Assessment of the Quality of Sinus Elevation with Lateral Window Approach Procedure Videos on YouTube: A Content-quality Analysis.

Although the lateral window approach allows for greater graft material delivery and bone formation, it is more challenging and invasive, prompting keen interest among dentists to master this method. YouTube is increasingly used for medical training; however, concerns regarding the quality of instructional videos exist. This study proposes new criteria for evaluating YouTube videos on maxillary sinus elevation with the aim of establishing standards for assessing instructional content in the field. We sourced 100 maxillary sinus elevation videos from YouTube and, following exclusion criteria, analyzed 65 remaining videos. The video characteristics, content quality, and newly developed criteria were evaluated. Statistical analyses, employing ordinal logistic regression, identified the factors influencing the quality of instructional videos and evaluated the significance of our new criteria. Although video interaction and view rate exhibited positive relations to content quality, they were not significant ( P =0.818 and 0.826, respectively). Notably, videos of fair and poor quality showed a significant negative relation ( P <0.001). Audio commentary, written commentary, and descriptions of preoperative data displayed positive but statistically insignificant relationships ( P =0.088, 0.228, and 0.612, respectively). The comparison of video evaluation results based on the developed criteria with content quality scores revealed significant negative relationships for good, fair, and poor videos ( P <0.001, Exp(B)=-4.306, -7.853, -10.722, respectively). Among the various video characteristics, only image quality showed a significant relationship with content quality. Importantly, our newly developed criteria demonstrated a significant relationship with video content quality, providing valuable insights for assessing instructional videos on maxillary sinus elevation and laying the foundation for robust standards.

Clinical profile and treatment outcomes of idiopathic intracranial hypertension: a multicenter study from Korea.

BACKGROUND: Currently, there is a relative lack of detailed reports regarding clinical presentation and outcome of idiopathic intracranial hypertension in Asians. This study aims to describe the clinical features and treatment outcomes of Korean patients with idiopathic intracranial hypertension. METHODS: We prospectively recruited patients with idiopathic intracranial hypertension from one hospital and retrospectively analyzed the medical records of 11 hospitals in Korea. We collected data regarding preceding medical conditions or suspected medication exposure, headache phenotypes, other associated symptoms, detailed neuroimaging findings, treatments, and outcomes after 1-2 and 3-6 months of treatment. RESULTS: Fifty-nine (83.1% women) patients were included. The mean body mass index was 29.11 (standard deviation, 5.87) kg/m2; only 27 patients (45.8%) had a body mass index of ≥ 30 kg/m2. Fifty-one (86.4%) patients experienced headaches, patterns of which included chronic migraine (15/51 [29.4%]), episodic migraine (8/51 [15.7%]), probable migraine (4/51 [7.8%]), chronic tension-type headache (3/51 [5.9%]), episodic tension-type headache (2/51 [3.9%]), probable tension-type headache (2/51 [3.9%]), and unclassified (17/51 [33.3%]). Medication overuse headache was diagnosed in 4/51 (7.8%) patients. After 3-6 months of treatment, the intracranial pressure normalized in 8/32 (25.0%), improved in 17/32 (53.1%), no changed in 7/32 (21.9%), and worsened in none. Over the same period, headaches remitted or significantly improved by more than 50% in 24/39 patients (61.5%), improved less than 50% in 9/39 (23.1%), and persisted or worsened in 6/39 (15.4%) patients. CONCLUSION: Our findings suggest that the features of Asian patients with idiopathic intracranial hypertension may be atypical (i.e., less likely obese, less female predominance). A wide spectrum of headache phenotypes was observed. Medical treatment resulted in overall favorable short-term outcomes; however, the headaches did not improve in a small proportion of patients.

Treatment pattern and response for cluster headache in Korea: A prospective multicenter observation study.

