A Comparative Investigation of Functional Connectivity Utilizing Electroencephalography in Insomnia Patients with and without Restless Leg Syndrome

Objective: The current study aimed to identify distinctive functional brain connectivity characteristics that differentiate patients with restless legs syndrome (RLS) from those with primary insomnia. Methods: Quantitative electroencephalography (QEEG) was employed to analyze connectivity matrices using the phaselocking value technique. A total of 107 patients with RLS (RLS group) and 17 patients with insomnia without RLS (primary insomnia group) were included in the study. Demographic variables were compared using t tests and chi-square tests, while differences in connectivity were examined through multiple analyses of covariance. Correlation analysis was conducted to explore the relationship between connectivity and the severity of RLS. Results: The results indicated significant differences in the primary somatosensory cortex (F = 4.377, r = 0.039), primary visual cortex (F = 4.215, r = 0.042), and anterior prefrontal cortex (F = 5.439, r = 0.021) between the RLS and primary insomnia groups. Furthermore, the connectivity of the sensory cortex, including the primary somatosensory cortex (r = -0.247, p = 0.014), sensory association cortex (r = -0.238, p = 0.028), retrosplenial region (r = -0.302, p = 0.002), angular gyrus (r = -0.258, p = 0.008), supramarginal gyrus (r = -0.230, p = 0.020), primary visual cortex (r = -0.275, p = 0.005) and secondary visual cortex (r = -0.226, p = 0.025) exhibited an inverse association with RLS symptom severity. Conclusion: The prefrontal cortex, primary somatosensory cortex, and visual cortex showed potential as diagnostic biomarkers for distinguishing RLS from primary insomnia. These findings indicate that QEEG-based functional connectivity analysis shows promise as a valuable diagnostic tool for RLS and provides insights into its underlying mechanisms. Further research is needed to explore this aspect further.

Difference between Quantitative Electroencephalography, Loudness Dependence of Auditory Evoked Potential, and Mismatch Negativity between a Manic and a Depressive Episode in a Single Bipolar Patient with Mixed Features.

This study compares the changes in Quantitative electroencephalography (QEEG), loudness dependence of auditory evoked potentials (LDAEP), and mismatch negativity (MMN) in the case of bipolar depression, mania, and euthymia in a single patient. the characteristic of QEEG in this patient with mixed depression was an increase in alpha; in mixed mania, there was little increase in alpha, and the decrease in delta, theta, and beta was noticeable. LDAEP increased more in the manic phase than in the depressive phase. In contrast, MMN decreased more in the manic than in the depressive phase. After remission of mania, QEEG, LDAEP, and MMN were re-measured. Compared with the manic phase, the decrease in delta, theta, and beta bands in the occipital, temporal, and parietal lobes improved significantly. The LDAEP decreased from LDAEP 1.67 to 0.97. However, in spite of the euthymic phase, MMN amplitude showed a further decrease, from -1.7 to -0.9. In conclusion, using QEEG, LDAEP, and MMN can help clinicians predict a patient's bipolar state and evaluate serotonin intensity and cognitive function, enabling customized treatment. However, there are still few consistent research results; therefore, there is a need to utilize a larger sample size.

Population-based cohort study to investigate the changes in prevalence, severity profile, and treatment modalities used in Korean atopic dermatitis patients.

In this retrospective study spanning from 2002 to 2019, we analyzed data from 355,277 Korean patients diagnosed with atopic dermatitis (AD) through the National Health Insurance System. Our objective was to comprehensively analyze the trends in prevalence, severity profiles, and treatment approaches for AD in Korea over this 18-year period. Initially, AD prevalence stood at 3.88% in 2002 but notably rose to 5.03% by 2019. During the same period, while AD prevalence decreased in the 0-1-year-old group (from 34.52% to 24.83%), it remained relatively stable in the 1-11-year-old group. Conversely, the 12-19-year-old and 20 years or older age groups witnessed substantial increases in AD prevalence, climbing from 2.55 to 6.02% and 1.44% to 3.53%, respectively. Moreover, the proportion of patients classified as having moderate to severe AD grew from 30.96 to 39.78%. Surprisingly, the prescription pattern, predominantly based on corticosteroid administration, exhibited minimal change despite the rising prevalence of moderate and severe AD cases. These findings underline a persistent reliance on corticosteroid-based treatments for AD, even as the condition's severity escalates among Korean adolescents and adults. Consequently, there is a pressing need to develop novel treatment guidelines emphasizing biologics that offer enhanced safety and efficacy.

