Integrated proteome and malonylome analyses reveal the potential meaning of TLN1 and ACTB in end-stage renal disease.

BACKGROUND: End-stage renal disease (ESRD) is a condition that is characterized by the loss of kidney function. ESRD patients suffer from various endothelial dysfunctions, inflammation, and immune system defects. Lysine malonylation (Kmal) is a recently discovered post-translational modification (PTM). Although Kmal has the ability to regulate a wide range of biological processes in various organisms, its specific role in ESRD is limited. METHODS: In this study, the affinity enrichment and liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques have been used to create the first global proteome and malonyl proteome (malonylome) profiles of peripheral blood mononuclear cells (PBMCs) from twenty patients with ESRD and eighty-one controls. RESULTS: On analysis, 793 differentially expressed proteins (DEPs) and 12 differentially malonylated proteins (DMPs) with 16 Kmal sites were identified. The Rap1 signaling pathway and platelet activation pathway were found to be important in the development of chronic kidney disease (CKD), as were DMPs TLN1 and ACTB, as well as one malonylated site. One conserved Kmal motif was also discovered. CONCLUSIONS: These findings provided the first report on the Kmal profile in ESRD, which could be useful in understanding the potential role of lysine malonylation modification in the development of ESRD.

Predictors of Primary Functional Maturation of Autogenous Radiocephalic Arteriovenous Fistula in a Cohort of Asian Patients.

BACKGROUND: The aim of this study was to investigate the predictors of autogenous radiocephalic arteriovenous fistula (RCAVF) maturation. METHODS: This was a retrospective analysis of patients undergoing RCAVF creation from June 2013 to December 2018 at a single medical center. Comparison of the variables between the matured and nonmatured group was performed. RESULTS: A total of 277 patients (men, 173; 62.5%) with a mean age of 56.6 ± 16.9 years underwent primary RCAVF creation during the study period. The mean diameter of the cephalic vein and radial artery were 2.4 ± 0.6 mm (range 1.5 to 4.3 mm) and 2.3 ± 0.5 mm (range 1.5 to 4.0 mm), respectively. Primary functional maturation was achieved in 236 patients (236/277, 85%). There was no statistical significance between the matured and nonmatured group in terms of age (56.4 ± 14.8 vs. 58.1 ± 15.1, respectively; P = 0.498), coronary arterial disease (12% vs. 17%, respectively; P = 0.449), diabetes mellitus (42% vs. 39%, respectively; P = 0.864), smoking (26% vs. 22%, respectively; P = 0.699), or antiplatelet therapy (23% vs. 24%, respectively; P = 0.844). However, female gender (35% vs. 54%, respectively; P = 0.024), peripheral arterial disease (9% vs. 22%, respectively; P = 0.025), and small vein (2.4 ± 0.5 mm vs. 2.0 ± 0.5 mm, respectively; P < 0.01) and artery (2.4 ± 0.5 vs. 2.1 ± 0.4, respectively; P < 0.01) diameter were associated with the failure of maturation. The best cutoff diameter for the cephalic vein and radial artery was 1.85 mm and 2.05 mm, respectively. CONCLUSIONS: In this cohort of patients undergoing RCAVF creation, vein and artery diameter on preoperative ultrasound mapping was the predictor of functional maturation. Female gender and presence of peripheral arterial disease were associated with failure of maturation.

Delayed diagnosis of Angioimmunoblast T-cell lymphoma presenting with type II Cryoglobulinemia and acute kidney injury: a case report and narrative review of the literature.