BACKGROUND: Only limited data are available regarding the treatment status and response to cluster headache in an Asian population. Therefore, this study aimed to provide a real-world treatment pattern of cluster headache and the response rate of each treatment in an Asian population. METHODS: Patients with cluster headache were recruited between September 2016 and January 2019 from 16 hospitals in Korea. At the baseline visit, we surveyed the patients about their previous experience of cluster headache treatment, and acute and/or preventive treatments were prescribed at the physician's discretion. Treatment response was prospectively evaluated using a structured case-report form at 2 ± 2 weeks after baseline visit and reassessed after three months. RESULTS: Among 295 recruited patients, 262 experiencing active bouts were included. Only one-third of patients reported a previous experience of evidence-based treatment. At the baseline visit, oral triptans (73.4%), verapamil (68.3%), and systemic steroids (55.6%) were the three most common treatments prescribed by the investigators. Most treatments were given as combination. For acute treatment, oral triptans and oxygen were effective in 90.1% and 86.8% of the patients, respectively; for preventive treatment, evidence-based treatments, i.e. monotherapy or different combinations of verapamil, lithium, systemic steroids, and suboccipital steroid injection, helped 75.0% to 91.8% of patients. CONCLUSION: Our data provide the first prospective analysis of treatment responses in an Asian population with cluster headache. The patients responded well to treatment despite the limited availability of treatment options, and this might be attributed at least in part by combination of medications. Most patients were previously undertreated, suggesting a need to raise awareness of cluster headache among primary physicians.

Characteristics of pre-cluster symptoms in cluster headache: A cross-sectional multicentre study.

BACKGROUND: Contrary to pre-attack symptoms before an individual cluster headache attack, little is known about the pre-cluster symptoms before the onset of cluster bouts. We previously described pre-attack symptoms before cluster headache attacks. The aim of this study was to investigate characteristics of pre-cluster symptoms in patients with episodic cluster headache. METHODS: In this multicentre study, 184 patients with episodic cluster headache were recruited between October 2018 and December 2020. They were interviewed by investigators and completed a structured questionnaire. To investigate pre-cluster and pre-attack symptoms, we assessed 20 symptoms and signs using the questionnaire. RESULTS: The upcoming cluster bout was predictable in 35.3% (n = 65/184) of the patients. When present, pre-cluster symptoms occurred at a median duration of 7 days (interquartile range, 2.3-14 days) before the onset of the cluster bout. Patients with pre-cluster symptoms showed a higher proportion of women, prevalence of pre-attack symptoms and seasonal rhythmicity, frequency of cluster headache attacks per day, and total number of cluster bouts compared to patients without pre-cluster symptoms. In univariable and multivariable logistic regression analyses, female sex was associated with the predictability of pre-cluster symptoms (odds ratio = 2.297, p = 0.016). CONCLUSIONS: The upcoming cluster bout was predicted in approximately 35% of patients with episodic cluster headache, which may allow for an earlier preventive treatment and help understand the pathophysiology.

Safety and Efficacy of Otaplimastat in Patients with Acute Ischemic Stroke Requiring tPA (SAFE-TPA): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study.

OBJECTIVE: Otaplimastat is a neuroprotectant that inhibits matrix metalloprotease pathway, and reduces edema and intracerebral hemorrhage induced by recombinant tissue plasminogen activator (rtPA) in animal stroke models. We aimed to assess the safety and efficacy of otaplimastat in patients receiving rtPA. METHODS: This was a phase 2, 2-part, multicenter trial in stroke patients (19-80 years old) receiving rtPA. Intravenous otaplimastat was administered <30 minutes after rtPA. Stage 1 was a single-arm, open-label safety study in 11 patients. Otaplimastat 80 mg was administered twice daily for 3 days. Stage 2 was a randomized, double-blind, placebo-controlled study involving 69 patients, assigned (1:1:1) to otaplimastat 40 mg, otaplimastat 80 mg, or a placebo. The primary endpoint was the occurrence of parenchymal hematoma (PH) on day 1. Secondary endpoints included serious adverse events (SAEs), mortality, and modified Rankin scale (mRS) distribution at 90 days (clinicaltrials.gov identifier: NCT02787278). RESULTS: No safety issues were encountered in stage 1. The incidence of PH during stage 2 was comparable: 0 of 22 with the placebo, 0 of 22 with otaplimastat 40 mg, and 1 of 21 with the 80 mg dose. No differences in SAEs (13%, 17%, 14%) or death (8.3%, 4.2%, 4.8%) were observed among the 3 groups. Three adverse events (chills, muscle rigidity, hepatotoxicity) were judged to be related to otaplimastat. INTERPRETATION: Intravenous otaplimastat adjunctive therapy in patients receiving rtPA is feasible and generally safe. The functional efficacy of otaplimastat needs to be investigated with further large trials. ANN NEUROL 2020;87:233-245.

