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Advances in acute ischemic stroke (AIS) treatment have been contingent on innovations in neuroimaging. Neuroimaging plays a pivotal role in the diagnosis and prognosis of ischemic stroke and large vessel occlusion, enabling triage decisions in the emergent care of the stroke patient. Current imaging protocols for acute stroke are dependent on the available resources and clinicians’ preferences and experiences. In addition, differential application of neuroimaging in medical decision-making, and the rapidly growing evidence to support varying paradigms have outpaced guideline-based recommendations for selecting patients to receive intravenous or endovascular treatment. In this review, we aimed to discuss the various imaging modalities and approaches used in the diagnosis and treatment of AIS.
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Background@#and Purpose Nelonemdaz (Neu2000) has both selective antagonism against 2B subunit of N-methyl-D-aspartate receptor and antioxidant activity. This drug provides sufficient evidence of neuroprotection in acute cerebral ischemia/reperfusion models. This phase III trial aims to determine this effect in patients.Design The Rescue on Reperfusion Damage in Cerebral Infarction by Nelonemdaz is a multicenter, double-blinded clinical trial. A total of 496 patients will be randomly assigned into the nelonemdaz (a total of 5,250 mg divided by 10 times for 5 days) and placebo groups. Patients will be included if they have an acute ischemic stroke (National Institutes of Health Stroke Scale score ≥8) caused by intracranial large vessel occlusion in the anterior circulation (Alberta Stroke Program Early CT Score ≥4), and if they are expected to undergo endovascular thrombectomy within 12 hours after stroke onset.Endpoints The primary endpoint is a favorable shift in the modified Rankin Scale (mRS) score at 90 days after the first dose of drug. The data will be analyzed by the Cochran–Mantel–Haenszel shift test. The secondary endpoints include functional independence (mRS 0–2) at 35 and 90 days, the favorable shift of mRS at 35 days, the proportion of mRS 0 at 35 and 90 days, and the occurrence rates of symptomatic intracranial hemorrhage within 7 days. @*Conclusion@#This trial will clarify the efficacy and safety of nelonemdaz in patients with acute ischemic stroke and endovascular thrombectomy. This study has been registered at ClinicalTrials. gov (NCT05041010).
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Mechanical thrombectomy (MT) has become the gold-standard for patients with acute large vessel occlusion strokes (LVOS). MT is highly effective in the treatment of embolic occlusions; however, underlying intracranial atherosclerotic disease (ICAD) represents a therapeutic challenge, often requiring pharmacological and/or mechanical rescue treatment. Glycoprotein IIb/IIIa inhibitors have been suggested as the best initial approach, if reperfusion can be achieved after thrombectomy, with angioplasty and/or stenting being reserved for the more refractory cases. In this review, we focus on the therapeutic considerations surrounding the endovascular treatment of ICAD-related acute LVOS.
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The efficacy of endovascular treatment (EVT) in patients with posterior circulation stroke has not been proven. Two recent randomized controlled trials failed to show improved functional outcomes after EVT for posterior circulation stroke (PC-EVT). However, promising results for two additional randomized controlled trials have also been presented at a recent conference. Studies have shown that patients undergoing PC-EVT had a higher rate of futile recanalization than those undergoing EVT for anterior circulation stroke. These findings call for further identification of prognostic factors beyond recanalization. The significance of baseline clinical severity, infarct volume, collaterals, time metrics, core-penumbra mismatch, and methods to accurately measure these parameters are discussed. Furthermore, their interplay on EVT outcomes and the potential to individualize patient selection for PC-EVT are reviewed. We also discuss technical considerations for improving the treatment efficacy of PC-EVT.
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Background@#and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. @*Methods@#We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). @*Results@#There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. @*Conclusions@#During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.
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Background and Objectives@#Coronavirus disease 2019 (COVID-19) is a worldwide pandemic, and some patients require mechanical ventilation and tracheostomy. Owing to the risks of aerosol spreading to health care workers, the protocols and guidelines related to the novel timing and technique for tracheostomy are rapidly changing. We investigated the characteristics of tracheostomy with patients with COVID-19 over a year.Subjects and Method We measured the mean time from intubation to the tracheostomy, survival rate, the incidence of infection to medical staff, and operation time, complications for tracheostomy, and the time of decannulation. All patients underwent a novel percutaneous tracheostomy without bronchoscope (hybrid modified percutaneous dilatational tracheostomy, hybrid MPDT) in the negative pressure intensive care unit. @*Results@#Of the 448 patients with COVID-19 patients, 34 required invasive mechanical ventilation at a tertiary hospital from February 2020 to April 2021. Of those, 15 patients underwent tracheostomy. Of the tracheostomy patients, survival rate was 93.33%. The mean time from intubation to the tracheostomy was 18.27±14.74 days (range, 8-36 days). The incidence of infection to medical staff was zero percent whereas racheostomy-related bleeding was the most common complication (2 patients). Operation time for hybrid MPDT was 5.45±1.12 min. @*Conclusion@#The optimal timing of tracheostomy procedure for COVID-19 patients is still unknown, but it is believed that the treatment of COVID-19 can be achieved better if the hybrid MPDT is used at the right time.
