Proximity extension assay proteomics and renal single cell transcriptomics uncover novel urinary biomarkers for active lupus nephritis.

OBJECTIVE: To identify urinary biomarkers that can distinguish active renal involvement in Lupus Nephritis (LN), a severe manifestation of systemic lupus erythematosus (SLE). METHODS: Urine from 117 subjects, comprised of inactive SLE, active non-renal lupus, active LN, and healthy controls, were subjected to Proximity Extension Assay (PEA) based comprehensive proteomics followed by ELISA validation in an independent, ethnically diverse cohort. Proteomic data is also cross-referenced to renal transcriptomic data to elucidate cellular origins of biomarkers. RESULTS: Systems biology analyses revealed progressive activation of cytokine signaling, chemokine activity and coagulation pathways, with worsening renal disease. In addition to validating 30 previously reported biomarkers, this study uncovers several novel candidates. Following ELISA validation in an independent cohort of different ethnicity, the six most discriminatory biomarkers for active LN were urinary ICAM-2, FABP4, FASLG, IGFBP-2, SELE and TNFSF13B/BAFF, with ROC AUC ≥80%, with most correlating strongly with clinical disease activity. Transcriptomic analyses of LN kidneys mapped the likely origin of these proteins to intra-renal myeloid cells (CXCL16, IL-1RT2, TNFSF13B/BAFF), T/NK cells (FASLG), leukocytes (ICAM2) and endothelial cells (SELE). CONCLUSION: In addition to confirming the diagnostic potential of urine ALCAM, CD163, MCP1, SELL, ICAM1, VCAM1, NGAL and TWEAK for active LN, this study adds urine ICAM-2, FABP4, FASLG, IGFBP-2, SELE, and TNFSF13B/BAFF as additional markers that warrant systematic validation in larger cross-sectional and longitudinal cohorts.

Hidradenitis Suppurativa Found Associated With Cytokine Storm.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that generates multiple cytokines. Here, we present an example of the cytokines forming a cytokine storm and its effects on the patient. CASE PRESENTATION: We report the case of a 55-year-old man who had severe but stable HS. Serum samples were collected from the patient and extraordinarily elevated cytokine concentrations were identified in the patient's serum.  Conclusion: Cytokine storms may be a condition associated with HS posing additional risk to patient survival. J Drugs Dermatol. 2024;23(5):e134-e136.     doi:10.36849/JDD.7860R1e.

Efficacy of personalized 3D-printed osteotomy guide in maximizing fibular utilization and minimizing graft length for reconstruction of large mandibular defect.

OBJECTIVE: The study addresses the long-standing challenge of insufficient length in vascularized fibular flaps when reconstructing large mandibular defects that require dual-barrel grafts. Employing personalized 3D-printed osteotomy guides, the study aims to optimize fibular utilization and minimize the required graft length. MATERIAL AND METHODS: Two reconstruction methods for distal bone defects were compared: a fold-down (FD) group that employed a specialized osteotomy guide for folding down a triangular bone segment, and a traditional double-barrel (DB) group. Metrics for comparison included defect and graft lengths, as well as the graft-to-defect length ratio. Postoperative quality of life was assessed using the University of Washington Quality of Life questionnaire (UW-QoL). RESULT: Both FD and DB groups achieved successful mandibular reconstruction. Despite larger defects in the FD group (117 ± 31.35 mm vs 84 ± 35.34 mm, p = 0.028), the used fibula length was not statistically longer in the FD group. The median ratio of graft-to-defect length was also lower in the FD group (1.327 vs 1.629, p = 0.024), suggesting that FD required only 82.47% of the graft length needed in the DB approach. Quality of life scores post-surgery were comparable between the groups. CONCLUSION: Personalized 3D-printed osteotomy guides enhance fibula graft efficacy for reconstructing larger mandibular defects, necessitating shorter graft lengths while preserving postoperative quality of life. CLINICAL RELEVANCE: This study confirms the utility of 3D printing technology as an effective and precise tool in orthopedic surgery, particularly for complex reconstructions like large mandibular defects. It suggests a viable alternative that could potentially revolutionize current practices in bone grafting.