Clinical characteristics of pre-attack symptoms in cluster headache: A large series of Korean patients.

BACKGROUND: Previous studies have reported notable differences in demographic and clinical features of cluster headache between Western and Asian populations, including lower prevalence of the chronic type and in women. Recently, prodromal symptoms of migraine and pre-attack symptoms of cluster headache have drawn attention regarding their potential pathophysiological implications and pre-emptive treatment. However, pre-attack symptoms of cluster headache have not been studied in the Asian population. METHODS: A total of 136 patients with cluster headache (21 first-onset, 110 episodic, and five chronic cases) were recruited in this multi-center study between October 2018 and December 2019. We evaluated the characteristics of pre-attack symptoms in a current bout using a structured questionnaire. Univariable and multivariable logistic regression analyses were performed to evaluate the factors associated with presence of pre-attack symptoms. RESULTS: Pre-attack symptoms were reported in 71.3% of our patients with cluster headache. When present, pre-attack symptoms occurred at a median of 20 minutes (range 1-120) before the attack. The prevalence of local and painful, local and painless sensory, autonomic, and general symptoms was 58.8%, 14.7%, 11.0%, and 30.1%, respectively. Multivariable logistic regression analysis revealed that higher number of bouts was associated with higher prevalence of pre-attack symptoms (OR = 1.464, p = 0.044). CONCLUSIONS: Pre-attack symptoms were frequently observed in Korean patients with cluster headache, which was consistent with previous Western studies.

Bipolar Membranes to Promote Formation of Tight Ice-Like Water for Efficient and Sustainable Water Splitting.

Bipolar membranes (BPMs) have recently received much attention for their potential to improve the water dissociation reaction (WDR) at their junction by utilizing catalysts. Herein, composite catalysts (Fe2 O3 @GO) comprising hematite nanoparticles (α-Fe2 O3 ) grown on 2D graphene oxide (GO) nanosheets are reported, which show unprecedentedly high water dissociation performance in the BPM. Furthermore, new catalytic roles in facilitating WDR at the catalyst-water interface are mechanistically elucidated. It is demonstrated that the partially dissociated bound water, formed by the strongly Lewis-acidic Fe atoms of the Fe2 O3 @GO catalyst, helps the "ice-like water" to become tighter, consequently resulting in weaker intramolecular OH bonds, which reduces activation barriers and thus significantly improves the WDR rate. Notably, Fe2 O3 @GO-incorporated BPM shows an extremely low water dissociation potential (0.89 V), compared to commercially available BPM (BP-1E, 1.13 V) at 100 mA cm-2 , and it is quite close to the theoretical potential required for WDR (0.83 V). This performance reduces the required electrical energy consumption for water splitting by ≈40%, as compared to monopolar (Nafion 212 and Selemion AMV) membranes. These results can provide a new approach for the development of water dissociation catalysts and BPMs for realizing highly efficient water splitting systems.

Temporal changes of circadian rhythmicity in cluster headache.

