Two-year outcome of ventricular assist device via a modified left atrium to aorta approach in cardiac amyloidosis.

Cardiac amyloidosis is a debilitating disease associated with poor long-term survival. Medical or palliative treatment is the usual course of therapy, but patients are often intolerant of conventional heart failure treatment. The current standard of care of sequential heart and bone marrow transplant is usually not feasible for ill or frail patients or in countries with limited organ donors or without transplant programmes. Left ventricular assist devices (LVAD) are not usually offered to these patients due to high peri-operative risks and risks of suction events with the LVAD in a small left ventricle. We report the 2 year outcome and discuss the challenges faced in the management of our patient with end-stage heart failure due to cardiac amyloidosis, who was successfully supported with an LVAD using a modified left atrium to aorta implantation technique.

Customized Two-Dimensional Computed Tomography-Guided Preoperative Pectus Bar Shaping.

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.

Trachea Reconstruction with Single-Stage Composite Flaps in a Rabbit Model.

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.

Prognostic Factors for Survival After Extracorporeal Membrane Oxygenation for Cardiogenic Shock.

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.

Restrictive mitral valve annuloplasty for chronic ischaemic mitral regurgitation: outcomes of flexible versus semi-rigid rings.

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.

Elucidating the genomic architecture of Asian EGFR-mutant lung adenocarcinoma through multi-region exome sequencing.

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.

Pulmonary sclerosing pneumocytoma with mediastinal lymph node metastasis.

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.

Prevalence of Healthcare-Associated Infections and Antimicrobial Use Among Adult Inpatients in Singapore Acute-Care Hospitals: Results From the First National Point Prevalence Survey.

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.

Therapeutic Hypothermia May Improve Neurological Outcomes in Extracorporeal Life Support for Adult Cardiac Arrest.

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 (34oC) 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.

Novel Use of Thalidomide in Recurrent Gastrointestinal Tract Bleeding in Patients with Left Ventricular Assist Devices: A Case Series.

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.

A rare case of unilateral severe bullous emphysema in a 32-year-old female.

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.

Therapeutic hypothermia in adult patients receiving extracorporeal life support: early results of a randomized controlled study.

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.

Ciliated muconodular papillary tumor: a solitary peripheral lung nodule in a teenage girl.

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.

Contained Rupture in HeartMate II Outflow Graft Bend Relief Disconnection.

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.

Successful removal of uterine leiomyosarcoma tumour thrombus propagating to the right atrium.

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.

Impact of Smoking and Brain Metastasis on Outcomes of Advanced EGFR Mutation Lung Adenocarcinoma Patients Treated with First Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

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.