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Hypothesis Solid lipid nanoparticles (SLNs), co-encapsulating superparamagnetic iron oxide nanoparticles and sorafenib, have been exploited for magnetic-guided drug delivery to the liver. Two different magnetic configurations, both comprising two small magnets, were under-skin implanted to investigate the effect of the magnetic field topology on the magnetic SLNP accumulation in liver tissues. A preliminary simulation analysis was performed to predict the magnetic field topography for each tested configuration. Experiments SLNs were prepared using a hot homogenization approach and characterized using complementary techniques. Their in vitro biological behavior was assessed in HepG-2 liver cancer cells; wild-type mice were used for the in vivo study. The magnet configuration that resulted in a higher magnetic targeting efficiency was investigated by evaluating the iron content in homogenated murine liver tissues. Findings SLNs, characterized by an average size smaller than 200 nm, retained their superparamagnetic behavior and relevant molecular resonance imaging properties as negative contrast agents. The evaluation of iron accumulation in the liver tissues was consistent with the magnetic induction profile of each magnet configuration, concurring with the results predicted by simulation analysis and obtained by measurements in living mice.

Background: A long-term follow-up study in patients with amnestic mild cognitive impairment (aMCI) is needed to elucidate the association between regional brain volume and psychopathological mechanisms of Alzheimer’s disease with psychosis (AD + P). Objective: The purpose of this study was to investigate the effect of the thickness of the angular cingulate cortex (ACC) on the risk of AD + P conversion in patients with aMCI. Methods: This was a hospital-based prospective longitudinal study including 174 patients with aMCI. The main outcome measure was time-to-progression from aMCI to AD + P. Subregions of the ACC (rostral ACC, rACC; caudal ACC, cACC) and hippocampus (HC) were measured as regions of interest with magnetic resonance imaging and the Freesurfer analysis at baseline. Survival analysis with time to incident AD + P as an event variable was calculated with Cox proportional hazards models using the subregions of the ACC and HC as a continuous variable. Results: Cox proportional hazard analyses showed that the risk of AD + P was associated with sub-regional ACC thickness but not HC volume: reduced cortical thickness of the left cACC (HR [95%CI], 0.224 [0.087–0.575], p = 0.002), right cACC (HR [95%CI], 0.318 [0.132–0.768], p = 0.011). This association of the cACC with the risk of AD also remained significant when adjusted for HC volume. Conclusion: We found that reduced cortical thickness of the cACC is a predictor of aMCI conversion to AD + P, independent of HC, suggesting that the ACC plays a vital role in the underlying pathogenesis of AD + P.

Objective: This study was designed to develop and prospectively validate a machine learning based algorithm that could predict patient response to the most common biologic drug classes used in the management of psoriasis patients. This type of tool would allow clinicians to have greater confidence that a given patient will respond to a specific drug class, which could lead to improved health outcomes and reduced wasted healthcare spend. Methods: Patients were enrolled into one of two observational studies (STAMP studies) where dermal biomarker patches (DBPs) were applied at baseline prior to drug exposure, followed by clinical evaluations at 12 weeks after exposure. PASI measurements were made at baseline and 12 weeks to evaluate clinical response to a clinical phenotype. Responders were defined as those who reached PASI75 at 12 weeks. The transcriptomes obtained from the DBPs were sequenced and analyzed to derive and/or validate classifiers for each biologic class, which were then combined to yield predictive responses for all three biologic drug classes (IL-23i, IL-17i, and TNFai). Results: A total of 242 psoriasis patients were enrolled in these studies, including 118 patients (49.6%) treated with IL-23i, 79 patients (33.2%) treated with IL-17i, 35 patients (14.7%) treated with TNFai, and 6 patients (2.5%) treated with IL-12/23i. The IL-23i predictive classifier was developed from the earlier enrolled patients and independently validated with the latter enrolled patients. IL-17i and TNFai predictive classifiers were developed using publicly available datasets and independently validated with patients from the STAMP studies. In the independent validation, positive predictive values for three classifiers (IL-23i, IL-17i, and TNFai) were 93.1%, 92.3% and 85.7% respectively. Over the entire cohort, 99.5% of patients were predicted to respond to at least one drug class. Conclusion: This study demonstrates the power of using baseline dermal biomarkers and machine learning methods as applied to the prediction of psoriasis biologic prior to drug exposure. Using this test, patients, physicians, and the health care system all can benefit in distinct ways. Precision medicine can be realized for individual patients as most will likely respond to their prescribed biologic the first time. Physicians can prescribe these drugs with increased confidence, and the healthcare system will realize lower net costs as well as greatly reduced wasted spend by significantly improving initial response rates to expensive biologic therapeutics.

Background Lower gastrointestinal bleeding (LGIB) often subsides without medical intervention; however, in some cases, the bleeding does not stop and the patient’s condition worsens. Therefore, predicting severe LGIB in advance can aid treatment. This study aimed to evaluate variables related to mortality from LGIB and propose a scoring system. Methods In this retrospective study, we reviewed the medical records of patients who visited the emergency room with hematochezia between January 2016 and December 2020. Through regression analysis of comorbidities, medications, vital signs, laboratory investigations, and duration of hospital stay, variables related to LGIB-related mortality were evaluated. A scoring system was developed and the appropriateness with an area under the receiver operating characteristics curve (AUROC) was evaluated and compared with other existing models. Results A total of 932 patients were hospitalized for LGIB. Variables associated with LGIB-related mortality were the presence of cancer, heart rate > 100 beats/min, blood urea nitrogen level ≥ 30 mg/dL, an international normalized ratio > 1.50, and albumin level ≤ 3.0 g/dL. The AUROCs of the models CNUH-4 and CNUH-5 were 0.890 (p p Conclusions The model developed for predicting the risk of LGIB-related mortality is simple and easy to apply clinically. The AUROC of the model was better than that of the existing models.

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that exhibit multiple extraglycemic effects. However, there are conflicting results regarding the effects of SGLT2 inhibition on energy expenditure and thermogenesis. Therefore, we investigated the effect of ipragliflozin (a selective SGLT2 inhibitor) on energy metabolism.Methods: Six-week-old male 129S6/Sv mice with a high propensity for adipose tissue browning were randomly assigned to three groups: normal chow control, 60% high-fat diet (HFD)-fed control, and 60% HFD-fed ipragliflozin-treated groups. The administration of diet and medication was continued for 16 weeks.Results: The HFD-fed mice became obese and developed hepatic steatosis and adipose tissue hypertrophy, but their random glucose levels were within the normal ranges; these features are similar to the metabolic features of a prediabetic condition. Ipragliflozin treatment markedly attenuated HFD-induced hepatic steatosis and reduced the size of hypertrophied adipocytes to that of smaller adipocytes. In the ipragliflozin treatment group, uncoupling protein 1 (Ucp1) and other thermogenesis-related genes were significantly upregulated in the visceral and subcutaneous adipose tissue, and fatty acid oxidation was increased in the brown adipose tissue. These effects were associated with a significant reduction in the insulin-to-glucagon ratio and the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver and adipose tissue.Conclusion: SGLT2 inhibition by ipragliflozin showed beneficial metabolic effects in 129S6/Sv mice with HFD-induced obesity that mimics prediabetic conditions. Our data suggest that SGLT2 inhibitors, through their upregulation of energy expenditure, may have therapeutic potential in prediabetic obesity.

