Identification of novel variants for complicating cardiac disease in the scrub typhus infection using whole genome sequencing

Background/Aims@#Scrub typhus infection has been known to complicate cardiovascular diseases mainly attributing to high mortality. Genetic susceptibility loci for complicating cardiac diseases such as atrial fibrillation, heart failure, and ischemic heart disease identified by genomic study have been limited in scrub typhus infection. Therefore, we investigated the genetic novel variants predicting complicating cardiac diseases in patients with confirmed scrub typhus infection using whole genome sequencing. @*Methods@#We performed a prospective study for eight consecutive patients with scrub typhus infection. During follow-up, six cases were clinically diagnosed with complicating cardiac diseases and two controls without complicating cardiac diseases. The whole genomes of the all patients were sequenced, and the individual sequence variants were compared between accordcase and control patients. Variant genotypes were compared and identified as a single nucleotide polymorphism (SNP) of the different genotype distributions between six cases and two controls. @*Results@#The GG genotype in SNP (rs4977397) of solute carrier 24 family member 2 (SLC24A2) gene and non-TT genotype in SNP (rs2676750) of adenosine deaminase, RNA specific, B2 (ADARB2) gene were distinctively found in the case patients with complicated cardiac disease, compared with control patents in the scrub typhus infection. @*Conclusions@#We suggest that the SNPs of SLC24A2 and ADARB2 might be genetic surrogate markers for complicating cardiac diseases in the scrub typhus infection. Our study show that early detection based on individual sequence variants might be feasible to predict complicating cardiac diseases in patients with scrub typhus infection, if further studies with more participants confirm these findings.

Social Stigma and Discrimination Toward People With Drug Addiction: A National Survey in Korea

Objective@#This study aims to understand the attitudes, stigma, and discrimination of the general adult population toward drug addiction. @*Methods@#We conducted a cross-sectional nationwide survey with 1,020 Korean adults using an Internet web-based panel. Self-reported data were collected on demographics, experience with substance abuse, perceptions of narcotic analgesic use, beliefs about the legalization of cannabis use, coping with substance abuse and addiction, and perceptions of drug risks. All statistical analysis in this study utilized the IBM SPSS Statistics 26 program. @*Results@#In this study, 1.6% of the participants reported abuse of opioid analgesics, 88.0% reported negative perceptions of drug addiction, and 76.9% reported agreeing to unfair treatment of drug addicts. Logistic regression analysis found that perceived stigma was more prevalent among women (odd ratio [OR]=2.087, p<0.01), old adults (OR=1.939, p<0.01), those with no personal experience of opioid misuse (OR=8.172, p<0.05), and those who were non-smoking (OR=2.011, p<0.01). In addition, the discriminatory attitude was more prevalent among participants with higher income (OR=1.989, p<0.001) and those who are non-smoking (OR=1.608, p<0.05). @*Conclusion@#This study provides information and guidelines for public intervention in drug addiction by identifying factors influencing social stigma and discriminatory behaviors toward drug addiction. The findings suggest that education on drug addiction prevention for the general adult population is necessary, and this education should include knowledge on coping with drug addiction and reducing stigma and discrimination toward drug addicts.

Post-percutaneous core needle biopsy sputum cytology: diagnostic value and factors for positive prediction in diagnosing malignancy / 고신대학교의과대학학술지

