Safety and outcome of treatment of latent tuberculosis infection in liver transplant recipients.

PURPOSE: Liver transplant (LT) recipients have an increased risk of tuberculosis (TB), which is associated with higher mortality rates. This retrospective cohort study assessed the outcome and tolerability of screening and treatment of latent tuberculosis infection (LTBI) in LT recipients. METHODS: Between March 2020 and February 2022, all adult LT candidates at our institution were screened for LTBI. The candidates who tested positive for interferon-γ-releasing assay or met epidemiological or clinical-radiological criteria for LTBI were treated and monitored. RESULTS: Among the 857 LT recipients, 199 (23.2%) were diagnosed with LTBI, of which 171 (85.9%) initiated LTBI treatment. The median duration of follow-up was 677 days. Adequate LTBI treatment occurred in 141/171 (82.5%) patients and was discontinued prematurely in 30/171 (17.5%) patients. The most common reason for discontinuation was liver enzyme elevation (11/30, 36.7%), although only five discontinued treatment due to suspicion of isoniazid-associated hepatotoxicity. None of the LTBI-treated patients developed active TB during the follow-up period, while 3.6% (1/28) of untreated LTBI patients and 0.6% (4/658) of patients without LTBI developed TB. CONCLUSION: These findings demonstrate that LTBI screening and treatment is a safe and effective strategy to prevent TB in LT recipients. However, monitoring for adverse events and liver enzyme elevation is recommended.

Routine ophthalmologic examination in Klebsiella pneumoniae bacteremia is not necessary: incidence of and risk factors for ocular involvement.

Klebsiella pneumoniae bacteremia is known to present a virulent clinical course, including multiple metastatic infections, which is not uncommon in Asia. However, there are limited data on the incidence and risk factors for ocular involvement in K. pneumoniae bacteremia. We retrospectively reviewed the medical records of all patients with K. pneumoniae bacteremia who underwent ophthalmologic examination in a tertiary center in Seoul, Korea, from February 2012 to December 2020. Two retinal specialists reviewed the findings of the ophthalmologic examinations and classified them as endophthalmitis, chorioretinitis, and no ocular involvement. Of 689 patients, 56 [8.1%; 95% confidence interval (CI) 6.2-10.4] had ocular involvement, and 9 (1.3%; 95% CI 0.6-2.5) were diagnosed with endophthalmitis. Of 47 patients with chorioretinitis, 45 (95.7%) improved with systemic antibiotic therapy alone. Community-onset bacteremia (100% vs 62.1% vs 57.4%, P = 0.04), cryptogenic liver abscess (55.6% vs 11.8% vs 8.5%, P = 0.003), and metastatic infection (66.7% vs 5.8% vs 10.6%, P < 0.001) were more common in endophthalmitis than in no ocular involvement or chorioretinitis. In the multivariable analysis, cryptogenic liver abscess [adjusted odds ratio (aOR), 6.63; 95% CI 1.44-35.20] and metastatic infection (aOR, 17.52; 95% CI 3.69-96.93) were independent risk factors for endophthalmitis. Endophthalmitis was not associated with 30-day mortality. Endophthalmitis is rare in Asian patients with K. pneumoniae bacteremia. Targeted ophthalmologic examination in those with cryptogenic liver abscess, metastatic infection, or ocular symptoms may be more appropriate than routine examination of all patients.

Clinical and microbiological characteristics of rifampicin-resistant MRSA bacteraemia.