Background/Aims: Relatively little data are available on how the response to the coronavirus disease 2019 (COVID-19) pandemic has affected treatment outcomes in patients receiving chemotherapy for lymphoma or multiple myeloma. We aimed to determine the effect of COVID-19 countermeasures on treatment outcomes in this patient population.Methods: We retrospectively analyzed data on patients treated for lymphoma or multiple myeloma in two tertiary hospitals in Seoul. Patients were divided into two groups: group 1 included patients who received chemotherapy between September and December 2019 (the control period), and group 2 included patients who received chemotherapy between September and December 2020 (the study period). Countermeasures to COVID-19 were applied to the patients in group 2. The countermeasures implemented included mask wearing and regular handwashing at home and in hospital; COVID-19 risk assessments on all hospital visitors; and pre-emptive COVID-19 screening for all newly hospitalized patients and their resident guardians.Results: No differences in treatment outcomes, including treatment response, incidence and duration of neutropenia or neutropenic fever, delays in chemotherapy, or number of deaths during chemotherapy, were observed between the g roups. None of the patients in group 2 tested positive for COVID-19, and there were no COVID-19-related deaths during the study period.Conclusions: Countermeasures to COVID-19 did not affect treatment outcomes in patients receiving chemotherapy for lymphoma or multiple myeloma. Data on the effect of countermeasures to COVID-19 on treatment outcomes should continue to be analyzed to ensure that treatment outcomes are not adversely affected.

OBJECTIVE We investigated (1) the associations of pre-stroke aspirin use with thrombus burden, infarct volume, hemorrhagic transformation, early neurological deterioration (END), and functional outcome, and (2) whether stroke subtypes modify these associations in first-ever ischemic stroke. METHODS This multicenter magnetic resonance imaging (MRI)-based study included 5,700 consecutive patients with acute first-ever ischemic stroke, who did not undergo intravenous thrombolysis or endovascular thrombectomy, from May 2011 through February 2014. Propensity score-based augmented inverse probability weighting was performed to estimate adjusted effects of pre-stroke aspirin use. RESULTS The mean age was 67 years (41% women), and 15.9% (n = 907) were taking aspirin before stroke. Pre-stroke aspirin use (vs nonuse) was significantly related to a reduced infarct volume (by 30%), particularly in large artery atherosclerosis stroke (by 45%). In cardioembolic stroke, pre-stroke aspirin use was associated with a ~50% lower incidence of END (adjusted difference = -5.4%, 95% confidence interval [CI] = -8.9 to -1.9). Thus, pre-stroke aspirin use was associated with ~30% higher likelihood of favorable outcome (3-month modified Rankin Scale score

The clinical efficacy of local ablative treatment for oligometastasis is widely accepted in most cancers. However, due to limited data, this has not been the case for hepatocellular carcinoma (HCC). Here, we report a case of pulmonary oligometastasis of a huge HCC that was treated by multimodality with liver-directed concurrent chemoradiotherapy (CCRT) plus subsequent resection of the primary lesion and local ablative radiotherapy (RT) for subsequent lung oligometastatic lesions. In this patient, liver-directed CCRT induced significant tumor shrinkage with compensatory hypertrophy of the non-tumor liver, followed by curative resection. Surgical resection of the first and second pulmonary metastatic lesions as well as local ablative RT of the third lesion achieved complete tumor regression, which led to long-term survival of 6 years. Therefore, the active use of local ablative RT requires full consideration in cases of oligometastatic HCC.

Background and ObjectivesWe evaluated the association between admission glycated hemoglobin (HbA1c) and subsequent risk of composite vascular events, including stroke, myocardial infarction (MI), and vascular death, in patients with acute ischemic stroke and diabetes.MethodsPatients who had a TIA or an acute ischemic stroke within 7 days of symptom onset and diabetes were included in a retrospective cohort design using the stroke registry of the Clinical Research Center for Stroke in Korea. The association between admission HbA1c and composite vascular events, including stroke, MI, and vascular death, during 1-year follow-up was estimated using the Fine-Gray model. The risk of composite vascular events according to the ischemic stroke subtype was explored using fractional polynomial and linear-quadratic models.ResultsOf the 18,567 patients, 1,437 developed composite vascular events during follow-up. In multivariable analysis using HbA1c as a categorical variable, the risk significantly increased at a threshold of 6.8%–7.0%. The influence of admission HbA1c level on the risk of composite vascular events was pronounced particularly among those in whom fasting glucose at admission was ≤130 mg/dL. The optimal ranges of HbA1c associated with minimal risks for composite vascular events were lowest for the small vessel occlusion subtype (6.6 [95% confidence internal [CI], 6.3–6.9]) compared to the large artery atherosclerosis (7.3 [95% CI, 6.8–7.9]) or the cardioembolic subtype (7.4 [95% CI, 6.3–8.5]).DicussionIn patients with ischemic stroke and diabetes, the risks of composite vascular events were significantly associated with admission HbA1c. The optimal range of admission HbA1c was below 6.8%–7.0% and differed according to the ischemic stroke subtype.

OBJECTIVES We investigated awakening time and characteristics of awakening compared nonawakening and factors contributing to poor neurologic outcomes in out-of-hospital cardiac arrest survivors in no withdrawal of life-sustaining therapy settings. DESIGN Retrospective analysis of the Korean Hypothermia Network Pro registry. SETTING Multicenter ICU. PATIENTS Adult (≥ 18 yr) comatose out-of-hospital cardiac arrest survivors who underwent targeted temperature management at 33-36°C between October 2015 and December 2018. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We measured the time from the end of rewarming to awakening, defined as a total Glasgow Coma Scale score greater than or equal to 9 or Glasgow Coma Scale motor score equals to 6. The primary outcome was awakening time. The secondary outcome was 6-month neurologic outcomes (poor outcome: Cerebral Performance Category 3-5). Among 1,145 out-of-hospital cardiac arrest survivors, 477 patients (41.7%) regained consciousness 30 hours (6-71 hr) later, and 116 patients (24.3%) awakened late (72 hr after the end of rewarming). Young age, witnessed arrest, shockable rhythm, cardiac etiology, shorter time to return of spontaneous circulation, lower serum lactate level, absence of seizures, and multisedative requirement were associated with awakening. Of the 477 who woke up, 74 (15.5%) had poor neurologic outcomes. Older age, liver cirrhosis, nonshockable rhythm, noncardiac etiology, a higher Sequential Organ Failure Assessment score, and higher serum lactate levels were associated with poor neurologic outcomes. Late awakeners were more common in the poor than in the good neurologic outcome group (38/74 [51.4%] vs 78/403 [19.4%]; p < 0.001). The awakening time (odds ratio, 1.005; 95% CIs, 1.003-1.008) and late awakening (odds ratio, 3.194; 95% CIs, 1.776-5.746) were independently associated with poor neurologic outcomes. CONCLUSIONS Late awakening after out-of-hospital cardiac arrest was common in no withdrawal of life-sustaining therapy settings and the probability of awakening decreased over time.

