Hong Kong Society of Clinical Blood Management recommendations for implementation of patient blood management.

Patient blood management (PBM) is a patient-centred, multidisciplinary approach to optimise red cell mass, minimise blood loss, and manage tolerance to anaemia in an effort to improve patient outcomes. Well-implemented PBM improves patient outcomes and reduces demand for blood products. The multidisciplinary approach of PBM can often allow patients to avoid blood transfusions, which are associated with less favourable clinical outcomes. In Hong Kong, there has been increasing demand for blood in the ageing population, and there are simultaneous blood safety and donor issues that are adversely affecting the blood supply. To address these challenges, the Hong Kong Society of Clinical Blood Management recommends implementation of a PBM programme in Hong Kong, including strategies such as optimising red blood cell mass, improving anaemia management, minimising blood loss, and rationalising the use of blood and blood products.

Correlation between kidney and peripheral nerve functions in Type 2 diabetes.

BACKGROUND: Although greater impairments in nerve functions parameters are most likely to occur with a lower kidney function, there is a paucity of information on the relationship between the kidney and peripheral nerve functions parameters in Type 2 diabetes. AIM: To address the impact of peripheral nerve functions in Type 2 diabetes patients in different stages of chronic kidney diseases (CKD). DESIGN: This prospective study enrolled 238 patients with Type 2 diabetes at a tertiary medical center. METHOD: We designed composite amplitude scores of nerve conductions (CAS) as a measure of severity of peripheral neuropathy (PN), and used estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) parameters to stage CKD in Type 2 diabetes patients. The intrapersonal mean, standard deviation and coefficient of variation of eGFR for 238 patients were obtained in the 3 years prior to the study. RESULTS: The patients who had lower eGFR and higher UACR were older, with longer diabetes duration, a greater percentage of retinopathy and PN and higher CAS. Multiple linear regression analysis revealed that diabetes duration and eGFR were independently associated with CAS, and a cut-off value of eGFR in the presence of PN was 65.3 ml/min/1.73 m2. CONCLUSION: We observed a close relationship between the severity of kidney and peripheral nerve function in patients with diabetes. If a patient's eGFR value is below 65.3 ml/min/1.73 m2 or the UACR value is above 98.6 mg/dl, caution is needed with the presence of PN even in diabetic patients who are asymptomatic.

The outcomes of statin therapy in patients with acute ischemic stroke in Taiwan: a nationwide epidemiologic study.

BACKGROUND: Acute stroke is the third leading cause of death in Taiwan. Although statin therapy is widely recommended for stroke prevention, little is known about the epidemiology of statin therapy after acute ischemic stroke (AIS) in Taiwan. To investigate the effects of statin therapy on recurrent stroke, intracranial hemorrhage (ICH), coronary artery disease (CAD), cost of hospitalization and mortality, we conducted a nationwide population-based epidemiologic study. METHODS: Cases of AIS were identified from the annual hospitalization discharge diagnoses of the National Health Insurance Research Database with the corresponding International Classification of Diseases, ninth revision codes from January 2001 to December 2010. We divided the AIS patients into three groups: non-statin, pre-stroke statin and post-stroke statin. RESULTS: A total of 422 671 patients with AIS (including 365 419 cases in the non-statin group, 22 716 cases in the pre-stroke statin group and 34 536 cases in the post-stroke statin group) were identified. When compared to the non-statin group, both statin groups had a lower recurrent stroke risk [pre-stroke statin: odds ratio (OR) = 0.84; 95% confidence interval (CI) = 0.82-0.87; P < 0.0001; post-stroke statin: OR = 0.89; 95% CI = 0.86-0.91; P < 0.0001], lower ICH risk (pre-statin: OR = 0.75; 95% CI = 0.69-0.82; P < 0.0001; post-stroke statin: OR = 0.75; 95% CI = 0.71-0.81; P < 0.0001), and a lower mortality rate (pre-stroke statin: OR = 0.56; 95% CI = 0.53-0.59; P < 0.0001; post-stroke statin: OR = 0.51; 95% CI = 0.48-0.53; P < 0.0001). In terms of CAD, only the post-statin group had a lower risk (OR = 0.81; 95% CI = 0.79-0.84; P < 0.0001) than the non-statin group. The post-statin group had the lowest 1-year medical costs after index discharge among the three groups. CONCLUSIONS: Statin therapy reduced the risks of recurrent stroke, CAD, ICH and the first year mortality in patients after AIS. Treatment with statin therapy after AIS is a cost-effective strategy in Taiwan.

