An abnormal increase in CD26(-)CD28(-) cytotoxic effector CD4 and CD8 T cell populations in patients with systemic lupus erythematosus.

CD26 is a human T cell costimulatory molecule as well as a T cell subset marker, and increase of CD26+ T cells in inflamed tissues and peripheral blood has been reported in diverse autoimmune diseases. In contrast, our group has previously shown that levels of circulating CD26+ T cells are decreased in patients with systemic lupus erythematosus (SLE), although the role of reduced CD26 T cell surface expression in SLE pathology remains to be elucidated. In the present study, we conducted CD26-based T cell subset analyses utilizing peripheral blood mononuclear cells from 57 SLE patients and 31 healthy adult volunteers. We show that the increase in CD26(-) T cell population reflects the abnormal expansion of CD26(-)CD28(-) cytotoxic subsets of both CD8 T cells and CD4 T cells in SLE patients. Single cell RNA sequencing analysis of the CD26(-)CD28(-) CD4 and CD8 T cell populations reveals unique characteristics with similarities to natural killer T cells. In addition, the level of CD26(-)CD28(-) T cells is increased in some active stage SLE patients with renal manifestation. Meanwhile, effect of prednisolone treatment on these populations varies from patient to patient, with levels of these cytotoxic effector populations still being elevated in some inactive stage SLE patients. Taken together, our data suggest that analysis of these populations in SLE may be a useful tool to classify this markedly heterogeneous condition.

Total knee arthroplasty and periprosthetic distal femoral fracture: looking beyond the osteoporosis to previous osteoporotic fracture.

Osteoporosis increases the risk of periprosthetic distal femoral fractures after TKA, especially in patients with a history of osteoporotic fractures. Therefore, careful assessment and proper treatment of osteoporosis need and the importance of taking osteoporotic medication needs to be recognized by the patients following primary TKA. PURPOSE: Osteoporosis is a risk factor for fractures, including those of the hip, vertebrae, and distal radius; however, the association between osteoporosis and periprosthetic fractures after total knee arthroplasty (TKA) has not been much investigated. Therefore, we aimed to investigate the association of the presence of systemic osteoporosis with periprosthetic fractures after TKA. METHODS: This study included 34 patients with periprosthetic fractures following primary TKA and 106 controls matched for age and sex. Bone mineral density was evaluated at the femoral neck, total hip, and lumbar spine using dual X-ray absorptiometry. Medical records were reviewed for age; sex; body mass index; smoking; rheumatoid arthritis, endocrine diseases, and cardiovascular diseases; history of glucocorticoid use; medication for osteoporosis; and history of previous osteoporotic fracture. In addition, anterior femoral notching after TKA was evaluated. Univariable and multivariable logistic regression analysis were used to determine factors associated with periprosthetic fracture. RESULTS: The prevalence of osteoporosis in the fracture group was higher than that in the control group (61.8% vs. 40.6%, p=0.045). The rate of medication for osteoporosis was significantly low in the fracture group (47.6 % vs 76.7%, p=0.026). History of previous osteoporotic fracture (odds ratio [OR], 9.1; p=0.015) and osteoporosis (OR, 3.6; p=0.013) were significant risk factors for periprosthetic fractures after TKA. Medication for osteoporosis could decrease the risk of periprosthetic fracture (OR 0.3; p=0.020). CONCLUSION: Osteoporosis is a major risk factor for periprosthetic distal femoral fractures after TKA. Therefore, careful assessment and proper treatment of osteoporosis need and the importance of taking osteoporotic medication needs to be recognized to the patients following primary TKA, especially in patients with a history of osteoporotic fracture. LEVEL OF EVIDENCE: Prognostic study, level III.

Distribution of urinary trace element exposure and dietary sources in women over 50 in an agricultural region- A community-based KoGES cohort study.

