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Osteoporosis is a common, but silent disease until it is complicated by fractures that are associated with morbidity and mortality. Over the past few years, although deep learning-based disease diagnosis on chest radiographs has yielded promising results, osteoporosis screening remains unexplored. Paired data with 13,026 chest radiographs and dual-energy X-ray absorptiometry (DXA) results from the Health Screening and Promotion Center of Asan Medical Center, between 2012 and 2019, were used as the primary dataset in this study. For the external test, we additionally used the Asan osteoporosis cohort dataset (1089 chest radiographs, 2010 and 2017). Using a well-performed deep learning model, we trained the OsPor-screen model with labels defined by DXA based diagnosis of osteoporosis (lumbar spine, femoral neck, or total hip T-score ≤ -2.5) in a supervised learning manner. The OsPor-screen model was assessed in the internal and external test sets. We performed substudies for evaluating the effect of various anatomical subregions and image sizes of input images. OsPor-screen model performances including sensitivity, specificity, and area under the curve (AUC) were measured in the internal and external test sets. In addition, visual explanations of the model to predict each class were expressed in gradient-weighted class activation maps (Grad-CAMs). The OsPor-screen model showed promising performances. Osteoporosis screening with the OsPor-screen model achieved an AUC of 0.91 (95% confidence interval [CI], 0.90-0.92) and an AUC of 0.88 (95% CI, 0.85-0.90) in the internal and external test set, respectively. Even though the medical relevance of these average Grad-CAMs is unclear, these results suggest that a deep learning-based model using chest radiographs could have the potential to be used for opportunistic automated screening of patients with osteoporosis in clinical settings. © 2021 American Society for Bone and Mineral Research (ASBMR).

Background Sarcopenia and osteoporosis frequently co‐occur in the elderly and have common pathophysiological determinants. Slit guidance ligand 3 (SLIT3) has been recently discovered as a novel therapeutic factor against osteoporosis, and a SLIT3 fragment containing the second leucine‐rich repeat domain (LRRD2) had a therapeutic efficacy against osteoporosis. However, a role of SLIT3 in the skeletal muscle is unknown. Methods Skeletal muscle mass, strength, and/or physical activity were evaluated in Slit3 −/−, ovariectomized, and aged mice, based on the measurements of muscle weight and grip strength, Kondziella's inverted hanging test, and/or wheel‐running test. Skeletal muscles were also histologically evaluated by haematoxylin and eosin staining and/or immunofluorescence. The ovariectomized and aged mice were intravenously injected with recombinant SLIT3 LRRD2 for 4 weeks. C2C12 cells were used to know cellular effects of SLIT3, such as in vitro myogenesis, fusion, cell viability, and proliferation, and also used to evaluate its molecular mechanisms by immunocytochemistry, immunoprecipitation, western blotting, real‐time PCR, siRNA transfection, and receptor‐ligand binding ELISA. Results Slit3‐deficient mice exhibited decreased skeletal muscle mass, muscle strength, and physical activity. The relative masses of gastrocnemius and soleus were lower in the Slit3 −/− mice (0.580 ± 0.039% and 0.033 ± 0.003%, respectively) than those in the WT littermates (0.622 ± 0.043% and 0.038 ± 0.003%, respectively) (all, P

OBJECTIVE This study aimed to investigate the impact of indices of adrenal venous sampling (AVS) on postsurgical outcomes in patients with primary aldosteronism (PA). DESIGN AND PATIENTS This retrospective study determined biochemical and clinical outcomes based on ACTH-stimulated AVS parameters (lateralisation index [LI], contralateral ratio [CLR], and ipsilateral ratio [ILR]) in 251 patients with PA at 3 months after surgery. RESULTS Modified complete biochemical success was achieved in 8 of 12 (66.7%) patients with LI = 3-4, 39 of 47 (83.0%) with LI = 4-10, and 155 of 169 (91.7%) with LI ≥ 10 (p = .004 for trend). Modified complete biochemical success was achieved in 29 of 38 (76.3%) patients with CLR ≥ 1 and ILR ≤ 2, 73 of 86 (84.9%) with CLR = 0.25-1 and ILR > 2, and 100 of 104 (96.2%) with CLR 2 (p = .001 for trend). After adjusting for confounders, modified complete biochemical success was associated with an LI ≥ 10 (odds ratio [OR] = 6.32; 95% confidence interval [CI] = 1.33-29.93) using LI = 3-4 as a reference and combined CLR 2 (OR = 11.49; 95% confidence interval [CI] = 2.49-53.01) using combined CLR ≥ 1 and ILR ≤ 2 as a reference. Using combined CLR ≥ 1 and ILR ≤ 2 as a reference, complete clinical success was associated with combined CLR 2 (OR = 3.10; 95% CI = 1.03-9.28) and combined CLR = 0.25-1 and ILR > 2 (OR = 4.92; 95% CI = 1.64-14.76). CONCLUSION LI ≥ 10 may be appropriate for achieving biochemical success. With ILR > 2, CLR

Growth and differentiation factor 15 (GDF-15) is associated with muscle, fat, and bone metabolism; however, this association has not been well characterized. Plasma GDF-15, appendicular skeletal muscle mass (ASM), fat mass (FM), and bone mineral density (BMD) were measured in 146 postmenopausal women. GDF-15 levels were higher in subjects with low Body Mass Index (BMI)-adjusted ASM than in those without (median [interquartile range] 831.3 [635.4-1011.4] vs. 583.8 [455.8-771.1] pg/mL, p = 0.018). The GDF-15 level was inversely correlated with BMI-adjusted ASM (r = - 0.377, p 0.001) and BMD at femur neck (FN-BMD; r = - 0.201, p = 0.015), and positively correlated with percent FM (pFM; r = 0.328, p 0.001). After adjusting for confounders, the GDF-15 level was inversely associated with BMI-adjusted ASM (β = -0.250, p = 0.006) and positively associated with pFM (β = 0.272, p = 0.004), and tended to be inversely associated with FN-BMD (β = - 0.176, p = 0.076). The area under the receiver-operating characteristic curve of GDF-15 level 618.4 pg/mL for sarcopenia was 0.706 (95% confidence interval (CI) 0.625-0.779) with a sensitivity of 83.3% and a specificity of 54.5%. Using a GDF-15 level of 618.4 pg/mL as a cut-off, the GDF-15 level was associated with a significantly greater likelihood of sarcopenia (odds ratio [OR] 2.35; 95% CI 1.00-5.51; p = 0.049), obesity (OR 3.28; 95% CI 1.48-7.27; p = 0.001), osteopenic obesity (OR 3.10; 95% CI 1.31-7.30; p = 0.010), and sarcopenic or osteosarcopenic obesity (OR 4.84; 95% CI 0.88-26.69; p = 0.070). These findings support the potential of GDF-15 as a biomarker for age-related changes in muscle, fat, and bone.

This study sought to evaluate clinical implications of the residual fractional flow reserve (FFR) gradient after angiographically successful percutaneous coronary intervention (PCI).Recent studies have demonstrated FFR measured after PCI is associated with clinical outcome after PCI. Although post-PCI FFR pull back tracings provide clinically relevant information on the residual FFR gradient, there are no objective criteria for assessing post-PCI FFR pull back tracings.A total of 492 patients who underwent angiographically successful PCI and post-PCI FFR measurement with pull back tracings were analyzed. The presence of the major residual FFR gradient after PCI was assessed by both conventional visual interpretation of the pull back tracings and objective analysis using the instantaneous FFR gradient per unit time (dFFR(t)/dt) with a cutoff value of dFFR(t)/dt ≥0.035. Classification agreement between 2 independent operators for the presence of the major residual FFR gradient was compared before and after providing dFFR(t)/dt results. Target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization at 2 years, was compared according to the presence of the major residual FFR gradient.Among the study population, 33.9% had the major residual FFR gradient defined by dFFR(t)/dt. The classification agreement between operators' assessments for the major residual FFR gradient increased with dFFR(t)/dt results compared with conventional visual assessment (Cohen's kappa = 0.633 to 0.819; P 0.001; intraclass correlation coefficient: 0.776 to 0.901; P 0.001). Patients with major residual FFR gradient were associated with a higher risk of TVF at 2 years than those without major residual FFR gradient (9.0% vs 2.2%; P 0.001). Inclusion of the major residual FFR gradient to a clinical prediction model significantly increased discrimination and reclassification ability (C-index = 0.539 vs 0.771; P = 0.006; net reclassification improvement = 0.668; P = 0.007; integrated discrimination improvement = 0.033; P = 0.017) for TVF at 2 years. The presence of the major residual FFR gradient was independently associated with TVF at 2 years, regardless of post-PCI FFR or percent FFR increase (adjusted hazard ratio: 3.930; 95% confidence interval: 1.353-11.420; P = 0.012).Objective analysis of post-PCI FFR pull back tracings using dFFR(t)/dt improved classification agreement on the presence of the major residual FFR gradient among operators. Presence of the major residual FFR gradient defined by dFFR(t)/dt after angiographically successful PCI was independently associated with an increased risk of TVF at 2 years. (Automated Algorithm Detecting Physiologic Major Stenosis and Its Relationship with Post-PCI Clinical Outcomes [Algorithm-PCI]; NCT04304677; Influence of FFR on the Clinical Outcome After Percutaneous Coronary Intervention [COE-PERSPECTIVE]; NCT01873560).

