PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted, but Functional in Patients with COVID-19.

Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8+ T cells by MHC class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer+ cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer+ cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-γ (IFN-γ)-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to influenza A virus. Importantly, the proportion of IFN-γ-producing cells was higher in PD-1+ cells than PD-1- cells among multimer+ cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8+ T cells elicited by infection or vaccination.

Epigenetic scars in regulatory T cells are retained after successful treatment of chronic hepatitis C with direct-acting antivirals.

BACKGROUND & AIMS: Chronic hepatitis C virus (HCV) infection results in abnormal immunological alterations, which are not fully normalized after viral elimination by direct-acting antiviral (DAA) treatment. Here we longitudinally examined phenotypic, transcriptomic, and epigenetic alterations in peripheral blood regulatory T (TREG) cells from patients with chronic HCV infection according to DAA treatment. METHODS: Patients with chronic genotype 1b HCV infection who achieved sustained virologic response (SVR) by DAA treatment and age-matched healthy donors were recruited. Phenotypic characteristics of TREG cells were investigated through flow cytometry analysis. Moreover, transcriptomic and epigenetic landscape of TREG cells were analyzed using RNA-seq and ATAC-seq analysis. RESULTS: The TREG cell population-especially the activated TREG cell subpopulation-was expanded in peripheral blood during chronic HCV infection, and this expansion was sustained even after viral clearance. RNA-seq analysis revealed that viral clearance did not abrogate the inflammatory features of these TREG cells, such as TREG activation and TNF signal. Moreover, ATAC-seq analysis showed inflammatory imprinting in the epigenetic landscape of TREG cells from patients, which remained after treatment. These findings were further confirmed by intracellular cytokine staining, demonstrating that TREG cells exhibited inflammatory features and TNF production in chronic HCV infection that were maintained after viral clearance. CONCLUSIONS: Overall, our results showed that during chronic HCV infection, the expanded TREG cell population acquired inflammatory features at phenotypic, transcriptomic, and epigenetic levels, which were maintained even after successful viral elimination by DAA treatment. Further studies are warranted to examine the clinical significance of sustained inflammatory features in the TREG cell population after recovery from chronic HCV infection. IMPACT AND IMPLICATIONS: During chronic HCV infection, several immune components are altered both quantitatively and qualitatively. The recent introduction of DAAs led to a high cure rate of chronic HCV infection. Nevertheless, we have demonstrated that inflammatory features of TREG cells are maintained at phenotypic, transcriptomic, and epigenetic levels even after successful DAA treatment. Further in-depth studies are required to investigate the long-term clinical outcomes of patients who have recovered from chronic HCV infection.

Triple immune modulator therapy for aberrant hyperinflammatory responses in severe COVID-19.

A dysregulated hyperinflammatory response is a key pathogenesis of severe COVID-19, but optimal immune modulator treatment has not been established. To evaluate the clinical effectiveness of double (glucocorticoids and tocilizumab) and triple (plus baricitinib) immune modulator therapy for severe COVID-19, a retrospective cohort study was conducted. For the immunologic investigation, a single-cell RNA sequencing analysis was performed in serially collected PBMCs and neutrophil specimens. Triple immune modulator therapy was a significant factor in a multivariable analysis for 30-day recovery. In the scRNA-seq analysis, type I and II IFN response-related pathways were suppressed by GC, and the IL-6-associated signature was additionally downregulated by TOC. Adding BAR to GC and TOC distinctly downregulated the ISGF3 cluster. Adding BAR also regulated the pathologically activated monocyte and neutrophil subpopulation induced by aberrant IFN signals. Triple immune modulator therapy in severe COVID-19 improved 30-day recovery through additional regulation of the aberrant hyperinflammatory immune response.

Quantitative interstitial lung disease scores in idiopathic inflammatory myopathies: longitudinal changes and clinical implications.

