Recommendations for Adult Immunization by the Korean Society of Infectious Diseases, 2023: Minor Revisions to the 3rd Edition.

The Korean Society of Infectious Diseases has been regularly developing guidelines for adult immunization since 2007. In 2023, the guidelines for the following seven vaccines were revised: influenza, herpes zoster, pneumococcal, tetanus-diphtheria-pertussis (Tdap), human papillomavirus (HPV), meningococcal, and rabies vaccines. For the influenza vaccine, a recommendation for enhanced vaccines for the elderly was added. For the herpes zoster vaccine, a recommendation for the recombinant zoster vaccine was added. For the pneumococcal vaccine, the current status of the 15-valent pneumococcal conjugate vaccine and 20-valent PCV was described. For the Tdap vaccine, the possibility of using Tdap instead of tetanus-diphtheria vaccine was described. For the HPV vaccine, the expansion of the eligible age for vaccination was described. For the meningococcal vaccine, a recommendation for the meningococcal B vaccine was added. For the rabies vaccine, the number of pre-exposure prophylaxis doses was changed. This manuscript documents the summary and rationale of the revisions for the seven vaccines. For the vaccines not mentioned in this manuscript, the recommendations in the 3rd edition of the Vaccinations for Adults textbook shall remain in effect.

Usefulness of oxygen uptake efficiency slope in a 6 min walk test in chronic heart failure.

AIMS: Frailty is an obstacle to performing cardiopulmonary exercise test (CPET) in patients with chronic heart failure (CHF). We evaluated the usefulness of oxygen uptake efficiency slope (OUES) using a 6 min walk test (6MWT) with portable gas analysis compared with CPET-derived parameters in patients with CHF. METHODS AND RESULTS: Patients with CHF who underwent both the 6MWT with portable gas analysis and CPET between December 2016 and May 2020 were retrospectively investigated. The 6MWT-derived and echocardiographic parameters were compared with the OUES and peak oxygen consumption (VO2) from the CPET. Forty patients were analysed; 50% were male with a mean age of 55.45 ± 14.70 years. Twenty-six patients (65%) had New York Heart Association Functional Classification II or III dyspnoea. Twenty-five patients (62.5%) had heart failure (HF) with preserved ejection fraction (EF) (left ventricular EF > 50%), and nine patients (22.5%) had HF with reduced EF (EF < 40%). During the 6MWT, the peak VO2 was 14.97 ± 3.80 mL/kg/min, which was only 74% of the peak VO2 in the CPET, 20.18 ± 5.64 mL/kg/min. The OUES in the 6MWT was lower than that in the CPET (1528.87 ± 579.01 in the 6MWT vs. 1638.69 ± 601.31 in the CPET). The 6 min walk distance (6MWD) and OUES in the 6MWT were positively correlated with the OUES in the CPET (6MWD, r = 0.434, P = 0.005; OUES, r = 0.729, P < 0.001). The OUES in the 6MWT showed the strongest correlation with the OUES in the CPET. When we divided patients into two groups according to peak VO2 in the CPET, the correlation between OUES values of the 6MWT and that of the CPET was consistently confirmed (peak VO2 ≥ 20 mL/kg/min group, r = 0.661, P = 0.001; peak VO2 < 20 mL/kg/min group, r = 0.526, P = 0.021). In addition, the 6MWD, OUES, and peak VO2 in the 6MWT were associated with peak VO2 in the CPET (6MWD, r = 0.627, P < 0.001; OUES, r = 0.452, P = 0.003; and peak VO2, r = 0.492, P = 0.001). CONCLUSIONS: In frail patients with CHF who have difficulty performing maximal exercises, the OUES through the 6MWT may be applied instead of the OUES and peak VO2 from the CPET.

Effects of intensive blood pressure control on left ventricular hypertrophy in aortic valve disease.

