Efficacy of vestibular rehabilitation and its facilitating and hindering factors from real-world clinical data.

Background and purpose: Customized vestibular rehabilitation improved dizziness and imbalance in several randomized controlled trials. In the present study, we determined the efficacy of customized vestibular rehabilitation using real-world observational data. Methods: In this retrospective observational study, we recruited 64 patients (median age = 60, interquartile range = 48-66.3) who completed the customized vestibular rehabilitation from January to December 2022. The outcomes of rehabilitation were evaluated using the dizziness handicap inventory (DHI) or vestibular disorders activities of daily living scale (VADL). The factors associated with outcomes were assessed with a generalized linear model, of which covariates included patients' age, sex, duration of illness, type of vestibular disorders, initial DHI and VADL scores, exercise compliance, and initial hospital anxiety and depression scale (HADS) scores. Results: After the median of 6 (4-6) weeks of rehabilitation, DHI and VADL scores significantly improved in patients with either peripheral or central vestibular disorders (Wilcoxon signed-rank test, p < 0.05). The initial DHI and VADL scores showed a positive while the sum of HADS scores showed a negative correlation with the outcome. In contrast, the age, sex, duration of illness, types of vestibular disorders, and exercise compliance did not affect the outcome. Discussion and conclusion: Customized vestibular rehabilitation is effective for central as well as peripheral disorders, especially when the symptoms are severe and the psychological distress is mild.

Loss of torsional quick eye movements during head roll in progressive supranuclear palsy: a new diagnostic marker.

BACKGROUND AND OBJECTIVES: Even though impaired horizontal and vertical saccades are well-known features of progressive supranuclear palsy (PSP), abnormalities of torsional quick phases of eye movements have not been defined in PSP and other Parkinsonian syndromes. This study aims to determine the diagnostic value of decreased torsional quick phases during head oscillations in the roll plane in patients with PSP. METHODS: Using video-oculography, we recorded the head and eye motion during passive head oscillations in the roll plane and determined the decrease of torsional quick phases in patients with PSP (n = 13) in comparison to normal controls (n = 13) and those with multiple system atrophy (MSA, n = 17) or idiopathic Parkinson's disease (PD, n = 6). RESULTS: Torsional quick phases were absent during the torsional vestibulo-ocular reflex (VOR) in 78.6% (11/13) of the patients with PSP, but only in 11.8% (2/17) of those with MSA and none with idiopathic PD or of normal controls (Chi-square tests, p < 0.001) while gains of the torsional VOR did not differ among the groups (Chi-square tests, p > 0.05). Furthermore, the torsional quick phases were smaller even when observed in patients with PSP. CONCLUSION: Loss of torsional quick phases is an early biological marker for diagnosis of PSP, and may be ascribed to degeneration of the rostral interstitial nucleus of the medial longitudinal fasciculus that contains the burst neurons for torsional as well as vertical saccades.

Risk factors for developing post-thymectomy myasthenia gravis in patients with thymoma.

BACKGROUND: Thymectomy is required for the treatment of thymoma-associated myasthenia gravis (MG). However, MG may develop only after thymectomy, a condition known as post-thymectomy MG. This study aimed to investigate the risk factors for post-thymectomy MG in patients with thymoma. METHODS: We retrospectively identified 235 patients with thymoma who underwent thymectomy at a single hospital from January 2008 to December 2017: 44 with preoperatively diagnosed MG were excluded, leaving 191 patients in the final analysis. Univariable survival analyses using Cox proportional hazards regression model and Kaplan-Meier estimate were conducted to identify risk factors for post-thymectomy MG. RESULTS: Post-thymectomy MG developed in 4.2% (8/191) of the patients with thymoma between 18 days and 108 mo after surgery. Hazard ratios (HRs) of pre- and postoperative anti-acetylcholine receptor antibody (AChR-Ab) titers were 2.267 (P = .002) and 1.506 (P < .001), respectively. Patients with extended thymectomy had a low chance of post-thymectomy MG (HR 0.035, P = .007). Larger thymoma (HR, 1.359; P = .005) and type A or AB thymoma according to World Health Organization histological classification (HR, 11.92; P = .021) were associated with higher chances of post-thymectomy MG. Within the subgroup of preoperatively AChR-Ab seropositive patients, post-thymectomy MG developed in 22.2% (6/27). CONCLUSIONS: Pre- and postoperative AChR-Ab levels should be measured in patients with thymoma. A large thymoma and partial thymectomy appear to be associated with a higher probability of post-thymectomy MG.

