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1.  Long-Term Outcomes After an Arterial Switch Operation for Simple Complete Transposition of the Great Arteries 
Korean Circulation Journal  2010;40(1):23-30.
Background and Objectives
Although coronary artery obstruction, aortic insufficiency (AI), and pulmonary stenosis (PS) have been reported after arterial switch operation (ASO), limited long-term studies on ASO exist. Our study aimed to examine long-term outcomes after ASO for simple complete transposition of the great arteries (TGA).
Subjects and Methods
All 108 patients with simple complete TGA who underwent ASO at Seoul National University Children's Hospital between 1987 and 2004 were enrolled. We retrospectively reviewed the patients' medical records and the results of various functional and imaging studies.
Results
Among 108 cases of ASO for simple TGA, 96 have been followed-up through the present time (mean follow-up duration was 11.7±8.6 years: range= 4 to 23 years). The 20-year rates of freedom from significant AI, PS, and coronary obstruction were 78.6%, 67.8%, and 95.8%, respectively. AI showed a tendency to progress as follow-up time increased in 21.4% of the population studied (p=0.014); however, AS, PS, and PI showed no such progression. Late coronary artery occlusion was not associated with the initial coronary arterial pattern. Re-operations were done for 13 patients (13.5%) at an average of 8±4.3 years after ASO. The survival rate was 96%, while the re-operation-free was 90% at 10 years and 83% at 20 years. Most patients showed normal physical growth with good activity {98%; New York Heart Association (NYHA) class 1 activity} and normal development (96%).
Conclusion
Although most patients showed normal physical growth and development after successful ASO, meticulous long-term follow-up is necessary because of progressive AI and coronary complications.
doi:10.4070/kcj.2010.40.1.23
PMCID: PMC2812794  PMID: 20111649
Transposition of great vessels; Outcomes assessment, patient; Coronary arteries; Aortic valve insufficiency; Stenosis, pulmonary
2.  Midterm results after arterial switch operation for transposition of the great arteries: a single centre experience 
Background
The arterial switch operation (ASO) has become the surgical approach of choice for d-transposition of the great arteries (d-TGA). There is, however an increased incidence of midterm and longterm adverse sequelae in some survivors. In order to evaluate operative risk and midterm outcome in this population, we reviewed patients who underwent ASO for TGA at our centre.
Methods
In this retrospective study 52 consecutive patients with TGA who underwent ASO between 04/1991 and 12/1999 were included. To analyze the predictors for mortality and adverse events (coronary stenoses, distortion of the pulmonary arteries, dilatation of the neoaortic root, and aortic regurgitation), a multivariate analysis was performed. The follow-up time was ranged from 1–10 years (mean 5 years, cumulative 260 patient-years).
Results
All over mortality rate was 15.4% and was only observed in the early postoperative period till 1994. The predictors for poor operative survival were low APGAR-score, older age at surgery, and necessity of associated surgical procedures. Late re-operations were necessary in 6 patients (13.6%) and included a pulmonary artery patch enlargement due to supravalvular stenosis (n = 3), coronary revascularisation due to coronary stenosis in a coronary anatomy type E, aortic valve replacement due to neoaortic valve regurgitation (n = 2), and patch-plasty of a pulmonary vein due to obstruction (n = 1). The dilatation of neoaortic root was not observed in the follow up.
Conclusions
ASO remains the procedure of choice for TGA with acceptable early and late outcome in terms of overall survival and freedom of reoperation. Although ASO is often complex and may be associated with morbidity, most patients survived without major complications even in a small centre.
doi:10.1186/1749-8090-7-83
PMCID: PMC3487745  PMID: 22958234
Arterial switch operation; Transposition of great arteries; Midterm outcome
3.  Center Variation in Hospital Costs for Patients Undergoing Congenital Heart Surgery 
Background
Congenital heart disease consumes significant health care resources; however, there are limited data regarding factors impacting resource utilization. The purpose of this study was to evaluate variation between centers in total hospital costs for four congenital heart operations of varying complexity, and associated factors.
Methods and Results
The Premier Database was used to evaluate total cost in children undergoing isolated atrial septal defect (ASD) repair, ventricular septal defect (VSD) repair, tetralogy of Fallot (TOF) repair, or arterial switch operation (ASO) from 2001-2007. Mixed models were used to evaluate the impact of center on total hospital costs adjusting for patient and center characteristics and length of stay (LOS).
A total of 2,124 patients were included: 719 ASD (19 centers), 792 VSD (20 centers), 420 TOF (17 centers), and 193 ASO (13 centers). Total cost increased with complexity of operation from median $12,761 (ASD repair) to $55,430 (ASO). In multivariable analysis, models which accounted for center effects vs. those which did not performed significantly better for all four surgeries (all p ≤ 0.01). The proportion of total cost variation explained by center was 19% (ASD repair), 11% (VSD repair), 6% (TOF repair), and 3% (ASO). Higher volume centers had significantly lower hospital costs for ASD and VSD repair, but not for TOF repair and ASO.
