Emergency attendances and hospitalisations for complications after transrectal ultrasound-guided prostate biopsies: a five-year retrospective multicentre study.

INTRODUCTION: Transrectal ultrasound-guided (TRUS) prostate biopsy is an established procedure for diagnosis of prostate cancer. Complications after TRUS biopsy are not well reported in Hong Kong. This study evaluated the 5-year incidences of TRUS biopsy complications and potential risk factors for those complications. METHODS: This was a retrospective review of biopsies performed from 2013 to 2017 in two local hospitals, using data retrieved from electronic medical records. The primary outcome was the occurrence of complications requiring either emergency attendances or hospitalisations within 30 days after biopsy. Potential risk factors were examined using multiple logistic regression analysis. RESULTS: In total, 1699 men were included (mean age ± standard deviation: 67 ± 7 years; median prostate-specific antigen level: 7.9 µg/L [interquartile range, 5.5-12.6 µg/L]); 4.3% had pre-biopsy bacteriuria. Overall, 5.7% and 3.8% of post-biopsy complications required emergency attendances and hospitalisations, respectively. Gross haematuria and rectal bleeding requiring emergency attendances developed in 2.1% and 0.4% of men; 0.8% and 0.4% required hospitalisations. Furthermore, 1.5% of men developed acute urinary retention requiring hospitalisations; 1.9% and 1.2% had post-biopsy infections requiring emergency attendances and hospitalisations, respectively, and 0.9% had urosepsis requiring hospitalisations. Prostate volume >48 cc was associated with an increased risk of post-biopsy retention (odds ratio 2.75, 95% confidence interval: 1.23-4.17). CONCLUSIONS: The rate of overall complications after TRUS biopsy was low. The most common complications requiring emergency attendances and hospitalisations were gross haematuria and acute urinary retention, respectively. Prostate volume >48 cc increased the risk of post-biopsy urinary retention.

Development of high-throughput and high sensitivity capillary gel electrophoresis platform method for Western, Eastern, and Venezuelan equine encephalitis (WEVEE) virus like particles (VLPs) purity determination and characterization.

In this paper, we describe development of a high-throughput, highly sensitive method based on Lab Chip CGE-SDS platform for purity determination and characterization of virus-like particle (VLP) vaccines. A capillary gel electrophoresis approach requiring about 41 s per sample for analysis and demonstrating sensitivity to protein initial concentrations as low as 20 µg/mL, this method has been used previously to evaluate monoclonal antibodies, but this application for lot release assay of VLPs using this platform is unique. The method was qualified and shown to be accurate for the quantitation of VLP purity. Assay repeatability was confirmed to be less than 2% relative standard deviation of the mean (% RSD) with interday precision less than 2% RSD. The assay can evaluate purified VLPs in a concentration range of 20-249 µg/mL for VEE and 20-250 µg/mL for EEE and WEE VLPs.

Initial results of selective renal parenchymal clamping with an adjustable kidney clamp in nephron-sparing surgery: an easy way to minimise renal ischaemia.

INTRODUCTION: A renal parenchymal clamp has been used at our centre since March 2012. It is used in position over the kidney to achieve optimal vascular control of a tumour while minimising parenchymal ischaemia. This study aimed to report the feasibility, surgical outcome, and oncological control of a kidney clamp in partial nephrectomy. METHODS: This study was conducted at a teaching hospital in Hong Kong. Partial nephrectomies performed from January 2009 to March 2015 were reviewed. The tumour characteristics and surgical outcomes of kidney clamp were studied and compared with traditional hilar clamping. RESULTS: A total of 92 patients were identified during the study period. Kidney clamps were used in 20 patients and hilar clamping in 72, with a mean follow-up of 27 and 37 months, respectively. For patients in whom a kidney clamp was applied, all tumours were exophytic to a different extent and the majority (90%) were located at the polar region. The PADUA (preoperative aspects and dimensions used for an anatomical) classification nephrometry score was also lower than those in whom hilar clamping was used (7.07 vs 8.34; P=0.002). The clamp was used in open, laparoscopic, and robot-assisted surgery. Operating time was shorter (207 ± 72 mins vs 306 ± 80 mins; P<0.001) and estimated blood loss was lower (205 ± 191 mL vs 331 ± 275 mL; P=0.045) with kidney clamp. No acute kidney injury occurred. Postoperative renal function was comparable between the two groups. CONCLUSIONS: Partial nephrectomy using parenchymal clamping is safe and feasible in selected cases. The postoperative renal function and oncological control were satisfactory.

