The 2022 focused update of the 2018 Korean Hypertension Society Guidelines for the management of hypertension.

Hypertension is the leading cause of death in human being, which shows high prevalence and associated complications that increase the mortality and morbidity. Controlling blood pressure (BP) is very important because it is well known that lowering high BP effectively improves patients' prognosis. This review aims to provide a focused update of the 2018 Korean Hypertension Society Guidelines for the management of hypertension. The importance of ambulatory BP and home BP monitoring was further emphasized not only for the diagnosis but also for treatment target. By adopting corresponding BPs, the updated guideline recommended out-of-office BP targets for both standard and intensive treatment. Based on the consensus on corresponding BPs and Systolic Blood Pressure Intervention Trial (SPRINT) revisit, the updated guidelines recommended target BP in high-risk patients below 130/80 mmHg and it applies to hypertensive patients with three or more additional cardiovascular risk factors, one or more risk factors with diabetes, or hypertensive patients with subclinical organ damages, coronary or vascular diseases, heart failure, chronic kidney disease with proteinuria, and cerebral lacunar infarction. Cerebral infarction and chronic kidney disease are also high-risk factors for cardiovascular disease. However, due to lack of evidence, the target BP was generally determined at < 140/90 mmHg in patients with those conditions as well as in the elderly. Updated contents regarding the management of hypertension in special situations are also discussed.

The effect of photodynamic therapy using Radachlorin on biofilm-forming multidrug-resistant bacteria.

OBJECTIVES: This study aimed to test the effect of photodynamic therapy (PDT) on the inhibition and removal of biofilms containing multidrug-resistant Acinetobacter baumannii. METHODS: Using multidrug-resistant A. baumannii strains, an antibiotic susceptibility test was performed using the Gram-negative identification card of the Vitek 2 system (bioMérieux Inc., France), as well as an analysis of resistance genes, the effects of treatment with a light-emitting diode (LED) array using Radachlorin (RADA-PHARMA Co., Ltd., Russia), and transmission and scanning electron microscopy to confirm the biofilm-inhibitory effect of PDT. RESULTS: The antibiotic susceptibility test revealed multiple resistance to the antibiotics imipenem and meropenem in the carbapenem class. A class-D-type ß-lactamase was found, and OXA-23 and OXA-51 were found in 100% of 15 A. baumannii strains. After PDT using Radachlorin, morphological observations revealed an abnormal structure due to the loss of the cell membrane and extensive morphological changes, including low intracellular visibility and small vacuoles attached to the cell membrane. CONCLUSION: PDT involving a combination of LED and Radachlorin significantly eliminated the biofilm of multidrug-resistant A. baumannii. Observations made using electron microscopy showed that PDT combining LED and Radachlorin was effective. Additional studies on the effective elimination of biofilms containing multidrug-resistant bacteria are necessary, and we hope that a treatment method superior to sterilization with antibiotics will be developed in the future.

Health risk assessment and source apportionment of PM2.5-bound toxic elements in the industrial city of Siheung, Korea.

The emission sources and their health risks of fine particulate matter (PM2.5) in Siheung, Republic of Korea, were investigated as a middle-sized industrial city. To identify the PM2.5 sources with error estimation, a positive matrix factorization model was conducted using daily mean speciated data from November 16, 2019, to October 2, 2020 (95 samples, 22 chemical species). As a result, 10 sources were identified: secondary nitrate (24.3%), secondary sulfate (18.8%), traffic (18.8%), combustion for heating (12.6%), biomass burning (11.8%), coal combustion (3.6%), heavy oil industry (1.8%), smelting industry (4.0%), sea salts (2.7%), and soil (1.7%). Based on the source apportionment results, health risks by inhalation of PM2.5 were assessed for each source using the concentration of toxic elements portioned. The estimated cumulative carcinogenic health risks from the coal combustion, heavy oil industry, and traffic sources exceeded the benchmark, 1E-06. Similarly, carcinogenic health risks from exposure to As and Cr exceeded 1E-05 and 1E-06, respectively, needing a risk reduction plan. The non-carcinogenic risk was smaller than the hazard index of one, implying low potential for adverse health effects. The probable locations of sources with relatively higher carcinogenic risks were tracked. In this study, health risk assessment was performed on the elements for which mass concentration and toxicity information were available; however, future research needs to reflect the toxicity of organic compounds, elemental carbon, and PM2.5 itself.

