Nitric Oxide Signal Transduction and Its Role in Skin Sensitization

Nitric oxide (NO) is a signaling molecule that plays a crucial role in numerous cellular physiological processes. In the skin, NO is produced by keratinocytes, fibroblasts, endothelial cells, and immune cells and is involved in skin functions such as vasodilation, pigmentation, hair growth, wound healing, and immune responses. NO modulates both innate and adaptive immune responses. As a signaling molecule and cytotoxic effector, NO influences the function of immune cells and production of cytokines. NO is a key mediator that protects against or contributes to skin inflammation. Moreover, NO has been implicated in skin sensitization, a process underlying contact dermatitis. It modulates the function of dendritic cells and T cells, thereby affecting the immune response to allergens. NO also plays a role in contact dermatitis by inducing inflammation and tissue damage. NO-related chemicals, such as nitrofatty acids and nitric oxide synthase (NOS) inhibitors, have potential therapeutic applications in skin conditions, including allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD). Further research is required to fully elucidate the therapeutic potential of NO-related chemicals and develop personalized treatment strategies for skin conditions.

Effects of angiotensin peptides on colonic motility in rats

Purpose@#Renin-angiotensin system (RAS) is involved in the pathophysiology of colonic inflammation. The aim of this study was to investigate whether small angiotensins (Angs) peptides play a role in the regulation of colonic motility and their roles are modulated in colitis. @*Methods@#Experimental colitis was induced by an intake of 5% dextran sulfate sodium (DSS) dissolved in tap water for 7 days in Sprague-Dawley rats. After sacrifice, plasma hormone concentrations and messenger RNAs (mRNAs) for RAS were measured. Functional analysis of colonic motility in response to Angs peptides was performed using Taenia coli. @*Results@#DSS-treated colon showed an increased necrosis with massive infiltration of inflammatory cells. The mRNA level of colonic angiotensin II receptor type 2 (AT2R) in DSS-treated rats was higher than that in control rats whereas the mRNA levels of angiotensin II converting enzyme (ACE), ACE2, AT1R, AT4R, and Mars receptor were not different from those in control rats. Ang III, Ang IV, and Ang-(1-9) (1, 3 μM) increased the frequency of basal colonic motility. Ang-(1-7) did not cause any significant changes in frequency and amplitude of basal motility. The order of potency for an increased frequency of basal motility seems to be Ang II>>Ang IV>Ang III=Ang-(1-9). The increased frequency of basal motility by Ang-(1-9) but not Ang IV was significantly enhanced in DSS-treated rat colon. @*Conclusion@#In conclusion, these data suggest that small Angs peptides are partly involved in the pathophysiological regulation of colonic motility in experimental colitis.

Effect of a Patient Blood Management Program on the Appropriateness of Red Blood Cell Transfusion and Clinical Outcomes in Elderly Patients Undergoing Hip Fracture Surgery

Background@#Elderly patients with hip fractures frequently receive perioperative transfusions, which are associated with increased morbidity and mortality. This study aimed to evaluate the impact of a patient blood management (PBM) program on the appropriateness of red blood cell (RBC) transfusion and clinical outcomes in geriatric patients undergoing hip fracture surgery. @*Methods@#In 2018, the revised PBM program was implemented at the Korea University Anam Hospital, Seoul, Republic of Korea. Elderly patients aged ≥ 65 years who underwent hip fracture surgery from 2017 to 2020 were evaluated. Clinical characteristics and outcomes were analyzed according to the timing of PBM implementation (pre-PBM, early-PBM, and late-PBM). Multiveriate regression analysis was used to evaluate the risk factors of the adverse outcomes, such as in-hospital mortality or 30-day readmission. @*Results@#A total of 884 elderly patients were included in this study. The proportion of patients who received perioperative RBC transfusions decreased significantly (43.5%, 40.1%, and 33.2% for pre-PBM, early-PBM, and late-PBM, respectively; P = 0.013). However, the appropriateness of RBC transfusion significantly increased (54.0%, 60.1%, and 94.7%, respectively; P < 0.001). The duration of in-hospital stay and 30-day readmission rates significantly decreased. Multivariable regression analysis revealed that RBC transfusion (odds ratio, 1.815; 95% confidence interval, 1.137–2.899; P = 0.013) was significantly associated with adverse outcomes. @*Conclusion@#Implementing the PBM program increased the appropriateness of RBC transfusion without compromising transfusion quality and clinical outcomes. Therefore, adopting the PBM program may improve the clinical management of elderly patients following hip fracture surgery.