BACKGROUND: There is a noticeable lack of information on the levels of both non-essential and essential trace elements in women aged over 50. The main objective of this study is to investigate trace element concentrations and explore the influence of sociodemographic factors and dietary sources of exposure in this demographic. METHODS: We analyzed 19 trace elements, including manganese, cobalt, copper, zinc, molybdenum, chromium, nickel, arsenic, strontium, cadmium, tin, antimony, cesium, barium, tungsten, mercury, thallium, lead, and uranium, using ICP-MS and mercury analyzer. Urine samples were obtained from a cohort of 851 women aged over 50 who participated in the 8th KoGES-Ansung study (2017-2018). Multiple linear models were employed to explore associations between urinary trace element concentrations and sociodemographic factors and dietary sources of exposure. We used K-means clustering to discern patterns of exposure to trace elements and identify contributing factors and sources. RESULTS: Our findings indicate higher concentrations of molybdenum (Mo), arsenic (As), cadmium (Cd), and lead (Pb) in our study population compared to women in previous studies. The study population were clustered into two distinct groups, characterized by lower or higher urinary concentrations. Significant correlations between age and urinary concentrations were observed in Ni. Smoking exhibited positive associations with urinary Cd and As. Associations with dietary sources of trace elements were more distinct in women in the high-exposure group. Urinary antimony (Sb) was positively linked to mushroom and egg intake, As to mushroom and fish, and Hg to egg, dairy products, fish, seaweed, and shellfish. CONCLUSIONS: Our study underscores the significant gap in understanding urinary concentrations of trace elements in women aged over 50. With higher concentrations of certain elements compared to previous studies and significant correlations between age, smoking, and specific food sources, it is imperative to address this gap through targeted dietary source-specific risk management.

Trajectory of lung function in diabetic adults: A 16-year follow-up study of community-based prospective cohorts.

BACKGROUND AND OBJECTIVE: To investigate the difference in lung function according to diabetes status in a community-based prospective study. METHODS: Individuals aged 40-69 years from two community-based cohorts were followed prospectively for 16 years. A spirometer was used to evaluate lung function at baseline, and lung function tests were carried out biennially thereafter. Multivariable linear regression analysis was performed for the cross-sectional and longitudinal analyses based on diabetes status. RESULTS: Among the 6483 subjects, 2114 (32.6%) had prediabetes and 671 (10.4%) had diabetes. The prediabetes and diabetes groups had lower baseline % predicted values of forced expiratory volume in 1 s (FEV1) (mean, -1.853; 95% confidence interval [CI] -2.715 to -0.990 for prediabetes and mean, -4.088; 95% CI -5.424 to -2.752 for diabetes) and forced vital capacity (FVC) (mean, -2.087; 95% CI -2.837 to -1.337 for prediabetes and mean, -4.622; 95% CI -5.784 to -3.460 for diabetes) compared to the normoglycemia group after adjusting for relevant covariates. The rate of decline in FEV1% predicted (mean, -0.227; 95% CI -0.366 to -0.089) and FVC % predicted (mean, -0.232; 95% CI -0.347 to -0.117) during follow-up were faster in the diabetes group than in the normoglycemia group. The diabetes group had a lower proportion of normal ventilation (ptrend = 0.048) and higher proportions of restrictive (ptrend = 0.001) and mixed (ptrend = 0.035) ventilatory disorders at the last follow-up. CONCLUSION: Diabetes is associated with a lower baseline lung function and a faster rate of deterioration.

Skin rejuvenation and photoaging protection using adipose-derived stem cell extracellular vesicles loaded with exogenous cargos.