A phase II open-label randomized clinical trial of preoperative durvalumab or durvalumab plus tremelimumab in resectable head and neck squamous cell carcinoma.

PURPOSE: Clinical implications of neoadjuvant immunotherapy in patients with locally advanced but resectable head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. PATIENTS AND METHODS: Patients with resectable HNSCC were randomized to receive a single dose of preoperative durvalumab (D) with or without tremelimumab (T) before resection, followed by postoperative (chemo)radiation based on multidisciplinary discretion and 1-year D treatment. Artificial intelligence (AI)-powered spatial distribution analysis of tumor-infiltrating lymphocytes and high-dimensional profiling of circulating immune cells tracked dynamic intratumoral and systemic immune responses. RESULTS: Of the 48 patients enrolled (D: 24 patients, D+T: 24 patients), 45 underwent surgical resection per protocol (D: 21 patients; D+T: 24 patients). D+/-T had a favorable safety profile and did not delay surgery. Distant recurrence-free survival (DRFS) was significantly better in patients treated with D+T than in those treated with D monotherapy. AI-powered whole-slide image analysis demonstrated that D+T significantly reshaped the tumor microenvironment toward immune-inflamed phenotypes, in contrast to D monotherapy or cytotoxic chemotherapy. High-dimensional profiling of circulating immune cells revealed a significant expansion of T cell subsets characterized by proliferation and activation in response to D+T therapy, which was rare following D monotherapy. Importantly, expansion of specific clusters in CD8+ T cells and non-regulatory CD4+ T cells with activation and exhaustion programs was associated with prolonged DRFS in patients treated with D+T. CONCLUSIONS: Preoperative D+/-T is feasible and may benefit patients with resectable HNSCC. Distinct changes in the tumor microenvironment and circulating immune cells were induced by each treatment regimen, warranting further investigation.

Preventive effect of aripiprazole once-monthly on relapse into mood episodes in bipolar disorder: A multicenter, one-year, retrospective, mirror image study.

BACKGROUND: We conducted a one-year, retrospective, mirror-image study to investigate the clinical effectiveness and safety of aripiprazole once monthly (AOM) in patients with bipolar disorder (BD). We compared pre-treatment conditions with outcomes after 12 months of AOM treatment. METHODS: Seventy-five bipolar patients were recruited from 12 hospitals in Korea. We included 75 patients with BD who had received at least three AOM treatments from September 2019 to September 2022 and had accessible electronic medical record (EMRs) for the year before and after the baseline visit. RESULTS: The overall number of mood episodes significantly decreased from a mean of 1.5 ± 1.2 episodes pre-AOM to 0.5 ± 1.2 episodes post-AOM. Manic episodes significantly decreased from 0.8 ± 0.8 episodes pre-AOM to 0.2 ± 0.5 episodes post-AOM, and depressive episodes significantly decreased from 0.5 ± 0.8 episodes pre-AOM to 0.2 ± 0.6 episodes post-AOM (p = 0.017). Moreover, the number of psychiatric medications and pills and the proportion of patients treated with complex polypharmacy were significantly decreased post-AOM. LIMITATIONS: The small sample size was insufficient to fully represent the entire population of individuals with BD, and potential selection bias was introduced due to only including subjects who received AOM three or more times. CONCLUSION: The results of this study suggest that AOM can reduce mood episode relapse and may be clinically beneficial in the treatment of BD patients, potentially reducing issues associated with polypharmacy in some individuals.

Estimation of the Three Phases by Direct Cost of Care for Non-surviving Patients with Cancer: A National Population-based Patient-level Study.

