parkinson’s disease and to provide source data for nursing intervention development that can be helpful in managing the health status of patients with Parkinson’s disease.
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Purpose@#The purpose of this study was to describe the health care experiences among patients with Parkinson’s disease. @*Methods@#Of the qualitative research methods, Colaizzi’s phenomenological method was used in this study. A total of nine patients, who were diagnosed with Parkinson’s disease and receiving outpatient treatment, were selected as the subjects of this study. Subsequently, data were collected through individual in-depth interview. @*Results@#The four categories obtained as a result were ‘strenuous efforts to control my own body,’ ‘subject of health that no one can replace,’ ‘focus on the current while expecting a breakthrough in health management,’ and ‘human dignity that cannot be lost to the end.’ @*Conclusion@#The study results are expected to help health care providers deeply understand the experiences in health care among patients with Parkinson’s disease and to provide source data for nursing intervention development that can be helpful in managing the health status of patients with Parkinson’s disease.
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BACKGROUND: Pathogenic variants of USH1C, encoding a PDZ-domain-containing protein called harmonin, have been known to cause autosomal recessive syndromic or nonsyndromic hearing loss (NSHL). We identified a causative gene in a large Korean family with NSHL showing a typical pattern of autosomal dominant (AD) inheritance.METHODS: Exome sequencing was performed for five affected and three unaffected individuals in this family. Following identification of a candidate gene variant, segregation analysis and functional studies, including circular dichroism and biolayer interferometry experiments, were performed.RESULTS: A novel USH1C heterozygous missense variant (c.667G>T;p.Gly223Cys) was shown to segregate with the NSHL phenotype in this family. This variant affects an amino acid residue located in the highly conserved carboxylate-binding loop of the harmonin PDZ2 domain and is predicted to disturb the interaction with cadherin-related 23 (cdh23). The affinity of the variant PDZ2 domain for a biotinylated synthetic peptide containing the PDZ-binding motif of cdh23 was approximately 16-fold lower than that of the wild-type PDZ2 domain and that this inaccessibility of the binding site was caused by a conformational change in the variant PDZ2 domain.CONCLUSIONS: A heterozygous variant of USH1C that interferes with the interaction between cdh23 and harmonin causes novel AD-NSHL.
Subject(s)
Humans , Binding Sites , Circular Dichroism , Exome , Hearing Loss , Hearing , Interferometry , Phenotype , WillsABSTRACT
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a subtype of dominantly inherited leukoencephalopathies caused by novel CSF1R gene mutation predominantly affecting the cerebral white matter. High signal lesions on diffusion weighted image (DWI) are characteristic. Herein, we describe a patent with ALSP with a novel mutation. The patient had persistent DWI lesions, worsening white matter changes associated with rapidly progressive clinical symptoms.
Subject(s)
Humans , Axons , Diffusion , Leukoencephalopathies , Neuroglia , White MatterABSTRACT
BACKGROUND: Prostate cancer (PC) is the second most common type of cancer in men worldwide and the fifth most common cancer among Korean men. Although most PCs grow slowly, it is unclear whether a longer time interval from diagnosis to treatment causes worse outcomes. This study aimed to investigate whether the time interval from diagnosis to radical prostatectomy (RP) in men with clinically localized PC affects postoperative oncologic outcomes. METHODS: We retrospectively analyzed data of 427 men who underwent RP for localized PC between January 2005 and June 2016. The patients were divided into two groups based on the cutoff median time interval (100 days) from biopsy to surgery. The associations between time interval from biopsy to surgery (< 100 vs. ≥ 100 days) and adverse pathologic outcomes such as positive surgical margin, pathologic upgrading, and upstaging were evaluated. Biochemical recurrence (BCR)-free survival rates were analyzed and compared based on the time interval from biopsy to surgery. RESULTS: Pathologic upgrading of Gleason score in surgical specimens was more frequent in the longer time interval group and showed marginal significance (38.8% vs. 30.0%; P = 0.057). Based on multivariable analysis, an association was observed between time interval from biopsy to surgery and pathologic upgrading (odds ratio, 2.211; 95% confidence interval [CI], 1.342–3.645; P = 0.002). BCR-free survival did not differ based on time interval from biopsy to surgery, and significant association was not observed between time interval from biopsy to surgery and BCR on multivariable analysis (hazard ratio, 1.285; 95% CI, 0.795–2.077; P = 0.305). CONCLUSION: Time interval ≥ 100 days from biopsy to RP in clinically localized PC increased the risk of pathologic upgrading but did not affect long-term BCR-free survival rates in Korean men.
