Search

Introduction Successful minimally invasive repair of pectus excavatum relies on a pectus bar that closely conforms to the desired shape of the sternum and ribs to produce optimal elevation and remodeling. However, the present method of empirical intraoperative bar shaping is tedious and risks trauma to surrounding structures. To overcome this, we devised a technique using a life-sized computed tomography (CT) printout of the patient's chest wall to guide preoperative bar bending. Methods A 5-cm-wide polymethylmethacrylate block placed on the sternum as the patient underwent chest CT was used as a marker to guide scaling of an axial screenshot of the patient's chest to life-size. This life-size image was printed and the planned correction of the patient's chest wall was traced onto it. The pectus bar was bent according to this template. Patient demographics, Haller index, surgical indications, operative technique, complications, aesthetic and functional improvements, and overall satisfaction were assessed. Results Thirty patients (4 women) underwent primary minimally invasive repair of pectus excavatum with a single pectus bar shaped preoperatively over an 8-year period. The average age and Haller index was 20.6 years and 5.4, respectively. The mean operative time was 66.4 minutes. Satisfactory sternal elevation was attained with a single attempt at bar insertion in all cases. Two patients had pneumothoraxes that resolved without intervention. The mean follow-up period was 50.1 months. There were no cases of bar migration or recurrence of deformity after bar removal. On a 5-point Likert scale, all patients indicated an improvement in aesthetic appearance (4.6), and patients with physical symptoms (10) reported an improvement in function (4.4). The overall satisfaction score was 4.7. Conclusions This technique of CT-guided preoperative pectus bar shaping is straightforward, eliminates the need for intraoperative revisions to bar shape, and achieves effective correction of the pectus excavatum deformity. All patients were satisfied with the aesthetic, functional, and overall outcomes.

The aim of this study is to examine factors that can predict mortality in patients that have veno-arterial extracorporeal membrane oxygenation (VA-ECMO) instituted for cardiogenic shock. A single-center, retrospective study of 127 patients who underwent VA-ECMO for cardiogenic shock between January 2003 and December 2017 was conducted. Eighty-three (65%) patients survived to weaning or bridging therapy. Complications on VA-ECMO include: hemorrhage (40%), stroke (14%), requirement for dialysis (42%), and limb ischemia (24%). Univariate analysis revealed shorter ECMO duration, higher body mass index, preimplantation creatinine > 100 mmol/l, lower preimplantation serum albumin, and the development of stroke or limb ischemia on ECMO to be significantly associated with mortality while on ECMO. Multivariate analysis by logistic regression found shorter ECMO duration and lower preimplantation serum albumin to be significantly associated with mortality. VA-ECMO is an effective strategy in treating patients with cardiogenic shock and provides a reasonable chance of survival to weaning or bridging to other therapy. Preimplantation hypoalbuminemia, preimplantation serum creatinine > 100 mmol/l, and the development of stroke and limb ischemia while on VA-ECMO are strongly associated with mortality.

EGFR-mutant lung adenocarcinomas (LUAD) display diverse clinical trajectories and are characterized by rapid but short-lived responses to EGFR tyrosine kinase inhibitors (TKIs). Through sequencing of 79 spatially distinct regions from 16 early stage tumors, we show that despite low mutation burdens, EGFR-mutant Asian LUADs unexpectedly exhibit a complex genomic landscape with frequent and early whole-genome doubling, aneuploidy, and high clonal diversity. Multiple truncal alterations, including TP53 mutations and loss of CDKN2A and RB1, converge on cell cycle dysregulation, with late sector-specific high-amplitude amplifications and deletions that potentially beget drug resistant clones. We highlight the association between genomic architecture and clinical phenotypes, such as co-occurring truncal drivers and primary TKI resistance. Through comparative analysis with published smoking-related LUAD, we postulate that the high intra-tumor heterogeneity observed in Asian EGFR-mutant LUAD may be contributed by an early dominant driver, genomic instability, and low background mutation rates., EGFR mutant lung adenocarcinoma (LUAD) exhibit diverse clinical outcomes in response to targeted therapies. Here the authors show that these LUADs involve a complex genomic landscape with high intratumor heterogeneity, providing insights into the evolutionary trajectory of oncogene-driven LUAD and potential mediators of EGFR TKI resistance.

Background Limited data exists on patients receiving therapeutic hypothermia during extracorporeal life support (ECLS). We investigated outcomes and prognostic factors in these patients. Methods A retrospective review was conducted for 225 consecutive adult patients treated with ECLS between July 2003 and January 2016. Extracorporeal life support was initiated for refractory cardiac arrest (>10 mins) in 79 patients (35.1%). Patient demographics, ECLS-related complications, in-hospital mortality and neurological outcomes were analysed. Results The mean age was 49.9±12.4 years. Sixty-two patients (78.5%) were male. The mean duration of CPR and ECLS were respectively, 32.0±23.3 mins and 5.4±4.0 days. Therapeutic hypothermia (34 o C) was maintained for 24hours in 14 patients (17.7%). Thirty-five patients (44.3%) were weaned off ECLS. Twenty-one patients (26.6%) survived to hospital discharge with 16 (20.3%) recovering good neurological function. Compared to ECLS at normothermia, neurologically favourable survival was higher in the hypothermia group (42.9% vs 15.4%, p=0.020). Multivariable analysis identified a non-shockable rhythm [odds ratio (OR) 5.1, confidence interval (CI) 1.5–16.8], ischaemic hepatitis (OR 6.2, CI 1.1–33.6) and hypoxic ischaemic encephalopathy (OR 5.1, CI 1.5–17.1) as predictors of in-hospital mortality. Therapeutic hypothermia (OR 4.9, CI 1.2–20.4) and acute renal failure (OR 0.19, CI 0.05–0.70) were predictors of neurologically favourable survival. Conclusions In this report of patients treated with ECLS, in-hospital survival and survival with good neurological performance were 26.6% and 20.3% respectively. A non-shockable rhythm, ischaemic hepatitis and hypoxic ischaemic encephalopathy were predictors of in-hospital mortality. Therapeutic hypothermia during ECLS was associated with improved neurological outcomes.

