Jin Hong Min

Extensively Drug‐Resistant Tuberculosis in South Korea: Risk Factors and Treatment Outcomes among Patients at a Tertiary Referral Hospital

BACKGROUND Extensively drug-resistant (XDR) tuberculosis (TB) is a major public health threat in South Korea. METHODS We analyzed baseline epidemiological data for 250 patients enrolled in an ongoing prospective observational study of TB at a large tertiary referral hospital in South Korea. RESULTS Twenty-six subjects with XDR TB were identified; all were patients who had previously received TB therapy. Cumulative previous treatment duration (range, 18-34 months; odds ratio [OR], 5.6; 95% confidence interval [CI], 1.0-59), number of previously received second-line anti-TB drugs (OR, 1.3; 95% CI, 1.1-1.5), and female sex (OR, 3.2; 95% CI, 1.1-8.3) were significantly associated with XDR TB in crude analyses. After controlling for other factors in a multivariable model, cumulative previous treatment duration remained significantly associated with XDR TB (OR, 5.8; 95% CI, 1.0-61). Subjects with XDR TB were more likely to produce culture-positive sputum at 6 months, compared with patients with non-multidrug resistant TB (risk ratio, 13; 95% CI, 5.1-53). Kanamycin resistance was found to be predictive of 6-month culture positivity after adjustment for ofloxacin and streptomycin resistance (risk ratio, 3.9; 95% CI, 1.9-11). CONCLUSIONS XDR TB was found to be associated with the cumulative duration of previous treatment with second-line TB drugs among subjects in a tertiary care TB hospital. Patients with XDR TB were more likely to not respond to therapy, and successful conversion of sputum culture results to negative was correlated with initial susceptibility to both fluoroquinolones and kanamycin but not to streptomycin.

Genetic Diversity of Mycobacterium tuberculosis Isolates from a Tertiary Care Tuberculosis Hospital in South Korea

ABSTRACT Tuberculosis (TB) remains an immense public health problem in the Republic of Korea despite a more than fivefold decrease in the prevalence of the disease over the last 3 decades. The rise in drug-resistant TB has compounded the situation. We analyzed 208 clinical isolates of M. tuberculosis from the National Masan Tuberculosis Hospital by spoligotyping, IS6110 restriction fragment length polymorphism (RFLP), and 24-locus-based mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing to assess the diversity and transmission dynamics of the tubercle bacilli in the Republic of Korea. The majority of the isolates (97.1%) belonged to the Beijing genotype. Cluster analysis by MIRU-VNTR yielded a low clustering rate of 22.3%, with most of the clusters comprising isolates with diverse drug resistance patterns. The discriminatory capacity of the typing methods was high for RFLP and MIRU-VNTR (allelic diversity [h] = 0.99) but low for spoligotyping (h = 0.31). Although analysis of 19 MIRU-VNTR loci was needed to achieve maximum discrimination, an informative set of 8 loci (960, 1955, 2163b, 2165, 2996, 3192, 4052, and 4348) (h = 0.98) that was able to differentiate most of the closely related strains was identified. These findings suggest that 24-locus-based MIRU-VNTR typing is a likely suitable alternative to RFLP to differentiate clinical isolates in this setting, which is dominated by M. tuberculosis Beijing strains. Within the study limits, our results also suggest that the problem of drug-resistant TB in the Republic of Korea may be largely due to acquired resistance as opposed to transmission.

Correlation between initial serum levels of lactate after return of spontaneous circulation and survival and neurological outcomes in patients who undergo therapeutic hypothermia after cardiac arrest

