Increased urinary angiotensinogen precedes the onset of albuminuria in normotensive type 2 diabetic patients

It was previously reported that intrarenal renin angiotensin system (RAS) plays a pivotal role in the onset and progression of diabetic nephropathy (DN). Urinary angiotensinogen (UAGT) was employed as a special index of the intrarenal RAS status and enhanced significantly at a very early stage of chronic kidney disease and type 1 diabetes. On the basis of these findings, the present study was performed to test the hypothesis that UAGT levels are increase even before the development of DN in type 2 diabetic patients without hypertension. 102 patients with type 2 diabetes mellitus (T2DM) and 18 healthy volunteers were studied cross-sectionally. Clinical data were collected and morning spot urine samples were obtained from all participants. UAGT levels were detected by an enzyme-linked immunosorbent assay (ELISA). As a result, UAGT to creatinine ratio (UAGT/Cr) was significantly enhanced in T2DM patients before the appearance of urinary albumin (UALB) and further increased to a greater degree in albuminuric patients. UAGT/Cr levels were positively correlated with Log (UALB to creatinine ratio) and diastolic blood pressure, but negatively correlated with estimated glomerular filtration rate. These data indicate that elevated UAGT levels precede the onset of albuminuria in normotensive T2DM patients. UAGT might potentially serve as an early marker to determine intrarenal RAS activity and predict progressive kidney disease in T2DM patients without hypertension.     

Immune system defects in DiGeorge syndrome and association with clinical course

We evaluated 18 DiGeorge syndrome (DGS) patients and aimed to investigate the immunological changes in this population. DGS patients with low naive CD4⁺T and CD8⁺T cells were defined as high‐risk (HR) patients, whereas patients with normal numbers of naive CD4⁺ and CD8⁺T cells were defined as standard risk (SR) patients. Level of serum IgM, CD3⁺ T cell counts and percentages of class‐switched memory B cells were significantly low in HR group compared to SR ones. Severe infections and persistent hypoparathyroidism were detected significantly higher in HR group. Patients with reduced percentages of class‐switched B cells had earlier onset of infection, lower blood IgM, lower CD4⁺ and CD8⁺T counts than patients with normal class‐switched memory B cells. Decreased levels of IgM were associated with low numbers of naive CD4⁺ and recent thymic emigrants T cells. Monitoring the immune changes of patients with DGS would be useful to predict the severe phenotype of disease.     

Idiopathic gingival fibromatosis. A case report.

Gingival fibromatosis is a progressive gingival enlargement caused by an over growth of the collagenous element of the gingival fibrous connective tissue. Pharmacologically induced, hereditary (familial) and idiopathic forms of gingival fibromatosis are recognized. This paper reports a case of idiopathic gingival fibromatosis in a 13 year old boy involving the right maxillary and mandibular arches who had also been treated 3 years back for a gingival enlargement involving the left maxillary and mandibular arches. The enlargement was quite sever and caused significant esthetic and functional problems on both occasions.     

Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations

We recently identified DEPDC5 as the gene for familial focal epilepsy with variable foci and found mutations in >10% of small families with nonlesional focal epilepsy. Here we show that DEPDC5 mutations are associated with both lesional and nonlesional epilepsies, even within the same family. DEPDC5‐associated malformations include bottom‐of‐the‐sulcus dysplasia (3 members from 2 families), and focal band heterotopia (1 individual). DEPDC5 negatively regulates the mammalian target of rapamycin (mTOR) pathway, which plays a key role in cell growth. The clinicoradiological phenotypes associated with DEPDC5 mutations share features with the archetypal mTORopathy, tuberous sclerosis, raising the possibility of therapies targeted to this pathway. Ann Neurol 2014;75:782–787     

A Necessary Step Toward Kidney Donor Safety: The Transition From Locking Polymer Clips to Transfixion Techniques in Laparoscopic Donor Nephrectomy

Donor safety is of paramount importance in addressing end-stage renal failure through living kidney transplantation. The United States Food and Drug Administration (FDA) issued a Class II recall on the use of Hem-o-lok (Teleflex, Limerick, Pennsylvania, United States) polymer clips on the renal artery in laparoscopic donor nephrectomy (LDN) in June 2006 following 3 reported cases of donor deaths secondary to slipped ligature. The National University Hospital of Singapore made the transition regarding hilar control in minimally invasive donor nephrectomy, from using polymer and titanium clips to transfixion techniques (pure or hand-assisted laparoscopic) via laparoscopic staples or intracorporeal suturing, respectively. This study assessed safety during the transition in arterial transfixion techniques in minimally invasive donor nephrectomy for both donors and recipients. Forty-five consecutive kidney donors underwent donor nephrectomy over a 2-year period starting from June 2010. A total of 37 donors who underwent LDN (pure laparoscopic or hand-assisted laparoscopic) were included in the analysis. Of the 37 patients, 23 kidney donors had renal arterial control using Hem-o-lok while 14 patients from November 2011 onward underwent transfixion of the renal artery. The 2 groups of donor who underwent renal arterial control by either clips ligature or transfixion technique were comparable. The outcomes for the recipients in each group were similar with no statistical difference between postoperative creatinine level, incidence of delayed graft function, or graft survival at 1 year. We conclude that the transition in renal arterial control technique to transfixion techniques in LDN in line with FDA recommendation is feasible and affords equivalent donor and recipient outcomes.     