Background This case report presents a case of Vulvar Crohn’s disease (VCD) in an adolescent, that is an uncommon manifestation of Crohn’s disease (CD) without gastrointestinal symptoms. Before treating CD itself with proper medication, vulvar abscess continued to recur without improvement. Case presentation We report the case of an 18-year-old woman with VCD. After treatment with azathioprine 50 mg daily and mesalazine 1 g three times daily, vulvar lesions resolved after 6 weeks. We collected electronic medical data on patient characteristics, and evaluated findings of physical examinations, pelvic MRI, and biopsy specimen obtained from gastroduodenoscopy/colonoscopy. Conclusions VCD is a rare manifestation of CD that may be misdiagnosed in the absence of gastrointestinal symptoms leading to delayed treatment. If a patient has an unexplained vulvar inflammatory lesion and with repeated failed surgical treatment, gynecologists should consider the possibility of a VCD.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

Paradoxical reactions to tuberculosis (TB) treatment are characterized by an initial improvement of the clinical symptoms followed by clinical or radiological deterioration of existing tuberculous lesions, or by development of new lesions. Intestinal perforation in gastrointestinal TB can occur as a paradoxical reaction to antitubercular therapy. A 55-year-old man visited the outpatient department with lower abdominal pain and weight loss. He was diagnosed with intestinal TB and started antitubercular therapy. After 3 months of antitubercular therapy, a colonoscopy revealed improvement of the disease. Three days after the colonoscopy, the patient visited the emergency room complaining of abdominal pain. Abdominal computed tomography revealed extraluminal air-filled spaces in the pelvic cavity. We diagnosed a small bowel perforation and performed an emergency laparotomy and a right hemicolectomy with small bowel resection. This report describes the case of intestinal perforation presenting as a paradoxical reaction to antitubercular and provides a brief literature review.

BackgroundNo study has thoroughly compared the effectiveness of combined antiplatelet treatments (other than clopidogrel–aspirin) versus clopidogrel–aspirin or aspirin alone for early secondary prevention in acute ischaemic stroke.MethodsWe identified patients with acute, minor, non-cardiogenic ischaemic stroke treated with aspirin alone, clopidogrel–aspirin or other combination treatment. Propensity scores considering the inverse probability of treatment weighting were used to adjust for baseline imbalances. The primary outcome was the composite of all strokes (ischaemic or haemorrhagic), myocardial infarction and all-cause mortality at 3 months.ResultsAmong 12 234 patients (male: 61.9%; age: 65.5±13 years) who met the eligibility criteria, aspirin, clopidogrel–aspirin and other combination treatments were administered in 52.2%, 42.9% and 4.9% of patients, respectively. In the crude analysis, the primary outcome event at 3 months occurred in 14.5% of the other combination group, 14.4% of the aspirin group and 13.0% of the clopidogrel–aspirin group. In the weighted Cox proportional hazards analysis, the 3-month primary outcome event occurred less frequently in the clopidogrel–aspirin group than in the other combination group (weighted HR: 0.82 (0.59–1.13)), while no association was found between the aspirin group (weighted HR: 1.04 (0.76–1.44)) or other combination group and the 3-month primary outcome.ConclusionOther combined antiplatelet treatment, compared with aspirin alone or clopidogrel–aspirin, was not associated with reduced risks of primary composite vascular events or recurrent stroke during the first 3 months after stroke. Therefore, the results suggest that other combination treatments, particularly the cilostazol-based combination, may not be effective alternatives for clopidogrel–aspirin to prevent early vascular events in patients with acute minor stroke. Further exploration in clinical trials will be needed.

Interleukin-2 (IL-2) and its α receptor in soluble form (sIL-2Rα) are considered biomarkers for cancers and immune-related diseases. Enzyme-linked immunosorbent assay is the most common method used to evaluate biomarkers in clinical practice; it is precise but time-consuming and involves complicated procedures. Here, we have developed a rapid yet accurate modality for cancer diagnosis that enables on-site evaluation of cancer markers, that is, IL-2 and sIL-2Rα, without complicated pretreatment of cancer patient-derived blood samples. Surface plasmon resonance and bioresponsive microgels conjugated with IL-2 receptors, that is, IL-2Rβ and IL-2Rγ, were utilized to measure IL-2 and sIL-2Rα levels via multivalent protein binding (MPB) between the ligands and their receptors. Our results showed that this novel method enables us to perform cancer diagnosis with a 1000-fold dilution of serum in 10 min. The advantage of MPB-based cancer diagnosis originates from its great selectivity for a target molecule and tolerance to a myriad of nonspecific substances in serum, which allows on-site clinical evaluation. Importantly, our finding implies that MPB-based cancer diagnosis provides a new paradigm not only for improving cancer treatment but also for evaluating a target molecule in unpurified and complex solutions such as blood.

Background and purpose A new approach was proposed to score the Montreal Cognitive Assessment (MoCA) index scores for 6 cognitive domains: orientation (OIS), attention (AIS), language (LIS), visuospatial function (VIS), memory (MIS), and executive function (EIS). This study investigated whether the MoCA index scores represent the functions of each cognitive domain by examining the correlations with the corresponding cognitive domain scores derived from conventional neuropsychological tests included in the Seoul Neuropsychological Screening Battery, 2nd Edition (SNSB-II). Methods The participants were 104 amnestic mild cognitive impairment (aMCI), 74 vascular mild cognitive impairment (VaMCI), 73 dementia of the Alzheimer's type (DAT), and 41 vascular dementia (VaD) patients. All participants were administered the Korean-MoCA and SNSB-II. Results Like the MoCA total score, the MoCA-OIS, MoCA-VIS, and MoCA-MIS showed differences between aMCI and AD groups and between VaMCI and VaD groups. The MoCA-AIS, MoCA-LIS, and MoCA-EIS showed significant differences between VaMCI and VaD groups, but no difference between aMCI and DAT groups. In the aMCI and VaMCI groups, all index scores of the MoCA showed significant correlations with the corresponding cognitive domain scores of the SNSB-II. Except for MoCA-MIS, the MoCA-AIS, MoCA-LIS, MoCA-VIS, and MoCA-EIS also showed significant correlations with the corresponding domain scores of the SNSB-II in the DAT and VaD groups. Conclusions These results indicate that all MoCA index scores, except for MoCA-MIS, which does not reflect the severity of memory impairment in dementia patients, provide highly valid information on the function of each cognitive domain in patients with mild cognitive impairment and dementia.