OBJECTIVE: To investigate the temporal changes of circadian rhythmicity in relation to the disease course in patients with cluster headache. METHODS: In this multicenter study, patients with cluster headache were recruited between September 2016 and July 2018. We evaluated the patients for circadian rhythmicity and time of cluster headache attacks in the current bout and any experience of bout-to-bout change in circadian rhythmicity. We analyzed the patterns of circadian rhythmicity in relation to the disease progression (the number of total lifetime bouts, grouped into deciles). RESULTS: Of the 175 patients in their active, within-bout period, 86 (49.1%) had circadian rhythmicity in the current bout. The prevalence of circadian rhythmicity in the active period was overall similar regardless of disease progression. Sixty-three (46.3%) out of 136 patients with ≥2 bouts reported bout-to-bout changes in circadian rhythmicity. The most frequent time of cluster headache attacks was distributed evenly throughout the day earlier in the disease course and dichotomized into hypnic and midday as the number of lifetime bouts increased (p = 0.037 for the homogeneity of variance). When grouped into nighttime and daytime, nighttime attacks were predominant early in the disease course, while daytime attacks increased with disease progression (up to 7th deciles of total lifetime bouts, p = 0.001) and decreased in patients with the most advanced disease course (p = 0.013 for the non-linear association). CONCLUSIONS: Circadian rhythmicity is not a fixed factor, and changes according to the disease course. Our findings will be valuable in providing a new insight into the stability of functional involvement of the suprachiasmatic nucleus in the pathophysiology of cluster headache.

The impact of remission and coexisting migraine on anxiety and depression in cluster headache.

BACKGROUND: Our aim was to investigate the relationship between coexisting cluster headache (CH) and migraine with anxiety and depression during active cluster bouts, and how symptoms change during remission. METHODS: We analyzed data from 222 consecutive CH patients and 99 age- and sex-matched controls using a prospective multicenter registry. Anxiety or depression was evaluated using the Generalized Anxiety Disorder-7 (GAD-7) or Patient Health Questionnaire-9 (PHQ-9), respectively. Moderate-to-severe anxiety or depression was defined as a score of ≥10 at baseline (during a cluster bout). We assessed for changes in anxiety and depression during CH remission periods. RESULTS: Among the CH patients, the prevalence of moderate-to-severe anxiety and depression was seen in 38.2% and 34.6%, respectively. Compared with controls, CH patients were associated with moderate-to-severe anxiety and depression (multivariable-adjusted odds ratio [aOR] = 7.32, 95% confidence intervals [CI] = 3.35-15.99 and aOR = 4.95, 95% CI = 2.32-10.57, respectively). CH patients with migraine were significantly more likely to have moderate-to-severe anxiety and depression (aOR = 32.53, 95% CI = 6.63-159.64 and aOR = 16.88, 95% CI = 4.16-68.38, respectively), compared to controls without migraine. The GAD-7 and PHQ-9 scores were significantly reduced between cluster bout and remission periods (from 6.8 ± 5.6 to 1.6 ± 2.8; P < 0.001, and from 6.1 ± 5.0 to 1.8 ± 2.4; P < 0.001, respectively). CONCLUSIONS: Our results indicate that CH patients are at increased risk of anxiety and depression, especially in the presence of coexisting migraine. However, the anxiety and depression can improve during remission periods.

Multicenter retrospective analysis of the clinicopathologic features of monomorphic epitheliotropic intestinal T-cell lymphoma.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a provisional entity in the 2017 World Health Organization classifications. To further elucidate the clinicopathologic features of this new disease, we carried out a retrospective, multicenter analysis of 42 patients with MEITL. The median age of the patients was 59 years (range, 20-84 years), and 27 patients (64 %) were male. Thirty-two patients (76 %) were Ann-Arbor stages I-II and 28 (67 %) were Lugano stages I-II1&2. The most frequent site of involvement was the jejunum (N = 21). Most cases expressed CD8 (79 %) and CD56 (95 %) and did not express CD30 (5 %) or EBER (0 %). The median progression-free survival was 6.9 months (95 % CI 4.3-9.6); the median OS was 14.8 months (2.4-27.2). Thirty-two patients (76 %) underwent surgery and 37 (88 %) received chemotherapy. A complete response (CR) rate was 38 %. Sixteen patients had undergone autologous stem cell transplantation (ASCT). Relapse or progression was documented in 24 cases, most frequently in the primary site (N = 23). Four cases showed central nervous system relapse. Age over 55 years, poor performance scale, advanced Lugano stage (IIE-IV), not achieving CR, and not receiving ASCT were associated with inferior OS. While the optimal management of MEITL remains undetermined, achieving CR and consolidative ASCT seem essential. As CHOP might be insufficient for achieving CR, more efficient combinations should be investigated. Additionally, considering the frequent local failure and CNS relapse, novel therapeutic approaches are required to improve survival.