Treatment for subarachnoid hemorrhage due to ruptured posterior cerebral arterial dolichoectasia with aortic arch anomaly

Subarachnoid hemorrhage (SAH) due to ruptured posterior cerebral artery (PCA) intracranial arterial dolichoectasia (IADE) is very rare. As these lesions are difficult to treat microsurgically, neurointervention is preferred because the dolichoectatic artery does not have a clear neck, and the surgical field of view was deep seated with the SAH. However, in some cases, neurointervention is difficult due to anatomical variation of the blood vessel to access the lesion. In this case, a 30-year-old male patient presented with a ruptured PCA IADE and an aortic arch anomaly. Aortic arch anomalies render it difficult to reach the ruptured PCA IADE via endovascular treatment. The orifice of the vertebral artery (VA) was different from the usual cases, so it was difficult to find the entrance. After only finding the VA and arriving at the lesion along the VA, trapping was performed. Herein, we report the PCA IADE with aortic arch anomaly endovascular treatment methods and results.

Clinical Utility of Procalcitonin on Antibiotic Stewardship: A Narrative Review

Procalcitonin (PCT) was discovered as a useful marker for bacterial infection. Following its discovery, there have been a substantial number of clinical studies conducted to evaluate the presence of bacterial infections, and to guide antibiotic treatment by the stratified levels of PCT. Clinical evidence suggests that antibiotic treatment by PCT-guided antibiotic stewardship has been associated with a reduction in antibiotic usage without an increase in adverse outcomes. The use of PCT was approved by the Food and Drug Administration in the United States of America in 2017 to guide antibiotic treatment in sepsis and lower respiratory tract infections (LRTIs). In Korea, the use of PCT for sepsis and for pneumonia was approved in 2015 and 2022, respectively. This review will discuss the clinical utility of PCT on antibiotic stewardship in the management of sepsis and LRTIs including pneumonia.

Implementation of Procalcitonin in Antibiotic Stewardship: Derivation of a Consensus Algorithm for Procalcitonin Use in Clinical Practice

Reducing antibiotics overuse is essential to minimize antibiotics related side effects and to prevent the emergence of multidrug-resistant bacteria. Procalcitonin (PCT) guided antibiotics therapy has been reported to be safe in patients with acute respiratory infections and sepsis, improving clinical outcomes as well as reducing the duration of antibiotics use.However, there is still no universal agreement on clinical guidelines in Korea for optimal PCT applications. Through this expert consensus meeting, clinical research findings in the PCT-guided antibiotics treatment interventions and real-world clinical applications were discussed. From the perspective of antibiotic stewardship, PCT application target groups, cut-offs, and testing cycles were discussed to reach a consensus on the PCT-guided antibiotics treatment algorithm for application in Korea. Combining clinical assessment for patients with an appropriate PCT-guided antibiotics treatment algorithm could improve the diagnosis and treatment of acute respiratory infections and sepsis. In addition, continuous education and regular feedback would improve the effectiveness of antibiotic stewardship.

Effects of Socioeconomic Status and Residence Areas on Long-Term Survival in Patients With Early-Onset Dementia: The Korean National Health Insurance Service Database Study

Background@#Early-onset dementia (EOD) is still insufficiently considered for healthcare policies. We investigated the effect of socio-environmental factors on the long-term survival of patients with EOD. @*Methods@#This retrospective cohort study utilized the Korean National Health Insurance Database from 2007 to 2018. We enrolled 3,825 patients aged 40 to 65 years old with all types of dementia newly diagnosed in 2009 as EOD cases. We defined socioeconomic status using the national health insurance premium (NHIP) levels. Residential areas were classified into capital, metropolitan, city, and county levels. All-cause mortality was the primary outcome. Kaplan-Meier curves and log-rank tests were employed. Further, Cox-proportional hazards models were established. @*Results@#The mean survival of the fourth NHIP level group was 96.31 ± 1.20 months, whereas that of the medical-aid group was 85.53 ± 1.30 months (P < 0.001). The patients living in the capital had a mean survival of 95.73 ± 1.34 months, whereas those living in the county had 89.66 ± 1.75 months (P = 0.035). In the Cox-proportional hazards model, the medical-aid (adjusted hazard ratio [aHR], 1.67; P < 0.001), first NHIP level (aHR, 1.26; P = 0.012), and second NHIP level (aHR, 1.26; P = 0.008) groups were significantly associated with a higher long-term mortality risk. The capital residents exhibited a significantly lower long-term mortality risk than did the county residents (aHR, 0.82; P = 0.041). @*Conclusion@#Socioeconomic status and residential area are associated with long-term survival in patients with EOD. This study provides a rational basis for establishing a healthcare policy for patients with EOD.