OBJECTIVES: The clinical significance of rifampicin resistance in Staphylococcus aureus infections has not been demonstrated. Here, we evaluated the clinical characteristics of rifampicin-resistant S. aureus infection. METHODS: Data were collected from adult patients who were hospitalized with MRSA bacteraemia between March 2007 and May 2020 at a tertiary hospital in South Korea. The clinical characteristics and treatment outcomes of patients infected with rifampicin-resistant MRSA were compared with those of rifampicin-susceptible isolates. All-cause death and recurrence of MRSA infection were assessed for 90 days. RESULTS: Of the 961 patients with MRSA bacteraemia, 61 (6.3%) were infected by rifampicin-resistant isolates. The type of infection focus and duration of bacteraemia did not significantly differ between the two groups. Rifampicin-resistant MRSA isolates were more likely to have multidrug resistance and a higher vancomycin MIC relative to the rifampicin-susceptible isolates. The 90-day recurrence rate was higher in the patients infected with rifampicin-resistant MRSA compared with those with rifampicin-susceptible MRSA (18.0% versus 6.2%, P < 0.001), whereas the 90-day mortality was comparable between the two groups (27.9% versus 29.2%, P = 0.94). After adjusting for potential confounding factors, rifampicin resistance was significantly associated with 90-day recurrence (subdistributional HR: 2.31; 95% CI: 1.05-5.10; P = 0.04). CONCLUSIONS: Rifampicin-resistant MRSA isolates showed distinct microbiological features in terms of multidrug resistance and a high vancomycin MIC. Although the management of MRSA bacteraemia was not significantly different between the two groups, recurrence was significantly more common in the rifampicin-resistant group. Rifampicin resistance may play a significant role in infection recurrence.

Severe Pneumonia Caused by Corynebacterium striatum in Adults, Seoul, South Korea, 2014-2019.

We investigated the proportion and characteristics of severe Corynebacterium striatum pneumonia in South Korea during 2014-2019. As part of an ongoing observational study of severe pneumonia among adult patients, we identified 27 severe C. striatum pneumonia cases. Most (70.4%) cases were hospital-acquired, and 51.9% of patients were immunocompromised. C. striatum cases among patients with severe hospital-acquired pneumonia (HAP) increased from 1.0% (2/200) during 2014-2015 to 5.4% (10/185) during 2018-2019, but methicillin-resistant Staphylococcus aureus (MRSA) infections among severe HAP cases decreased from 12.0% to 2.7% during the same timeframe. During 2018-2019, C. striatum was responsible for 13.3% of severe HAP cases from which bacterial pathogens were identified. The 90-day mortality rates were similarly high in the C. striatum and MRSA groups. C. striatum was a major cause of severe HAP and had high mortality rates. This pathogen is emerging as a possible cause for severe pneumonia, especially among immunocompromised patients.

Risk Factors of Recurrent Infection in Patients with Staphylococcus aureus Bacteremia: a Competing Risk Analysis.

Although several clinical variables have been reported as risk factors for recurrence of Staphylococcus aureus infection, most studies have not considered competing risk events that may overestimate the risk. In this study, we performed competing risk analysis to identify risk factors related to 90-day recurrence in patients with S. aureus bacteremia (SAB) using a large cohort data from a single tertiary hospital in South Korea. All adults who experienced SAB during admission were prospectively enrolled from August 2008 to December 2019. After the day of the first positive blood culture, recurrence and all-cause mortality were assessed for 90 days. Recurrence was defined as a development of symptoms or signs of infection with or without repeated bacteremia after >7 days of negative blood culture and clinically apparent improvement. Subdistribution hazard ratios (sHR) for recurrence and all-cause mortality were estimated using Fine and Gray models. Of 1,725 SAB patients, including 885 cases (51.3%) of methicillin-resistant S. aureus (MRSA) bacteremia, 85 (5.0%) experienced recurrence during the study period. In a multivariate Fine and Gray regression model, the presence of a vascular graft (subdistribution HR [sHR], 3.48; 95% confidence interval [CI], 1.90-6.40), nasal MRSA carriage (sHR, 2.10; 95% CI, 1.28-3.44), methicillin resistance (sHR, 1.69; 95% CI, 1.00-2.84), and rifampicin resistance (sHR, 2.20; 95% CI, 1.12-4.33) were significantly associated with 90-day recurrence. In a large cohort of SAB patients with a high prevalence of MRSA, indwelling vascular graft, nasal MRSA carriage, methicillin resistance, and rifampicin resistance were potential risk factors for recurrence of S. aureus infection.

Enterococcus raffinosus bacteremia: clinical experience with 49 adult patients.