BACKGROUND: Angioimmunoblastic T cell lymphoma (AITL) is an infrequent hematological malignancy with variable and often atypical presentations. The presence of dysproteinemia, autoantibodies and systemic involvement in AITL has often led to a delay in diagnosis or even misdiagnosis in practice. We herewith present a case of AITL that primarily presented with acute kidney injury associated with type II Cryoglobulinemia, the underlying cause was only identified 8 months after the emergence of initial symptoms. CASE PRESENTATION: A 67-year old woman presented with 2-month history of intermittent joint pain and a 3-day history of bilateral lower limb edema and acute kidney injury. Initial laboratory investigations showed marked hypocomplementemia with positive autoantibodies of ANA, anti-cardiolipin-IgM and direct antiglobulin. The serum and urinary Immunofixation and serum cryoglobulin tests were negative, while the serum free κ to λ light chain ratio was 0.231. A renal biopsy showed a diffuse proliferative glomerulonephritis with intracapillary pseudothrombi formation. There were orderly arranged microtubular structures of 20-35 nm in diameter in the subendothelial and mesangial area on electron microscopy. Shortly afterwards, the patient developed tingling affecting her finger tips and weak hands and legs. A diagnosis of cryoglobulinemia complicated with cryoglobulinemic glomerulonephritis and polyneuropathy was made. She responded well to methylprednisolone, plasma exchange and rituximab. However, 3 months later, she presented with generalized pruritic rash, weight loss, and inguinal lymphadenopathy. A subsequent inguinal excisional lymph node biopsy at month 8 revealed AITL as the underlying disease. CONCLUSIONS: AITL and its associated B cell dysregulation can give rise to autoimmunity and cryoglobulinemia which may conceal itself as the underlying disorder. In various clinical scenarios of auto-immune diseases, it is advisable that the clinicians should take into consideration the multi-faceted lymphoma.

Misplacement of Tunneled Hemodialysis Catheter into Azygos Vein: Left or Right Jugular Insertion Has Similar Susceptibility.

BACKGROUND: Central venous catheter (CVC) is commonly used to provide access for hemodialysis (HD) when arteriovenous access is not available. The misplacement of CVC into azygos vein (AV) is a rare but a potential serious complication. Previous reports communicated the opinion that left-sided catheterization predisposed to AV misplacement, but these reports concentrated on peripherally inserted CVCs, placed for indications rather than HD. Unintended AV misplacement of HD catheters (HDCs) has not been well studied. We seek to investigate factors associated with inadvertent AV miscannulation during HDC placement. METHODS: We are to present a case of unintentional misplacement of a tunneled HD catheter (tHDC) into the azygos arch from right internal jugular vein (RIJV) despite real-time fluoroscopy guidance. Additionally, we have undertaken a systematic literature search in Pubmed to study the anatomical and other factors related to unintended AV misposition in HD setting. RESULTS: From 2005 to August 31, 2018, a total of 11 articles containing 16 cases of misplacement of HDCs into AV were identified. Of the 17 cases of unintentional AV misposition including ours, the majority of the misguided HDCs (94.1%, 16/17) were tHDCs and only 1 case was related to a temporary (non-tunneled) catheter. Most catheter misplacements (88.2%, 15/17) were performed without real-time radiological guidance. The reported incidence of inadvertent AV cannulation from different institutions varied between 0.6% and 3.8%. Among the 16 misplaced tHDCs, the rates of AV misposition that arose from RIJV and left internal jugular vein (LIJV) insertion are even at 50%. CONCLUSIONS: Based upon anatomical and case studies, we have found that AV may join posterior aspect of superior vena cava at different directions and levels. Hence, this might explain why AV misplacement might occur whether an HDC is inserted from the LIJV or RIJV approach. By raising the awareness of this potential complication and how we may minimize it, we hope to reduce the future complication of AV misposition.

The transition of renal histopathology after immunosuppressive therapy in a woman with renal limited ANCA-associated vasculitis: a case report and literature review.

OBJECTIVES: The kidneys are frequently involved in antineutrophil cytoplasmic autoantibody (ANCA) associated small-vessel vasculitis (AASVV). The pathological hallmark of ANCA-associated glomerulonephritis (AAGN) is a pauci-immune necrotising crescentic glomerulonephritis. The histopathology of AAGN may change during the course of the disease as a consequence of immunosuppressive therapy. Herein, we report the pathological evolution of a case of AAGN. METHODS: We report a female presented with renal-limited AASVV, hypocomplementemia and nephrotic syndrome. The first renal biopsy revealed "crescentic" changes at presentation, but after treatment with immunosuppressive treatment, a second renal biopsy four years later showed "mixed" changes of AAGN and immune complex deposition mimicking a mesangial proliferative glomerulonephritis. A literature review was undertaken in order to understand these transformations and factors which determine the pathological transitions. RESULTS: AAGN is commonly described as a pauci-immune necrotising crescentic glomerulonephritis, but immune complex depositions have been frequently identified under electronic microscopy and is associated with greater levels of proteinuria. Acute lesions such as fibrinoid necrosis or glomerular crescent may completely disappear or reduce significantly after immunosuppressive therapy, but chronic changes may increase over time. CONCLUSIONS: Based on our review and the illustration of this case, the initial histopathology of an AAGN and its active fibrinoid necrosis and cellular glomerular crescent may disappear or resolve after immunosuppressive therapy with resulting non-distinctive feature. Understanding the transition may facilitate the clinical diagnosis and provide further insight into this disease.