Background: Restrictive mitral annuloplasty is the mainstay of surgical correction of chronic ischaemic mitral regurgitation (CIMR). Long-term data on the various types of annuloplasty rings is limited. The aim of this study was to investigate the clinical and echocardiographic outcomes of restrictive mitral annuloplasty in patients with CIMR, comparing the use of flexible versus semi-rigid annuloplasty rings. Methods: A retrospective review was conducted for 133 patients with CIMR who underwent restrictive mitral annuloplasty at our institution between 1999 and 2015. Patient demographics and postoperative outcomes were analyzed. Results: Mean age was 61.9±9.2 years and 103 patients (77.4%) were male. All patients underwent coronary artery bypass grafting, with a mean of 3.3±0.8 grafts. Flexible rings was implanted in 39 patients (29.3%, group F) and semi-rigid rings in 94 (70.7%, group R). Preoperative New York Heart Association class was III/IV in 104 patients (78.2%). Mean preoperative left ventricular ejection fraction was 28.8%±10.2%. Preoperative mitral regurgitation was moderate in 51 patients (38.3%) and severe in 82 (61.7%). In-hospital mortality occurred in 11 patients (8.3%). Overall survival at 1, 5 and 10 years were, respectively, 86.4%, 69.7% and 45.9%. At 10 years, overall survival (group F 53.1%, group R 40.0%, P=0.330) and freedom from moderate to severe MR (group F 53.1%, group R 53.8%, P=0.725) did not differ significantly. Freedom from hospitalization for heart failure was 59.3%. Left ventricular reverse remodelling, defined as a reduction of left ventricular end-systolic volume index >15%, occurred more commonly in Group R (51.1%) compared to Group F (23.1%), P=0.003. Conclusions: Restrictive mitral annuloplasty was associated with an operative mortality of 8.3%. Heart failure symptoms and significant MR recur in approximately 40% of patients after 10 years. Survival remained suboptimal and was not influenced by the type of annuloplasty ring.

Background Trachea reconstruction requires creation of a functional lining, semirigid support, and vascularity. We aimed to design composite flaps with these three components in a rabbit model. Methods Circumferential (n = 9) and partial anterior (n = 8) tracheal defects were created in rabbits. A circumferential defect was reconstructed with a tubed ear flap incorporating cartilage for support and skin for lining. This was pedicled on the posterior auricular vessels and tunneled into the neck to bridge the defect. In the second experiment, a longitudinal anterior trachea defect was patched with a pedicled rib cartilage and intercostal muscle flap based on the internal mammary vessels. The vascularized fascia over the intercostal muscles replaced the lining while the cartilage provided support. Postoperatively, the rabbits were monitored clinically and endoscopically. The tracheal constructs were examined histologically after the animals were sacrificed. Results Rabbits with circumferential defects reconstructed with the ear flap survived up to 6 months. Histology demonstrated vascularized cartilage with good integration of the flap with native trachea. However, hair growth and skin desquamation resulted in airway obstruction in the long term. In the second experiment, all the rabbits survived without respiratory distress, and the intercostal muscle fascia was completely covered by native respiratory epithelium. Conclusion We described two experimental techniques using autologous composite flaps for single-stage trachea reconstruction in a rabbit model. Skin was a poor lining replacement, whereas vascularized muscle fascia became covered with respiratory epithelium. A rib cartilage and muscle flap could potentially be used for reconstruction of partial defects in humans.

Congenital bullous emphysema is defined as large bullae involving at least one-third of a hemithorax. We describe the case of a 32-year-old female who presented with increasing shortness of breath. Radiological investigations revealed severe emphysema with hyperexpansion of the right lung and a mediastinal shift to the left. A lung perfusion scan showed reduced perfusion in the right lung. The patient underwent a right pneumonectomy with a diagnosis of congenital bullous emphysema. She was doing well 6 years later.

Papillary tumors of the peripheral lung containing ciliated cells and extracellular mucin include solitary peripheral ciliated glandular papilloma, ciliated muconodular papillary tumor, and well-differentiated papillary adenocarcinoma with cilia formation. We report the case of a 19-year-old woman who was a nonsmoker and presented with an incidental small peripheral lung nodule. The resection specimen showed a soft grayish nodule. Histologic examination further revealed a relatively circumscribed mucinous nodule featuring a tubulopapillary tumor composed of ciliated columnar cells and goblet cells, accompanied with abundant extracellular mucin. No lepidic growth pattern was evident. The tumor cells were immunoreactive for cytokeratin 7, thyroid transcription factor-1, and carcinoembryonic antigen, whereas p63 and cytokeratin 5/6 highlighted the presence of basal cells. Next-generation sequencing did not identify any genetic alterations in targeted regions and mutational hotspots of a panel of 22 genes commonly implicated in lung and colon cancers. Taken together, our case was most likely a ciliated muconodular papillary tumor.

Introduction Reflex molecular testing plays a critical role in identifying actionable targets and allocating patients to appropriate treatment. We report the clinicopathologic features and treatment outcomes of non-squamous non-small cell lung cancer (NSCLC) patients who underwent reflex testing for EGFR and ALK . Methods We analyzed the data of NSCLC patients diagnosed from 2010 to 2014 who underwent reflex testing for EGFR (from 2010) and ALK (from 2012) alterations and compared the outcome of those positive for the alterations against those who were wild-type (WT). Using multivariate cox regression, we determined the significant prognostic clinical factors that predicted for an improved survival outcome. Results EGFR mutation was more prevalent among females and never-smokers. The median OS (months) for the positive group was 24.8 versus 13.3 for the WT group (p EGFR tyrosine kinase inhibitor (TKI) treatment (all p ALK fusion was more prevalent among Malay patients (p=0.031). There were no significant survival differences in OS between positive and WT groups. Prognostic factors include gender, ethnicity, ECOG status, treatment intent, number of palliative treatment and metastatic sites (all p ALK TKI treatment (p=0.06). Conclusion This study found significant differences in demographic and clinical characteristics, and treatment outcomes between positive and WT patients for EGFR and ALK profiles, reinforcing the importance of reflex testing in patient management.