BACKGROUND: Small extracellular vesicles from adipose-derived stem cells (ASC-sEVs) have gained remarkable attention for their regenerative and protective properties against skin aging. However, the use of ASC-sEVs to further encapsulate certain natural anti-aging compounds for synergistic effects has not been actively explored. For large-scale production in skincare industry, it is also crucial to standardize cost-effective methods to produce highly pure ASC-sEVs. METHODS: Human ASCs were expanded in serum-free media with different compositions to first optimize the sEV production. ASC-sEVs from different batches were then purified using tangential flow filtration and sucrose cushion ultracentrifugation, followed by extensive characterization for identity and content profiling including proteomics, lipidomics and miRNA sequencing. ASC-sEVs were further loaded with nicotinamide riboside (NR) and resveratrol by sonication-incubation method. The therapeutic effect of ASC-sEVs and loaded ASC-sEVs was tested on human keratinocyte cell line HaCaT exposed to UVB by measuring reactive oxygen species (ROS). The loaded ASC-sEVs were later applied on the hand skin of three volunteers once a day for 8 weeks and skin analysis was performed every 2 weeks. RESULTS: Our standardized workflow produced ASC-sEVs with high yield, high purity and with stable characteristics and consistent biocargo among different batches. The most abundant subpopulations in ASC-sEVs were CD63+ (∼30%) and CD81+ -CD63+ (∼35%). Purified ASC-sEVs could be loaded with NR and resveratrol at the optimized loading efficiency of ∼20%. In UVB-exposed HaCaT cells, loaded ASC-sEVs could reduce ROS by 38.3%, higher than the sEVs (13.3%) or compounds (18.5%) individually. In human trial, application of loaded ASC-sEVs after 8 weeks substantially improved skin texture, increased skin hydration and elasticity by 104% and reduced mean pore volume by 51%. CONCLUSIONS: This study demonstrated a robust protocol to produce ASC-sEVs and exogenously load them with natural compounds. The loaded ASC-sEVs exhibited synergistic effects of both sEVs and anti-aging compounds in photoaging protection and skin rejuvenation.

The incidence of dermatitis following application of foam tape in healthy volunteers-A prospective trial.

BACKGROUND: Foam tape is commonly used in the emergency department as a dressing over chest tubes owing to its occlusive and compressible properties. There is a paucity of data regarding the incidence of significant cutaneous reactions to this material. We conducted a prospective trial to evaluate the incidence of dermatitis following application of foam tape to the upper arm of a cohort of healthy volunteers. METHODS: This was a prospective, interventional trial. We enrolled a cohort of consenting, healthy physicians, nurses, and ancillary staff at a teaching facility who did not have known hypersensitivity to foam tape. Study investigators applied a 2 × 2 inch piece of 3 M microfoam adhesive to the medial aspect of each subject's upper arm. The contralateral arm served as a reference for comparison. The adhesive remained in place for 48 h and the study authors assessed patients utilizing the previously validated Cutaneous Irritancy Scoring System (CISS). Categorical variables analyzed by chi-square, continuous variables with t-tests. RESULTS: There were 40 subjects in the study group; 52% female, mean age 40±7 years, 55% non-White race. 10/40 (25%; 95%CI[14%, 41%]) of subjects had erythema; 9/40 (22%) had an erythema score of 1 and 1/40 (2.5%) had a score of 2. With respect to edema, 2/40 (5%; 95% CI[1%,18%]); 1/40(2.5%) had an edema score of 1, and 1/40(2.5%) had a score of 2. There were 9/40 subjects with an irritancy score > 0; (22%; 95%CI[12%,38%]); 7/40(18%) had an irritancy score of 1, and 2/4(5.0%) had a score of 2. In terms of the severity score, 10/40 (25%; 95%CI[14%, 41%]) had a score > 0; 9/40(22%) had a score of 1, and 1/40(2.5%) had a score of 2. Overall, 10/40 (25%; 95%CI[14%, 41%]) of subjects had at least one positive measure of a reaction of any kind. Subjects' age, gender and race were not found to be statistically significantly associated with the incidence of erythema, edema, or irritancy. In addition, these characteristics were not statistically significantly associated with severity score > 0. The p values for all the above bivariate analyses were > 0.05. CONCLUSIONS: Cutaneous reactions occurred in 25% of healthy volunteers after the application of foam tape to the arm. Patient characteristics were not associated with risk of a skin reaction. CLINICAL TRIALS REGISTRATION: #NCT06059417.

A Novel Mechanism for Bone Loss: Platelet Count Negatively Correlates with Bone Mineral Density via Megakaryocyte-Derived RANKL.

A potential association between hematopoietic stem cell status in bone marrow and surrounding bone tissue has been hypothesized, and some studies have investigated the link between blood count and bone mineral density (BMD), although their exact relationship remains controversial. Moreover, biological factors linking the two are largely unknown. In our present study, we found no clear association between platelet count and BMD in the female group, with aging having a very strong effect on BMD. On the other hand, a significant negative correlation was found between platelet count and BMD in the male group. As a potential mechanism, we examined whether megakaryocytes, the source of platelet production, secrete cytokines that regulate BMD, namely OPG, M-CSF, and RANKL. We detected the production of these cytokines by megakaryocytes derived from bone marrow mononuclear cells, and found that RANKL was negatively correlated with BMD. This finding suggests that RANKL production by megakaryocytes may mediate the negative correlation between platelet count and BMD. To our knowledge, this is the first report to analyze bone marrow cells as a mechanism for the association between blood count and BMD. Our study may provide new insights into the development and potential treatment of osteoporosis.