Background@#This study evaluated the diagnostic yield and positive predictive factors of post-percutaneous core needle biopsy (PCNB) sputum cytology in diagnosing malignancy. @*Methods@#This retrospective study included patients who underwent PCNB at a single center from January 2014 to March 2022. Patient demographics, lung lesion characteristics on computed tomography, underlying lung disease, post-PCNB complications, histopathologic results of PCNB, post-PCNB sputum specimens, and final diagnoses were reviewed. The diagnostic yields and related factors were analyzed. @*Results@#Overall, 177 consecutive patients with sputum specimens obtained after PCNB for intrapulmonary lesions were enrolled. Among them, 152 patients had a final diagnosis of malignancy. Diagnostic sputum specimens with atypical or malignant cells were obtained in 12 patients. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of sputum cytology were 7.89%, 100%, 20.90%, 100%, and 15.15%, respectively. Lesion size, air-bronchogram, lesion multiplicity, and the cell type of squamous cell and adenocarcinoma differed significantly between the groups with diagnostic versus non-diagnostic sputum (p<0.05). The lesion size (odds ratio [OR], 1.035; 95% confidence interval [CI], 1.008–1.064; p=0.013), presence of air-bronchogram (OR, 23.485; 95% CI, 2.532–217.316; p=0.005), and squamous cell carcinoma (OR, 7.397; 95% CI, 1.773–30.865; p=0.006) were significantly associated with a diagnostic sputum specimen post-PCNB. @*Conclusions@#Although post-PCNB sputum cytology had low sensitivity in diagnosing lung cancer, it showed diagnostic results in some peripheral lung cancer patients who have squamous cell types, relatively large tumors, and air-bronchograms in the lesions.

Use of cutting-edge RNA-sequencing technology to identify biomarkers and potential therapeutic targets in canine and feline cancers and other diseases

With the growing interest in companion animals and the rapidly expanding animal healthcare and pharmaceuticals market worldwide. With the advancements in RNAsequencing (RNA-seq) technology, it has become a valuable tool for understanding biological processes in companion animals and has multiple applications in animal healthcare.Historically, veterinary diagnoses and treatments relied solely on clinical symptoms and drugs used in human diseases. However, RNA-seq has emerged as an effective technology for studying companion animals, providing insights into their genetic information. The sequencing technology has revealed that not only messenger RNAs (mRNAs) but also noncoding RNAs (ncRNAs) such as long ncRNAs and microRNAs can serve as biomarkers. Based on the examination of RNA-seq applications in veterinary medicine, particularly in dogs and cats, this review concludes that RNA-seq has significant potential as a diagnostic and research tool. It has enabled the identification of potential biomarkers for cancer and other diseases in companion animals. Further research and development are required to maximize the utilization of RNA-seq for improved disease diagnosis and therapeutic targeting in companion animals.

Multifocal Peripheral Neuropathies, Rhabdomyolysis, and Dermal Change in Carbon Monoxide Intoxication

Carbon monoxide poisoning is common cause of fatal intoxication. When carbon monoxide is absorbed into the blood, it interferes with the oxygen supply to the cells, causing damage to tissues and organs. Delayed neuropsychiatric sequelae (DNS) manifested by cognitive dysfunction, motor disorder, micturition disorder are widely known complication of carbon monoxide intoxication. But neuromuscular complication is a rare DNS of carbon monoxide intoxication. We herein report a 42-year-old patient with multifocal neuropathies, rhabdomyolysis, and dermal change due to carbon monoxide intoxication.

The Direction of Neurosurgery to Overcome the Living with COVID-19 Era : The Possibility of Telemedicine in Neurosurgery