Positive response of a hemodialysis patient with pure red cell aplasia on recombinant human erythropoietin therapy to cyclosporine and Roxadustat.

Recombinant human erythropoietin (rHuEPO) is commonly used to treat anemia associated with chronic kidney disease (CKD). EPO-induced Pure Red Cell Aplasia (PRCA) is a rare condition of profound anemia with EPO treatment. Upon finding the development of EPO-induced PRCA, the treatment requires immediate withdrawal of EPO therapy and initiate new treatments with immunosuppression or renal transplantation. Anti-EPO antibody assay is not always positive in EPO-induced PRCA. Here, we report a case on the sudden development of PRCA in a hemodialysis patient receiving EPO and how we treated the condition successfully with cyclosporine and subsequently maintained the hemoglobin with Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). Even though the anti-EPO antibody was negative by Enzyme Linked Immunosorbent Assay (ELISA) in our case, the clinical course, the markedly reduced reticulocyte count < 10,000/µL, the bone marrow (BM) biopsy revealing reduced erythroblasts, and its subsequent response to cyclosporine, were similar to EPO-induced PRCA. The clinical picture of EPO-induced PRCA, the limitation of the EPO-neutralizing antibody (Ab) assay, and treatment strategies were discussed.

Meticulous catheter care and aseptic approach reduce catheter-related bloodstream infections significantly in hemodialysis patients: A 5-year single center study.

AIM: The use of central venous catheters as hemodialysis vascular access is a major contributor to high bloodstream infection rate. In our dialysis unit in Shenzhen Guangdong Province China, we have developed and used our own dialysis catheter care protocol since May 2013 with good results. In this study, we would like to share our experience with the other units. METHODS: We have undertaken a 5-year retrospective analysis to determine our tunneled dialysis catheter-related blood stream infection rate by adding the number of infections divided by total number of catheter days × 1000. The results were compared with another study carried out in Henan Province China. Demographic data were summarized using descriptive statistics. Continuous and categorical variables were compared using t-test and χ2 test respectively. RESULTS: Between 2017 and 2021, a total of 216 tunneled dialysis catheters were managed by following our own dialysis access pathway and catheter care protocol. The tunneled dialysis catheter-related bloodstream infection rate was 0.0229 per 1000 catheter days in the 5-year period. CONCLUSION: Comparing with other published studies in China, our unit has achieved a very low rate of tunneled dialysis catheter-related bloodstream infection which has been sustained over time. This paper explores how our protocol and implementation might have contributed to the results.

The combination use of inclisiran and statins versus statins alone in the treatment of dyslipidemia in mainland China: a cost-effectiveness analysis.

Objective: Statin is well-established as a classical lipid-lowering drug, and its cost has reduced considerably in the past years. Inclisiran is a new and effective lipid-lowering drug given as a subcutaneous injection at 6-month intervals. This study aims to evaluate the cost-effectiveness of the combination use of inclisiran and statin versus statin alone for dyslipidemia in the mainland China population. Methods: The Markov decision-making model was used, and the clinical data and real-world data were collected at the University of Hong Kong-Shenzhen Hospital (HKU-SZH). Patients with cardiovascular disease (CVD) and blood lipid levels above the target on statin therapy were included as the target population and analyzed for cardiovascular events, future medical expenses, and the calculation made for the total life cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity analysis was conducted to evaluate the influence of parameter uncertainty on the base-case analysis results. Results: If inclisiran was priced at Chinese renminbi (RMB) 20,000.00 (USD 2,973.49) per injection, patients in the inclisiran and statin group would incur an incremental cost of RMB 449,233.56 (USD 66,789.60) compared with the statin group, and they would obtain 0.21 more QALYs in their life cycle. The subsequent ICER of RMB 2,127,756.78 (USD 316,343.32)/QALY was significantly higher than the willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China, which was RMB 257,094.00 (USD 38,223.33)/QALY, suggesting that the combined use of inclisiran and statin was not cost-effective. If the price of inclisiran were reduced to RMB 2,500.00 (USD 371.69)/injection, the ICER of patients in the inclisiran and statin group would become RMB 257,790.63 (USD 38,326.91)/QALY, which is slightly lower than the WTP threshold of 3 times the per capita GDP of China, indicating that the combined use of inclisiran and statin would be cost-effective. Conclusion: If inclisiran is priced at RMB 20,000.00 (USD 2,973.49)/injection, then the combined use of inclisiran and statins is not cost-effective compared with statin alone. It will be economical only if the price of inclisiran is reduced by more than 88%.