Subject(s)
Humans , Male , Biopsy , Diagnosis , Neoplasm Grading , Prostate , Prostatectomy , Prostatic Neoplasms , Recurrence , Retrospective Studies , Survival Rate , Time Factors , Treatment OutcomeABSTRACT
PURPOSE: To evaluate changes in the peripapillary retinal nerve fiber layer (RNFL) thicknesses using spectral-domain optical coherence tomography (SD-OCT) in hydroxychloroquine (HCQ) users. METHODS: The medical records of HCQ users were retrospectively reviewed. In these HCQ users, an automated perimetry, fundus autofluorescence photography, and SD-OCT with peripapillary RNFL thickness measurements were performed. The peripapillary RNFL thicknesses were compared between the HCQ users and the control groups. The relationships between the RNFL thicknesses and the duration or cumulative dosage of HCQ use were analyzed. RESULTS: This study included 77 HCQ users and 20 normal controls. The mean duration of HCQ usage was 63.6 ± 38.4 months, and the cumulative dose of HCQ was 528.1 ± 3.44 g. Six patients developed HCQ retinopathy. Global and six sectoral RNFL thicknesses of the HCQ users did not significantly decrease compared to those of the normal controls. No significant correlation was found between the RNFL thickness and the duration of use or cumulative dose. The eyes of those with HCQ retinopathy had temporal peripapillary RNFL thicknesses significantly greater than that of normal controls. CONCLUSIONS: The peripapillary RNFL thicknesses did not change in the HCQ users and did not correlate with the duration of HCQ use or cumulative doses of HCQ. RNFL thickness is not a useful biomarker for the early detection of HCQ retinal toxicity.
Subject(s)
Humans , Hydroxychloroquine , Medical Records , Nerve Fibers , Photography , Retinaldehyde , Retrospective Studies , Tomography, Optical Coherence , Visual Field TestsABSTRACT
PURPOSE: The quality of bowel preparation is a major determinant of the quality of colonoscopy. This study evaluated lifestyle factors, including usual dietary style, associated with bowel preparation. METHODS: This retrospective study evaluated 1,079 consecutive subjects who underwent complete colonoscopy from December 2012 to April 2014 at National Cancer Center of Korea. Questionnaires on bowel preparation were completed by the subjects, with the quality of bowel preparation categorized as optimal (excellent or good) or suboptimal (fair, poor or inadequate). Lifestyle factors associated with bowel preparation were analyzed. RESULTS: The 1,079 subjects included 680 male (63.0%) and 399 female patietns (37.0%), with a mean age of 49.6 ± 8.32 years. Bowel preparation was categorized as optimal in 657 subjects (60.9%) and as suboptimal in 422 (39.1%). Univariate analyses showed no differences between groups in lifestyle factors, such as regular exercise, alcohol intake, smoking, and dietary factor. Body mass index (BMI) > 25 kg/m2 was the only factor associated with suboptimal bowel preparation on both the univariate (P = 0.007) and the multivariate (odds ratio, 1.437; 95% confidence interval, 1.104–1.871; P = 0.007) analyses. CONCLUSION: Most lifestyle factors, including dietary patterns, exercise, alcohol intake and smoking, were not associated with suboptimal bowel preparation in Koreans. However, BMI > 25 kg/m2 was independently associated with suboptimal bowel preparation. More intense preparation regimens before colonoscopy can be helpful in subjects with BMI > 25 kg/m2.