Pre- and postcapillary pulmonary hypertension in dogs: Circulating biomarkers.

Background: Pulmonary hypertension (PH) in dogs is a syndrome that could be primary or secondary due to pulmonary disease, pulmonary thromboembolism, heartworm disease, and heart failure. Due to the inability of right heart catheterization in veterinary patients, there is a lack of differential criteria between PH forms. In some acute cases, it is impossible to provide a full EchoCG or catheterization study. In this situation, circulating markers may be useful to discover the possible mechanism of PH form and provide specific therapy. Aim: Following all previous data in human and veterinary studies, we assumed that plasm concentration of serotonin, endothelin-1 (ET-1), and vascular endothelial growth factor D (VEGF-D) would show a predominance in affected part of pulmonary circulation. Methods: We studied 59 small-breed dogs of different sexes and ages. Groups were formed according to a primary pathology: healthy dogs (n = 8); dogs with myxomatous mitral valve disease (MMVD) and postcapillary PH (PostPH, n = 23); dogs with MMVD and precapillary PH (PrePH, n = 28). Animals in the study were diagnosed with the primary disease by standard echocardiographic methods and algorithms. Blood samples were collected at the moment of presentation and frozen in a -80°C fridge. For biochemistry analysis, we used species-specific ELISA kits, provided by Cloud-Clone Corp. (USA). The tests were provided by the means of Almazov National Medical Research Center, IEM laboratory. Results: Dogs with EchoCG-proved PostPH had a higher concentration of VEGF-D in comparison to control and PrePH (р <0.001, for both). There was no difference between the control and PrePH groups (р >0.05). ET-1 was higher in PrePH in comparison to PostPH and control dogs (р <0.001, for both). In addition, there was no difference between the control and PostPH groups (р >0.05). Serotonin concertation did not have a difference between controls and PostPH. However, it was higher in PrePH than in control (р <0.033) and PostPH group (р <0.006). Receiver operating curve analysis showed that plasma concentrations of ET-1 (0.99) and VEGF-D (0.92) had high effectiveness in the differentiation of PostPH and PrePH. Conclusion: This study showed a correlation between circulating biomarkers (serotonin, ET-1, and VEGF-D). We found a connection between ET-1 and right-sided heart failure as well as VEGF-D and left heart failure in the PH context.

Deep inspiratory breath-hold radiotherapy for left-sided breast cancer: Initial experience with Active Breathing Coordinator™ in a regional hospital.

INTRODUCTION: Deep inspiratory breath-hold (DIBH) has become standard in radiotherapy for left-sided breast cancer to reduce the heart dose. This study evaluated breath-hold stability and reproducibility using Elekta's Active Breathing Coordinator™ (ABC) and its effectiveness and feasibility in left-sided breast cancer patients undergoing radiotherapy. METHODS: Eligible patients were planned with free breathing (FB) and DIBH protocols. DIBH treatment was considered if the mean heart dose (MHD) was ≥2 Gy on the FB plan. Those who proceeded with DIBH treatment were enrolled for the pilot study. Electronic portal images of DIBH treatment beams were taken using the movie-exposure mode for breath-hold stability and reproducibility analysis. DIBH effectiveness in heart dose reduction and impact on simulation and treatment durations were compared with FB protocol. RESULTS: Out of 56 eligible patients, 15 proceeded with DIBH treatment. The mean difference of patient setup within a single breath-hold was 0.4 mm; between different breath-holds of the same beam 1.1 mm and between different days 2.6 mm. DIBH reduced the MHD by 47% and the mean left anterior descending artery (LAD) dose by 35%. DIBH took longer time than FB in simulation and treatment. At least 14% of the eligible patients did not tolerate DIBH during simulation. CONCLUSIONS: ABC leads to stable and reproducible breath-holds and results in significant heart dose reductions. It may not be tolerated by all patients and has resource implications.

The role of motion tracking in assessing technical skill acquisition using a neonatal 3D-printed thoracoscopic esophageal atresia/tracheo-esophageal fistula simulator.