Background: Adrenal venous sampling (AVS) is performed to distinguish the subtype of primary aldosteronism (PA). The clinical implication of contralateral suppression (CS; aldosterone/cortisolnondominant0.26 after adjusting for other factors.Conclusion: CS may not predict postoperative clinical and biochemical outcomes in subjects with unilateral aldosterone excess, but it is associated with postsurgical deterioration of renal function in subjects over 50 years with CSI ≤0.26.

The aim of this study was to evaluate prognostic implications of physiological 2-dimensional disease patterns on the basis of distribution and local severity of coronary atherosclerosis determined by quantitative flow ratio (QFR) virtual pull back.The beneficial effect of percutaneous coronary intervention (PCI) is determined by physiological distribution and local severity of coronary atherosclerosis.The study population included 341 patients who underwent angiographically successful PCI and post-PCI fractional flow reserve (FFR) measurement. Using pre-PCI virtual pull backs of QFR, physiological distribution was determined by pull back pressure gradient index, with a cutoff value of 0.78 to define predominant focal versus diffuse disease. Physiological local severity was assessed by instantaneous QFR gradient per unit length, with a cutoff value of ≥0.025/mm to define a major gradient. Suboptimal post-PCI physiological results were defined as both post-PCI FFR ≤0.85 and percentage FFR increase ≤15%. Clinical outcome was assessed by target vessel failure (TVF) at 2 years.QFR pull back pressure gradient index was correlated with post-PCI FFR (R = 0.423; P 0.001), and instantaneous QFR gradient per unit length was correlated with percentage FFR increase (R = 0.370; P 0.001). Using the 2 QFR-derived indexes, disease patterns were classified into 4 categories: predominant focal disease with and without major gradient (group 1 [n = 150] and group 2 [n = 21], respectively) and predominant diffuse disease with and without major gradient (group 3 [n = 115] and group 4 [n = 55], respectively). Proportions of suboptimal post-PCI physiological results were significantly different according to the 4 disease patterns (18.7%, 23.8%, 22.6%, and 56.4% from group 1 to group 4, respectively; P 0.001). Cumulative incidence of TVF after PCI was significantly higher in patients with predominant diffuse disease (8.1% in group 3 and 9.9% in group 4 vs 1.4% in group 1 and 0.0% in group 2; overall P = 0.024).Both physiological distribution and local severity of coronary atherosclerosis could be characterized without pressure-wire pull backs, which determined post-PCI physiological results. After successful PCI, TVF risk was determined mainly by the physiological distribution of coronary atherosclerosis. (Automated Algorithm Detecting Physiologic Major Stenosis and Its Relationship With Post-PCI Clinical Outcomes [Algorithm-PCI], NCT04304677; Influence of FFR on the Clinical Outcome After Percutaneous Coronary Intervention [PERSPECTIVE], NCT01873560).

OBJECTIVES We aimed to develop a novel wire- and adenosine-free microcirculatory resistive index from functional angiography (angio-IMR) to estimate coronary microcirculatory resistance, and to investigate how this method can improve clinical interpretation of physiological stenosis assessment with quantitative flow ratio (QFR). BACKGROUND Hyperemic index of coronary microcirculatory resistance (IMR) is a widely used tool to assess microcirculatory dysfunction. However, the need of dedicated intracoronary wire and hyperemia limits its adoption in clinical practice. METHODS We performed our study in two separate stages: (1) development of a formula (angio-IMR) to estimate IMR from resting angiograms and aortic pressure (Pa), and (2) validation of the method in a clinical population using invasively measured IMR as reference. Additionally, QFR diagnostic performance was assessed considering angio-IMR values. RESULTS We developed the formula: angio-IMR = (Pa-[0.1*Pa])*QFR*e-Tmn (where e-Tmn is an estimation of hyperaemic mean transit time) and validated it in 115 vessels (104 patients). Angio-IMR correlated well with IMR (Spearman's rho = 0.70, p

Despite the potential roles of sphingosine 1-phosphate (S1P) as a biomarker of osteoporotic fracture (OF), independent of bone mineral density (BMD) and clinical risk factors (CRFs), its association with bone microarchitecture, a key determinant of bone quality, have not been studied yet. We here investigated the association of S1P with the trabecular bone score (TBS), an index of the bone microarchitecture. The plasma S1P concentrations, TBS, and BMD were measured in the 339 postmenopausal women. The S1P level was inversely correlated with the TBS (γ=-0.096, p=0.049) and BMD at the femur neck (FN-BMD: γ=-0.122, p=0.025) and tended to be inversely correlated the BMD at the total hip (TH-BMD: γ=-0.096, p=0.079), but not at the lumbar spine (LS-BMD). After adjusting for fracture risk assessment tool probabilities of major OF from CRFs, the S1P level was inversely associated with the TBS (β=-0.096, p=0.049) and FN-BMD (β=-0.118, p=0.025) and tended to be inversely associated with the TH-BMD (β=-0.092, p=0.083). Compared with subjects in the lowest S1P tertile, those in the highest S1P tertile had a significantly lower TBS (p=0.032) and BMD at femur (p=0.004-0.036). These findings indicated that a high S1P level in postmenopausal women was inversely associated with the both bone mass and microarchitecture, reflecting the compromised bone strength.

Background With the development of evidence-based guidelines for the diagnosis and antibiotic treatment of patients with pyogenic vertebral osteomyelitis, various nonsurgical and surgical treatment strategies have achieved favorable results. However, sufficient administration of appropriate antibiotics is a prerequisite for treatment success, which cannot be guaranteed in patients with culture-negative pyogenic vertebral osteomyelitis. Unfortunately, previous studies on culture-negative pyogenic vertebral osteomyelitis were limited by small patient groups, short follow-up periods, varied treatment protocols, and inconsistently defined clinical endpoints. Questions/purposes Among patients treated according to our center's treatment protocol for culture-negative pyogenic vertebral osteomyelitis, which included patients treated without surgery, with surgery but without spinal instrumentation, as well as patients treated with instrumented surgery, (1) what proportion of patients in each treatment group experienced recurrence (or persistence) of infection, complications of treatment, and death; and (2) what factors were independently associated with recurrent or persistent infection after treatment under this algorithm? Methods This was a retrospective evaluation of a treatment protocol in use at one center from 2008 to 2020. During that time, we treated 183 patients for culture-negative pyogenic vertebral osteomyelitis. The diagnosis was based on clinical, laboratory, and radiological features excluding disease that presents similar features to pyogenic vertebral osteomyelitis. For those patients, our protocol included three possible approaches: nonsurgical treatment, including the use of empirical antibiotics (nonoperative group, n = 82); spinal decompression without instrumentation (noninstrumented group, n = 41); and spinal decompression with instrumentation (instrumented group, n = 60). The indications for each treatment during the period remained relatively consistent. Nonsurgical treatment including empirical antibiotics was applied to all patients according to the specified antibiotic protocol. Spinal decompression without instrumentation was employed when a patient presented substantial or aggravating neurologic deficits or intractable pain from an abscess. Instrumentation was added in patients with mechanical instability before or after spinal decompression. Minimum follow-up to be included in this study was 1 year, and 91% (252 of 277) of patients were accounted for at that time, with no differential loss to follow-up among the study groups (12, five, and four patients missing from the three groups, respectively, at 1 year). Chart review was performed to ascertain the proportion of patients in each group who experienced recurrence, complications, and death. Factors associated with recurrence were assessed across the entire cohort using a multivariable logistic model. We analyzed 1-year recurrence and mortality rates using the Kaplan-Meier method, and their 95% confidence intervals were calculated using the method by Hosmer and Lemeshow. Results At 1 year, the recurrence-free survival rate was 87% (95% confidence interval 78% to 93%) in the nonoperative group, 87% (95% CI 72% to 94%) in the noninstrumented group, and 91% (95% CI 80% to 96%) in the instrumented group. The proportion of patients who experienced a major medical complication in each group was 12% (10 of 82), 10% (4 of 41), and 8% (5 of 60), respectively. At 1 year, the survival rate with patient death as the endpoint was 95% (95% CI 88% to 98%) in the nonoperative group, 95% (95% CI 82% to 99%) in the noninstrumented group, and 97% (95% CI 87% to 99%) in the instrumented group. After controlling for potentially confounding variables including age, medical comorbidities, and anatomical involvement of infection, the following factors were independently associated with increased odds of infection recurrence or persistence: higher Charlson Comorbidity Index (CCI) score (odds ratio 1.6 per point on the CCI [95% CI 1.2 to 2.1]; p = 0.004) and the presence of a psoas abscess (OR 4.7 [95% CI 1.6 to 13.9]; p = 0.005). Conclusion Among patients with negative initial nonoperative culture results, spinal decompression and abscess drainage can be used in those with substantial or aggravating neurological deficits or intractable pain caused by an abscess, while additional early spinal instrumentation can be applied upon consideration of their medical comorbidities and the presence of a psoas abscess when mechanical instability is present before or after the spinal decompression. Reasonable clinical results can be expected, regardless of the results from subsequent operative cultures. However, our study results should be replicated by other centers, and further studies that consider individual differences such as bone mineral density and include patients with previous spinal instrumentation or recurrent infection should be performed to establish a more comprehensive treatment protocol. Level of evidence Level IV, therapeutic study.