Background: Determining the cost structure of medical care from diagnosis to the death of patients with cancer is crucial for establishing budgets to support patients with cancer. The breakdown of the cost estimation in distinct phases of survival is essential for optimizing the allocation of limited funds. Therefore, this study aims to examine the patterns of direct medical costs of cancer care associated with seven major cancer types and estimate cost thresholds to distinguish each phase based on the incurred cost. Methods: In this nationwide, population-based study, we used claims data from the National Health Insurance Service, Korea. Patients newly diagnosed with cancer since 2006 and who died in 2016-2017 were enrolled, and their use of medical services during cancer survival from at least 6 months up to 12 years was observed. The monthly cost exhibited a non-linear function with two unknown thresholds resembling a U-shape; therefore, we fitted three linear segment models. Individual costs were assessed by dividing the survival time into the initial, continuing, and terminal phases by estimated thresholds, and the average medical cost for each phase was calculated. Results: Based on survival durations of 12 years or less, the initial phase occurred within 1.1-4.8 months after diagnosis, while the terminal phase was observed in 1.4-4.7 months before death. The length of these two phases increased with the increased survival time of the patients. Medical costs in these phases ranged from $4067-7431 and $3127-6114 (US dollars), respectively, regardless of the variations in survival time. However, the average costs in the continuing phase were higher for patients with a short survival time. Conclusions: This study highlights the cost dynamics in cancer care through a breakdown of the phases of survival. It suggests that through a more refined definition of the initial and terminal phases, the average cost in these stages increases, indicating the significant implications of the findings for resource allocation and tailored financial support strategies for patients with cancer with varying prognoses.

Non-suicidal Self-injury and Quantified Electroencephalogram in Adolescents and Young Adults with Depression.

Objective: : This study investigated the association between non-suicidal self-injury (NSSI) and quantified electroencephalogram (QEEG) in patients with depression. We aimed to identify clinical features of NSSI and differences in QEEG findings. Methods: : This retrospective study used the medical records of 52 inpatients with major depressive episodes, aged from 15 to 30. The patients were categorized according to their history of NSSI. Their main diagnosis and sex were also considered. To evaluate clinical symptoms, self-reported scales were used. The absolute power and the Z-scores of various waves were included. Results: : NSSI was associated with suicidal ideations (p = 0.001) and trauma history (p = 0.014). In the binary logistic regression analysis, the Z-score of absolute alpha power was higher on the FP2 node (p = 0.029), lower on the F4 node (p = 0.029) in the NSSI group. The absolute high beta power in the NSSI group was higher on the FP2 and the F3 node, but lower on the F7 and F8 node. Patients with NSSI showed higher Z-score of the absolute delta power at the FP2 node (p = 0.044). The absolute gamma power was higher on the FP2 (p = 0.012) and the F3 node (0.043), lower on the FP1 (p = 0.019) and the F7 node (0.018) in the NSSI group. The absolute high gamma power at the FP2 (p = 0.017) and F8 nodes (p = 0.045) were higher in the NSSI group. Conclusion: : Patients with NSSI may have clinical features distinct from those of patients without NSSI. QEEG results have shown some differences, although it is less applicable due to some limitations.

Risk of Subsequent Vitiligo in Transplant Recipients With Comorbid Graft-vs-Host Disease.