Tacrolimus for Treating Orbital and Cranial Form of Idiopathic Inflammatory Pseudotumors.

BACKGROUND AND PURPOSE: Orbital and cranial form of idiopathic inflammatory pseudotumors (IIPs) are rare disorders with heterogeneous clinical presentations. Corticosteroids have been the first-line treatment for IIPs, but they are not always effective. METHODS: We reviewed the medical records of three patients with orbital or cranial form of IIP who were treated with tacrolimus as an adjuvant treatment. RESULTS: The three patients showed favorable outcomes with the addition of tacrolimus, which is a calcineurin inhibitor that inhibits T-cell activation and T-cell-dependent B-cell activation. CONCLUSIONS: Tacrolimus may be a safe and effective immunosuppressant for refractory or relapsing form of orbital or cranial IIPs.

Searching for an ideal cervical cancer screening model to reduce false-negative errors in a country with high prevalence of cervical cancer.

The purpose of this study was to develop an ideal cervical cancer screening model to reduce false-negative errors in Korea where there is a high prevalence of cervical cancer. We conducted a cross-sectional study including 33,531 women who underwent routine cervical cancer screening in Korea. Colposcopic examinations were performed after abnormal results on their screening tests. Diagnostic capacities including sensitivity, specificity, and false-negative rate of each screening scenario were analysed at the CIN1 or worse (CIN1+) threshold with colposcopic biopsy results considered the gold standard. A total of 4117 women had valid results for Papanicolaou (Pap) cytology, human papilloma virus (HPV) tests, cervicography, and colposcopically directed biopsy were included in this study. The disease prevalence of CIN1+ was 38.1%. Pap-alone resulted in the highest false-negative rate of 46.9%, followed by HPV-alone at 25.1%, cervicography-alone at 18.7%, Pap/HPV-combined at 15.0%, Pap/cervicography-combined at 6.9% and Pap/HPV/cervicography-combined at 2.9% in a sample of 1570 women with CIN1+ lesions. Therefore, cervicography demonstrated excellent performance for the detection of CIN or cervical cancer and markedly reduced false-negative errors when used in combination with Pap cytology and HPV tests.IMPACT STATEMENTWhat is already known on this subject? False-negative rate of Pap smears is as high as approximately 40-50%. Limitations of the Papanicolaou (Pap) test have led to the development of new screening programmes for cervical cancer, such as combination screenings with human papillomavirus (HPV) tests or cervicography.What do the results of this study add? Pap-alone resulted in the highest false-negative rate of 46.9%, followed by HPV-alone at 25.1%, cervicography-alone at 18.7%, Pap/HPV-combined at 15.0%, Pap/cervicography-combined at 6.9% and Pap/HPV/cervicography-combined at 2.9% in a sample of 1570 women with CIN1+ lesions.What are the implications of these findings for clinical practice and/or further research? Cervicography demonstrated excellent performance for the detection of CIN or cervical cancer and markedly reduced false negative errors when used in combination with Pap cytology and HPV tests.

Screening capacity and cost-effectiveness of the human papillomavirus test versus cervicography as an adjunctive test to Pap cytology to detect high-grade cervical dysplasia.

