Delayed diagnosis of tuberculosis: risk factors and effect on mortality among older adults in Hong Kong.

OBJECTIVE: To assess the risk factors and effects of delayed diagnosis on tuberculosis (TB) mortality in Hong Kong. METHODS: All consecutive patients with TB notified in 2010 were tracked through their clinical records for treatment outcome until 2012. All TB cases notified or confirmed after death were identified for a mortality survey on the timing and causes of death. RESULTS: Of 5092 TB cases notified, 1061 (20.9%) died within 2 years of notification; 211 (4.1%) patients died before notification, 683 (13.4%) died within the first year, and 167 (3.3%) died within the second year after notification. Among the 211 cases with TB notified after death, only 30 were certified to have died from TB. However, 52 (24.6%) died from unspecified pneumonia/sepsis possibly related to pulmonary TB. If these cases are counted, the total TB-related deaths increases from 191 to 243. In 82 (33.7%) of these, TB was notified after death. Over 60% of cases in which TB diagnosed after death involved patients aged ≥80 years and a similar proportion had an advance care directive against resuscitation or investigation. Independent factors for TB notified after death included female sex, living in an old age home, drug abuse, malignancy other than lung cancer, sputum TB smear negative, sputum TB culture positive, and chest X-ray not done. CONCLUSIONS: High mortality was observed among patients with TB aged ≥80 years. Increased vigilance is warranted to avoid delayed diagnosis and reduce the transmission risk, especially among elderly patients with co-morbidities living in old age homes.

Angiogenesis in spontaneous tumors and implications for comparative tumor biology.

Blood supply is essential for development and growth of tumors and angiogenesis is the fundamental process of new blood vessel formation from preexisting ones. Angiogenesis is a prognostic indicator for a variety of tumors, and it coincides with increased shedding of neoplastic cells into the circulation and metastasis. Several molecules such as cell surface receptors, growth factors, and enzymes are involved in this process. While antiangiogenic therapy for cancer has been proposed over 20 years ago, it has garnered much controversy in recent years within the scientific community. The complex relationships between the angiogenic signaling cascade and antiangiogenic substances have indicated the angiogenic pathway as a valid target for anticancer drug development and VEGF has become the primary antiangiogenic drug target. This review discusses the basic and clinical perspectives of angiogenesis highlighting the importance of comparative biology in understanding tumor angiogenesis and the integration of these model systems for future drug development.

Aspirin desensitisation for Chinese patients with coronary artery disease.

OBJECTIVE. To assess the efficacy and safety of aspirin desensitisation in Chinese patients with coronary artery disease. DESIGN. Case series. SETTING. A regional hospital in Hong Kong. PATIENTS. Chinese patients with coronary artery disease and a history of a hypersensitivity reaction to aspirin or non-steroidal anti-inflammatory drug, who underwent aspirin desensitisation between February 2008 and July 2012. RESULTS. There were 24 Chinese patients with coronary artery disease who were admitted to our unit for aspirin desensitisation during this period. The majority (79%) were clinical admissions for desensitisation; eight (33%) of them developed a hypersensitivity reaction during desensitisation. Half of the latter had only limited cutaneous reactions and were able to complete the desensitisation protocol and developed aspirin tolerance. Overall, 20 (83%) of the patients were successfully desensitised at the initial attempt. No serious adverse reactions occurred in the cohort. Twelve of the patients had significant coronary artery disease revealed by coronary angiography and received a percutaneous coronary intervention, nine of whom received drug-eluting stents while three received bare metal stents due to financial constraints. All 11 successfully desensitised patients received aspirin and clopidogrel as double antiplatelet therapy after percutaneous coronary intervention. The remaining patient had a bare metal stent implant due to failed aspirin desensitisation. CONCLUSION. Given the potentially different genetic basis of aspirin hypersensitivity in different ethnicities, recourse to desensitisation in the Chinese population has not previously been addressed. This study demonstrated that aspirin desensitisation using a rapid protocol can be performed effectively and safely in Chinese patients. Our results were comparable to those in other reported studies involving other ethnicities. Successful aspirin desensitisation permits patients to pursue long-term double antiplatelet therapy that includes aspirin after percutaneous coronary intervention, and thus allows the use of drug-eluting stents as a feasible option.