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Buerger’s disease (BD) is a chronic inflammatory vasculitis of unknown etiology. The infectious etiology of BD was proposed by Buerger in 1914. Furthermore, there are scattered reports insisting that BD may be related to rickettsial infection, first asserted by Goodman since 1916, followed by Giroud and other French investigators from the 1940s through the 1960s, Nicolau in the 1960s, Bartolo (1980s), and Fazeli (2010s). However, their causal relationship has hardly been accepted because rickettsial infections are known to be acute febrile, vector-borne illnesses, whereas BD is a chronic afebrile illness. In this article we review the relevant literature on the chronic nature of Rickettsia and Orientia infections and on the rickettsial etiology of BD. Excellent initial responses to doxycycline in three patients with BD are briefly described. Based on these findings, we hypothesize that BD patients acquired a rickettsial infection far before the onset of BD. Over years, the infected area expands to become a segment of the infected vessel. Subsequently, thrombus develops on the luminal surface of the infected endothelial cells, which produces the vascular obstructive manifestations of BD. Collectively, it is postulated that BD is a chronic infection with a member of the family Rickettsiaceae with superimposed thrombosis.
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Although randomized control trials about endovascular treatment (EVT) of emergent large vessel occlusion (LVO) have demonstrated the success of mechanical thrombectomy as the choice of treatment, a wide range of caveats remain unaddressed. Asian patients were rarely included in the trials, thereby raising the question of whether the treatment could be generalized. In addition, there remains a concern on the feasibility of the method with respect to its application against intracranial atherosclerosis (ICAS)-related LVO, frequently observed in the Asian population. It is important to include evidence on ICAS LVO from Asian countries in the future for a comprehensive understanding of LVO etiology. Besides the issues with EVT, prognostic concerns in diabetes patients, acute kidney injury following EVT, neuroprotective management against reperfusion injury, and other peri-EVT issues should be considered in clinical practice. In the current article, we present an in-depth review of the literature that revises information pertaining to such concerns.
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Background@#Pregnant women are at a high-risk of influenza infection. We have previously reported a low influenza vaccination coverage rate (4.0%) in Korea during the 2006–2007 influenza season. We conducted follow-up studies in 2011–2012 and 2018–2019 to observe changes in influenza vaccination coverage. @*Methods@#Women who delivered at Inha University Hospital (Incheon, Korea) in 2011–2012 and 2018–2019 were enrolled in the study. We surveyed the rate of influenza vaccination, perception scores, and related factors through telephonic interviews and compared the results from 2011–2012 and 2018–2019 with those from 2006–2007. @*Results@#The number of survey respondents was 227 in 2006–2007, 152 in 2011–2012, and 171 in 2018–2019. The rate of vaccination coverage increased from 4.0% in 2006–2007 to 42.0% in 2011–2012 and 59.3% in 2018–2019. Perception scores also increased progressively from 3.8 in 2006–2007 to 4.2 in 2011–2012 and 5.1 in 2018–2019. Physician recommendations for influenza vaccination also increased from 4.8% in 2006–2007 to 36.8% in 2011–2012 and 49.7% in 2018–2019. The most common reason for not getting vaccinated was the lack of awareness of influenza vaccination during pregnancy (36.9%). The perception scores and physician recommendation rates were significantly lower for unvaccinated women (3.87 and 8.4%, respectively) than for vaccinated women (5.14 and 69.1%, respectively). @*Conclusion@#The influenza vaccination coverage rate in pregnant women has increased significantly since our study in 2006–2007. However, further improvement in the coverage rate is needed. There is a need for active and comprehensive publicity and education regarding this issue among physicians and pregnant women.
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Although randomized control trials about endovascular treatment (EVT) of emergent large vessel occlusion (LVO) have demonstrated the success of mechanical thrombectomy as the choice of treatment, a wide range of caveats remain unaddressed. Asian patients were rarely included in the trials, thereby raising the question of whether the treatment could be generalized. In addition, there remains a concern on the feasibility of the method with respect to its application against intracranial atherosclerosis (ICAS)-related LVO, frequently observed in the Asian population. It is important to include evidence on ICAS LVO from Asian countries in the future for a comprehensive understanding of LVO etiology. Besides the issues with EVT, prognostic concerns in diabetes patients, acute kidney injury following EVT, neuroprotective management against reperfusion injury, and other peri-EVT issues should be considered in clinical practice. In the current article, we present an in-depth review of the literature that revises information pertaining to such concerns.