Objective@#: Due to the implementation of vaccinations and the development of therapeutic agents, the coronavirus disease 2019 (COVID-19) pandemic that started at the end of 2019 has entered a new phase. As a result, neurosurgeons should reconsider the way they treat their patients. As the COVID-19 situation prolongs, the change in neurosurgical emergency patients according to the number of confirmed cases is no longer clear. Outpatient treatment by telephone was permitted according to government policy. In addition, visits to caregivers in the intensive care unit were limited. @*Methods@#: The electronic medical records of patients who had been treated over the phone for a month (during April 2020, while the hospital was closing) were reviewed. Meanwhile, according to the limited visits to the intensive care unit, a video meeting was held with the caregivers. After the video meeting, satisfaction was evaluated using a questionnaire. @*Results@#: During April 2020, 1021 patients received non-face-to-face care over the telephone. Among the patients, no critical medical problem occurred due to non-face-to-face care. From July 2021 to December 2021, 321 patients were admitted to the neurosurgical intensive care unit and 107 patients (33.3%) including their caregivers agreed to video visits. Twice a week, advance notice was given that access would be made through a mobile device and the nurse explained to caregivers how to use the mobile device. The time for the video meeting was approximately 20 minutes per patient. Based on the questionnaire, 81 respondents (75.7%) answered that they agreed, and 26 respondents (24.3%) answered that they strongly agreed that was easy to communicate through video meetings. Fifty-two (48.6%) agreed and 55 (51.4%) strongly agreed that they were easy to understand the doctor’s explanation. For overall satisfaction with this video meeting, three respondents (2.8%) gave 4/5 points and 95 respondents (88.8%) gave 5/5 points, and nine (8.4%) gave 3/5 points. Their reason was that there was not enough time. @*Conclusion@#: In situations where patient visits are limited, video meetings through a mobile device can provide sufficient satisfaction to caregivers. Telemedicine will likely become common in the near future. Health care professionals should prepare and respond to these needs and changes. Therefore, establishing a system with institutional support is necessary.

Effect of a Motivational InterviewingBased Brief Intervention on Alcohol Use Behavior in Korean Internal Medicine Settings

A motivational interviewing (MI)-based brief intervention was performed with high-risk drinking outpatients screened at internal medicine settings in Korea after the doctor advised them to reduce alcohol consumption. Participants were assigned to a MI group or a control group where they received a brochure with information on the harm of high-risk drinking and tips on managing drinking habits. Four-week follow-up results showed that Alcohol Use Disorders Identification Test-Concise (AUDIT-C) scores decreased in the MI group and the control group compared to baseline scores. The difference between groups was not significant; however, group by time interaction was significant between the two groups: the slope of decreasing AUDIT-C scores over time was greater in the intervention group than in the control group (P = 0.042). The findings suggest that short comments received from doctors might be a key component in performing brief interventions for high-risk drinking management in Korean clinical settings.

CycloZ Improves Hyperglycemia and Lipid Metabolism by Modulating Lysine Acetylation in KK-Ay Mice

Background@#CycloZ, a combination of cyclo-His-Pro and zinc, has anti-diabetic activity. However, its exact mode of action remains to be elucidated. @*Methods@#KK-Ay mice, a type 2 diabetes mellitus (T2DM) model, were administered CycloZ either as a preventive intervention, or as a therapy. Glycemic control was evaluated using the oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) levels. Liver and visceral adipose tissues (VATs) were used for histological evaluation, gene expression analysis, and protein expression analysis. @*Results@#CycloZ administration improved glycemic control in KK-Ay mice in both prophylactic and therapeutic studies. Lysine acetylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, liver kinase B1, and nuclear factor-κB p65 was decreased in the liver and VATs in CycloZ-treated mice. In addition, CycloZ treatment improved mitochondrial function, lipid oxidation, and inflammation in the liver and VATs of mice. CycloZ treatment also increased the level of β-nicotinamide adenine dinucleotide (NAD+), which affected the activity of deacetylases, such as sirtuin 1 (Sirt1). @*Conclusion@#Our findings suggest that the beneficial effects of CycloZ on diabetes and obesity occur through increased NAD+ synthesis, which modulates Sirt1 deacetylase activity in the liver and VATs. Given that the mode of action of an NAD+ booster or Sirt1 deacetylase activator is different from that of traditional T2DM drugs, CycloZ would be considered a novel therapeutic option for the treatment of T2DM.