Identifying and quantifying secondhand smoke in source and receptor rooms: logistic regression and chemical mass balance approaches.

Identifying and quantifying secondhand tobacco smoke (SHS) that drifts between multiunit homes is critical to assessing exposure. Twenty-three different gaseous and particulate measurements were taken during controlled emissions from smoked cigarettes and six other common indoor source types in 60 single-room and 13 two-room experiments. We used measurements from the 60 single-room experiments for (i) the fitting of logistic regression models to predict the likelihood of SHS and (ii) the creation of source profiles for chemical mass balance (CMB) analysis to estimate source apportionment. We then applied these regression models and source profiles to the independent data set of 13 two-room experiments. Several logistic regression models correctly predicted the presence of cigarette smoke more than 80% of the time in both source and receptor rooms, with one model correct in 100% of applicable cases. CMB analysis of the source room provided significant PM2.5 concentration estimates of all true sources in 9 of 13 experiments and was half-correct (i.e., included an erroneous source or missed a true source) in the remaining four. In the receptor room, CMB provided significant estimates of all true sources in 9 of 13 experiments and was half-correct in another two.

Controlled experiments measuring personal exposure to PM2.5 in close proximity to cigarette smoking.

Few measurements of exposure to secondhand smoke (SHS) in close proximity to a smoker are available. Recent health studies have demonstrated an association between acute (<2 h) exposures to high concentrations of SHS and increased risk of cardiovascular and respiratory disease. We performed 15 experiments inside naturally ventilated homes and 16 in outdoor locations, each with 2-4 non-smokers sitting near a cigarette smoker. The smoker's and non-smokers' real-time exposures to PM2.5 from SHS were measured by using TSI SidePak monitors to sample their breathing zones. In 87% of the residential indoor experiments, the smoker received the highest average exposure to SHS, with PM2.5 concentrations ranging from 50-630 µg/m(3) . During the active smoking period, individual non-smokers sitting within approximately 1 m of a smoker had average SHS exposures ranging from negligible up to >160 µg/m(3) of PM2.5 . The average incremental exposure of the non-smokers was higher indoors (42 µg/m(3) , n = 35) than outdoors (29 µg/m(3) , n = 47), but the overall indoor and outdoor frequency distributions were similar. The 10-s PM2.5 averages during the smoking periods showed great variability, with multiple high concentrations of short duration (microplumes) both indoors and outdoors.

Laparoscopic liver resection: lessons learnt after 100 cases.

OBJECTIVE: To share our institutional experience in laparoscopic liver resection and our learning curve after the first 100 cases of laparoscopic liver resection. DESIGN: Case series with internal comparison. SETTING: A regional hospital in Hong Kong. PATIENTS: Our institution started performing laparoscopic liver resection since 2006. All patients who underwent laparoscopic liver resections from March 2006 to October 2012 were identified in a prospectively collected database. The demographic data and operative outcomes of these patients were extracted, and results of the early (from March 2006 to May 2010) and late (from June 2010 to October 2012) study periods were compared. RESULTS: Between March 2006 and October 2012, 100 laparoscopic liver resections were performed for 98 patients in the Department of Surgery, Kwong Wah Hospital, Hong Kong. They were 69 (70%) males and 29 (30%) females, and the median age was 65 years. The final histological diagnoses were as follows: hepatocellular carcinoma (n=72), colorectal liver metastases (n=14), intrahepatic cholangiocarcinoma (n=4), and benign disease (n=10). There were more anatomical resections, major hepatectomies as well as resections of more anatomically challenging right-sided and posterosuperior lesions in the late versus the early period; however, operative outcomes remained comparable in both periods. CONCLUSION: Laparoscopic hepatectomies are feasible with growing experience. Bearing in mind the diversity in the level of operative techniques with various types of laparoscopic liver resections, more experience is needed to overcome the learning curve.

Clinical Outcomes of Conservative Treatment for Low-Risk Ductal Carcinoma in Situ: A Systematic Review and Pooled Analysis.