Coronary physiological assessment using fractional flow reserve or nonhyperemic pressure ratios has become a standard of care for patients with coronary atherosclerotic disease. However, most evidence has focused on the pre-interventional use of physiological assessment to aid revascularization decision-making, whereas post-interventional physiological assessment has not been well established. Although evidence for supporting the role of post-interventional physiological assessment to optimize immediate revascularization results and long-term prognosis has been reported, a more thorough understanding of these data is crucial in incorporating post-interventional physiological assessment into daily practice. Recent scientific efforts have also focused on the potential role of pre-interventional fractional flow reserve or nonhyperemic pressure ratio pullback tracings to characterize patterns of coronary atherosclerotic disease to better predict post-interventional physiological outcomes, and thereby identify the appropriate revascularization target. Pre-interventional pullback tracings with dedicated post-processing methods can provide characterization of focal versus diffuse disease or major gradient versus minor gradient stenosis, which would result in different post-interventional physiological results. This review provides a comprehensive look at the current evidence regarding the evolving role of physiological assessment as a functional optimization tool for the entire process of revascularization, and not merely as a pre-interventional tool for revascularization decision-making.

This study reports the first two clinical cases of spirometrosis caused by Spirometra sp. in cats in Korea. In these two cases, the cats vomited, and long proglottids of tapeworm were recovered. The sick cats presented with anorexia and lethargy. However, they unexpectedly showed no diarrhea, which is the main symptom of spirometrosis. Based on a fecal floatation test as well as morphological and molecular analyses, the parasite was diagnosed as Spirometra sp. The 2 cases were treated with praziquantel. This study suggests regular monitoring of health and deworming in companion animals, even when animals are well cared for, with regular preventive medication. Additionally, spirometrosis should be considered in the differential diagnosis in cases of gastrointestinal symptoms in Spirometra endemic areas.

Background: Guidelines by the Endocrine Society Guideline on bypassing adrenal vein sampling (AVS) in patients P15.9 ng/dL) and unilateral lesion, accuracy of CT was 84.6% (11/13) in patients aged 29.6 ng/dL, respectively. The significant difference in accuracy of CT in 198 patients with marked PA and a unilateral lesion between the P=0.044) disappeared in 139 of 198 patients with PAC > 30.0 ng/dL (91.9% vs. 87.7%, P=0.590).Conclusion: Patients with hypokalemia, PAC >30.0 ng/dL, and unilateral lesion were at high risk of unilateral PA regardless of age.

In recent years, electroceuticals have been spotlighted as an emerging treatment for various severe chronic brain diseases, owing to their intrinsic advantage of electrical interaction with the brain, which is the most electrically active organ. However, the majority of research has verified only the short-term efficacy through acute studies in laboratory tests owing to the lack of a reliable miniaturized platform for long-term animal studies. The construction of a sufficient integrated system for such a platform is extremely difficult because it requires multi-disciplinary work using state-of-the-art technologies in a wide range of fields. In this study, we propose a complete system of an implantable platform for long-term preclinical brain studies. Our proposed system, the extra-cranial brain activator (ECBA), consists of a titanium-packaged implantable module and a helmet-type base station that powers the module wirelessly. The ECBA can also be controlled by a remote handheld device. Using the ECBA, we performed a long-term non-anesthetic study with multiple canine subjects, and the resulting PET-CT scans demonstrated remarkable enhancement in brain activity relating to memory and sensory skills. Furthermore, the histological analysis and high-temperature aging test confirmed the reliability of the system for up to 31 months. Hence, the proposed ECBA system is expected to lead a new paradigm of human neuromodulation studies in the near future.

This study sought to develop an automated algorithm using pre-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) pullback recordings to predict post-PCI physiological results in the pre-PCI phase.Both FFR and percent FFR increase measured after PCI showed incremental prognostic implications. However, there is no current method to predict post-PCI physiological results using physiological assessment in the pre-PCI phase.An automated algorithm that analyzes instantaneous FFR gradient per unit time (dFFR(t)/dt) was developed from the derivation cohort (n = 30). Using dFFR(t)/dt, the pattern of atherosclerotic disease in each patient was classified into 3 groups (major, mixed, and minor FFR gradient groups) in both the internal validation cohort with constant pullback method (n = 234) and the external validation cohort with nonstandardized pullback methods (n = 252). All patients in the validation cohorts underwent PCI on the basis of pre-PCI FFR ≤0.80. Suboptimal post-PCI physiological results were defined as both post-PCI FFR0.84 and percent FFR increase ≤15%. From the derivation cohort, cutoffs of dFFR(t)/dt for major and minor FFR gradient were 0.035/s and 0.015/s, respectively.In validation cohorts, dFFR(t)/dt showed significant correlations with percent FFR increase (R = 0.801; p 0.001) and post-PCI FFR (R = 0.099; p = 0.029). In both the internal and external validation cohorts, the major FFR gradient group showed significantly higher post-PCI FFR and percent FFR increase compared with those in the mixed or minor FFR gradient groups (all p values 0.001). The proportions of suboptimal post-PCI physiological results were significantly different among 3 groups (10.4% vs. 25.8% vs. 45.7% for the major, mixed, and minor FFR gradient groups, respectively; p 0.001) in validation cohorts. Absence of major FFR gradient lesion (odds ratio: 2.435, 95% [CI]: 1.252 to 4.734; p = 0.009) and presence of minor FFR gradient lesion (odds ratio: 2.756, 95% confidence interval: 1.629 to 4.664; p 0.001) were independent predictors for suboptimal post-PCI physiological results.The automated algorithm analyzing pre-PCI pullback curve was able to predict post-PCI physiological results. The incidence of suboptimal post-PCI physiological results was significantly different according to algorithm-based classifications in the pre-PCI physiological assessment. (Automated Algorithm Detecting Physiologic Major Stenosis and Its Relationship with Post-PCI Clinical Outcomes [Algorithm-PCI]; NCT04304677).

The biological activity and effects of circulating sphingosine 1-phosphate (S1P) might be dependent on the carrier protein. Although S1P is known to be a biomarker for osteoporotic fracture (OF), its role according to its carrier protein (high-density lipoprotein (HDL), low-density lipoprotein (LDL), or albumin) has not yet been studied. We measured the protein-bound S1P levels and bone mineral density (BMD) in 58 postmenopausal women with OF and 58 age-matched and body mass index-matched postmenopausal women without OF. Albumin-bound S1P was the most abundant. Before adjustment, women with OF had higher total S1P (p=0.046) and albumin-bound S1P (p=0.026) levels than those without OF, but there was no difference in the levels of HDL-bound or LDL-bound S1P. After adjustment for confounders including BMD, women with OF had only higher levels of total S1P than those without OF (p=0.047). Before adjustment, the OR for OF was higher in subjects in the highest quartile for total S1P (OR 5.36, 95% CI 1.22 to 23.63) or albumin-bound S1P (OR 4.48, 95% CI 1.22 to 16.42). After adjustment for confounders including BMD, statistical significance persisted only for total S1P (OR 2.23, 95% CI 1.12 to 4.81). These findings suggest that the positive association of S1P with OF is mainly due to level of total plasma S1P and not due to the differing contributions from specific carrier protein-bound fractions.