AI-based classification of three common malignant tumors in neuro-oncology: A multi-institutional comparison of machine learning and deep learning methods.

PURPOSE: To determine if machine learning (ML) or deep learning (DL) pipelines perform better in AI-based three-class classification of glioblastoma (GBM), intracranial metastatic disease (IMD) and primary CNS lymphoma (PCNSL). METHODOLOGY: Retrospective analysis included 502 cases for training (208 GBM, 67 PCNSL and 227 IMD), with external validation on 86 cases (27:27:32). Multiparametric MRI images (T1W, T2W, FLAIR, DWI and T1-CE) were co-registered, resampled, denoised and intensity normalized, followed by semiautomatic 3D segmentation of the enhancing tumor (ET) and peritumoral region (PTR). Model performance was assessed using several ML pipelines and 3D-convolutional neural networks (3D-CNN) using sequence specific masks, as well as combination of masks. All pipelines were trained and evaluated with 5-fold nested cross-validation on internal data followed by external validation using multi-class AUC. RESULTS: Two ML models achieved similar performance on test set, one using T2-ET and T2-PTR masks (AUC: 0.885, 95% CI: [0.816, 0.935] and another using T1-CE-ET and FLAIR-PTR mask (AUC: 0.878, CI: [0.804, 0.930]). The best performing DL models achieved an AUC of 0.854, (CI [0.774, 0.914]) on external data using T1-CE-ET and T2-PTR masks, followed by model derived from T1-CE-ET, ADC-ET and FLAIR-PTR masks (AUC: 0.851, CI [0.772, 0.909]). CONCLUSION: Both ML and DL derived pipelines achieved similar performance. T1-CE mask was used in three of the top four overall models. Additionally, all four models had some mask derived from PTR, either T2WI or FLAIR.

Humanized anti-IL-26 monoclonal antibody as a novel targeted therapy for chronic graft-versus-host disease.

IL-26 is a Th17 cytokine, with its gene being absent in rodents. To characterize the in vivo immunological effects of IL-26 in chronic systemic inflammation, we used human IL26 transgenic (hIL-26Tg) mice and human umbilical cord blood mononuclear cells (hCBMC) in mouse allogeneic-graft-versus-host disease (GVHD) and chronic xenogeneic-GVHD model, respectively. Transfer of bone marrow and spleen T cells from hIL-26Tg mice into B10.BR mice resulted in GVHD progression, with clinical signs of tissue damage in multiple organs. IL-26 markedly increased neutrophil levels both in the GVHD-target tissues and peripheral blood. Expression levels of Th17 cytokines in hIL-26Tg mice-derived donor CD4 T cells were significantly increased, whereas IL-26 did not affect cytotoxic function of donor CD8 T cells. In addition, granulocyte-colony stimulating factor, IL-1ß, and IL-6 levels were particularly enhanced in hIL-26Tg mice. We also developed a humanized neutralizing anti-IL-26 monoclonal antibody (mAb) for therapeutic use, and its administration after onset of chronic xenogeneic-GVHD mitigated weight loss and prolonged survival, with preservation of graft-versus-leukemia effect. Taken together, our data elucidate the in vivo immunological effects of IL-26 in chronic GVHD models and suggest that a humanized anti-IL-26 mAb may be a potential therapeutic agent for the treatment of chronic GVHD.

Laparoscopic intraperitoneal versus enhanced-view totally extraperitoneal retromuscular mesh repair for ventral hernia: a retrospective cohort study.