Reperfusion strategy for ST-segment elevation myocardial infarction: trend over a 10-year period.

OBJECTIVES. To review the 10-year trend of reperfusion strategies in patients with ST-segment elevation myocardial infarction, and the adoption rate of percutaneous coronary interventions as opposed to thrombolytic therapy. Also to explore why some patients did not receive reperfusion therapy, and document changes in reperfusion strategies after the introduction of primary percutaneous coronary intervention programmes. DESIGN. Case series. SETTING. A regional hospital, Hong Kong. PATIENTS. All patients with ST-segment elevation myocardial infarction from January 2000 to December 2009. RESULTS. There were 1835 patients with ST-segment elevation myocardial infarction in that period, of which 1179 (64.3%) received reperfusion therapy (thrombolytic therapy, 46.0%; primary percutaneous coronary intervention, 17.5%; emergency coronary artery bypass graft, 0.7%). After introduction of the primary percutaneous coronary intervention programme, significantly more ST-segment elevation myocardial infarction cases underwent that particular intervention (1.6% in 2000 increasing to 30.6% in 2009), while the proportion receiving thrombolytic therapy declined (57.4% in 2000 decreasing to 35.0% in 2009). Seven reasons for no reperfusion therapy were identified. The commonest ones were delayed presentation (45.1%), succumbed before reperfusion (16.0%), multiple medical co-morbidities (15.2%), and contra-indication to thrombolytic therapy (14.8%). The proportion without reperfusion therapy due to a contra-indication to thrombolytic therapy declined (22.7% in 2000 decreasing to 4.9% to 2009), whilst an increasing proportion received primary percutaneous coronary interventions. CONCLUSIONS. Primary percutaneous coronary intervention is increasingly used as the reperfusion therapy in ST-segment elevation myocardial infarction and is replacing thrombolytic therapy, though the latter still remains a mainstay of therapy. A significant proportion of ST-segment elevation myocardial infarction cases received no reperfusion due to various reasons.

Primary percutaneous coronary intervention for ST elevation myocardial infarction: performance with focus on timeliness of treatment.

OBJECTIVE: To review primary percutaneous coronary interventions performed for patients with ST elevation myocardial infarction with a focus on door-to-treatment time, especially after introduction of a new management programme in November 2003. DESIGN: Retrospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: All patients with ST elevation myocardial infarction who underwent primary percutaneous coronary intervention in our hospital from January 2002 to December 2007. RESULTS: In all, 209 patients with ST elevation myocardial infarction had primary percutaneous coronary interventions between January 2002 and December 2007; 140 of them were admitted within office hours, 125 of whom came directly from Accident and Emergency Department. The mean door-to-balloon time of these patients was 115 minutes, and in 41% the time was less than 90 minutes (as recommended by the American College of Cardiology/American Heart Association guidelines). Since introduction of the new programme, the mean door-to-balloon time has diminished significantly, from 146 to 116 minutes (P=0.047). Delay in diagnosis (28%) and Cardiac Catheterization Laboratory being occupied (20%) were the two most common reasons for prolonged door-to-balloon times. CONCLUSION: We achieved satisfactory performance in our primary percutaneous coronary intervention programme, providing timely reperfusion therapy for patients with ST elevation myocardial infarction. A well-organised and systematic clinical pathway is a prerequisite for a centre that provides a timely and effective primary percutaneous coronary intervention service for patients with ST elevation myocardial infarction. Better public education and greater awareness on the part of medical service providers are needed, so as to facilitate urgent revascularisation and improve outcomes in patients with ST elevation myocardial infarction.

Analyses of fluoroquinolones and Clostridium difficile-associated diarrhoea in tuberculosis patients.