Potential of (18)~F-FDG-PET as a valuable adjunct to clinical and response assessment in rheumatoid arthritis and seronegative spondyloarthropathies

AIM: To evaluate the role of fluorine-18-labeled fluorodeoxyglucose positron emission tomography (18F-FDG PET) in various rheumatic diseases and its potential in the early assessment of treatment response in a limited number of patients. METHODS: This study involved 28 newly diagnosed patients, of these 17 had rheumatoid arthritis (RA) and 11 had seronegative spondyloarthropathy (SSA). In the SSA group, 7 patients had ankylosing spondylitis, 3 had psoriatic arthritis, and one had non-specific SSA. Patients with RA were selected as per the American College of Rheumatology criteria. One hour after FDG injection, a whole body PET scan was performed from the skull vertex to below the knee joints using a GE Advance dedicated PET scanner. Separate scans were acquired for both upper and lower limbs. Post-treatment scans were performed in 9 patients in the RA group (at 6-9 wk from baseline) and in 1 patient with psoriatic arthropathy. The pattern of FDG uptake was analysed visually and quantified as maximum standardized uptake value (SUVmax) in a standard region of interest. Metabolic response on the scan was assessed qualitatively and quantitatively and was correlated with clinical assessment. RESULTS: The qualitative FDG uptake was in agreement with the clinically involved joints, erythrocyte sedimentation rate, C-reactive protein values and the clinical assessment by the rheumatologist. All 17 patients in the RA group showed the highest FDG avidity in painful/swollen/tender joints. The uptake pattern was homogeneous, intense and poly-articular in distribution. Hypermetabolism in the regional nodes (axillary nodes in the case of upper limb joint involvement and inguinal nodes in lower limb joints) was a constant feature in patients with RA. Multiple other extra-articular lesions were also observed including thyroid glands (in associated thyroiditis) and in the subcutaneous nodules. Treatment response was better appreciated using SUVmax values than visual interpretation, when compared with clinical evaluation. Four patients showed a favourable response, while 3 had stable disease and 2 showed disease progression. The resolution of regional nodal uptake (axillary or inguinal nodes based on site of joint involvement) in RA following disease modifying anti-rheumatoid drugs was noteworthy, which could be regarded as an additional parameter for identifying responding patients. In the SSA group, uptake in the affected joint was heterogeneous, low grade and nonsymmetrical. In particular, there was intense tendon and muscular uptake corresponding to symptomatic joints. The patients with psoriatic arthritis showed intense FDG uptake in the joints and soft tissue. CONCLUSION: 18F-FDG PET accurately delineates the ongoing inflammatory activity in various rheumatic diseases (both at articular and extra-articular sites) and relates well to clinical symptoms. Different metabolic patterns on FDG-PET scanning in RA and SSA can have important implications for their diagnosis and management in the future with the support of larger studies. FDG-PET molecular imaging is also a sensitive tool in the early assessment of treatment response, especially when using quantitative information. With these benefits, FDG-PET could play a pivotal clinical role in the management of inflammatory joint disorders in the future.     

血液透析患者血清铜兰蛋白与铁缺乏、炎症反应及过氧化反应的关系

目的探讨维持性血液透析患者血清铜兰蛋白与铁缺乏、炎症反应及过氧化反应之间的关系.方法检测68名维持性血液透析患者血清铜兰蛋白、血清铁、转铁蛋白、铁蛋白以及白细胞介素-6、肿瘤坏死因子-α、丙二醛,分析铜兰蛋白与上述各指标间的相互关系. 结果与正常人相比,透析患者血清铜兰蛋白显著增高,血清铁和转铁蛋白显著降低,白细胞介素-6、肿瘤坏死因子-α和丙二醛显著增高;血清铁和转铁蛋白与铜兰蛋白水平呈显著负相关,白细胞介素-6、肿瘤坏死因子-α和丙二醛与铜兰蛋白水平呈显著正相关. 结论血清铜兰蛋白水平检测可综合反映透析患者体内铁缺乏、炎症状态和过氧化反应水平.     

Anticoagulation for coexisting bioprosthetic aortic valve thrombosis and anticoagulant-related bleeding: “A double edge sword”

The choice of anticoagulant agents for newly implanted bioprosthetic valve varies significantly, particularly in the presence of postoperative atrial fibrillation with increasing use of nonvitamin K oral anticoagulation (NOACs) in recent years. We reported a challenging case with a coexisting bioprosthetic aortic valve thrombosis and significant anticoagulant-related bleeding. Clinical management strategy and brief literature review were presented.     

Post-operative Abdominal Wall Mucormycosis—a Case Series

Mucormycosis is caused by saprophtytic fungi which cause acute invasive zygomycosis. It clinically presents with necrosis, and on histopathology, acute and chronic infiltrates are seen. It rarely infects a healthy host, but is devastating in an immunocompromised host. We studied five cases with post-operative abdominal wall mucormycosis, three females and two males. Three patients were post-operative while the other two had mucormycosis following trauma and infection was found in sutured wound. All were initially diagnosed as cases of necrotizing fasciitis. Two patients eventually survived after intensive medical therapy and extensive debridements.