BACKGROUND: Laparoscopic enhanced-view totally extraperitoneal retromuscular repair (eTEP-RM) was recently introduced as a new technique for ventral hernia repair. The aim of the current study was to examine the outcomes of laparoscopic eTEP-RM compared with laparoscopic IPOM for patients with primary ventral and incisional hernia. METHODS: This was a retrospective cohort study of patients undergoing laparoscopic ventral hernia repair at a single University Hospital from June 2017 to November 2020. Medical charts of all patients subjected to IPOM and eTEP-RM were evaluated to identify patient- and procedure related variables, as well as postoperative 30-day outcomes. RESULTS: A total of 72 patients were included in the study, 43 and 29 of whom underwent IPOM and eTEP-RM repair, respectively. Patient demographics showed no differences in terms of gender, age, smoking and comorbidity. The median age was 57 years and body mass index 30.5 kg/m2. The rate of patients with incisional hernia was higher in the IPOM group (39.5% vs. 20.7%, p = 0.154). There was no difference in horizontal and vertical hernia size defect. The duration of surgery was significantly shorter for IPOM (mean 82.4 vs. 103.4 min, p = 0.010), whereas the length of stay was significantly longer after IPOM (median 1 days vs. 0 days (p < 0.001). The rate of patients requiring postoperative transversus abdominis plane (TAP) block or epidural analgesia was significantly higher after IPOM (33% vs. 0%, p = 0.002). A subgroup analysis on patients undergoing primary ventral hernia showed similar results. CONCLUSION: The study found laparoscopic eTEP-RM safe and effective compared to traditional laparoscopic IPOM. The patients undergoing eTEP-RM had significantly reduced need for additional analgesic treatment and length of stay.

Enhancing Covid-19 virus spread modeling using an activity travel model.

Coronavirus 2019 (COVID-19) and its variants are still spreading rapidly with deadly consequences and profound impacts on the global health and world economy. Without a suitable vaccine, mobility restriction has been the most effective method so far to prevent its spreading and avoid overwhelming the heath system of the affected country. The compartmental model SIR (or Susceptible, Infected, and Recovered) is the most popular mathematical model used to predict the course of the COVID-19 pandemic in order to plan the control actions and mobility restrictions against its spreading. A major limitation of this model in relation to modeling the spreading of COVID-19, and the mobility limitation strategy, is that the SIR model does not include mobility or take into account changes in mobility within its structure. This paper develops and tests a new hybrid SIR model; SIR-M which is integrated with an urban activity travel model to explore how it might improve the prediction of pandemic course and the testing of mobility limitation strategies in managing virus spread. The paper describes the enhanced methodology and tests a range of mobility limitation strategies on virus spread outcomes. Implications for policy and research futures are suggested.

Integrase strand transfer inhibitor treatment does not increase the incidence of immune reconstitution inflammatory syndrome in HIV-infected Koreans.

OBJECTIVES: Immune reconstitution inflammatory syndrome (IRIS) is a major concern when starting antiretroviral therapy (ART) in patients with advanced HIV infection. The aim of this study was to determine the incidence and risk factors of IRIS in HIV-infected Koreans initiating ART, and whether integrase strand transfer inhibitor (INSTI) treatment increases the risk of IRIS. METHODS: This retrospective analysis included adults living with HIV, seen at four university-affiliated hospitals in South Korea, who were naïve to ART and had a CD4 T-cell count < 200 cells/µL between January 2004 and May 2019. IRIS was determined through a medical record review within 6 months of ART initiation. Propensity score-matched case-control study between the non-INSTI and INSTI groups was performed. RESULTS: The study included 501 patients; 192 were assigned to the INSTI group, who started ART based on INSTIs as the initial treatment. There were opportunistic infections (OIs) in 253 (50.5%) cases before ART initiation. The three most common OIs were Pneumocystis jirovecii pneumonia, candidiasis and tuberculosis (TB). We identified 47 cases of IRIS; TB-IRIS was the most common type. The incidence of IRIS within 6 months of ART initiation was 9.4%, and there were no significant differences in baseline characteristics and incidence of IRIS between the matched groups. The risk factors for IRIS were pre-ART CD4 T-cell count (< 30 cells/µL), higher pre-ART viral load (≥ 75 000 copies/mL), and TB-OI. CONCLUSIONS: The incidence of IRIS was 9.4% in Korean HIV patients. The INSTI regimen was not related to IRIS occurrence.