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Background@#Pregnant women are at a high-risk of influenza infection. We have previously reported a low influenza vaccination coverage rate (4.0%) in Korea during the 2006–2007 influenza season. We conducted follow-up studies in 2011–2012 and 2018–2019 to observe changes in influenza vaccination coverage. @*Methods@#Women who delivered at Inha University Hospital (Incheon, Korea) in 2011–2012 and 2018–2019 were enrolled in the study. We surveyed the rate of influenza vaccination, perception scores, and related factors through telephonic interviews and compared the results from 2011–2012 and 2018–2019 with those from 2006–2007. @*Results@#The number of survey respondents was 227 in 2006–2007, 152 in 2011–2012, and 171 in 2018–2019. The rate of vaccination coverage increased from 4.0% in 2006–2007 to 42.0% in 2011–2012 and 59.3% in 2018–2019. Perception scores also increased progressively from 3.8 in 2006–2007 to 4.2 in 2011–2012 and 5.1 in 2018–2019. Physician recommendations for influenza vaccination also increased from 4.8% in 2006–2007 to 36.8% in 2011–2012 and 49.7% in 2018–2019. The most common reason for not getting vaccinated was the lack of awareness of influenza vaccination during pregnancy (36.9%). The perception scores and physician recommendation rates were significantly lower for unvaccinated women (3.87 and 8.4%, respectively) than for vaccinated women (5.14 and 69.1%, respectively). @*Conclusion@#The influenza vaccination coverage rate in pregnant women has increased significantly since our study in 2006–2007. However, further improvement in the coverage rate is needed. There is a need for active and comprehensive publicity and education regarding this issue among physicians and pregnant women.
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Purpose@#Immune checkpoint inhibitors (ICI) and targeted small-molecule drugs are mainstay elements of lung cancer chemotherapy. However, they are associated with development of pneumonitis, a rare, but potentially life-threatening event. We analyzed lung cancer patients treated with ICI to evaluate the effect of sequential therapeutic administration on the incidence of pneumonitis. @*Materials and Methods@#In this retrospective study, 242 patients were included. Serial radiologic findings taken during and immediately after ICI treatment were reviewed. Factors that increased pneumonitis and the relationship between peri-ICI chemotherapy and the development of pneumonitis were evaluated. @*Results@#Pneumonitis developed in 23 patients (9.5%); severe pneumonitis (grade ≥ 3) occurred in 13 of 23 patients (56%); pneumonitis-related death occurred in six. High-dose thoracic radiation (≥ 6,000 cGy) revealed a tendency toward high risk of pneumonitis (odds ratio, 2.642; 95% confidence interval, 0.932 to 7.490; p=0.068). Among 149 patients followed for ≥ 8 weeks after the final ICI dose, more patients who received targeted agents within 8-weeks post-ICI experienced pneumonitis (3/16, 18.8%) compared with patients who received cytotoxic agents (4/54, 7.4%) or no chemotherapy (4/79, 5.1%) (p=0.162). Targeted therapy was associated with earlier-onset pneumonitis than treatment with cytotoxic agents (35 vs. 62 days post-ICI, p=0.007); the resulting pneumonitis was more severe (grade ≥ 3, 100% vs. 0%, p=0.031). @*Conclusion@#Sequential administration of small-molecule targeted agents immediately after ICI may increase the risk of severe pneumonitis. The sequence of chemotherapy regimens that include ICI and targeted agents should be carefully planned to reduce the risk of pneumonitis in lung cancer patients.
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Purpose@#Squamous cell carcinomas (SqCC) of the lung often express high levels of thymidylate synthase (TS), which is associated with primary resistance to pemetrexed. We explored the efficacy of pemetrexed in a selected population of patients with lung SqCC with low TS expression. @*Materials and Methods@#In this single-arm phase II trial, we enrolled 32 previously-treated patients with advanced lung SqCC exhibiting low immunohistochemical staining for TS (i.e., in 10% or less of tumor cells). The primary endpoint was 12-week progression-free survival (PFS) rate. @*Results@#Of 32 patients, eight patients (25%) had an Eastern Cooperative Oncology Group performance status of 2, and seven patients (22%) had previously received three or more lines of chemotherapy. The disease control rate from pemetrexed treatment was 30%, and no objective response was observed. The 12-week PFS rate was 24.5% (95% confidence interval [CI], 13.0 to 46.1). Median PFS was 1.3 months (95% CI, 1.3 to 2.7), and median overall survival was 11.8 months (95% CI, 8.1 to not applicable). Most of adverse events were grade 1 or 2. @*Conclusion@#Pemetrexed demonstrated modest activity as a salvage chemotherapy in patients with advanced lung SqCC with low TS expression, although its toxicity was generally manageable.