Lung cancer has the highest cancer associated mortality rate in many countries across the world. In contrast to western populations, approximately half of lung adenocarcinoma cases in Singapore harbour activating epidermal growth factor receptor (EGFR) mutations, with preponderance for never smokers and female gender. Although EGFR tyrosine kinase inhibitors (TKIs) confer high response rates of up to 70%, drug resistance invariably ensues - most commonly through the “acquisition” of EGFR T790M mutation. While the extent and pattern of intratumoral heterogeneity (ITH) in non-small cell lung cancer (NSCLC) were recently described, these studies examined histologically and molecularly diverse cohort of patients, majority being current or ex-smokers. Here we report ITH in eight never-smoker EGFR mutant lung adenocarcinoma cases of Asian ethnicity. All eight patients had no prior treatment history and harboured an activating EGFR mutation (5 L858R , 2 exon 19 deletion, 1 exon 20 insertion). They underwent lobectomy for Stage IA, IB NSCLC. Tumors were harvested using a systematic sectoring protocol according to standard operation procedures, with tissue banked for exome sequencing, RNA-sequencing and SNP array. A total of 46 tumor sectors (at least 4 regions from each of the 8 tumors) were subject to whole exome sequencing, with matched normal samples. With an average sequencing depth of 100x, we identified 860 somatic exonic SNVs (601 being non-synonymous) and 49 indels across all samples. The median number of SNVs per patient was 112 and per sector was 49. Notably, activating EGFR mutations were identified across all tumor sectors of all but two patients (for whom it was identified in 3 of 5 and 5 of 7 sectors respectively). In addition, we did not identify the EGFR T790M mutation in any of the sequenced tumor sectors, suggesting that, this resistance mutation is not present at detectable frequencies even as a branch or subclonal event in a treatment naïve scenario. Of 20 genes that were significantly mutated across 46 individual tumor sectors, only two overlapped with published recurrently mutated genes in NSCLC. In conclusion, we show that activating EGFR mutations are ubiquitous truncal events in 6 of 8 Asian never-smoker lung adenocarcinoma – consistent with its role as a therapeutically tractable driver gene. The T790M mutation commonly associated with TKI resistance was not detected as a subclonal event in treatment naïve patients. Further, our study reveals the unique mutation spectra of Asian EGFR mutant lung adenocarcinoma, highlighting the value of multi-region sequencing in characterising the genomic architecture of defined molecular subsets of NSCLC from different ethnic backgrounds. Citation Format: Rahul Nahar, Weiwei Zhai, Angela Takano, Alexis Jiaying Khng, Xingliang Liu, Chong Hee Lim, Audrey S.M. Teo, Cheryl Xueli Chan, Apoorva Gogna, Kiat-Hon Lim, Tina Koh, Huay Mei Poh, Yin Yeng Lee, Liang He Chen, Tong Zhang, Vidhya Gomathi Krishnan, N Gopalakrishna Iyer, Pauline Ng, Wan Teck Lim, Bing Lim, Eng-Huat Tan, Daniel S.W. Tan, Axel M. Hillmer. Intratumor heterogeneity in never-smoker Asian EGFR mutant lung adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B2-54.

Lung cancer has the highest cancer associated mortality rate in many countries across the world. In contrast to western populations, approximately half of lung adenocarcinoma cases in Singapore harbour activating epidermal growth factor receptor (EGFR) mutations, with preponderance for never smokers and female gender. Although EGFR tyrosine kinase inhibitors (TKIs) confer high response rates of up to 70%, drug resistance invariably ensues - most commonly through the “acquisition” of EGFR T790M mutation. While the extent and pattern of intratumoral heterogeneity (ITH) in non-small cell lung cancer (NSCLC) were recently described, these studies examined histologically and molecularly diverse cohort of patients, majority being current or ex-smokers. Here we report ITH in eight never-smoker EGFR mutant lung adenocarcinoma cases of Asian ethnicity. All eight patients had no prior treatment history and harboured an activating EGFR mutation (5 L858R, 2 exon 19 deletion, 1 exon 20 insertion). They underwent lobectomy for Stage IA, IB NSCLC. Tumors were harvested using a systematic sectoring protocol according to standard operation procedures, with tissue banked for exome sequencing, RNA-sequencing and SNP array. A total of 46 tumor sectors (at least 4 regions from each of the 8 tumors) were subject to whole exome sequencing, with matched normal samples. With an average sequencing depth of 100x, we identified 860 somatic exonic SNVs (601 being non-synonymous) and 49 indels across all samples. The median number of SNVs per patient was 112 and per sector was 49. Notably, activating EGFR mutations were identified across all tumor sectors of all but two patients (for whom it was identified in 3 of 5 and 5 of 7 sectors respectively). In addition, we did not identify the EGFR T790M mutation in any of the sequenced tumor sectors, suggesting that, this resistance mutation is not present at detectable frequencies even as a branch or subclonal event in a treatment naïve scenario. Of 20 genes that were significantly mutated across 46 individual tumor sectors, only two overlapped with published recurrently mutated genes in NSCLC. In conclusion, we show that activating EGFR mutations are ubiquitous truncal events in 6 of 8 Asian never-smoker lung adenocarcinoma – consistent with its role as a therapeutically tractable driver gene. The T790M mutation commonly associated with TKI resistance was not detected as a subclonal event in treatment naïve patients. Further, our study reveals the unique mutation spectra of Asian EGFR mutant lung adenocarcinoma, highlighting the value of multi-region sequencing in characterising the genomic architecture of defined molecular subsets of NSCLC from different ethnic backgrounds. Citation Format: Rahul Nahar, Weiwei Zhai, Angela Takano, Alexis Jiaying Khng, Xingliang Liu, Chong Hee Lim, Audrey S.M. Teo, Cheryl Xueli Chan, Apoorva Gogna, Kiat-Hon Lim, Tina Koh, Huay Mei Poh, Yin Yeng Lee, Liang He Chen, Tong Zhang, Vidhya Gomathi Krishnan, N Gopalakrishna Iyer, Pauline Ng, Wan Teck Lim, Bing Lim, Eng-Huat Tan, Daniel S.W. Tan, Axel M. Hillmer. Intratumor heterogeneity in never-smoker Asian EGFR mutant lung adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-25.