PURPOSE: Patients with triple negative breast cancer (TNBC) who do not achieve pathological complete response (pCR) following neoadjuvant chemotherapy have a high risk of recurrence and death. Molecular characterization may identify patients unlikely to achieve pCR. This neoadjuvant trial was conducted to determine the pCR rate with docetaxel and carboplatin, and to identify molecular alterations and/or immune gene signatures predicting pCR. EXPERIMENTAL DESIGN: Patients with clinical stages II/III TNBC received 6 cycles of docetaxel and carboplatin. The primary objective was to determine if neoadjuvant docetaxel and carboplatin would increase the pCR rate in TNBC compared to historical expectations. We performed whole exome sequencing (WES) and immune profiling on pre-treatment tumor samples to identify alterations that may predict pCR. Thirteen matching on-treatment samples were also analyzed to assess changes in molecular profiles. RESULTS: Fifty-eight of 127 (45.7%) patients achieved pCR. There was a non-significant trend towards higher mutation burden for patients with residual cancer burden (RCB) 0/I versus RCB II/III (median 80, versus 68 variants, p 0.88). TP53 was the most frequently mutated gene, observed in 85.7% of tumors. EGFR, RB1, RAD51AP2, SDK2, L1CAM, KPRP, PCDHA1, CACNA1S, CFAP58, COL22A1, and COL4A5 mutations were observed almost exclusively in pre-treatment samples from patients who achieved pCR. Seven mutations in PCDHA1 were observed in pre-treatment samples from patients who did not achieve pCR. Several immune gene signatures including IDO1, PD-L1, interferon gamma signaling, CTLA4, cytotoxicity, tumor inflammation signature, inflammatory chemokines, cytotoxic cells, lymphoid, PD-L2, exhausted CD8, Tregs, and immunoproteosome were upregulated in pre-treatment samples from patients who achieved pCR. CONCLUSIONS: Neoadjuvant docetaxel and carboplatin resulted in a pCR of 45.7%. WES and immune profiling differentiated patients with and without pCR. TRIAL REGISTRATION: Clinical trial information: NCT02124902, Registered 24 April 2014, & NCT02547987, Registered 10 September 2015.

Background Post-stroke cognitive impairment (PSCI) occurs in approximately half of people in the first year after stroke. Infarct location is a potential determinant of PSCI, but a comprehensive map of strategic infarct locations predictive of PSCI is unavailable. We aimed to identify infarct locations most strongly predictive of PSCI after acute ischaemic stroke and use this information to develop a prediction model. Methods In this large-scale multicohort lesion-symptom mapping study, we pooled and harmonised individual patient data from 12 cohorts through the Meta-analyses on Strategic Lesion Locations for Vascular Cognitive Impairment using Lesion-Symptom Mapping (Meta VCI Map) consortium. The identified cohorts (as of Jan 1, 2019) comprised patients with acute symptomatic infarcts on CT or MRI (with available infarct segmentations) and a cognitive assessment up to 15 months after acute ischaemic stroke onset. PSCI was defined as performance lower than the fifth percentile of local normative data, on at least one cognitive domain on a multidomain neuropsychological assessment or on the Montreal Cognitive Assessment. Voxel-based lesion-symptom mapping (VLSM) was used to calculate voxel-wise odds ratios (ORs) for PSCI that were mapped onto a three-dimensional brain template to visualise PSCI risk per location. For the prediction model of PSCI risk, a location impact score on a 5-point scale was derived from the VLSM results on the basis of the mean voxel-wise coefficient (ln[OR]) within each patient's infarct. We did combined internal-external validation by leave-one-cohort-out cross-validation for all 12 cohorts using logistic regression. Predictive performance of a univariable model with only the location impact score was compared with a multivariable model with addition of other clinical PSCI predictors (age, sex, education, time interval between stroke onset and cognitive assessment, history of stroke, and total infarct volume). Testing of visual ratings was done by three clinicians, and accuracy, inter-rater reliability, and intra-rater reliability were assessed with Cohen's weighted kappa. Findings In our sample of 2950 patients (mean age 66 & middot;8 years [SD 11 & middot;6]; 1157 [39 & middot;2%] women), 1286 (43 & middot;6%) had PSCI. We achieved high lesion coverage of the brain in our analyses (86 & middot;9%). Infarcts in the left frontotemporal lobes, left thalamus, and right parietal lobe were strongly associated with PSCI (after false discovery rate correction, q20). On cross-validation, the location impact score showed good correspondence, based on visual assessment of goodness of fit, between predicted and observed risk of PSCI across cohorts after adjusting for cohort specific PSCI occurrence. Cross-validations showed that the location impact score by itself had similar performance to the combined model with other PSCI predictors, while allowing for easy visual assessment. Therefore the univariable model with only the location impact score was selected as the final model. Correspondence between visual ratings and actual location impact score (Cohen's weighted kappa: range 0 & middot;88-0 & middot;92), inter-rater agreement (0 & middot;85-0 & middot;87), and intra-rater agreement (for a single rater, 0 & middot;95) were all high. Interpretation To the best of our knowledge, this study provides the first comprehensive map of strategic infarct locations associated with risk of PSCI.A location impact score was derived from this map that robustly predicted PSCI across cohorts.Furthermore, we developed a quick and reliable visual rating scale that might in the future be applied by clinicians to identify individual patients at risk of PSCI.

Purpose To investigate the long-term progression of pericentral hydroxychloroquine retinopathy. Design Multicenter, retrospective cohort study. Participants Eighty eyes (60 with pericentral pattern) of 41 Korean patients with hydroxychloroquine retinopathy followed up for 2 years or more after drug cessation. Methods Patients were screened for hydroxychloroquine retinopathy using spectral-domain or swept-source OCT, fundus autofluorescence (FAF), and Humphrey visual field (VF) tests. Follow-up was divided into short-term (≤2 years) and subsequent periods, and progression was evaluated in each period and severity group. Retinopathy progression on OCT was defined as increased length of the ellipsoid zone defect, decreased distance from the fovea to the photoreceptor defects, or newly developed or enlarged retinal pigment epithelium defects. On FAF, progression was defined as an increase in the area of hyperautofluorescence or hypoautofluorescence. Functional progression was defined as a regression coefficient of less than 0 dB/year for mean deviation and more than 0 dB/year for pattern standard deviation, based on linear regression analysis of 3 or more VF tests. Structural and functional progression rates were calculated using the slopes of retinal thicknesses on the Early Treatment Diabetic Retinopathy Study grid and perimetric parameters over time, respectively. Main Outcome Measures Structural and functional progression of retinopathy. Results Approximately one third of eyes with early pericentral retinopathy showed limited progression during the short-term period after drug cessation, but they subsequently showed stable or improved photoreceptors. Most eyes with moderate pericentral retinopathy showed continuous progression, particularly when converted to the severe stage. Severe eyes showed progressive damage throughout the follow-up period. In all severity groups, the rates of retinal thinning decreased over time. In eyes with pericentral retinopathy showing progression, circumferential enlargement of retinal damage was prominent in earlier stages, whereas centripetal enlargement of the ring-shaped lesion was noted in advanced stages. Functional progression, noted in 58.7% of the pericentral eyes, corresponded with structural progression. Conclusions Pericentral hydroxychloroquine retinopathy showed severity-dependent progression. Moderate pericentral retinopathy usually progressed, but centripetal progression threatening the fovea was remarkable mostly in severe retinopathy. Our results suggest that early detection of retinopathy may minimize the risk of progression to foveal involvement in pericentral retinopathy.