Novel Asian-Specific Visceral Adiposity Indices Are Associated with Chronic Kidney Disease in Korean Adults

Background@#The Chinese visceral adiposity index (CVAI) and new visceral adiposity index (NVAI) are novel indices of visceral adiposity used to predict metabolic and cardiovascular diseases in Asian populations. However, the relationships of CVAI and NVAI with chronic kidney disease (CKD) have not been investigated. We aimed to characterize the relationships of CVAI and NVAI with the prevalence of CKD in Korean adults. @*Methods@#A total of 14,068 participants in the 7th Korea National Health and Nutrition Examination Survey (6,182 men and 7,886 women) were included. Receiver operating characteristic (ROC) analyses were employed to compare the associations between indices of adiposity and CKD, and a logistic regression model was used to characterize the relationships of CVAI and NVAI with CKD prevalence. @*Results@#The areas under the ROC curves for CVAI and NVAI were significantly larger than for the other indices, including the visceral adiposity index and lipid accumulation product, in both men and women (all P<0.001). In addition, high CVAI or NVAI was significantly associated with a high CKD prevalence in both men (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.31 to 3.48 in CVAI and OR, 6.47; 95% CI, 2.91 to 14.38 in NVAI, P<0.05) and women (OR, 4.87; 95% CI, 1.85 to 12.79 in CVAI and OR, 3.03; 95% CI, 1.35 to 6.82 in NVAI, P<0.05); this association remained significant after adjustment for multiple confounding factors in men and women. @*Conclusion@#CVAI and NVAI are positively associated with CKD prevalence in a Korean population. CVAI and NVAI may be useful for the identification of CKD in Asian populations, including in Korea.

Medical disputes related to advanced endoscopic procedures with endoscopic retrograde cholangiopancreatography or endoscopic ultrasonography for the management of pancreas and biliary tract diseases

Background/Aims@#This study aimed to evaluate the characteristics of endoscopic retrograde cholangiopancreatography (ERCP) or endoscopic ultrasonography (EUS)-related adverse events (AEs) that eventually lead to medical disputes or claims on medical professional liability. @*Methods@#Medical disputes for ERCP/EUS-related AEs filed in the Korea Medical Dispute Mediation and Arbitration Agency between April 2012 and August 2020 were evaluated using corresponding medical records. AEs were categorized into three sections: procedure-related, sedation-related, and safety-related AEs. @*Results@#Among a total of 34 cases, procedure-related AEs were 26 (76.5%; 12 duodenal perforations, 7 post-ERCP pancreatitis, 5 bleedings, 2 perforations combined with post-ERCP pancreatitis); sedation-related AEs were 5 (14.7%; 4 cardiac arrests, 1 desaturation), and safety-related AEs were 5 (8.8%; 1 follow-up loss for stent removal, 1 asphyxia, 1 fall). Regarding clinical outcomes, 20 (58.8%) were fatal and eventually succumbed to AEs. For the types of medical institutions, 21 cases (61.8%) occurred at tertiary or academic hospitals, and 13 (38.2%) occurred at community hospitals. @*Conclusions@#The ERCP/EUS-related AEs filed in Korea Medical Dispute Mediation and Arbitration Agency showed distinct features: duodenal perforation was the most frequent AE, and clinical outcomes were fatal, resulting in at least more than permanent physical impairment.

The association between adverse childhood experiences and self-harm among South Korean children and adolescents: a cross-sectional study

Purpose@#Adolescent self-harm is a public health problem. Research suggests a link between adverse childhood experiences (ACEs) and self-destructive behaviors. Few studies, however, have examined the effects of ACEs on self-harm among Asian adolescents. This study explored the association between lifetime ACEs and a history of self-harm among Korean children and adolescents in elementary, middle, and high schools. @*Methods@#A cross-sectional, retrospective medical record review was conducted on a dataset of a national psychiatrist advisory service for school counselors who participated in the Wee Doctor Service from January 1 to December 31, 2020. The data were analyzed using multiple logistic regression to predict self-harm. @*Results@#Student cases (n=171) were referred to psychiatrists by school counselors for remote consultation. Multiple logistic regression analyses revealed that the odds of self-harm were higher among high school students (adjusted odds ratio [aOR]=4.97; 95% confidence interval [CI]=1.94-12.76), those with two or more ACEs (aOR=3.27; 95% CI=1.43-7.47), and those with depression (aOR=3.06; 95% CI=1.32-7.10). @*Conclusion@#The study's findings provide compelling evidence that exposure to ACEs can increase vulnerability to self-harm among Korean students. Students with a history of ACEs and depression, as well as high school students, require increased attention during counseling. School counselors can benefit from incorporating screening assessment tools that include questions related to ACEs and depression. Establishing a systematic referral system to connect students with experts can enhance the likelihood of identifying self-harm tendencies and offering the essential support to prevent self-harm.