OBJECTIVE: This study compared the screening capacities and cost-effectiveness of the human papillomavirus (HPV) test versus cervicography as an adjunctive test to Papanicolaou (Pap) cytology to detect high-grade cervical neoplasia in Korea, a country with a high prevalence of cervical cancer. STUDY DESIGN: Of 33,531 Korean women who underwent cervicography as a screening test for cervical cancer between January 2015 and December 2016, we retrospectively analyzed the records of 4117 women who simultaneously or subsequently underwent Pap cytology, an HPV test, cervicography, and colposcopically directed biopsy. At a threshold of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), based on colposcopic biopsy, we compared the diagnostic capacities and cost-effectiveness of these screening tools. RESULTS: The CIN2+ prevalence was 10.8% (446 of 4117 women) and the positive rate of high-risk HPV was 61.0% (2511 of 4117 women). Cervicography as an adjunctive to Pap cytology was a more sensitive test (97.5% vs 93.7%) with a higher odds ratio (15.65 vs 5.86) than the HPV test for detection of CIN2+ (P-value = 0.003). Moreover, the cost of cervicography co-testing was 23% less than that of HPV co-testing, decreasing the cost per patient with CIN2+ lesions from $1474 to $1135. CONCLUSION: Cervicography and Pap co-testing had superior screening capacity and cost-effectiveness for detection of preinvasive cervical lesions than HPV and Pap co-testing and may be an effective and cost-saving screening strategy in clinical practice in country with a high prevalence of cervical cancer.

Acute Ischemic Stroke Mimicking Non-Convulsive Status Epilepticus.

Status epilepticus and stroke are occasionally characterized by indistinguishable symptoms. Diffusion-weighted imaging (DWI) could not only help differentiating seizure from stroke, but also assist in localizing a focus of seizure and reflect resolution of seizure. We report a case of non-convulsive status epilepticus that presented as acute ischemic stroke, mimicking the latter's clinical manifestations. A 77-year-old right-handed man visited the emergency room with complaints of impaired awareness and fluency with right hemiparesis. Moreover, he presented with first-onset focal to bilateral tonic-clonic seizure with eyeball deviation to the right for 1 minute. Magnetic resonance imaging showed hyperintensity on DWI with a reduced apparent diffusion coefficient (ADC) value in the left pulvinar and left temporo-occipital areas. However, eyeball deviation to the right was not matched with left hemispheric stroke. Electroencephalography (EEG) confirmed ictal discharges in the left temporal area, which were compatible with impaired awareness, ictal aphasia, and eyeball deviation to the right. In cases of conflicting results from neurological examination and DWI/ADC findings, clinicians should consider employing EEG for diagnosing and treating non-convulsive status epilepticus.

Right ventricular metastatic tumor from a primary carcinoma of uterine cervix: A cause of pulmonary embolism.

The presence of intracavitary cardiac metastasis from squamous cell carcinoma of the uterine cervix is extremely rare. The diagnosis is made almost exclusively postmortem. Apart from causing intracardiac obstruction, it can present as pulmonary emboli and the prognosis is extremely poor. It is important to suspect this diagnosis in patient with recurrent pulmonary emboli. Due to the rarity of this condition it is very difficult to standardize care for these patients. However, it is possible that aggressive therapy may lengthen patients' survival and quality of life. We present a case of isolated intracavitary cardiac metastasis arising from a squamous cell carcinoma of the cervix, 44-year-old woman, diagnosed as stage complaint of fatigue and dyspnea on mild exertion. The echocardiogram showed a mass in the right ventricle and suspicious pulmonary embolism. We took an aggressive therapeutic approach. The pathological examination of the resected tissue revealed metastatic squamous cell carcinoma.

Development and validation of novel digitalized cervicography system.

OBJECTIVE: Digital cervicography systems would be expected to reduce the costs of film cervicography, and provide the opportunity for "telemedicine-based" screening. We aimed to develop web-based digital cervicography system, and validate it compared with conventional film cervicography. METHODS: A hundred cases from five centers were prospectively included, and cervical images (analogue, digitalized by scanning analogue, and digital) were taken separately using both analogue (Cerviscope) and digital camera (Dr. Cervicam) in each patient. Nine specialists evaluated the three kinds of images of each case with time interval between evaluations of each image. To validate novel digitalized system, we analyzed intra-observer variance among evaluation results of three kinds of images. RESULTS: Sixty-three cases were finally analyzed after excluding technically defective cases that cannot be evaluable on analogue images. The generalized kappa for analogue versus digital image was 0.83, for analogue versus scanned image 0.72, and for digital versus scanned image was 0.71; all were in excellent consensus. CONCLUSION: Digitalized cervicography system can be substituted for the film cervicography very reliably, and can be used as a promising telemedicine tool for cervical cancer screening.