Background Glycemic variability is associated with the development of diabetic complications and hypoglycemia. However, the effect of sodium-glucose transporter 2 (SGLT2) inhibitors on glycemic variability is controversial. We aimed to examine the effect of dapagliflozin as an add-on therapy to insulin on the glycemic variability assessed using continuous glucose monitoring (CGM) in subjects with type 2 diabetes mellitus. Methods In this multicenter, placebo-controlled, double-blind, randomized study, 84 subjects received 10 mg of dapagliflozin (n=41) or the placebo (n=43) for 12 weeks. CGM was performed before and after treatment to compare the changes in glycemic variability measures (standard deviation [SD], mean amplitude of glycemic excursions [MAGEs]). Results At week 12, significant reductions in glycosylated hemoglobin (−0.74%±0.66% vs. 0.01%±0.65%, P

Branchial cleft cysts are the most common lateral neck mass, and usually have well-delineated cystic structures under ultrasonography. Ultrasonography and fine needle aspiration cytology is very helpful during preoperative diagnosis. However, these cysts may occur in unusual locations and have a sonographic morphology similar to malignant thyroid neoplasm. A 61-year-old woman presented with thyroid nodules, and ultrasonography revealed a 0.8-cm, hypoechoic, solid nodule with microcalcifications in the right lobe of thyroid in the lower portion. Postoperative histopathological examination revealed the 0.8-cm hypoechoic nodule to be a branchial cleft cyst. In addition, concurrent medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) were found. Herein, we present a rare case of branchial cleft cyst mimicking malignant thyroid neoplasm concurrent with medullary and PTC.

Background Direct oral anticoagulants (DOACs) have replaced vitamin K antagonists as the standard of care for stroke prevention in patients with atrial fibrillation (AF). However, DOAC prescriptions at dosages that do not adhere to labeling are common in daily practice. This analysis from the observational Global Edoxaban Treatment in routiNe clinical prActice (ETNA)-AF program focuses on edoxaban-treated patients from South Korea and Taiwan to identify patient baseline characteristics that may be associated with non-recommended dosing. Methods We report baseline data from ETNA-AF, including patient demographics, clinical characteristics, and bleeding/stroke history of patients receiving recommended or non-recommended edoxaban dosing. Results A total of 2677 patients were enrolled. Among 1543 patients who did not meet dose-reduction criteria, 1033 (66.9%) were prescribed the recommended 60-mg dose, and 510 (33.1%) were prescribed the non-recommended 30-mg dose. Among 1134 patients meeting ≥1 of the dose-reduction criteria, 863 (76.1%) were prescribed the recommended 30-mg dose; 271 (23.9%) were prescribed the nonrecommended 60-mg dose. Compared with the recommended 60-mg group, the nonrecommended 30-mg group had a higher proportion of patients aged ≥75 years, higher stroke and bleeding risks, and a history of major bleeding. The non-recommended 60-mg group had a lower proportion of patients aged ≥75 years, a higher history of stroke, and lower history of bleeding compared with the recommended 30-mg group. Conclusion The baseline data from ETNA-AF indicate that physicians take patient clinical characteristics (e.g., bleeding risks) into consideration when deviating from the dosing recommendation per label.

Mesenchymal stromal cells (MSCs) are considered as a promising therapeutic tool for liver fibrosis, a main feature of chronic liver disease. Because small extracellular vesicles (sEVs) harboring a variety of proteins and RNAs are known to have similar functions with their derived cells, MSC-derived sEVs carry out the regenerative capacities of MSCs. Human tonsil-derived MSCs (T-MSCs) are reported as a novel source of MSCs, but their effects on liver fibrosis remain unclear. In the present study, we investigated the effects of T-MSC-derived sEVs on liver fibrosis. The expression of profibrotic genes decreased in human primary hepatic stellate cells (pHSCs) co-cultured with T-MSCs. Treatment of T-MSC-sEVs inactivated human and mouse pHSCs. Administration of T-MSC-sEVs ameliorated hepatic injuries and fibrosis in chronically damaged liver induced by carbon tetrachloride (CCl4). miR-486-5p highly enriched in T-MSC-sEVs targeting the hedgehog receptor, smoothened (Smo), was upregulated, whereas Smo and Gli2, the hedgehog target gene, were downregulated in pHSCs and liver tissues treated with T-MSC-sEVs or miR-486-5p mimic, indicating that sEV-miR-486 inactivates HSCs by suppressing hedgehog signaling. Our results showed that T-MSCs attenuate HSC activation and liver fibrosis by delivering sEVs, and miR-486 in the sEVs inactivates hedgehog signaling, suggesting that T-MSCs and their sEVs are novel anti-fibrotic therapeutics for treating chronic liver disease.

Background/aims Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus (HBV). Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (p = 0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (p = 0.75 and p = 0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (Date: September 10, 2013).

International audience; After an ischemic stroke with evidence of atherosclerosis, lipid-lowering treatment with a target LDL cholesterol of

The prevalence of non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, is rapidly increasing in Korean populations and is estimated to reach 39% among Korean adults. NAFLD is one of the strongest risk factors of type 2 diabetes mellitus (T2DM), and the presence of NAFLD in T2DM patients is associated with a worse natural course of diabetic complications. The gold standard for diagnosing NAFLD is liver biopsy, which involves sampling error, high cost, and other disadvantages related to its invasive nature. We summarize non-invasive diagnostic NAFLD algorithms including biomarkers and four major imaging tools (ultrasonography, computed tomography, magnetic resonance imaging, and liver FibroScanⓇ) for diagnosing NAFLD including hepatic fibrosis. To prevent NASH (nonalcoholic steatohepatitis) or liver fibrosis, a combination of lifestyle modification with a low caloric diet and exercise, anti-diabetic agents, and non-anti-diabetic agents should be applied.

BACKGROUND Children with adolescent idiopathic scoliosis (AIS) have reduced quality of life related to poor self-image, perhaps because of cosmetic concerns. However, there has not been a large-database epidemiologic study on the association between psychiatric disorders and scoliosis. QUESTIONS/PURPOSES Using the Korean National Health Insurance database, we asked: (1) How common are psychiatric disorders among children with AIS? (2) After controlling for gender, age, insurance type, and residential district, are psychiatric disorders more common among children with AIS than among age-matched controls? METHODS A retrospective analysis was conducted using sample datasets from the Health Insurance Review and Assessment Service from 2012 to 2016, which is a 10% randomly extracted sample of total inpatients and outpatients each year. The mean number of total patients in each dataset was 1,047,603 ± 34,534. The mean number of children with AIS was 7409 ± 158 for each year. The age criteria was 10 to 19 years for the matching. Mood disorders, anxiety disorders, and behavioral disorders were selected as disorders possibly associated with AIS. We identified children with AIS who had any of the disorders above, and we obtained the prevalence of these disorders based on diagnostic codes. As an exploratory analysis, clinically meaningful variables were selected among the available codes in the dataset, and a univariable logistic regression test was performed for each variable. A multivariable logistic regression test with advanced variables was performed to identify the adjusted odds ratios of psychiatric disorders in children with AIS. RESULTS The median (range) prevalence of psychiatric disorders in children with AIS from 2012 to 2016 was 7% (6% to 7%). Compared with children who did not have AIS, and after controlling for gender, age, insurance type, and residential district, children with AIS were more likely to have psychiatric disorders in all 5 years. The adjusted ORs of psychiatric disorders in children with AIS compared with children who did not have AIS ranged from 1.47 to 1.74 (2012: OR 1.60 [95% CI 1.46 to 1.75]; p < 0.001; 2013: OR 1.73 [95% CI 1.58 to 1.89]; p < 0.001; 2014: OR 1.74 [95% CI 1.59 to 1.91]; p < 0.001; 2015: OR 1.71 [95% CI 1.56 to 1.88]; p < 0.001; 2016: OR 1.47 [95% CI 1.33 to 1.62]; p < 0.001). CONCLUSION Considering the higher prevalence of psychiatric disorders in children with AIS compared with children who did not have AIS, children with AIS and their parents should be counseled about the increased risk of deteriorating mental health of the patients, and surgeons should provide early referral to pediatric psychiatrists. Further studies should investigate the effect of the factors related to AIS, such as curve type, Cobb angle, and treatment modality. LEVEL OF EVIDENCE Level III, prognostic study.