Many chest wall reconstruction algorithms have been proposed, but there is still no general consensus. The purpose of this study is to review our single institutional experience in chest wall reconstruction and identify a working algorithm based on our retrospective analysis. This is a retrospective analysis of 54 patients who underwent chest wall reconstruction in our department from 1996 to 2011. The mean follow-up was 38 months. Central chest wall defects were the most common, while infection and tumour resection were the two most common indications. The pedicled latissimus dorsi flap was a versatile flap, used as a single or combination flap for anterolateral, lateral and posterior defects. The pectoralis major flap was suitable for central and anterolateral defects and the rectus abdominis flap for lower central defects. Omentum flaps were useful in radiation-damage skin or in patients with recurrent infection. Locoregional flaps are the mainstay of chest wall reconstruction. Most skeletal reconstruction, when required, is safely accomplished with the use of prosthetic materials. Free flaps are usually only indicated for large defects or when regional flaps are unavailable. Level of Evidence: Level IV, therapeutic study.

Pulmonary sclerosing pneumocytoma is a rare tumour with 23 cases reported to have metastasis to lymph nodes, but to date, only 6 had involved mediastinal nodal stations. Our patient was a 40-year-old Asian female with a 2.5 cm nodule in her right lower lobe. Positron-emission tomography suggested no nodal disease; but after resection, the intra-lobular, hilar and subcarinal nodes were all found to be involved. As prognosis of this rare disease is uncertain, we aim to report our findings against available literature and similar cases.

Background. We conducted a national point prevalence survey (PPS) to determine the prevalence of healthcare-associated infections (HAIs) and antimicrobial use (AMU) in Singapore acute-care hospitals. Methods. Trained personnel collected HAI, AMU, and baseline hospital-and patient-level data of adult inpatients from 13 private and public acute-care hospitals between July 2015 and February 2016, using the PPS methodology developed by the European Centre for Disease Prevention and Control. Factors independently associated with HAIs were determined using multivariable regression. Results. Of the 5415 patients surveyed, there were 646 patients (11.9%; 95% confidence interval [CI], 11.1%-12.8%) with 727 distinct HAIs, of which 331 (45.5%) were culture positive. The most common HAIs were unspecified clinical sepsis (25.5%) and pneumonia (24.8%). Staphylococcus aureus (12.9%) and Pseudomonas aeruginosa (11.5%) were the most common pathogens implicated in HAIs. Carbapenem nonsusceptibility rates were highest in Acinetobacter species (71.9%) and P. aeruginosa (23.6%). Male sex, increasing age, surgery during current hospitalization, and presence of central venous or urinary catheters were independently associated with HAIs. A total of 2762 (51.0%; 95% CI, 49.7%-52.3%) patients were on 3611 systemic antimicrobial agents; 462 (12.8%) were prescribed for surgical prophylaxis and 2997 (83.0%) were prescribed for treatment. Amoxicillin/clavulanate was the most frequently prescribed (24.6%) antimicrobial agent. Conclusions. This survey suggested a high prevalence of HAIs and AMU in Singapore's acute-care hospitals. While further research is necessary to understand the causes and costs of HAIs and AMU in Singapore, repeated PPSs over the next decade will be useful to gauge progress at controlling HAIs and AMU.

To review our experience of surgical management of infective endocarditis (IE) over a 13-year period and analyse the outcomes and associated prognostic factors.A retrospective review was conducted for 191 consecutive patients who underwent surgery for native and prosthetic valve endocarditis (PVE) between January 2000 and December 2012. Surgical outcomes were reviewed to include survival and postoperative complications. Follow-up was complete for 172 of 179 patients (96.1%) surviving to hospital discharge, with a mean follow-up of 6.6 ± 3.7 years.Mean age was 47.4 ± 14.9 years with 113 (63.9%) males. Native valve endocarditis was present in 177 patients (92.7%). Sixty-three patients (33.0%) presented with embolic complications. The brain was the most common site of embolism, involving 25 patients (13.1%). Streptococcus viridans was the most common infective organism, isolated in 68 patients (35.7%), followed by Staphylococcus aureus in 30 patients (15.7%). Eighty-seven patients (45.5%) had active endocarditis at the time of surgery. The mitral valve was infected in 136 patients (71.2%), the aortic valve in 66 (34.6%), the tricuspid valve in 29 (15.2%) and multiple valves in 38 (19.9%). Nineteen patients (9.9%) were intravenous drug users (IVDU). Twelve IVDUs (63.2%) suffered from tricuspid valve IE, compared with 7 of 162 patients (4.3%) in the non-IVDU population (P0.001). The most common indication for early surgery was intractable cardiac failure. Twelve patients (6.3%) died during the hospital stay for surgical treatment of IE. Logistic multivariate analysis identified preoperative creatinine clearance and stroke as independent predictors of in-hospital mortality. Overall 10-year survival and freedom from valve-related reoperation were 74.8 and 90.3%, respectively. Age, PVE, S. aureus endocarditis and postoperative left ventricular ejection fraction (LVEF) ≤45% were factors influencing long-term survival.Surgical management of endocarditis continues to be challenging and is associated with significant morbidity and mortality. This report of 191 patients who underwent valve surgery for IE shows that in-hospital mortality is influenced by preoperative renal function and stroke at the time of presentation. The optimal timing for surgery in patients with stroke remains controversial. Long-term survival was negatively influenced by increasing age, moderate to severely impaired LVEF, prosthetic valve IE and S. aureus infection.