Field testing the diagnostic criteria of cluster headache in the third edition of the International Classification of Headache Disorders: A cross-sectional multicentre study.

BACKGROUND: *These authors are shared first authors. The recently published third edition of the International Classification of Headache Disorders (ICHD-3) revised the criteria for accompanying symptoms of cluster headache (CH) and the remission period of chronic cluster headache (CCH). This study aimed at testing the validity of the ICHD-3 criteria for CH by using data from the Korean Cluster Headache Registry. METHODS: Consecutive patients with CH and probable cluster headache (PCH) were prospectively recruited from 15 hospitals. We analysed the validity of the revised ICHD-3 criteria for CH against the beta version of the third edition of the ICHD (ICHD-3ß). RESULTS: In total, 193 patients were enrolled: 140 (72.5%), 5 (2.6%) and 22 (11.4%) had episodic cluster headache (ECH), CCH, and PCH, respectively. The remaining 26 (13.5%) had CH with undetermined remission periods. One patient with ECH and one with PCH had only forehead and facial flushing and were diagnosed with PCH and non-cluster headache, respectively, according to the ICHD-3. Four participants with ECH according to the ICHD-3ß had remission periods of > 1 month and between 1 and 3 months and were newly diagnosed with CCH according to the ICHD-3. CONCLUSION: The change from ICHD-3ß to ICHD-3 resulted in few differences in the diagnoses of CH and PCH.

Increased suicidality in patients with cluster headache.

OBJECTIVE: To investigate suicidality related to cluster headache and factors associated with increased suicidality in cluster headache patients. METHODS: In this multicenter study, 193 cluster headache patients were recruited between September 2016 and August 2018. Patients were asked about their suicidality during and between attacks, specifically about passive suicidal ideation, active suicidal ideation, suicide plan, and suicide attempt. Univariable and multivariable logistic regression analyses were performed to evaluate the factors associated with high ictal suicidality (sum of positive response ≥ 2). Patients were followed up when they were in the between-bouts period. RESULTS: A total of 175 cluster headache patients in the in-bout period were included in this study. Passive suicidal ideation, active suicidal ideation, suicidal planning, and suicidal attempt were reported by 111 (64.2%), 62 (35.8%), 10 (5.8%), and four (2.3%) patients during attacks; seven (4.0%), six (3.5%), five (2.9%) and two (1.2%) patients interictally; and none (0%), one (1.9%), one (1.9%), and none (0%) among patients in the between-bouts period. Factors associated with high ictal suicidality were longer disease duration, the Headache Impact Test score, and the Patient Health Question-9 score (multivariable OR = 1.90 per 10-year increase in disease duration, 95% CI = 1.18-3.05, p = 0.008; multivariable OR = 3.19 per 10-point increase in HIT-6, 95% CI = 1.73-5.87, p < 0.001; multivariable OR = 2.11 per 10-point increase in PHQ-9, 95% CI = 1.13-3.95, p = 0.020, respectively). CONCLUSIONS: Cluster headache attack carries a high suicidality compared to the interictal or between-bouts state. An intensive treatment to reduce cluster headache burden may be helpful to alleviate suicide risk in cluster headache patients.

Arthroscopic Coracoclavicular Fixation Using Multiple Low-Profile Devices in Acute Acromioclavicular Joint Dislocation.