Delayed Detection of a 5-Aminolevulinic Acid In Vivo: A Case of Metastatic Breast Cancer

A 44-year-old female patient who had been diagnosed with breast cancer visited our oncology department. She had developed right-side weakness and mild dysarthria, and MRI revealed a 4-cm cysticenhancing lesion in her left frontal lobe. Her surgery was postponed 48 hours after receiving 5-aminolevulinic acid (5-ALA), because a problem with thyroid function that had not been noticed before was discovered. The main lesion was enhanced on navigation and appeared to be a gross tumor; its 5-ALA uptake was very high. Specimens obtained from this location were histologically confirmed to contain tumor cells. The operation was completed, and removal of all enhancing lesions was confirmed by MRI within 24 hours postoperatively. The pathology report confirmed metastatic ductal carcinoma. The clinical efficacy of 5-ALA was confirmed even 48 hours after administration into a metastatic brain tumor from breast cancer.

Distinct Specialized Center of Excellence, the Story of Hwasun Neurosurgery at Chonnam National University Hwasun Hospital

The paper provides a comprehensive overview of the growth and development of Hwasun Neurosurgery at Chonnam National University Hwasun Hospital over the past 18 years. As the first brain tumor center in Korea when it was established in April 2004, Hwasun Neurosurgery has since become one of the leading institutions in brain tumor education and research in the country. Its impressive clinical and basic research capabilities, dedication to professional education, and numerous academic achievements have all contributed to its reputation as a top-tier institution. We hope this will become a useful guide for other brain tumor centers or educational institutions by sharing the story of Hwasun Neurosurgery.

Factors Affecting Nutritional Index and Length of Stay in Pancreatic Cancer in the Older Adults

Purpose@#This retrospective study aimed to clarify the relation between nutritional index and length of hospital stay in elderly patients undergoing pancreatic cancer surgery, and to identify factors affecting the length of hospital stay. @*Methods@#Total 102 patients aged over 65 years who underwent pancreaticoduodenectomy were retrospectively enrolled from January 1, 2010 to September 30, 2020. All patients were subjected to nutritional screening using Geriatric Nutritional Risk Index (GNRI) and Prognostic Nutritional Index (PNI). @*Results@#The GNRI average was 95. 66±6.95, with 67.6% of patients having a low GNRI score (malnutrition group). The average regarding PNI was 45.46±5.65, with 54.9% of patients having a low PNI (malnutrition group). The average total length of hospital stay was 23.12±10.69 days. Total length of hospital stay according to the nutritional indexes of the subjects was longer in the low GNRI (t=-2.09, p=.039) and low PNI (t=-2.29, p=.024) groups. @*Conclusion@#Poorer preoperative nutritional status increased total length of hospital stay in elderly patients with pancreatic cancer. Assessment of nutritional status of patients using GNRI and PNI is a good strategy for evaluating elderly patients at high risk of having to stay in hospital for more extended periods of time.

Summary of Korean Asthma Guideline / 결핵및호흡기질환

Asthma is a chronic inflammatory airway disease that is characterized by variable airflow obstruction. The Korean Asthma Study Group of the Korean Academy of Tuberculosis and Respiratory Diseases has recently updated the Korean Asthma Guideline. This review summarizes the updated Korean Asthma Guideline. Asthma prevalence is increasing worldwide, and in Korea. Variable airflow obstruction can be confirmed by bronchodilator response or other tests, and should be established prior to the controller medication. A low-dose inhaled corticosteroid-formoterol is used to alleviate symptoms in all treatment step, and it can be used as a controller as well as reliever in steps 3–5. This approach is preferred, because it reduces the risk of severe exacerbations, compared to the use of short-acting β2-agonist as reliever. In severe asthma, phenotype/endotype based on the underlying inflammation should be evaluated. For type 2 severe asthma, the biologics should be considered.