This study is to evaluate the clinical characteristics and outcomes of Enterococcus raffinosus bacteremia in adults. We analyzed the medical records of adult patients with E. raffinosus bacteremia who were diagnosed and treated between 1997 and 2020 at a tertiary care teaching hospital in Seoul, Republic of Korea. The demographic, clinical, and laboratory data were collected and assessed. A total of 49 cases of E. raffinosus bacteremia were identified. E. raffinosus accounted for 0.6% of all enterococcal bacteremia events, and the incidence was 0.02 cases per 1,000 admissions. Of the 49 cases of E. raffinosus bacteremia, 35 (71.4%) had underlying malignancy. The biliary tract was the most common source of infection (81.6%, 40/49) and polymicrobial bacteremia was found in 25 cases (51.0%). The resistance rates of E. raffinosus bacteremia cases to penicillin, ampicillin, vancomycin, and linezolid were 61.2%, 49.0%, 2.0%, and 0%, respectively. In our case series, there was one case of vanA-type vancomycin-resistant E. raffinosus. The all-cause 60-day mortality rate was 22.4% (11/49), and the E. raffinosus bacteremia-related mortality rate was 4.1% (2/49). Cases of E. raffinosus bacteremia mainly originated from biliary tract infection and had a low rate of bacteremia-related mortality.

C-reactive protein predicts persistent bacteremia caused by community-acquired methicillin-resistant Staphylococcus aureus strain.

There is limited data on persistent bacteremia (PB) caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Here, we aimed to investigate the clinical and microbiological characteristics of PB caused by the major CA-MRSA strain in Korea (ST72-SCCmecIV). All adult patients with S. aureus bacteremia were prospectively investigated from August 2008 to December 2018. Patients with ST72 MRSA bacteremia were included in the study. Patients were stratified into the PB group (defined as positive blood cultures for ≥ 3 days) and short bacteremia (SB) group. A total of 291 patients were included, comprising 115 (39.5%) with PB and 176 (60.5%) with SB. Although the 30-day mortality did not differ between PB and SB, recurrent bacteremia within 12 weeks was significantly more common in PB (8.7% vs 1.7%; P = 0.01). Multivariate analysis showed risk factors of PB were liver cirrhosis (adjusted odds ratio [aOR], 3.27; 95% confidence interval [CI], 1.50-7.12), infective endocarditis (aOR, 7.13; 95% CI, 1.37-37.12), bone and joint infections (aOR, 3.76; 95% CI, 1.62-8.77), C-reactive protein ≥ 10 mg/dL (aOR, 2.20; 95% CI, 1.22-3.95), metastatic infection (aOR, 7.35; 95% CI, 3.53-15.29), and agr dysfunction (aOR, 2.47; 95% CI, 1.05-5.81). PB occurred in approximately 40% of bacteremia caused by ST72 MRSA with a significantly higher recurrence rate. Patients with risk factors of PB, including liver cirrhosis, high initial CRP, infective endocarditis, or bone and joint infections, might require early aggressive treatment.

Diagnostic yield of a bronchoalveolar lavage fluid galactomannan assay in patients with negative serum galactomannan results suspected to have invasive pulmonary aspergillosis.

BACKGROUND AND OBJECTIVES: There are limited data in real clinical practice on the diagnostic value of a bronchoalveolar lavage (BAL) fluid galactomannan (GM) assay in patients with suspected invasive pulmonary aspergillosis (IPA) who had negative serum GM results. Thus, we investigated the diagnostic performance of a BAL GM assay in patients with negative serum GM assay results who were suspected to have IPA. METHODS: This retrospective study was performed between May 2008 and April 2019 at a tertiary-care hospital in Seoul, South Korea. All patients with suspected IPA whose serum GM assays revealed negative results who sequentially underwent BAL were enrolled in this study. RESULTS: A total of 341 patients with suspected IPA including four cases of proven IPA, 38 cases of probable IPA, 107 cases of possible IPA and 192 patients without IPA were enrolled. Of these 341 patients, 107 (31%) with possible IPA were excluded from the final analysis. Of 42 patients with proven and probable IPA who had initial negative serum GM results, 24 (57%) had positive BAL GM results (n = 24) or BAL fungal culture results (n = 8). In addition, BAL revealed evidence of other opportunistic infections including Pneumocystis jirovecii pneumonia (14% [26/190]), cytomegalovirus (CMV) pneumonia (5% [9/188]) and respiratory viral pneumonia (6% [12/193]). CONCLUSION: Sequential BAL in patients with suspected IPA who had initial negative serum GM results provided additional diagnostic yield in approximately half of patients with evidence of another co-infection.