SETTING: Systematic studies of fluoroquinolones (FQs) and Clostridium difficile-associated diarrhoea (CDAD) are scarce among tuberculosis (TB) patients, in whom fluoroquinolones (FQs) are increasingly used. OBJECTIVE: To evaluate the relationship between FQs and CDAD among TB patients. DESIGN: Retrospective cohort and nested case-control analyses were conducted among 3319 hospital patients on anti-tuberculosis treatment from 1999 to 2005. Each case of CDAD was matched by three sex- and age-matched controls randomly selected from the rest of the cohort. Not every case was confirmed by C. difficile cytotoxins. RESULTS: Among 38 cases studied, the incidence of CDAD, which was 28.2 (95%CI 20.3-38.3) per 100 000 patient-days overall, increased from 12.9 (95%CI 5.8-25.3) for patients aged <60 years to 26.6 (95%CI 15.5-42.8) for those aged between 60 and 79 years, and 66.9 (95%CI 39.8-106.1) for those aged >79 years. Univariate analysis showed a significant association between CDAD and age, FQs, non-FQ antibiotics, serum albumin level, duration of hospital stay and nasogastric feeding. Only duration of hospital stay and nasogastric feeding remained significant on multivariable analysis. CONCLUSION: The risk of CDAD due to FQs among TB patients is probably modest after controlling for sex, age, non-FQ antibiotics, serum albumin level, duration of hospital stay and nasogastric feeding.

Non-operative management of small cell carcinoma of esophagus.

Primary small cell carcinoma of the esophagus (SmCC) is an uncommon aggressive tumor characterized by early systemic dissemination and poor prognosis, regardless of the methods of treatment. The optimal treatment strategy remains uncertain. A retrospective study was conducted to review the results of non-operative treatment for patients with limited and metastatic esophageal SmCC. Between 1993 and 2003, 10 patients were diagnosed to have primary esophageal SmCC in our institution. Six of them had disseminated diseases, whereas the other four had limited disease upon diagnosis. All patients were managed non-operatively by either chemotherapy and/or radiotherapy. The overall median survival was 8 months (range, 2-62 months). The survival was 4-62 months for patients with limited disease, whereas it was 2-10 months for patients with disseminated disease at initial diagnosis. In summary, the current study demonstrated satisfactory palliation could be achieved with chemo-radiation for patients with limited disease; however, the ultimate role of primary chemo-radiation for esophageal SmCC must await results from randomized trials.

Relationship between glutathione S-transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics.

BACKGROUND: Asthma is a disease associated with oxidative stress. The glutathione S-transferases (GST) are a group of enzymes that protect cells from oxidative stress. Functional genetic polymorphisms of GST genes (GSTT1, GSTM1 and GSTP1) have previously been reported. OBJECTIVE: To investigate the association of GST gene polymorphisms and its enzyme activity with the risk of asthma in Hong Kong Chinese adults. METHODS: An age- and smoking status-matched case-control study was carried out on 315 patients with asthma and 315 healthy controls. Genotyping was carried out on genomic DNA using the PCR and/or restriction fragment length polymorphism (PCR-RFLP). Plasma GST activity was measured by fluorometric assay. RESULTS: The distribution of various genotypes or alleles of the GSTT1, GSTM1 and GSTP1 was not significantly different between patients with asthma and healthy controls. The GSTM1 null genotype was found to be protective from the development of asthma in atopic subjects (odds ratios 0.55, 95% confidence interval 0.34-0.90; P=0.017). However, there was no association between GSTT1 and GSTM1 null genotypes and enzyme activity. GSTP1 codon 105 Val variants led to reduced plasma GST activity in healthy controls. Asthma patients had elevated plasma GST activity compared with healthy controls irrespective of their genotypes (P<0.001). CONCLUSION: Our data suggest that among atopic subjects, the GSTM1 null genotype is associated with a decreased risk for asthma despite increased level of plasma GST activity in asthma, but it could not distinguish whether this increase is a potentially protective compensatory effect or a pathogenic factor.

Non-operative management of endoscopic iatrogenic haemobilia: case report and review of literature.

Haemobilia denotes an abnormal communication between a vessel of the splanchnic circulation and the biliary system. Patients typically presents with the triad of abdominal pain, upper gastrointestinal haemorrhage, and jaundice. Common causes for haemobilia are iatrogenic causes secondary to hepatobiliary system instrumentation and trauma. Management of patients with haemodynamic significant haemobilia is aimed at stopping bleeding, maintaining continuous flow of biliary system, and cure of the underlying aetiology. Iatrogenic haemobilia after ERCP polyethylene biliary endoprosthesis placement is extremely uncommon. Herein we present a case of iatrogenic haemobilia triggered by biliary endoprosthesis placement and was successfully managed by non-operative treatment. The management algorithm for a rational approach to haemobilia is discussed.