Outcomes of Heart Transplant Recipients With Preexisting Malignancies.

BACKGROUND: Ensuring careful selection of heart transplant recipients with pretransplant malignancies (PTM) has been suggested in several retrospective studies. However, cancer survival rates continue to increase and we still lack outcomes data on PTM patients who have undergone heart transplantation (HT) within the Asian region. Herein we report pretransplant characteristics and outcomes among PTM patients with HT. METHODS: A total of 354 patients underwent HT from January 2004 to January 2016. Eight of these patients had a history malignancy that was being treated before transplantation. Posttransplant outcomes and clinical characteristics were collected and possible prognostic factors analyzed. RESULTS: The median age of the patients with a preexisting malignancy was 60 years. The PTM group included 5 males and 3 females, with a median duration of follow-up of 43 months. In this group there were 2 patients with lymphoma after chemotherapy, 1 with colon cancer postoperatively, and 1 was on chemotherapy. In the other 4 patients, nasopharyngeal cancer, thyroid cancer, breast cancer, and endometrial cancer were identified, and each had undergone treatment. Only 1 premalignancy patient, with nasopharyngeal cancer, had disease recurrence. The 5-year overall survival of these patients was 50.0 ± 17.7%, but 5-year survival for those without PTM was 68.7 ± 2.0%. CONCLUSION: PTM was 2.3% in our cohort. PTM is associated with an increased risk of all-cause mortality. Thus, our findings suggest careful consideration when selecting PTM patients for HT.

Heart Transplantation in a Patient Without a Heart: A Case Report.

We report a heart transplantation in a patient with no heart. A 60-year-old man suffered from severe infective endocarditis, and due to extensive involvement of the myocardium, only minimal myocardium was left after debridement of the necrotic myocardium and aortic annulus. We finally excised the entire heart to eradicate the infection source and employed 2 extracorporeal membrane oxygenations for full life support. The infection was controlled with strong antibiotics. The patient underwent successful heart transplantation 16 days following the excision and the patient fully recovered without any complications.

Implication of Major Adverse Postoperative Events and Myocardial Injury on Disability and Survival: A Planned Subanalysis of the ENIGMA-II Trial.

BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery. METHODS: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients. All were ≥45 years of age and had moderate to high cardiac risk. The primary outcome was mortality within 1 postoperative year. We defined 4 separate types of postoperative adverse events. Major adverse cardiac events (MACEs) included myocardial infarction (MI), cardiac arrest, and myocardial revascularization with or without troponin elevation. MI was defined using the third Universal Definition and was blindly adjudicated. A second cohort consisted of patients with isolated troponin increases who did not meet the definition for MI. We also considered a cohort of patients who experienced major adverse postoperative events (MAPEs), including unplanned admission to intensive care, prolonged mechanical ventilation, wound infection, pulmonary embolism, and stroke. From this cohort, we identified a group without troponin elevation and another with troponin elevation that was not judged to be an MI. Multivariable Cox proportional hazard models for death at 1 year and assessments of proportionality of hazard functions were performed and expressed as an adjusted hazard ratio (aHR) and 95% confidence intervals (CIs). RESULTS: MACEs were observed in 469 patients, and another 754 patients had isolated troponin increases. MAPEs were observed in 631 patients. Compared with control patients, patients with a MACE were at increased risk of mortality (aHR, 3.36 [95% CI, 2.55-4.46]), similar to patients who suffered a MAPE without troponin elevation (n = 501) (aHR, 2.98 [95% CI, 2.26-3.92]). Patients who suffered a MAPE with troponin elevation but without MI had the highest risk of death (n = 116) (aHR, 4.29 [95% CI, 2.89-6.36]). These 4 types of adverse events similarly affected 1-year disability-free survival. CONCLUSIONS: MACEs and MAPEs occur at similar frequencies and affect survival to a similar degree. All 3 types of postoperative troponin elevation in this analysis were associated, to varying degrees, with increased risk of death and disability.