INTRODUCTION: Acquiring the technical skills required for thoracoscopic repair of esophageal atresia with tracheo-esophageal fistula (EA/TEF) is challenging. A high-fidelity 3D-printed pediatric thoracoscopic EA/TEF simulator has been developed to address this issue. This study explored motion-tracking as an assessment tool to distinguish between surgeons of different expertise using the simulator. METHODS: Participants performed a single intracorporeal suture between the esophageal ends in EA with TEF. Total relative path lengths of the right and left surgical instruments were recorded during the task. Each video-recorded attempt was assessed by a blinded pediatric surgeon using a modified Objective Structured Assessment of Technical Skills (OSATS) score. Data recorded as median (range) and statistical significance as p<0.05. RESULTS: The task was performed by 17 participants. The median OSATS scores identified a significant difference between experts and novices. A difference between left- and right-hands was only found in the mid-skill level group. Right-hand path length was greatest in novices and lowest in experts. Left-hand path length was greatest in novices and the mid-skill level group compared to experts. CONCLUSION: Experts had the lowest total path length for either hand, suggesting they had the greatest efficiency of movement. The similar high path lengths in both hands for novices indicate their relatively low level of skill with either hand. The difference between right- and left-hand path lengths in the mid-skill level group likely reflects the improved right-handed technical skills in contrast to the still developing left hand. Further focus on the left hand during simulation training may improve left-handed economy of movement.

Construct validation of a 3D printed neonatal thoracoscopic simulator: Can it measure expertise?

BACKGROUND: acquiring technical expertise for neonatal thoracoscopy is challenging. To address this, we designed a fully synthetic thoracoscopic simulator for which we established its construct validity. METHODS: three thoracoscopic tasks were assessed: ring transfer, needle pass and incision of a blind upper esophageal pouch (EA cut). Participants watched instructional videos with accompanying written instructions for each task before having their attempt video recorded. All tasks were marked by three blinded pediatric surgeons using a modified Objective Structured Assessment of Technical Skills (OSATS). Scores were assessed using appropriate statistical analysis and inter-rater reliability was analyzed by interclass correlation coefficient (ICC). RESULTS: 23 participants completed the ring transfer and needle pass and 21 the EA cut: 5 experts (consultant surgeons), 5 intermediate (registrars on a training program) and 13 novices (medical students, house surgeons or non-training registrars). All three tasks distinguished between novice and intermediate/expert (ring transfer p = 0.00001, needle pass p = 0.0004 and EA cut p = 0.0014, respectively). Interrater reliability was good for ring transfer and needle pass but poor for EA cut. CONCLUSION: the tasks distinguished between novice and intermediate/expert but not between expert and intermediate. In needle pass and EA cut, there was a trend for the experts to score higher than intermediate participants. Ring transfer and needle pass tasks achieved construct validity, had good interrater reliability and were found to be useful in assessing a novice surgeon's progression towards the intermediate level. Distinguishing between intermediate and expert may require assessment of more complex tasks such as intracorporeal suturing and tying. LEVEL OF EVIDENCE: II.

Master and Apprentice or a Slave to Technology? A Randomized Controlled Trial of Minimal Access Surgery Simulation-Based Training Techniques.

Introduction: This study set out to assess the efficacy of three different approaches to simulation-based minimal access surgery (MAS) training using a three-dimensional printed neonatal thoracoscopic simulator and a virtual simulator. Materials and Methods: Randomized controlled trial of medical students (N = 32), as novices to MAS. The participants performed two construct validated tasks on a thoracoscopic simulator and were then randomly allocated into four intervention groups: (1) three consultant-led sessions on a thoracoscopic simulator; (2) three self-directed learning sessions on the same simulator; (3) self-directed "virtual training" on the "SimuSurg" application; and (4) control. Postintervention participants repeated both tasks. Videos of all task attempts were de-identified and marked by a blinded consultant pediatric surgeon. Results: There were no statistically significant differences in baseline objective structured assessment of technical skills (OSATS) scores or demographics in any group. For the "ring transfer" task, Groups 1 and 2 showed significant improvement after intervention, with no significant change in Groups 3 or 4. There was no significant difference between Groups 1 or 2 in postintervention scores. For the "needle pass" task, no group demonstrated a statistically significant improvement after intervention. Conclusion: Practice on a physical simulator either consultant-led or self-directed led to improved scores for MAS novices compared with a virtual simulator or no intervention for a simple "ring transfer" task. This suggests that time on the physical simulator was the most important factor and implies that trainees could usefully practice simple tasks at their convenience rather than require consultant supervision. This improvement is not seen in more challenging tasks such as the "needle pass."

Acute diverticulitis: an ongoing economic burden on the health system.