Objectives This study sought to investigate the prognostic implications of post–percutaneous coronary intervention (PCI) nonhyperemic pressure ratios compared with that of post-PCI fractional flow reserve (FFR). Background FFR measured after PCI has been shown to possess prognostic implications. However, the prognostic value of post-PCI nonhyperemic pressure ratios has not yet been clarified. Methods A total of 588 patients who underwent PCI with available both post-PCI FFR and resting distal coronary pressure-to-aortic pressure ratio (Pd/Pa) were analyzed. Post-PCI FFR and Pd/Pa were measured after successful angiographic stent implantation. The primary outcome was target vessel failure (TVF) up to 2 years, defined as a composite of cardiac death, target vessel–related myocardial infarction, and clinically driven target vessel revascularization. Prognosis of patients according to post-PCI Pd/Pa was compared with that of post-PCI FFR. Results Despite angiographically successful PCI, 18.5% had post-PCI FFR ≤0.80 and 36.9% showed post-PCI Pd/Pa ≤0.92. In post-PCI Pd/Pa >0.92 group, 93.8% of patients showed post-PCI FFR >0.80. Conversely, 60.4% of patients showed post-PCI FFR >0.80 in post-PCI Pd/Pa ≤0.92 group. Although there was significant difference in TVF according to post-PCI FFR (≤0.80 vs. >0.80: 10.3% vs. 2.5%; p 0.92: 6.2% vs. 2.5%; p = 0.029), the reclassification ability of model for TVF was increased only with post-PCI FFR (net reclassification index 0.627; p = 0.003; integrated discrimination index 0.019; p = 0.015), but not with post-PCI Pd/Pa, compared with model including clinical factors. Compared with patients with post-PCI Pd/Pa >0.92, patients with post-PCI Pd/Pa ≤0.92 and FFR ≤0.80 had significantly higher risk of TVF (10.4% vs. 2.5%; adjusted hazard ratio: 4.204; 95% confidence interval: 1.521 to 11.618; p = 0.006); however, those with post-PCI Pd/Pa ≤0.92 but FFR >0.80 showed similar risk of TVF (3.5% vs. 2.5%; adjusted hazard ratio: 1.327; 95% confidence interval: 0.398 to 4.428; p = 0.645). Conclusions Over one-half of the patients with abnormal post-PCI Pd/Pa ≤0.92 showed post-PCI FFR >0.80. Compared with post-PCI FFR, post-PCI Pd/Pa showed limited reclassification ability for the occurrence of TVF. Among patients with abnormal post-PCI Pd/Pa, only patients with positive post-PCI FFR showed significantly higher risk of TVF than did those with post-PCI Pd/Pa >0.92. (Prognostic Perspective of Invasive Hyperemic and Non-Hyperemic Physiologic Indices Measured After Percutaneous Coronary Intervention [PERSPECTIVEPCI]; NCT04265443)

Despite the importance of sleep and the evidence on its relationship with various chronic diseases, quality of sleep is not considered in patients with lumbar spinal stenosis (LSS). This prospective comparative study aimed to investigate the changes in sleep disturbance after treatment in patients with LSS. Patients with LSS and sleep disturbance (n = 201; 147 conservatively treated and 54 patients with surgical treatment) were included. The Pittsburgh sleep quality index (PSQI) was used to evaluate sleep quality. Propensity score matching was used to attenuate the potential bias. Clinical outcome of surgery, as determined by the Oswestry disability index, and the PSQI was compared between the two groups at 6 weeks, 3 months, and 6 months after enrollment. Multivariate logistic analysis was performed to adjust for possible confounders within the matched cohorts. Among the 201 patients, 96 (47.7%) patients were finally matched (48 patients in each group). Sleep quality was initially improved after treatment, regardless of the treatment method. Sleep quality in the surgical group was improved by 6 weeks after surgery and consistently improved during the 6-month follow-up period, despite less use of pain killer. Conversely, the improvement in sleep quality at 6-weeks following conservative treatment was not maintained during the follow-up, although the treatment outcome for LSS measured by ODI was continuously improved. After multivariate logistic regression analysis within propensity score matched cohorts, surgical treatment had a significantly greater chance to improve sleep quality compared to conservative treatment. The failure of sleep improvement in conservative group was significantly associated with depression presented by worse score in Hamilton depression rating scale, and more severe degree of foraminal-type stenosis, which should be carefully considered for conservative treatment of LSS patients with sleep disturbance.

Poly-para-xylylene C (Parylene C) and Aluminium Nitride (AlN) multilayered thin films using a single chamber are proposed to achieve transparent passivation for organic light-emitting diodes (OLED). Parylene C-AlN multilayered thin films were obtained through a sequential deposition of Parylene C layers by an optimized chemical vapor deposition as well as deposition of AlN layers by radio frequency reactive sputtering within a short process time at room temperature. An OLED passivated with the thin film showed a significant extension of shelf-life of 400 h at 25 °C and 30% RH without any formation of dark spots during the shelf-life analysis, while a reference OLED without any passivation film was degraded within 24 h. In addition, the multilayered passivation films exhibited considerable optical transparency with transmittance greater than 85% in the visible range. This result demonstrates that Parylene C-AlN multilayered films can be successfully deposited within a short time at room temperature in a single chamber for passivation applications in transparent flexible OLEDs and other organic electronic devices.

Background: The purpose of this study was to evaluate the long-term survival rates of very elderly (age ≥80) critically ill patients admitted to a medical intensive care unit (MICU) at a regional tertiary-care hospital in Korea. Methods: We retrospectively analyzed data from patients who survived after discharged from the MICU of our hospital. Survival rates at 90 days, 1 year, 2 years, and 3 years were assessed between patients age ≥80 and those age

Purpose The purpose of this study was to develop algorithms and software that can track the trajectory of table tennis balls using image-processing algorithms to obtain information quickly for under and establish tactics used in table tennis. Methods The algorithms used in the field of computer vision were applied on two matches played by novice and two matches during international competitions by elite athletes. Reliability analysis was performed by comparing the table tennis ball bounce frequency in each zone obtained through the automatic method and the manual method. Results The mean reliability of the two novice games was only 85.1 ± 3.69%, total error was 14.9 ± 3.69%, overestimation error was 52.2 ± 9.78%, and underestimation error was 47.8 ± 9.78%. While the mean reliability of the two international tournaments was 71.8 ± 0.87%, the total error was 28.2 ± 0.87%, overestimation error was 82.0 ± 8.03%, and underestimation error was 19.2 ± 7.75%. Conclusions Although the target reliability of algorithms and software developed in this study was achieved only in novice competitions with 80%, the over-estimation errors were generally high in international competitions, showing the potential for further improvement.

Background The number of human Q fever cases in South Korea has been rapidly increasing since 2015. We report the first isolation of Coxiella burnetii in Korea in two patients who initially presented with non-specific febrile illness and were finally diagnosed with acute Q fever in South Korea. Case presentation Two adult patients with fever had serologic tests against C. burnetii initially negative, and polymerase chain reaction against 16S rRNA using whole blood was also negative. After bacterial amplification of C. burnetii in immune-depressed mice, we isolated C. burnetii from patients with acute Q fever. The isolates KZQ2 and KZQ3 were confirmed by polymerase chain reaction, nucleotide sequence analysis, and morphologic observation using a transmission electron microscope. Conclusions These results can help us understand the clinical and epidemiologic features of Q fever in South Korea.