Conclusions
Total hospital costs varied significantly by center for all congenital heart surgeries evaluated, even after adjustment for patient and center characteristics and LOS. Differences among centers were most prominent for lower complexity procedures.
doi:10.1161/CIRCOUTCOMES.110.958959
PMCID: PMC3326639  PMID: 21505154
heart defects; congenital; cost
4.  Resource Utilization After Introduction of a Standardized Clinical Assessment and Management Plan 
Congenital Heart Disease  2010;5(4):374-381.
Introduction
A Standardized Clinical Assessment and Management Plan (SCAMP) is a novel quality improvement initiative that standardizes the assessment and management of all patients who carry a predefined diagnosis. Based on periodic review of systemically collected data the SCAMP is designed to be modified to improve its own algorithm. One of the objectives of a SCAMP is to identify and reduce resource utilization and patient care costs.
Methods
We retrospectively reviewed resource utilization in the first 93 arterial switch operation (ASO) SCAMP patients and 186 age-matched control ASO patients. We compared diagnostic and laboratory testing obtained at the initial SCAMP clinic visit and control patient visits. To evaluate the effect of the SCAMP over time, the number of clinic visits per patient year and echocardiograms per patient year in historical control ASO patients were compared to the projected rates for ASO SCAMP participants.
Results
Cardiac magnetic resonance imaging (MRI), stress echocardiogram, and lipid profile utilization were higher in the initial SCAMP clinic visit group than in age-matched control patients. Total echocardiogram and lung scan usage were similar. Chest X-ray and exercise stress testing were obtained less in SCAMP patients. ASO SCAMP patients are projected to have 0.5 clinic visits and 0.5 echocardiograms per year. Historical control patients had more clinic visits (1.2 vs. 0.5 visits/patient year, P < .01) and a higher echocardiogram rate (0.92 vs. 0.5 echocardiograms/patient year, P <.01)
Conclusion
Implementation of a SCAMP may initially lead to increased resource utilization, but over time resource utilization is projected to decrease.
doi:10.1111/j.1747-0803.2010.00434.x
PMCID: PMC3376534  PMID: 20653704
Congenital Heart Disease; Tests; Practice Guidelines; Resource Utilization; Health Policy and Outcomes
5.  Arterial Switch Operation in Patients with Intramural Coronary Artery: Early and Mid-term Results 
Background
The intramural coronary artery has been known as a risk factor for early death after an arterial switch operation (ASO). We reviewed the morphological characteristics and evaluated the early and mid-term results of ASO for patients with an intramural coronary artery.
Materials and Methods
From March 1994 to September 15th 2010, 158 patients underwent ASO at Dong-A and Pusan National University Hospitals for repair of transposition of the great arteries and double outlet right ventricle. Among these patients, 14 patients (8.9%) had an intramural coronary artery. Mean age at operation was 13.4±10.2 days (4 to 39 days) and mean body weight was 3.48±0.33 kg (2.88 to 3.88 kg). All patients except one were male. Eight patients had TGA/IVS and 4 patients had an aortic arch anomaly. Two patients (14.3%) had side-by-side great artery relation, of whom one had an intramural right coronary artery and the other had an intramural left anterior descending coronary artery. Twelve patients had anterior-posterior relation, all of whom had an intramural left coronary artery (LCA). The aortocoronary flap technique was used in coronary transfer in 8 patients, of whom one patient required a switch to the individual coronary button technique 2 days after operation because of myocardial ischemia. An individual coronary button implantation technique was adopted in 6, of whom 2 patients required left subclavian artery free graft to LCA during the same operation due to LCA injury during coronary button mobilization and LCA torsion.
Results
There was 1 operative death (7.1%), which occurred in the first patient in our series. This patient underwent an aortocoronary flap procedure for coronary transfer combining aortic arch repair. Overall operative mortality for 144 patients without an intramural coronary artery was 13.2% (19/144). There was no statistical difference in operative mortality between the patients with and without an intramural coronary artery (p>0.1). There was no late death. The mean follow-up duration was 52.1±43.0 months (0.5 to 132 months). One patient who had a subclavian artery free graft required LCA stenting 6.5 years after surgery for LCA anastomotic site stenosis. No other surviving patient needed any intervention for coronary problems. All patients had normal ventricular function at latest echocardiography and were in NYHA class 1.
Conclusion
The arterial switch operation in Transposition of Great Arteries or Double Outlet Right Ventricle patients with intramural coronary can be performed with low mortality; however, there is a high incidence of intraoperative or postoperative coronary problems, which can be managed with conversion to the individual coronary button technique and a bypass procedure using a left subclavian free graft. Both aortocoronary flap and individual coronary button implantation techniques for coronary transfer have excellent mid-term results.
doi:10.5090/kjtcs.2011.44.2.115
PMCID: PMC3249286  PMID: 22263137
Congenital heart disease; Transposition of the great arteries; Arterial switch operation; Coronary artery; Coronary artery anatomy
6.  Predicting antisense oligonucleotide inhibitory efficacy: a computational approach using histograms and thermodynamic indices. 