Minimally Invasive Proximal Transverse Metatarsal Osteotomy Followed by Intramedullary Plate Fixation for Hallux Valgus Deformity: A Case Report / 대한족부족관절학회지

More than 120 surgical methods for the correction of hallux valgus deformities have been reported. For the correction of moderate to severe hallux valgus deformities with aesthetic demands, minimally invasive surgery at the proximal area can be considered. This paper reports a case of moderate hallux valgus deformity treated by a minimally invasive proximal transverse metatarsal osteotomy followed by intramedullary plate fixation.

Incidence and Reappraisal of Known Risk Factors Associated With Carpal Tunnel Syndrome: A Nationwide, 11-Year, Population-Based Study in South Korea

Background@#and PurposePrevious studies have revealed various risk factors for carpal tunnel syndrome (CTS), but few large-scale studies have been conducted. We used data from the 11-year, longitudinal, nationwide population-based National Health Insurance Service–National Health Screening cohort to identify the actual risk factors for CTS. @*Methods@#We collected patients with CTS newly diagnosed using electrodiagnostic studies while excluding radiculopathy, plexopathy, or polyneuropathy, which can be confused with CTS. The crude and standardized incidence rates of CTS were calculated. Univariate and multivariate Cox analyses and the incidence of CTS were used to identify the risk factors for newly diagnosed CTS. @*Results@#The standardized incidence was 130.8/100,000 person-years based on the World Health Organization World Standard Population as a reference. Multivariate Cox analysis identified that the risk factors for CTS were being middle-aged, female, and obese, and having rheumatoid arthritis and Raynaud's syndrome, whereas gout and hypothyroidism were not risk factors. Diabetes and end-stage renal disease did not show a significant hazard ratio, although it is implicit that the durations of these diseases affect the development of CTS. @*Conclusions@#This study calculated the incidence of CTS and reappraised the associated risk factors found in previous studies. This information will be helpful for determining the pathophysiology of CTS, and hence aid the establishment of effective new public health policies.

Establishment of the Korea National Health and Nutrition Examination Survey air pollution study dataset for the researchers on the health impact of ambient air pollution / 한국역학회지

To provide a nationwide representative dataset for the study on health impact of air pollution, we combined the data from the Korea National Health and Nutrition Examination Survey with the daily air quality and weather data by matching the date of examination and the residential address of the participants. The database of meteorological factors and air quality as sources of exposure data were estimated using the Community Multiscale Air Quality model. The linkage dataset was merged by three ways; administrative district, si-gun-gu (city, county, and district), and geocode (in latitude and longitude coordinate units) based on the participants’ residential address, respectively. During the study period, the exposure dataset of 85,018 individuals (38,306 men and 46,712 women) whose examination dates were recorded were obtained. According to the definition of exposure period, the dataset was combined with the data on short-term, mid-term, and long-term exposure to air pollutants and the meteorological indices. Calculation of the daily merged dataset’s average air pollution linked by si-gun-gu and geocode units showed similar results. This study generated a daily average of meteorological indices and air pollution exposure dataset for all regions including rural and remote areas in Korea for 11 years. It is expected to provide a platform for the researchers studying the health impact of air pollution and climate change on the representative population and area, which may facilitate the establishment of local health care plans by understanding the residents’ health status at the local as well as national level.