The aim of this study was to evaluate temporal changes in coronary hemodynamic and physiological indexes in the non-infarct-related artery (IRA), which might be affected by adjacent infarcted myocardium, using an experimental animal model of acute myocardial infarction.There has been debate on the reliability of fractional flow reserve and resting pressure-derived indexes, including instantaneous wave-free ratio, in the non-IRA in patients with acute ST-segment elevation myocardial infarction.In Yorkshire swine, acute myocardial infarction was simulated with selective balloon occlusion at the left circumflex coronary artery as the IRA for 30 min. Non-IRA stenosis was created using bare-metal stent implantation in the left anterior descending coronary artery 4 weeks before the experiments. Serial changes in systemic hemodynamic status, coronary pressure, and Doppler-derived coronary flow velocity were measured in a nonoccluded left anterior descending coronary artery as the non-IRA from baseline, balloon occlusion of the left circumflex coronary artery, and 15 min after reperfusion of the left circumflex coronary artery.Among the 6 experimental subjects, the median diameter stenosis of the non-IRA was 33.9% (interquartile range: 21.7% to 46.1%). During balloon occlusion of the IRA, there were transient significant changes in both resting and hyperemic aortic pressure, distal coronary pressure, averaged peak velocity, transstenotic pressure gradient, and microvascular resistance of the non-IRA (p 0.020 for all). After reperfusion of the IRA, the resting averaged peak velocity (p = 0.002) and resting transstenotic pressure gradient (p = 0.004) were significantly increased and resting microvascular resistance (p = 0.004) was significantly decreased compared with their values in the baseline phase. However, the hyperemic averaged peak velocity (p = 0.479), hyperemic transstenotic pressure gradient (p = 0.778), and hyperemic microvascular resistance (p = 0.816) were not significantly different compared with those in the baseline phase. After reperfusion, fractional flow reserve in the non-IRA was not significantly different (0.94 ± 0.01 vs. 0.93 ± 0.01; p = 0.353), while coronary flow reserve (1.93 ± 0.07 vs. 1.36 ± 0.07; p = 0.025) and instantaneous wave-free ratio (0.97 ± 0.01 vs. 0.93 ± 0.01; p = 0.001) were significantly lower than baseline values.In a porcine model of acute myocardial infarction, occlusion of the IRA induced significant changes in systemic hemodynamic status and coronary circulatory indexes of the non-IRA. However, after reperfusion of the IRA, fractional flow reserve did not change significantly, whereas coronary flow reserve and instantaneous wave-free ratio showed significant changes compared with baseline values.

Background/aims Minimising total ischemic time (TIT) is important for improving clinical outcomes in patients with ST-segment elevation myocardial infarction who have undergone percutaneous coronary intervention (PCI). TIT has not shown a significant improvement due to persistent pre-hospital delay. This study aimed to investigate the risk factors associated with pre-hospital delay. Methods Individuals enrolled in the Korea Acute Myocardial Infarction Registry-National Institutes of Health between 2011 and 2015 were included in this study. The study population was analyzed according to the symptom-to-door time (STDT; within 60 or > 60 minutes), and according to the type of hospital visit (emergency medical services [EMS], non-PCI center, or PCI center). Results A total of 4,874 patients were included in the analysis, of whom 28.4% arrived at the hospital within 60 minutes of symptom-onset. Old age (> 65 years), female gender, and renewed ischemia were independent predictors of delayed STDT. Utilising EMS was the only factor shown to reduce STDT within 60 minutes, even when cardiogenic shock was evident. The overall frequency of EMS utilisation was low (21.7%). Female gender was associated with not utilising EMS, whereas cardiogenic shock, previous myocardial infarction, familial history of ischemic heart disease, and off-hour visits were associated with utilising EMS. Conclusion Factors associated with delayed STDT and not utilising EMS could be targets for preventive intervention to improve STDT and TIT.

Tick-borne diseases (TBD) cause enormous losses for farmers. Backyard raising comprises majority of the livestock population in the Philippines, but TBD information in backyard livestock is scarce. In this study, 48 cattle and 114 water buffalo samples from Quezon province, Philippines were molecularly screened for tick-borne pathogens. Anaplasma marginale (16.67%) and hemoplasma (20.99%) were detected in the samples. A. marginale infection (P=0.0001) was significantly higher in cattle, while hemoplasma infection (P=0.011) was significantly higher in water buffaloes. A. marginale isolates from this study were highly similar to previous isolates from the Philippines while Mycoplasma wenyonii and Candidatus Mycoplasma haemobos were the identified hemoplasma species. Our findings reveal additional information on the TBD situation of Philippine backyard livestock.

Background Despite advances in devices and techniques, coronary bifurcation lesion remains a challenging lesion subset in the field of percutaneous coronary intervention (PCI). We evaluate 10‐year trends in bifurcation PCI and their effects on patient outcomes. Methods and Results We analyzed 10‐year trends in patient/lesion characteristics, devices, PCI strategy, stent optimization techniques, and clinical outcomes using data from 5498 patients who underwent bifurcation PCI from 2004 to 2015. Clinical outcomes 2 years after the index procedure were evaluated in terms of target vessel failure (a composite of cardiac death, myocardial infarction, and target vessel revascularization) and a patient‐oriented composite outcome (a composite of all‐cause death, myocardial infarction, and any revascularization). During the 10‐year study period, patient and lesion complexity, such as multivessel disease, diabetes mellitus, chronic kidney disease, and left main bifurcation, increased continuously (all P P P P values were Conclusions During the past decade of bifurcation PCI, patient and lesion characteristics, devices, PCI techniques, and patient prognosis have all significantly changed. Despite increased patient and lesion complexity, clinical outcomes after bifurcation PCI have improved, mainly because of better devices and more widespread adoption of procedural optimization techniques and appropriate treatment strategies. Registration URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT01642992 and NCT03068494.

Background and Objectives: Extracorporeal membrane oxygenation (ECMO) can be helpful in patients with cardiogenic shock associated with myocardial infarction, and its early use can improve the patient survival rate. In this study, we report a mortality rate-difference analysis that examined the time and location of shock occurrence. Materials and Methods: We enrolled patients who underwent ECMO due to cardiogenic shock related to myocardial infarction and assigned them to either a pre- or post-admission shock group. The primary outcome was the 1-month mortality rate, a subgroup analysis was conducted to assess the effect of bailout ECMO. Results: Of the 113 patients enrolled, 67 (38 with pre-admission shock, 29 with post-admission shock) were analysed. Asystole was more frequently detected in the pre-admission shock group than in the post-admission group. In both groups, the commonest culprit lesion location was in the left anterior descending artery. Cardiopulmonary resuscitation was performed significantly more frequently and earlier in the pre-admission group. The 1-month mortality rate was significantly lower in the pre-admission group than in the post-admission group. Male sex and ECMO duration (≥6 days) were factors significantly related to the reduced mortality rate in the pre-admission group. In the subgroup analysis, the mortality rate was lower in patients receiving bailout ECMO than in those not receiving it, the difference was not statistically significant. Conclusions: ECMO application resulted in lower short-term mortality rate among patients with out-of-hospital cardiogenic shock onset than with in-hospital shock onset, early cardiopulmonary resuscitation and ECMO might be helpful in select patients.

BACKGROUND Because no data were available regarding the effect of preexisting left ventricular filling pressure (LVFP) on clinical outcomes in patients with acute myocardial infarction (AMI), we evaluated whether preexisting high LVFP can determine outcomes of subsequent AMI events.Methods and Results:Among 399,613 subjects who underwent echocardiography for various reason from August 2004 to June 2019, 231 had experienced subsequent AMI and were stratified according to preexisting LVFP: low LVFP (E/e' ≤14) and high LVFP (E/e' >14). The primary outcome was cardiac death at 30 days and 1 year after AMI. Overall, 19.5% had high LVFP prior to AMI events. Preexisting high LVFP was associated with an increased risk of cardiac death at 30 days (3.8% vs. 11.6%; adjusted hazard ratio (HR) 4.56, 95% confidence interval (CI) 1.20-17.24, P=0.026) and 1 year after AMI (7.9% vs. 35.9%; adjusted HR 4.14, 95% CI 1.79-9.57, P

Coffee roasting is the process of applying heat to green coffee beans to bring out flavors through chemical changes. This study aimed to investigate the effect of roasting degree on the antioxidant capacities of espresso and drip coffee extracted from Coffea arabica cv. Java in Laos. Green coffee beans were roasted under four conditions (Light-medium, Medium, Moderately dark, and Very dark), and espresso and drip coffee were extracted. The contents of total phenolics (TP), total flavonoids (TF), and chlorogenic acids (CGA) decreased as the roasting degree increased, whereas the caffeine content increased. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity was lower in the Medium, Moderately dark, and Very dark compared to the Light-medium. The ferric reducing antioxidant power (FRAP) was lower in the Very dark than the Light-medium, Medium, and Moderately dark. Principal component analysis showed that TP, TF, CGA, caffeine, DPPH radical scavenging activity, and FRAP distinguish coffee extracts with various roasting degrees. Therefore, it is concluded that roasting degree is a modifiable factor for the use of coffee as an antioxidant material in the food industry, and TF, TP, CGA, and caffeine contents, DPPH radical scavenging activity and FRAP are good indicators for determining the antioxidant capacity of coffee.