OBJECTIVES: To investigate computer-aided quantitative scores from high-resolution CT (HRCT) images and determine their longitudinal changes and clinical significance in patients with idiopathic inflammatory myopathies (IIMs)-related interstitial lung disease (IIMs-ILD). METHODS: The clinical data and HRCT images of 80 patients with IIMs who underwent serial HRCT scans at least twice were retrospectively analysed. Quantitative ILD (QILD) scores (%) were calculated as the sum of the extent of lung fibrosis, ground-glass opacity, and honeycombing. The individual time-estimated ΔQILD between two consecutive scans was derived using a linear approximation of yearly changes. RESULTS: The baseline median QILD (interquartile range) scores in the whole lung were 28.1% (19.1-43.8). The QILD was significantly correlated with forced vital capacity (r = -0.349, P = 0.002) and diffusing capacity for carbon monoxide (r = -0.381, P = 0.001). For ΔQILD between the first two scans, according to the visual ILD subtype, QILD aggravation was more frequent in patients with usual interstitial pneumonia (UIP) than non-UIP (80.0% vs 44.4%, P = 0.013). Multivariable logistic regression analyses identified UIP was significantly related to radiographic ILD progression (ΔQILD >2%, P = 0.015). Patients with higher baseline QILD scores (>28.1%) had a higher risk of lung transplantation or death (P = 0.015). In the analysis of three serial HRCT scans (n = 41), dynamic ΔQILD with four distinct patterns (improving, worsening, convex and concave) was observed. CONCLUSION: QILD changes in IIMs-ILD were dynamic, and baseline UIP patterns seemed to be related to a longitudinal progression in QILD. These may be potential imaging biomarkers for lung function, changes in ILD severity and prognosis in IIMs-ILD.

Methotrexate, leflunomide and tacrolimus use and the progression of rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVE: To examine the association between MTX, LEF and tacrolimus use and the progression of RA-associated interstitial lung disease (ILD). METHODS: The Korean RA-ILD cohort prospectively enrolled patients with RA-associated ILD at multiple centres from 2015 to 2018 and followed up with them for 3 years. ILD progression was defined by any of the followings: a decrease of ≥10% in forced vital capacity, a decrease of ≥15% in the diffusing capacity of the lung for carbon monoxide, or death from respiratory failure. RESULTS: Of 143 patients, 64 patients experienced ILD progression during a median follow-up period of 33 months. The use of MTX [adjusted hazard ratio (aHR), 1.06; 95% CI, 0.59, 1.89], LEF (aHR, 1.75; 95% CI, 0.88, 3.46) and tacrolimus (aHR, 0.94; 95% CI, 0.52, 1.72) did not increase the risk of ILD progression. However, the association between LEF use and the risk of ILD progression was significant in subgroups with poor lung function (aHR, 8.42; 95% CI, 2.61, 27.15). Older age, male sex, a shorter RA duration, higher RA disease activity and extensive disease at baseline were independently associated with ILD progression. CONCLUSION: None of the three treatments increased the risk of RA-associated ILD progression, except for LEF, which increased the risk of ILD progression in patients with severe ILD. The appropriate use of conventional synthetic disease-modifying antirheumatic drugs considering RA disease activity and ILD severity would be important for the management of RA-associated ILD.

Lung function trajectory of rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVES: To explore the course of lung function and RA disease activity and predictive factors for deteriorating lung function in patients with RA-interstitial lung disease (ILD). METHODS: The Korean Rheumatoid Arthritis-Interstitial Lung Disease cohort is a multicentre, prospective observational cohort. Patients with RA-ILD were enrolled and followed up annually for 3 years for RA disease activity and ILD status assessment. Group-based modelling was used to cluster a similar predicted percentage of forced vital capacity (FVC%) patterns into trajectories. RESULTS: This study included 140 patients who underwent at least two pulmonary function tests. Four distinctive trajectories for predicted FVC% were 'improving' [n = 11 (7.9%)], 'stable' [n = 68 (38.4%)], 'slowly declining' [n = 54 (48.6%)] and 'rapidly declining' [n = 7 (5.0%)]. Most (77.7%) patients maintained or improved to low RA disease activity. The lung function trajectory was not comparable to the RA disease activity trajectory. Age ≥70 years [relative risk (RR) 10.8 (95% CI 1.30, 89.71)] and early RA diagnosed within the preceding 2 years [RR 10.1 (95% CI 1.22, 84.2)] were associated with increased risk for rapidly declining predicted FVC%. The risk for deterioration or mortality increased in patients with a simultaneous diagnosis of RA and ILD within 24 weeks [RR 9.18 (95% CI 2.05, 41.0)] and the extent of lung involvement [RR 3.28 (95% CI 1.12, 9.60)]. CONCLUSION: Most patients with RA-ILD experienced stable or slowly declining lung function. In 5% of patients, predicted FVC% deteriorated rapidly, especially in older adults with early RA. The lung function trajectory was not comparable to the RA disease activity trajectory.