We investigated global and regional effects of myocardial transplantation of human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) in infarcted myocardium. Acute myocardial infarction (MI) was induced by ligation of left coronary artery of severe combined immunodeficient mice before 2 × 10(5) iMSCs or cell-free saline were injected into peri-infarcted anterior free wall. Sham-operated animals received no injection. Global and regional myocardial function was assessed serially at 1-week and 8-week by segmental strain analysis by using two dimensional (2D) speckle tracking echocardiography. Early myocardial remodelling was observed at 1-week and persisted to 8-week with global contractility of ejection fraction and fractional area change in saline- (32.96 ± 14.23%; 21.50 ± 10.07%) and iMSC-injected (32.95 ± 10.31%; 21.00 ± 7.11%) groups significantly depressed as compared to sham control (51.17 ± 11.69%, P < 0.05; 34.86 ± 9.82%, P < 0.05). However, myocardial dilatation was observed in saline-injected animals (4.40 ± 0.62 mm, P < 0.05), but not iMSCs (4.29 ± 0.57 mm), when compared to sham control (3.74 ± 0.32 mm). Furthermore, strain analysis showed significant improved basal anterior wall strain (28.86 ± 8.16%, P < 0.05) in the iMSC group, but not saline-injected (15.81 ± 13.92%), when compared to sham control (22.18 ± 4.13%). This was corroborated by multi-segments deterioration of radial strain only in saline-injected (21.50 ± 5.31%, P < 0.05), but not iMSC (25.67 ± 12.53%), when compared to sham control (34.88 ± 5.77%). Improvements of the myocardial strain coincided with the presence of interconnecting telocytes in interstitial space of the infarcted anterior segment of the heart. Our results show that localized injection of iMSCs alleviates ventricular remodelling, sustains global and regional myocardial strain by paracrine-driven effect on neoangiogenesis and myocardial deformation/compliance via parenchymal and interstitial cell interactions in the infarcted myocardium.

Recent advances in medical and device therapies in heart failure have improved the survival of patients with heart failure. However, due to the limited availability of suitable heart donors, left ventricular assist devices (LVADs) have become an important tool as a bridge-to-heart transplantation for patients with refractory heart failure in Singapore. We report our experience with the HeartMate II (HMII) LVAD (Thoratec Corporation, Pleasanton, CA, USA) as a bridge-to-heart transplant in our center from 2009 to 2012. This was a retrospective review of 23 consecutive patients who underwent HMII LVAD implantation in our center between May 2009 and December 2012. All patients were classified as Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) levels 1 to 3 and underwent LVAD implantation as a bridge-to-heart transplant. There were 17 male and 6 female patients. The mean age was 43.6 years old (range 14 to 64). The etiologies of heart failure included ischemic heart disease [8], idiopathic dilated cardiomyopathy [11], viral myocarditis [2], and chemotherapy-induced cardiomyopathy [2]. Nine patients were INTERMACS level 1, 12 patients level 2, and two patients level 3. All patients successfully underwent HMII LVAD implantation. There was no mortality within the first 30 postoperative days. Postoperative complications included stroke with full neurological recovery (21.7%), mediastinal infection (21.7%), cardiac tamponade or mediastinal collection requiring reopening of the chest (39.1%), cardiac arrhythmia (13.0%), and pump thrombosis with pump replacement (4.3%). All patients were discharged from hospital after LVAD implantation. Three patients experienced driveline infections during outpatient follow-up. There were 19 readmissions due to the following conditions: sub-therapeutic anticoagulation (13.0%), gastrointestinal bleeding (13.0%), suspected pump thrombosis (13.0%), transient ischemic attack (8.7%), arrhythmia (8.7%), congestive cardiac failure due to severe aortic regurgitation (8.7%), right ventricular failure (4.3%), rhabdomyolysis (4.3%), and hematuria (4.3%). Post-LVAD implantation, 20 patients were functionally New York Heart Association (NYHA) class I, while 3 reported NYHA III symptoms. Three patients were successfully bridged to heart transplantation. One patient was successfully explanted 11 months after LVAD implantation. There were two mortalities during the follow-up period. The average duration of LVAD support was 522 days (range 47 to 1316 days). The HeartMate II LVAD has proven to be effective in our Asian population. Driveline infection rate remains low even in the tropical hot, humid climate in Singapore. With more patients ending up on extended periods of LVAD support, increased emphasis in the detection and management of long-term complications of ventricular assist devices will be needed.

Background Bleeding is an important and common complication of left ventricular assist devices (LVADs). One of the common causes of gastrointestinal bleeding is arteriovenous malformations. However, the source of bleeding is often hard to identify. Thalidomide is efficacious in treatment of gastrointestinal (GI) bleeding in non-LVAD patients. We report our experience of the use of thalidomide in the treatment of GI bleeding in four patients with LVAD. Method and Results Four patients who had recurrent GI bleeding from May 2009 to December 2014 were started on thalidomide. All of them responded to treatment and had no further gastrointestinal bleeding while on thalidomide. One patient developed constipation, requiring thalidomide to be stopped. Another patient developed symptomatic neuropathy, that resolved with reduction of dosage. Conclusion Thalidomide appears safe and efficacious in LVAD patients with recurrent gastrointestinal bleeding.