Algorithm for diagnosing hypertension using out-of-office blood pressure measurements.

The authors developed and validated a diagnostic algorithm using the optimal upper and lower cut-off values of office and home BP at which ambulatory BP measurements need to be applied. Patients presenting with high BP (≥140/90 mm Hg) at the outpatient clinic were referred to measure office, home, and ambulatory BP. Office and home BP were divided into hypertension, intermediate (requiring diagnosis using ambulatory BP), and normotension zones. The upper and lower BP cut-off levels of intermediate zone were determined corresponding to a level of 95% specificity and 95% sensitivity for detecting daytime ambulatory hypertension by using the receiver operator characteristic curve. A diagnostic algorithm using three methods, OBP-ABP: office BP measurement and subsequent ambulatory BP measurements if office BP is intermediate zone; OBP-HBP-ABP: office BP, subsequent home BP measurement if office BP is within intermediate zone and subsequent ambulatory BP measurement if home BP is within intermediate zone; and HBP-ABP: home BP measurement and subsequent ambulatory BP measurements if home BP is within intermediate zone, were developed and validated. In the development population (n = 256), the developed algorithm yielded better diagnostic accuracies than 75.8% (95%CI 70.1-80.9) for office BP alone and 76.2% (95%CI 70.5-81.3) for home BP alone as follows: 96.5% (95%CI: 93.4-98.4) for OBP-ABP, 93.4% (95%CI: 89.6-96.1) for OBP-HBP-ABP, and 94.9% (95%CI: 91.5-97.3%) for HBP-ABP.  In the validation population (n = 399), the developed algorithm showed similarly improved diagnostic accuracy. The developed algorithm applying ambulatory BP measurement to the intermediate zone of office and home BP improves the diagnostic accuracy for hypertension.

Author Correction: Freeform micropatterning of living cells into cell culture medium using direct inkjet printing.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Novel Method for S1 Transforaminal Epidural Steroid Injection.

BACKGROUND: S1 transforaminal epidural steroid injection (S1-TFESI) results in positive clinical outcomes for the treatment of pain associated with the S1 nerve root. S1-TFESI via the transforaminal approach is commonly performed under fluoroscopic guidance. Ultrasound guidance is an alternative to mitigate radiation exposure. However, performing spinal procedures under ultrasound guidance has some limitations in confirming the position of the needle tip and vascular uptake. New techniques are therefore needed to make ultrasound and fluoroscopy complementary. Our objective was to describe a novel technique for S1-TFESI and confirm its reproducibility. METHODS: Records of patients with S1 radiculopathy were reviewed retrospectively; those treated using the new S1-TFESI technique were selected. Initially, ultrasound was used to distinguish anatomy of the sacral foramen and guide initial placement of the needle entry point. Fluoroscopy was subsequently used to confirm needle tip position and vascular injection. The number of times the needle required reinsertion was recorded, and ultrasound and C-arm images were stored. RESULTS: Sixty-seven S1-TFESIs were performed in 56 patients. All injections exhibited epidural spread of contrast media, not only to the S1 nerve. The cephalad angle was 16.25 ± 6.75° (range, 5-27°), the oblique angle was 2.48 ± 2.62° (range, 0-7°), and the mean number of attempts was 1.24 ± 1.25. CONCLUSIONS: The new technique, involving the use of ultrasound to guide initial placement of the needle entry point, followed by confirmatory imaging and any needed adjustment with the use of fluoroscopy, can be a technique to complement the shortcomings of using ultrasound or fluoroscopy alone.

Corrigendum to "Epidemiological Characterization of Imported Systemic Mycoses Occurred in Korea" [Osong Public Health Res Perspect 2018;9(5):255-60].