Nucleic Acids Research  1992;20(13):3501-3508.
Antisense oligonucleotides (ASOs) are designed to bind to a specific mRNA and selectively suppress its translation. To facilitate selection of optimal ASO targets, we have developed three thermodynamic indices to evaluate putative structural complexes important in ASO action. These indices are: a secondary structure score (Sscore), which estimates the strength of local mRNA secondary structures at the ASO target site; a duplex score (Dscore), which estimates the delta Gformation for the ASO:mRNA target sequence duplex; and a competition score (Cscore), which is the difference between the Dscore and the Sscore. We also present two histograms to graphically display these indices from different regions of the mRNA. The indices are compared to the inhibition reported in five studies of ASO-mediated suppression of gene expression. The Dscore is the most consistent predictor of ASO efficacy in four of the five studies (r2 from 0.44 to 0.99), while the results of the fifth study could not be predicted by any thermodynamic or physical index. Thus the Dscores and their histogram may prove useful in selection of ASO targets.
Images
PMCID: PMC312508  PMID: 1352874
7.  Right ventricular hypertrophy and diastolic dysfunction in arterial switch patients without pulmonary artery stenosis 
Heart  2007;93(12):1604-1608.
Objective
To assess pulmonary flow dynamics and right ventricular (RV) function in patients without significant anatomical narrowing of the pulmonary arteries late after the arterial switch operation (ASO) by using magnetic resonance imaging (MRI).
Methods
17 patients (mean (SD), 16.5 (3.6) years after ASO) and 17 matched healthy subjects were included. MRI was used to assess flow across the pulmonary trunk, RV systolic and diastolic function, and RV mass.
Results
Increased peak flow velocity (>1.5 m/s) was found across the pulmonary trunk in 14 of 17 patients. Increased RV mass was found in ASO patients: 14.9 (3.4) vs 10.0 (2.6) g/m2 in normal subjects (p<0.01). Delayed RV relaxation was found after ASO: mean tricuspid valve E/A peak flow velocity ratio = 1.60 (0.96) vs 1.92 (0.61) in normal subjects (p = 0.03), and E‐deceleration gradients = −1.69 (0.73) vs −2.66 (0.96) (p<0.01). After ASO, RV mass correlated with pulmonary trunk peak flow velocity (r = 0.49, p<0.01) and tricuspid valve E‐deceleration gradients (r = 0.35, p = 0.04). RV systolic function was well preserved in patients (ejection fraction = 53 (7)% vs 52 (8)% in normal subjects, p = 0.72).
Conclusions
Increased peak flow velocity in the pulmonary trunk was often observed late after ASO, even in the absence of significant pulmonary artery stenosis. Haemodynamic consequences were RV hypertrophy and RV relaxation abnormalities as early markers of disease, while systolic RV function was well preserved.
doi:10.1136/hrt.2006.109199
PMCID: PMC2095768  PMID: 17277348
arterial switch operation; pulmonary artery; right ventricle; magnetic resonance imaging; congenital heart disease
8.  Transcatheter closure of atrial septal defects in adults with the Amplatzer septal occluder 
Heart  1999;82(5):559-562.
OBJECTIVE—To assess the efficacy and complications of device occlusion of atrial septal defects in adults, using the Amplatzer septal occluder (ASO).
DESIGN—A prospective interventional study.
SETTING—Paediatric cardiology departments in two European teaching hospitals.
PATIENTS—The first 20 patients accepted for atrial septal defect device occlusion, on the basis of transoesophageal echocardiography. Sixteen patients had larger defects with right heart dilatation, while the primary indication for closure in four was a history of early paradoxical embolism.
INTERVENTIONS—Transcatheter atrial septal defect occlusions performed under transoesophageal echocardiography and fluoroscopic guidance between December 1996 and June 1998.
OUTCOME MEASURES—Success of deployment of ASO devices, procedure and fluoroscopic times, complications, and symptoms.
RESULTS—The ASO device was successfully implanted in all 20 patients (14 female), median age 44.2 years, with no complications. Of the 16 patients with right heart dilatation, the median Qp:Qs was 2.5:1. Defects measured 11-22 mm (median 18) on transoesophageal echocardiography, with balloon sized diameter (and device size) of 13-28 mm (median 20). For all 20 patients, the procedure time ranged from 38-78 minutes (median 61), and fluoroscopy 8.4-24.7 minutes (median 15.2). There were residual shunts in three patients at the end of the procedure, which were trivial (⩽ 1 mm) as assessed by transoesophageal echocardiography, and persisted for more than six months in only one patient. Follow up ranged from 0.1-1.5 years (median 0.7). There have been no late complications.
CONCLUSIONS—The ASO device can be used successfully to close selected oval fossa defects in adults, with minimal procedural morbidity and excellent early results.