BACKGROUND: Hypertension adds to the pressure overload on the left ventricle (LV) in combination with aortic valve (AV) disease, but the optimal blood pressure (BP) targets for patients with AV disease remain unclear. We tried to investigate whether intensive BP control reduces LV hypertrophy in asymptomatic patients with aortic stenosis (AS) or aortic regurgitation (AR). METHODS: A total of 128 hypertensive patients with mild to moderate AS (n = 93) or AR (n = 35) were randomly assigned to intensive therapy, targeting a systolic BP <130 mm Hg, or standard therapy, targeting a systolic BP <140 mm Hg. The primary end point was the change in LV mass from baseline to the 24-month follow-up. Secondary end points included changes in severity of AV disease, LV volumes, ejection fraction and global longitudinal strain (GLS). RESULTS: The treatment groups were generally well balanced regarding the baseline characteristics. The mean (±SD) age of the patients was 68 ± 8 years and 48% were men. The mean BP was 145 ± 12/81 ± 10 mm Hg at baseline. Medication at baseline was similar between the 2 groups. The 2 treatment strategies resulted in a rapid and sustained difference in systolic BP (P < .05). At 24-month, the mean systolic BP was 129 ± 12 mm Hg in the intensive therapy group and 135 ± 14 mm Hg in the standard therapy group. No patient died or underwent AV surgery during follow-up in either of the groups. LV mass was changed from 189.5 ± 41.3 to 185.6 ± 41.5 g in the intensive therapy group (P = .19) and from 183.8 ± 38.3 to 194.0 ± 46.4 g in the standard therapy group (P < .01). The primary end point of change in LV mass was significantly different between the intensive therapy and the standard therapy group (-3.9 ± 20.2 g vs 10.3 ± 20.4 g; P = .0007). The increase in LV mass index was also significantly greater in the standard therapy group (P = .01). No significant differences in secondary end points (changes in severity of AV disease, LV volumes, ejection fraction and GLS) were observed between the treatment groups. CONCLUSIONS: Among hypertensive patients with AV disease, intensive hypertensive therapy resulted in a significant reduction in LV hypertrophy, although progression of AV disease was similar between the treatment groups. CLINICAL TRIAL REGISTRATION: http://ClinicalTrials.gov (Number NCT03666351).

Exercise-induced desaturation during a six-minute walk test is associated with poor clinical outcomes in patients with pulmonary arterial hypertension.

BACKGROUND: The six-minute walk test (6MWT) is an established exercise test for patients with pulmonary arterial hypertension (PAH), affording insight into both exercise intolerance and overall prognosis. Despite the widespread application of the 6MWT, the prognostic implications of exercise-induced desaturation (EID) during this test has been inadequately studied in PAH patients. Thus, we evaluated the occurrence of EID and its prognostic significance in PAH patients. METHODS: We analyzed PAH patients in a single-center cohort from April 2016 to March 2021. EID was defined as a reduction in oxygen saturation exceeding 4% from the baseline or to below 90% at any point during the test. RESULTS: We analyzed 20 PAH patients in this cohort, primarily consisting of 16 females with an average age of 48.4 ± 13.3 years. Among them, ten exhibited EID. Baseline characteristics, echocardiographic data and right heart catheterization data were similar between the two groups. However, total distance (354.3 ± 124.4 m vs. 485.4 ± 41.4 m, P = 0.019) and peak oxygen uptake (12.9 ± 3.2 mL/kg⋅min vs. 16.4 ± 3.6 mL/kg⋅min, P = 0.019) were significantly lower in the EID group. During the total follow-up duration of 51.9 ± 25.7 months, 17 patients had at least one adverse clinical event (2 deaths, 1 lung transplantation, and 13 hospital admissions). The presence of EID was associated with poor clinical outcome (hazard ratio = 6.099, 95% confidence interval = 1.783-20.869, P = 0.004). CONCLUSIONS: During the 6MWT, EID was observed in a half of PAH patients and emerged as a significant prognostic marker for adverse clinical events.

Impact of statins based on high-risk plaque features on coronary plaque progression in mild stenosis lesions: results from the PARADIGM study.

AIMS: To investigate the impact of statins on plaque progression according to high-risk coronary atherosclerotic plaque (HRP) features and to identify predictive factors for rapid plaque progression in mild coronary artery disease (CAD) using serial coronary computed tomography angiography (CCTA). METHODS AND RESULTS: We analyzed mild stenosis (25-49%) CAD, totaling 1432 lesions from 613 patients (mean age, 62.2 years, 63.9% male) and who underwent serial CCTA at a ≥2 year inter-scan interval using the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (NCT02803411) registry. The median inter-scan period was 3.5 ± 1.4 years; plaques were quantitatively assessed for annualized percent atheroma volume (PAV) and compositional plaque volume changes according to HRP features, and the rapid plaque progression was defined by the ≥90th percentile annual PAV. In mild stenotic lesions with ≥2 HRPs, statin therapy showed a 37% reduction in annual PAV (0.97 ± 2.02 vs. 1.55 ± 2.22, P = 0.038) with decreased necrotic core volume and increased dense calcium volume compared to non-statin recipient mild lesions. The key factors for rapid plaque progression were ≥2 HRPs [hazard ratio (HR), 1.89; 95% confidence interval (CI), 1.02-3.49; P = 0.042], current smoking (HR, 1.69; 95% CI 1.09-2.57; P = 0.017), and diabetes (HR, 1.55; 95% CI, 1.07-2.22; P = 0.020). CONCLUSION: In mild CAD, statin treatment reduced plaque progression, particularly in lesions with a higher number of HRP features, which was also a strong predictor of rapid plaque progression. Therefore, aggressive statin therapy might be needed even in mild CAD with higher HRPs. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02803411.