Primary closure versus T-tube drainage after laparoscopic choledochotomy for common bile duct stones.

BACKGROUND/AIMS: To demonstrate the safety and feasibility of primary closure of the common bile duct (CBD) after laparoscopic choledochotomy in patients with CBD stones. Traditionally, the CBD is closed with T-tube drainage after choledochotomy and removal of CBD stones. However, the insertion of a T-tube is not without complication and the patients have to carry it for several weeks before removal. In the laparoscopic era, surgery is performed with minimally invasive techniques in order to reduce the trauma inflicted on patients, hasten their recovery and hence reduce the hospital stay. T-tube insertion seems to negate these benefits and we believe that primary closure can be as safe as closure with T-tube drainage. METHODOLOGY: This is a retrospective analysis of patients who underwent primary closure of the CBD after successful laparoscopic choledochotomy for ductal stones between January 2000 and December 2003. A concurrent control group of patients who underwent T-tube drainage was used for comparison. RESULTS: Of the 64 patients that underwent laparoscopic exploration of the CBD, 24 (37%) underwent transcystic duct approach and 40 (63%) underwent choledochotomy. There were three open conversions (5%). Stone clearance was achieved in all patients with successful laparoscopic choledochotomy (100%). Of the 38 successful laparoscopic choledochotomies, 12 had primary closure of the CBD and 26 had closure with T-tube drainage. There was no mortality in both groups. One patient in the primary closure group suffered from paralytic ileus and small subhepatic collection which was treated conservatively. The median operative time (90 vs. 120 minutes, p=0.002) and postoperative stay (5 vs. 8.5 days, p=0.003) were shorter in the primary closure group when compared with the T-tube group. CONCLUSIONS: Primary closure of the CBD is feasible and as safe as T-tube insertion after laparoscopic choledochotomy for stone disease.

Laparoscopic exploration of common bile duct in difficult choledocholithiasis.

BACKGROUND: This review investigated the role played by laparoscopic exploration of the common bile duct (LECBD) in the management of difficult choledocholithiasis. METHODS: This retrospective study reviewed a prospective database of LECBD for difficult choledocholithiasis during the period 1995 to 2003. RESULTS: Of the 97 LECBDs performed in the authors' center from 1995 to 2003, 25 were performed for difficult choledocholithiasis. Difficult choledocholithiasis was defined as failure of endoscopic stone retrieval for the following reasons: access and cannulation difficulty, the difficult nature of common bile duct (CBD) stones, and the presence of endoscopic retrograde cholangiopancreatography (ERCP)-related complications. There were seven unsuccessful cannulations because of previous gastrectomy (n = 5) and periampullary diverticulum (n = 2). Among the 18 patients with failed endoscopic extraction, there were 10 impacted stones, 2 incomplete stone clearances after multiple attempts, 2 type 2 Mirizzi syndromes, 1 proximal stent migration, 1 repeated post-ERCP pancreatitis, 1 situs inversus, and 1 stricture at the distal common bile duct. There were 14 male and 11 female patients with a mean age of 67.8 +/- 15 years. Initial presentations included cholangitis (n = 14, 56%), biliary colic (n = 3, 12%), jaundice/deranged liver function ( n = 5, 20%), cholecystitis (n = 2, 8%), and pancreatitis (n = 1, 4%). Regarding the approach for LECBD, there were 2 transcystic duct explorations and 23 choledochotomies. The mean operative time was 149.4 +/- 49.3 min, and there were three conversions (12%). The stone clearance rate was 100%, and no recurrence was detected during a mean follow-up period of 16.8 months. Five complications were encountered, which included bile leak (3 patients) and wound infection (2 patients). When the results were compared with the remaining 72 LECBDs for nondifficult stones during the same period, the complication rate, conversion rate, and rate of residual stones were similar despite a longer operation time (149.4 +/- 49.4 min vs 121.6 +/- 50.5 min). CONCLUSION: When ERCP is impossible or stone retrieval is incomplete, LECBD is the solution to difficult CBD stones.

Routine use of laparoscopic repair for perforated peptic ulcer.