Keywords: atrial septal defect; interventional cardiac catheterisation; Amplatzer septal occluder
PMCID: PMC1760778  PMID: 10525508
9.  Effect of technique and timing of tracheostomy in patients with acute traumatic spinal cord injury undergoing mechanical ventilation 
Objective
To assess the effect of timing and techniques of tracheostomy on morbidity, mortality, and the burden of resources in patients with acute traumatic spinal cord injuries (SCIs) undergoing mechanical ventilation.
Design
Review of a prospectively collected database.
Setting
Intensive and intermediate care units of a monographic hospital for the treatment of SCI.
Participants
Consecutive patients admitted to the intensive care unit (ICU) during their first inpatient rehabilitation for cervical and thoracic traumatic SCI. A total of 323 patients were included: 297 required mechanical ventilation and 215 underwent tracheostomy.
Outcome measures
Demographic data, data relevant to the patients’ neurological injuries (level and grade of spinal cord damage), tracheostomy technique and timing, duration of mechanical ventilation, length of stay at ICU, incidence of pneumonia, incidence of perioperative and early postoperative complications, and mortality.
Results
Early tracheostomy (<7 days after orotracheal intubation) tracheostomy was performed in 101 patients (47%) and late (≥7 days) in 114 (53%). Surgical tracheostomy was employed in 119 cases (55%) and percutaneous tracheostomy in 96 (45%). There were 61 complications in 53 patients related to all tracheostomy procedures. Two were qualified as serious (tracheoesophageal fistula and mediastinal abscess). Other complications were mild. Bleeding was moderate in one case (late, percutaneous tracheostomy). Postoperative infection rate was low. Mortality of all causes was also low.
Conclusion
Early tracheostomy may have favorable effects in patients with acute traumatic SC. Both techniques, percutaneous and surgical tracheostomy, can be performed safely in the ICU.
doi:10.1179/107902610X12886261091875
PMCID: PMC3066483  PMID: 21528630
Spinal cord injuries; Cervical; Thoracic; Mechanical ventilation; Tracheostomy; Percutaneous; Surgical; Complications; Spine surgery
10.  Ambulatory laparoscopic cholecystectomy: An audit of day case vs overnight surgery at a community hospital in Japan 
AIM: To evaluate the applicability and safety of ambulatory laparoscopic cholecystectomy (LC) and to compare day case and overnight stay LC.
METHODS: Data were collected retrospectively and consecutively for day case and overnight stay LC patients from July 1, 2009 to April 30, 2011. Outcomes were analyzed for patient demographics, operation time, blood loss during operation and frequency and reasons for unexpected or prolonged hospitalization in each group.
RESULTS: There was no hospital mortality and no patient was readmitted with serious morbidity after discharge. 50 patients received a day case LC and 19 had an overnight stay LC. There was a significant difference in age between both groups (P < 0.02). There were no significant differences between the day case LC performed (n = 41) and failed (n = 9) groups and between the day case LC performed and the one night stay LC (n = 12) groups. There was a significant difference in age between the one night stay and more nights stay LC groups (P < 0.05). Thus, elderly patients showed a tendency to like to stay in hospital rather than being a day case. The proportion of unexpected or prolonged hospitalization was not significantly different between the day case and overnight stay LC groups, when the patient’s request was excluded.
CONCLUSION: Day case LC can be performed with a low rate of complications. In overnight stay patients, there are many who could be performed safely as a day case. Moreover, we need to take special care to treat elderly patients.
doi:10.4240/wjgs.v4.i12.296
PMCID: PMC3596527  PMID: 23493831
Laparoscopic cholecystectomy; Day case vs overnight
11.  Myocardial ischemia following arterial switch operation: An uncommon etiology 
Annals of Pediatric Cardiology  2012;5(2):194-196.
Myocardial ischemia following arterial switch operation (ASO) usually occurs due to coronary ostial narrowing that might result from technical failure in translocation of the coronary arteries to the neoaorta. We present an unusual case report of neonatal myocardial ischemia caused by coronary steal secondary to aortopulmonary collaterals, following ASO in transposition of great arteries.
doi:10.4103/0974-2069.99626
PMCID: PMC3487212  PMID: 23129913
Arterial switch operation; coronary steal; MAPCA; myocardial ischemia
12.  Assessment of left ventricular function long term after arterial switch operation for transposition of the great arteries by dobutamine stress echocardiography 
Heart  2005;91(1):68-72.
Objectives: To use dobutamine stress echocardiography to determine left ventricular (LV) function and wall motion of children long term after arterial switch operation (ASO) for transposition of the great arteries.
Design and patients: 31 patients (24 boys) with ASO performed at a mean (SD) of 15.5 (4.3) days of life were studied at an age of 9.4 (2.0) years. All had normal coronary angiographic findings. LV echocardiographic indexes, including fractional shortening, ejection fraction, rate corrected velocity of circumferential fibre shortening (VCFc), and wall stress, as well as LV wall motion abnormalities were determined at rest and under dobutamine stress. The results were compared with those of 20 healthy age matched control participants.
