Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

PURPOSE: An oral cholera vaccine (OCV), Euvichol, with thimerosal (TM) as preservative, was prequalified by the World Health Organization (WHO) in 2015. In recent years, public health services and regulatory bodies recommended to eliminate TM in vaccines due to theoretical safety concerns. In this study, we examined whether TM-free Euvichol induces comparable immunogenicity to its TM-containing formulation in animal model. MATERIALS AND METHODS: To evaluate and compare the immunogenicity of the two variations of OCV, mice were immunized with TM-free or TM-containing Euvichol twice at 2-week interval by intranasal or oral route. One week after the last immunization, mice were challenged with Vibrio cholerae O1 and daily monitored to examine the protective immunity against cholera infection. In addition, serum samples were obtained from mice to measure vibriocidal activity and vaccine-specific IgG, IgM, and IgA antibodies using vibriocidal assay and enzyme-linked immunosorbent assay, respectively. RESULTS: No significant difference in immunogenicity, including vibriocidal activity and vaccine-specific IgG, IgM, and IgA in serum, was observed between mice groups administered with TM-free and -containing Euvichol, regardless of immunization route. However, intranasally immunized mice elicited higher levels of serum antibodies than those immunized via oral route. Moreover, intranasal immunization completely protected mice against V. cholerae challenge but not oral immunization. There was no significant difference in protection between two Euvichol variations. CONCLUSION: These results suggested that TM-free Euvichol could provide comparable immunogenicity to the WHO prequalified Euvichol containing TM as it was later confirmed in a clinical study. The pulmonary mouse cholera model can be considered useful to examine in vivo the potency of OCVs.
Animals* ; Antibodies ; Cholera Vaccines ; Cholera* ; Clinical Study ; Enzyme-Linked Immunosorbent Assay ; Immunization ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin M ; Mice ; Models, Animal* ; Public Health ; Thimerosal ; Vaccines ; Vibrio cholerae O1 ; World Health Organization

BACKGROUND: It is important to ensure that patients are normothermic during surgery. In total knee arthroplasty, the pneumatic tourniquet affects body temperature. We compared the ability of two warming devices to preserve core temperature in patients using a lower limb tourniquet under general anesthesia. METHODS: We included 132 patients with American Society of Anesthesiologists physical status I-II who were scheduled to undergo total knee arthroplasty. The patients were randomly divided into four groups (n = 33): group 1, without any heating method; group 2, with fluid warming; group 3, with forced-air warming; and group 4, with a combination of the two heating methods. After the induction of anesthesia, the esophageal and urinary bladder temperatures were monitored and recorded every 5 min before tourniquet deflation and every 1 min after tourniquet deflation. RESULTS: Before tourniquet deflation, compared with group 1, the odds ratios of groups 3 and 4 were less than 1. After tourniquet deflation, compared with group 1, the odds ratios of all groups using warming devices were less than 1. In particular, group 4 showed the largest hypothermia-preventive effect among the four groups. There was a significant correlation between esophageal temperature and bladder temperature before and after tourniquet deflation. CONCLUSIONS: After tourniquet deflation, a combination of a fluid warmer and forced-air warmer is the most effective method to prevent hypothermia, although either a fluid warmer or forced-air warmer alone could help to prevent hypothermia. Urinary bladder temperature changes correlate well with esophageal temperature changes throughout this operation.
Anesthesia ; Anesthesia, General ; Arthroplasty* ; Arthroplasty, Replacement, Knee ; Body Temperature ; Heating ; Hot Temperature ; Humans ; Hypothermia ; Knee* ; Lower Extremity ; Methods* ; Odds Ratio ; Tourniquets* ; Urinary Bladder