AIMS: The current gold standard of treatment for ductal carcinoma in situ (DCIS) is surgical resection with or without adjuvant radiotherapy. However, the increased detection and radical treatment of DCIS did not result in a declined incidence of invasive breast cancers, leading to the debate if DCIS has been overtreated. While ongoing randomised controlled trials on active surveillance of DCIS are still in progress, this systematic review aims to evaluate the best evidence on conservative treatment for DCIS from the literature. MATERIALS AND METHODS: This systematic review was conducted in line with the PRISMA statement. We included all relevant studies published up to June 2022 for analysis. The primary outcomes were overall survival and breast cancer-specific survival (BCSS) of conservative treatment for DCIS. RESULTS: Three studies, with a total of 34 007 women with low-risk DCIS, were included in the analysis. Active and conservative treatments both resulted in excellent 10-year BCSS, with no statistically insignificant difference (98.6% versus 96.0%, 31 478 women). One study comparing 5-year BCSS of active and conservative treatments only in subjects aged over 80 years also reported [AQ1]an insignificant difference (98.2% versus 96.0%, 2529 women). One study measuring 5- and 10-year overall survival between the treatment groups also reported [AQ1]an insignificant difference (5-year: 96.2% versus 92.4%; 10-year: 85.6% versus 86.7%, 31 106 women). CONCLUSION: BCSS between active and conservative treatment for women with low-risk DCIS is both excellent and comparable, suggesting that conservative treatment is a possible alternative without compromising survival.

Plasma glucose-lowering action of allantoin is induced by activation of imidazoline I-2 receptors in streptozotocin-induced diabetic rats.

Allantoin, an active principle of yam, is documented to lower plasma glucose in diabetic rats. However, action mechanisms of allantoin remain obscure. It has been indicated that metformin shows ability to activate imidazoline I-2 receptors (I-2R) to lower blood sugar. Allantoin has also a chemical structure similar to metformin; both belong to guanidinium derivative. Thus, it is of special interest to know the effect of allantoin on I-2R. In the present study, the marked plasma glucose-lowering action of allantoin in streptozotocin-induced type-1 like diabetic rats was blocked by specific I-2R antagonist, BU224, in a dose-dependent manner. Also, the increase of ß-endorphin release by allantoin was blocked by BU224 in the same manner. Otherwise, amiloride at the dose sufficient to block I-2AR abolished the allantoin-induced ß-endorphin release and inhibited the blood glucose-lowering action of allantoin markedly but not completely. The direct effect of allantoin on glucose uptake in isolated skeletal muscle was also blocked by BU224. Also, the phosphorylation of AMPK in isolated skeletal muscle was raised by allantoin in a concentration-dependent manner. More-over, insulin sensitivity in diabetic rats was markedly increased by allantoin and this action was also blocked by BU224. These results suggest that allantoin has an ability to activate imidazoline I-2R while I-2AR is linked to the increase of ß-endorphin release and I-2BR is related to other actions including the influence in skeletal muscle for lowering of blood glucose in type-1 like diabetic rats. Thus, allantoin can be developed to treat diabetic disorders in the future.

Inhibition of insulin degrading enzyme by racecadotril in the brain of Wistar rats.

Racecadotril is an enkephalinase inhibitor used to treat abdominal discomfort in the clinic. The blood-glucose lowering action of racecadotril has been observed in rats; however, the mechanisms remain obscure. 8-week-old Wistar rats were intravenously injected with racecadotril and the levels of insulin in the brain were measured. Additionally, brain homogenates were co-incubated with racecadotril or thiorphan to evaluate insulin degrading enzyme (IDE) activity. Otherwise, rats were pretreated by intracerebroventricular (i. c. v.) injection of insulin antibody or glibenclamide at a dose sufficient to inhibit K (ATP) channels prior to injection of racecadotril. Moreover, rats were vagotomized to evaluate the role of the cholinergic nerve. Racecadotril significantly decreased the plasma glucose in rats; this action of racecadotril was abolished by i. c. v. pretreatment with insulin antibody or glibenclamide. Also, i. c. v. injection of thiorphan, the active form of racecadotril, lowered blood glucose, but this effect disappeared in the presence of the insulin antibody. In rat brain homogenates, racecadotril and thiorphan inhibited IDE activity and increased the cerebral insulin level. The blood-glucose lowering action of racecadotril or thiorphan was diminished in vagotomized rats. Our results suggest that racecadotril lowers blood glucose mainly through inhibition of IDE activity and increases endogenous insulin in the brain. Subsequently, the increased insulin might activate insulin receptor, which opens the K (ATP) channel and induces peripheral insulin release through the vagal nerve. Thus, we provide the new finding that racecadotril has the ability to inhibit IDE in rat brain.