Photosensitizer fluorescence and singlet oxygen luminescence as dosimetric predictors of topical 5-aminolevulinic acid photodynamic therapy induced clinical erythema.

The need for patient-specific photodynamic therapy (PDT) in dermatologic and oncologic applications has triggered several studies that explore the utility of surrogate parameters as predictive reporters of treatment outcome. Although photosensitizer (PS) fluorescence, a widely used parameter, can be viewed as emission from several fluorescent states of the PS (e.g., minimally aggregated and monomeric), we suggest that singlet oxygen luminescence (SOL) indicates only the active PS component responsible for the PDT. Here, the ability of discrete PS fluorescence-based metrics (absolute and percent PS photobleaching and PS re-accumulation post-PDT) to predict the clinical phototoxic response (erythema) resulting from 5-aminolevulinic acid PDT was compared with discrete SOL (DSOL)-based metrics (DSOL counts pre-PDT and change in DSOL counts pre/post-PDT) in healthy human skin. Receiver operating characteristic curve (ROC) analyses demonstrated that absolute fluorescence photobleaching metric (AFPM) exhibited the highest area under the curve (AUC) of all tested parameters, including DSOL based metrics. The combination of dose-metrics did not yield better AUC than AFPM alone. Although sophisticated real-time SOL measurements may improve the clinical utility of SOL-based dosimetry, discrete PS fluorescence-based metrics are easy to implement, and our results suggest that AFPM may sufficiently predict the PDT outcomes and identify treatment nonresponders with high specificity in clinical contexts.

ZNF281 knockdown induced osteogenic differentiation of human multipotent stem cells in vivo and in vitro.

ZNF281 is one of the core transcription factors in embryonic stem cells (ESCs) and has activation and repression roles in the transcription of ESC genes. A known target molecule of Zfp281 (the mouse homologue of ZNF281) is Nanog. However, NANOG is not expressed in most human multipotent stem cells (hMSCs). Here, we investigated the roles of ZNF281 with a gain- and loss-of-function study. The knockdown of ZNF281 in vivo and in vitro resulted in spontaneous osteochondrogenic differentiation and reduced the proliferation of hMSCs, as determined by cell morphology and molecular markers. When ZNF281-knockdown hMSCs were subcutaneously implanted into mice along with ß-tricalcium phosphate (ß-TCP), many cells were converted into osteoblasts within 4 weeks. In contrast, the overexpression of ZNF281 in hMSCs resulted in accelerated proliferation. The expression pattern of ZNF281 correlated well with the expression of ß-CATENIN during differentiation and in the gain/loss-of-function study in hMSCs. The binding of ZNF281 to the promoter region of ß-CATENIN was observed using a chromatin immunoprecipitation (ChIP) assay. In conclusion, we propose that ZNF281 plays an important role in the maintenance and osteogenic differentiation of stem cells via the transcriptional regulation of genes including ß-CATENIN.

Genetic polymorphism of PRKCDBP is associated with an increased risk of endometrial cancer.

PRKCDBP is a putative tumor suppressor located at 11p15.4, where frequent genomic loss has been observed in human cancers. We explored the possible association between an intra-exonic single nucleotide polymorphism (SNP), rs1051992, that results in a Leu to Pro substitution, and risk for endometrial carcinogenesis. We assessed the genotype of rs1051992 in endometrial cancer tissues from 147 patients and normal endometrial tissue from 191 healthy individuals by restriction endonuclease PvuII-based genotyping. Allele frequencies in the cancer specimens were compared with those in the healthy controls. We also evaluated the association between polymorphisms at this locus and histopathological features of endometrial cancer.

Correlation between FDG uptake by PET/CT and the expressions of glucose transporter type 1 and hexokinase II in cervical cancer.