Long-term outcomes and surveillance timing of patients with large non-pedunculated colorectal polyps with histologically incomplete resection in endoscopic resection.

BACKGROUND: Histologically incomplete resection of large colorectal polyps is frequently encountered; however, the long-term outcomes or surveillance timing is not well known. We evaluated the incidence rate and time of recurrence of these cases during a long-term follow-up. METHODS: We performed a retrospective analysis of patients who underwent endoscopic resection for large (≥10 mm in size) non-pedunculated colorectal polyps at a tertiary academic hospital. Patients who had positive or indeterminate lateral margin in the histology and underwent completed surveillance colonoscopy first at 3-12 months and finally at ≥2 years after initial resection were included. RESULTS: Of 169 polyps (148 patients), 37 (21.9%) and 132 (78.1%) polyps had positive and indeterminate lateral margins, respectively. The median time intervals of the first and last surveillance from the initial resection were 6 (3-12) and 48 (24-114) months, respectively. The recurrence rate was 9.5% (16/169) during follow-up, and the mean time to recurrence was 31.9 months. Thirteen (81.3%) polyps recurred after ≥12 months. Most (14/16, 87.5%) recurrent polyps were benign, and 2 cases had advanced cancer. The only factor that was significantly associated with recurrence in the univariate and multivariate analyses was ≥3 piecemeal resections (odds ratio in the multivariate analysis, 16.92; 95% CI, 1.19-241.81; p = 0.037). CONCLUSION: During the long-term follow-up, the only factor that was significantly associated with recurrence was ≥3 piecemeal resections, and most recurrences occurred after ≥12 months. Thus, a histologically incomplete resection with ≤2 piecemeal resections and no findings of suspected submucosal cancer may be considered as complete resection, and these patients may undergo first surveillance colonoscopy after 1-2 years.

Severe protein C deficiency in a newborn caused by a homozygous pathogenic variant in the PROC gene: a case report.

BACKGROUND: Severe protein C deficiency is a rare and inherited cause of thrombophilia in neonates. Protein C acts as an anticoagulant, and its deficiency results in vascular thrombosis. Herein, we report a case of protein C deficiency with a homozygous pathogenic variant in a term neonate, with good outcomes after proper treatment. CASE PRESENTATION: A four-day-old male newborn was transferred to the Seoul National University Hospital on account of dark red to black skin lesions. He was born full-term with an average birth weight without perinatal problems. There were no abnormal findings in the prenatal tests, including intrauterine sonography. The first skin lesion was observed on his right toes and rapidly progressed to proximal areas, such as the lower legs, left arm, and buttock. Under the impression of thromboembolism or vasculitis, we performed a coagulopathy workup, which revealed a high D-dimer level of 23.05 µg/ml. A skin biopsy showed fibrin clots in most capillaries, and his protein C activity level was below 10%, from which we diagnosed protein C deficiency. On postnatal day 6, he experienced an apnea event with desaturation and an abnormal right pupillary light reflex. Brain computed tomography showed multifocal patchy intracranial hemorrhage and intraventricular hemorrhage with an old ischemic lesion. Ophthalmic examination revealed bilateral retinal traction detachments with retinal folds. Protein C concentrate replacement therapy was added to previous treatments including steroids, prostaglandin E1, and anticoagulation. After replacement therapy, there were no new skin lesions, and the previous lesions recovered with scarring. Although there were no new brain hemorrhagic infarctions, there was ongoing ischemic tissue loss, which required further rehabilitation. Ophthalmic surgical interventions were performed to treat the bilateral retinal traction detachments with retinal folds. Molecular analysis revealed a homozygous pathogenic variant in the PROC gene. CONCLUSION: Severe protein C deficiency can manifest as a fatal coagulopathy in any organ. Early diagnosis and proper treatment, including protein C concentrate replacement, may improve outcomes without serious sequelae.

A Novel Prediction Model for Determining Coronal Length of Calcaneus Using CT: A Guide for Surgery of Calcaneal Fracture.