Ibrutinib plus lenalidomide and rituximab has promising activity in relapsed/refractory non-germinal center B-cell-like DLBCL.

The outcome of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is poor, particularly in patients ineligible for stem cell transplantation or who fail induction therapy or salvage therapy. The phase 1b portion of this open-label, dose-escalation (3+3+3 design) study examined the maximum tolerated dose (MTD) and preliminary safety and activity of the regimen in transplant-ineligible adults with histologically confirmed relapsed/refractory DLBCL after at least 1 prior therapy. Patients received once-daily 560 mg ibrutinib, 375 mg/m2 intravenous rituximab day 1 of cycles 1 to 6, and 10, 15, 20, or 25 mg lenalidomide days 1 to 21 of each 28-day cycle. Forty-five patients were treated; median time since diagnosis was 14.1 months, and 51% of the patients had non-germinal center B-cell-like (non-GCB) DLBCL, 33% had transformed DLBCL, 60% were refractory, and 27% were primary refractory. Because of dose-limiting toxicities, a de-escalation cohort (10 mg lenalidomide) was initiated, and with subsequent re-escalation up to 25 mg lenalidomide, the MTD was not reached. In response-evaluable patients, the overall response rate (ORR) was 44% (complete response [CR], 28%); among them, the ORR was 65% (CR, 41%) in non-GCB and 69% and 56% in relapsed (n = 16) and secondary refractory (n = 27) disease, respectively. Overall and for non-GCB, median response duration was 15.9 months, with 2 patients receiving therapy beyond 3 years. Phase 2 was initiated with 20 mg lenalidomide in relapsed/refractory non-GCB, whereas the phase 1b 25-mg lenalidomide cohort was being completed; an additional 25-mg cohort in phase 2 is currently ongoing. This study was registered at www.clinicaltrials.gov as #NCT02077166.

Radiomics-based differentiation between glioblastoma and primary central nervous system lymphoma: a comparison of diagnostic performance across different MRI sequences and machine learning techniques.

OBJECTIVES: Despite the robust diagnostic performance of MRI-based radiomic features for differentiating between glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL) reported on prior studies, the best sequence or a combination of sequences and model performance across various machine learning pipelines remain undefined. Herein, we compare the diagnostic performance of multiple radiomics-based models to differentiate GBM from PCNSL. METHODS: Our retrospective study included 94 patients (34 with PCNSL and 60 with GBM). Model performance was assessed using various MRI sequences across 45 possible model and feature selection combinations for nine different sequence permutations. Predictive performance was assessed using fivefold repeated cross-validation with five repeats. The best and worst performing models were compared to assess differences in performance. RESULTS: The predictive performance, both using individual and a combination of sequences, was fairly robust across multiple top performing models (AUC: 0.961-0.977) but did show considerable variation between the best and worst performing models. The top performing individual sequences had comparable performance to multiparametric models. The best prediction model in our study used a combination of ADC, FLAIR, and T1-CE achieving the highest AUC of 0.977, while the second ranked model used T1-CE and ADC, achieving a cross-validated AUC of 0.975. CONCLUSION: Radiomics-based predictive accuracy can vary considerably, based on the model and feature selection methods as well as the combination of sequences used. Also, models derived from limited sequences show performance comparable to those derived from all five sequences. KEY POINTS: • Radiomics-based diagnostic performance of various machine learning models for differentiating glioblastoma and PCNSL varies considerably. • ML models using limited or multiple MRI sequences can provide comparable performance, based on the chosen model. • Embedded feature selection models perform better than models using a priori feature reduction.

Tumor-to-tumor metastasis of diffuse large B cell lymphoma to gastric adenocarcinoma via CXCL12 (SDF-1)/CXCR4 axis: a case report.