BACKGROUND: The aim of this study was to explore the association between 2-deoxy-2-F18-fluoro-D-glucose uptake and the expressions of glucose transporter type 1 (GLUT-1) and hexokinase II (HK-II) in the lymph nodes of patients with cervical cancer. METHODS: This prospective study included 20 women with International Federation of Gynecology and Obstetrics stage IB to stage IIA cervical cancer who underwent positron emission tomography (PET)-computed tomography (CT) (PET/CT) before surgical treatment. In 333 dissected lymph nodes (LNs) obtained, we examined the size, tumor involvement, and expressions of GLUT-1 and HK-II. These characteristics were compared with PET/CT and pathological findings. RESULTS: Pathological analysis found that 21% (70) of the 333 surgically dissected LNs were metastatic. Positron emission tomography/CT detected metastasis with 22.8% sensitivity and 98.5% specificity. The levels of GLUT-1 and HK-II expression in false-positive LNs were higher than those in pathologically confirmed negative nodes (P = 0.015 and P = 0.001, respectively). In metastatic LNs, PET/CT-positive nodes were significantly different from PET/CT-negative nodes in mean size (P = 0.043), tumor involvement (P = 0.008), and proportion of GLUT-1-positive tumor cells (P = 0.042). CONCLUSIONS: Our results indicate that overexpression of GLUT-1 and HK-II may be related to 2-deoxy-2-F18-fluoro-D-glucose uptake in false-positive tissues on PET/CT. In metastatic lymph nodes, the ability of PET/CT to detect cancer may depend on tumor involvement, lymph node size, and GLUT-1 expression.

Dual-channel imaging system for singlet oxygen and photosensitizer for PDT.

A two-channel optical system has been developed to provide spatially resolved simultaneous imaging of singlet molecular oxygen ((1)O(2)) phosphorescence and photosensitizer (PS) fluorescence produced by the photodynamic process. The current imaging system uses a spectral discrimination method to differentiate the weak (1)O(2) phosphorescence that peaks near 1.27 µm from PS fluorescence that also occurs in this spectral region. The detection limit of (1)O(2) emission was determined at a concentration of 500 nM benzoporphyrin derivative monoacid (BPD) in tissue-like phantoms, and these signals observed were proportional to the PS fluorescence. Preliminary in vivo images with tumor laden mice indicate that it is possible to obtain simultaneous images of (1)O(2) and PS tissue distribution.

Current status in the management of uterine corpus cancer in Korea.

Uterine corpus cancer has increased in prevalence in Korean women over the last decade. Recently, elegant studies have been reported from many institutes. To improve treatment strategies, a review of our own data is warranted. This work will discuss the risks and prognostic factors for uterine corpus cancer, and the radiologic evaluation, prediction of lymph node metastasis, systematic lymphadenectomy, minimally invasive surgery, ovarian-saving surgery, fertility-sparing treatment, and adjuvant treatment in women with uterine cancer.

Frequent inactivation of hSRBC in ovarian cancers by promoter CpG island hypermethylation.

OBJECTIVE: To explore the implication of human SRBC gene [serum deprivation response factor-related gene product that binds to the c-kinase (hSRBC)] abnormality in ovarian tumorigenesis. DESIGN: Retrospective study. SETTING: Medical center. SAMPLE: Twenty-two epithelial ovarian cancer and six normal ovary tissues. MEASURES: Mutation and altered expression of hSRBC gene. METHODS: hSRBC expression was characterized by polymerase chain reaction (PCR) analysis. Promoter CG dinucleotide (CpG) site methylation was determined using methylation specific PCR and bisulfite sequencing. RESULTS: Expression of hSRBC transcript was easily detectable in all normal tissues we examined, but 50% (two of four) of cancer cell lines and 41% (nine of 22) of primary carcinomas exhibited undetectable or substantially decreased expression. While genomic deletion or somatic mutations of the gene was not identified, its expression was reactivated in tumor cells by 5-aza-2'-deoxycytidine treatment, suggesting epigenetic inactivation of the gene in tumors. Promoter methylation was detected in all nine tumors with low expression but in only one of 13 (7.7%) tumors with normal expression. Bisulfite DNA sequencing analysis of 23 CpG sites within the promoter region revealed that the CpG sites are highly methylated in low-expressing tumors. In addition, promoter CpG sites methylation status showed a tight association with gene expression level. CONCLUSION: Our data demonstrate that epigenetic inactivation of hSRBC due to aberrant promoter hypermethylation is a common event and might be implicated in human ovarian tumorigenesis.