The objective of this study was to determine the anatomical relationship between the calcaneus and its neighboring bones. Furthermore we tested a prediction model that enables to estimate safe screw length during the surgery of calcaneus fractures. A total of 169 feet were used for the study based on CT scans. We measured two horizontal and two parallel lines. The coronal length of the cuboid bone (CL) was a horizontal line anterior to the calcaneocuboidal joint, and W1 of calcaneus was a horizontal line posterior to the articular surface of the calcaneocuboidal joint. The subtalar articular length (STA) was a parallel line above the talocalcaneal joint, and W2 of calcaneus was a parallel line below to the talocalcaneal joint. Relationship of each measurement was determined through correlation analysis. A prediction model was developed based on observed correlations and the quality analyzed and validated. The CL and W1 had a significant positive correlation (r = 0.899, p < .001). The STA and W2 also had a significant positive correlation (r = 0.939, p < .001). Based on these correlations, the prediction model was made. In the quality analysis, the values of concordance correlation coefficient (CCC) for W1 and W2 were 0.894, and 0.937 respectively. In the validation analysis, the values of CCC for W1, W2 were 0.79, and 0.8, respectively. This study made it possible to predict the anatomical reference point using preoperative coronal length of the calcaneus to guide safety margin of screw length, and thereby to prevent the iatrogenic injuries on medial neurovascular structures of the calcaneus.

Efficacy of Lesion Specific Portals in Endoscopic Treatment of Calcaneal Bone Cyst: A Case Report and Literature Review.

Background: Calcaneal bone cysts rarely occur and most of them are known to be benign. Among them, simple bone cysts (SBCs) third most commonly occur in the calcaneus and of the many surgical treatment options, endoscopic curettage is recently gaining popularity among surgeons due to its advantages of minimal invasiveness and optimal visualization. As for portal placement for endoscopy, two lateral portals are considered a standard technique, but no rationale has been established for SBCs with abnormal geometry. This case report suggests an SBC with secondary aneurysmal change located outside the Ward's triangle, as well as an appropriate endoscopic approach. Case Presentation: An 18-year-old male high school student presented with a main complaint of pain at the hind foot level for the past one year, without significant improvement from conservative treatment. An endoscopic curettage through the lesion specific two posterior portals and bone graft using allogeneic cancellous bone were performed. SBC with a secondary aneurysmal bone cyst was diagnosed on pathology. At a one-year follow-up, the patient was painless and had returned to his regular activities. Physical and radiographic examinations revealed that the lesion was completely healed without any evidence of recurrence. Conclusion: For calcaneal bone cysts located at the posterior aspect of the calcaneus, eccentrically medial and abnormally long anterior-posteriorly, we suggest an endoscopic procedure using lesion specific portals such as two posterior portals.

Restoration of the inferomedial orbital strut using a standardized three-dimensional printing implant.

The inferomedial orbital strut (IOS) is the thin bony junction of the orbital medial wall and floor. Its fracture is common and leads to serious complications, including enophthalmos, globe dystopia and diplopia. However, anatomical restoration of the IOS is challenging owing to reduced structural support; sound anatomical background and accurate implants are therefore essential. The aim of the present study was to incorporate data from cadaveric orbit anatomy into three-dimensional (3D) printing technology and to reconstruct the complex orbital fracture elaborately. After averaging the data from computed tomography (CT) images of 100 adult cadavers, the dimensions of the IOS were extracted, and a tangent sphere was created using a computer-aided design program. The curves were compared with the CT data of 10 adult patients from the simulation test. Based on these data, a standardized 3D implant, 1.15 mm thick, was designed using polycaprolactone. The implant was placed in five patients with complex orbital fractures. The radius of the sphere in contact with the orbit, measuring 33.54 mm, was confirmed to be appropriate. A comparison between the normal side volume (V0) and the postoperative volume (Vpost ) showed that they were statistically similar. Furthermore, a comparison between V0 and the preoperative volume (Vpre ), and Vpost compared with Vpre also showed a statistically significant difference (P < 0.05). On follow-up, the preoperative ocular symptoms were resolved. The orbital data obtained from 100 cadavers provided standardized orbital anatomy, and 3D printed implants were created. The implants were anatomically accurate with regard to the orbital cavity and adequately covered the simulation model. The implant also showed satisfactory results when applied clinically in actual patients.

Risk prediction model in rheumatoid arthritis-associated interstitial lung disease.