Monocyte distribution width (MDW) as a useful indicator for early screening of sepsis and discriminating false positive blood cultures.

BACKGROUND: Severe sepsis and septic shock are the leading cause of in-hospital death. As sepsis progresses, expression and activity of endogenous mediators of inflammation change. Early detection of biomarkers can play a role in sepsis screening and in improvement of patient outcomes. Recent studies suggest that increase in monocyte volume may be helpful in early detection of sepsis. Therefore, we evaluated the utility of monocyte distribution width (MDW) for the early assessment of sepsis compared with the blood culture and other inflammatory biomarkers. METHODS: Medical records of 1,404 patients (aged ≥19 years) who were admitted to the emergency department owing to clinically suspected infectious disease and requested blood cultures from Oct 2019 to Jan 2021 were reviewed. The patients were grouped based on Sepsis-3 criteria. They had undergone other laboratory tests to evaluate their clinical status. MDW was analyzed using DxH900 hematology analyzer (Beckman Coulter, Brea, California, USA). To determine the diagnostic performance of MDW, C-reactive protein (CRP), and procalcitonin (PCT) for sepsis, the area under the curve (AUC) of receiver operating characteristics curves and their sensitivity and specificity were measured. RESULTS: Among 1,404 patients, 520 patients were designated the sepsis group based on Sepsis-3 criteria. In the sepsis group, MDW value was 24.1 (median, IQR 21.6-28.1); AUC values for MDW, CRP, and PCT were 0.67 (95% CI, 0.64-0.69), 0.66 (95% CI, 0.63-0.68), and 0.75 (95% CI, 0.72-0.77), respectively. For diagnosis of the sepsis, the cut-off value of MDW was 21.7 (sensitivity 74% and specificity 54%). Measured values of MDW were higher for the blood culture positive group than that of the blood culture contamination group (P<0.001, 95% CI, -5.9 to -3.0) or blood culture negative group (P<0.001, 95% CI = -5.8 to -4.2). CONCLUSIONS: MDW is a new hematological parameter that is simultaneously calculated during complete blood cell counting by Beckman Coulter hematology analyzer. MDW is expected to serve as a useful indicator for early screening of sepsis in conjunction with CRP and PCT. MDW is especially useful for sepsis assessment in patients with a suspected infection. MDW can also assist in discriminating false positive blood cultures.

Glycemic control is independently associated with rapid progression of coronary atherosclerosis in the absence of a baseline coronary plaque burden: a retrospective case-control study from the PARADIGM registry.

BACKGROUND: The baseline coronary plaque burden is the most important factor for rapid plaque progression (RPP) in the coronary artery. However, data on the independent predictors of RPP in the absence of a baseline coronary plaque burden are limited. Thus, this study aimed to investigate the predictors for RPP in patients without coronary plaques on baseline coronary computed tomography angiography (CCTA) images. METHODS: A total of 402 patients (mean age: 57.6 ± 10.0 years, 49.3% men) without coronary plaques at baseline who underwent serial coronary CCTA were identified from the Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry and included in this retrospective study. RPP was defined as an annual change of ≥ 1.0%/year in the percentage atheroma volume (PAV). RESULTS: During a median inter-scan period of 3.6 years (interquartile range: 2.7-5.0 years), newly developed coronary plaques and RPP were observed in 35.6% and 4.2% of the patients, respectively. The baseline traditional risk factors, i.e., advanced age (≥ 60 years), male sex, hypertension, diabetes mellitus, hyperlipidemia, obesity, and current smoking status, were not significantly associated with the risk of RPP. Multivariate linear regression analysis showed that the serum hemoglobin A1c level (per 1% increase) measured at follow-up CCTA was independently associated with the annual change in the PAV (ß: 0.098, 95% confidence interval [CI]: 0.048-0.149; P < 0.001). The multiple logistic regression models showed that the serum hemoglobin A1c level had an independent and positive association with the risk of RPP. The optimal predictive cut-off value of the hemoglobin A1c level for RPP was 7.05% (sensitivity: 80.0%, specificity: 86.7%; area under curve: 0.816 [95% CI: 0.574-0.999]; P = 0.017). CONCLUSION: In this retrospective case-control study, the glycemic control status was strongly associated with the risk of RPP in patients without a baseline coronary plaque burden. This suggests that regular monitoring of the glycemic control status might be helpful for preventing the rapid progression of coronary atherosclerosis irrespective of the baseline risk factors. Further randomized investigations are necessary to confirm the results of our study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02803411.