PURPOSE: To introduce an arthroscopically assisted coracoclavicular (CC) fixation technique using multiple low-profile devices to evaluate the clinical and radiologic outcomes in patients with acute high-grade acromioclavicular (AC) joint dislocation. METHODS: Between July 2014 and September 2015, cases of AC joint dislocation that were treated with arthroscopic CC fixation using multiple low-profile devices with a minimum follow-up of 24 months were included. We measured the vertical coracoclavicular distance (CCD) on the anteroposterior view and the horizontal acromioclavicular distance on 3-dimensional computed tomography images to evaluate the changes in radiologic outcomes before and after surgery. We compared final radiologic outcomes between initial AC reduction groups based on hierarchical clustering. Clinical outcomes were evaluated using the Constant-Murley score. RESULTS: We enrolled 27 patients in total, and the mean follow-up period was 27.2 months. The mean CCD of the injured shoulder was 13.68 ± 3.98 mm preoperatively and decreased to 5.72 ± 1.68 mm immediately postoperatively but increased to 7.32 ± 2.29 mm at last follow-up (P = .07). Horizontal displacement of the distal clavicle was 1.1 ± 1.0 mm immediately postoperatively but decreased to 0.9 ± 0.6 mm at last follow-up (P < .05). In particular, in the 2 groups that were determined using the hierarchical cluster analysis, patients with excellent recovery of the initial CCD (20 patients) showed less of an increase in the CCD at last follow-up than did those in the other group (7 patients) (P < .001). The Constant-Murley score was 93.5 ± 2.7 points on the injured side at last follow-up (P = .074). CONCLUSIONS: Our CC fixation technique with multiple low-profile devices exhibited satisfactory clinical and radiologic outcomes. In particular, ensuring good initial recovery of the CCD and the precise placement and location of the AC joints was important in maintaining the proper AC position at the final follow-up. LEVEL OF EVIDENCE: Level IV, case series.

DR3 signaling modulates the function of Foxp3+ regulatory T cells and the severity of acute graft-versus-host disease.

CD4+Foxp3+ regulatory T cells (Treg) are a subpopulation of T cells, which regulate the immune system and enhance immune tolerance after transplantation. Donor-derived Treg prevent the development of lethal acute graft-versus-host disease (GVHD) in murine models of allogeneic hematopoietic stem cell transplantation. We recently demonstrated that a single treatment of the agonistic antibody to DR3 (death receptor 3, αDR3) to donor mice resulted in the expansion of donor-derived Treg and prevented acute GVHD, although the precise role of DR3 signaling in GVHD has not been elucidated. In this study, we comprehensively analyzed the immunophenotype of Treg after DR3 signal activation, demonstrating that DR3-activated Treg (DR3-Treg) had an activated/mature phenotype. Furthermore, the CD25+Foxp3+ subpopulation in DR3-Treg showed stronger suppressive effects in vivo. Prophylactic treatment of αDR3 to recipient mice expanded recipient-derived Treg and reduced the severity of GVHD, whereas DR3 activation in mice with ongoing GVHD further promoted donor T-cell activation/proliferation. These data suggest that the function of DR3 signaling was highly dependent on the activation status of the T cells. In conclusion, our data demonstrated that DR3 signaling affects the function of Treg and T-cell activation after alloantigen exposure in a time-dependent manner. These observations provide important information for future clinical testing using human DR3 signal modulation and highlight the critical effect of the state of T-cell activation on clinical outcomes after activation of DR3.

Stress Is Associated with Poor Outcome of Acute Treatment for Chronic Migraine: A Multicenter Study.

Background: Chronic migraine (CM) is associated with severe psychological symptoms and disabilities. Information on the relationship between stress and the outcomes of acute CM treatment is limited. Methods: We evaluated the clinical presentation and stress levels of patients with CM who visited the neurology departments of 14 hospitals between September and December 2015. The patients were divided into stress and reference groups on the basis of the Korean version of the Brief Encounter Psychosocial Instrument (BEPSI-K). Quality of life was evaluated using EuroQol Five Dimension Questionnaire Three-Level. The Migraine Assessment of Current Therapy questionnaire was used to assess the outcomes of acute treatment. Results: This study included 186 CM patients. On the basis of the BEPSI-K score, 79 and 107 patients were assigned to the stress and reference groups, respectively. The stress group had more patients with poor outcomes of acute treatment than the reference group (67.1% vs 40.2%, P < 0.001). In a multivariate analysis, female gender (odds ratio [OR] = 3.266, 95% confidence interval [CI] = 1.172-9.103, P = 0.024), the number of headache-free days per month (OR = 0.932, 95% CI = 0.883-0.985, P = 0.012), and BEPSI-K score (OR = 1.667, 95% CI = 1.051-2.643, P = 0.030) predicted poor outcomes of acute treatment. Conclusions: High levels of stress were reported by 42.5% of patients with CM. The association between stress and the outcomes of acute treatment suggests that stress is an important clinical variable for improving the management of CM.