Importance: Vitiligo is a multifactorial, depigmenting skin disorder characterized by selective loss of melanocytes. Large-scale studies are lacking to determine the risk of vitiligo in transplant recipients with graft-vs-host disease (GVHD). Objective: To investigate the incidence rates and risk of vitiligo in patients who had received solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT) overall and by HSCT graft type and concomitant GVHD. Design, Setting, and Participants: This population-based cohort study included data from the National Health Insurance Service database of Korea for patients aged 20 years or older who had received a transplant (SOT or HSCT) between January 2010 and December 2017, with follow-up until December 2019. A cohort of age- and sex-matched (1:5) control individuals who did not receive a transplant was included for comparison. Data were analyzed from July 2021 to December 2021. Exposure: Transplant (SOT or HSCT) and GVHD. Main Outcomes and Measures: The main outcome was risk of vitiligo, assessed using multivariable Cox proportional hazards regression analyses adjusting for potential confounding factors. Results: The study included 23 829 patients who had undergone SOT or HSCT (62.78% male; mean [SD] age, 49.58 [11.59] years) and 119 145 age- and sex-matched controls. Patients who had undergone transplant had a significantly higher risk of vitiligo compared with controls (adjusted hazard ratio [AHR], 1.73; 95% CI, 1.35-2.22). Risk of vitiligo was also slightly higher in kidney transplant recipients and liver transplant recipients compared with the controls but was highest in HSCT recipients (AHR, 12.69; 95% CI, 5.11-31.50). Patients who had received allogeneic grafts (AHR, 14.43; 95% CI, 5.61-37.15), those who had received autologous grafts (AHR, 5.71; 95% CI, 1.20-3.18), those with comorbid GVHD (AHR, 24.09; 95% CI, 9.16-63.35), and those without GVHD (AHR, 8.21; 95% CI, 3.08-21.87) had a higher risk of vitiligo compared with controls. Conclusion and Relevance: In this study, risk of vitiligo was significantly higher in transplant recipients, especially in HSCT recipients and those with allogeneic grafts or comorbid GVHD. These findings provide new insights into the association between the risk of vitiligo and transplant and GVHD. Clinicians should be aware of these risks, implementing a multidisciplinary approach for monitoring.

Aggregation of Ag nanoparticle based on surface acoustic wave for surface-enhanced Raman spectroscopy detection of dopamine.

BACKGROUND: Dopamine (DA), a vital neurotransmitter, plays a critical role in the human brain and relates to neuropsychiatric disorders such as Parkinson's disease and schizophrenia. Numerous studies have explored detection of such biomarkers through surface-enhanced Raman spectroscopy (SERS). However, most of the studies focused on SERS detection face significant challenges with plasmonic nanostructure development. Such challenges often include time-consuming processes, complex fabrication, specialized chemical labeling, poor reproducibility, and random hotspot generation. Therefore, the need for simple and rapid nanostructure development is evident in SERS. RESULTS: We propose an innovative SERS-active sensing technique for 50 nm silver nanoparticle (AgNP) clustering based on surface acoustic wave (SAW). When a 1 µL droplet of AgNP colloid is dispensed onto the SAW-propagation zone, the AgNP cluster is deposited after the droplet completely evaporates, developing plasmonic nanogaps for SERS hotspot caused by spherical AgNP aggregation. By optimizing the SAW system through the hydrophobic treatment and modulation of the operational power, the SAW-induced AgNP clustering showed densely packed AgNP within a dot-like configuration (∼2200 AgNP µm-2), effectively preventing particle welding. The characterization of 4-mercaptobenzoic acid as a probe analyte revealed that concentrations as low as 1.14 pM was detected using our SAW-SERS system under 785 nm laser excitation. Moreover, DA was detected up to 4.28 nM with a determination of 0.99 (R2). SIGNIFICANCE: This technique for AgNP clustering induced by SAW provides a rapid, in situ, label-free SERS sensing method with outstanding sensitivity and linearity. A mere act of dropping can create extensive plasmonic hotspots featuring nanogap of ∼1.5 nm. The SAW-induced AgNP clustering can serve as an ultrasensitive SERS-active substrate for diverse molecular detections, including neurotransmitter detection.

Impact of COVID-19 on ophthalmic medical access during successive waves: Demographics, disease factors, and wave locations.