Purpose This retrospective study was aimed to evaluate the clinical characteristics and treatment outcomes in patients with osteonecrosis of the jaw who were receiving oral versus intravenous (IV) bisphosphonate (BP). Materials and methods This retrospective study enrolled subjects who had been diagnosed with medication-related osteonecrosis of the jaw (MRONJ) during the period from July 2010 to June 2014. Information regarding the following demographic and clinical characteristics was collected: demographic data, administration route and type of BP, duration of BP medication, primary disease, number of involved sites, location of the lesion, number of surgeries, outcome of treatments, and laboratory test. All the patients were divided into oral and IV BP groups; and the between-group differences were compared. Results Total 278 patients were divided into two groups as per the route of BP administration. The proportion of oral BP-related MRONJ group were more dominant over IV BP group (oral BP, n = 251; IV BP, n = 27). In the IV BP group, the average dosing duration (31.4 months) was significantly shorter than that in the oral BP group (53.1 months) (P < 0.001). The average number of involved sites in the oral BP group (1.21 ± 0.48) was smaller than that in the IV BP group (1.63 ± 0.84) (P < 0.001). The average number of surgeries was higher in the IV BP group (1.65 ± 0.95) as compared to that in the oral BP group (0.98 ± 0.73) (P < 0.001). Outcome after the surgery for MRONJ after IV BP was poor than oral BP group. Conclusion IV administration of BP causes greater inhibition of bone remodeling and could lead more severe inflammation. Therefore, even if the duration of IV administration of BP is shorter than that of oral BP, the extent of the lesion could be more extensive. Therefore, the result suggests that the MRONJ after IV BP for cancer patients needs to be considered as different characteristics to oral BP group for osteoporosis patents.

Background In tandem stenoses, nonhyperemic pressure ratio pullback is the preferred method to fractional flow reserve (FFR), based on the assumption of stable resting coronary flow. This study aimed to evaluate temporal changes of coronary circulatory indexes in tandem stenoses before and after angioplasty for proximal stenosis. Methods and Results Coronary tandem stenoses were created by porcine restenosis model with 2 bare metal stents in the left anterior descending artery. Four weeks later, changes in distal coronary pressure (Pd), averaged peak velocity, microvascular resistance, transstenotic pressure gradient across distal stenosis, resting Pd/aortic pressure, and FFR were measured before and 1, 5, 10, 15, and 20 minutes after balloon angioplasty for proximal stenosis. After angioplasty, there were significant changes in both resting and hyperemic Pd, averaged peak velocity, microvascular resistance, and transstenotic pressure gradient across distal stenosis (all P values P =0.712 and 0.972, respectively). Conversely, resting averaged peak velocity remained increased (10.1±0.7 to 17.8±0.7; P P P =0.040) and hyperemic conditions (11.0±3.0 to 27.4±3.3 mm Hg; P P P Conclusions After angioplasty for proximal stenosis, transstenotic pressure gradient across distal stenosis showed similar changes between resting and hyperemic conditions. Both actual post–percutaneous coronary intervention resting Pd/aortic pressure and FFR were significantly lower than predicted values.

This study analyzes the optimal location of gas detectors through the gas dispersion in a cargo compressor room of a 174K LNG carrier equipped with high-pressure cargo handling equipment; in addition, we propose a reasonable method for determining the safety regulations specified in the new International Code of the Construction and Equipment of Ships Carrying Liquefied Gases in Bulk (IGC). To conduct an LNG gas dispersion simulation in the cargo compressor room-equipped with an ME-GI engine-of a 174 K LNG carrier, the geometry of the room as well as the equipment and piping, are designed using the same 3D size at a 1-to-1 scale. Scenarios for a gas leak were examined under high pressure of 305 bar and low pressure of 1 bar. The pinhole sizes for high pressure are 4.5, 5.0, and 5.6mm, and for low pressure are 100 and 140 mm. The results demonstrate that the cargo compressor room will not pose a serious risk with respect to the flammable gas concentration as verified by a ventilation assessment for a 5.6 mm pinhole for a high-pressure leak under gas rupture conditions, and a low-pressure leak of 100 and 140 mm with different pinhole sizes. However, it was confirmed that the actual location of the gas detection sensors in a cargo compressor room, according to the new IGC code, should be moved to other points, and an analysis of the virtual monitor points through a computational fluid dynamics (CFD) simulation.

Couette–Taylor flow reactor is a mixing device that offers wide range of mixing regimes within a single reactor and operates in continuous flow mode. This reactor is recently used in manufacturing the cathode material of lithium ion batteries. Here, we simulate the agglomeration process of Li(NixMnyCoz)O2 particles using computational fluid dynamics. Quadrature method of moments is implemented for modeling of aggregation and breakage in Couette-Taylor flow reactor. We conduct an experiment of the preparation of Li(NixMnyCoz)O2 precursors, and the experimental data are compared with simulated results for the validation of numerical model. The predicted evolutions of mean particle size are well agreed with experimental data. For the practical application, we investigate the effects of density ratio of particle to fluid and initial volume fraction of particles on the particle size. The results show that the particle diameter increases with increasing of density ratio, but it decreases with increasing of initial volume fraction of particles. On the other hand, the particle sizes become similar at high rotational speed.

Despite many studies about local and systemic interactions between bone and muscle, the more dominant interaction remains unclear. We aimed to compare the association of skeletal muscle mass with bone mineral density (BMD) at the femur, which seemed more likely affected by local interaction, and the association of skeletal muscle mass with BMD at the lumbar spine (LS-BMD) and the trabecular bone score (TBS), which seemed more likely affected by systemic interaction. In 279 women, we measured the femoral neck BMD (FN-BMD), total hip BMD (TH-BMD), LS-BMD, and TBS. Appendicular skeletal muscle mass (ASM), lean mass (LM), and other LM (OLM; remaining LM excluding ASM) were measured using bioelectrical impedance analysis. ASM (β = 0.008–0.014, p

The purpose of this study was 2-fold: 1) to investigate the prevalence of gastrointestinal parasite infection in cats reared in Daegu, Republic of Korea and 2) to assess the efficacy and safety of a topical emodepside/praziquantel formulation for cats with parasitic infections. The gastrointestinal parasite infections were examined microscopically using the flotation method. Of 407 cats, 162 (39.8%) were infected by at least one gastrointestinal parasite, including Toxocara cati (63.0%), Toxascaris leonina (31.5%), Taenia taeniaeformis (3.7%), and Cystoisospora felis (1.9%). None of the infected animals had multiple infections. When the data were analyzed according to sex, age, and type of cat, stray cats showed statistically higher prevalence than companion cats (Plt;0.05). On the 5th day after treatment, no parasitic eggs were detected using microscopic examination. In addition, no adverse effects, such as abnormal behaviors and clinical symptoms, were observed in the cats treated with the drug. These results quantify the prevalence of gastrointestinal parasites in cats in Daegu, Republic of Korea, and show that topical emodepside/praziquantel is a safe and effective choice for treating the parasitic infections in cats.

The water buffalo industry is a vital part of the Philippine livestock economy and is an essential contributor to the developing local dairy industry. Although relatively less susceptible to diseases, water buffaloes can still be infected and can act as reservoirs of tick-borne pathogens (TBPs). However, limited information is available regarding the prevalence of tick-borne infections in water buffaloes in the Philippines. This study was conducted to identify TBPs harbored by water buffaloes and to characterize these pathogens molecularly. One hundred water buffalo blood samples collected from three areas in Bohol, Visayas region, Philippines were screened for various TBPs using pathogen-specific PCR assays. TBPs were detected in 46% of the samples (39% singly infected, 7% coinfected). The pathogens detected were Anaplasma marginale (29%), Babesia bovis (21%), and B. bigemina (3%). None of the blood samples were positive for Theileria annulata, T. orientalis, and B. ovata. A. marginale infection rates were significantly higher (37.5%) among water buffaloes aged ≤6 years (P = 0.046) than those >6 years old (18.2%) and was detected only in Bulgarian Murrah (36.1%) and US Murrah (25.9%) breeds. Phylogenetic analyses revealed that groEL sequences of A. marginale were 100% identical with isolates from the Philippines (Batangas and Cebu) and China. Two B. bigemina RAP-1a gene sequences were identical to each other and were homologous with previous isolates from Thailand, Indonesia, Uruguay, and the Philippines. Moreover, four B. bovis SBP-2 partial sequences obtained in this study had 92.4–99.7% identities. This study is the first molecular detection and characterization of A. marginale, B. bigemina and B. bovis in water buffaloes in the Visayas region, and the first molecular confirmation of B. bovis infection in water buffaloes in the country. The findings presented in this study may serve as baseline data for crafting effective tick-borne disease surveillance and prevention programs in Bohol and in the Philippines.

Publisher's version (útgefin grein)., Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 – 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10−42, β = −0.090) and confers risk of hip fracture (P = 1.0 × 10−8, OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density., We thank all the study subjects for their valuable participation, the staff from all studies and the participating physicians. A part of this research has been conducted using the UK Biobank Resource under Application Number 23359. arcOGEN (http://www.arcogen.org.uk/) was funded by a special purpose grant from Arthritis Research UK (grant 18030).