Impact of cluster headache on employment status and job burden: a prospective cross-sectional multicenter study.

BACKGROUND: Cluster headaches (CH) are recurrent severe headaches, which impose a major burden on the life of patients. We investigated the impact of CH on employment status and job burden. METHODS: The study was a sub-study of the Korean Cluster Headache Registry. Patients with CH were enrolled from September 2016 to February 2018 from 15 headache clinics in Korea. We also enrolled a headache control group with age-sex matched patients with migraine or tension-type headache. Moreover, a control group including individuals without headache complaints was recruited. All participants responded to a questionnaire that included questions on employment status, type of occupation, working time, sick leave, reductions in productivity, and satisfaction with current occupation. The questionnaire was administered to participants who were currently employed or had previous occupational experience. RESULTS: We recruited 143 patients with CH, 38 patients with other types of headache (migraine or tension-type headache), and 52 headache-free controls. The proportion of employees was lower in the CH group compared with the headache and headache-free control groups (CH: 67.6% vs. headache controls: 84.2% vs. headache-free controls: 96.2%; p = 0.001). The CH group more frequently experienced difficulties at work and required sick leave than the other groups (CH: 84.8% vs. headache controls: 63.9% vs. headache-free controls: 36.5%; p <  0.001; CH: 39.4% vs. headache controls: 13.9% vs. headache-free controls: 3.4%; p <  0.001). Among the patients with CH, sick leave was associated with younger age at CH onset (25.8 years vs. 30.6 years, p = 0.014), severity of pain rated on a visual analogue scale (9.3 vs. 8.8, p = 0.008), and diurnal periodicity during the daytime (p = 0.003). There were no significant differences with respect to the sick leave based on sex, age, CH subtypes, and CH recurrence. CONCLUSIONS: CH might be associated with employment status. Most patients with CH experienced substantial burdens at work.

Burden of Intracranial Atherosclerosis Is Associated With Long-Term Vascular Outcome in Patients With Ischemic Stroke.

BACKGROUND AND PURPOSE: Ischemic stroke patients often have intracranial atherosclerosis (ICAS), despite heterogeneity in the cause of stroke. We tested the hypothesis that ICAS burden can independently reflect the risk of long-term vascular outcome. METHODS: This was a retrospective cohort study analyzing data from a prospective stroke registry enrolling consecutive patients with acute ischemic stroke or transient ischemic attack. A total of 1081 patients were categorized into no ICAS, single ICAS, and advanced ICAS (ICAS ≥2 different intracranial arteries) groups. Primary and secondary end points were time to occurrence of recurrent ischemic stroke and composite vascular outcome, respectively. Study end points by ICAS burden were compared using Cox proportional hazards models in overall and propensity-matched patients. RESULTS: ICAS was present in 405 patients (37.3%). During a median 5-year follow-up, recurrent stroke and composite vascular outcome occurred in 6.8% and 16.8% of patients, respectively. As the number of ICAS increased, the risk for study end points increased after adjustment of potential covariates (hazard ratio per 1 increase in ICAS, 1.19; 95% confidence interval, 1.01-1.42 for recurrent ischemic stroke and hazard ratio, 1.18; 95% confidence interval, 1.05-1.33 for composite vascular outcome). The hazard ratios (95% confidence interval) for recurrent stroke and composite vascular outcome in patients with advanced ICAS compared with those without ICAS were 1.56 (0.88-2.74) and 1.72 (1.17-2.53), respectively, in the overall patients. The corresponding values in the propensity-matched patients were 1.28 (0.71-2.30) and 1.95 (1.27-2.99), respectively. CONCLUSIONS: ICAS burden was independently associated with the risk of subsequent composite vascular outcome in patients with ischemic stroke. These findings suggest that ICAS burden can reflect the risk of long-term vascular outcome.