Neuropsychiatric symptoms in Alzheimer's disease: associations with caregiver burden and treatment outcomes.

BACKGROUND: Caregivers play a major role in providing care for patients with Alzheimer's disease (AD) and are themselves at higher risk of health comorbidities. AIM: To address the impact of neuropsychiatric symptoms of patients in different stages of AD on their caregivers' burden. DESIGN: This prospective study enrolled 260 AD patients with clinical dementia rating (CDR) of 0.5, 1 and 2 at a tertiary medical center. METHODS: All patients were tested using the mini-mental state examination (MMSE), the cognitive abilities screening instrument (CASI), the neuropsychiatric inventory (NPI) and the CDR scale. Data regarding therapeutic outcomes of anti-Alzheimer's drugs were also collected. Caregivers were tested using NPI. RESULTS: The mean follow-up interval was 25.0 ± 12.2 months, and two patients died during follow-up. NPI-burden was positively correlated with NPI-sum ( r = 0.822, P < 0.001) but negatively correlated with years of education ( r = -0.140, P = 0.024), CASI score ( r = -0.259, P < 0.001) and MMSE score ( r = -0.262, P <0.001). Multiple linear regression analysis showed that only NPI-sum was independently associated with mean NPI-burden. Both higher mean CASI and MMSE scores had better therapeutic outcome of anti-Alzheimer's drugs ( P = 0.001 and P = 0.005, respectively). CONCLUSIONS: The severity of neuropsychiatric symptoms in patients with AD was positively associated with caregiver's stress, and patients with better cognitive functions, under treatment with anti-Alzheimer's drugs, had better therapeutic outcomes. To reduce the impact of neuropsychiatric symptoms, it is crucial to detect dementia in its early phases and provide early intervention with anti-Alzheimer's drugs, which might help decrease the caregiver burden, thereby improving their quality of life.

Long-term results of coronary artery bypass grafting in patients with dialysis-dependent renal failure.

AIM: Coronary artery disease is the main cause of mortality and morbidity in dialysis-dependent renal failure patients. Both the prevalence and incidence of renal failure are high in Taiwan. However, there were few reports exploring the outcome of coronary aortic bypass grafting (CABG) in these patients. The aim of this study was to determine the survival outcome and risk factors for mortality from CABG in this population. METHODS: The operative, early postoperative and late results of 170 dialysis patients undergoing isolated coronary artery bypass grafting from January, 2000 to January, 2012 were retrospectively reviewed. Operative mortality, long-term survival, and risk factors were analyzed. RESULTS: One hundred and seventeen patients (68.8%) were male, and the mean age was 61.5±10.3 years (range, 34-86 years). Follow-up was 40.3±32.1 months. Operative mortality was 8.2%. Actuarial survival, including operative mortality, was 81±3% at 1 year, 68±4% at 3 years, 58±5% at 5 years and 49±6% at 10 years, better than the natural course of dialysis-dependent renal failure patients. Age, emergent operation, postoperative ventricular tachycardia or fibrillation, postoperative intra-aortic balloon pump insertion, gastrointestinal bleeding, and left internal mammary artery graft were significant predictors of operative or long term mortality. Most causes of late death were due to infection or cardiac events. CONCLUSION: CABG in dialysis patients is associated with a higher incidence of complications, but has acceptable mortality. CABG is beneficial in this population. Internal mammary artery grafting may provide more favorable long term outcomes.

Neuroprotective effect of agmatine in rats with transient cerebral ischemia using MR imaging and histopathologic evaluation.