Impact of a screening protocol for blood pressure level for hypertension in the Korean community health survey.

PURPOSE: A community program is an efficient model for improving the management of chronic diseases such as hypertension, diabetes, and dyslipidemia. A specific blood pressure (BP) measurement protocol was developed for community settings in which BP was measured by the interviewer at the interviewee's home. MATERIALS AND METHODS: In the 2018 Korean Community Health Survey, BP was measured twice at a five-minute interval after a five-minute resting period at the beginning of the survey. In 2019, BP was measured at the end of the survey after a two-minute rest and was obtained as three measurements at one-minute intervals. As factors related to BP level, stressful stimuli within 30 min before BP measurement such as smoking, caffeine, and/or exercise; duration of rest; and survey year were analysed. RESULTS: The mean age of participants was 55.2 years, and females accounted for 55.4% of the participants (n = 399,838). Stressful stimuli were observed in 21.9% of the participants in 2018 (n = 188,440) and 11.3% in 2019 (n = 211,398). Duration of rest was 0 min (2.1%), two minutes (55.0%), and five minutes (47.9%). When adjusted for age, sex, body mass index, antihypertensive medication, the arm of measurement, survey year (beta= -4.092), stressful stimuli (beta = 0.834), and resting time (beta = -1.296 per one minute of rest) were significant factors for mean systolic BP. A two-minute rest was not a significant factor in mean BP. The differences in adjusted mean systolic BPs were significant for rest times of five minutes vs. two minutes (3.1 mmHg, p < 0.0001), for stressful stimuli (0.8 mmHg, p < 0.0001), and for survey year (127.8 ± 0.2 mmHg vs. 122.2 ± 0.3 mmHg for 2018 vs. 2019, p < 0.0001). CONCLUSION: For the community-based home visit survey, avoidance of stressful stimuli, five-minute rest, and allocation of BP measurement in the last part of the survey was useful for obtaining a stable BP level.

Analysis of a COVID-19 Prescreening Process in an Outpatient Clinic at a University Hospital during the COVID-19 Pandemic.

BACKGROUND: To minimize nosocomial infection against coronavirus disease 2019 (COVID-19), most hospitals conduct a prescreening process to evaluate the patient or guardian of any symptoms suggestive of COVID-19 or exposure to a COVID-19 patient at entrances of hospital buildings. In our hospital, we have implemented a two-level prescreening process in the outpatient clinic: an initial prescreening process at the entrance of the outpatient clinic (PPEO) and a second prescreening process is repeated in each department. If any symptoms or epidemiological history are identified at the second level, an emergency code is announced through the hospital's address system. The patient is then guided outside through a designated aisle. In this study, we analyze the cases missed in the PPEO that caused the emergency code to be applied. METHODS: All cases reported from March 2020 to April 2021 were analyzed retrospectively. We calculated the incidence of cases missed by the PPEO per 1,000 outpatients and compared the incidence between first-time hospital visitors and those visiting for the second time or more; morning and afternoon office hours; and days of the week. RESULTS: During the study period, the emergency code was applied to 449 cases missed by the PPEO. Among those cases, 20.7% were reported in otorhinolaryngology, followed by 11.6% in gastroenterology, 5.8% in urology, and 5.8% in dermatology. Fever was the most common symptom (59.9%), followed by cough (19.8%). The incidence of cases per 1,000 outpatients was significantly higher among first-time visitors than among those visiting for the second time or more (1.77 [confidence interval (CI), 1.44-2.10] vs. 0.59 [CI, 0.52-0.65], respectively) (P < 0.001). CONCLUSION: Fever was the most common symptom missed by the PPEO, and otorhinolaryngology and gastroenterology most frequently reported missed cases. Cases missed by the PPEO were more likely to occur among first-time visitors than returning visitors. The results obtained from this study can provide insights or recommendations to other healthcare facilities in operating prescreening processes during the COVID-19 pandemic.

Association between Aortic Valve Calcification Progression and Coronary Atherosclerotic Plaque Volume Progression in the PARADIGM Registry.