BACKGROUND: Laparoscopic repair of perforated peptic ulcer was reported in 1990 but has not gained wide acceptance. The aim of this study was to evaluate the safety and efficacy of laparoscopic repair for perforated peptic ulcer in routine clinical practice. METHODS: This was a prospective analysis of 172 patients who underwent laparoscopic repair of a perforated peptic ulcer between July 1997 and June 2003. RESULTS: One hundred and seventy-two patients of mean age 54 (range 14-93) years had perforated peptic ulcer diagnosed by laparoscopy. There were 172 duodenal ulcers, 22 prepyloric and 13 non-juxtapyloric gastric ulcers. One hundred and sixty-five patients underwent omental patch closure of perforations; there were six Pólya gastrectomies and one ulcerectomy. Thirty-seven patients (21.5 per cent) required conversion to laparotomy. The mean operating time was 64.8 (range 14-180) min. The median postoperative requirement for intramuscular pethidine was one dose. The median postoperative hospital stay was 6 days. Complications occurred in 28 patients (16.3 per cent) resulting in three reoperations. Six patients with intra-abdominal collections were managed by percutaneous drainage. Two patients who underwent conversion developed a wound infection. Fourteen patients (8.1 per cent) died, 11 of whom were American Society of Anesthesiologists grade III and IV. CONCLUSION: Laparoscopic repair of perforated peptic ulcer is a safe emergency procedure in routine clinical practice for patients with perforated pyloroduodenal ulcer.

Chondroitinase ABC enhances axonal regrowth through Schwann cell-seeded guidance channels after spinal cord injury.

Grafting of Schwann cell-seeded channels into hemisected adult rat thoracic spinal cords has been tested as a strategy to bridge the injured cord. Despite success in guiding axonal growth into the graft, regeneration across the distal graft-host interface into the host spinal cord was limited. We hypothesized that chondroitin sulfate (CS) glycoforms deposited at the gliotic front of the interface constitute a molecular barrier to axonal growth into the host cord. Because CS glycoforms deposited by purified astrocytes in vitro were removable by digestion with chondroitinase ABC, we attempted to achieve likewise by infusion of the enzyme to the host side of the interface. By 1 month post-treatment, significant numbers of regenerating axons crossed an interface that was subdued in macrophage/microglia reaction and decreased in CS-immunopositivity. The axons extended as far into the caudal cord as 5 mm, in contrast to nil in vehicle-infused controls. Fascicular organizations of axon-Schwann cell units within the regenerated tissue cable were better-preserved in enzyme-treated cords than in vehicle-infused controls. We conclude that CS glycoforms deposited during gliosis at the distal graft-host interface could be cleared by the in vivo action of chondroitinase ABC to improve prospects of axonal regeneration into the host spinal cord.

Smoking and tuberculosis in Hong Kong.

OBJECTIVE: To study the relationship between smoking and tuberculosis in Hong Kong. METHOD: Indirect sex and age adjustment was used to compare the prevalence of ever smokers between a sample of 851 patients from the 1996 tuberculosis notification registry and the general population. The clinical characteristics of smokers and non-smokers were compared by stratified univariate analysis and multiple logistic regression. RESULTS: Tuberculosis patients were more likely to have smoked than population controls. The respective odds ratios for ever smoking between tuberculosis patients and population controls were 2.44 and 2.08 for males and females aged 16-64 (Mantel-Haenszel weighted OR = 2.40, P < 0.001), and 2.09 and 2.83 for males and females aged > or = 65 (Mantel-Haenszel weighted odds ratio = 2.19, P < 0.001). Male sex, age > or = 65, working at onset of illness, regular alcohol use, drug abuse and absence of contact history were associated with ever smokers (all P < 0.05). Ever smokers were more likely to have cough (OR 1.69), dyspnoea (OR 1.84), upper zone involvement (OR 1.67), cavity (OR 1.76), miliary lung involvement (OR 2.77), positive sputum culture (OR 1.43), but less isolated extrathoracic involvement (OR 0.31), even after controlling for the confounding background variables (all P < 0.05). CONCLUSION: There was a consistent association between smoking and tuberculosis. More aggressive lung involvement was also found among ever smokers.