Setting: Tertiary paediatric cardiac centre.
Results: Fractional shortening, ejection fraction, and VCFc were significantly lower in patients than in controls at rest (all with p < 0.001). Stress–velocity index detected impaired LV contractility in 19 (61%) patients at rest. An older age at operation (p  =  0.01), longer bypass (p  =  0.01) and circulatory arrest times (p  =  0.045), and an unusual coronary artery pattern (p  =  0.059) were associated with impaired resting LV contractility. Dobutamine stress echocardiography unmasked wall motion abnormalities in 23 (74%) patients. Exercise myocardial perfusion scan, performed in 22 patients, showed reversible myocardial perfusion defects in 17. These defects corresponded to segments of hypokinesia as detected by dobutamine stress echocardiography.
Conclusion: A significant proportion of children, albeit asymptomatic, had impaired baseline LV contractility and reversible myocardial perfusion defects and mild wall motion abnormalities on stress after ASO.
doi:10.1136/hrt.2003.027524
PMCID: PMC1768615  PMID: 15604338
transposition of the great arteries; ventricular function; dobutamine stress echocardiography; arterial switch operation
13.  The role of structured observational research in health care 
Quality & safety in health care  2003;12(Suppl 2):ii13-ii16.
Structured observational research involves monitoring of healthcare domains by experts to collect data on errors, adverse events, near misses, team performance, and organisational culture. This paper describes some of the results of structured observational studies carried out in health care. It evaluates the strengths, weaknesses, and future challenges facing observational researchers by drawing lessons from the human factors and neonatal arterial switch operation (ASO) study in which two human factors specialists observed paediatric cardiac surgical procedures in 16 UK centres. Lessons learned from the ASO study are germane to other research teams embarking on studies that involve observational data collection. Future research needs robust observer training, clear measurable criteria to assess each researcher's domain knowledge, and observational competence. Measures of inter-rater reliability are needed where two or more observers participate in data collection. While it is important to understand the factors that lead to error and excellence among healthcare teams, it is also necessary to understand the characteristics of a good observer and the key types of error that can occur during structured observational studies like the human factors and ASO project.
doi:10.1136/qhc.12.suppl_2.ii13
PMCID: PMC1765776  PMID: 14645890
14.  Use of isolated Roux loop for pancreaticojejunostomy reconstruction after pancreaticoduodenectomy 
AIM: To evaluate the efficacy of the isolated Roux loop technique in decreasing the frequency of pancreaticojejunal anastomosis failure.
METHODS: We retrospectively reviewed 88 consecutive patients who underwent pancreaticoduodenectomy (standard or pylorus-preserving). Single jejunal loop was used in 42 patients (SL group) while isolated Roux loop was used in 46 patients (RL group). Demographic characteristics (age, gender) and perioperative results (major/minor complications, mortality, hospital stay) were compared between the two groups.
RESULTS: Mortality was almost equal in both groups and overall mortality was 2.27%. Leak rate from the pancreaticojejunal anastomosis and hospital stay were lower in the RL group without significant difference. Morbidity was 39.1% in the RL group, insignificantly higher than the SL group. Operative time was almost 30 min longer in the RL group.
CONCLUSION: The isolated Roux loop, although an equally safe alternative, does not present advantages over the traditional use of a single jejunal loop. Randomized controlled studies are required to further clarify its efficacy.
doi:10.3748/wjg.v16.i25.3178
PMCID: PMC2896755  PMID: 20593503
Pancreaticojejunal anastomosis; Isolated Roux loop; Whipple pancreaticoduodenectomy; Pancreatic leak
15.  Analysis of safety of short-stay thyroid surgery 
Summary
The duration of hospital stay, following surgical procedures, has undergone a significant reduction in recent years. However, there are some risks associated with short-stay thyroid surgery. An analysis has been made of data from patients who underwent short-stay thyroid surgery, analyzing the complications associated with this procedure. Overall 270 consecutive patients undergoing thyroidectomy in 2007 and 2008 were prospectively analyzed. Post-operative care included routine ward overnight observation. The discharge criteria were: stable vital signs; apyretic; no wound or airway problems; tolerating diet; and established autonomy at discharge. Data were collected regarding patients’ discharge criteria status, length of hospital stay and readmission, as well as morbidity (post-operative haemorrhage, recurrent laryngeal nerve injury and hypocalcaemia) and mortality. This series comprised 175 total thyroidectomies, 93 hemi-thyroidectomies and 2 isthmusectomies. No cases of death or post-operative haemorrhage occurred in any of these patients. Permanent unilateral recurrent laryngeal nerve injury was observed in 4 patients (1.48%). Transient post-operative hypocalcaemia occurred in 23 patients, whereas permanent post-operative hypocalcaemia was observed in 8 patients (2.96%); 4 patients were re-admitted and required early calcium supplementation. Five patients failed to tolerate the diet during the immediate post-operative period. The average duration of hospital stay was 1.02 days. Considering the 4 patients who required re-admission due to hypocalcaemia, the total length of hospital stay was 1.05 days. In conclusion, the one-day surgery model is safe and effective in patients undergoing surgery for thyroid disorders.