PURPOSE: This study aimed to further investigate the effects of agmatine on brain edema in the rats with middle cerebral artery occlusion (MCAO) injury using magnetic resonance imaging (MRI) monitoring and biochemical and histopathologic evaluation. MATERIALS AND METHODS: Following surgical induction of MCAO for 90min, agmatine was injected 5min after beginning of reperfusion and again once daily for the next 3 post-operative days. The events during ischemia and reperfusion were investigated by T2-weighted images (T2WI), serial diffusion-weighted images (DWI), calculated apparent diffusion coefficient (ADC) maps and contrast-enhanced T1-weighted images (CE-T1WI) during 3h-72h in a 1.5T Siemens MAGNETON Avanto Scanner. Lesion volumes were analyzed in a blinded and randomized manner. Triphenyltetrazolium chloride (TTC), Nissl, and Evans Blue stainings were performed at the corresponding sections. RESULTS: Increased lesion volumes derived from T2WI, DWI, ADC, CE-T1WI, and TTC all were noted at 3h and peaked at 24h-48h after MCAO injury. TTC-derived infarct volumes were not significantly different from the T2WI, DWI-, and CE-T1WI-derived lesion volumes at the last imaging time (72h) point except for significantly smaller ADC lesions in the MCAO model (P<0.05). Volumetric calculation based on TTC-derived infarct also correlated significantly stronger to volumetric calculation based on last imaging time point derived on T2WI, DWI or CE-T1WI than ADC (P<0.05). At the last imaging time point, a significant increase in Evans Blue extravasation and a significant decrease in Nissl-positive cells numbers were noted in the vehicle-treated MCAO injured animals. The lesion volumes derived from T2WI, DWI, CE-T1WI, and Evans blue extravasation as well as the reduced numbers of Nissl-positive cells were all significantly attenuated in the agmatine-treated rats compared with the control ischemia rats (P<0.05). CONCLUSION: Our results suggest that agmatine has neuroprotective effects against brain edema on a reperfusion model after transient cerebral ischemia.

A randomised comparison of InnoScope and Macintosh laryngoscope in simulated difficult tracheal intubation in manikins.

We conducted a crossover randomised study to evaluate the performance of a novel optical stylet, the InnoScope, for tracheal intubation in simulated normal and difficult airways. Twenty-five anaesthetists attempted tracheal intubation on a SimMan 3G simulator using the InnoScope first followed by the Macintosh laryngoscope or vice versa. Three airway scenarios were tested: (1) normal airway; (2) difficult airway with swollen pharynx; and (3) limited neck movement. In each scenario, the laryngeal view, duration of and success rate for tracheal intubation were recorded. Compared with the Macintosh laryngoscope, the use of InnoScope increased the percentage of glottic opening seen by 17% in normal airway, 23% in the difficult airway and 32% with limited neck movement, p < 0.01. Despite this better laryngeal view, successful tracheal intubation achieved with the InnoScope (88.0%) was lower than that for the Macintosh laryngoscope (98.7%), p = 0.008. Using the InnoScope, tracheal intubation during the first attempt was only successful in 48% of cases with difficult airway. In this scenario, the median (interquartile range [range]) duration of tracheal intubation was significantly longer with [corrected] InnoScope compared with the Macintosh laryngoscope, (70 (19-120 [15-120)] s vs 30 [21-58 (15-120)] s, [corrected] p = 0.01. We conclude that an improved laryngeal view with the use of the InnoScope did not translate into better conditions for tracheal intubation.

A double-blind randomised comparison of intravenous patient-controlled remifentanil with intramuscular pethidine for labour analgesia.

In a prospective, double-blind, randomised controlled trial, we compared the efficacy of patient-controlled analgesia using remifentanil (25-30 µg per bolus) with intramuscular pethidine (50-75 mg) for labour analgesia in 69 parturients. Parturients receiving patient-controlled analgesia reported less pain than those receiving intramuscular pethidine throughout the study period (p < 0.001), with maximal reduction in visual analogue pain score at 2 h after commencement of analgesia (mean (SD) 20 (17) in the patient-controlled analgesia group and 36 (22) in the intramuscular pethidine group. The median (95% CI) time to the first request for rescue analgesics was significantly longer with patient-controlled analgesia (8.0 (6.8-9.2) h) compared with intramuscular pethidine (4.9 (3.8-5.4) h, p < 0.001). Maternal satisfaction scores were also higher with remifentanil compared with intramuscular pethidine (p= 0.001). There was no report of sedation, aponea or oxygen desaturation in either group, and Apgar scores were similar between groups. We conclude that patient-controlled analgesia with remifentanil provides better labour analgesia and maternal satisfaction than intramuscular pethidine. At this dose, maternal and fetal side effects were uncommon.