Tissue-engineered scaffolds may improve experimental outcomes in cardiac cell therapy by targeted delivery of stem cells and mechanically support an infarcted left ventricular (LV) wall. We transplanted cardiomyocyte-like cells (5×105) with scaffolding via epicardial patching (cell patch, n=17) or a low-dose intramyocardial hydrogel (LD hydrogel, n=18), a high-dose (5×106) intramyocardial hydrogel (HD hydrogel, n=18) or transplanting a serum-free medium control (control, n=13), a blank patch (n=14), and a blank gel (n=16) for targeted cardiomyoplasty in a myocardial infarcted rat model. LV real-time hemodynamics were assessed using a 1.9-F pressure–volume catheter 7 weeks after stem cell transplantation. All mode of scaffold transplantation protected diastolic function by preserving LV wall integrity that resulted in a lower end diastolic pressure–volume relationship (EDPVR) as compared to a control medium-injected group. Moreover, epicardial patching, but not hydrogel injection, reduced ventricular wall stress with a significantly better LV end diastolic pressure (EDP: 5.3±2.4 mmHg vs. 9.6±6.9 mmHg, p

OBJECTIVES: Intestinal ischaemia is an uncommon (

Pleural space problems after lung resection and persistent air leaks are among the commonest challenges posed to thoracic surgeons. Surgical repair of air leaks are indicated when conventional tube thoracostomy has failed to solve the problem. We would like to propose the novel application of the combined latissimus dorsi-serratus anterior transposition flap for selected cases of air leaks that are recalcitrant to conventional treatment. We discuss its indications and the surgical technique. Five patients underwent the procedure between 2004 and 2007. They were male patients aged between 32 and 70 years. Four patients had alveolar-pleural fistulas resulting in persistent air leaks while the fifth patient had, in addition, a space problem following lung volume reduction surgery. All patients had prolonged treatment with chest drains without success. With the patient in a lateral decubitus position, a lazy-S incision was used to expose the entire latissimus dorsi and the proximal slips of the serratus anterior muscles. They were raised as pedicled flaps and transferred in tandem. The latissimus dorsi was introduced into the pleural cavity via a thoracic window and used to reinforce the fistula repair. The serratus anterior muscle closed the rib window. In all cases, the lungs reexpanded and chest drains were removed within 5 days post surgery. There were no recurrent air leaks at 1-year follow-up with all patients. Conservative treatment in all our patients was unsuccessful. The dual flap technique has the advantage of allowing normal ventilation while providing a seal over the alveolar-pleural fistula. The muscle bulk of the latissimus dorsi fills the pleural dead space and the serratus anterior muscle seals the axilla preventing subcutaneous emphysema. There was minimal morbidity associated with the use of this dual muscle flap technique. This technique is an effective treatment option for recalcitrant air leaks.

Although intravenous leiomyomatosis is widely documented, intravenous extension of leiomyosarcoma into the inferior vena cava (IVC) and subsequently into the right atrium is extremely rare. Less than five such cases have been reported in the literature worldwide. Uterine leiomyosarcoma is an aggressive smooth muscle tumour occurring with an incidence of 1% in all female genital tract cancers and comprises about 3–7% of uterine cancers. It carries a generally poor prognosis with 5-year survival rates ranging from 18.8% to 65% across all stages. We report a case of primary uterine leiomyosarcoma with intravascular tumour propagation extending to the renal vein, IVC and right atrium of the heart, which was successfully resected in a one stage operation by a multidisciplinary team. This case demonstrates the importance of preoperative radiological staging and multidisciplinary planning.

Cardiac arrest with cerebral ischaemia frequently leads to severe neurological impairment. Extracorporeal life support (ECLS) has emerged as a valuable adjunct in resuscitation of cardiac arrest. Despite ECLS, the incidence of permanent neurological injury remains high. We hypothesize that patients receiving ECLS for cardiac arrest treated with therapeutic hypothermia at 34 °C have lower neurological complication rates compared to standard ECLS therapy at normothermia. Early results of this randomized study suggest that therapeutic hypothermia is safe in adult patients receiving ECLS, with similar complication rates as ECLS without hypothermia. Further studies are warranted to measure the efficacy of this therapy.

Heparin resistance (HR) is occasionally encountered in cardiac surgery. The objective of this study is to identify possible factors predisposing patients to heparin resistance. Four hundred patients scheduled for elective cardiac surgery requiring the use of cardiopulmonary bypass (CPB) were enrolled in this study. Data collection included: demographic data, types of preoperative anticoagulant/antiplatelet therapy, preoperative haematological and biochemical laboratory results, medical condition, baseline activated clotting time (ACT) and infusion volume prior to heparinisation. Patients who require 5 mg/kg or more to achieve ACT greater than 400 seconds before CPB were considered to be heparin resistant. All data was tested with a preliminary univariate analysis and factors associated with HR (p valueB /0.05) were entered into a multivariate logistic regression analysis. Factors associated with HR with a p valueB /0.05 are considered predictors for HR. Thirty-two (8.0%) of the 400 patients fulfilled the criteria for HR. Preoperative heparin (p /0.025), low molecular weight heparin (p /0.049), plateletcount ] /300,000/ml (p /0.022) and albumin plasma concentration 5 /35 g/dl 0, /0.044) are significantly associated with HR. HR patients also tend to require more volume replacement prior to CPB to maintain haemodynamic stability p /0.007). Perfusion (2006) 21, 99/103.

Thoratec recalled their HeartMate II ventricular assist device in March 2012 after some problems related to disconnection of the bend relief. Abrasion on the pump outflow graft caused by a disconnected bend relief is rare. We report the case of a 49-year-old man in whom a disconnected bend relief caused a puncture in the outflow graft, resulting in a contained hematoma, requiring outflow graft replacement.