BACKGROUND: Tumor-to-tumor metastasis is the rare phenomenon in which one tumor exhibits metastatic deposits from another. To the best of our knowledge, there has been no prior reported case of tumor-to-tumor metastasis of a diffuse large B cell lymphoma (DLBCL) to a primary gastric adenocarcinoma. CASE PRESENTATION: A 70-year-old man presented with chest discomfort. An echocardiogram showed the presence of a right ventricular tumor. A positron emission tomogram showed multiple foci of abnormal activity in right cervical lymph nodes, cardiac wall, and stomach. A right cervical lymph node biopsy specimen revealed histological features of DLBCL. An esophagogastroduodenoscopy showed a large circumferential ulceration on the gastric body. Subsequent biopsy revealed adenocarcinoma cells surrounded by infiltrating lymphoma cells. On immunohistochemical staining, lymphoma cells were positive for CXCR4 and adenocarcinoma cells were positive for CXCL12/SDF-1. The patient was treated with six cycles of R-CHOP chemotherapy regimen, resulting in a complete remission. CONCLUSIONS: This patient's case implies that the interaction between a chemokine and its receptor may be the underlying mechanism for the observed tumor-to-tumor metastasis. Specifically, our case would suggest an involvement of the CXCL12 (SDF-1)/CXCR4 axis in the observed metastasis of DLBCL to primary gastric adenocarcinoma.

Hyperattenuating lesions after mechanical thrombectomy in acute ischaemic stroke: factors predicting symptomatic haemorrhage and clinical outcomes.

AIM: To evaluate the clinical significance of hyperattenuating lesions on CT after mechanical thrombectomy for acute ischaemic stroke, and to identify imaging factors that predict symptomatic haemorrhage and unfavourable outcomes. MATERIALS AND METHODS: Seventy-eight patients with acute ischaemic stroke in the anterior circulation who underwent mechanical thrombectomy were evaluated. All patients underwent post-interventional unenhanced computed tomography (CT) within 24 h and follow-up CT or magnetic resonance imaging (MRI) within 7 days. Baseline characteristics and clinical outcomes were compared between patients with and without hyperattenuating lesions. In patients with hyperattenuating lesions, clinical and imaging factors that predict symptomatic haemorrhage and unfavourable outcomes were determined. RESULTS: Fifty-six of 78 patients (71.8%) demonstrated hyperattenuating lesions on post-interventional CT. Patients with hyperattenuating lesions showed lower Alberta Stroke Program Early CT score (ASPECTS), persistent/symptomatic haemorrhage, and unfavourable outcomes than those without. In patients with hyperattenuating lesions, larger hyperattenuating lesion volume (>21.3 ml; OR, 55.60, p<0.001) and perilesional oedema (OR, 46.04, p=0.015) were independent factors predicting symptomatic haemorrhage. Older age (OR, 1.2, p=0.006) and lower ASPECTS (OR, 0.45, p=0.046) were independent factors predicting unfavourable outcomes in patients with hyperattenuating lesions. Adding the volume of the hyperattenuating lesion to age and ASPECTS increased the predictive performance of unfavourable outcomes (area under the curve 0.874 versus 0.934, p=0.043). CONCLUSIONS: Hyperattenuating lesions on post-interventional CT are associated with increased risk of symptomatic haemorrhage and unfavourable outcomes. Larger hyperattenuating lesion volume is an independent factor of symptomatic haemorrhage and it has added predictive value for unfavourable outcomes.

Challenges and Opportunities of System-Level Prognostics.

Prognostics and health management (PHM) has become an essential function for safe system operation and scheduling economic maintenance. To date, there has been much research and publications on component-level prognostics. In practice, however, most industrial systems consist of multiple components that are interlinked. This paper aims to provide a review of approaches for system-level prognostics. To achieve this goal, the approaches are grouped into four categories: health index-based, component RUL-based, influenced component-based, and multiple failure mode-based prognostics. Issues of each approach are presented in terms of the target systems and employed algorithms. Two examples of PHM datasets are used to demonstrate how the system-level prognostics should be conducted. Challenges for practical system-level prognostics are also addressed.

Association between body mass index and stroke severity in acute ischaemic stroke with non-valvular atrial fibrillation.