[This corrects the article on p. 255 in vol. 9, PMID: 30402381.].

Epidemiological Characterization of Imported Systemic Mycoses Occurred in Korea.

OBJECTIVES: Imported systemic mycoses is a severe fungal infection that can cause diseases in healthy people. However, there is a serious lack of epidemiological data about imported systemic mycoses. Therefore, an epidemiological characterization of imported systemic mycoses in Korea was performed. METHODS: We collected health insurance data between 2008 and 2012 from the Health Insurance Corporation and analyzed the data to determine the prevalence and treatment management of imported systemic mycoses. RESULTS: The prevalence of imported systemic mycoses between 2008 and 2012 increased slowly by 0.49/100,000 to 0.53/100,000 persons. The prevalence of coccidioidomycosis increased from 0.28/100,000 in 2008 to 0.36/100,000 persons in 2012. A mean of 229.6 cases occurred each year. Children and the elderly showed higher prevalence than adults in the 20- to 59-year-old age group. The rate of infection according to region ranged from 0.18/100,000 persons in Ulsan, to 0.59/100,000 persons in Gyeonggi. The prevalence in females was higher than that in males. Inpatient treatment was 3.3% (38 cases), with 96.7% treated as outpatients. Hospitalizations cost 272.7 million won and outpatient treatments cost 111.7 million won. The treatment cost for coccidioidomycosis from 2008 to 2012 was 330.9 million won, with personal charges of 79.2 million won and insurance charges of 251.7 million won. Most of the expenses for the coccidioidomycosis treatment were for inpatient treatment. CONCLUSION: The results in this study may be a useful resource for determining the changes in the trend of imported systemic mycoses.

Publisher Correction: Freeform micropatterning of living cells into cell culture medium using direct inkjet printing.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

Characterization of Clostridium difficile Strains Isolated from Patients with C. difficile-associated Disease in Korea.

OBJECTIVES: Studies on Clostridium difficile are rare in Korea. We investigated the epidemiological characteristics of C. difficile isolates from patients with C. difficile-associated disease (CDAD) in Korea. METHODS: Multiplex polymerase chain reaction was performed to detect the presence of tcdA and tcdB toxin genes. Antimicrobial susceptibility test was carried out by the disk-dilution method. C. difficile strains were subtyped by automated repetitive-element palindromic PCR (rep-PCR). RESULTS: Among patients with CDAD, 73 (25.8%), 32 (11.3%), 32 (11.3%), and 26 (9.2%) suffered from pneumonia, cancer or neoplasm, diabetes, and colitis, respectively. Of all stool samples, 43 samples (15.2%) were positive for C. difficile strains. We observed two expression patterns of toxin genes: tcdA+/tcdB+ (86% isolates) and tcdA-/tcdB+ (14% isolates), with all isolates expressing tcdB. Furthermore, some isolates were resistant to clindamycin (65%), ampicillin (56%), and cefazolin (40%), but all were susceptible to vancomycin and metronidazole. The tested samples were classified into diverse clusters using automated rep-PCR. CONCLUSION: Our findings revealed the characteristics and antibiotic resistance of C. difficile isolates from patients in Korea. The epidemiological data may provide valuable insight into development of treatment strategies for C. difficile infections in Korea.

Freeform micropatterning of living cells into cell culture medium using direct inkjet printing.

Microfabrication methods have widely been used to control the local cellular environment on a micron scale. However, accurately mimicking the complexity of the in vivo tissue architecture while maintaining the freedom of form and design is still a challenge when co-culturing multiple types of cells on the same substrate. For the first time, we present a drop-on-demand inkjet printing method to directly pattern living cells into a cell-friendly liquid environment. High-resolution control of cell location is achieved by precisely optimizing printing parameters with high-speed imaging of cell jetting and impacting behaviors. We demonstrated the capabilities of the direct cell printing method by co-printing different cells into various designs, including complex gradient arrangements. Finally, we applied this technique to investigate the influence of the heterogeneity and geometry of the cell population on the infectivity of seasonal H1N1 influenza virus (PR8) by generating A549 and HeLa cells printed in checkboard patterns of different sizes in a medium-filled culture dish. Direct inkjet cell patterning can be a powerful and versatile tool for both fundamental biology and applied biotechnology.