PMCID: PMC2868204  PMID: 20463838
Thyroidectomy; Lenght of hospital stay; Post-operative complications; Post-operative haemorrhage; Hypocalcaemia; Post-operative pain
16.  Allele-Selective Inhibition of Mutant Huntingtin Expression with Antisense Oligonucleotides Targeting the Expanded CAG Repeat 
Biochemistry  2010;49(47):10166-10178.
Huntington's disease (HD) is a currently incurable neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat within the huntingtin (HTT) gene. Therapeutic approaches include selectively inhibiting the expression of the mutated HTT allele while conserving function of the normal allele. We have evaluated a series of antisense oligonucleotides (ASOs) targeted to the expanded CAG repeat within HTT mRNA for their ability to selectively inhibit expression of mutant HTT protein. Several ASOs incorporating a variety of modifications, including bridged nucleic acids and phosphorothioate internucleotide linkages, exhibited allele-selective silencing in patient-derived fibroblasts. Allele-selective ASOs did not affect the expression of other CAG repeat-containing genes and selectivity was observed in cell lines containing minimal CAG repeat lengths representative of most HD patients. Allele-selective ASOs left HTT mRNA intact and did not support ribonuclease H activity in vitro. We observed cooperative binding of multiple ASO molecules to CAG repeat-containing HTT mRNA transcripts in vitro. These results are consistent with a mechanism involving inhibition at the level of translation. ASOs targeted to the CAG repeat of HTT provide a starting point for the development of oligonucleotide-based therapeutics that can inhibit gene expression with allelic discrimination in patients with HD.
doi:10.1021/bi101208k
PMCID: PMC2991413  PMID: 21028906
Locked nucleic acid (LNA); allele-selective inhibition; Huntington's Disease; huntingtin; antisense oligonucleotide; CAG repeat; triplet repeat
17.  Morbidity associated with systemic corticosteroid preparation for coronary artery bypass grafting in patients with chronic obstructive pulmonary disease: a case control study 
Background
Coronary artery bypass grafting (CABG) is associated with high morbidity in patients with chronic obstructive pulmonary disease (COPD).
We examine the effect of preoperative systemic corticosteroids on morbidity in this setting.
Methods
Ninety candidates for elective CABG participated in a prospective, open randomized trial, including 30 patients with COPD who received a single injection of a long-acting corticosteroid, 30 with COPD who received placebo, and 30 without COPD who served as controls. Primary end-points were postoperative pulmonary and nonpulmonary complications. Secondary end-points were length of hospital stay (LOS), ICU stay of less than 24 hours and more than 48 hours, duration of mechanical ventilation, and time to walking and sitting.
Results
The rate of pulmonary complications was similar in the two COPD groups and in the COPD patients and controls. The placebo group had more major nonpulmonary complications than the treatment group, but the difference was not statistically significant (26% vs. 17%, P = NS). The non-COPD control group had significantly fewer nonpulmonary complications than the COPD patients (treatment+placebo) (33% vs 70%, P = 0.014) and a similar rate of pulmonary complications. There was a statistically significant difference between the treated and placebo COPD groups in ICU stay less than 24 hours (P ≤ 0.001) and more than 48 hours (P = 0.03) and hospital stay (P = 0.013). On stepwise analysis, only age and number of coronary grafts were predictors of pulmonary complications.
Conclusion
The use of preoperative systemic corticosteroids in patients with COPD undergoing CABG may shorten ICU and hospital stay.
doi:10.1186/1749-8090-2-25
PMCID: PMC1892551  PMID: 17547746
18.  Pancreaticoduodenectomy in a Government Medical College—Should We Proceed!!! 
The Indian Journal of Surgery  2010;72(5):381-385.
The value of standard Pancreaticoduodenectomy for Periampullary carcinomas has long been a matter of debate. Though the mortality has dramatically reduced in high volume centers with dedicated hepatobiliary surgery units, the rate is still high in peripheral institutes. In this study our aim was to access the overall post operative outcome associated with pancreaticoduodenectomy performed in a government medical college. A total of 44 patients who underwent pancreaticoduodenectomy for operable periampullary cancers were evaluated. The overall morbidity rate was 31.1%. A total of 13 (29.5%) died following the operation and of its complications though the rate has reduced drastically to 14.2% in2008. The average length of hospital stay was 22 days. The mean survival was 15 months. Pancreaticoduodenectomy can safely be performed in government medical colleges with good results. In view of the majority of the patients in rural and suburban communities, not all patients need referral to higher centers.
doi:10.1007/s12262-010-0153-x
PMCID: PMC3077146  PMID: 21966137
Pancreaticoduodenectomy; Outcome; Government medical colleges
19.  Elevated red cell distribution width predicts poor outcome in young patients with community acquired pneumonia 
Critical Care  2011;15(4):R194.