Activation of imidazoline I-2B receptor by metformin to increase glucose uptake in skeletal muscle.

Metformin (dimethylbiguanide) belongs to guanidinium-derivative and is widely used for treatment of diabetic disorders in clinic. Metformin lowers blood glucose in diabetic animals through increase of glucose uptake into skeletal muscle. Recent evidence indicates that activation of imidazoline I2B receptor (I2BR) by guanidinium-derivatives also increased glucose uptake; however, the effect of metformin on I2BR is still unknown. The blood glucose levels were determined by a glucose kit. The ability of glucose uptake into isolated skeletal muscle or cultured C2C12 cells was determined using 2-[14C]-deoxyglucose as tracer. The expressions of 5' AMP-activated protein kinase (AMPK) and glucose transporter 4 (GLUT-4) were identified by Western blotting analysis. The metformin-induced blood glucose-lowering action was dose-dependently blocked by BU224, a specific I2R antagonist, in Wistar rats. Also, similar reversion by BU224 was observed in isolated skeletal muscle regarding the metformin-induced glucose uptake. Moreover, AMPK phosphorylation by metformin was concentration-dependently reduced by BU224 in isolated skeletal muscle. In addition, signals for metformin increased glucose uptake were identified via I2R/PI3K/PKC/AMPK dependent pathway in C2C12 cells. Thus, we suggest that metformin can activate I2BR to increase glucose uptake and I2BR will be a new target for diabetic therapy.

Decrease of blood lipids induced by Shan-Zha (fruit of Crataegus pinnatifida) is mainly related to an increase of PPARα in liver of mice fed high-fat diet.

Hyperlipidemia is an important risk factor for cardiovascular diseases. Agents for the treatment of hyperlipidemia are well-developed in the clinic while PPARα is a target for lipid-lowering agents. Shan-Zha (Crataegus pinnatifida) is a traditional Chinese medicine used to increase digestion. Also, Shan-Zha fruit extract showed merit to improve obesity and hyperlipidemia in hamsters; however, the mechanism remained obscure. In the present study, hypertriglycemia and hypercholesterolemia were induced by high fat diet in C57BL/6 J male mice. Then, they were orally administered with Shan-Zha fruit extract at an effective dose of 250 mg/kg for 7 days. The liver was removed to estimate the expressions of PPARα and ß-oxidation-related enzyme. Oral intake of Shan-Zha extract significantly improved hyperlipidemia in high fat diet-fed mice with an increase of PPARα expression in liver. Also, expression of PPARα-regulated ß-oxidation-related enzymes was raised in liver by Shan-Zha extract. However, adipose tissue and others were not modified by this treatment of Shan-Zha fruit extract. Thus, Shan-Zha can increase the expression of PPARα to facilitate ß-oxidation-related enzymes in liver for lipid degradation and blood lipid decrement. Also, this is the first report showing Shan-Zha fruit extract can influence liver to lower hyperlipidemia prior to the action in adipose tissue.

A novel mechanism for decreasing plasma lipid level from imidazoline I-1 receptor activation in high fat diet-fed mice.