Comparison of effects between calcium channel blocker and diuretics in combination with angiotensin II receptor blocker on 24-h central blood pressure and vascular hemodynamic parameters in hypertensive patients: study design for a multicenter, double-blinded, active-controlled, phase 4, randomized trial.

BACKGROUND: Hypertension is a risk factor for coronary heart disease and stroke, and is one of the leading causes of death. Although over a billion people are affected worldwide, only half of them receive adequate treatment. Current guidelines on antihypertensive treatment recommend combination therapy for patients not responding to monotherapy, but as the number of pills increase, patient compliance tends to decrease. As a result, fixed-dose combination drugs with different antihypertensive agents have been developed and widely used in recent years. CCBs have been shown to be better at reducing central blood pressure and arterial stiffness than diuretics. Recent studies have reported that central blood pressure and arterial stiffness are associated with cardiovascular outcomes. This trial aims to compare the efficacy of combination of calcium channel blocker (CCB) or thiazide diuretic with an angiotensin receptor blocker (ARB). METHODS: This is a multicenter, double-blinded, active-controlled, phase 4, randomized trial, comparing the antihypertensive effects of losartan/amlodipine and losartan/hydrochlorothiazide in patients unresponsive to treatment with losartan. The primary endpoint is changes in mean sitting systolic blood pressure (msSBP) after 4 weeks of treatment. Secondary endpoints are changes in msSBP, mean 24-h ambulatory mobile blood pressure, mean 24-h ambulatory mobile central SBP, mean 24-h ambulatory carotid-femoral pulse wave velocity, ambulatory augmentation index, and microalbuminuria/proteinuria after 20 weeks of treatment. The sample size will be 119 patients for each group in order to confer enough power to test for non-inferiority regarding the primary outcome. CONCLUSION: The investigators aim to prove that combination of a CCB with ARB shows non-inferiority in lowering blood pressure compared with a combination of thiazide diuretic and ARB. We also hope to distinguish the subset of patients that are more responsive to certain types of combination drugs. The results of this study should aid physicians in selecting appropriate combination regimens to treat hypertension in certain populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT02294539. Registered 12 November 2014.

Efficacy and Tolerability of Combination Therapy Versus Monotherapy with Candesartan and/or Amlodipine for Dose Finding in Essential Hypertension: A Phase II Multicenter, Randomized, Double-blind Clinical Trial.

PURPOSE: Intensive blood pressure (BP) lowering is important for the treatment of hypertension; however, it has been a challenge to achieve target BP in many patients. The purpose of this study was to explore the optimal dosage of a fixed-dose combination of candesartan cilexetil (CAN) and amlodipine besylate (AML), by examining the tolerability and efficacy of CAN/AML combination therapy compared with those of monotherapy with either drug in patients with essential hypertension. METHODS: This Phase II multicenter, randomized, double-blind clinical trial enrolled patients aged 19 years or older with essential hypertension, defined as a mean sitting diastolic BP (msDBP) between 95 and 115 mm Hg, and a mean sitting systolic BP (msSBP) of <200 mm Hg after a 2-week placebo run-in period. A total of 635 patients were screened, of whom 439 were randomized to receive treatment; 425 patients were included in the full analysis set (combination therapy, 212; monotherapy, 213). Participants were randomly assigned to receive 1 of 8 treatments: CAN (8 or 16 mg), AML (5 or 10 mg), CAN/AML (8 mg/5 mg, 8 mg/10 mg, 16 mg/5 mg, or 16 mg/10 mg), once daily for 8 weeks. FINDINGS: After 8 weeks of treatment, changes in msDBP were significantly greater in the groups receiving CAN/AML combination therapies compared with monotherapies at matched doses, with the exception of CAN 8 mg/AML 10 mg versus AML 10 mg. The response to treatment and the achievement of target BP (both msSBP and msDBP) at week 8 were significantly greater overall in the groups that received combination therapy versus monotherapy. All medications were relatively well tolerated in each group. IMPLICATIONS: Eight-week administration of CAN/AML (8 mg/5 mg, 16 mg/5 mg, and 16 mg/10 mg) resulted in a significantly greater BP reduction than that with CAN or AML monotherapy, and was determined to be well tolerated. ClinicalTrials.gov identifier: NCT02944734.