Objectives This purpose of this study was to examine clinical-pathologic factors – particularly smoking and brain metastases – in EGFR mutation positive (M+) lung adenocarcinoma (ADC) to determine their impact on survival in patients treated with first line EGFR TKI. Methods A retrospective review of EGFR mutation reflex testing experience for all ADC diagnosed at a tertiary Asian cancer centre from January 2009 to April 2013. Amongst this cohort, patients with advanced EGFR M+ ADC treated with first line EGFR TKI were identified to determine factors that influence progression free and overall survival. Results 444/742 (59.8%) ADC reflex tested for EGFR mutations were EGFR M+. Amongst never-smokers (n=468), EGFR M+ were found in 74.5% of females and 76.3% of males, and amongst ever smokers (n=283), in 53.3% of females and 35.6% of males. Exon 20 mutations were found more commonly amongst heavy smokers (> 50 pack years and > 20 pack years, Pearson’s chi square p=0.044, and p=0.038 respectively). 211 patients treated with palliative first line TKI had a median PFS and OS of 9.2 and 19.6 months respectively. 26% of patients had brain metastasis at diagnosis. This was significantly detrimental to overall survival (HR 1.85, CI 1.09-3.16, p=0.024) on multivariate analysis. There was no evidence that smoking status had a significant impact on survival. Conclusions The high prevalence of EGFR M+ in our patient population warrants reflex testing regardless of gender and smoking status. Smoking status and dosage did not impact progression free or overall survival in patients treated with first line EGFR TKI. The presence of brain metastasis at diagnosis negatively impacts overall survival.

Recent advances in medical and device therapies in heart failure have improved the survival of patients with heart failure. However, due to the limited availability of suitable heart donors, left ventricular assist devices (LVADs) have become an important tool as a bridge-to-heart transplantation for patients with refractory heart failure in Singapore. We report our experience with the HeartMate II (HMII) LVAD (Thoratec Corporation, Pleasanton, CA, USA) as a bridge-to-heart transplant in our center from 2009 to 2012. This was a retrospective review of 23 consecutive patients who underwent HMII LVAD implantation in our center between May 2009 and December 2012. All patients were classified as Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) levels 1 to 3 and underwent LVAD implantation as a bridge-to-heart transplant. There were 17 male and 6 female patients. The mean age was 43.6 years old (range 14 to 64). The etiologies of heart failure included ischemic heart disease [8], idiopathic dilated cardiomyopathy [11], viral myocarditis [2], and chemotherapy-induced cardiomyopathy [2]. Nine patients were INTERMACS level 1, 12 patients level 2, and two patients level 3. All patients successfully underwent HMII LVAD implantation. There was no mortality within the first 30 postoperative days. Postoperative complications included stroke with full neurological recovery (21.7%), mediastinal infection (21.7%), cardiac tamponade or mediastinal collection requiring reopening of the chest (39.1%), cardiac arrhythmia (13.0%), and pump thrombosis with pump replacement (4.3%). All patients were discharged from hospital after LVAD implantation. Three patients experienced driveline infections during outpatient follow-up. There were 19 readmissions due to the following conditions: sub-therapeutic anticoagulation (13.0%), gastrointestinal bleeding (13.0%), suspected pump thrombosis (13.0%), transient ischemic attack (8.7%), arrhythmia (8.7%), congestive cardiac failure due to severe aortic regurgitation (8.7%), right ventricular failure (4.3%), rhabdomyolysis (4.3%), and hematuria (4.3%). Post-LVAD implantation, 20 patients were functionally New York Heart Association (NYHA) class I, while 3 reported NYHA III symptoms. Three patients were successfully bridged to heart transplantation. One patient was successfully explanted 11 months after LVAD implantation. There were two mortalities during the follow-up period. The average duration of LVAD support was 522 days (range 47 to 1316 days). The HeartMate II LVAD has proven to be effective in our Asian population. Driveline infection rate remains low even in the tropical hot, humid climate in Singapore. With more patients ending up on extended periods of LVAD support, increased emphasis in the detection and management of long-term complications of ventricular assist devices will be needed.

Most, though not all, heart valve banks performed routine histopathological examination of heart tissues after valve donation. Histopathological examination will enhance the safety of heart valve homografts for transplantation. This is highlighted by a milestone case of cardiac sarcoidosis, a potentially fatal condition which can involve valve leaflet, in a live donor. Since then, testing is mandated for all our bank’s donors, with the objective of detecting any cardiac-related contraindications, which might be missed during donor screening. It is also a valuable tool in providing additional information about the cardiac cause of death in deceased donors, especially those who passed away suddenly or from unknown cause. A review of histopathological findings in our donors’ heart tissues revealed numerous pathological features despite the small sample size (n=50). Of the deceased donors, 62.9% were diagnosed with pathological features, among which 72.7% had multiple abnormalities. 30% of our bank’s donors were heart recipients, who had multiple cardiac abnormalities. Some pathological findings were found to be interrelated. A donor heart with cardiomegaly revealed no pathological features, emphasising the necessity to correlate pathological results with clinical data collated during donor screening for a comprehensive clinical picture in the determination of tissue suitability.

Sternoclavicular joint infection is rare and tends to present insidiously in debilitated and immunocompromised patients. Between August 1996 and July 1998, we managed 7 patients with 8 sternoclavicular joint infections. Three were women. Their age ranged from 42 to 63 years. Five of the patients had significant associated medical conditions. Six patients, including 1 with bilateral involvement, underwent surgical resection, which consisted of radical excision of the involved joint, medial third of the clavicle, first and second ribs and adjacent muscular wall, and part of the manubrium. All of them underwent delayed reconstruction with either pectoralis major or latissimus dorsi flaps. There was 1 operative mortality from continuing sepsis from another source. All the surviving patients showed no sign of local recurrent infection and no functional deficits at follow-up. We conclude that infection of the sternoclavicular joint often presents late in debilitated patients. Medical therapy often fails in these cases. Radical excision is effective in eradicating the septic focus, and functional results after reconstruction are excellent.