Introduction
Community acquired pneumonia (CAP) is a major cause of morbidity and mortality. While there is much data about risk factors for severe outcome in the general population, there is less focus on younger group of patients. Therefore, we aimed to detect simple prognostic factors for severe morbidity and mortality in young patients with CAP.
Methods
Patients of 60 years old or younger, who were diagnosed with CAP (defined as pneumonia identified 48 hours or less from hospitalization) between March 1, 2005 and December 31, 2008 were retrospectively analyzed for risk factors for complicated hospitalization and 90-day mortality.
Results
The cohort included 637 patients. 90-day mortality rate was 6.6% and the median length of stay was 5 days. In univariate analysis, male patients and those with co-morbid conditions tended to have complicated disease. In multivariate analysis, variables associated with complicated hospitalization included post chest radiation state, prior neurologic damage, blood urea nitrogen (BUN) > 10.7 mmol/L and red cell distribution width (RDW) > 14.5%; whereas, variables associated with an increased risk of 90-day mortality included age ≥ 51 years, prior neurologic damage, immunosuppression, and the combination of abnormal white blood cells (WBC) and elevated RDW. Complicated hospitalization and mortality rate were significantly higher among patients with increased RDW regardless of the white blood cell count. Elevated RDW was associated with a significant increase in complicated hospitalization and 90-day mortality rates irrespective to hemoglobin levels.
Conclusions
In young patients with CAP, elevated RDW levels are associated with significantly higher rates of mortality and severe morbidity. RDW as a prognostic marker was unrelated with hemoglobin levels.
Trial registration
ClinicalTrials.Gov NCT00845312
doi:10.1186/cc10355
PMCID: PMC3387636  PMID: 21835005
Pneumonia; Red Blood Cell Width; Mortality; Prognosis; Complicated Hospitalization
20.  RealHand High Dexterity Instruments for the Treatment of Stage I Uterine Malignancy 
Background:
The purpose of this pilot study was to evaluate the impact of RealHand instruments on laparoscopic-assisted vaginal hysterectomy (LAVH) for the treatment of stage I uterine cancer.
Methods:
This was a single-center, nonrandomized, consecutive patient pilot study. Patient status was evaluated in terms of operative morbidity, length of surgery, anesthesia time, body mass index (BMI), estimated blood loss, uterine weight, and hospital stay.
Results:
In the group of 10 patients, mean operative time was 1.7 hours, and anesthesia time was 2.3 hours. Mean estimated blood loss was 70mL, and patient hospital stay was 31.8 hours. No intra- or postoperative complications occurred. Blood loss, anesthesia time, BMI, and uterine weight were significant predictors of operative time. In one patient, LAVH using the RealHand instruments was canceled because of deep pelvic visualization difficulties, resulting in a conversion to laparotomy.
Conclusion:
We present the first reported individual physician LAVH experience using RealHand instruments for the treatment of clinical stage I uterine cancer. The reported operative time, reasonable patient complication rates, and acceptable postoperative stay suggest that these innovative surgical instruments may have significant promise in the treatment of patients diagnosed with this gynecologic disease.
PMCID: PMC3015891  PMID: 19366537
RealHand; LAVH; Uterine malignancy; Complications
21.  Post-operative complications of gastric cancer surgery: female gender at high risk 
European Journal of Cancer Care  2009;18(2):202-208.
We applied physiological and operative severity score for the enumeration of morbidity and mortality (POSSUM) to evaluate overall surgical outcome and investigated the role of gender for early post-operative complications in gastric cancer surgery. The data from a total of 357 patients of gastric cancer were analysed by univariate and multivariate analysis. Post-operative complications were recorded according to definition of POSSUM. Post-operative complications of male and female patients were compared separately. The observed to estimated morbidity ratio (O:E) was 1.01. Among the pre-operative variables, patient gender was one of the independent risk factors for a higher rate of post-operative complications (risk ratio 1.777, P = 0.024). Post-operative complication was significantly higher in female patients. Similarly, post-operative length of stay was significantly longer and more severe complications were observed in female patients (P = 0.03). In conclusion, POSSUM system is a valid algorithm for risk-adjusted surgical audit. We conclude that a patient's gender influences the early post-operative complications after gastric cancer surgery. A detailed understanding on disparity of early post-operative complications between men and women may provide valuable information to improve surgical outcome of gastric cancer. However, results of this study need further confirmation by a prospective study involving a larger cohort.