Fournier Gangrene in a Patient With Type 2 Diabetes Mellitus Treated With Dapagliflozin: A Case Report

Rare cases of Fournier gangrene (FG) possibly associated with sodium-glucose cotransporter 2 inhibitors have been reported. We present a case of a 66-year-old male patient with type 2 diabetes mellitus on oral metformin, glimepiride, and dapagliflozin therapy. He presented with pain in the perineum and scrotum for 5 days. The clinical finding, computed tomography finding, and laboratory data were matched with FG. Emergency surgical drainage, debridement of necrotic tissue, and diverting loop ileostomy formation were performed by a urologist and a surgeon. The patient had no complications from diabetes before the onset of FG, and serum glucose management was good at the onset of FG. This case shows an FG patient with good glucose management taking dapagliflozin and suggests a possible association between dapagliflozin and FG. Further evaluation and additional research on this relationship are needed.

Minimally Invasive Proximal Transverse Metatarsal Osteotomy Followed by Intramedullary Plate Fixation for Hallux Valgus Deformity: A Case Report / 대한족부족관절학회지

More than 120 surgical methods for the correction of hallux valgus deformities have been reported. For the correction of moderate to severe hallux valgus deformities with aesthetic demands, minimally invasive surgery at the proximal area can be considered. This paper reports a case of moderate hallux valgus deformity treated by a minimally invasive proximal transverse metatarsal osteotomy followed by intramedullary plate fixation.

Incidence and Reappraisal of Known Risk Factors Associated With Carpal Tunnel Syndrome: A Nationwide, 11-Year, Population-Based Study in South Korea

Background@#and PurposePrevious studies have revealed various risk factors for carpal tunnel syndrome (CTS), but few large-scale studies have been conducted. We used data from the 11-year, longitudinal, nationwide population-based National Health Insurance Service–National Health Screening cohort to identify the actual risk factors for CTS. @*Methods@#We collected patients with CTS newly diagnosed using electrodiagnostic studies while excluding radiculopathy, plexopathy, or polyneuropathy, which can be confused with CTS. The crude and standardized incidence rates of CTS were calculated. Univariate and multivariate Cox analyses and the incidence of CTS were used to identify the risk factors for newly diagnosed CTS. @*Results@#The standardized incidence was 130.8/100,000 person-years based on the World Health Organization World Standard Population as a reference. Multivariate Cox analysis identified that the risk factors for CTS were being middle-aged, female, and obese, and having rheumatoid arthritis and Raynaud's syndrome, whereas gout and hypothyroidism were not risk factors. Diabetes and end-stage renal disease did not show a significant hazard ratio, although it is implicit that the durations of these diseases affect the development of CTS. @*Conclusions@#This study calculated the incidence of CTS and reappraised the associated risk factors found in previous studies. This information will be helpful for determining the pathophysiology of CTS, and hence aid the establishment of effective new public health policies.

Establishment of the Korea National Health and Nutrition Examination Survey air pollution study dataset for the researchers on the health impact of ambient air pollution / 한국역학회지

To provide a nationwide representative dataset for the study on health impact of air pollution, we combined the data from the Korea National Health and Nutrition Examination Survey with the daily air quality and weather data by matching the date of examination and the residential address of the participants. The database of meteorological factors and air quality as sources of exposure data were estimated using the Community Multiscale Air Quality model. The linkage dataset was merged by three ways; administrative district, si-gun-gu (city, county, and district), and geocode (in latitude and longitude coordinate units) based on the participants’ residential address, respectively. During the study period, the exposure dataset of 85,018 individuals (38,306 men and 46,712 women) whose examination dates were recorded were obtained. According to the definition of exposure period, the dataset was combined with the data on short-term, mid-term, and long-term exposure to air pollutants and the meteorological indices. Calculation of the daily merged dataset’s average air pollution linked by si-gun-gu and geocode units showed similar results. This study generated a daily average of meteorological indices and air pollution exposure dataset for all regions including rural and remote areas in Korea for 11 years. It is expected to provide a platform for the researchers studying the health impact of air pollution and climate change on the representative population and area, which may facilitate the establishment of local health care plans by understanding the residents’ health status at the local as well as national level.