Adverse Reactions of the Second Dose of the BNT162b2 mRNA COVID-19 Vaccine in Healthcare Workers in Korea.

We conducted a prospective, mobile-based survey on the self-reported adverse reactions in healthcare workers (HCWs) who received both doses of the BNT162b2 mRNA vaccine. Of the 342 HCWs who completed the two-dose vaccination, 265 (77.5%) responded to the survey at least once. Overall, the rates of adverse reactions were higher after the second dose compared with the first dose (89.1% vs. 80.1%, P = 0.006). The most common systemic reactions were muscle ache (69.1%), fatigue (65.7%), headache (48.7%), chills (44.2%), and fever (32.1%), and were notably more common after the second dose vaccine as well. We also noted a sex difference in which the frequency of adverse reactions after the second dose of the vaccine was significantly higher in females, which was not observed after the first dose. The rates of adverse reactions were lower in older age groups, and the rates and severities of the adverse reactions decreased during the 3-day period following vaccination.

Adverse Reactions Following the First Dose of ChAdOx1 nCoV-19 Vaccine and BNT162b2 Vaccine for Healthcare Workers in South Korea.

BACKGROUND: We performed a prospective survey on the adverse reactions following the first dose of two types of vaccines against coronavirus disease 2019 (COVID-19) in healthcare workers (HCWs) in South Korea. METHODS: HCWs at a tertiary referral hospital in Seoul, South Korea, received a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) or an mRNA-based vaccine (BNT162b2) between March 5 and March 26, 2021. The HCWs were asked to report adverse reactions through a mobile self-report questionnaire for three days after vaccination. RESULTS: A total of 7,625 HCWs received the first dose of ChAdOx1 or BNT162b2 vaccine during the study period. Of them, 5,866 (76.9%) HCWs (ChAdOx1, n = 5,589 [95.3%]; BNT162b2, n = 277 [4.7%]) participated at least once in the survey, of whom 77% were female and 86% were younger than 50 years. The overall adverse reaction rate was 93% in the ChAdOx1 group and 80% in the BNT162b2 group (P < 0.001). Both local and systemic reactions were more commonly reported in the ChAdOx1 group, and the difference was larger in systemic reactions such as fever and fatigue. In the ChAdOx1 group, the incidence of adverse reactions was significantly higher in females and those in the younger age groups, while the BNT162b2 group showed such difference according to age. CONCLUSION: In our prospective survey, vaccine-associated adverse reactions were more commonly reported in the ChAdOx1 group than in the BNT162b2 group. Females and younger age groups experienced vaccine-associated adverse reactions more frequently.

Dual-line fabrication method in direct laser lithography to reduce the manufacturing time of diffractive optics elements.

To reduce the manufacturing time of DOEs (Diffractive Optics Elements) and POEs (Periodical Optics Elements), a new fabrication method in direct laser lithography is proposed based on the laser ablation phenomenon and the thermochemical effect of chrome. The basic mechanism of the proposed method and experimental results are also presented. It was found that when a 3 × 3 rectangular pattern is fabricated, the proposed method can reduce the total lithographic length by approximately 33%. The manufacturing time is reduced by nearly 52%. When fabricating a 1,000 × 1,000 rectangular pattern, the manufacturing time was reduced by more than 90%. The time reduction rate is drastically improved when the number of patterns is increased. Various patterns including rectangular, triangular, parallelogram, and diamond shape were fabricated by using the proposed method.

Phase, current, absorbance, and photoluminescence of double and triple metal ion-doped synthetic and salmon DNA thin films.