Background Aortic valve calcification (AVC) is a key feature of aortic stenosis, and patients with aortic stenosis often have coronary -artery disease. Therefore, proving the association between the progression of AVC and coronary atherosclerosis could improve follow-up and treatment strategies. Purpose To explore the association between the progression of AVC and the progression of total and plaque volume composition from a large multicenter registry of serial coronary CT angiographic examinations. Materials and Methods A prospective multinational registry (PARADIGM) of consecutive participants who underwent serial coronary CT angiography at intervals of every 2 years or more was performed (January 2003-December 2015). AVC and the total and plaque volume composition at baseline and follow-up angiography were quantitatively analyzed. Plaque volumes were normalized by using the mean total analyzed vessel length of the study population. Multivariable linear mixed-effects models were constructed. Results Overall, 594 participants (mean age ± standard deviation, 62 years ± 10; 330 men) were included (mean interval between baseline and follow-up angiography, 3.9 years ± 1.5). At baseline, the AVC score was 31 Agatston units ± 117, and the normalized total plaque volume at baseline was 122 mm3 ± 219. After adjustment for age, sex, clinical risk factors, and medication use, AVC was independently associated with total plaque volume (standardized ß = 0.24; 95% CI: 0.16, 0.32; P < .001) and both calcified (ß = 0.26; 95% CI: 0.18, 0.34; P < .001) and noncalcified (ß = 0.17; 95% CI: 0.08, 0.25; P < .001) plaque volumes at baseline. The progression of AVC was associated with the progression of total plaque volume (ß = 0.13; 95% CI: 0.03, 0.22; P = .01), driven solely by calcified plaque volume (ß = 0.24; 95% CI: 0.14, 0.34; P < .001) but not noncalcified plaque volumes (ß = -0.06; 95% CI: -0.14, 0.03; P = .17). Conclusion The overall burden of coronary atherosclerosis was associated with aortic valve calcification at baseline. However, the progression of aortic valve calcification was associated with only the progression of calcified plaque volume but not with the -progression of noncalcified plaque volume. Clinical trial registration no. NCT02803411 © RSNA, 2021 See also the editorial by Sinitsyn in this issue.

The Practice Guideline for Vaccinating Korean Patients with Autoimmune Inflammatory Rheumatic Disease.

To develop a clinical practice guideline for vaccination in patients with autoimmune inflammatory rheumatic disease (AIIRD), the Korean College of Rheumatology and the Korean Society of Infectious Diseases developed a clinical practice guideline according to the clinical practice guideline development manual. Since vaccination is unlikely to cause AIIRD or worsen disease activities, required vaccinations are recommended. Once patients are diagnosed with AIIRD, treatment strategies should be established and, at the same time, monitor their vaccination history. It is recommended to administer vaccines when the disease enters the stabilized stage. Administering live attenuated vaccines in patients with AIIRD who are taking immunosuppressants should be avoided. Vaccination should be considered in patients with AIIRD, prior to initiating immunosuppressants. It is recommended to administer influenza, Streptococcus pneumoniae, hepatitis A, hepatitis B, herpes zoster, measles-mumps-rubella virus, human papillomavirus, and tetanus-diphtheria-pertussis vaccines in patients with AIIRD; such patients who planned to travel are generally recommended to be vaccinated at the recommended vaccine level of healthy adults. Those who live in a household with patients with AIIRD and their caregivers should also be vaccinated at levels that are generally recommended for healthy adults.

Fungal arthritis with adjacent osteomyelitis caused by Candida pelliculosa: a case report.

BACKGROUND: Candida sp. osteoarticular infection is rare and most often due to hematogenous seeding during an episode of candidemia in immunocompromised patients. However, the diagnosis can be delayed in patients with subtle symptoms and signs of joint infection without a concurrent episode of candidemia. CASE PRESENTATION: A 75-year-old woman presented with a three-year history of pain and swelling of the left knee. Candida pelliculosa was detected from the intraoperative tissue when the patient had undergone left total knee arthroplasty 32 months ago, but no antifungal treatment was performed. One year after the total knee arthroplasty, C. pelliculosa was repeatedly isolated from the left knee synovial fluid and antifungal treatment comprising amphotericin B deoxycholate and fluconazole was administered. However, joint infection had extended to the adjacent bone and led to progressive joint destruction. The patient underwent surgery for prosthesis removal and received prolonged antifungal treatment with micafungin and fluconazole. CONCLUSIONS: This case shows that C. pelliculosa, an extremely rare non-Candida albicans sp., can cause fungal arthritis and lead to irreversible joint destruction owing to delayed diagnosis and treatment.

Clinical and Laboratory Predictors associated with Complicated Scrub Typhus.