The imidazoline I-1 receptor (I-1 R) agonists are widely used to lower blood pressure, but their effects on hyperlipidemia are still obscure. The present study is aimed to evaluate the possible mechanism(s) of I-1 R in the regulation of lipid homeostasis. Farnesoid X receptor (FXR) plays an important role in blood lipid homeostasis; however, the role of FXR in rilmenidine-induced blood lipid lowering action is still unknown. Thus, we administered rilmenidine, a selective agonist of I-1 R, into high fat diet-fed (HFD) mice showing hypertriglyceridemia and hypercholesterolemia. Rilmenidine significantly ameliorated hyperlipidemia in HFD mice after 7 days of administration. Pretreatment with efaroxan, at a dose sufficient to inhibit I-1 R activation, blocked the effects of rilmenidine. Also, in cultured HepG2 cells, rilmenidine dose-dependently induced the expression of farnesoid X receptor (FXR). The rilmenidine-induced FXR expression and FXR-related genes were blocked by efaroxan. However, rilmenidine treatment did not affect the expression of enzymes related to ß-oxidation. In conclusion, activation of I-1 R may activate FXR to lower plasma lipids, suggesting I-1 R as a new target for the treatment of hyperlipidemia.

Pharmacological activation of peroxisome proliferator-activated receptor δ improves insulin resistance and hepatic steatosis in high fat diet-induced diabetic mice.

The mechanisms regarding hepatic steatosis related to hepatic insulin resistance have been well documented. However, the agents for treatment of hepatic steatosis and insulin resistance remain poorly developed. Peroxisome proliferator-activated receptors (PPARs) are transcription factors that are responsible for the regulation of glucose and/or lipid metabolism. There are 3 distinct isoforms of PPARs family: PPARα, PPARγ, and PPARδ. Both PPARα and PPARγ agonists are widely used in clinic for the treatment of hyperlipidemia and hyperglycemia. However, the therapeutic efficacy of PPARδ agonists for diabetic disorders remains obscure. In the present study, we used L-165041 as PPARδ agonist to treat the high fat diet (HFD) fed mice. Administration of L-165041 improved the hepatic steatosis and increased the insulin sensitivity in HFD-mice. In addition to the histological identification of hepatic steatosis, the improvement of insulin sensitivity was characterized by the enhanced insulin signals and the increase of hepatic glycogen content. This is the first report showing that pharmacological activation of PPARδ improves insulin resistance in diet-induced diabetic mice. Thus, we suggest that pharmacological activation of PPARδ may be a new strategy for the treatment of diabetic patients with hepatic steatosis.

Multimedia manuscript: laparoscopic resection of hepatocellular carcinoma at segment 7: the posterior approach to anatomic resection.

BACKGROUND: Open anatomical liver resections remain one of the most effective treatments of hepatocellular carcinoma (HCC) and results in better recurrence-free and overall survival compared to nonanatomical resections [1]. On the other hand, laparoscopic hepatectomies for HCC have recently emerged with the benefits of reduced blood loss, shorter hospital stay, and less severe wound pain [2, 3]. Classically, liver lesions considered suitable for laparoscopic resection were those small tumors (<4 cm) located over the anterior and left lateral segments [3]. However, we would like to expand the current indications and here we present our techniques of laparoscopic anatomical resection for a HCC that was located at right posteriosuperior segment 7. METHODS: Our patient was a 60-year-old gentleman who had Child's A hepatitis B cirrhosis and was on entecavir. During a follow-up CT scan, a 2.6-cm segment 7 lesion with early arterial enhancement and contrast washout was noted and was subsequently confirmed with arteriogram. α-Fetoprotein was 3 ng/ml (normal < 20 ng/ml). The video demonstrates a posterior approach to laparoscopic resection of segment 7. RESULTS: Operative time was 510 min. Blood loss was 800 ml and no perioperative transfusion was required. Postoperative recovery was uneventful and only simple oral analgesics were required for pain control. He was discharged on postoperative day 6. Histology showed a moderately differentiated hepatocellular carcinoma and all resection margins were clear. Subsequent follow-up CT scan 6 months after the operation showed no evidence of recurrence and α-fetoprotein level was normal. CONCLUSIONS: Laparoscopic hepatectomy for HCC over the right posterior segment of the liver is feasible in selected patients with favorable results in terms of wound size, postoperative recovery, and hospital stay. Maximal liver conservation was achieved in performing oncologic anatomical resection of segment 7 instead of a posterior sectionectomy. On the other hand, a posterior approach was recommended because it allowed early intrahepatic control of pedicles and identification of the right hepatic vein to guide parenchymal transection along the intersegmental plane.

Evolution of the haemagglutinin gene of the influenza A(H1N1)2009 virus isolated in Hong Kong, 2009-2011.