We fabricated synthetic double-crossover (DX) DNA lattices and natural salmon DNA (SDNA) thin films, doped with 3 combinations of double divalent metal ions (M2+)-doped groups (Co2+-Ni2+, Cu2+-Co2+, and Cu2+-Ni2+) and single combination of a triple M2+-doped group (Cu2+-Ni2+-Co2+) at various concentrations of M2+ ([M2+]). We evaluated the optimum concentration of M2+ ([M2+]O) (the phase of M2+-doped DX DNA lattices changed from crystalline (up to ([M2+]O) to amorphous (above [M2+]O)) and measured the current, absorbance, and photoluminescent characteristics of multiple M2+-doped SDNA thin films. Phase transitions (visualized in phase diagrams theoretically as well as experimentally) from crystalline to amorphous for double (Co2+-Ni2+, Cu2+-Co2+, and Cu2+-Ni2+) and triple (Cu2+-Ni2+-Co2+) dopings occurred between 0.8 mM and 1.0 mM of Ni2+ at a fixed 0.5 mM of Co2+, between 0.6 mM and 0.8 mM of Co2+ at a fixed 3.0 mM of Cu2+, between 0.6 mM and 0.8 mM of Ni2+ at a fixed 3.0 mM of Cu2+, and between 0.6 mM and 0.8 mM of Co2+ at fixed 2.0 mM of Cu2+ and 0.8 mM of Ni2+, respectively. The overall behavior of the current and photoluminescence showed increments as increasing [M2+] up to [M2+]O, then decrements with further increasing [M2+]. On the other hand, absorbance at 260 nm showed the opposite behavior. Multiple M2+-doped DNA thin films can be used in specific devices and sensors with enhanced optoelectric characteristics and tunable multi-functionalities.

3D surface mapping of freeform optics using wavelength scanning lateral shearing interferometry.

Freeform optics have emerged as promising components in diverse applications due to the potential for superior optical performance. There are many research fields in the area ranging from fabrication to measurement, with metrology being one of the most challenging tasks. In this paper, we describe a new variant of lateral shearing interferometer with a tunable laser source that enables 3D surface profile measurements of freeform optics with high speed, high vertical resolution, large departure, and large field-of-view. We have verified the proposed technique by comparing our measurement result with that of an existing technique and measuring a representative freeform optic.

Correction of rotational inaccuracy in lateral shearing interferometry for freeform measurement.

A lateral shearing interferometer has an advantage over previous wavefront measuring interferometers since it requires no reference. Therefore the lateral shearing interferometer can be a powerful solution to measure a freeform surface. It, however, has some issues to be resolved before it can be implemented. One of them is the orthogonality problem between two shearing directions in LSI. Previous wavefront reconstruction algorithms assume that the shearing directions are perfectly orthogonal to each other and lateral shear is obtained simultaneously in the sagittal and tangential directions. For practical LSI, however, there is no way to guarantee perfect orthogonality between two shearing directions. Motivated by this, we propose a new algorithm that is able to compensate the rotational inaccuracy. The mathematical model is derived in this paper. Computer simulations and experiments are also displayed to verify our algorithm.

Multifunctional 3D-Printed Pollen Grain-Inspired Hydrogel Microrobots for On-Demand Anchoring and Cargo Delivery.

While a majority of wireless microrobots have shown multi-responsiveness to implement complex biomedical functions, their functional executions are strongly dependent on the range of stimulus inputs, which curtails their functional diversity. Furthermore, their responsive functions are coupled to each other, which results in the overlap of the task operations. Here, a 3D-printed multifunctional microrobot inspired by pollen grains with three hydrogel components is demonstrated: iron platinum (FePt) nanoparticle-embedded pentaerythritol triacrylate (PETA), poly N-isopropylacrylamide (pNIPAM), and poly N-isopropylacrylamide acrylic acid (pNIPAM-AAc) structures. Each of these structures exhibits their respective targeted functions: responding to magnetic fields for torque-driven surface rolling and steering, exhibiting temperature responsiveness for on-demand surface attachment (anchoring), and pH-responsive cargo release. The versatile multifunctional pollen grain-inspired robots conceptualized here pave the way for various future medical microrobots to improve their projected performance and functional diversity.

Clinical Sensitivity of the (1-3)-ß-D-glucan Test for Predicting Candidemia.

The sensitivity of the (1-3)-ß-D-glucan (BDG) diagnostic test for candidemia varies in different clinical settings, and its usefulness in early diagnosis of candidemia is suboptimal. We evaluated the sensitivity of the test for early candidemia prediction. All adult patients with culture-proven candidemia who underwent a serum Goldstream Fungus (1-3)-ß-D-Glucan Test within seven days prior to candidemia onset at a tertiary referral hospital between January 2017 and May 2021 were included. Any-positive BDG results within seven days prior to candidemia onset were obtained in 38 out of 93 (40.9%) patients. The positive rate increased when the test was performed near the day of candidemia onset (P=0.04) but reached only 52% on the day of candidemia onset. We observed no significant differences between BDG-positive and -negative groups in terms of underlying disease, risk factors for candidemia, clinical presentation, origin of candidemia, and 30-day mortality. Candida albicans was significantly associated with positive BDG results than with all-negative BDG results (P=0.04). The Goldstream BDG test is unreliable for candidemia prediction because of its low sensitivity. Negative BDG results in patients with a high risk of invasive candidiasis should be interpreted with caution.