BACKGROUND: The increasing rate of drug-resistant tuberculosis (TB) is a threat to the public health and TB control. In Korea, about 75~80% of TB patients are treated in private hospitals and the rate has been continuously increasing since 2000. METHODS: On a retrospective basis, we enrolled 170 newly diagnosed with or retreated for multidrug-resistant TB (MDR-TB) in 2004 from 21 private hospitals. We extracted the following demographics and treatment history from patient medical records: initial treatment outcomes, cumulative survival rates, treatment outcomes, and prognostic factors. RESULTS: Of the 170 patients, the majority were male (64.1%), the mean age was 44.5 years old, and mean body-mass-index was 20.2 kg/m2. None of the patients tested positive for HIV. Eleven (6.5%) were confirmed to have extensively drug-resistant TB (XDR-TB) at treatment initiation. Treatment success rates were not different between XDR-TB (36.4%, 4/11) and non-XDR MDR-TB (51.6%, 82/159). Default rate was high, 21.8% (37/170). Far advanced disease on X-ray was a significant negative predictor of treatment success; advanced disease and low BMI were risk factors for all-cause mortality. CONCLUSION: In private hospitals in Korea, the proportion of XDR-TB in MDR-TB was comparable to previous data. The treatment success rate of MDR-/XDR-TB remains poor and the failure rate was quite high. Adequate TB control policies should be strengthened to prevent the further development and spread of MDR-/XDR-TB in Korea.
Demography ; Extensively Drug-Resistant Tuberculosis ; HIV ; Hospitals, Private ; Humans ; Korea ; Male ; Public Health ; Retrospective Studies ; Risk Factors ; Survival Rate ; Tuberculosis, Multidrug-Resistant

BACKGROUND: Three isoforms of the neuronal acetylcholine receptors (AChRs) have been described in muscle epsilonAChRs, gammaAChRs and alpha7AChRs. The adult neuromuscular junctions are composed of epsilonAChRs. During immobilization, new AChRs with subunit compositions of gammaAChRs and alpha7AChRs appear in the perijunctional and extrajunctional area. This study evaluated the contribution of these isoforms to neurotransmission during immobilization, by using waglerin-1 which selectively blocks the epsilonAChRs. METHODS: Male mice (n = 20) were used and each group was divided into sham operated or immobilized. A leg was immobilized in mice for 14 days by pinning, after which nerve-evoked twitch tension was examined under anesthesia in tibialis muscle of both legs, with the contralateral leg serving as control. Neuromuscular transmission was monitored by using a peripheral nerve stimulator with the tibialis muscle and sciatic nerve. Electrical stimuli of 0.2 msec duration were applied to sciatic nerve 2 Hz for 2 sec every 30 sec. After administration of waglerin-1, the evoked twitch was recorded. The percent depression of T1 relative to baseline was transformed to probit scale to determine the effective dose of waglerin-1 for 5%, 50%, and 95% twitch depression. RESULTS: The twitch tension in the control group was higher than immobilized group, confirming the efficacy of immobilization. Waglerin-1 produced 99% twitch suppression on the control group. But on the immobilized group, waglerin-1 produced only 70% twitch suppression even at 37 pg. CONCLUSIONS: The functional role of epsilonAChRs in neurotransmission decreases during immobilization while that of gammaAChRs and alpha7AChRs increases.
Adult ; Anesthesia ; Animals ; Depression ; Hindlimb ; Humans ; Immobilization ; Leg ; Male ; Mice ; Muscles ; Neuromuscular Junction ; Neurons ; Peripheral Nerves ; Protein Isoforms ; Receptors, Cholinergic ; Salicylamides ; Sciatic Nerve ; Synaptic Transmission

BACKGROUND: The precise measurement of body temperature during anesthesia is important to prevent hypothermia.The aim of this study was to compare the urinary bladder temperature to the esophageal, nasopharyngeal, rectal and skin temperatures, and to compare three heating methods during spine surgery. METHODS: Forty-two patients with ASA physical status I-II, who were scheduled to undergo spine surgery in the prone position, were included in this study.The patients were randomly divided into 4 groups:Group I was treated without any heating methods; group 2, with fluid-warmers; group 3, with forced air-warmers; and group 4, with a combination of both heating methods.After the induction of anesthesia, the esophageal, nasopharyngeal, rectal, urinary bladder and skin temperature was monitored every 15 minute for 3 hours.The urinary bladder temperature was compared to the esophageal, nasopharyngeal, rectal and skin temperatures. RESULTS: The urinary bladder temperature was found to be higher than the esophageal and the nasopharyngeal temperatures (P < 0.01).The urinary bladder temperature of group 3 was higher than that of group 1 at 180 minutes after induction of anesthesia (P < 0.05).The urinary bladder temperature of group 4 was higher than that of group 1 at 150 minutes (P < 0.05), as well as at 165 and 180 minutes (P < 0.05).The skin temperatures of groups 3 and 4 were higher than group 1 (P < 0.001). CONCLUSIONS: The urinary bladder temperature was higher than the esophageal temperature and correlated with the esophageal, nasopharyngeal and rectal temperatures.During spine surgery in the prone position, a forced air-warmer was found to be the most effective but a combination of all the methods tested was found to be even more effective.
Anesthesia ; Body Temperature ; Heating ; Hot Temperature ; Humans ; Prone Position ; Skin ; Skin Temperature ; Spine ; Urinary Bladder