BACKGROUND AND PURPOSE: The objective of this study was to investigate the association between body mass index (BMI) and both initial stroke severity at presentation and functional outcomes after acute ischaemic stroke (AIS) in patients with non-valvular atrial fibrillation (NVAF). METHODS: Patients were categorized on the basis of their BMI into underweight (BMI <18.5, n = 111), normal (18.5 ≤ BMI <25, n = 1036) and overweight to obese (BMI ≥25, n = 472) groups. Initial stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score and functional outcomes were assessed using the modified Rankin Scale score at discharge. The differences in stroke severity and functional outcomes were compared between groups using robust log-linear regression with a Poisson distribution and binary logistic regression analysis. RESULTS: A total of 1619 AIS patients with NVAF from six hospitals were included. Compared with the NIHSS scores [median 5, interquartile range (IQR) 2-14] of normal-weight patients, the NIHSS scores (median 9, IQR 4-19) of underweight patients were more likely to be higher, whereas those of overweight to obese patients were lower (median 4, IQR 1-12) (P < 0.001). In terms of functional outcomes after stroke, underweight patients had a higher risk of poor functional outcomes (odds ratio 1.78, 95% confidence interval 1.09-2.56, P = 0.01) but overweight to obese patients had no significant difference in functional outcomes compared with normal-weight patients. CONCLUSION: An inverse association was found between BMI and stroke severity in AIS patients with NVAF. This suggests the presence of an obesity paradox for short-term outcomes in patients with NVAF.

Post Transplant Lymphoproliferative Disorder risk factors in children: Analysis of a 23-year single-institutional experience.

INTRODUCTION: PTLD is the most frequent malignancy following SOT in children and the second most common SOT complication in adults. However, factors determining outcomes in children are poorly understood due to its relative rarity. METHODS: This study was performed at the University of Florida. Univariate and multivariate analyses were used to identify prognostic factors in pediatric patients diagnosed with PTLD. RESULTS: We reviewed records of 54 pediatric (younger than 18 years old at diagnosis) patients diagnosed with PTLD from 1994 to 2017. The median follow-up was 28.8 months. The estimated 5-year survival rate was 87.6% (95% CI 74.3-94.2%). Univariate analysis showed that organ transplanted (specifically heart transplant), poor response to initial treatment, allograft rejection, and low Karnofsky score were statistically significant for negative prognostic factors in determining survival. Multivariate analysis determined progression in response to initial treatment and presence of allograft rejection as statistically significant prognostic factors affecting overall survival. We found no statistically significant impact of EBV serological status on PTLD prognosis. CONCLUSIONS: Disease progression and allograft rejection were strong negative prognostic indicators in our study cohort. Close attention to graft status and development of therapies that protect the graft from rejection while bolstering anti-EBV immunity will be essential to further improving PTLD outcomes in children.

Spontaneous ketonuria and risk of incident diabetes: a 12 year prospective study.

AIMS/HYPOTHESIS: Ketones may be regarded as a thrifty fuel for peripheral tissues, but their clinical prognostic significance remains unclear. We investigated the association between spontaneous fasting ketonuria and incident diabetes in conjunction with changes in metabolic variables in a large population-based observational study. METHODS: We analysed 8703 individuals free of diabetes at baseline enrolled in the Korean Genome and Epidemiology Study, a community-based 12 year prospective study. Individuals with (n = 195) or without fasting ketonuria were matched 1:4 by propensity score. Incident diabetes was defined as fasting plasma glucose ≥7.0 mmol/l, post-load 2 h glucose ≥11.1 mmol/l on biennial OGTTs, or current use of glucose-lowering medication. Using Cox regression models, HRs for developing diabetes associated with the presence of ketonuria at baseline were analysed. RESULTS: Over 12 years, of the 925 participants in the propensity score-matched cohort, 190 (20.5%) developed diabetes. The incidence rate of diabetes was significantly lower in participants with spontaneous ketonuria compared with those without ketonuria (HR 0.63; 95% CI 0.41, 0.97). Results were virtually identical when participants with fasting ketonuria were compared against all participants without ketonuria (after multivariate adjustment, HR 0.66; 95% CI 0.45, 0.96). During follow-up, participants with baseline ketonuria maintained lower post-load 1 h and 2 h glucose levels and a higher insulinogenic index despite comparable baseline values. CONCLUSIONS/INTERPRETATION: The presence of spontaneous fasting ketonuria was significantly associated with a reduced risk of diabetes, independently of metabolic variables. Our findings suggest that spontaneous fasting ketonuria may have a potential preventive role in the development of diabetes.