In the immune oncology era, the clinical efficacy of immune checkpoint inhibitors (ICIs) against most solid cancers is well known. In hepatocellular carcinoma, the recent success of combination therapy with targeting agents has accelerated the search for novel combination strategies. Radiotherapy (RT), an attractive modality, can be combined with ICIs, which act as strong modulators of the tumor immune microenvironment. Herein, we discuss immune modulation caused by radiation and the current trials of RT-ICI combination treatment as well as future perspectives.

Background/Aim: This study aimed to establish the real-world effectiveness and safety of grazoprevir/elbasvir (EBR/GZR) therapy in South Korea. Methods: A total of 242 patients with chronic hepatitis C virus (HCV) genotype 1 or 4 infection who started EBR/GZR were consecutively enrolled from seven tertiary hospitals. Retrospective analysis of the fractions of patients that achieved sustained virological response (SVR) was performed, and the incidence of adverse events was noted. Results: The mean age of enrolled patients was 59.0 ± 12.6 years and 47.5% were males. Patients with HCV genotype 1b accounted for 93.8% (n = 227), and patients with HCV of unspecified genotype 1 accounted for 5.8% (n = 14). Hypertension was the most common comorbid disease (29.8%) followed by diabetes (22.7%) and chronic kidney disease (CKD, 12.4%). SVR rates of treatment-naive and treatment-experienced patients were 85.5% (182/213) and 93.1% (27/29), respectively, in the intention-to-treat analyses, whereas in the per-protocol analyses, those were 97.8% (179/183) and 100% (28/28), respectively. Fewer patients with HCV genotype 1 of unspecified subtype achieved SVR (81.8%, n = 11) compared to the patients with SVR infected with genotype 1b (99%, n = 198, p < 0.001). All patients with CKD showed SVR. Itching (12%) and dyspepsia (4.1%) were common adverse events. Of the four patients who discontinued the antiviral therapy, one experienced mild fatigue but neither treatment withdrawal was because of an adverse event. Conclusions: EBR/GZR showed high real-world effectiveness and safety in Korean patients with chronic HCV infection regardless of the previous antiviral treatment, liver cirrhosis, or CKD status.

Multiple myeloma is a malignant cancer of plasma cells. Despite recent progress with immunomodulatory drugs and proteasome inhibitors, it remains an incurable disease that requires other strategies to overcome its recurrence and non-response. Based on the high expression levels of programmed death-ligand 1 (PD-L1) in human multiple myeloma isolated from bone marrow and the murine myeloma cell lines, NS-1 and MOPC-315, we propose PD-L1 molecule as a target of anti-multiple myeloma therapy. We developed a novel anti-PD-L1 antibody containing a murine immunoglobulin G subclass 2a (IgG2a) fragment crystallizable (Fc) domain that can induce antibody-dependent cellular cytotoxicity. The newly developed anti-PD-L1 antibody showed significant antitumor effects against multiple myeloma in mice subcutaneously, intraperitoneally, or intravenously inoculated with NS-1 and MOPC-315 cells. The anti-PD-L1 effects on multiple myeloma may be related to a decrease in the immunosuppressive myeloid-derived suppressor cells (MDSCs), but there were no changes in the splenic MDSCs after combined treatment with lenalidomide and the anti-PD-L1 antibody. Interestingly, the newly developed anti-PD-L1 antibody can induce antibody-dependent cellular cytotoxicity in the myeloma cells, which differs from the existing anti-PD-L1 antibodies. Collectively, we have developed a new anti-PD-L1 antibody that binds to mouse and human PD-L1 and demonstrated the antitumor effects of the antibody in several syngeneic murine myeloma models. Thus, PD-L1 is a promising target to treat multiple myeloma, and the novel anti-PD-L1 antibody may be an effective anti-myeloma drug via antibody-dependent cellular cytotoxicity effects.

Ametropia is reported as a common ophthalmic manifestation in craniosynostosis. We retrospectively compared childhood refractive error and ocular biometric features of fibroblast growth factor receptor (FGFR)-related syndromic craniosynostosis patients with those of non-syndromic craniosynostosis and control subjects. Thirty-six eyes (18 patients) with FGFR-related syndromic craniosynostosis, 76 eyes (38 patients) with non-syndromic craniosynostosis, and 114 eyes (57 patients) of intermittent exotropes were included in the analysis. Mean age at examination was 7.82 ± 2.51 (range, 4–16) years and mean spherical equivalent was -0.09 ± 1.46 Diopter. Mean age and refractive error were not different between groups, but syndromic craniosynostosis patients had significantly longer axial length, lower corneal power, and lower lens power than other groups (p p p

Objective Even though the importance of stress-coping, there is no reliable and valid scale to measure the stress-coping behavior yet. The purpose of this study is to explore the psychometric properties of Behavioral Checklist for Coping with Stress (BCCS).Methods A total of 458 subjects including healthy subjects and patients with bipolar or depressive disorders were analyzed. The reliability and validity of BCCS were examined by Chronbach’s alpha and exploratory factor analysis using Principal Component Analysis. In order to evaluate criterion-related validity, the Pearson’s correlation analyses between factors of BCCS and relevant scales were performed.Results BCCS showed good Chronobach’s alpha (0.695–0.833) and had acceptable validity. Factor 1 and factor 4 of BCCS were negatively correlated with depression, anxiety and positivity correlated with task and problem-solving, avoidance, tension-releasing copings in common. Factor 2 and 3 were positively correlated with impulsivity, emotionality, avoidance, behavioral and verbal aggression and tension-releasing copings in common. Different from factor 2, factor 3 was positively correlated with depression, anxiety and anger-suppression.Conclusion The results of this study suggest that this BCCS might be a reliable and valid scale for measuring stress-coping behaviors. This scale could facilitate research to investigate clinical implications related to behavioral stress-coping.