Between-visit reproducibility of inter-arm systolic blood pressure differences in treated hypertensive patients: the coconet study.

Inter-arm systolic blood pressure (BP) differences (sIADs) have recently been recognized as a risk factor for cardiovascular mortality. However, sIAD reproducibility remains unresolved from a controlled trial perspective. We evaluated the between-visit reproducibility of sIADs in hypertensive patients. We examined 1875 hypertensive participants aged 20 years and older (mean age: 62.3 years, 45.4% female) from nine primary clinics and 27 secondary and tertiary hospitals. The BPs in both arms were automatically and simultaneously measured in triplicate with a cuff-oscillometric BP device. BP measurements were obtained at baseline and at 3-month follow-up time points. Increased sIAD was defined as an absolute difference of ⩾10 mm Hg in the average systolic BPs between the left and right arms. The overall mean sIAD was 4.33±4.17 mm Hg. The prevalences of increased sIAD at baseline and at the 3-month measurements were 7.6% and 7.1%, respectively. The intraclass correlation coefficient for the between-visit sIADs was 0.304 (95% confidence interval (CI) 0.262-0.344). The κ-value between the baseline and follow-up increased sIADs was 0.165 (95% CI 0.096-0.234). The percentage of patients who exhibited an increased sIAD at 3 months compared with the initially increased sIAD at baseline was 21.8%. The reproducibility of sIAD determination between baseline and the 3-month follow-up measurements lacked agreement in the hypertensive patients. Further studies should identify the relevant variables and characteristics of this poor reproducibility (CRIS number; KCT0001235).

Drop-on-demand inkjet-based cell printing with 30-µm nozzle diameter for cell-level accuracy.

We present drop-on-demand inkjet-based mammalian cell printing with a 30-µm nozzle diameter for cell-level accuracy. High-speed imaging techniques have been used to analyze the go-and-stop movement of cells inside the nozzle under a pulsed pressure generated by a piezo-actuator and the jet formation after ejection. Patterning of an array of 20 × 20 dots on a glass substrate reveals that each printed drop contains 1.30 cells on average at the cell concentration of 5.0 × 106 cells ml-1 for the very small nozzle, whereas larger nozzles with the diameter of 50 and 80 µm deliver 2.57 and 2.88 cells per drop, respectively. The effects of the size and concentration of printed cells on the number of cells have also been investigated. Furthermore, the effect of the nozzle diameter on printed cells has been evaluated through an examination of viability, proliferation, and morphology of cells by using a live/dead assay kit, CCK-8 assay, and cellular morphology imaging, respectively. We believe that the 30-µm inkjet nozzle can be used for precise cell deposition without any damages to the printed mammalian cells.

Comparison of dual antiplatelet therapy prescribed as one-pill versus two-pill regimen. A pooled analysis of individual patient data from the three MR-CAPCIS trials.

