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Introduction Over the past 17 years (2002–2018), 898,831 people participated in the Hong Kong Standard Chartered Marathon (HKSCM). Purpose We aim to study the incidence of marathon-related sudden cardiac arrest (SCA) and non-fatal myocardial injury (NFMI). Methods All the HKSCM related admissions between 2002 and 2017 were retrieved from the accident and emergency department admission records. We reviewed the data of HKSCM runners admitted for SCA and NFMI. Results Fourteen and thirty-nine runners were admitted for SCA (Mean age 38±13 years-old, 12 men) and NFMI (Mean age 42±12 years-old; 34 men) respectively. Among the SCA runners, the arrest rhythms could not be retrieved in 3 cases. In the remaining 11 SCA runners, the arrest rhythms were ventricular fibrillation (VF) (N=6), pulseless-electrical activity (PEA) (N=3), and asystole (N=2). Nine of the 14 SCA runners were successfully resuscitated. Only 2 out of the 14 SCA runners had significant atherosclerotic coronary artery disease (CAD) requiring coronary angioplasty. Among the SCA runners, the etiologies of cardiac arrest were myocardial infarction (MI) (N=2), ischemic cardiomyopathy with VF (N=1), idiopathic VF (N=3), malignant coronary anomaly (N=1), and idiopathic (N=5). Percutaneous coronary intervention (PCI) was performed in 2 SCA runner with MI. Implantable cardioverter-defibrillators were implanted in 1 resuscitated runner with VF. Postmortem examination of the 3 deceased runners showed significant CAD in two and was unrevealing in one. Among the 39 NFMI runners, coronary angiograms (CAG) or CT coronary angiogram were performed in 14 cases (36%), which showed minor CAD or unremarkable findings in 7 runners, and significant CAD in 7 runners. PCI and coronary artery bypass were performed in 5 and 2 NFMI runners respectively. Only 8 out of 39 NFMI runners reported chest pain. Significant ischemic ECG changes were detected in 9 out of 39 NFMI runners. Invasive CAGs were not performed in the remaining NFMI runners due to low pre-test likelihood of CAD and normal non-invasive test results. Conclusions The incidence of SCA and mortality among HKSCM runners was 1.56 per 100,000 and 0.56 per 100,000 respectively. The incidence of NFMI was 4.3 per 100,000. Coronary artery disease, coronary anomaly and idiopathic VF were the commonest etiologies of SCA.

Background The role of the kallikrein-kinin system in diabetic nephropathy remains controversial. Methods and results High-glucose (HG) super-induced interleukin (IL)-6, CCL-2, transforming growth factor (TGF)-beta, vascular endothelial growth factor (VEGF) and B(2)K receptor (B(2)KR) mRNA in cultured proximal tubular epithelial cells (PTEC), whereas bradykinin (BK) upregulated IL-6, CCL-2 and TGF-beta mRNA. HG activated mitogen-activated protein kinase (MAPK) p42/p44 and protein kinase C (PKC) signals, whereas BK only activated MAPK. Tubular expression of these mediators and tissue kallikrein 1 (KLK1) was confirmed in human diabetic kidney biopsies. Inhibition of MAPK p42/p44 by PD98059 partially reduced HG and BK induction of IL-6, CCL-2 and TGF-beta, whereas inhibition of PKC by staurosporine partially reduced HG- but not BK-induced overexpression of these cytokines and that of VEGF. Staurosporine and PD98059 synergistically reduced the effect of HG on IL-6, CCL-2 and TGF-beta expression. The B(2)KR blocker, icatibant, downregulated BK- and HG-induced MAPK p42/p44 but not HG-induced PKC activation and partially reduced both HG- and BK-induced IL-6, CCL-2 and TGF-beta secretion. HG stimulated expression of KLK1 and low-molecular-weight kininogen (LMWK) and its downstream effects were attenuated by aprotinin (tissue kallikrein inhibitor). The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, rosiglitazone, attenuated HG-induced PKC but not HG- or BK- induced MAPK p42/44 activation and reduced HG-stimulated VEGF, along with IL-6, CCL-2 and TGF-beta secretion. Rosiglitazone plus icatibant further reduced these effects of HG. Conclusions In conclusion, HG stimulates tubular proinflammatory, profibrotic and angiogenic signals, which is partly mediated through BK via MAPK signalling and partly through PKC independent of BK. The potential therapeutic role of complementary B(2)KR blockade and PPAR-gamma activation deserves clinical investigation.