BACKGROUND: Acute diverticulitis (AD) is an increasingly common cause of acute hospital admissions. An understanding of its economic burden is necessary to plan resource allocation, and for targeting health research funding. The aim of this study is to obtain an accurate estimate of the cost of AD, accounting not only for the initial episode, but all related costs incurred during long-term follow-up. METHODS: The study captures a cohort of patients who had an initial admission for AD from 1 January 2012-31 December 2012, and their treatment over a 6-year period. Cases were identified from a prospectively maintained database, with AD confirmed by computed tomography scan. The primary outcome was total healthcare cost related to AD. RESULTS: The study included 170 patients. The total cost was NZD1 956 859 with a median cost per patient of NZD4814. A total of 57% of the cost was incurred for the initial inpatient admission, with the remaining 43% incurred through re-admission, follow-up appointments, investigations and management. Half of the total cost was incurred by 11.8% of the cohort. In multivariate analysis, high cost of care was significantly associated with complicated and recurrent disease, operative intervention and length of stay. CONCLUSION: This study provides an accurate estimate of the overall cost of AD and its sequelae. There are considerable long-term costs associated with the index episode and a large proportion of the expenditure is incurred by a small group that included those with complicated disease. These findings are important for healthcare resource allocation and for targeting health research funding.

30-day mortality following palliative radiotherapy.

INTRODUCTION: Patients dying a short time after receiving palliative radiation are unlikely to have received benefit and may experience harm. To monitor the potential for avoidable harm, 30-day mortality following palliative radiation has been recommended for use as a quality indicator and the Royal College of Radiologist have recommended a rate of lower than 20%. At the Canterbury Regional Cancer and Haematology Service in Christchurch, New Zealand (CRCHS), we investigated 30-day mortality and evaluated the prognostic value of the TEACHH model in our population. METHODS: Palliative treatments from two, two-year periods (2012/2013 and 2016/2017) were retrospectively reviewed. We analysed 30-day mortality and several influencing variables. Patients were divided into three groups using the TEACHH model (type of cancer, performance status, age, prior palliative chemotherapy, prior hospitalizations and hepatic metastases). RESULTS: There were 1744 patients; 30-day mortality was 10% and was higher in patients with lung cancer (17% vs. 8% in non-lung cancer patients, P < 0.0001), patients having less than five fractions (13% vs. 9%, P: 0.0199) and patients in TEACHH group B/C (21% in C, 11% in B and 2% in group A, P < 0.0001). The majority of treatments (84%) used five fractions or less. CONCLUSIONS: The mortality rate is within the suggested quality indicator, and the decreasing mortality with increasing fractionation demonstrates suitable selection of patients for longer treatment regimens. The TEACHH model can be used to increase precision in estimating prognosis, identifying patients who should not receive treatment and conversely identifying those for whom a prolonged fractionation schedule may be appropriate.

Determinants of vancomycin nephrotoxicity when administered to outpatients as a continuous 24-hour infusion.

Vancomycin continuous infusion (VCI) is used to treat serious Gram-positive infections in outpatients. This study was conducted to retrospectively investigate the rate of nephrotoxicity and associated risk factors in out-patients on VCI between May 2013 and November 2018. Vancomycin concentration was monitored twice-weekly to ensure adequate concentrations while avoiding high concentrations linked to nephrotoxicity (a rise in serum creatinine of ≥50% or 44 µmol/L from baseline). The likelihood of developing nephrotoxicity was evaluated using multivariable logistic regression. The 223 patients treated had a mean (standard deviation) age of 61 (16.7) years, baseline serum creatinine of 83.9 (21.2) µmol/L and estimated glomerular filtration rate (eGFR) of 80.6 (20.1) mL/min/1.73m2. Most patients (66%) were treated for bone and joint infections. Eight patients (3.6%) developed nephrotoxicity. In the most parsimonious model, nephrotoxicity was independently associated with an increased median (interquartile range) weighted-average serum vancomycin concentration (28.0 [24.3-32.6] vs. 22.4 [20.2-24.5] mg/L; odds ratio [OR] 1.25; 95% confidence interval [95% CI] 1.09-1.46; P<0.002) and Charlson co-morbidity index (OR 1.62; 95% CI 1.07-2.47; P=0.02). Post-hoc analysis identified 26 patients with a lower nephrotoxicity threshold (rise in serum creatinine of ≥30% or 27 µmol/L). Independent predictors of nephrotoxicity in this group were an increased weighted-average vancomycin concentration, diabetes, con-gestive heart failure and exposure to non-loop diuretics. The nephrotoxicity rate during VCI in this study was lower than previously reported (3.6% vs 15.0-17.0%).  Reducing the weighted-average serum vancomycin concentration may reduce nephrotoxicity while maintaining efficacy.

End-User Input into the Design and Validation of a Synthetic Thoracoscopic Esophageal Atresia/Tracheo-Esophageal Fistula Simulator.