Treatment with agonistic DR3 antibody results in expansion of donor Tregs and reduced graft-versus-host disease.

The paucity of regulatory T cells (Tregs) limits clinical translation to control aberrant immune reactions including graft-versus-host disease (GVHD). Recent studies showed that the agonistic antibody to DR3 (αDR3) expanded CD4(+)FoxP3(+) Tregs in vivo. We investigated whether treating donor mice with a single dose of αDR3 could alleviate acute GVHD in a MHC-mismatched bone marrow transplantation model. αDR3 induced selective proliferation of functional Tregs. CD4(+) T cells isolated from αDR3-treated mice contained higher numbers of Tregs and were less proliferative to allogeneic stimuli. In vivo GVHD studies confirmed that Tregs from αDR3-treated donors expanded robustly and higher frequencies of Tregs within donor CD4(+) T cells were maintained, resulting in improved survival. Conventional T cells derived from αDR3-treated donors showed reduced activation and proliferation. Serum levels of proinflammatory cytokines (IFNγ, IL-1ß, and TNFα) and infiltration of donor T cells into GVHD target tissues (gastrointestinal tract and liver) were decreased. T cells from αDR3-treated donors retained graft-vs-tumor (GVT) effects. In conclusion, a single dose of αDR3 alleviates acute GVHD while preserving GVT effects by selectively expanding and maintaining donor Tregs. This novel strategy will facilitate the clinical application of Treg-based therapies.

Donor Requirements for Regulatory T Cell Suppression of Murine Graft-versus-Host Disease.

Adoptive transfer of freshly isolated natural occurring CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) prevents graft-versus-host disease (GVHD) in several animal models and following hematopoietic cell transplantation (HCT) in clinical trials. Donor-derived Treg have been mainly used, as they share the same MHC with CD4(+) and CD8(+) conventional T cells (Tcon) that are primarily responsible for GVHD. Third party-derived Treg are a promising alternative for cellular therapy, as they can be prepared in advance, screened for pathogens and activity, and banked. We explored MHC disparities between Treg and Tcon in HCT to evaluate the impact of different Treg populations in GVHD prevention and survival. Third-party Treg and donor Treg are equally suppressive in ex vivo assays, whereas both donor and third-party but not host Treg protect from GVHD in allogeneic HCT, with donor Treg being the most effective. In an MHC minor mismatched transplantation model (C57BL/6 → BALB/b), donor and third-party Treg were equally effective in controlling GVHD. Furthermore, using an in vivo Treg depletion mouse model, we found that Treg exert their main suppressive activity in the first 2 d after transplantation. Third-party Treg survive for a shorter period of time after adoptive transfer, but despite the shorter survival, they control Tcon proliferation in the early phases of HCT. These studies provide relevant insights on the mechanisms of Treg-mediated protection from GVHD and support for the use of third-party Treg in clinical trials.

First Blindness Cases of Horses Infected with Setaria Digitata (Nematoda: Filarioidea) in the Republic of Korea.

Ocular setariases of cattle were reported but those of equine hosts have never been reported in the Republic of Korea (Korea). We found motile worms in the aqueous humor of 15 horses (Equus spp.) from 12 localities in southern parts of Korea between January 2004 and November 2017. After the affected animals were properly restrained under sedation and local anesthesia, 10 ml disposable syringe with a 16-gauge needle was inserted into the anterior chamber of the affected eye to successfully remove the parasites. The male worm that was found in 7 of the cases showed a pair of lateral appendages near the posterior terminal end of the body. The papillar arrangement was 3 pairs of precloacal, a pair of adcloacal, and 3 pairs of postcloacal papillae, plus a central papilla just in front of the cloaca. The female worms found in the eyes of 8 horses were characterized by the tapering posterior terminal end of the body with a smooth knob. Worms were all identified as Setaria digitata (von Linstow, 1906) by the morphologic characteristics using light and electron microscopic observations. This is the first blindness cases of 15 horses infected with S. digitata (Nematoda: Filarioidea) in Korea.