Bleeding Risk in Hemodialysis Patients.

Cardiovascular diseases are highly prevalent among patients on dialysis. For these diseases, antiplatelets and antithrombotic therapies including heparin, vitamin K antagonists, and direct oral anticoagulants, are being used. However, the benefit-risk balance of these therapies could differ for dialysis patients compared with the general population. This review article focuses on the bleeding risk associated with the use of heparin, antiplatelets, vitamin K antagonists, and direct oral anticoagulants in patients receiving hemodialysis.

Relationship of serum copper and zinc with kidney function and urinary albumin to creatinine ratio: Cross-sectional data from the NHANES 2011-2016.

BACKGROUND & OBJECTIVE: Chronic kidney disease (CKD) is a common condition in worldwide with underlying causes. The role of trace elements such as copper and zinc in CKD is uncertain. We aimed to examine the relationship of serum copper and zinc with kidney function status and explore its possible effect modifiers in the general population. METHODS: Data from 5353 National Health and Nutrition Examination Survey (NHANES) participants from 2011 to 2016 were analyzed for the role of trace elements in the age range 18 to 80 years. The kidney outcomes were reduced estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and increased urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g. RESULTS: Findings showed a significant positive association between serum copper and urinary ACR (OR = 1.04, 95% CI = 1.00-1.07). Serum copper levels of 18.0 µmol/L (median) or higher (reference level <18.0 µmol/L) were significantly associated with increased urinary ACR (OR = 1.67, 95% CI = 1.21-2.31) after adjusting for confounding factors. In contrast, there was a significant inverse association between serum zinc and reduced eGFR (OR = 0.89,95% CI = 0.81-0.99). Where serum zinc level was greater than 12.3 µmol/L (median), the prevalence of reduced eGFR was lower (OR = 0.65, 95% CI = 0.16-0.60). In addition, a stratified analysis based on various risk factors found that in those individuals with serum albumin greater than 43 g/L or systolic blood pressure greater than 120 mmHg, positive correlations between serum copper and risk of increased urinary ACR was more significant. CONCLUSIONS: Our findings suggest that the reference levels of serum copper and zinc levels in healthy individuals may be different from current understanding. If further studies substantiate the same, the results will be a useful guide for designing future clinical trials and nutritional guidelines.

The Causes and Consequences of miR-503 Dysregulation and Its Impact on Cardiovascular Disease and Cancer.

microRNAs (miRs) are short, non-coding RNAs that regulate gene expression by mRNA degradation or translational repression. Accumulated studies have demonstrated that miRs participate in various biological processes including cell differentiation, proliferation, apoptosis, metabolism and development, and the dysregulation of miRs expression are involved in different human diseases, such as neurological, cardiovascular disease and cancer. microRNA-503 (miR-503), one member of miR-16 family, has been studied widely in cardiovascular disease and cancer. In this review, we summarize and discuss the studies of miR-503 in vitro and in vivo, and how miR-503 regulates gene expression from different aspects of pathological processes of diseases, including carcinogenesis, angiogenesis, tissue fibrosis and oxidative stress; We will also discuss the mechanisms of dysregulation of miR-503, and whether miR-503 could be applied as a diagnostic marker or therapeutic target in cardiovascular disease or cancer.

In vivo development of heterogeneous glycopeptide-intermediate Staphylococcus aureus (hGISA), GISA and daptomycin resistance in a patient with meticillin-resistant S. aureus endocarditis.

We report a patient who developed a meticillin-resistant Staphylococcus aureus (MRSA) central venous catheter infection complicated by infective endocarditis. The patient was initially treated with glycopeptides, which led to the development of heterogeneous glycopeptide resistance, the detection of which required the use of a macro Etest screening test. Subsequently, the causative strain, confirmed by PFGE as a UK epidemic MRSA-15, was treated with daptomycin, and again resistance developed in vivo. The development in vivo of resistance to both these agents suggests that the resistance mechanisms may be associated. We suggest that the clinician managing MRSA infection should anticipate daptomycin resistance when reduced glycopeptide susceptibility is detected.