Comparative analysis of GoPro and digital cameras in head and neck flap harvesting surgery video documentation: an innovative and efficient method for surgical education.

BACKGROUND: An urgent need exists for innovative surgical video recording techniques in head and neck reconstructive surgeries, particularly in low- and middle-income countries where a surge in surgical procedures necessitates more skilled surgeons. This demand, significantly intensified by the COVID-19 pandemic, highlights the critical role of surgical videos in medical education. We aimed to identify a straightforward, high-quality approach to recording surgical videos at a low economic cost in the operating room, thereby contributing to enhanced patient care. METHODS: The recording was comprised of six head and neck flap harvesting surgeries using GoPro or two types of digital cameras. Data were extracted from the recorded videos and their subsequent editing process. Some of the participants were subsequently interviewed. RESULTS: Both cameras, set at 4 K resolution and 30 frames per second (fps), produced satisfactory results. The GoPro, worn on the surgeon's head, moves in sync with the surgeon, offering a unique first-person perspective of the operation without needing an additional assistant. Though cost-effective and efficient, it lacks a zoom feature essential for close-up views. In contrast, while requiring occasional repositioning, the digital camera captures finer anatomical details due to its superior image quality and zoom capabilities. CONCLUSION: Merging these two systems could significantly advance the field of surgical video recording. This innovation holds promise for enhancing technical communication and bolstering video-based medical education, potentially addressing the global shortage of specialized surgeons.

A near-infrared probe for detecting and interposing amyloid beta oligomerization in early Alzheimer's disease.

BACKGROUND: The misfolding and deposition of amyloid beta (Aß) in human brain is the main hallmark of Alzheimer's disease (AD) pathology. One of the drivers of Alzheimer´s pathogenesis is the production of soluble oligomeric Aß, which could potentially serve as a biomarker of AD. METHODS: Given that the diphenylalanine (FF) at the C-terminus of Aß fragments plays a key role in inducing the AD pathology, based on the hydrophobic structure of FF, we synthesized a near-infrared BF2-dipyrrolmethane fluorescent imaging probe (NB) to detect both soluble and insoluble Aß. RESULTS: We found that NB not only binds Aß, particularly oligomeric Aß, but also interposes self-assembly of Aß through π-π interaction between NB and FF. CONCLUSION: This work holds great promise in the early detection of AD and may also provide an innovative approach to decelerate and even halt AD onset and progression.

Recent Advances in Bioengineering Bone Revascularization Based on Composite Materials Comprising Hydroxyapatite.

The natural healing process of bone is impaired in the presence of tumors, trauma, or inflammation, necessitating external assistance for bone regeneration. The limitations of autologous/allogeneic bone grafting are still being discovered as research progresses. Bone tissue engineering (BTE) is now a crucial component of treating bone injuries and actively works to promote vascularization, a crucial stage in bone repair. A biomaterial with hydroxyapatite (HA), which resembles the mineral makeup of invertebrate bones and teeth, has demonstrated high osteoconductivity, bioactivity, and biocompatibility. However, due to its brittleness and porosity, which restrict its application, scientists have been prompted to explore ways to improve its properties by mixing it with other materials, modifying its structural composition, improving fabrication techniques and growth factor loading, and co-cultivating bone regrowth cells to stimulate vascularization. This review scrutinizes the latest five-year research on HA composite studies aimed at amplifying vascularization in bone regeneration.

OLR1 Is a Pan-Cancer Prognostic and Immunotherapeutic Predictor Associated with EMT and Cuproptosis in HNSCC.