BACKGROUND: The number of elderly patients undergoing orthopedic surgery is steadily growing. Aging modifies the physiology, pharmacokinetics and pharmacodynamics, and co-morbidity is common in the elderly. Therefore, it is important and necessary to evaluate the anesthetic management for orthopedic surgery in elderly patients. METHODS: Four hundred and twenty two patients, older than 80 yr, who underwent orthopedic surgery, between September 1996 and March 2004, were retrospectively reviewed according to age, sex, operation site, preexisting concomitant disease, anesthetic techniques, postoperative complications and mortality. RESULTS: Three hundred and fifty seven patients had a pre-existing concomitant disease. There were no meaningful differences in the postoperative morbidity and mortality according to the anesthetic technique employed, although there was a clearly reduced incidence of deep vein thrombosis with regional anesthesia. There were significantly higher postoperative morbidity and mortality among patients with a pre-existing concomitant disease. CONCLUSIONS: Appropriate anesthetic management is suggested for patients older than 80 yr undergoing orthopedic surgery, which will require proper preoperative evaluation, sufficient vigilance of their hemodynamics and an awareness of impaired circulatory function, as well as other age related concerns.
Aged ; Aging ; Anesthesia* ; Anesthesia, Conduction ; Hemodynamics ; Humans ; Incidence ; Mortality ; Orthopedics* ; Pharmacokinetics ; Physiology ; Postoperative Complications ; Retrospective Studies ; Venous Thrombosis

BACKGROUND:Rocuronium is a non depolarizing muscle relaxant of rapid onset and of intermediate duration. It is useful for short operations and for rapid control of the airway in pediatric patients. However the intravenous injection of rocuronium cause pain and a withdrawal movement. The purpose of this study was to evaluate the effect of lidocaine pretreatment in pediatric patients receiving rocuronium (10 mg/ml) and diluted rocuronium (1 mg/ml) on withdrawal movement METHODS: The study was approved by our institutional review board, and informed consent was obtained from all parents. One hundred and twenty five patients, aged from 4 months to 10 years, ASA physical status 1-2 undergoing general anesthesia for elective surgery were randomly enrolled in the study. Allergy history to a trial drug, pediatric patients on analgesics, difficult vein access and severely crying pediatric patients on arrival were excluded. All patients were non-premedicated and had a 22 G i.v. catheter inserted into the dorsum of hand before operation. On arrival in the operation room, routine non invasive monitors were placed and a free flow of i.v. fluid without edema, redness, hardness or pain was confirmed. After the administration of glycopyrrolate 0.004 mg/kg, inhalational induction was performed with 4-8 vol% sevoflurane by face mask fitting. One group received rocuronium 0.3 mg/kg (RS group) or vecuronium 0.05 mg/kg (VS group) was administered after 0.5 ml of 0.9% NaCl. A second group received rocuronium 0.3 mg/kg (RL group) or vecuronium 0.5 mg/kg (VL group) after lidocaine 1 mg/kg. A third group received rocuronium 1 mg/ml diluted with 0.9% NaCl (1:9) (RD group). Muscle relaxant-induced withdrawal movements were assessed by using a 4-grade scales (0-3). We also observed pulse rate alterations. Vein redness was evaluated just after administration and vein hardness five minutes after intubation by using a 4-grade scale (0-3). RESULTS: Withdrawal movements were more intense in the rocuronium group (R group, 3.8 times, P < 0.01) than in the vecuronium group (V group). Lidocaine pretreatment (L group, 1.8 times, P < 0.01) or diluted rocuronium (RD group, 1.9 times, P < 0.01) decreased withdrawal movement incidence. Withdrawal movement incidence was positive correlated with a change in pulse rate (Spearman's rho = 0.36, P < 0.01). CONCLUSIONS: Lidocaine pretreatment in patients receiving rocuronium (10 mg/ml) or diluted rocuronium (1 mg/ml) effectively reduces withdrawal movement during the administration of rocuronium.
Analgesics ; Anesthesia, General ; Catheters ; Crying ; Edema ; Ethics Committees, Research ; Glycopyrrolate ; Hand ; Hardness ; Heart Rate ; Humans ; Hypersensitivity ; Incidence ; Informed Consent ; Injections, Intravenous ; Intubation ; Lidocaine* ; Masks ; Parents ; Vecuronium Bromide ; Veins ; Weights and Measures