Assessing the chronic neuropsychologic sequelae of human immunodeficiency virus-negative cryptococcal meningitis by using diffusion tensor imaging.

BACKGROUND AND PURPOSE: The high rate of neuropsychologic sequelae in CM survivors indicates that initial antifungal therapy is far from being satisfactory. This prospective cross-sectional study applied DTI on HIV-negative CM patients to determine whether microstructural changes in brain tissue are associated with subsequent cognitive symptoms. MATERIALS AND METHODS: Fifteen patients with HIV-negative CM and 15 sex- and age-matched healthy volunteers were evaluated and compared. All underwent complete medical and neurologic examinations and neuropsychologic testing. Brain DTI was obtained to derive the FA and ADC of several brain regions. Correlations among DTI parameters, neuropsychologic rating scores, and cryptococcal-antigen titer in CSF were analyzed. RESULTS: Significant ADC values increased and FA values decreased in HIV-negative CM patients in multiple selected regions of interest, including the genus of the corpus callosum and the frontal, parietal, orbito-frontal, and periventricular white matter and lentiform nucleus. Higher CSF cryptococcal-antigen titer on admission was associated with poorer DTI parameters (r = -0.666, P = .018), which were linearly related to worse cognitive performance during follow-up. CONCLUSIONS: The decline in brain DTI parameters in the associated brain areas indicates an HIV-negative CM microstructural pathology that is related to neuropsychologic consequences.

Clinical value of CYFRA21-1, NSE, CA15-3, CA19-9 and CA125 assay in the elderly patients with pleural effusions.

The aim of this study was to evaluate the individual and combined diagnostic value of five tumour markers in the elderly patients with pleural effusions. Serum and pleural fluid levels of cytokeratin fragment 19 (CYFRA21-1), neuron-specific enolase (NSE), carbohydrate antigen 15-3 (CA15-3), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 125 (CA125) were assayed in 32 elderly patients with malignant pleural effusions resulting from advanced lung cancer and in 30 elderly patients with benign pleural effusions by ELISA. Serum levels of CYFRA21-1, NSE, CA15-3, CA19-9 and CA125 in patients with malignant pleural effusions were 12.84 +/- 6.48 microg/l, 22.07 +/- 11.25 microg/l, 65.74 +/- 30.26 kU/l, 56.32 +/- 25.6 kU/l and 71.86 +/- 31.45 kU/l, respectively, and were significantly higher than those in patients with benign pleural effusions (p < 0.01). Pleural fluid levels of CYFRA21-1, CA15-3, CA19-9 and CA125 except NSE in patients with malignant pleural effusions were 18.64 +/- 8.15 microg/l, 59.31 +/- 27.35 kU/l, 48.24 +/- 21.56 kU/l and 62.16 +/- 27.79 kU/l, respectively, and were significantly higher than those in patients with benign pleural effusions (p < 0.01). The parallel combined testing of five tumour markers in serum increased the diagnostic sensitivity to 90.6%, and serial combined testing increased the diagnostic specificity to 93.3%. The sensitivity (%) and specificity (%) of these tumour markers in pleural fluid were as follows: CYFRA21-1, 84.4/90; CA15-3, 62.5/73.3; CA19-9, 37.5/66.7; CA125, 56.3/70; for differentiating malignant effusions from benign effusions. When CYFRA21-1 and CA15-3 combined, the sensitivity and specificity were increased (100% and 90% respectively). Serum and pleural fluid levels of the five tumour markers shows certain values in the diagnosis and differentiate diagnosis for malignant pleural effusions in the elderly patients from benign. The combined assay of five tumour markers in serum and the CYFRA21-1 combined with CA15-3 in pleural fluid were helpful and can increase the sensitivity and specificity in diagnosing malignant pleural effusions.

Successful outpatient treatment of renal vein thrombosis by low-molecular weight heparins in 3 patients with nephrotic syndrome.