Metabolism plays a critical role in cancer. OLR1 has been implicated in cardiovascular and metabolic disorders, while its association with tumorigenesis and tumor immunity remains poorly defined in the literature. We conducted comprehensive pan-cancer analyses based on the TCGA database to examine OLR1 expression and its prognostic implications. Correlations between OLR1 expression level and tumor immunity and immunotherapy were investigated by immune infiltration, enrichment, and TIDE analysis methods. Immunohistochemistry detected OLR1 expression in HNSCC. We used the GSEA method to explore the potential signaling pathways in which OLR1 is involved, and a correlation analysis to investigate the relationships between OLR1 and epithelial-mesenchymal transition (EMT) and cuproptosis. In addition, the effects of OLR1 knockdown on the EMT process, invasion, stemness, and cuproptosis of HNSCC cells were examined by scratch, Transwell, CCK8, sphere formation, and flow cytometry, while changes in related proteins were detected using the immunoblotting method. OLR1 is highly expressed in most cancers, and it is associated with patient prognosis. OLR1 expression positively correlates with immunosuppressive cell infiltration and immune checkpoint molecules, while being negatively associated with effector T cells. Moreover, significant correlations are observed between OLR1 expression and tumor mutation burden (TMB) and microsatellite instability (MSI) in some cancers. In HNSCC, OLR1 expression is related to advanced clinicopathological factors and unfavorable outcomes. Patients with high OLR1 expression levels are prone to experience immune escape and benefit less from immune checkpoint inhibitor (ICI) therapy. Moreover, OLR1 expression may affect EMT, stemness, and cuproptosis resistance outcomes. OLR1 is an immune-related prognostic biomarker with potential as a prognostic indicator for immunotherapy, and it may also be involved in regulating the EMT process and cuproptosis in HNSCC.

Preliminary Evaluation of a System with On-Body and Aerial Sensors for Monitoring Working Dogs.

This paper presents a system for behavioral, environmental, and physiological monitoring of working dogs using on-body and aerial sensors. The proof of concept study presented here includes two trained dogs performing nine scent detection tasks in an uncontrolled environment encompassing approximately two acres. The dogs were outfitted with a custom designed wearable harness to monitor their heart rate, activity levels and skin temperature. We utilized a commercially available micro-air vehicle to perform aerial sensing by tracking the terrain and movement of the dog in the outdoor space. The dogs were free to explore the space working at maximal speeds to complete a scent-based search-and-retrieval task. Throughout the experiment, the harness data was transferred to a base station via Wi-Fi in real-time. In this work, we also focused on testing the performance of a custom 3D electrode with application specific ergonomic improvements and adaptive filter processing techniques to recover as much electrocardiography data as possible during high intensity motion activity. We were able to recover and use 84% of the collected data where we observed a trend of heart rate generally increasing immediately after successful target localization. For tracking the dogs in the aerial video footage, we applied a state-of-the-art deep learning algorithm designed for online object tracking. Both qualitative and quantitative tracking results are very promising. This study presents an initial effort towards deployment of on-body and aerial sensors to monitor the working dogs and their environments during scent detection and search and rescue tasks in order to ensure their welfare, enable novel dog-machine interfaces, and allow for higher success rate of remote and automated task performance.

Virtual Surgical Planning for Successful Second-Stage Mandibular Defect Reconstruction Using Vascularized Iliac Crest Bone Flap: A Valid and Reliable Method.

PURPOSE: Second-stage reconstruction of mandibular defects faces problems of anatomic disorder and bone displacement due to tumor resection. As a newer technique, virtual surgical planning (VSP) may help to increase the accuracy and efficiency of the complicated reconstruction. This study aims to evaluate the application of VSP and splint-guided surgery in second-stage mandibular reconstruction using vascularized iliac crest bone flap. METHODS: Between October 2016 and February 2018, 5 patients (3 men and 2 women) with mandibular defects of duration between 8 months and 8 years underwent VSP-aided secondary reconstruction in the School and Hospital of Stomatology of Wuhan University (Wuhan, China). Virtual surgical planning was performed and serial guiding splints were printed to replicate the design into the actual operation. The linear and 3-dimensional deviations after surgery were analyzed. Patient complications and feedback were recorded during follow up. RESULTS: All 5 patients underwent successful reconstruction using vascularized iliac crest bone flap. No serious donor sites or recipient site complications were observed after 10- to 28-month follow-up. In comparison with the presurgery designs, the linear deviations in coronal plane were 2.7 ± 0.4 mm (range, -2.2 to 3.9 mm) in measurements from the condylar head to the condylar head and 0.70 ± 0.6 mm (range, -0.1 to 1.7 mm) from the gonial angle to the gonial angle, and that in sagittal plane was 2.4 ± 0.88 mm (range, -3 to 4.4 mm) from the anterior inferior mandibular border to the center point on the condylar head to the condylar head line. The whole 3-dimensional deviation was 1.2 ± 1.7 mm in all patients. CONCLUSION: Well-designed splints can assist in precise mandibular reconstruction with high efficiency and accuracy, and thus are a reliable method for complicated second-stage mandibular reconstruction. However, to achieve a better outcome, a satisfactory design is required to adapt the complicated and varied defect.