BACKGROUND: Scrub typhus, a mite-borne disease caused by bites of Orientia tsutsugamushi-infected chiggers, is endemic in Asia-Pacific countries. In Korea, it is a seasonal disease prevalent in autumn and one of the important causes of acute undifferentiated febrile illness. The purpose of this study was to identify the risk factors for the prediction of the severe clinical course of scrub typhus and to investigate the differences in the clinical and laboratory findings of hospitalized elderly and non-elderly patients with scrub typhus. MATERIALS AND METHODS: This study retrospectively reviewed the medical records of patients diagnosed with scrub typhus. RESULTS: A total of 710 patients were enrolled and 43.9% of them were elderly patients. The number of patients with complicated scrub typhus was 168 (23.7%) and the most common complication of severe scrub typhus was hepatic dysfunction (10.7%) followed by pneumonia (7.2%), acute kidney injury (4.9%) and shock (2.4%). Blood urea nitrogen ≥20 mg/dL, adenosine deaminase (ADA) ≥100 IU/L, pulmonary edema or pleural effusion, lactate dehydrogenase ≥500 U/L, alkaline phosphatase ≥400 IU/L, ferritin ≥500 ng/mL and absence of skin rash were independently associated with severe scrub typhus. There was no significant difference in the incidence of complicated scrub typhus between elderly and non-elderly patients. Absence of skin rash, pulmonary edema, pleural effusion, serum creatinine ≥1.5 mg/dL, total bilirubin ≥1.5 mg/dL, ADA ≥100 IU/L and ferritin ≥500 ng/mL were significantly associated with a longer hospitalization (≥10 days). CONCLUSION: The several independent predictors of complicated scrub typhus were identified in this study. Absence of skin rash, the increased levels of serum ADA and ferritin were identified as the predictors of complicated scrub typhus, which were also associated with a prolonged hospitalization.

Epidemiology and Antifungal Susceptibility Profile of Aspergillus Species: Comparison between Environmental and Clinical Isolates from Patients with Hematologic Malignancies.

Global data on the epidemiology and susceptibility of Aspergillus are crucial in the management of invasive aspergillosis. Here, we aimed to determine the characteristics of clinical and environmental Aspergillus isolates, focusing mainly on hematologic malignancy patients. We prospectively collected all consecutive cases and clinical isolates of culture-positive proven/probable invasive aspergillosis patients from January 2016 to April 2018 and sampled the air inside and outside the hospital. Cryptic species-level identification of Aspergillus, antifungal susceptibilities, and cyp51 gene sequencing were performed, and clinical data were analyzed. This study was conducted as part of the Catholic Hematology Hospital Fungi Epidemiology (CAFÉ) study. A total of 207 proven/probable invasive aspergillosis and 102 clinical and 129 environmental Aspergillus isolates were included in this analysis. The incidence of proven/probable invasive aspergillosis was 1.3 cases/1,000 patient-days during the study period. Cryptic Aspergillus species accounted for 33.8%, with no differences in proportions between the clinical and environmental isolates. Section Nigri presented a high proportion (70.5%) of cryptic species, mainly from A. tubingensis and A. awamori: the former being dominant in environmental samples, and the latter being more common in clinical isolates (P < 0.001). Of 91 A. fumigatus isolates, azole-resistant A. fumigatus was found in 5.3% of all A. fumigatus isolates. Three isolates presented the TR34/L98H mutation of the cyp51A gene. Patients with invasive aspergillosis caused by azole-resistant A. fumigatus showed 100% all-cause mortality at 100 days. This study demonstrates the significant portion of cryptic Aspergillus species and clinical implications of azole resistance and underscores the comparison between clinical and environmental isolates.

Effect of intracoronary adenosine on ergonovine-induced vasoconstricted coronary arteries.

BACKGROUND: This study aimed to evaluate the effect of adenosine on epicardial coronary artery diameter during ergonovine provocation testing. METHODS: A total of 158 patients who underwent an ergonovine provocation test with intracoronary adenosine injection between 2011 and 2014 were selected. Patients were divided into four groups based on the severity of percent diameter stenosis following intracoronary ergonovine administration: Group 1, induced spasm < 50%; Group 2, 50-89%; Group 3, 90-99%; and Group 4, total occlusion. RESULTS: Spasm positivity was observed in 44 (27.8%) cases in the study population (mean age, 57.4 ± ± 10.7 years). Intracoronary adenosine increased the diameter of the ergonovine-induced epicardial artery by 0.51 ± 0.31 mm, 0.73 ± 0.39 mm, 0.44 ± 0.59 mm, and 0.01 ± 0.04 mm in Groups 1, 2, 3, and 4, respectively. Subsequent administration of nitroglycerin further increased vessel diameter by 0.49 ± 0.28 mm, 0.93 ± 0.68 mm, 2.11 ± 1.25 mm, and 2.23 ± 0.69 mm in Groups 1, 2, 3, and 4, respectively. The ratios of adenosine-induced diameter to reference diameter were significantly lower in patients with spasm positive results (0.68 [0.59-0.76] vs. 0.18 [0.00-0.41], p < 0.001 in the study population; 0.60 [0.54-0.67] vs. 0.40 [0.27-0.44], p < 0.001 in Group 2) with the best cut-off value of 0.505 (sensitivity 0.955, specificity 0.921). CONCLUSIONS: Intracoronary administration of adenosine dilated the ergonovine-induced vasoconstricted epicardial coronary artery. The ratio of adenosine-induced diameter to reference diameter was significantly lower in patients with spasm positive results.