BACKGROUND AND OBJECTIVE: RA-ILD has a variable clinical course, and its prognosis is difficult to predict. Moreover, risk prediction models for prognosis remain undefined. METHODS: The prediction model was developed using retrospective data from 153 patients with RA-ILD and validated in an independent RA-ILD cohort (n = 149). Candidate variables for the prediction models were screened using a multivariate Cox proportional hazard model. C-statistics were calculated to assess and compare the predictive ability of each model. RESULTS: In the derivation cohort, the median follow-up period was 54 months, and 38.6% of the subjects exhibited a UIP pattern on HRCT imaging. In multivariate Cox analysis, old age (≥60 years, HR: 2.063), high fibrosis score (≥20% of the total lung extent, HR: 4.585), a UIP pattern (HR: 1.899) and emphysema (HR: 2.596) on HRCT were significantly poor prognostic factors and included in the final model. The prediction model demonstrated good performance in the prediction of 5-year mortality (C-index: 0.780, P < 0.001); furthermore, patients at risk were divided into three groups with 1-year mortality rates of 0%, 5.1% and 24.1%, respectively. Predicted and observed mortalities at 1, 2 and 3 years were similar in the derivation cohort, and the prediction model was also effective in predicting prognosis of the validation cohort (C-index: 0.638, P < 0.001). CONCLUSION: Our results suggest that a risk prediction model based on HRCT variables could be useful for patients with RA-ILD.

Evaluation of Auricular Cartilage Reconstruction Using a 3-Dimensional Printed Biodegradable Scaffold and Autogenous Minced Auricular Cartilage.

Auricular cartilage reconstruction represents one of the greatest challenges for otolaryngology-head and neck surgery. The native structure and composition of the auricular cartilage can be achieved by combining a suitable chondrogenic cell source with an appropriate scaffold. In reconstructive surgery for cartilage tissue, autogenous cartilage is considered to be the best chondrogenic cell source. Polycaprolactone is mainly used as a tissue-engineered scaffold owing to its mechanical properties, miscibility with a large range of other polymers, and biodegradability. In this study, scaffolds with or without autogenous minced auricular cartilage were implanted bilaterally in rabbits for auricular regeneration. Six weeks (n = 4) and 16 weeks (n = 4) after implantation, real-time quantitative reverse transcription polymerase chain reaction and histology were used to assess the regeneration of the auricular cartilage. Quantitative reverse transcription polymerase chain reaction analysis revealed that the messenger RNA expression of aggrecan, collagen I, and collagen II was higher in scaffolds with 50% minced cartilage than the scaffold-only groups or scaffolds with 30% minced cartilage (P < 0.05). Furthermore, histological analysis demonstrated significantly superior cartilage regeneration in scaffolds with the minced cartilage group compared with the scaffold-only and control groups (P < 0.05). Autogenous cartilage can be easily obtained and loaded onto a scaffold to promote the presence of chondrogenic cells, allowing for an improvement of the reconstruction of auricular cartilage. Here, the regeneration of auricular cartilage was also successful in the 50% minced cartilage group. The results presented in this study could have clinical implications, as they demonstrate the potential of a 1-stage process for auricular reconstruction.

Performance of the 2015 American College of Rheumatology/European League against Rheumatism Classification Criteria for Gout in Korean Patients with Acute Arthritis.

BACKGROUND: We aimed to assess the performance of the 2015 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for gout in Korean patients with acute arthritis and to compare the performance of the ACR/EULAR criteria to that of other sets of criteria for gout classification. METHODS: Patients with acute arthritis who underwent diagnostic arthrocentesis at one of the four participating rheumatology clinics were consecutively enrolled between February and December 2017. Crystal-proven gout was diagnosed upon confirming the presence of monosodium urate (MSU) crystals in patients with a clinical impression of gout as judged by the rheumatologist. The performance of the ACR/EULAR and other gout classification criteria, including the Rome, New York, American Rheumatism Association (ARA), Mexico, and Netherlands criteria, was analyzed regardless of the presence/absence of MSU crystals. RESULTS: The study enrolled 118 gout patients (all crystal-proven) and 95 non-gout patients. According to the area under the curve, the diagnostic performance was the highest for the ACR/EULAR classification criteria (sensitivity, 80.5%; specificity, 95.8%; area under the curve, 0.966), followed by the Netherlands, Rome, ARA, New York, and Mexico criteria. All six sets of criteria demonstrated lower sensitivity in patients exhibiting the first episode of acute arthritis. CONCLUSION: In Korean patients with acute arthritis, the ACR/EULAR classification criteria outperformed other sets of gout classification criteria even in the absence of information regarding the presence of MSU crystals. However, to enhance diagnostic sensitivity, synovial fluid analysis should be considered in patients with the first episode of acute arthritis.

Nonthrombotic proliferative vasculopathy associated with antiphospholipid antibodies: A case report and literature review.