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The Pfizer-BioNTech COVID-19 vaccine has shown excellent clinical effectiveness; however, adverse events of the vaccine remain a concern in Korea. We surveyed adverse events in 2498 healthcare workers vaccinated with the Pfizer-BioNTech COVID-19 vaccine at a university hospital. The survey was conducted using a diary card for 7 days following each injection. The questionnaire response rate was 75.1% (1876/2498) for the first dose and 73.8% (1840/2493) for the second dose. Among local reactions, pain was the most commonly reported (84.9% after the first dose and 90.4% after the second dose). After the second dose, two people visited the emergency room due to severe local pain, but no hospitalization or skin necrosis occurred. Among systemic reactions, fatigue was most frequently reported (52.8% after the first dose and 77.0% after the second dose), followed by myalgia (49.0% and 76.1%), headache (28.7% and 59.2%), chills (16.7% and 54.0%), and arthralgia (11.4% and 39.2%). One or more critical adverse events occurred in 0.2% and 0.7% of the vaccinees. Except for urticaria, more adverse events were reported after the second dose than after the first dose. In the future, adverse events should be investigated in older adults, and a future study with a longer observation period should be conducted.
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The benefit of mechanical thrombectomy (MT) in acute ischemic stroke (AIS) due to large vessel intracranial occlusions is directly related to the technical success of the procedures in achieving fast and complete reperfusion. While a precise definition of refractoriness is lacking in the literature, it may be considered when there is reperfusion failure, long procedural times, or high number of passes with the MT devices. Detailed knowledge about the causes for refractory MT in AIS is limited; however, it is most likely a multifaceted problem including factors related to the vascular anatomy and the underlying nature of the occlusive lesion amongst other factors. We aim to review the impact of several key unfavorable anatomical factors that may be encountered during endovascular AIS treatment and discuss potential bail-out strategies to these challenging situations.
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Many previous studies have shown reduced glucose uptake in the ischemic brain. In contrast, in a permanent unilateral common carotid artery occlusion (UCCAO) mouse model, our pilot experiments using 18F-fluorodeoxyglucose positron emission tomography (FDG PET) revealed that a subset of mice exhibited conspicuously high uptake of glucose in the ipsilateral hemisphere at 1 week post-occlusion (asymmetric group), whereas other mice showed symmetric uptake in both hemispheres (symmetric group). Thus, we aimed to understand the discrepancy between the two groups. Cerebral blood flow and histological/metabolic changes were analyzed using laser Doppler flowmetry and immunohistochemistry/Western blotting, respectively. Contrary to the increased glucose uptake observed in the ischemic cerebral hemisphere on FDG PET (p<0.001), cerebral blood flow tended to be lower in the asymmetric group than in the symmetric group (right to left ratio [%], 36.4±21.8 vs. 58.0±24.8, p=0.059). Neuronal death was observed only in the ischemic hemisphere of the asymmetric group. In contrast, astrocytes were more activated in the asymmetric group than in the symmetric group (p<0.05). Glucose transporter-1, and monocarboxylate transporter-1 were also upregulated in the asymmetric group, compared with the symmetric group (p<0.05, respectively). These results suggest that the increased FDG uptake was associated with relatively severe ischemia, and glucose transporter-1 upregulation and astrocyte activation. Glucose metabolism may thus be a compensatory mechanism in the moderately severe ischemic brain.
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Coronavirus disease 2019 (COVID-19) is rapidly spreading around the world, causing much morbidity and mortality everywhere. However, effective treatments or vaccines are still not available. Although convalescent plasma (CP) therapy can be useful in the treatment of COVID-19, it has not been widely used in Korea because of the concerns about adverse effects and the difficulty in matching patients to donors. The use of ABO-incompatible plasma is not contraindicated in treatment, but can be hesitated due to the lack of experience of physicians. Here, we describe a 68-year old man with COVID-19 who was treated ABO-incompatible plasma therapy; additionally, we comment on the acute side effects associated with ABO mismatch transfusion. To overcome the obstacles of donor-recipient connections (schedule and distance), we propose the storage of frozen plasma, modification of the current Blood Management Law, and the establishment of a CP bank. We suggest that experience gained in CP therapy will be useful for not only the treatment of COVID-19, but also for coping with new emerging infectious diseases.