Fournier Gangrene in a Patient With Type 2 Diabetes Mellitus Treated With Dapagliflozin: A Case Report

Rare cases of Fournier gangrene (FG) possibly associated with sodium-glucose cotransporter 2 inhibitors have been reported. We present a case of a 66-year-old male patient with type 2 diabetes mellitus on oral metformin, glimepiride, and dapagliflozin therapy. He presented with pain in the perineum and scrotum for 5 days. The clinical finding, computed tomography finding, and laboratory data were matched with FG. Emergency surgical drainage, debridement of necrotic tissue, and diverting loop ileostomy formation were performed by a urologist and a surgeon. The patient had no complications from diabetes before the onset of FG, and serum glucose management was good at the onset of FG. This case shows an FG patient with good glucose management taking dapagliflozin and suggests a possible association between dapagliflozin and FG. Further evaluation and additional research on this relationship are needed.

Reassessment of Inclusion Criteria in the 2013 the American College of Cardiology and the American Heart Association Cholesterol Guidelines for Cardiovascular Disease Prevention

Background@#and Purpose The American College of Cardiology and the American Heart Association (ACC-AHA) have released new guidelines and expanded indications for statin treatment. We aimed to reveal the clinical efficacy of each indication in the guidelines using a large-scale national cohort. @*Methods@#We used National Health Screening Cohort data to determine the proportions of participants for whom statin therapy would be recommended using the different guidelines.We assessed the cumulative incidence rates of major adverse cardiovascular events (MACE) using the Cox proportional-hazards model. @*Results@#Under the 2013 ACC-AHA guidelines, 111,600 participants were additionally eligible to receive statins, compared with 50,023 participants according to the Third Adult Treatment Panel (ATP-III). Most of the additional statin-eligible participants in the ACC-AHA guidelines were indicated by their 10-year cardiovascular disease risk. The increase in statineligible participants in the ACC-AHA guidelines mainly involved elderly patients aged 60–75 years. Among participants not requiring statin, participants who were eligible for a statin under the ACC-AHA guidelines had a significantly higher hazard ratio of MACE when compared with those eligible under the ATP-III guidelines. Among the not-recommended groups, patients with diabetes and low-density lipoprotein <70 mg/dL constituted the group with the highest risk of MACE. @*Conclusions@#The 2013 ACC-AHA guidelines increase the number of statin-eligible participants, especially among the elderly. These guidelines provide a stronger recommendation for statins to high-risk groups, but it remains necessary to consider the characteristics of the population in the risk equation. In addition, the aggressive use of statin in diabetes patients and further studies of older subjects are needed.

Characteristics of Klebsiella pneumoniae Isolates from Stool Samples of Patients with Liver Abscess Caused by Hypervirulent K. pneumoniae

BACKGROUND@#Hypervirulent Klebsiella pneumoniae (hvKP) has been the most significant pathogen for liver abscesses in East Asia including the Republic of Korea (ROK). Although gastrointestinal colonization of K. pneumoniae may cross the intestinal barrier to invade the liver, characteristics of gastrointestinal carriage K. pneumoniae of hvKP liver abscess patients in the ROK are not well known.@*METHODS@#Characteristics of K. pneumoniae isolated from stool samples and liver aspirate samples of patients with hvKP liver abscess at a tertiary care hospital in the ROK between 2017 and 2018 were evaluated.@*RESULTS@#Out of 37 patients with hvKP liver abscess, 11 patients were noted to have K. pneumoniae isolated from stool samples and were enrolled for analysis. The median age was 71 years. For hvKP isolates from the liver aspirate samples, the most common serotype was K1 (72.7%) followed by K2 (27.3%). For K. pneumoniae isolates from the stool sample, the majority was non-K1/K2 serotype (72.7%). Among non-K1/K2 serotype isolates, high variability of sequence type (ST; ST15, ST307, ST37, ST273, ST2622, and ST42) with high rate of presence of extended-spectrum beta-lactamase (100.0%) was noted. The concordance rate of the K. pneumoniae isolates between the liver aspirate samples and the stool samples from the primary hvKP liver abscess was low (27.3%).@*CONCLUSION@#This study suggests that significant heterogeneity of K. pneumoniae colonizing intestinal tract of the hvKP liver abscess patients. Further studies involving a larger number of hvKP liver abscess patients with continuing surveillance are needed to define the changing epidemiology and the role of gastrointestinal K. pneumoniae in the hvKP liver abscess patients in the ROK.