A 20-year-old man presented with recurrent hemoptysis for seven months. A small subpleural nodule in his right lower lobe was found and excised surgically. Based on the presence of antiphospholipid antibodies (aPL) and vascular wall hypertrophy without vasculitis or an intraluminal thrombus, nonthrombotic proliferative vasculopathy (NTPV) affecting pulmonary arteries was diagnosed. Recently, aPL have been postulated to directly induce the proliferation of vascular cells in the intima and media, leading to NTPV. We review 5 cases of NTPV-associated aPL with critical ischemia in the lower extremities and gastrointestinal infarction. NTPV-associated aPL might be distinct from classic antiphospholipid syndrome and should be considered in aPL-positive patients who present with vascular occlusions of medium-sized vessels in the absence of atherosclerotic risk factors and systemic or local inflammation.

Cleft Alveolus Reconstruction Using a Three-Dimensional Printed Bioresorbable Scaffold With Human Bone Marrow Cells.

Bone tissue engineering technology based on scaffold has been applied for cleft lip and palate treatment. However, clinical applications of patient-specific three-dimensional (3D) scaffolds have rarely been performed. In this study, a clinical case using patient-specific 3D-printed bioresorbable scaffold with bone marrow stromal cells collected from iliac crest in the operating room has been introduced. At 6-month after transplantation, the bone volume of the newly regenerated bone was approximately 45% of the total defect volume. Bone mineral density of the newly regenerated bone was about 75% compared to the surrounding bone. The Hounsfield unit value was higher than that of cancellous maxillary alveolar bone and lower than that of the cortical maxillary alveolar bone. Bone-marrow-derived mesenchymal stem cells-seeded 3D-printed patient-specific polycaprolactone scaffolds offer a promising alternative for alveolar cleft reconstruction and other bony defects.

Pharmacological and Mechanical Thromboprophylaxis in Critically Ill Patients: a Network Meta-Analysis of 12 Trials.

Thromboprophylaxis for venous thromboembolism is widely used in critically ill patients. However, only limited evidence exists regarding the efficacy and safety of the various thromboprophylaxis techniques, especially mechanical thromboprophylaxis. Therefore, we performed meta-analysis of randomized controlled trials (RCTs) that compared the overall incidence of deep vein thrombosis (DVT) for between unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and intermittent pneumatic compression (IPC) in critically ill patients. A Bayesian random effects model for multiple treatment comparisons was constructed. The primary outcome measure was the overall incidence of DVT at the longest follow-up. The secondary outcome measure was the incidence of major bleeding, as defined by the original trials. Our analysis included 8,622 patients from 12 RCTs. The incidence of DVT was significantly lower in patients treated with UFH (OR, 0.45; 95% CrI, 0.22-0.83) or LMWH (OR, 0.38; 95% CrI, 0.18-0.72) than in patients in the control group. IPC was associated with a reduced incidence of DVT compared to the control group, but the effect was not statistically significant (OR, 0.50; 95% CrI, 0.20-1.23). The risk of DVT was similar for patients treated with UFH and LMWH (OR, 1.16; 95% CrI, 0.68-2.11). The risk of major bleeding was similar between the treatment groups in medical critically ill patients and also in critically ill patients with a high risk of bleeding. In critically ill patients, the efficacy of mechanical thromboprophylaxis in reducing the risk of DVT is not as robust as those of pharmacological thromboprophylaxis.

Energy Calibration of a CdTe Photon Counting Spectral Detector with Consideration of its Non-Convergent Behavior.

Fast and accurate energy calibration of photon counting spectral detectors (PCSDs) is essential for their biomedical applications to identify and characterize bio-components or contrast agents in tissues. Using the x-ray tube voltage as a reference for energy calibration is known to be an efficient method, but there has been no consideration in the energy calibration of non-convergent behavior of PCSDs. We observed that a single pixel mode (SPM) CdTe PCSD based on Medipix-2 shows some non-convergent behaviors in turning off the detector elements when a high enough threshold is applied to the comparator that produces a binary photon count pulse. More specifically, the detector elements are supposed to stop producing photon count pulses once the threshold reaches a point of the highest photon energy determined by the tube voltage. However, as the x-ray exposure time increases, the threshold giving 50% of off pixels also increases without converging to a point. We established a method to take account of the non-convergent behavior in the energy calibration. With the threshold-to-photon energy mapping function established by the proposed method, we could better identify iodine component in a phantom consisting of iodine and other components.