Curcumin Attenuates Both Acute and Chronic Immune Nephritis.

Curcumin is known to have immunomodulatory potential in addition to anti-oxidant, anti-inflammatory and anti-carcinogenic effects. The aim of the present study is to investigate the therapeutic effects of curcumin on immune-mediated renal disease in an anti-glomerular basement membrane (GBM) model (representing acute kidney Injury, AKI) and murine lupus model (representing chronic kidney disease, CKD). In the AKI model, female anti-GBM 129/svj mice were administered with curcumin right before disease induction. In the CKD model, female MRL.lpr mice at the age of 8-10 weeks old were treated with curcumin or placebo via oral gavage daily for two months. After treatment, serum autoantibody levels, splenomegaly and spleen cellularity were reduced in murine lupus. Collectively, curcumin ameliorated kidney disease in the two mouse models with either acute or chronic nephritis, as marked by reduced proteinuria, blood urea nitrogen, glomerulonephritis, crescent formation, tubule-interstitial disease, and renal infiltration by lymphocytes. In addition, curcumin treatment reduced activation of the NFkB, MAPK, AKT and pBAD pathways either systemically, or within the inflamed kidneys. These findings suggest that natural food supplements could become an alternative approach to ameliorating immune-mediated kidney diseases.

Elevated oxidized lipids, anti-lipid autoantibodies and oxidized lipid immune complexes in active SLE.

BACKGROUND: Here, we explore the serum levels of anti-oxidized lipid autoantibodies as well as immune complexes in patients with SLE and determine their correlation with disease. METHODS: Serum levels of oxidized-LDL immune complexes, autoantibodies to dsDNA, ox-LDL, MDA-LDL, 9-HODE, 13-HODE and POVPC were detected by ELISA in 64 SLE patients and 9 healthy controls. RESULTS: Active SLE patients exhibited increased serum levels of autoantibodies compared to healthy controls, including anti-MDA-LDL-IgG (p = .003), anti-ox-LDL-IgG (p = .004), anti-9-HODE-IgG (p = .001), anti-13-HODE-IgG (p = .0003), anti-POVPC-IgG (p = .001) and ox-LDL-IC (p = .003). Serum anti-ox-LDL-IgG was positively correlated with SLEDAI (r = 0.34; p = .01), and negatively with C3 (r = -0.40; p = .01). Anti-9-HODE-IgG and anti-POVPC-IgG were positively correlated with SLEDAI and negatively with C4. CONCLUSIONS: Active SLE patients exhibit significantly increased serum levels of IgG anti-oxidized-lipid autoantibodies. Coordinated elevation of oxidized lipids, autoantibodies to these lipids, and immune complexes of these lipid-antibody components could potentially serve as pathogenic drivers and serum markers of SLE disease activity.

SERS substrate based on the flexible hybrid of polydimethylsiloxane and silver colloid decorated with silver nanoparticles.

Various flexible SERS sensors have attracted widespread concern in performing the direct identification of the analytes adsorbed on arbitrary surfaces. Here, a sample method was proposed to integrate plasmonic nanoparticles into polydimethylsiloxane (PDMS) to fabricate flexible substrate for the decoration of silver nanoparticles (AgNPs). The flexible SERS sensor based on AgNPs/AgNPs-PDMS offers highly sensitive Raman detection with enhancement factor up to 8.3 × 109, which can be attributed to the integrative effects from both the increase of the light absorption of the embedded AgNPs in PDMS substrate and the EM enhancement from the adjacent top-top, bottom-bottom and top-bottom AgNPs. After undergoing the cyclic mechanical deformation, the SERS substrate still maintains high mechanical stability and stable SERS signals. However, upon stretching the flexible substrate, there was an amusing phenomenon that SERS signals can be highly increased, which results from that the reduction of lateral nanogaps between top and bottom of the PDMS boundary strengthens the trigger of the plasmon coupling as demonstrated by the simulated result. This result reveals that the tuning and the coupling of the electromagnetic fields can be effectively controlled by the macroscopic mechanical solicitation. That will have an important significance for practical applications in strain-dependent sensors and detectors.