Comparison of prescription rates and clinical outcomes in acute coronary syndrome patients who underwent percutaneous coronary intervention using different P2Y12 inhibitors in a large observational study.

BACKGROUND: To compare the prescription rates, safety, and efficacy of contemporary P2Y12 inhibitors in acute coronary syndrome (ACS) patients following percutaneous coronary intervention (PCI). METHODS: From 9684 ACS patients who underwent PCI in a nationwide, real-world registry, we compared prescription rates, bleeding, and major adverse cardiac events (MACEs: cardiac death, nonfatal myocardial infarction, or stroke) according to ticagrelor, prasugrel, or clopidogrel use. RESULTS: The prescription rates of ticagrelor, prasugrel, and clopidogrel were 15.2%, 11.7%, and 73.0%, respectively. In-hospital bleeding occurred in 565 (5.8%) patients, with 108 (7.3%), 80 (7.9%), and 377 (5.3%) patients using ticagrelor, prasugrel, and clopidogrel, respectively, with significantly higher incidence in ticagrelor (p = 0.008) and prasugrel (p = 0.026) users than in clopidogrel users. Ticagrelor and prasugrel were not different in terms of in-hospital bleeding (p = 0.159). MACEs occurred in 804 patients (8.3%), with 82 (5.6%), 69 (6.1%), and 653 (9.2%) patients in ticagrelor, prasugrel, and clopidogrel, respectively (median follow-up, 468 days). Ticagrelor (p = 0.001) and prasugrel (p = 0.001) were associated with fewer MACEs than clopidogrel; the difference between ticagrelor and prasugrel for fewer MACEs was nonsignificant (p = 0.235). CONCLUSIONS: In real-world ACS patients following PCI, ticagrelor and prasugrel were not prescribed at higher rates than clopidogrel, but were found to improve clinical outcomes, albeit they induced bleeding more frequently. No differences were observed in bleeding and outcomes in ticagrelor versus prasugrel.

Prolonged electromechanical delay as an early predictor of trastuzumab-induced cardiotoxicity in patients undergoing treatment for breast cancer.

BACKGROUND: We aimed to investigate if left ventricular electromechanical delay (LVEMD) prolongation predicts trastuzumab-induced cardiotoxicity (TIC) in breast cancer patients. HYPOTHESIS: LVEMD prolongation on serial echocardiograms could be an indicator of subclinical TIC. METHODS: We included 237 breast cancer patients receiving trastuzumab chemotherapy, who underwent echocardiography at baseline and at 6 and 12 months after trastuzumab initiation. LVEMD was defined as the time from electrical activation to myocardial contraction. TIC was defined as left ventricular ejection fraction (LVEF) worsening to <55%, either as symptomatic decrease of ≥5% or asymptomatic decrease of ≥10%. RESULTS: During a mean follow-up of 547 days, TIC occurred in 27 patients (11.4%). Changes in the time intervals from QRS onset on electrocardiography to the beginning and peak of transaortic flow on pulsed-wave Doppler echocardiography (ie, ΔLVEMDi and ΔLVEMDp, respectively) were independent predictors of TIC. On receiver operating characteristic curve analysis, the optimal cutoff value for TIC prediction was 23 milliseconds for ΔLVEMDi (sensitivity, 0.85; specificity, 0.78; area under the curve [AUC], 0.882) and 21 milliseconds for ΔLVEMDp (sensitivity, 0.96; specificity, 0.68; AUC, 0.860). The C-index for TIC prediction increased significantly after adding ΔLVEMDi and ΔLVEMDp to conventional models that included clinical variables, baseline LVEF, and changes in global longitudinal peak systolic strain. Similarly, adding ΔLVEMDi or ΔLVEMDp to conventional models provided significant improvement in discrimination capability for TIC prediction (integrated discrimination improvement and continuous net reclassification improvement index). CONCLUSION: ΔLVEMDi and ΔLVEMDp may serve as predictors of subclinical cardiac dysfunction in breast cancer patients receiving trastuzumab.