BACKGROUND: The coronavirus disease (COVID-19) pandemic significantly impacted medical care, including ophthalmology. This study aimed to identify factors associated with reduced ophthalmic medical access during the pandemic. METHODS: This nationwide population-based cohort study analysed South Korean health insurance claims data from January 2019 to November 2021. Outpatient visits and surgeries for age-related macular degeneration, cataract, diabetic retinopathy, glaucoma, and retinal detachment during the two pandemic waves were compared with those in the non-pandemic period. Poisson regression was used to estimate incidence rate ratios and changes in outpatient visits and surgeries between waves concerning patient age, sex, residential location, and health insurance type. RESULTS: Outpatient visits for five eye diseases decreased in the first wave (0.733-0.985, P < 0.001). In the second wave, only outpatient visits for age-related macular degeneration, cataract, and glaucoma decreased (0.754, 0.878, and 0.874, respectively, all P < 0.001). Age-related macular degeneration, cataract, and glaucoma surgeries were significantly reduced in the first wave (0.829, P < 0.001; 0.836, P < 0.001; 0.904, P = 0.030, respectively). Age-related macular degeneration (0.852) and cataract (0.716) surgeries dropped in the second wave. Women and elderly (>65 years) patients curtailed outpatient visits and surgeries more throughout the pandemic and were less resilient during the second wave. Wave location was also related to outpatient visits and surgeries. CONCLUSIONS: The COVID-19 pandemic decreased outpatient visits and surgeries for eye diseases, with more significant impact on women, older patients, and those residing near wave locations. These findings can inform healthcare policies to minimise future pandemic impacts on healthcare delivery.

Relationship between Loudness Dependence of Auditory-evoked Potentials and Suicidality.

Objective: : Serotonin concentration is associated with suicide in patients with major depressive disorder. Loudness dependence of auditory-evoked potentials (LDAEPs), a representative neurophysiological indicator, is related to serotonin activity. Therefore, this study aimed to investigate the relationship between LDAEPs and suicidal ideation, suicide attempts, and the severity of depression. Methods: : We evaluated the scalp N1, P2, and N1/P2 LDAEPs along with standardized low-resolution brain electromagnetic tomography (sLORETA)-localized N1, P2, and N1/P2 LDAEPs of 221 patients with major depressive disorder. The demographic and clinical data of the patients, including data on suicidal ideation and previous suicide attempts, were obtained from clinical interviews and medical records. The severity of depression was assessed using the Beck Depression Inventory and Hamilton Depression Rating Scale, whereas suicidal ideation was evaluated using the Beck Scale for Suicidal Ideation (BSS). Results: : The total BSS score was associated with low N1/P2 LDAEP (p = 0.045), whereas P2 sLORETA-LDAEP was associated with lower previous suicide attempts (p = 0.043). In addition, suicide attempt was correlated with an elevated P2 left sLORETA-LDAEP (coefficient = 4.638, p = 0.038). Conclusion: : These findings suggest that suicidal ideation is associated with decreased LDAEP, whereas suicide attempt is associated with increased LDAEP.

Comparative Evaluation of Matrix Metalloproteinase-9 Immunoassay and Tear Osmolarity Measurement for Diagnosing Severity of Dry Eye Disease.

PURPOSE: To evaluate and compare the clinical efficacy of matrix metalloproteinase-9 (MMP-9) immunoassay and tear osmolarity measurement in diagnosing dry eye severity. METHODS: Dry eye disease (DED) patients underwent diagnostic tests including MMP-9 assay, tear osmolarity measurement, fluorescein tear breakup time, ocular surface staining, anesthetized Schirmer test, Ocular Surface Disease Index questionnaire, and slit-lamp examination. The dry eye parameters were compared according to positive MMP-9 status and increased tear osmolarity. The correlation between dry eye profiles and MMP-9 positivity and high tear osmolarity was also analyzed. RESULTS: Those who tested positive in MMP-9 immunoassay had significantly higher corneal fluorescein staining score and worse DED severity than those who tested negative. The intensity of MMP-9 positivity showed positive correlation with the corneal staining score and DED severity. However, DED patients with high tear osmolarity above 308 mOsm/L did not show significantly different dry eye signs and symptoms compared to those with lower tear osmolarity values. Tear osmolarity was associated with ocular surface staining score in severe DED patients. CONCLUSIONS: MMP-9 positivity was associated with ocular surface staining and worse dry eye severity. Therefore, it may be used as a useful indicator of disease severity in conjunction to other diagnostic tests.