Background: Pressure changes related to temperature variation during cupping may lead to dropout. This study aimed to investigate pressure changes related to temperature variations in the cup during the cupping procedure.Methods: Changes in temperature and pressure were measured for 15 minutes after the procedure was performed using the alcohol rub method with glass cups and with the addition of infrared irradiation. Changes in temperature and pressure were also measured for 15 minutes after pumping 3 times using the valve suction method, and with the addition of infrared irradiation.Results: In a comparison between the alcohol rub method with glass cups and with the addition of infrared irradiation, the negative pressure increased over time in the absence of infrared irradiation, whereas it decreased when performed with infrared irradiation p = 0.094. However, in a comparison between pumping 3 times using the valve suction method, and with the addition of infrared irradiation, the negative pressure decreased in both cases, but this was more significant with infrared irradiation p = 0.172. There was a significantly higher temperature in the glass cups (p = 0.004) and the valve cups (p = 0.001) exposed to infrared radiation, compared with no infrared irradiation.Conclusion: The reduction in negative pressure inside the cups exposed to infrared radiation was greater than without infrared irradiation. Temperature increases inside the cup can lead to the risk of dropout.

Various treatment modalities are used for head and neck cancer (HNC). This study analyzed the incidence and risks of myocardial infarction (MI) and stroke by cancer site and treatment modality in 22,737 patients newly diagnosed with HNC registered in the Korean National Health Insurance Service database in 2007–2013. An additional 68,211 patients without HNC, stroke, or MI were identified as the control group. The risks for MI (hazard ratio [HR] = 1.38, 95% confidence interval [CI] 1.24–1.53), stroke (HR = 1.48, 95% CI 1.37–1.60), and mortality (HR = 5.30, 95% CI 5.14–5.47) were significantly higher in the HNC group. Analysis by cancer site showed the risk of MI and mortality was highest in hypopharynx cancer, while the risk of stroke was highest in nasopharynx and paranasal sinus cancer. Analysis by treatment modality showed the highest risks for MI (HR = 1.88, 95% CI 1.31–2.69) and mortality (HR = 2.95, 95% CI 2.75–3.17) in HNC patients receiving chemotherapy (CT) alone, while HNC patients receiving CT with surgery had the highest risk for stroke (HR = 1.81, 95% CI 1.14–2.88). Careful attention to MI and stroke risks in HNC patients is suggested, especially those who received both CT and radiotherapy.

Background Post-stroke cognitive impairment can occur after damage to various brain regions, and cognitive deficits depend on infarct location. The Mini-Mental State Examination (MMSE) is still widely used to assess post-stroke cognition, but it has been criticized for capturing only certain cognitive deficits. Along these lines, it might be hypothesized that cognitive deficits as measured with the MMSE primarily involve certain infarct locations. Aims This comprehensive lesion-symptom mapping study aimed to determine which acute infarct locations are associated with post-stroke cognitive impairment on the MMSE. Methods We examined associations between impairment on the MMSE (Results Impairment on the MMSE was present in 420 patients (35%). Large voxel clusters in the left middle cerebral artery territory and thalamus were significantly (p 15) in the thalamus and superior temporal gyrus. In comparison, domain-specific impairments were related to various infarct patterns across both hemispheres including the left medial temporal lobe (verbal memory) and right parietal lobe (visuospatial functioning). Conclusions Our findings indicate that post-stroke cognitive impairment on the MMSE primarily relates to infarct locations in the left middle cerebral artery territory. The MMSE is apparently less sensitive to cognitive deficits that specifically relate to other locations.

Unlike appendicular motor symptoms, such as bradykinesia and rigidity, in Parkinson's disease (PD), which have already been reported to respond well to deep brain stimulation (DBS), there is limited literature on the effects of DBS on swallowing function in patients with PD. The field lacks consensus as there are conflicting reports among existing studies regarding whether swallowing function improves or declines following DBS implantation. This narrative review aims to summarize and analyze the studies published on the effect of DBS on swallowing function in patients with PD. We collated studies published up to February 2020 using a comprehensive electronic database search of PubMed, SCOPUS, EMBASE, and the Cochrane Library. Two reviewers independently assessed the studies using strict inclusion and exclusion criteria. The primary literature search yielded 529 relevant papers. After reading their titles and abstracts and assessing their eligibility based on the full-text, we finally included and reviewed 14 publications. Nine of these studies reported positive effects of DBS on swallowing function and four studies showed no significant positive results. The remaining study showed decreased swallowing function after unilateral subthalamic nucleus-DBS surgery. In conclusion, we found that DBS has the potential to improve swallowing function in patients with PD. However, high-quality evidence is lacking. To clearly elucidate the effect of DBS on swallowing function in patients with PD, high-quality randomized controlled trials should be conducted in the future.

Background Ambulatory and balance functions are important for maintaining general health in humans. Gait analysis allows clinicians and researchers to identify the parameters to be focused on when assessing balance and ambulatory functions. In this study, we performed gait analysis with pressure sensors to identify the gait-analysis parameters related to balance and ambulatory functions in hemiplegic stroke patients. Methods We retrospectively reviewed the medical records of 102 patients with hemiplegic stroke who underwent gait analysis. Correlations between various temporospatial parameters in the gait analysis and the motor and balance functions assessed using functional ambulation category, modified Barthel index, and Berg balance scale were analyzed. Results Gait speed/height and the lower-limb stance-phase time/height were the only temporal and spatial parameters, respectively, that showed a statistical correlation with motor and balance functions. Conclusions Measurements of walking speed and stance-phase time of the unaffected lower limb can allow clinicians to easily assess the ambulatory and balance functions of hemiplegic stroke patients. Rehabilitative treatment focusing on increasing gait speed and shortening the stance-phase time of the unaffected side may improve the ambulatory and balance functions in these patients.

Background/Aim: The association between preoperative ultrasound (US) echogenicity and histopathological characteristics of papillary thyroid cancer (PTC) has been rarely investigated is not well characterized. This study evaluated a relationship between the clinical characteristics of PTC, histopathological phenomena including tumor growth patterns (TGPs) and tumor fibrosis (TF), and US echogenicity. Patients and Methods: In total, 170 patients with PTC (

Retinal implants electrically stimulate surviving retinal neurons to restore vision in people blinded by outer retinal degeneration. Although the healthy retina is known to transmit a vast amount of visual information to the brain, it has not been studied whether prosthetic vision contains a similar amount of information. Here, we assessed the neural information transmitted by population responses arising in brisk transient (BT) and brisk sustained (BS) subtypes of ON and OFF retinal ganglion cells (RGCs) in the rabbit retina. To correlate the response heterogeneity and the information transmission, we first quantified the cell-to-cell heterogeneity by calculating the spike time tiling coefficient (STTC) across spiking patterns of RGCs in each type. Then, we computed the neural information encoded by the RGC population in a given type. In responses to light stimulation, spiking activities were more heterogeneous in OFF than ON RGCs (STTCAVG = 0.36, 0.45, 0.77 and 0.55 for OFF BT, OFF BS, ON BT, and ON BS, respectively). Interestingly, however, in responses to electric stimulation, both BT and BS subtypes of OFF RGCs showed remarkably homogeneous spiking patterns across cells (STTCAVG = 0.93 and 0.82 for BT and BS, respectively), whereas the two subtypes of ON RGCs showed slightly increased populational heterogeneity compared to light-evoked responses (STTCAVG = 0.71 and 0.63 for BT and BS, respectively). Consequently, the neural information encoded by the electrically-evoked responses of a population of 15 RGCs was substantially lower in the OFF than the ON pathway: OFF BT and BS cells transmit only ~23% and ~53% of the neural information transmitted by their ON counterparts. Together with previously-reported natural spiking activities in ON RGCs, the higher neural information may make ON responses more recognizable, eliciting the biased percepts of bright phosphenes.