Vaccinia-related kinase 2 modulates role of dysbindin by regulating protein stability.

Vaccinia-related kinase 2 (VRK2) is a serine/threonine kinase that belongs to the casein kinase 1 family. VRK2 has long been known for its relationship with neurodegenerative disorders such as schizophrenia. However, the role of VRK2 and the substrates associated with it are unknown. Dysbindin is known as one of the strong risk factors for schizophrenia. The expression of dysbindin is indeed significantly reduced in schizophrenia patients. Moreover, dysbindin is involved in neurite outgrowth and regulation of NMDA receptor signaling. Here, we first identified dysbindin as a novel interacting protein of VRK2 through immunoprecipitation. We hypothesized that dysbindin is phosphorylated by VRK2 and further that this phosphorylation plays an important role in the function of dysbindin. We show that VRK2 phosphorylates Ser 297 and Ser 299 of dysbindin using in vitro kinase assay. In addition, we found that VRK2-mediated phosphorylation of dysbindin enhanced ubiquitination of dysbindin and consequently resulted in the decrease in its protein stability through western blotting. Over-expression of VRK2 in human neuroblastoma (SH-SY5Y) cells reduced neurite outgrowth induced by retinoic acid. Furthermore, a phosphomimetic mutant of dysbindin alleviated neurite outgrowth and affected surface expression of N-methyl-d-aspartate 2A, a subunit of NMDA receptor in mouse hippocampal neurons. Together, our work reveals the regulation of dysbindin by VRK2, providing the association of these two proteins, which are commonly implicated in schizophrenia. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

Risk factors and clinical outcomes of breakthrough yeast bloodstream infections in patients with hematological malignancies in the era of newer antifungal agents.

Although yeast bloodstream infections (BSIs) are increasingly being reported in patients with hematological malignancies undergoing antifungal therapy, clinical information regarding breakthrough infections is scarce. The aim of this study was to determine the risk factors for and clinical outcomes of breakthrough yeast BSIs in patients with hematological malignancies in the era of newer antifungal agents. Between 2011 and 2014, all consecutive patients with hematological malignancies who developed yeast BSIs were included in a case-control study wherein breakthrough infections (cases) and de novo infections (controls) were compared. Of 49 patients with yeast BSIs, 21 (43%) met the criteria for breakthrough infections. The proportions of Candida krusei and Candida tropicalis in the cases and controls were significantly different (32% [7/22] vs. 3% [1/29], P = .015; 5% [1/22] vs. 38% [11/29], P = .007, respectively). Acute leukemia, presence of a central venous catheter and neutropenia in the 3 days prior to BSI were significant risk factors for breakthrough infections. Six-week mortality rates was 33% [7/21] in the cases and 43% [12/28] in the controls (P = .564). Refractory neutropenia and the Pitt bacteremia score were independent predictors of 6-week mortality. In conclusion, breakthrough infections accounted for a significant proportion of yeast BSIs in patients with hematological malignancies. However, these infections did not increase the risk of death by themselves. Our results suggest that current clinical management of breakthrough yeast BSIs, which includes switching to a different antifungal class and prompt catheter removal is reasonable.

The demanding attention of tuberculosis in allogeneic hematopoietic stem cell transplantation recipients: High incidence compared with general population.

BACKGROUND: The risk of developing tuberculosis (TB) in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is expected to be relatively high in an intermediate TB burden country. This single-center retrospective study was conducted to investigate risk factors and the incidence of TB after allogeneic HSCT. METHODS: From January 2004 to March 2011, 845 adult patients were enrolled. Starting April 2009, patients were given isoniazid (INH) prophylaxis based on interferon-γ release assay results. The incidence of TB was analyzed before and after April 2009, and compared it with that of the general population in Korea. RESULTS: TB was diagnosed in 21 (2.49%) of the 845 allogeneic HSCT patients. The median time to the development of TB was 386 days after transplantation (range, 49-886). Compared with the general population, the standardized incidence ratio of TB was 9.10 (95% CI; 5.59-14.79). Extensive chronic graft-versus-host disease (GVHD) was associated with the development of TB (P = 0.003). Acute GVHD, conditioning regimen with total body irradiation and conditioning intensity were not significantly related. INH prophylaxis did not reduce the incidence of TB (P = 0.548). Among 21 TB patients, one patient had INH prophylaxis. CONCLUSION: Allogeneic HSCT recipients especially those who suffer from extensive chronic GVHD are at a high risk of developing TB. INH prophylaxis did not statistically change the incidence of TB, however, further well-designed prospective studies are needed.