Background To review the experience of surgical repair of post-infarction ventricular septal rupture (VSR) and analyze the associated outcomes and prognostic factors. Methods Following approval from the Singhealth Centralised Institutional Review Board (reference: 2011/881/C), a retrospective review was performed on 38 consecutive patients who had undergone surgical repair of post-infarction VSR between 1999 and 2011. Continuous variables were expressed as either mean ± standard deviation or median with 25th and 75th percentiles. These were compared using two-tailed t-test or Mann–Whitney U test respectively. Categorical variables were compared using chi-square or Fisher’s exact test. To identify predictors of operative mortality, univariate analysis of perioperative variables followed by multivariate analysis of significant univariate risk factors was performed. A two-tailed p-value < 0.05 was used to indicate statistical significance. Results Mean age was 65.7 ± 9.4 years with 52.6% males. The VSR was anterior in 28 (73.7%) and posterior in 10 patients. Median interval from myocardial infarction to VSR was 1 day (1, 4). Pre-operative intra-aortic balloon pump was inserted in 37 patients (97.8%). Thirty-six patients (94.7%) underwent coronary angiography. Thirty-five patients (92.1%) underwent patch repair. Mean aortic cross clamp time was 82 ± 40 minutes and mean cardiopulmonary bypass time was 152 ± 52 minutes. Coronary artery bypass grafting (CABG) was performed in 19 patients (50%), with a mean of 1.5 ± 0.7 distal anastomoses. Operative mortality within 30 days was 39.5%. Univariate analysis identified emergency surgery, New York Heart Association (NYHA) class, inotropic support, right ventricular dysfunction, EuroSCORE II, intra-operative red cell transfusion, post-operative renal failure and renal replacement therapy (RRT) as predictors of operative mortality. Multivariate analysis identified NYHA class and post-operative RRT as predictors of operative mortality. Ten year overall survival was 44.4 ± 8.4%. Right ventricular dysfunction, LVEF and NYHA class at presentation were independent factors affecting long-term survival. Concomitant CABG did not influence early or late survival. Conclusions Surgical repair of post-infarction VSR carries a high operative mortality. NYHA class at presentation and post-operative RRT are predictors of early mortality. Right ventricular dysfunction, LVEF and NYHA class at presentation affect long-term survival. Concomitant CABG does not improve survival.

While experimental studies on tracheal transplantation are numerous, these have failed to translate into wider clinical application due to various factors. This review discusses on the current techniques of processing, decontamination and storage of human tracheal allografts for clinical transplantation. We also present our lack of success in our attempt in tracheal allograft banking. With few allografts available for research, it is difficult to validate the effectiveness of various decontamination and preservation protocols. Some tissue banks adopt the use of controversial chemicals and irradiation for decontamination. While these methods may completely eliminate the risk of transmission of infectious diseases and micro-organisms, their effect on the integrity of the allograft and possible long-term side-effects to the patients remains unknown.

Prolonged air leak is one of the most common post-operative complications encountered after thoracic surgical operations involving mobilization or resection of lung parenchyma. Air leak typically manifests as persistent bubbling in a chest tube drainage system, but may also present with increasing subcutaneous emphysema or pneumothorax in a post-operative patient. No universal consensus exist as to the exact duration of air leak which constitutes a prolonged air leak, but it is generally regarded to exist if it is present for more than 5 days(14) or 7 days(2, 5-7) after initial surgery. It is an important complication that results in increased length of stay(8-15) and has been associated with other post-operative complications such as pneumonia(12, 14, 16), empyema(9, 10, 16) and ICU re-admission(12).

This study aims to examine iliofemoral anatomy and predictors of vessel size and tortuosity in Asian patients as transfemoral transcatheter aortic valve implantation (TAVI) may be limited by the smaller Asian physique.Characteristics and vessel dimensions of 549 patients undergoing ultrasonography were reviewed. The minimal luminal diameter (MLD) along the iliofemoral vasculature of each side was identified and the larger of the two sides was used to determine suitability for transfemoral TAVI.The mean age was 66 ± 11 years (68% males). Mean iliac MLD was 7.6 ± 1.7 mm, females smaller than males (7.2 ± 1.7 vs 7.8 ± 1.7, p0.001). Mean iliac MLD decreased with age: 7.9 ± 1.7 mm, 7.4 ± 1.9 mm and 7.3 ± 1.6mm for ages70 years, 70-79 years and ≥ 80 years respectively (p=0.038). Mean femoral MLD was 7.0 ± 1.7 mm, females smaller than males (6.3 ± 1.5mm vs 7.3 ± 1.8mm, p0.001). Females were more likely than males to have iliac and femoral MLD6mm (20% vs 12%, p=0.019 and 34% vs 21%, p=0.001). Independent predictors of smaller iliofemoral dimensions were female gender, lower body surface area, diabetes mellitus, dyslipidemia and smoking history. Significant iliac tortuosity was present in 11.8%, more frequent in males than females (15% vs 6%, p=0.005), and in those with logistic EuroSCORE ≥ 15 than15 (27% vs 10%, p=0.001).This study establishes the mean iliac and femoral artery diameters in a cohort of relatively young Asian patients. Age and female gender were associated with smaller vessel dimension and several independent predictors of smaller vasculature and tortuosity were identified. These results have implications for TF TAVI in Asia.

Stem cell-based therapy has emerged as a potential therapeutic option for patients with acute myocardial infarction. The ability of granulocyte colony-stimulating factor (G-CSF) to mobilize endogenous stem cells as well as to protect cardiomyocytes at risk via paracrine effects has attracted considerable attention. In the past decade, a number of clinical trials were carried out to study the efficacy of G-CSF in cardiac repair. These trials showed variable outcomes in terms of improved cardiac contractile function and suppressed left ventricular negative remodelling. Critical examinations of these results have raised doubts concerning the effectiveness of G-CSF in modulating functional recovery. However, these cumulative clinical experiences are helpful in the understanding of mechanisms and roles of signalling pathways in regulating homing and engraftment of bone marrow stem cells to the infarcted heart. In this review, we discuss some of the observations that may have influenced the clinical outcomes. Improving strategies that target the critical aspects of G-CSF-driven cardiac therapy may provide a better platform to augment clinical benefits in future trials.

Giant coronary aneurysm presented initially as acute ventricular septal rupture in a 65-year-old man. At surgery, aneurysms measuring more than 10 cm each were found in the right coronary and left anterior descending arteries. The right coronary artery was bypassed and the aneurysm was plicated. A 2-cm ventricular septal defect was patched. Postoperatively, the patient's condition deteriorated and he succumbed to septic shock.