Regulatory T cells (Treg) naturally rein in immune attacks, and they can inhibit rejection of transplanted organs and even reverse the progression of autoimmune diseases in mice. The initial safety trials of Treg against graft-versus-host disease (GVHD) provided evidence that the adoptive transfer of Treg is safe and capable of limiting disease progression. Supported by such evidence, numerous clinical trials have been actively investigating the efficacy of Treg targeting autoimmune diseases, type I diabetes, and organ transplant rejection, including kidney and liver. The limited quantity of Treg cells harvested from peripheral blood and subsequent in vitro culture have posed a great challenge to large-scale clinical application of Treg; nevertheless, the concept of CAR (chimeric antigen receptor)-Treg has emerged as a potential resolution to the problem. Recently, two CAR-T therapies, tisagenlecleucel and axicabtagene ciloleucel, were approved by the US FDA for the treatment of refractory or recurrent acute lymhoblastic leukemia. This approval could serve as a guideline for the production protocols for other genetically engineered T cells for clinical use as well. The phase I and II clinical trials of these agents has demonstrated that genetically engineered and antigen-targeting T cells are safe and efficacious in humans. In conclusion, both the promising results of Treg cell therapy from the clinical studies and the recent FDA approval of CAR-T therapies are paving the way for CAR-Treg therapy in clinical use.
Adoptive Transfer ; Animals ; Autoimmune Diseases ; Cell- and Tissue-Based Therapy* ; Disease Progression ; Graft vs Host Disease ; Humans ; In Vitro Techniques ; Kidney ; Leukemia ; Liver ; Mice ; T-Lymphocytes ; T-Lymphocytes, Regulatory* ; Transplantation ; Transplants

Objectives: Public healthcare data have become crucial to the advancement of medicine, and recent changes in legal structure on privacy protection have expanded access to these data with pseudonymization. Recent debates on public healthcare data use by private insurance companies have shown large discrepancies in perceptions among the general public, healthcare professionals, private companies, and lawmakers. This study examined public attitudes toward the secondary use of public data, focusing on differences between public and private entities. Methods: An online survey was conducted from January 11 to 24, 2022, involving a random sample of adults between 19 and 65 of age in 17 provinces, guided by the August 2021 census. Results: The final survey analysis included 1,370 participants. Most participants were aware of health data collection (72.5%) and recent changes in legal structures (61.4%) but were reluctant to share their pseudonymized raw data (51.8%). Overall, they were favorable toward data use by public agencies but disfavored use by private entities, notably marketing and private insurance companies. Concerns were frequently noted regarding commercial use of data and data breaches. Among the respondents, 50.9% were negative about the use of public healthcare data by private insurance companies, 22.9% favored this use, and 1.9% were “very positive.” Conclusions This survey revealed a low understanding among key stakeholders regarding digital health data use, which is hindering the realization of the full potential of public healthcare data. This survey provides a basis for future policy developments and advocacy for the secondary use of health data.

Phage display technology provides a powerful tool to screen a library for a binding molecule via an enrichment process. It has been adopted as a critical technology in the development of therapeutic antibodies. However, a major drawback of phage display technology is that because the degree of the enrichment cannot be controlled during the bio-panning process, it frequently results in a limited number of clones. In this study, we applied next-generation sequencing (NGS) to screen clones from a library and determine whether a greater number of clones can be identified using NGS than using conventional methods. Three chicken immune single-chain variable fragment (scFv) libraries were subjected to bio-panning on prostate-specific antigen (PSA). Phagemid DNA prepared from the original libraries as well as from the Escherichia coli pool after each round of bio-panning was analyzed using NGS, and the heavy chain complementarity-determining region 3 (HCDR3) sequences of the scFv clones were determined. Subsequently, through two-step linker PCR and cloning, the entire scFv gene was retrieved and analyzed for its reactivity to PSA in a phage enzyme immunoassay. After four rounds of bio-panning, the conventional colony screening method was performed for comparison. The scFv clones retrieved from NGS analysis included all clones identified by the conventional colony screening method as well as many additional clones. The enrichment of the HCDR3 sequence throughout the bio-panning process was a positive predictive factor for the selection of PSA-reactive scFv clones.
Antibodies ; Bacteriophages ; Chickens ; Clone Cells* ; Cloning, Organism ; Complementarity Determining Regions ; DNA ; Escherichia coli ; Immunoenzyme Techniques ; Mass Screening ; Methods ; Polymerase Chain Reaction ; Prostate-Specific Antigen ; Single-Chain Antibodies