Background Extracorporeal shock wave therapy (ESWT) has been suggested as a useful treatment for spasticity in patients with stroke. To date, most studies have used clinical or biomechanical assessments to determine the effects of treatment. Objectives To assess the effect of a single session of ESWT through ultrasonographic assessment on spasticity in patients with chronic stroke. Design Randomized controlled trial. Setting Rehabilitation center. Participants Eighteen patients with chronic stroke. Methods Participants were randomly assigned to an ESWT group (n = 9) or control group (n = 9). In the ESWT group, a single session of ESWT was given in the medial head of the gastrocnemius muscle of the spastic side at 4 Hz, 2000 shots with intensity of stimulation using energy of 0.1 mJ/mm 2 . Sham stimulation was provided by only making sound without putting the device into contact with the skin in the control group. The clinical trial registration number of this study is KCT0002582. Main Outcome Measures Participants were evaluated prior to the treatment, 30 minutes, 1 week, and 4 weeks after treatment. Clinical measures included Modified Ashworth Scale (MAS), passive range of motion (PROM), and Fugl-Meyer Assessment (FMA). As the primary outcome measure, the ultrasonographic measures were Achilles tendon length (ATL), muscle fascicle length (MFL), muscle thickness (MT), and pennation angle (PA). Results There were no significant differences between the 2 groups for any demographic or baseline measures. At all follow-up evaluations, improvement was shown in MAS as well as changes from baseline of ultrasonographic measures in the ESWT group compared to the control group. In the case of ultrasonographic measures, the difference between the group was greatest at 4 weeks. At follow-up of 4 weeks, between-group difference was 0.66 points ( P = .04) on MAS scores, 5.45 points ( P = .004) on ATL scores, 4.95 points ( P = .002) on MFL scores, 1.83 points ( P P Conclusions Some ultrasonographic measures of spasticity as well as MAS were improved after a single session of ESWT. Future studies with larger numbers of subjects compared with other spasticity metrics are necessary to further evaluate the treatment effect of ESWT. Level of Evidence I

Pre-operative chemoradiotherapy (CRT) is a preferable treatment option for patients with locally advanced rectal cancer. However, few data are available regarding pre-operative CRT for locally advanced colon cancer. Here, we describe two cases of successful treatment with pre-operative CRT and establish evidence supporting this treatment option in patients with locally advanced colon cancer. In the first case, a 65-year-old woman was diagnosed with ascending colon cancer with duodenal invasion. In the second case, a 63-year-old man was diagnosed with a colonic-duodenal fistula due to transverse colon cancer invasion. These case reports will help to establish a treatment consensus for pre-operative CRT in patients with locally advanced colon cancer.

Analyses using the largest Korean cohort of adrenal incidentaloma (AI) revealed that subtle cortisol excess in premenopausal women and reduced dehydroepiandrosterone-sulfate (DHEA-S) in postmenopausal women and men are associated with bone mineral density (BMD) reduction in Asian patients with subclinical hypercortisolism (SH). Few studies evaluated bone metabolism in Asians with SH. We investigated associations of cortisol and DHEA-S, an adrenal androgen, with BMD in Asians with AI, with or without SH. We used cross-sectional data of a prospective multicenter study from Korea. We measured BMD, bone turnover markers, cortisol levels after 1-mg dexamethasone suppression test (1-mg DST), DHEA-S, and baseline cortisol to DHEA-S ratio (cort/DHEA-S) in 109 AI patients with SH (18 premenopausal, 38 postmenopausal women, and 53 men) and 686 with non-functional AI (NFAI; 59 premenopausal, 199 postmenopausal women, and 428 men). Pre- and postmenopausal women, but not men, with SH had lower BMDs at lumbar spine (LS) than those with NFAI (P = 0.008~0.016). Premenopausal women with SH also had lower BMDs at the hip than those with NFAI (P = 0.009~0.012). After adjusting for confounders, cortisol levels after 1-mg DST demonstrated inverse associations with BMDs at all skeletal sites only in premenopausal women (β = − 0.042~− 0.033, P = 0.019~0.040). DHEA-S had positive associations with LS BMD in postmenopausal women (β = 0.096, P = 0.001) and men (β = 0.029, P = 0.038). The cort/DHEA-S had inverse associations with LS BMD in postmenopausal women (β = − 0.081, P = 0.004) and men (β = − 0.029, P = 0.011). These inverse associations of cort/DHEA-S remained significant after adjusting for cortisol levels after 1-mg DST (β = − 0.079~− 0.026, P = 0.006~0.029). In postmenopausal women, the odds ratios of lower BMD by DHEA-S and cort/DHEA-S was 0.26 (95% CI, 0.08–0.82) and 3.40 (95% CI, 1.12–10.33), respectively. Subtle cortisol excess in premenopausal women and reduced DHEA-S in postmenopausal women and men may contribute to BMD reduction in Asians with SH.

Bone is a highly dynamic tissue that is continuously being renewed in a lifelong remodeling process that is guided by mechanical and biochemical signals. Imbalances between the underlying processes result in metabolic bone diseases, such as osteoporosis and osteopetrosis; therefore, all phases of bone remodeling are tightly controlled by systemic or local factors to maintain bone homeostasis. The sympathetic nervous system (SNS), one of the two main divisions of the autonomic nervous system, operates through a series of interconnected neurons and finalizes the actions by binding catecholamines, released from postganglionic neurons and from adrenal medulla to adrenergic receptors on peripheral target tissues. Because bone is a metabolically active organ with a significant neural innervation, it is reasonable to assume that neuronal control may constitute a key mechanism in bone remodeling. Pheochromocytoma is a neuroendocrine tumor arising from the chromaffin cells of the adrenal medulla and is characterized by an excessive production of catecholamines. Considering that catecholamines are the main neurotransmitters of SNS, pheochromocytoma might be an ideal human model to determine the role of sympathetic outflow on the pathogenesis of a variety of diseases. This review highlights the importance of SNS activity in human skeletal homeostasis based on insights gained from pheochromocytoma, combined with evidence from a variety of experimental studies.

BACKGROUND: Although P2Y(12) inhibitor monotherapy has emerged as a promising alternative for dual antiplatelet therapy (DAPT), there remains concern regarding the safety of clopidogrel monotherapy. AIMS: We sought to investigate clinical outcomes of clopidogrel monotherapy in patients with and without on-treatment high platelet reactivity (HPR). METHODS: In the SMART-CHOICE study, three-month DAPT followed by P2Y(12) inhibitor monotherapy was compared with 12-month DAPT in patients undergoing percutaneous coronary intervention. A platelet function test was performed for 833 patients with clopidogrel-based therapy. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE: a composite of all-cause death, myocardial infarction, or stroke) at 12 months. RESULTS: Overall, 108 (13.0%) patients had HPR on clopidogrel. Patients with HPR had a significantly higher rate of MACCE than patients without HPR (8.7% vs 1.5%, adjusted HR 3.036, 95% CI: 1.060-8.693, p=0.038). The treatment effect of clopidogrel monotherapy for the 12-month MACCE was not significantly different compared with DAPT among patients with HPR (8.0% vs 9.4%, adjusted HR 0.718, 95% CI: 0.189-2.737, p=0.628) and without HPR (2.2% vs 0.9%, adjusted HR 2.587, 95% CI: 0.684-9.779, p=0.161; adjusted p for interaction=0.170). CONCLUSIONS: Clopidogrel monotherapy showed treatment effects comparable to DAPT for MACCE in patients with or without HPR. However, HPR was significantly associated with an increased risk of MACCE in clopidogrel-treated patients regardless of maintenance of aspirin. Clinical Trial Registration: Comparison Between P2Y(12) Antagonist Monotherapy and Dual Antiplatelet Therapy After DES (SMART-CHOICE) (ClinicalTrials.gov: NCT02079194).