Intervention effects in the transmission of COVID-19 depending on the detection rate and extent of isolation / 한국역학회지

Objectives@#In 2020, the coronavirus disease 2019 (COVID-19) respiratory infection is spreading in Korea. In order to prevent the spread of an infectious disease, infected people must be quickly identified and isolated, and contact with the infected must be blocked early. This study attempted to verify the intervention effects on the spread of an infectious disease by using these measures in a mathematical model. @*Methods@#We used the susceptible-infectious-recovery (SIR) model for a virtual population group connected by a special structured network. In the model, the infected state (I) was divided into I in which the infection is undetected and Ix in which the infection is detected. The probability of transitioning from an I state to Ix can be viewed as the rate at which an infected person is found. We assumed that only those connected to each other in the network can cause infection. In addition, this study attempted to evaluate the effects of isolation by temporarily removing the connection among these people. @*Results@#In Scenario 1, only the infected are isolated; in Scenario 2, those who are connected to an infected person and are also found to be infected are isolated as well. In Scenario 3, everyone connected to an infected person are isolated. In Scenario 3, it was possible to effectively suppress the infectious disease even with a relatively slow rate of diagnosis and relatively high infection rate. @*Conclusions@#During the epidemic, quick identification of the infected is helpful. In addition, it was possible to quantitatively show through a simulation evaluation that the management of infected individuals as well as those who are connected greatly helped to suppress the spread of infectious diseases.

Trends of accidental carbon monoxide poisoning in Korea, 1951-2018 / 한국역학회지

OBJECTIVES@#Carbon monoxide (CO) poisoning from coal briquette combustion has been a major public health problem in Korea. In this study, we estimated the time trends of the consumption of anthracite coal and the number of CO poisoning victims over the past 7 decades, in the context of changes in heating facilities. @*METHODS@#Using Population and Housing Census data and energy statistics, we estimated the number of houses using briquettes as heating fuel between 1951 and 2018. After estimating the incidence of CO poisoning in housing units by heating facility type, we determined the ratio of the number of household members who experienced CO poisoning to the overall number of household members. Finally, we estimated the distribution of the victims according to poisoning severity, excluding victims of intentional exposure. @*RESULTS@#We estimated that, overall, over 26 million people experienced CO poisoning between 1951 and 2018 in Korea. The household consumption of anthracite peaked in 1986, but the number of victims of CO poisoning peaked at approximately 1 million people in 1980. From 1951 to 2018, the cumulative number of CO poisoning victims comprised approximately 22,830,000 mild cases, 3,570,000 severe cases, and 65,000 deaths. @*CONCLUSIONS@#The peak in the number of CO poisoning victims occurred 6 years earlier than the peak in the number of people using briquettes for heating. This gap resulted from improvements in briquette heating systems. This finding provides a quantitative basis for epidemiological studies on the health outcomes of CO poisoning in the Korean population.

A small window into the status of malaria in North Korea: estimation of imported malaria incidence among visitors from South Korea / 한국역학회지

OBJECTIVES@#This study aimed to develop hypotheses on trends in malaria incidence in North Korea using malaria incidence among South Korean visitors to North Korea. @*METHODS@#The number of South Korean tourists who visited Mount Kumgang from 2000 to 2008 and the number of South Korean employees at the Kaesong Industrial Complex from 2005 to 2015 were obtained from the Korean Statistical Information Service. The number of malaria cases among South Koreans who visited North Korea was obtained from a previous report. The incidence of malaria per 100,000 person-years was calculated using these data and compared with the malaria incidence in North Korea derived from published articles. @*RESULTS@#A high incidence of malaria in 2001 and a sharp decline in the following years were observed in both South and North Korean data. Since then, North Korean data showed a relatively low and stable incidence, but the incidence among South Koreans visiting North Korea increased in 2006. Considering the trends in mass primaquine preventive treatment, floods, and economic growth rate, the incidence of malaria may have increased in North Korea in 2006. Since 2009, the incidence of malaria decreased gradually according to both South and North Korean data. @*CONCLUSIONS@#The trends of malaria incidence in North Korea could be reflected through its incidence among South Koreans who visited North Korea. For future inter-Korean collaboration aiming to eradicate malaria, we propose that a North Korean malaria monitoring system be established applying this method.