Serum vascular endothelial growth factor receptor 3 as a potential biomarker in psoriasis.

To discover novel biomarkers of psoriasis, a target-specific antibody array screening of serum samples from psoriasis patients was initially performed. The results revealed that vascular endothelial growth factor receptor 3 (VEGFR-3) was significantly elevated in the sera of psoriasis patients, compared to healthy controls. Next, ELISA validation studies in a larger cohort of psoriasis patients (N = 73) were conducted, which confirmed that serum VEGFR-3 was indeed significantly increased in patients with psoriasis compared to healthy controls (P < 0.001). Furthermore, receiver operating characteristic curve analysis demonstrated that serum VEGFR-3 exhibited potential in distinguishing healthy controls from psoriasis patients: area under the curve = 0.85, P < 0.001. In addition, serum levels of VEGFR-3 were correlated with Psoriasis Area Severity Index scores (R = 0.32, P = 0.008) in psoriasis patients. Interestingly, serum VEGFR-3 levels were significantly elevated in psoriatic arthritis compared to non-psoriatic arthritis (P = 0.026). A pilot longitudinal study demonstrated that serum levels of VEGFR-3 could reflect disease progression in psoriasis. Collectively, serum VEGFR-3 may have a clinical value in monitoring disease activity of psoriasis.

Three-Dimensional Printed Plate-Guided 125I Brachytherapy for Malignant Parotid Tumors.

PURPOSE: The treatment of malignant parotid tumors with 125I brachytherapy is rarely reported. This study evaluated the efficacy and dose and response of 125I brachytherapy in patients with malignant tumors. MATERIALS AND METHODS: From July 2014 through August 2017, 39 patients with malignant parotid tumors were treated with 125I brachytherapy. Thirty-five patients were treated with conservative surgical resection before brachytherapy. Four patients were treated with brachytherapy alone. Clinical outcomes and side effects were evaluated. Clinical factors were investigated to determine correlations with local control (LC) and side effects. RESULTS: Mean follow-up was 25 months (range, 7 to 47 months). The LC rate was 87.2% and the overall survival rate was 97.4%. High tumor grade and large tumor showed a propensity for local recurrence. Acute skin toxicity occurred in 87.2% of patients and grade 3 and 4 radioepidermitis was found in 20.5% of patients. In total, 89.7% of patients with facial nerve dysfunction recovered within 12 months. CONCLUSIONS: 125I brachytherapy was a feasible treatment option for patients with malignant parotid tumors. Although side effects were minimal, strict follow-up was necessary for patients treated with a high dose.

Expression and associations of TRAF1, BMI-1, ALDH1, and Lin28B in oral squamous cell carcinoma.

Tumor necrosis factor receptor-associated factor 1, an adaptor protein of tumor necrosis factor 2, is involved in classical nuclear factor (NF)-κB activation and lymphocyte recruitment. However, less is known about the expression and association of tumor necrosis factor receptor-associated factor 1 with cancer stem cell markers in oral squamous cell carcinoma. This study aimed to investigate the expression of tumor necrosis factor receptor-associated factor 1 and stem cell characteristic markers (lin28 homolog B, B cell-specific Moloney murine leukemia virus integration site 1, and aldehyde dehydrogenase 1) in oral squamous cell carcinoma and analyze their relations. Paraffin-embedded tissues of 78 oral squamous cell carcinomas, 39 normal oral mucosa, and 12 oral dysplasia tissues were employed in tissue microarrays, and the expression of tumor necrosis factor receptor-associated factor 1, B cell-specific Moloney murine leukemia virus integration site 1, aldehyde dehydrogenase 1, and lin28 homolog B was measured by immunohistostaining and digital pathological analysis. The expression of tumor necrosis factor receptor-associated factor 1 was higher in the oral squamous cell carcinoma group as compared with the expression in the oral mucosa (p < 0.01) and oral dysplasia (p < 0.001) groups. In addition, the expression of tumor necrosis factor receptor-associated factor 1 was associated with those of B cell-specific Moloney murine leukemia virus integration site 1, aldehyde dehydrogenase 1, and lin28 homolog B (p = 0.032, r2 = 0.109; p < 0.0001, r2 = 0.64; and p < 0.001, r2 = 0.16) in oral squamous cell carcinoma. The patient survival rate was lower in the highly expressed tumor necrosis factor receptor-associated factor 1 group, although the difference was not significant. The clustering analysis showed that tumor necrosis factor receptor-associated factor 1 was most related to aldehyde dehydrogenase 1. These findings suggest that tumor necrosis factor receptor-associated factor 1 has potential direct/indirect regulations with the cancer stem cell markers in oral squamous cell carcinoma, which may help in further analysis of the cancer stem cell characteristics.