Laparoscopic adrenalectomy is a standard surgical procedure for benign adrenal diseases. Laparoscopic posterior retroperitoneal adrenalectomy (LPRA) has many benefits. However, it is associated with factors such as prolong operation time. The aim of the study was to determine the predictive factors associated with prolonged operation time in LPRA.This study retrospectively analyzed data from 284 patients who underwent LPRA between 2014 and 2019 at Asan Medical Center. Then, we analyzed the predictive factors prolonging operation time using multivariate logistic regression analysis and classified the differences according to the learning curve using cumulative sum analysis.In multivariate logistic regression analysis, the following were determined as factors associated with prolonged operation time: male sex (OR, 2.540; 95% CI, 1.225-5.266), pheochromocytoma (OR, 3.669; 95% CI, 1.548-8.694), right site (OR, 2.499; 95% CI, 1.086-5.748), surgeon A (OR, 3.293; 95% CI, 1.522-7.122), depth of descended adrenal tumor location to kidney (OR, 3.793; 95% CI, 1.660-8.667), large periadrenal fat volume (OR, 2.366; 95% CI, 1.120-4.996), and posterior adiposity index (PAI) (OR, 2.171; 95% CI, 1.090-4.324) (all p 0.05). However, in the period after the learning curve, periadrenal fat volume was not a significant predictor of surgery time prolongation.This study demonstrates that depth of descended adrenal tumor location to kidney is a new and important independent predictive factor for prolonged operation time in LPRA. In addition, periadrenal fat volume is a predictor of surgery time prolongation for beginner surgeons before the learning curve.

Background As an initial treatment strategy, percutaneous coronary intervention (PCI) for coronary chronic total occlusion (CTO) did not show midterm survival benefits compared with optimal medical therapy (OMT). We sought to evaluate the benefit of PCI compared with OMT in patients with CTO over extended long‐term follow‐up. Methods and Results Between March 2003 and February 2012, 2024 patients with CTO were enrolled in a single‐center registry and followed for ≈10 years. We excluded patients with CTO who underwent coronary artery bypass graft (n=477) and classified patients into the CTO‐PCI group (n=883) or OMT group (n=664) according to initial treatment strategy. Patients with multivessel disease received PCI for obstructive non‐CTO lesions in both groups. In the CTO‐PCI group, 699 patients (79.2%) underwent successful revascularization. The CTO‐PCI group had a lower 10‐year rate of cardiac death (10.4% versus 22.3%; hazard ratio [HR], 0.44 [95% CI, 0.32–0.59]; P P =0.01) than the OMT group. The relative reduction in cardiac death at 10 years was mainly driven by a relative reduction between 3 and 10 years (8.3% versus 16.6%; HR, 0.43 [95% CI, 0.27–0.71]; P P =0.71). The beneficial effects of CTO‐PCI were consistent among subgroups. Conclusions As an initial treatment strategy, CTO‐PCI might reduce late cardiac death compared with OMT in patients with CTO. Extended follow‐up of randomized trials may confirm the findings of the present study.

The aim of this study was to evaluate the diagnostic accuracy and prognostic implications of angiography-derived index of microcirculatory resistance (angio-IMR) in patients with ST-segment elevation myocardial infarction (STEMI).The index of microcirculatory resistance (IMR) is a reliable invasive measure of coronary microvascular dysfunction in patients with STEMI. A functional coronary angiography-derived method to estimate IMR is a wire- and hyperemic agent-free alternative to IMR.The study population consisted of 2 independent cohorts. The diagnostic cohort comprised patients with IMR from the culprit vessel immediately after successful primary percutaneous coronary intervention (n = 31). The prognostic cohort was patients with STEMI who were successfully treated with primary percutaneous coronary intervention and followed for 10 years from the index procedure (n = 309). Angio-IMR was calculated using computational flow and pressure simulation. The primary outcome was a composite of cardiac death and readmission for heart failure over 10 years of follow-up.In the diagnostic cohort, angio-IMR correlated well with IMR (R = 0.778; P 0.001). Sensitivity, specificity, accuracy, and area under the curve of angio-IMR to predict IMR40 U were 75.0%, 84.2%, 80.6%, and 0.899 (95% confidence interval: 0.786-0.949), respectively. In the prognostic cohort, patients with angio-IMR40 U showed significantly higher risk for cardiac death or readmission for heart failure than did those with angio-IMR ≤40 U (46.7% vs 16.6%; adjusted hazard ratio: 2.909; 95% CI: 1.670-5.067; P 0.001). Angio-IMR40 U was an independent predictor of cardiac death or readmission for heart failure (hazard ratio: 2.173; 95% CI: 1.157-4.079; P = 0.016) and showed incremental prognostic value compared with a model with clinical risk factors only (C index = 0.726 vs 0.666 [P 0.001], net reclassification index = 0.704 [P 0.001]).Angio-IMR showed high correlation and diagnostic accuracy to predict IMR. Patients with STEMI with angio-IMR40 U showed a significantly higher risk for cardiac death or readmission for heart failure than those with preserved angio-IMR values. (Prognostic Implication of Angiography-Derived IMR in STEMI Patients; NCT04628377).

Clinical advantages of sutureless rapid-deployment (RD) aortic valve replacement (AVR) for severe aortic valve stenosis (AS) have not been elucidated compared with surgical (SAVR) or transcatheter (TAVR) aortic valve replacement.This study sought to investigate comparative effectiveness and safety of RD-AVR compared with SAVR and TAVR in a prospective cohort of patients with severe AS.The primary outcome was a composite of death, stroke, or rehospitalization at 12 months. Propensity score matching was used to assemble a cohort of patients with similar baseline characteristics.Among 1,020 eligible patients, 107 (10.5%) underwent RD-AVR, 437 (42.8%) underwent SAVR, and 476 (46.7%) underwent TAVR. In the matched cohorts of RD-AVR and SAVR (n = 107), the incidence of primary composite outcome at 12 months was similar between the 2 groups (8.0% vs 10.8%, respectively; hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.30-1.84;In this propensity-matched cohort of patients who underwent AVR for severe AS, we did not detect significant differences in the rates of the primary composite of death, stroke, or rehospitalization at 12 months when comparing RD-AVR with SAVR and TAVR. Because the study was underpowered, the results should be considered as hypothesis generating highlighting the need for further research. (ASAN Medical Center Aortic Valve Replacement Registry [ASAN-AVR]; NCT03298178).

Background and aims: Frequent failure of adrenal vein (AV) cannulation is a major obstacle to the universal use of adrenal vein sampling (AVS) for subtyping primary aldosteronism (PA). This study aimed to confirm and modify the value of a previously reported AVS parameter for PA subtyping in the case of cannulation failure on one side. Methods: Successfully catheterized AVS studies in 157 patients (121 patients as a derivation cohort and 36 patients as a validation cohort) from two tertiary hospitals were retrospectively reviewed. The AV/inferior vena cava (IVC) index was defined by dividing the aldosterone/cortisol ratio (ACR) of AV by the ACR of the IVC. Cutoff values for lateralized PA were obtained from two methods: scatterplots and the values corresponding to Youden’s index in receiver operating characteristic (ROC) curves, on the assumption of catheterization failure on one side. Results: Due to multiple samplings in a single AVS procedure, 252 left AV/IVC ratios (LIRs) and 272 right AV/IVC ratios (RIRs) were calculated. Scatterplot cutoffs of LIR >5.4 or 7.0 showed a sensitivity of 55.1% and a specificity of 98.6%. ROC curve cutoffs of LIR ⩽0.8 or >3.1 predicted unilateral PA with a sensitivity of 82.5% and a specificity of 69.6%. ROC curve cutoffs of RIR ⩽0.8 or >3.9 resulted in 87.4% sensitivity and 80.7% specificity. Conclusion: In the case of unilateral AVS failure, the AV/IVC index may help in diagnosing PA subtype.

Tumor-induced osteomalacia (TIO) is an uncommon paraneoplastic syndrome presenting with sustained hypophosphatemia. Treatment of choice is removal of the tumor causing the TIO, but identification of the culprit tumor by routine imaging is challenging. This study aimed to assess the usefulness of somatostatin receptor imaging, called 68Ga-DOTATOC PET/CT, in the management of patients with TIO. Twelve patients who were suspected of having TIO underwent 68Ga-DOTATOC PET/CT. Lesion detectability and maximum standardized uptake value (SUVmax) were determined and retrospectively compared with the clinical/imaging surveillance and histopathologic diagnosis. The median duration of suspected TIO with hypophosphatemia was 7.8 years (range 2.1–21.0). Conventional radiologic and/or nuclear medicine images failed to identify the culprit tumors. However, 68Ga-DOTATOC PET/CT scans showed that 8 of the 12 patients had positive lesions, suggesting the presence of focal culprit tumors. The SUVmax of positive tumors was 1.9–45.7 (median: 11.5). Six skeletal lesions and two extra-skeletal lesions were identified. Seven of the lesions were pathologically confirmed as potential culprits of TIO. Hypophosphatemia was resolved in five patients who underwent lesion excision. The 68Ga-DOTATOC PET/CT is a useful whole-body imaging modality for the detection of causative tumors in patients with suspected TIO.