Enhancement of height resolution in direct laser lithography.

To address the requirements of multi-level semiconductors, we propose a new technique for overcoming the height limitation of direct laser lithography. In the proposed system, an original source beam is fed into an interference generator that divides the input beam by 50: 50 into two output beams. After going through an imaging lens, these two beams make two focusing spots, which are slightly separated in the axial direction. In the overlapped region, these two spots generate a small interferogram that shortens the depth of focus. By using this phenomenon, we are able to overcome the height limitation of direct laser lithography. The governing equations are also derived in this manuscript by using the Gaussian beam model.

Novel compact dual-band LOROP camera with telecentricity.

We report a new dual band compact oblique photography camera (LC11) that is the first to benefit from the incorporation of telecentricity. LC11 has a common front end F/6.6 telescope with 280 mm in aperture that forms its electro-optical (EO, F/7.5) and MWIR (F/5.6) modules. The design allows a substantial reduction in volume and weight due to i) the EO/MWIR compensator and relay lens groups arranged very close to the primary mirror (M1), and ii) light-weighted M1 and SiC main frame (MF) structure. Telecentricity of up to 2 and 0.2 degrees for the EO and MWIR modules, respectively, is achieved by balancing optical power among all lenses. The initial field test shows 0.32 ± 0.05 (EO)/0.20 ± 0.06 (MWIR) in measured MTF at 28 (EO) and 13 (MWIR) cycles/mm in target frequency, and an improved operability with a greater reduction in operational volume and mass than other existing LOROP cameras.

Adjustable bipod flexures for mounting mirrors in a space telescope.

A new mirror mounting technique applicable to the primary mirror in a space telescope is presented. This mounting technique replaces conventional bipod flexures with flexures having mechanical shims so that adjustments can be made to counter the effects of gravitational distortion of the mirror surface while being tested in the horizontal position. Astigmatic aberration due to the gravitational changes is effectively reduced by adjusting the shim thickness, and the relation between the astigmatism and the shim thickness is investigated. We tested the mirror interferometrically at the center of curvature using a null lens. Then we repeated the test after rotating the mirror about its optical axis by 180° in the horizontal setup, and searched for the minimum system error. With the proposed flexure mount, the gravitational stress at the adhesive coupling between the mirror and the mount is reduced by half that of a conventional bipod flexure for better mechanical safety under launch loads. Analytical results using finite element methods are compared with experimental results from the optical interferometer. Vibration tests verified the mechanical safety and optical stability, and qualified their use in space applications.

A Tissue Adhesion-Controllable and Biocompatible Small-Scale Hydrogel Adhesive Robot.

Recently, the realization of minimally invasive medical interventions on targeted tissues using wireless small-scale medical robots has received an increasing attention. For effective implementation, such robots should have a strong adhesion capability to biological tissues and at the same time easy controlled detachment should be possible, which has been challenging. To address such issue, a small-scale soft robot with octopus-inspired hydrogel adhesive (OHA) is proposed. Hydrogels of different Young's moduli are adapted to achieve a biocompatible adhesive with strong wet adhesion by preventing the collapse of the octopus-inspired patterns during preloading. Introduction of poly(N-isopropylacrylamide) hydrogel for dome-like protuberance structure inside the sucker wall of polyethylene glycol diacrylate hydrogel provides a strong tissue attachment in underwater and at the same time enables easy detachment by temperature changes due to its temperature-dependent volume change property. It is finally demonstrated that the small-scale soft OHA robot can efficiently implement biomedical functions owing to strong adhesion and controllable detachment on biological tissues while operating inside the body. Such robots with repeatable tissue attachment and detachment possibility pave the way for future wireless soft miniature robots with minimally invasive medical interventions.