Antibody-Array-Based Proteomic Screening of Serum Markers in Systemic Lupus Erythematosus: A Discovery Study.

A discovery study was carried out where serum samples from 22 systemic lupus erythematosus (SLE) patients and matched healthy controls were hybridized to antibody-coated glass slide arrays that interrogated the level of 274 human proteins. On the basis of these screens, 48 proteins were selected for ELISA-based validation in an independent cohort of 28 SLE patients. Whereas AXL, ferritin, and sTNFRII were significantly elevated in patients with active lupus nephritis (LN) relative to SLE patients who were quiescent, other molecules such as OPN, sTNFRI, sTNFRII, IGFBP2, SIGLEC5, FAS, and MMP10 exhibited the capacity to distinguish SLE from healthy controls with ROC AUC exceeding 90%, all with p < 0.001 significance. These serum markers were next tested in a cohort of 45 LN patients, where serum was obtained at the time of renal biopsy. In these patients, sTNFRII exhibited the strongest correlation with eGFR (r = -0.50, p = 0.0014) and serum creatinine (r = 0.57, p = 0.0001), although AXL, FAS, and IGFBP2 also correlated with these clinical measures of renal function. When concurrent renal biopsies from these patients were examined, serum FAS, IGFBP2, and TNFRII showed significant positive correlations with renal pathology activity index, while sTNFRII displayed the highest correlation with concurrently scored renal pathology chronicity index (r = 0.57, p = 0.001). Finally, in a longitudinal cohort of seven SLE patients examined at ∼3 month intervals, AXL, ICAM-1, IGFBP2, SIGLEC5, sTNFRII, and VCAM-1 demonstrated the ability to track with concurrent disease flare, with significant subject to subject variation. In summary, serum proteins have the capacity to identify patients with active nephritis, flares, and renal pathology activity or chronicity changes, although larger longitudinal cohort studies are warranted.

Heightened cleavage of Axl receptor tyrosine kinase by ADAM metalloproteases may contribute to disease pathogenesis in SLE.

Systemic lupus erythematosus (SLE) is characterized by antibody-mediated chronic inflammation in the kidney, lung, skin, and other organs to cause inflammation and damage. Several inflammatory pathways are dysregulated in SLE, and understanding these pathways may improve diagnosis and treatment. In one such pathway, Axl tyrosine kinase receptor responds to Gas6 ligand to block inflammation in leukocytes. A soluble form of the Axl receptor ectodomain (sAxl) is elevated in serum from patients with SLE and lupus-prone mice. We hypothesized that sAxl in SLE serum originates from the surface of leukocytes and that the loss of leukocyte Axl contributes to the disease. We determined that macrophages and B cells are a source of sAxl in SLE and in lupus-prone mice. Shedding of the Axl ectodomain from the leukocytes of lupus-prone mice is mediated by the matrix metalloproteases ADAM10 and TACE (ADAM17). Loss of Axl from lupus-prone macrophages renders them unresponsive to Gas6-induced anti-inflammatory signaling in vitro. This phenotype is rescued by combined ADAM10/TACE inhibition. Mice with Axl-deficient macrophages develop worse disease than controls when challenged with anti-glomerular basement membrane (anti-GBM) sera in an induced model of nephritis. ADAM10 and TACE also mediate human SLE PBMC Axl cleavage. Collectively, these studies indicate that increased metalloprotease-mediated cleavage of leukocyte Axl may contribute to end organ disease in lupus. They further suggest dual ADAM10/TACE inhibition as a potential therapeutic modality in SLE.