Clinical Practice Guidelines for Oropharyngeal Dysphagia.

OBJECTIVE: Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one's physical health and quality of life as its severity increases. Therefore, proper assessment and management of dysphagia are critical for improving swallowing function and preventing complications. Thus a guideline was developed to provide evidence-based recommendations for assessment and management in patients with dysphagia. METHODS: Nineteen key questions on dysphagia were developed. These questions dealt with various aspects of problems related to dysphagia, including assessment, management, and complications. A literature search for relevant articles was conducted using Pubmed, Embase, the Cochrane Library, and one domestic database of KoreaMed, until April 2021. The level of evidence and recommendation grade were established according to the Grading of Recommendation Assessment, Development and Evaluation methodology. RESULTS: Early screening and assessment of videofluoroscopic swallowing were recommended for assessing the presence of dysphagia. Therapeutic methods, such as tongue and pharyngeal muscle strengthening exercises and neuromuscular electrical stimulation with swallowing therapy, were effective in improving swallowing function and quality of life in patients with dysphagia. Nutritional intervention and an oral care program were also recommended. CONCLUSION: This guideline presents recommendations for the assessment and management of patients with oropharyngeal dysphagia, including rehabilitative strategies.

Optic Nerve Head Morphology is Associated with the Initial Location of Structural Progression in Early Open Angle Glaucoma.

PRCIS: Glaucoma eyes with a small cup-to-disk ratio (CDR) tend to show retinal nerve fiber layer progression earlier than ganglion cell-inner plexiform layer progression. PURPOSE: To investigate the effects of clinical variables on the temporal relationship between macular ganglion cell-inner plexiform layer (mGCIPL) loss and peripapillary retinal nerve fiber layer (pRNFL) loss in glaucoma. METHODS: This retrospective observational study used medical records of patients diagnosed with open angle glaucoma. Structural change was determined using guided progression analysis software of Cirrus optical coherence tomography. Based on the time of detection of pRNFL and mGCIPL changes, eyes showing progressive layer loss were categorized into the pRNFL-first and mGCIPL-first groups. The association between sites of layer thinning and clinical variables such as major retinal arterial angles and several optic disk measurements, including disk area, average CDR, and vertical CDR, were analyzed. RESULTS: A total of 282 eyes were included in the study, of which 104 showed structural progression either in the mGCIPL or pRNFL. Out of these, 49 eyes showed the first progression in pRNFL, while 37 eyes showed the first progression in mGCIPL. The minimum mGCIPL thickness, pRNFL thickness, average CDR, vertical CDR, and location of progression were significantly different between the 2 groups ( P =0.041, P =0.034, P =0.015, P <0.001, and P <0.001, respectively). In multivariate analysis, average CDR and vertical CDR were significantly associated with the progression site ( P =0.033 and P =0.006, respectively). The structural changes in the inferoinferior area and the superior vulnerability zone were significantly associated with RNFL-first progression ( P <0.001 for both). CONCLUSION: The location of layer loss and CDR are related to the layer where loss is first detected (either pRNFL or mGCIPL) in open angle glaucoma.

Surgical margin status and role of adjuvant therapy in human papillomavirus-positive oropharyngeal cancer.

BACKGROUND: We analyzed the difference in treatment results according to safety margin range and studied the role of adjuvant therapy in patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: A total of 279 patients with HPV+ OPSCC were included in this study. RESULTS: Surgical margin and T classification were significant prognostic factors related to death. The difference in locoregional recurrence was analyzed by dividing the safety margin into groups of <1, 1-5, and >5 mm. There was no significant difference in local-regional recurrence for T1-T2 lesions between the three groups. Adjuvant therapy can significantly reduce disease recurrence in HPV+ OPSCC patients with risk factors. CONCLUSIONS: In T1-T2 lesions without other risk factors, even with a safety margin ≥1 mm, adjuvant therapy can potentially be omitted. Adjuvant therapy can significantly reduce disease recurrence in HPV+ OPSCC patients with risk factors.