Rare Anatomic Variation of Anterior Communicating Artery Associated with a Rupture of Saccular Aneurysm / 대한법의학회지

Although most cerebral aneurysms are considered as acquired degenerative lesions, diverse anatomical variations in the circle of Willis have been encountered, some of which may play an important role in lesion hemodynamics and pathogenesis. The coalescence of the small vascular plexus to form the anterior communicating artery at the 6-7-week embryological stage may lead to developmental variations, such as fenestration and duplication. Herein, we report a rare anatomical variant of the anterior communicating artery that was concomitantly identified with a ruptured aneurysm. Both the right and left anterior cerebral arteries were connected by three anterior communicating arteries. A vertical segmental artery was present and connected the two anterior communicating arteries, forming an H-shape or plexiform structure. Furthermore, a 0.6×0.4 cm-sized saccular aneurysm with antero-inferior projection was present in the middle anterior communicating artery. The combination of triplication and H-shape in the present case was compared to previously reported anatomical variants.

Sudden Death Associated With Possible Flare-Ups of Multiple Sclerosis After COVID-19 Vaccination and Infection: A Case Report and Literature Review

We present an autopsy case of a 19-year-old man with a history of epilepsy whose unwitnessed sudden death occurred unexpectedly in the night. About 4 years before death, he was diagnosed with unilateral optic neuritis (ON). Demyelinating disease was suspected, but he was lost to follow up after the recovery. Six months before death, he received a second dose of mRNA coronavirus disease 2019 (COVID-19) vaccine. Three months before death, he experienced epileptic seizures for the first time. Seventeen days before death, he was infected with COVID-19, which showed self-limited course under home isolation. Several days before death, he complained of seizures again at night. Autopsy revealed multifocal gray-tan discoloration in the cerebrum. Histologically, the lesions consisted of active and inactive demyelinated plaques in the perivenous area of the white matter. Perivascular lymphocytic infiltration and microglial cell proliferation were observed in both white matter and cortex. The other major organs including heart and lung were unremarkable. Based on the antemortem history and postmortem findings, the cause of death was determined to be multiple sclerosis with suspected exacerbation. The direct or indirect involvement of cortex and deep gray matter by exacerbated multiple sclerosis may explain the occurrence of seizures. Considering the absence of other structural abnormalities except the inflammatory demyelination of the cerebrum, fatal arrhythmia or laryngospasm in the terminal epileptic seizure may explain his sudden unexpected death in the benign circumstances. In this case, the onset of seizure was preceded by COVID-19 vaccination, and the exacerbation of seizure was preceded by COVID-19 infection, respectively. Literature reporting first manifestation or relapse of multiple sclerosis temporally associated with COVID-19 vaccination or infection are reviewed.

Rapid FEV 1 /FVC Decline Is Related With Incidence of Obstructive Lung Disease and Mortality in General Population