Hyperamylasemia as an Early Predictor of Mortality in Patients with Acute Paraquat Poisoning.

BACKGROUND Paraquat (PQ) is a non-selective and fast-acting contact herbicide which has been widely used in developing countries. Hyperamylasemia was reported in patients with PQ poisoning. This study investigated the predictive value and clinical characteristics of hyperamylasemia in patients with PQ poisoning. MATERIAL AND METHODS This study included 87 patients with acute PQ poisoning admitted from July 2012 to May 2015. Data were collected from medical records. Receiver operating characteristic (ROC) analysis was conducted to analyze the discriminatory potential of serum amylase with respect to 90-day mortality. RESULTS Of 87 patients, 29 patients had elevated serum amylase. We found that serum amylase was significantly higher among patients with AKI than those with non-AKI (p<0.001), and was an independent predictor of mortality (hazard ratio [HR]=3.644; 95% [CI], 1.684-7.881; p=0.001). The area under the ROC curve for the serum amylase (area under curve [AUC]=0.796; 95% [CI], 0.690-0.903) had a better discriminatory potential than plasma PQ concentration (0.698;0.570-0.825) or urinary PQ concentration (0.647;0.514-0.781) in predicting 90-day mortality. CONCLUSIONS Hyperamylasemia is a valuable early predictor of 90-day mortality in PQ poisoning.

Paraquat Poisoning Followed by Toxic Epidermal Necrolysis: A Report of Two Cases and Published Work Review.

Toxic epidermal necrolysis (TEN) is a life-threatening, typically drug-induced, mucocutaneous disease. Whether paraquat, one of the most widely used herbicides, could induce TEN is not known. We describe 2 paraquat-poisoned patients with TEN. Both patients presented erythema after hospital discharge following initial paraquat poisoning and then developed a widespread eruption of diffuse erythema on almost the whole body, with bullae, epidermal necrosis and sloughing. They were successfully treated with intravenous immunoglobulin and methylprednisolone. These clinical features were consistent with TEN caused by medications with a high risk to induce Stevens-Johnson syndrome/TEN. Moreover, it is suggested that both skin exposure and ingestion of paraquat could induce TEN. To our knowledge, this is the first case report of TEN related to paraquat poisoning.

Urinary angiostatin--a novel putative marker of renal pathology chronicity in lupus nephritis.

There is a critical need to identify biomarkers for Systemic Lupus Erythematosus (SLE) which has a high prevalence of renal failure. When urine from patients with lupus nephritis was recently screened for the levels of ∼280 molecules using an exploratory array-based proteomic platform, elevated angiostatin levels were noted. Angiostatin is a bioactive fragment of plasminogen, and has been known to have modulatory function in angiogenesis and inflammation. The significant elevation in urinary angiostatin was next validated in an independent cohort of SLE patients (n = 100) using ELISA. Among patients with SLE, urine angiostatin was significantly increased in active SLE compared with inactive SLE, correlating well with the SLEDAI disease activity index and SLICC renal activity score (r = 0.66, p < 0.0001). ROC curve analysis further confirmed that urinary angiostatin had the capacity to discriminate patients with active SLE from those with inactive disease. Patients with Class IV lupus nephritis exhibited the highest levels of urinary angiostatin. Immunohistochemistry staining localized angiostatin expression to the renal tubular cells in these patients. Finally, when paired urine-kidney samples procured concurrently from patients with LN were next examined, urine angiostatin levels correlated strongly with the renal pathology chronicity index, but not with the activity index. Given that Class IV lupus nephritis and renal pathology chronicity changes forebode poor renal and patient survival, urinary angiostatin emerges as a novel noninvasive marker of renal disease in SLE. Longitudinal studies are in progress to further assess the disease-predictive potential of urinary angiostatin.