PURPOSE: National Emergency X-Radiography Utilization Study (NEXUS) criteria and the Canadian Cervical Spine rule (CCR) are commonly used in cervical trauma patients to determine whether a plain cervical X-ray should be performed. However, plain cervical X-rays are so inaccurate that cervical spine computed tomography (CT) is often considered as a screening test. We studied the usefulness of the NEXUS criteria and the CCR for determining the need for a CT evaluation in the emergency department (ED). METHODS: This prospective observational study was conducted from January 2007 to March 2008. Plain Xray and CT scans of the cervical spine were performed on blunt trauma patients with neck pain. The relevancy of CT was examined using the NEXUS criteria and the CCR. Sensitivity, specificity, positive predicted value, and negative predicted value analyses were performed to diagnose the cervical spine injury. RESULTS: During the study period, 284 patients were enrolled in this study. The sensitivity, specificity, positive predicted value, and negative predicted value of the NEXUS criteria were 87.5%, 1.1%, 5.0%, and 60.0% respectively, while those of the CCR were 87.5%, 8.2%, 5.3%, and 91.6%. There were two missed fracture cases when the NEXUS criteria and the CCR were applied independently, however, no cases were missed when both were applied. CONCLUSION: This study suggests the NEXUS and the CCR in combination can be used as a guide to CT evaluation for cervical spine injury in the ED.
Cervical Vertebrae ; Emergencies ; Female ; Humans ; Mass Screening ; Neck Pain ; Prospective Studies ; Resin Cements ; Sensitivity and Specificity ; Spine

Background and Objectives: The diagnosis of hearing impairment is based on repeated audiometry, including pure tone audiometry (PTA), speech reception threshold test (SRT), and speech discrimination test (SDT). SDT results particularly show a wide discrepancy upon repeated testing, while malingering is suspected when having more than 12% difference between 3 individual SDT results. Therefore, in this study, we compared the proportion of malingering found in repeated SDT with that found in other audiometric tests and analyzed the characteristics of malingering group in order to reevaluate the current criteria of defining malingering.Subjects and Method We retrospectively assessed the audiometry results of 113 patients (226 ears) with hearing impairment. Each ear was divided into a malingering group and a true hearing loss group. The proportion of ears corresponding to each malingering criterion was compared using a chi-square test. An independent sample t-test was performed to identify the differences between the characteristics between the two groups. Results: The number of ears that met the malingering criteria were 19 (8.41%) in PTA, 15 (6.64%) in SRT, and 75 (33.19%) in SDT. There was a significant difference in the proportion of malingering between the 3 hearing test modalities (p<0.001). There was no significant difference in auditory brainstem response, mean age and sex distribution between the malingering group and the true hearing loss group. Conclusion When conducting repeated SDT, there is a risk of misdiagnosing an actual hearing loss patient as a malingering patient under the current malingering criteria. Therefore, the current criteria on SDT requires reevaluation.

PURPOSE: According to the 2010 guidelines for cardiopulmonary resuscitation (CPR) of the American Heart association, administration of atropine for non-shockable rhythm is no longer recommended, however, there are insufficient data in humans. This study was conducted to evaluate the results of CPR, whether the combined administration of atropine and epinephrine (Atropine combined group, AG) compared with epinephrine only injection (epinephrine only group, EG) for patients with non-shockable rhythm. METHODS: A total of 449 patients who underwent CPR in the emergency department from 2009 to 2012 were included. Retrospective analysis was performed according to atropine administration during CPR. We investigated Return of Spontaneous Circulation (ROSC), sustained ROSC, 30-day survival, and 30-day neurological outcome using Utstein templates. RESULTS: There were 178 (48.9%) patients in the AG. There were no significant differences in the baseline characteristics. The two groups had similar rates of ROSC, sustained ROSC, and 30-day survival. However, AG had a significantly poor neurological outcome compared to EG, with an adjusted odds ratio of 0.074 (95% CI 0.012-0.452, p=0.005). CONCLUSION: The combination therapy of atropine and epinephrine during CPR showed poor neurological outcome compared with epinephrine alone. Atropine is not useful for adults with non-shockable rhythm in terms of 30-day neurological outcome.
Adult ; American Heart Association ; Atropine* ; Cardiopulmonary Resuscitation* ; Emergency Service, Hospital ; Epinephrine ; Heart Arrest ; Humans ; Odds Ratio ; Retrospective Studies