Fixed-dose combination (FDC) drugs can simplify the medication regimen and potentially improve adherence. However, evidence is lacking about the efficacy and safety of FDC drugs of clopidogrel plus aspirin. Individual data from the three independent MR-CAPCIS trials were pooled and analysed. In those trials, subjects who had been treated with either dual antiplatelet therapy (DAPT) or aspirin alone after drug-eluting stent (DES) implantation were randomly assigned to one-pill or to two-pill DAPT group. Platelet reactivity was measured with VerifyNow-P2Y12 and aspirin point-of-care assays at baseline and eight weeks after treatment. In the present study, primary efficacy endpoint was changes in platelet reactivity unit (PRU) between baseline and eight weeks. A total of 965 subjects were analysed. In prior clopidogrel and aspirin users, PRU was well maintained regardless of switching to either one-pill or two-pill DAPT (ΔPRU=0.4 vs 0.0, p=0.939). In prior aspirin users, PRU was decreased by 73.7 in one-pill DAPT and 77.5 in two-pill DAPT group, with no differences between them (p=0.499). The incidence of high on-treatment platelet reactivity at eight weeks, defined as PRU≥235 in Western people, was 34.8 % in one-pill DAPT group and 37.6 % in two-pill DAPT group (p=0.380), and that defined as PRU ≥275 in Oriental people was 17.7 vs 21.7 % (p=0.129). Independent predictors of high platelet reactivity on clopidogrel were female gender, increasing age, and diabetes. Study drugs were well tolerated. In conclusion, FDC one-pill DAPT showed similar efficacy to two-pill DAPT in terms of platelet reactivity in patients receiving DES in Korea.

Spontaneous Bleeding from Internal Pudendal Artery associated with Abciximab after Primary Percutaneous Coronary Intervention: Successful Treatment with Percutaneous Gel-Foam Embolization.

We describe a case of spontaneous bleeding from a branch of the right internal pudendal artery that resulted in massive scrotal swelling in a patient who had underwent primary percutaneous coronary intervention with the use of abciximab concurrent with conventional anticoagulation and dual antiplatelet therapies for the treatment of acute ST-segment elevation myocardial infarction. This unusual complication was promptly identified by percutaneous peripheral arteriography and successfully treated with gel-foam embolization.

Epidemiological Characterization of Opportunistic Mycoses between the Years 2006 and 2010 in Korea.

In order to perform an epidemiological characterization of opportunistic mycosis infections, we collected health insurance data between the years 2006 and 2010 from the Health Insurance Corporation and analyzed the data to determine the prevalence of opportunistic mycoses and treatment management of opportunistic mycoses. The prevalence within the study increased consecutively by 0.02% to 0.12% every year. The annual prevalence of opportunistic mycoses increased from 2.437% in 2006 to 2.709% in 2010. The average annual prevalence was 2.605%. Candidiasis occurred the most frequently, followed by aspergillosis, zygomycosis, and cryptococcosis. The regions with the highest incidences were the capital areas, Gyeonggi and Seoul. By sex, the prevalence in females (4.851%) was 14 times higher than that in males (0.352%). Interestingly, the adults from the 20- to 49-year-old age group showed higher prevalence than children and the elderly. The average duration of hospitalized treatment was 17.31 days and of outpatient treatment was 2.21 days; 3,577 hundred million won was used in total for medical expenses. This study provides useful data to study trends of opportunistic mycoses.

Identification of mucorales from clinical specimens: a 4-year experience in a single institution.

Mucormycosis, a fatal opportunistic infection in immunocompromised hosts, is caused by fungi belonging to the order Mucorales. Early diagnosis based on exact identification and multidisciplinary treatments is critical. However, identification of Mucorales fungi is difficult and often delayed, resulting in poor prognosis. This study aimed to compare the results of phenotypic and molecular identification of 12 Mucorales isolates collected from 4-yr-accumulated data. All isolates were identified on the basis of phenotypic characteristics such as growth rate, colony morphology, and reproductive structures. PCR and direct sequencing were performed to target internal transcribed spacer (ITS) and/or D1/D2 regions. Target DNA sequencing identified five Lichtheimia isolates, two Rhizopus microsporus isolates, two Rhizomucor pusillus isolates, one Cunninghamella bertholletiae isolate, one Mucor fragilis isolate, and one Syncephalastrum racemosum isolate. Five of the 12 (41.7%) isolates were incorrectly identified on the basis of phenotypic identification. DNA sequencing showed that of these five isolates, two were Lichtheimia isolates, one was Mucor isolate, one was Rhizomucor isolate, and one was Rhizopus microspores. All the isolates were identified at the species level by ITS and/or D1/D2 analyses. Phenotypic differentiation and identification of Mucorales is difficult because different Mucorales share similar morphology. Our results indicate that the molecular methods employed in this study are valuable for identifying Mucorales.