OBJECTIVES We analysed the relationship between serum levels of lactate within 1h of return of spontaneous circulation (ROSC) and survival and neurological outcomes in patients who underwent therapeutic hypothermia (TH). METHODS This was a multi-centre retrospective and observational study that examined data from the first Korean Hypothermia Network (KORHN) registry from 2007 to 2012. The inclusion criteria were out-of-hospital cardiac arrest (OHCA) and examination of serum levels of lactate within 1h after ROSC, taken from KORHN registry data. The primary endpoint was survival outcome at hospital discharge, and the secondary endpoint was poor neurological outcome (Cerebral Performance Category, CPC, 3-5) at hospital discharge. Initial lactate levels and other variables collected within 1h of ROSC were analysed via multivariable logistic regression. RESULTS Data from 930 cardiac arrest patients who underwent TH were collected from the KORHN registry. In a total of 443 patients, serum levels of lactate were examined within 1h of ROSC. In-hospital mortality was 289/443 (65.24%), and 347/443 (78.33%) of the patients had CPCs of 3-5 upon hospital discharge. The odds ratios of lactate levels for CPC and in-hospital mortality were 1.072 (95% confidence interval (CI) 1.026-1.121) and 1.087 (95% CI=1.031-1.147), respectively, based on multivariate ordinal logistic regression analyses. CONCLUSION High levels of lactate in serum measured within 1h of ROSC are associated with hospital mortality and high CPC scores in cardiac arrest patients treated with TH.

Efficacy of diffusion-weighted magnetic resonance imaging performed before therapeutic hypothermia in predicting clinical outcome in comatose cardiopulmonary arrest survivors

AIM OF THE STUDY To develop a clinically relevant and qualitative brain magnetic resonance imaging (MRI) scoring system for acute stage comatose cardiac arrest patients. METHODS Consecutive comatose post-cardiopulmonary arrest patients were prospectively enrolled. Routine brain MRI sequences were scored by two independent and blinded experts. Predefined brain regions were qualitatively scored on diffusion-weighted imaging (DWI) sequences according to the severity of the abnormality on a scale from 0 to 4. The mean score provided by the raters determined poor outcome defined under the Cerebral Performance Categories 3, 4, or 5. DWI scans were repeated after therapeutic hypothermia (TH). The same qualitative scoring system was applied and results were compared to the initial scores. RESULTS Out of 24 recruited patients, 19 with brain MRI scans were included. Of the 19 included patients, seven showed a good outcome at hospital discharge and 12 patients showed poor neurologic outcome. Median time from the arrest to the initial DWI was 166min (IQR 114-240min). At 100% specificity, the overall, cortex, and cortex plus deep grey nuclei scores predicted poor patient outcome with a sensitivity of 91.7-100% (95% CI). Follow-up DWI scans after TH showed worse results than initial scans. CONCLUSION A qualitative MRI scoring system effectively assessed the severity of hypoxic-ischaemic brain injury following cardiopulmonary arrest. The scoring system may provide useful prognostic information in comatose cardiopulmonary arrest patients.

Outcome and current status of therapeutic hypothermia after out-of-hospital cardiac arrest in Korea using data from the Korea Hypothermia Network registry

Objective Therapeutic hypothermia (TH) has become the standard strategy for reducing brain damage in the postresuscitation period. The aim of this study was to investigate current TH performance and outcomes in out-of-hospital cardiac arrest (OHCA) survivors using data from the Korean Hypothermia Network (KORHN) registry. Methods We used the KORHN registry, a web-based multicenter registry that includes 24 participating hospitals throughout the Republic of Korea. Adult comatose OHCA survivors treated with TH between 2007 and 2012 were included. The primary outcomes were neurological outcome at hospital discharge and in-hospital mortality. The secondary outcomes were TH performance and adverse events during TH. Results A total of 930 patients were included, of whom 556 (59.8%) survived to discharge and 249 (26.8%) were discharged with good neurologic outcomes. The median time from return of spontaneous circulation (ROSC) to the start of TH was 101 minutes (interquartile range [IQR], 46 to 200 minutes). The induction, maintenance, and rewarming durations were 150 minutes (IQR, 80 to 267 minutes), 1,440 minutes (IQR, 1,290 to 1,440 minutes), and 708 minutes (IQR, 420 to 900 minutes), respectively. The time from the ROSC to coronary angiography was 1,045 hours (IQR, 121 to 12,051 hours). Hyperglycemia (46.3%) was the most frequent adverse event. Conclusion More than one-quarter of the OHCA survivors (26.8%) were discharged with good neurologic outcomes. TH performance was appropriately managed in terms of the factors related to its timing, including cooling start time and rewarming duration.