Gastrointestinal infection-related disseminated intravascular coagulation mimicking Shiga toxin-mediated hemolytic uremic syndrome - implications of classical clinical indexes in making the diagnosis: A case report and literature review.

BACKGROUND: Thrombocytopenia associated with acute kidney injury is a challenging disorder. Thrombotic microangiopathy (TMA) is a potentially life- or organ-threatening syndrome that can be induced by several disorders or medical interventions. There is overlap between the clinical presentation and pathophysiology of thrombotic thrombocytopenia purpura and hemolytic uremic syndrome (HUS), and to a lesser extent, disseminated intravascular coagulation (DIC). We describe a case to illustrate the potential diagnostic difficulty, especially at initial presentation. CASE SUMMARY: We reported a case of a 44-year-old woman that presented with diarrhea, thrombocytopenia, schistocytes, elevated serum lactate dehydrogenase (LDH) level and acute kidney injury. While the clinical presentation resembled that of Shiga toxin-induced HUS, the disease course was more consistent with gastrointestinal infection-related DIC. To aid in the accurate diagnosis of TMA and other associated disorders, we have undertaken a review and provided a clear interpretation of some typical biomarkers including schistocytes, LDH and platelet count, coagulation profile and more specific indexes of ADAMTS13, complement profile, and the isolation of Shiga toxin-producing Escherichia coli (commonly referred to as STEC). CONCLUSION: The use and correct interpretation of classical indexes of schistocyte, LDH, and platelet count is vital in diagnosing TMA and associated disorders. Understanding the characteristics of these biomarkers in the context of thrombocytopenia purpura, HUS and DIC will facilitate the accurate diagnosis and early initiation of appropriate treatment.

Fracture of a femoral hemodialysis catheter during placement in a man with metastatic cancer.

Central venous catheterization can be challenging in patients that had undergone repeated catheter placements. Ultrasound scan may overlook venous stenosis which is better visualized using venography. The use of venography should be considered to assess for venous stenosis or vascular anomalies in individuals with multiple catheterizations or in close proximity to cancer.

Fatal pancytopenia due to albendazole treatment for strongyloidiasis.

We report 7 cases of strongyloidiasis that had occurred from 2016 through 2017 in a tertiary hospital of southern China. Three of the 7 patients (age 66-77) with farming exposure many years ago developed symptomatic infection while receiving immunosuppressant for underlying medical conditions. The majority of them were treated with albendazole due to unavailability of ivermectin in mainland China. One of the 7 patients, with underlying IgG4 sclerosing cholangitis and secondary biliary cirrhosis was on immunosuppressives and developed severe pancytopenia 15 days after albendazole treatment. He ultimately died of polymicrobial sepsis. This was the second fatal case being reported in the literature as a consequence of albendazole-induced myelosuppression. We have undertaken a review of the literature regarding the use of albendazole for strongyloidiasis and its adverse effect with a focus on myelosuppression as a rare but potentially serious event.

Myelitis in systemic lupus erythematosus.

SLE-associated acute transverse myelitis (ATM) is a rare, but potentially severe complication of Systemic lupus erythematosus (SLE), and may lead to significant motor, sensory and autonomic dysfunctions in the central nervous system resulting in marked neurological deficits. It is important to recognize its clinical feature to allow timely diagnosis and management of this condition. In this review, we aimed to provide the reader with the understanding of its clinical presentation and classification, the underlying pathological, MRI (magnetic resonance imaging) appearance, and current status of management, with an emphasis on recent discoveries and advancements.

A new great wall: commissioning a new hospital in China.

A nationwide healthcare reform in China began in 2009, when the government injected GBP 85 billion to improve the healthcare coverage for its 1.3 billion population. Healthcare in China is primarily a market-based system, driven principally by demand, but the necessary supervision is relatively ineffective. There is a lack of trust between patients, who act as paying clients, and doctors, who often put the institution first, leading to frequent medical disputes. The University of Hong Kong Shenzhen Hospital is a joint venture between the city of Shenzhen and the University, with the mission to provide a new healthcare model in China. A clear process is in place to improve the clinical standard while a clean governance structure is set up. The hospital has ushered in many new initiatives. It is hoped that these will serve as a model for healthcare reform in China.