Renal vein thrombosis (RV Thromb) is a serious complication ofnephrotic syndrome. Anticoagulation is usually recommended as the treatment of choice. This study reports 3 nephrotic patients diagnosed to have RVThromb combined with thromboembolic events. Low-molecular weight heparin (LMWHep) was given subcutaneously every 12 hours following the diagnosis of RVTromb, which continued at the outpatient clinic after an average of 11 in-hospital days. The patients visited the nephrology outpatient clinic every other week and underwent magnetic resonance image (MRI) studies at 6-week intervals for follow-up of patency of the involved renal vein. LMWHep was discontinued when MRI showed this patency. The average outpatient treatment period was 74 days. There was no recurrent RVThromb in the follow-up course of 6 months after discontinuation of LMWHep. Kidney function was preserved, as indicated by image studies and serial renal function tests. LMWHep produced a more predictable anti-coagulant effect, a superior bioavailability, a longer half-life and a dose-independent effect than unfractionated heparin and coumadin. These benefits made the outpatient treatment of RVThromb possible. Our report recommends outpatient treatment of RVThromb by LMWHep because it is feasible, effective and safe.

Interleukin-20 promotes angiogenesis in a direct and indirect manner.

IL-20 belongs to the IL-10 family and is involved in the pathogenesis of keratinocyte hyperproliferation in vivo. Endothelial cells express IL-20 receptors. To explore the function of IL-20 on endothelial cells, we treated human umbilical vein endothelial cells (HUVECs) and human microvascular endothelial cells (HMECs) with human IL-20 and analyzed its effect on endothelial cells. IL-20 induced proliferation of endothelial cells and the activity was specifically blocked by anti-human-IL-20 monoclonal antibody and soluble (s)IL-20 receptor (R)1 and sIL-20R2. An alternatively spliced variant of IL-20 was isolated and also was shown to induce proliferation of HUVECs and HMECs. Treatment of HUVECs with both IL-10 and IL-20 demonstrated that IL-10 antagonized the activity of IL-20 because it diminished IL-20-induced proliferation of HUVECs. IL-20 significantly induced HUVECs migration and vascular tube formation on Matrigel in vitro. In vivo, IL-20 also enhanced tumor angiogenesis. Incubation of IL-20 with HUVECs induced transcripts of bFGF, VEGF, MMP-2, MMP-9, and IL-8. Furthermore, incubation of HUVECs with IL-20 induced phosphorylation of ERK1/2, p38, and JNK. Thus, IL-20 is a pleiotropic cytokine and promotes angiogenesis.

Surgical treatment for upper or middle esophageal carcinoma occurring after gastrectomy: a study of 52 cases.

Fifty-two patients presenting with upper or middle esophageal carcinoma after gastrectomy between 1980 and 2003 were analyzed retrospectively. Among them, there were five cases of total gastrectomy, six cases of proximal partial gastrectomy and 41 cases of distal subtotal gastrectomy. The interval between gastrectomy and the diagnosis of esophageal carcinoma ranged from 2 to 22 years. Surgical procedures included resection of the esophageal lesion with esophageal replacement using non-reversed or reversed gastric tubes (2 and 3 cases respectively), and short or long segment colon (5 and 40 cases respectively); two cases underwent a palliative procedure (jejunostomy). Complications included cervical anastomotic leaks (3 cases), pulmonary infection (3 cases), atelectasis (2 cases) and cordis arrhythmia (5 cases), all of which responded to treatment. In our group, resection of the esophageal lesions and reconstruction of the esophagus was performed in 45 cases (86.5%), exclusion and bypass procedure of esophageal carcinoma and following radiotherapy and chemotherapy in four (7.7%), eternal jejunostomy for intestinal nutrition in two (3.9%) and death occurred in one case (1.9%) due to multiple organ dysfunction syndrome (MODS). Esophageal resection combined with lymph node dissection is indicated for the treatment of upper or middle esophageal carcinoma following gastrectomy. While esophageal substitutes can include non-reversed or reversed gastric tubes as well as short or long segment colon interpositions, we usually recommend the use of colon interposition. The 1-, 3- and 5-year survival rate of cases with resection of the esophageal lesions and reconstruction of the esophagus was 84.6%, 57.7% and 26.7% respectively.