Comparison of overlapping (OP) and adjacent thumb positions (AP) for cardiac compressions using the encircling method in infants

Objectives The aim of this manikin study was to compare the efficiency between overlapping (OP) and adjacent thumb positions (AP) for cardiac compressions using the encircling method in infants. Methods The study conducted from December 2010 to August 2011 involved 48 volunteers who were students in the emergency medical technician course. The authors let volunteers practice OP and AP as a crossover design. The authors monitored the simulated mean arterial pressure (MAP) generated during a 5-min chest compression. The fatigue level of the volunteers after the chest compression was evaluated with the Likert scale. Results There were no significant differences in MAP between the dominant hand and the non-dominant hand as the lower thumb of OP. Significant differences were observed in simulated systolic blood pressure, MAP and simulated pulse pressure between OP and AP at 1, 2, 3, 4 and 5 min. There were no significant differences among the changes in heart rate, respiratory rate and end-tidal CO2 during a 5-min chest compression by OP and AP. The Likert scale scores (1 no fatigue to 5= extreme fatigue) during the 5-min chest compressions were higher in AP than in OP at 2, 3 and 5 min. Conclusion Higher intrathoracic pressures were achieved by OP in this study. However, further studies are needed to validate these effects of overlapping thumbs technique in infant cardiopulmonary resuscitation, not manikin.

Genomic analysis of [d-Ala2, d-Leu5] enkephalin preconditioning in cortical neuron and glial cell injury after oxygen deprivation.

[d-Ala2, d-Leu5] enkephalin (DADLE) is a synthetic δ-opioid agonist that induces hibernation and promotes survival of neurons and glial cells in the central nervous system. Several mechanisms for the attenuation of hypoxic injury have been suggested, including control of intracellular signaling pathways via the δ-opioid receptor (DOR). However, the cellular and molecular mechanisms of DADLE in hypoxic injury are largely unknown. To investigate neuronal injury after oxygen-deprivation (OD) and DOR stimulation by DADLE, we used a lactate dehydrogenase assay, MTT assay, and immunofluorescence live/dead staining. And we used cDNA microarrays to investigate the influence of DADLE exposure on transcription after OD in rat cortical glial and neuronal co-culture. DADLE reduced neuronal injury after 24 h of OD. Preconditioning with DADLE before 24 h hypoxia exposure also altered gene expression in comparison with 24h OD without pretreatment. After DADLE exposure and hypoxia, 1917 of 39,511 genes (4.9%) were significantly induced or repressed at least 2.5-fold. Assigning differentially expressed ESTs (expressed sequence tags) to molecular functional groups revealed that DADLE affected many pathways including apoptosis, intracellular ion homeostasis, molecular chaperones, and glucose metabolism. We observed a coordinated change in expression of many genes (increased expression of potentially protective genes and decreased expression of potentially harmful genes) after DADLE exposure. A comprehensive list of regulated genes should prove valuable in advancing our understanding of the neuroprotective mechanisms of DADLE under OD.

Successful treatment of methemoglobinemia and acute renal failure after indoxacarb poisoning

Context. We report a case of systemic toxicity induced by indoxacarb, an oxadiazine insecticide. Previous reports have suggested the occurrence of methemoglobinemia after indoxacarb ingestion, but no case of indoxacarb-induced systemic toxicity, such as acute renal failure, has been reported thus far. Case details. A 71-year-old woman presented with indoxacarb poisoning, resulting in methemoglobinemia and acute renal failure. The methemoglobinemia improved after methylene blue administration, but rapidly progressive acute renal failure occurred 7 h after admission. She was treated with continuous veno-venous hemofiltration and intravenous sodium bicarbonate and recovered successfully. Discussion. Ingestion of indoxacarb may produce not only methemoglobinemia, but also systemic toxicities like acute renal failure, which can be successfully treated with aggressive therapy such as continuous veno-venous hemofiltration. Physicians should be alert to acute renal failure as a possible complication of indoxacarb ingestion, and treat it accordingly.

Acute Myocardial Infarction Due to Stent Thrombosis After Administration of Intravenous Epinephrine for Anaphylaxis.