doi:10.1111/j.1365-2354.2008.01036.x
PMCID: PMC2702005  PMID: 19267738
post-operative complications; gastric cancer; POSSUM; gender difference
22.  Peri-operative physiotherapy 
Postoperative pulmonary complications (PPC) are a major cause of morbidity, mortality, prolonged hospital stay, and increased cost of care. Physiotherapy (PT) programs in post-surgical and critical area patients are aimed to reduce the risks of PPC due to long-term bed-rest, to improve the patient’s quality of life and residual function, and to avoid new hospitalizations. At this purpose, PT programs apply advanced cost-effective therapeutic modalities to decrease complications and patient’s ventilator-dependency. Strategies to reduce PPC include monitoring and reduction of risk factors, improving preoperative status, patient education, smoking cessation, intra-operative and postoperative pulmonary care. Different PT techniques, as a part of the comprehensive management of patients undergoing cardiac, upper abdominal, and thoracic surgery, may prevent and treat PPC such as secretion retention, atelectasis, and pneumonia.
doi:10.1186/2049-6958-8-4
PMCID: PMC3600709  PMID: 23343253
23.  Bench-to-bedside review: Therapeutic options and issues in the management of ventilator-associated bacterial pneumonia 
Critical Care  2004;9(3):259-265.
Despite progress in the diagnosis, prevention and therapy for hospital-acquired infections, ventilator-associated pneumonia (VAP) continues to complicate the course of a significant proportion of patients receiving mechanical ventilation. Mortality rates among patients with VAP have been reported to be as high as 72%, and the morbidity associated with VAP is also considerable, adding days to the hospital stay and increasing health care costs. Appropriate initial antimicrobial therapy for patients with VAP has been shown to reduce mortality rates and improve outcomes; therefore, rapid identification of infected patients and timely, accurate selection of effective antimicrobial agents are important clinical goals. The primary organisms responsible for VAP include Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus. However, aetiologies differ considerably between intensive care units, and the increase in antibiotic resistance and nosocomial outbreaks worldwide have presented clinicians with a serious dilemma with respect to selecting appropriate empirical therapy. To date, no optimal antimicrobial regimen for the treatment of VAP has been identified, largely because none of the currently marketed antibiotics has a sufficiently extended spectrum of activity to cover all of the potential key pathogens. More active, less toxic antibacterial agents are still needed, in particular to combat problematic pathogens such as multiresistant Gram-negative bacilli and resistant Gram-positive organisms (e.g. methicillin-resistant S aureus).
doi:10.1186/cc3014
PMCID: PMC1175866  PMID: 15987380
antibiotic resistance; nosocomial infection; ventilator-associated pneumonia
24.  Laparoscopic Diagnosis and Treatment in Gynecologic Emergencies 
Objective:
To present an analysis of our experience with 22 consecutive cases of acute abdominal gynecologic emergencies managed with a laparoscopic approach.
Methods:
From March 1997 to October 1998, 22 patients with a diagnosis of acute abdominal gynecologic emergencies underwent laparoscopic intervention. A transvaginal ultrasound was performed on all patients preoperatively to supplement the diagnostic workup. Surgical time, complications, and length of hospital stay were evaluated, and the laparoscopic diagnosis was compared with the preoperative diagnosis.
Results:
The laparoscopic diagnosis was different from the preoperative diagnosis in 31.8% of patients. Of the 22 patients, laparoscopic therapeutic procedures were performed in 18 (81.8%), all satisfactorily, and with no need for conversion to open surgery. No morbidity or mortality occurred.
Conclusion:
Laparoscopy is a safe and effective method for diagnosing and treating gynecologic emergencies.
PMCID: PMC3021278  PMID: 14558712
Acute abdomen; Gynecology; Gynecgolgic emergencies
25.  The Role of Nitric Oxide Synthase in Post-Operative Hyperglycaemia 
The Libyan Journal of Medicine  2008;3(3):144-147.
Post-operative hyperglycaemia is important with regard to outcomes of surgical operations. It affects post-operative morbidity, length of hospital stay, and mortality. Poor peri-operative blood glucose control leads to a higher risk of post-operative complication. Insulin resistance as a cause of post-operative hyperglycaemia has been blamed for some time. Nitric Oxide (NO) is produced by nitric oxide synthase (NOS) isoenzymes. Inducible nitric oxide synthase (iNOS) is not a normal cellular constitute. It is expressed by cytokines and non-cytokines e.g. fasting, trauma, intravenous glucose, and lipid infusion, which are encountered in surgical operations. Review of current published data on postoperative hyperglycaemia was completed. Our studies and others were explored for the possible role of NO in this scenario. Induction and expression of iNOS enzyme in pancreatic islet cells is included in the chaotic postoperative blood glucose control. The high concentrations of iNOS derived NO are toxic to pancreatic β-cells and may inhibit insulin secretion postoperatively. Hence, current peri-operative management is questionable regarding post-operative hyperglycaemia and necessitates development of a new strategy.
doi:10.4176/080416
PMCID: PMC3074270  PMID: 21516149
NO; glucotoxicity; lipotoxicity; post-operative hyperglycaemia; pancreatic islets

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