Background@#Forced expiratory volume in 1 second (FEV1 )/forced vital capacity (FVC) naturally decreases with age; however, an excessive decline may be related with increased morbidity and mortality. This study aimed to evaluate the FEV1 /FVC decline rate in the Korean general population and to identify whether rapid FEV1 /FVC decline is a risk factor for obstructive lung disease (OLD) and all-cause and respiratory mortality. @*Methods@#We evaluated individuals aged 40−69 years who underwent baseline and biannual follow-up spirometric assessments for up to 18 years, excluding those with airflow limitations at baseline. Based on the quartiles of the annual FEV1 /FVC decline rate, the most negative FEV1 /FVC change (1 st quartile of annual FEV1 /FVC decline rate) was classified as rapid FEV1 / FVC decline. We investigated the risk of progression to OLD and all-cause and respiratory mortality in individuals with rapid FEV1 /FVC decline. @*Results@#The annual FEV1 /FVC decline rate in the eligible 7,768 patients was 0.32 percentage point/year. The incidence rate of OLD was significantly higher in patients with rapid FEV1 / FVC decline than in those with non-rapid FEV1 /FVC decline (adjusted incidence rate, 2.119; 95% confidence interval [CI], 1.932–2.324). Rapid FEV1 /FVC decline was an independent risk factor for all-cause mortality (adjusted hazard [HR], 1.374; 95% CI, 1.105–1.709) and respiratory mortality (adjusted HR, 1.353; 95% CI, 1.089–1.680). @*Conclusion@#The annual FEV1 /FVC decline rate was 0.32%p in the general population in Korea. The incidence rate of OLD and the hazards of all-cause and respiratory mortality were increased in rapid FEV1 /FVC decliners.

A Randomized, Double-Blind, Active-Control, Noninferiority, Multicenter, Phase 4 Study to Evaluate the Efficacy and Safety of Esomeprazole/Sodium Bicarbonate 20/800 mg in Patients with Nonerosive Gastroesophageal Reflux Disease

Background/Aims@#Efficacy of proton pump inhibitors is limited in patients with nonerosive reflux disease (NERD). The aim of this study was to comparatively evaluate the efficacy and safety of esomeprazole with sodium bicarbonate and esomeprazole alone. @*Methods@#This was a multicenter, randomized, double-blind, active-controlled, noninferiority comparative study. A total of 379 patients with NERD were randomly allocated to receive either EsoduoⓇ/sup> (esomeprazole 20 mg with sodium bicarbonate 800 mg) or NexiumⓇ/sup> (esomeprazole 20 mg) once daily for 4 weeks from January 2019 to December 2019. The patients had a history of heartburn for at least 2 days in the week before randomization as well as in the last 3 months and no esophageal mucosal breaks on endoscopy. The primary endpoint was a complete cure of heartburn at week 4. The secondary and exploratory endpoints as well as the safety profiles were compared in the groups at weeks 2 and 4. @*Results@#A total of 355 patients completed the study (180 in the EsoduoⓇ/sup> group and 175 in the NexiumⓇ/sup> group). The proportions of patients without heartburn in the entire 4th week of treatment were not different between the two groups (33.33% in the EsoduoⓇ/sup> group and 35% in the NexiumⓇ/sup> group, p=0.737). There were no significant differences in most of the secondary and exploratory endpoints as well as the safety profiles. @*Conclusions@#EsoduoⓇ/sup> is as effective and safe as NexiumⓇ/sup> for managing typical symptoms in patients with NERD (ClinicalTrial.gov identifier: NCT03928470).

The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4

Sarcopenia, defined as a progressive loss of muscle mass and function, is typified by mitochondrial dysfunction and loss of mitochondrial resilience. Sarcopenia is associated not only with aging, but also with various metabolic diseases characterized by mitochondrial dyshomeostasis. Pyruvate dehydrogenase kinases (PDKs) are mitochondrial enzymes that inhibit the pyruvate dehydrogenase complex, which controls pyruvate entry into the tricarboxylic acid cycle and the subsequent adenosine triphosphate production required for normal cellular activities. PDK4 is upregulated in mitochondrial dysfunction-related metabolic diseases, especially pathologic muscle conditions associated with enhanced muscle proteolysis and aberrant myogenesis. Increases in PDK4 are associated with perturbation of mitochondria-associated membranes and mitochondrial quality control, which are emerging as a central mechanism in the pathogenesis of metabolic disease-associated muscle atrophy. Here, we review how mitochondrial dysfunction affects sarcopenia, focusing on the role of PDK4 in mitochondrial homeostasis. We discuss the molecular mechanisms underlying the effects of PDK4 on mitochondrial dysfunction in sarcopenia and show that targeting mitochondria could be a therapeutic target for treating sarcopenia.