To the Editor: The guidelines of several collaborating organizations recommend epinephrine injection for prompt initial treatment of anaphylaxis.[1] The dose and route of administration are generally based on the severity of symptoms and the rapidity with which a response is desired. Although, epinephrine is widely used to treat anaphylaxis, reports of severe complications such as acute coronary syndrome, arrhythmia, and intracranial bleeding are rare.[2] A 50-year-old man was admitted to the hospital Emergency Department complaining of weakness, clamminess, and angioedema of the face and tongue, after a bee sting on the proximal tibia area. Upon admission, his consciousness and electrocardiography (ECG) results were normal but his blood pressure was 75/50 mmHg, leading to a diagnosis of anaphylaxis. He was immediately administered 0.1 mg epinephrine at a 1:100,000 dilutions intravenously. This was done by placing 0.1 mg of epinephrine (0.1 ml of the 1:1000 dilution) in 10 ml of normal saline solution and infusing it over 5 min. He was also given intravenous methylprednisolone (125 mg), intravenous chlorpheniramine maleate (4 mg), and intravenous ranitidine (100 mg). When 0.04 mg of epinephrine was intravenously infused, the patient began to complain of severe chest pain. ECG revealed ST elevation in leads I, aVL, and V2-5 and ST depression and T wave inversion in leads III and aVF, correlating to reciprocal changes of anterolateral ischemia [Figure 1]. The first and second doses of 0.4 mg sublingual nitroglycerin were administered with minimal effect. Therefore, the patient was then administered intravenous nitroglycerin, but his pain did not decrease (he maintained a score of 10/10 on the visual assessment scale for pain). He had a significant history of coronary artery disease and had undergone percutaneous coronary intervention to the proximal left anterior descending artery (LAD) with bare-metal stents 7 years previously. Two years following the intervention, he had developed in-stent restenosis in the LAD stent, which was treated by further percutaneous coronary intervention with 3 overlapping drug-eluting stents. Due to ongoing chest pain, emergent cardiac catheterization was performed. This revealed total occlusion in the proximal LAD stent and 90% stenosis with tissue growth in the mid-stent (TIMI 0) [Figure 2]. Thus, we were not able to perform intravascular ultrasound in the thrombosed stent. Percutaneous coronary intervention was then performed by stent implantation after balloon angioplasty, but there was evidence of stent restenosis in the mid-LAD. The postpercutaneous coronary intervention included conventional medical management with dual antiplatelet agents. On the second day of hospitalization, an allergen-specific immunoglobulin E (IgE) blood test was performed. Total IgE was 226 kU/L, with an upper normal limit of 113 kU/L. In particular, a specific IgE value of 1.26 kUA/L was found for yellow jacket venom. Five days later, the patient was discharged without any complications. Figure 1 Twelve-lead electrocardiography obtained during chest pain demonstrating ST-segment elevation in the anterolateral leads. Figure 2 Right anterior oblique view at emergency coronary angiography showing proximal stent area occlusion of the left anterior descending (white arrow). Acute myocardial infarction associated with anaphylaxis is classified into two types, Kounis syndrome and myocardial infarction induced by epinephrine used in the treatment of anaphylaxis. Jackson et al. have reported the occurrence of acute coronary stent thrombosis after the administration of intramuscular epinephrine for anaphylaxis due to the ingestion of peanuts.[3] Further, Kasim et al. have reported the occurrence of coronary thrombosis after the administration of intramuscular epinephrine for anaphylaxis due to wasp stings.[4] In these cases, the proposed pathophysiology was as follows: In humans, exogenous epinephrine promotes platelet aggregation by increasing platelet production from thromboxane B2, heightening the sensitivity of platelets to ADP and promoting the thrombin-induced binding of platelets to fibrinogen. Interestingly, platelets in patients with angina are more sensitive to increased endogenous serum catecholamine levels and thus, more prone to aggregation compared to normal controls.[5] We are concluded that acute myocardial infarction in our patient occurred due to acute stent thrombosis caused by exogenous epinephrine administration. To our knowledge, this is the first reported case of acute stent thrombosis after the intravenous administration of epinephrine for anaphylaxis. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Hemichorea after multiple bee stings

Bee sting is one of the most commonly encountered insect bites in the world. Despite the common occurrence of local and systemic allergic reactions, there are few reports of ischemic stroke after bee stings. To the best our knowledge, there have been no reports on involuntary hyperkinetic movement disorders after multiple bee stings. We report the case of a 50-year-old man who developed involuntary movements of the left leg 24 hours after multiple bee stings, and the cause was confirmed to be a right temporal infarction on a diffusion magnetic resonance imaging scan. Thus, we concluded that the involuntary movement disorder was caused by right temporal infarction that occurred after multiple bee stings.