TWIST, a helix-loop-helix transcription factor, is highly expressed in many types of human cancer. We have previously found that TWIST confers prostate cancer cells with an enhanced metastatic potential through promoting epithelial-mesenchymal transition (EMT) and a high TWIST expression in human prostate cancer is associated with an increased metastatic potential. The predilection of prostate cancer cells to metastasize to bone may be due to two interplaying mechanisms (i) by increasing the rate of bone remodeling and (ii) by undergoing osteomimicry. We further studied the role of TWIST in promoting prostate cancer to bone metastasis. TWIST expression in PC3, a metastatic prostate cancer cell line, was silenced by small interfering RNA and we found that conditioned medium from PC3 with lower TWIST expression had a lower activity on stimulating osteoclast differentiation and higher activity on stimulating osteoblast mineralization. In addition, we found that these effects were, at least partly, associated with TWIST-induced expression of dickkopf homolog 1 (DKK-1), a factor that promotes osteolytic metastasis. We also examined TWIST and RUNX2 expressions during osteogenic induction of an organ-confined prostate cancer cell, 22Rv1. We observed increased TWIST and RUNX2 expressions upon osteogenic induction and downregulation of TWIST through short hairpin RNA reduced the induction level of RUNX2. In summary, our results suggest that, in addition to EMT, TWIST may also promote prostate cancer to bone metastasis by modulating prostate cancer cell-mediated bone remodeling via regulating the expression of a secretory factor, DKK-1, and enhancing osteomimicry of prostate cancer cells, probably, via RUNX2.

The effect of phospholipids on gentamicin-induced nephrotoxicity was studied in Sprague-Dawley rats. Group 1a (5 rats) were given daily intraperitoneal injections of 100 mg/kg of gentamicin and sacrificed on day 7. Group 1b (10 rats) were similarly treated but were sacrificed on day 14. Group 2a (5 rats) were given 30 mg/kg of phospholipids for 6 days and sacrificed on day 7, serving as phospholipid controls. Group 2b (5 rats) were similarly treated, and from day 7 onwards daily intraperitoneal injections of 100 mg/kg of gentamicin were given while oral phospholipids were continued until the rats were sacrificed 7 days after gentamicin treatment. Group 2c (10 rats) were treated in the same manner as group 2b but the animals were sacrificed on day 28 after gentamicin treatment. Group 3 (10 rats) were given 30 mg/kg of phospholipids concurrently with intraperitoneal gentamicin injections and were sacrificed on day 28. Protein concentrations, N-acetyl-beta-glucosaminidase (NAG) activities and creatinine were measured in 24-h urine samples. Serum creatinine concentrations were measured in blood samples and 24-h creatinine clearance calculated. Gentamicin concentrations were determined in kidney tissues from which sections were also taken for light- and electron-microscopy. Results showed that gentamicin induced a marked increase in NAG and protein excretion, and a marked decrease in creatinine clearance with six rats succumbing to uraemia. Phospholipid treatment, whether started before or concurrently with gentamicin injections, reduced gentamicin-induced nephrotoxicity. The rats did not lose weight. Urinary excretion of NAG and protein was significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

A retrospective analysis of the records of 46 patients with adult-onset mesangiocapillary glomerulonephritis seen over a period of 15 years is reported. There were 28 males and 18 females with a mean age of 34 years. Mean observation period was 60 months. All patients had renal biopsies and characteristic changes, but no dense deposit variant was seen. HBsAg was positive in 20 per cent of the patients tested whereas in the general population it was about 10 per cent. Nephrotic syndrome was the commonest presentation. There was a mean delay of 8.5 months between the onset of symptoms and renal biopsy. Nineteen patients were given steroid/immunosuppressive therapy while 27 received no specific treatment. At the time of review, renal function was stable in 13 patients but progressively deteriorating in 33. In the latter, the slope of the graph of reciprocal of creatinine versus time could be accurately determined. Steroid/immunosuppressive therapy did not influence the rate of progression of renal failure but appeared to hasten and induce more partial remissions of the nephrotic state. There was no difference in cumulative renal survival between treated and untreated patients, and between HBsAg-positive and negative patients. Overall, 23 patients required dialysis/renal transplantation and an additional four had died of end-stage renal failure at the time of this review.