Purpose To investigate the use of a retinal thickness deviation map generated from swept-source (SS) OCT images for hydroxychloroquine retinopathy screening. Design Retrospective cohort study. Participants This study included 1192 Korean patients with a history of hydroxychloroquine treatment: 881 patients (1723 eyes) in the discovery set and 311 patients (591 eyes) in the validation set. Patients were screened for retinal toxicity using SS OCT, fundus autofluorescence, and standard automated perimetry. Methods According to the 2016 American Academy of Ophthalmology guidelines, hydroxychloroquine retinopathy was diagnosed by the presence of abnormalities on ≥1 objective structural tests alongside corresponding visual field defects. The 12 × 9-mm2 macular volume SS OCT scan was performed, and the retinal thickness deviation map was generated automatically using the built-in software. On this map, yellow (retinal thickness, Main Outcome Measures The rate and patterns of abnormalities on the retinal thickness deviation map and sensitivity and specificity of the diagnostic criteria. Results The retinal thickness deviation map showed the following abnormal patterns in eyes with hydroxychloroquine retinopathy: pericentral (36.0%) or parafoveal (6.1%) ring, mixed-ring (34.2%), central island (13.2%), and whole macular thinning (10.5%). The criterion of ≥5 contiguous red pixels showing 1 of the 5 characteristic patterns in both eyes yielded the greatest diagnostic performance (sensitivity and specificity of 98.2% and 89.1% and of 100% and 87.5% in the discovery and validation set data, respectively). Moreover, the area of abnormal pixels on the map was correlated significantly with the mean deviation (P Conclusions The retinal thickness deviation map may facilitate the objective evaluation of hydroxychloroquine retinopathy because it does not require subjective, morphologic evaluation of the outer retinal layers. The map has the potential to enhance hydroxychloroquine retinopathy screening when used in conjunction with conventional screening methods.

AIM To evaluate the effectiveness and safety of adding either a sodium-glucose co-transporter-2 inhibitor (SGLT2i) or thiazolidinedione (TZD) in patients with type 2 diabetes (T2D) inadequately controlled with triple therapy. MATERIALS AND METHODS In this prospective, open-label, multicentre, 24-week clinical trial, we randomly assigned 119 patients with T2D who failed to achieve glycaemic control (7%

This report presents 2 cases of sinus fungus ball and describes the characteristic radiographic features of fungus ball in the maxillary sinus. Two female patients, aged 62 and 40 years, sought consultations at a dental hospital for the treatment of dental implants and tooth pain, respectively. Panoramic radiography and small field-of-view (FOV) cone-beam computed tomography (CBCT) did not provide detailed information for the radiographic diagnosis of fungus ball due to the limited images of the maxillary sinus. Additional paranasal sinus computed tomographic images showed the characteristic features of fungus ball, such as heterogeneous opacification and intralesional calcification of the maxillary sinus. The calcified materials of the fungus balls were located in the middle and superior regions of the maxillary sinus. It is necessary to use large-FOV CBCT for the detection of calcified materials in the upper maxillary sinus to confirm the diagnosis of fungus ball.

The effectiveness of pharmacological treatment on dysphagia in Parkinson’s disease (PD) is debatable. We reviewed the literature for analyzing the effect of pharmacological treatment on the improvement of dysphagia in PD patients. We searched the PubMed database for papers published before June 21, 2020, that evaluated the effect of pharmacologic treatments for improving dysphagia in patients with PD. The following inclusion criteria were applied for the selection of articles: 1) studies performed on patients with dysphagia due to PD, 2) studies where pharmacologic treatment was applied for improvement of dysphagia, and 3) those where follow-up evaluation was performed after the treatment. The primary literature search yielded 415 relevant papers. After reading their titles and abstracts and assessing their eligibility based on the full-text articles, we finally included nine studies in this review. In five previous studies, the positive effects of dopaminergic drugs on dysphagia were reported, whereas two showed no significant positive results. The remaining two studies showed equivocal results. We found that dopaminergic drugs have some potential to improve dysphagia in patients with PD. However, studies with high-quality evidence are lacking. For the clear elucidation of the effect of dopaminergic drugs on dysphagia in patients with PD, randomized controlled trials with large cohorts and detailed analyses should be conducted in the future.

Salivary gland dysfunction is a common symptom that occurs after menopause. This study was performed to investigate the mechanism of salivary gland dysfunction to confirm the relationship between ferroptosis and salivary gland dysfunction by ovariectomy. Forty-eight female rats were randomly divided into four groups (12 rats in each group). Histology, real time PCR, western blot, immunohistochemistry, electron microscopy, cytosolic iron assay, and salivary function were analyzed. Human salivary gland tissue analysis was also done. Lipogenesis and lipid deposition in the submandibular gland tissue occurred after ovariectomy. ROS generation, MDA+HAE was increased and GPX4 activity was decreased and in the OVX group compared to the CON group. Iron deposition in the submandibular gland tissue was increased in the OVX group. Submandibular gland fibrosis was increased and saliva secretion was decreased in the OVX group. In human submandibular gland analysis, lipid and iron deposition was also increased in the postmenopause group. This is the first in vivo study in which salivary gland dysfunction is associated with the ferroptosis in postmenopausal animal model. Increased lipid and iron deposition in normal submandibular gland tissues of postmenopausal women can suggest that the salivary gland dysfunction after menopause may be associated with the ferroptosis.

Congenital agenesis of the unilateral internal carotid artery is a rare anomaly. The agenesis of the internal carotid artery is associated with a higher incidence of intracranial aneurysms. This report describes a rare case of internal carotid artery agenesis associated with an aneurysm of the left superior cerebellar artery in a 52-year-old woman. The left middle cerebral artery was supplied from the vertebrobasilar system through the dilated left posterior communicating artery associated with anomalous origin of the left ophthalmic artery from the left posterior communicating artery. This report demonstrates a rare combination of left internal carotid artery agenesis with associated intracranial aneurysm and anomalous origin of the ophthalmic artery, discussion of embryogenesis, clinical significance, and imaging findings.

Introduction Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely prescribed for type 2 diabetes (T2D) and their glycemic control effects are well studied. However, information regarding the effects of switching DPP-4 inhibitors is limited, especially in older patients. Research Design and Methods We investigated whether switching from linagliptin to teneligliptin decreases blood glucose in older (≥65 years) T2D patients. In total, 164 patients with T2D who switched from linagliptin to teneligliptin for >12 weeks were included and the primary outcome was glycemic changes. Results Switching from linagliptin to teneligliptin ameliorated fasting blood glucose (148.1 ± 47.1 to 139.6 ± 43.4 mg/dL), glycated hemoglobin (HbA1c; 7.9 ± 1.3 to 7.5 ± 1.2%), and postprandial blood glucose (224.8 ± 77.4 to 205.8 ± 70.8 mg/dL) levels (all P 8.0%) and chronic kidney disease (estimated glomerular filtration rate