Hemorrhage through the pancreatic duct into the duodenum, so called 'hemosuccus pancreaticus', is a rare cause of gastrointestinal bleeding with diagnostic difficulties. We report a 44-year-old man with recurrent upper gastrointestinal bleeding due to rupture of pseudoaneurysm into the pancreatic duct. Initial upper gastrointestinal endoscopy failed to identity the site of the hemorrhage. Active bleeding from the ampulla of Vater in duodenum was found on repeat endoscopy. Abdominal computed tomography disclosed pseudoaneurysm arising from the splenic artery caused by chronic pancreatitis. Splenic angiogram showed large psudoaneurysmal sac with wide neck, arising from distal splenic artery. Angiographic embolization was successful in controlling the arterial hemorrhage. The patient remained symptom-free 5 months after the embolization. Hemosuccus pancreaticus, although rare, remains important in the differential diagnosis of upper gastrointestinal bleeding of obscure orgin.
Adult ; Ampulla of Vater* ; Aneurysm, False ; Diagnosis, Differential ; Duodenum ; Endoscopy ; Endoscopy, Gastrointestinal ; Hemorrhage* ; Humans ; Neck ; Pancreatic Ducts ; Pancreatitis, Chronic ; Rupture ; Splenic Artery

PURPOSE: Our examination was designed to determine the diagnostic properties of the cutoff point for the prediction of bacteremia in febrile children less than 3 years of age. Cutoff point is the value that simultaneously maximizes both sensitivity and specificity. METHODS: We conducted a retrospective study of febrile children, less than 3 years of age, who clinically have no identifiable source of fever. Peripheral blood leukocyte count(WBC), absolute neutrophil count(ANC), erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) were measured at the same time. All patients received blood culture, urine culture and/or CSF culture. Bacterial infection was defined as single pathogen isolated from the CSF or blood or a urinary tract infection (UTI). Patients were dichotomized into two groups: those with bacterial infection and no bacterial infection. We analyzed the characteristics of the children in the two groups. RESULTS: Seventy-one patients(44 males; 27 females) were enrolled in the study. Twenty patients (28%) had a serious bacterial infection(twelve urinary tract infection, five bacteremia, three meningitis) and fifty-one(72%) had no serious bacterial infection. WBC, ESR and CRP were significantly different between the two groups(P<0.05). The cutoff point of WBC, ESR and CRP were 20,000/mm3, 30 mm/hr and 3.0 mg/dL, respectively. The sensitivity and specificity of each cutoff point were WBC(75%, 75%), ESR(79%, 68%) and CRP(83%, 77%), respectively. CONCLUSION: These data show the ability of predictors to identify febrile children less than 3 years of age with bacterial infection. Febrile children who reach the cutoff point must be treated intensively and those who do not reach the cutoff point can be carefully managed without administering antimicrobial agents.
Anti-Infective Agents ; Bacteremia ; Bacterial Infections* ; Blood Sedimentation ; Child* ; Fever ; Humans ; Leukocytes ; Male ; Neutrophils ; Retrospective Studies ; Sensitivity and Specificity ; Urinary Tract Infections