Phylogenetic analysis of the haemagglutinin (HA) gene shows that the influenza A(H1N1)2009 viruses collected in Hong Kong clustered in two main branches characterised by the E391E and E391K amino acids. The main branch E391K evolved in two sub-branches with N142D and S202T mutations that first appeared in March and July 2010, respectively, with the latter becoming the predominant strain. These genetic variants that emerged display similar antigenic characteristics.Concurrent with genetic surveillance, laboratories should continue monitoring the circulating viruses antigenically.

Observation of symmetrical reflection sidebands in a silica suspended-core fiber Bragg grating.

We have observed symmetrical sidebands in reflection from Bragg grating written in a silica suspended-core fiber, which are caused by longitudinal periodic refractive index modulation in the Ge-doped suspended-core fiber with a core diameter of approximately 1.3 microm. Our simulation shows that the effective refractive index of the guided mode varied by 0.023% along the fiber with a period of approximately 650 microm. The periodic index variation can lead to amplitude modulation of fiber Bragg gratings, which can be studied by observing the spectra of a fiber Bragg grating written in the Ge-doped core. In addition, we have also characterized the temperature and strain responses of the fiber Bragg gratings, and showed that both responses in the suspended-core fiber are 20 to 25% lower than that of a fiber Bragg grating written on a conventional fiber.

Increase of plasma insulin by racecadotril, an inhibitor of enkephalinase, in Wistar rats.

Racecadotril is known as an inhibitor of enkephalinase. Increase of plasma insulin by racecadotril has been observed in rats while the mechanism of the action remains obscure. In the present study, intravenous injection of male Wistar rats with racecadotril significantly decreased blood glucose levels. However, this effect of racecadotril was not modified by naloxone at the dose sufficient to block opioid receptors. Thus, the blood glucose-lowering action of racecadotril might be through an endogenous opioid independent mechanism. Otherwise, we found that C-peptide content was also raised by racecadotril in parallel with the increase of insulin in Wistar rats. Thus, the blood glucose-lowering action of racecadotril was related to insulin secretion, but not through the inhibition of plasma insulin degradation. In addition, racecadotril showed no direct effect on insulin secretion in isolated islets or cultured HIT-T15 beta cells. The increase of plasma insulin and blood glucose-lowering action induced by racecadotril were reduced by pretreatment with atropine and enhanced by physotigmine. Direct inhibition of cholinesterase was not observed in brain homogenates treated with racecadotril. Moreover, actions of racecadotril were significantly reduced in rats receiving hemicholinium-3 at a sufficient dose to decrease endogenous acetylcholine. Activation of cholinergic tone is possibly involved in the blood glucose-lowering effect of racecadotril. Our results suggested that racecadotril increased insulin secretion to lower blood glucose mainly via regulation of parasympathetic tone in Wistar rats.

Indomethacin activates peroxisome proliferator-activated receptor γ to improve insulin resistance in cotton pellet granuloma model.

Inflammation is involved in the development of insulin resistance and diabetes. However, the effectiveness of anti-inflammatory drugs in diabetic therapy remains obscure. In the present study, the possible mechanisms of indomethacin, one of the nonsteroidal anti-inflammatory drugs, in the improvement of insulin resistance were investigated. Indomethacin treatment significantly decreased cotton pellet implantation induced white blood cell count elevation and immune cells infiltration in epididymal white adipose tissue. Also, cotton pellet implantation induced impaired glucose utilization and insulin resistance were improved by indomethacin. The decrement in phosphoinsulin receptor and phospho-Akt levels induced by cotton pellet implantation was improved by indomethacin as well. Moreover, indomethacin decreased cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in epididymal white adipose tissue with a marked reduction of prostaglandin 2 (PGE2) and nitrite/nitrate (NOx) levels in cotton pellet-implanted mice. Furthermore, pretreatment of peroxisome proliferator-activated receptor γ (PPARγ) antagonist, GW9662 not only reversed indomethacin-modified COX-2 and iNOS levels but also reversed indomethacin-improved insulin sensitivity determined by homeostasis model assessment-insulin resistance (HOMA-IR). Taken together, indomethacin might elevate the expression of PPARγ to decrease serum NOx and PGE2 to result in the improvement of insulin resistance.