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Purpose@#The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program. @*Materials and Methods@#Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected. @*Results@#Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data. @*Conclusion@#This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.
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BACKGROUND@#Lamivudine and abacavir sulfate are widely used nucleoside/tide reverse transcriptase inhibitors (NRTI) backbone agents, which are recommended in major international treatment guidelines. The fixed-dose combination of lamivudine and abacavir sulfate has been developed to contribute to low pill burden of antiretroviral therapy (ART) regimen and patient adherence. A mandatory post-marketing surveillance was conducted in Korea to monitor the safety of Kivexa (lamivudine 300 mg/abacavir 600 mg).@*MATERIALS AND METHODS@#An open label, multi-center, non-interventional post-marketing surveillance was conducted to monitor the safety of Kivexa from July 2011 to July 2017 in 23 hospitals in Korea. Subjects over 12 years old taking Kivexa per prescribing information were enrolled. The primary outcome was defined as the occurrence of any adverse events during the study period. Secondary outcomes included the occurrence of adverse drug reaction, the occurrence of serious adverse events and the effectiveness of Kivexa.@*RESULTS@#A total of 600 patients from 23 hospitals were enrolled within the 6 years of study. The total observation period was 1,004 person-years. Three hundred and ten patients reported 674 adverse events. The incidence of upper respiratory infection (65 cases, 10.9%) was the highest, followed by diarrhea (20 cases, 3.3%), and nausea (18 cases, 3.0%). 109 subjects reported 71 events of adverse drug reactions, and the most common reaction was nausea in 2.33% of the subjects. Thirty-one subjects reported serious adverse events, none of them were considered drug related. From the total of 600 subjects, excluding 48 subjects who were ‘effectiveness unassessable’ by investigators, 552 patients were eligible for the subjective effectiveness analysis. 459 (83.2%) were evaluated as ‘improved’. Proportion of subjects whose human immunodeficiency virus-RNA is <50 copies/ml was 61.2% (309/505) at the beginning of observation and increased to 91.9% (464/505) at the end of study period.@*CONCLUSIONS@#The post-marketing surveillance showed the safety of Kivexa in HIV-1 patients in Korea. Ischemic cardiovascular events and hypersensitivity associated with Kivexa were few. There was no significant new safety information. This data may be helpful in implementing Kivexa and lamivudine/abacavir sulfate containing drugs in Korea.
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BACKGROUND@#Tsutsugamushi disease, or scrub typhus, is an acute febrile illness caused by Orientia tsutsugamushi, which is followed by chronic latent infection. People who reside in areas endemic of tsutsugamushi disease may be frequently reinfected with this organism. Volunteers who are experimentally reinfected with O. tsutsugamushi manifest various systemic and local reactions, including the presence of small-sized eschar. The present study recorded the morphology and size of eschars in patients with tsutsugamushi disease on Jeju Island, Korea.@*MATERIALS AND METHODS@#From March 2018 to February 2019, 23 patients manifesting clinical characteristics and epidemiologic features of tsutsugamushi disease on Jeju Island were investigated. For comparison of eschar sizes between the two regions, 12 patients with tsutsugamushi disease in Incheon were similarly examined.@*RESULTS@#Three patients, two on the first day and one on the fourth day of fever, presented with papules of 2 – 5 mm in diameter. Another three patients, one on the second day and two on the fourth day, presented with ruptured vesicles of 5 – 8 mm in diameter. Thirteen patients presented with eschars covered with dark scabs, with a median diameter of 5 (95% confidence interval [CI], 5 – 7.5) × 4 (95% CI, 3 – 5) mm. The medians of the eschar sizes did not differ between the two cities (P = 0.46 by Mann-Whitney U test), but eschars ≥10 mm in diameter were more frequent in Incheon than in Seogwipo-si (4 of 12 vs. 0 of 13 patients, P = 0.04 by Fisher's exact test). One patient presented with multiple eschars, and no eschar was detected in the remaining three patients. Among 11 Jeju Island patients with positive IgG and IgM antibodies, seven patients revealed higher IgG than IgM antibody titers during the acute phase of the illness, i.e., the IgG antibody response, two patients had equal IgG and IgM titers, and two patients presented the IgM antibody response. Life-threatening complications and death were not observed in this study.@*CONCLUSION@#The patients in Seogwipo-si had small-sized eschars and occasionally exhibited non-necrotic lesions. Many patients had serologically reinfected tsutsugamushi disease. Further studies are needed to investigate the association between these findings.