PURPOSE: Transfer from long-term care (LTC) hospitals to the emergency department (ED) of larger hospitals has increased due to limited capability for management of patients needing special diagnostic tools or emergency treatment in the LTC hospital. We investigated the characteristics of geriatric trauma patients transferred from LTC hospitals to the ED. METHODS: A retrospective analysis included data on geriatric trauma patients (age> or =65) who visited two EDs in Korea. All data of patients transferred from the LTC hospital were compared with those of patients who visited the ED from home. Patients visiting from home were selected according to age, sex, and main diagnosis, using the statistical matching method. RESULTS: A total of 44 patients were transferred, and 132 patients were selected after matching. No differences in mechanism of injury, injury severity score (ISS), outcomes, transfusion, length of hospital stay, or mortality were observed between the two groups. The odds ratios (OR) of transferred patients for stroke and dementia were 5.027 (95% confidence interval (CI) 1.292-16.915) and 13.941 (95% CI: 5.112-38.015), respectively. In addition, the OR of transferred patients for dependent activities of daily living was 8.165 (95% CI: 2.886-23.104). Thirty five transferred patients (79.5%) had been injured in the LTC hospital (p<0.001). CONCLUSION: The transferred patients had more stroke, dementia, and dependent activities, but showed no significant difference in severity or prognosis. Most transferred patients had been injured in the hospital. Greater attention to hospitalized patients and system development are required in order to prevent injuries in the LTC hospital.
Activities of Daily Living ; Dementia ; Diagnosis ; Emergency Service, Hospital ; Emergency Treatment ; Geriatrics ; Humans ; Injury Severity Score ; Korea ; Length of Stay ; Long-Term Care* ; Mortality ; Odds Ratio ; Prognosis ; Propensity Score* ; Retrospective Studies ; Stroke

PURPOSE: The primary prevention and proper initial treatment of childhood injuries is important, as it encompasses a bigger social and economic burden than cancer and ischemic heart disease. The Pediatric Risk of Mortality III (PRISM III) scoring system, used to evaluate the severity or mortality of pediatric patients in critical condition, was investigated for children with injuries in an emergency department (ED). METHODS: A retrospective analysis included data on 293 injured children (age<16) who visited the ED in two hospitals from March 2010 to February 2012. Physiologic and laboratory data were collected to calculate the PRISM III score and the Injury Severity Score (ISS). The correlation was analyzed between PRISM III scores, the Revised Trauma Scale (RTS), and ISS. The PRISM III score and ISS were assessed for their ability to predict mortality by comparing their receiver operating characteristic (ROC) curves. RESULTS: The median PRISM III score was 5.0 (Interquartile Range, 5.0-9.0) and correlated with RTS and ISS (the Spearman's rho were -0.19 (p=0.001) and 0.20 (p=0.001), respectively. Five children did not survive after ED admission. The area under the ROC (AUC) was 1.00 for PRISM III (95% confidence interval [CI], 0.99-1.00), and the cutoff value was placed over 20 to predict mortality. The AUC of ISS and RTS was 0.99 (95% CI, 0.98-1.00) and 0.99 (95% CI, 0.98-1.00), respectively. CONCLUSION: The PRISM III score excellently predicts the mortality of injured children in the ED, and can be used to sort minor pediatric trauma patients in the ED. However, the PRISM III score had no great difference or advantage compared with RTS. The development of other tools for effective prognosis is needed to efficiently predict mortality and severity in the ED.
Area Under Curve ; Child ; Emergencies ; Humans ; Imidazoles ; Injury Severity Score ; Myocardial Ischemia ; Nitro Compounds ; Primary Prevention ; Prognosis ; Retrospective Studies ; ROC Curve

The complement system is a part of the innate immune system that potentiates the ability of antibodies and phagocytic cells to clear microbes and damaged cells. The complement system consists of a number of proteins circulating as inactive precursors. It is stimulated mainly by three pathways: the classical pathway, the alternative pathway, and the lectin pathway. There are many genetic polymorphisms in this system, which can over-activate the immune system. In this study, we collected the polymorphisms reported to over-activate complement cascades that affect the immune system and induce autoimmune diseases.
Antibodies ; Autoimmune Diseases ; Complement System Proteins* ; Immune System ; Phagocytes ; Polymorphism, Genetic*

This case series evaluated the clinical efficacy of autogenous tooth bone graft material (AutoBT) in alveolar ridge preservation of an extraction socket. Thirteen patients who received extraction socket graft using AutoBT followed by delayed implant placements from Nov. 2008 to Aug. 2010 were evaluated. A total of fifteen implants were placed. The primary and secondary stability of the placed implants were an average of 58 ISQ and 77.9 ISQ, respectively. The average amount of crestal bone loss around the implant was 0.05 mm during an average of 22.5 months (from 12 to 34 months) of functional loading. Newly formed tissues were evident from the 3-month specimen. Within the limitations of this case, autogenous tooth bone graft material can be a favorable bone substitute for extraction socket graft due to its good bone remodeling and osteoconductivity.
Alveolar Process* ; Bone Remodeling ; Bone Substitutes ; Dental Implants ; Humans ; Prospective Studies* ; Tooth* ; Transplantation ; Transplants*