Introduction: Thoracoscopic repair of esophageal atresia and tracheo-esophageal fistula (EA/TEF) is challenging. We addressed this by designing a fully synthetic simulator of the procedure and described the design process and how its content validity was assessed. Methods: An iterative design and assessment of content validity was undertaken in three stages. Data were collected from participants who trialed the model and completed a survey of their experience (adapted from Barsness et al.). Results: The model was trialed by participants of varying experience. Each design refinement improved the model's fidelity and validity. For the last iteration of the simulator, the observed averages (out of a maximum of 5) were: value as a training tool 4.8, relevance 4.6, physical attributes 4.5, realism of material 4.25, realism experience 4.17, and ability to perform tasks 3.77. Conclusion: An iterative design process based on end-user feedback has led to a synthetic simulator that has achieved a high level of content validity. This model has advantages over other EA/TEF simulators in that it is relatively inexpensive and does not use animal tissue, thus removing ethical and procurement issues. It was rated highly for its value and relevance to training.

Radiotherapy for metastatic spinal cord compression; can the Rades score predict survival?

INTRODUCTION: Metastatic spinal cord compression (MSCC) can be debilitating and painful and carries a poor prognosis. There is increasing evidence that MSCC can be treated with single-fraction radiotherapy. The Rades score is designed to assist in identifying better prognosis patients who may benefit from longer radiotherapy courses. This study aims to study patterns of care for MSCC at a single center in New Zealand, and assess the Rades score and other variables as predictors of survival. METHODS: An audit of patients receiving palliative radiotherapy for MSCC at a single center over a 5- year period (2010-2014) was performed. Independent variables and the Rades score were gathered for each patient for statistical analysis to investigate associations between potential prognostic factors, treatments and survival. RESULTS: A total of 83 patients underwent analysis. Median overall survival was 14 weeks. Twenty Gray in five fractions (20 Gy/5) was the most frequently delivered radiotherapy course (89%). The simplified Rades score effectively stratified patients with Group 3 patients having significantly better survival with 40% surviving to 6 months compared to Group 1 and 2. Cancer type, receiving chemotherapy and receiving surgery were also significantly associated with survival. CONCLUSION: Overall survival at our centre is consistent with other published series. The Rades score is valid for predicting more prolonged survival in our population and could be used in selecting patients for longer radiotherapy courses.

High-grade Glioma - A decade of care in Christchurch.

INTRODUCTION: High-grade glioma (HGG) is a devastating illness. Our study aimed to investigate outcomes for patients with HGG treated in Christchurch focussing particularly on those diagnosed with glioblastoma mulitforme (GBM); compare GBM survival with international standards; examine factors associated with better prognosis; and assess the involvement of various allied health disciplines. METHODS: A 10-year retrospective study of patients who were diagnosed and treated for HGG at Christchurch Hospital. Kaplan-Meier method was used to estimate survival. Predefined multivariate analysis was performed to investigate potential prognostic and predictive factors. RESULTS: A total of 363 patients were diagnosed with HGG at a median age of 64 years with a 5-year overall survival of 6.1%. Patients with grade IV tumours had a poorer outcome than grade III patients (P = 0.0002, log-rank test). Eighty-two per cent of patients had a surgical resection or biopsy of the tumour. For those patients with GBM, gross tumour resection followed by radical chemoradiation was associated with better survival compared with needle biopsy (HR = 1.93, P = 0.018); increasing age was negatively associated with survival (HR = 1.02 per additional age year, P = 0.037); however, waiting time between neurosurgery and radiation did not affect survival. Six per cent of patients received formal psychological input. CONCLUSION: Our survival outcomes were comparable with internationally published series. More research is required to improve survival in HGG, including molecular guided treatment, and better define treatment paradigms, such as for the elderly and frail.

Ischaemic heart disease following conventional and hypofractionated radiation treatment in a contemporary breast cancer series.

INTRODUCTION: We report the incidence of ischaemic cardiac toxicity in a contemporary cohort of patients receiving conventional (CFRT) or hypofractionated (HFRT) radiation after surgery for early breast cancer and investigate the interplay of cardiac risk factors and fractionation. METHODS: Included were patients receiving external beam radiation treatment from 2002 to 2006 at the Christchurch public hospital. Hospital coding databases, oncology databases and medical records were reviewed for baseline characteristics, treatment details and outcomes. The primary outcome was cardiac toxicity (including myocardial infarction, admission for cardiac chest pain, coronary angiogram positivity and ischaemic cardiac death). Kaplan-Meier methods were used to derive ischaemic cardiac event free and overall survival. Predefined univariate and multivariate analysis was performed to investigate interaction with radiation fraction size, cardiac risk factors, age and side of cancer. Standardised mortality ratios were constructed. RESULTS: Five hundred and one patients were identified, 220 treated with CFRT and 281 with HFRT. The median age was 56 and median follow-up 10.33 years. The 10-year breast cancer specific survival was 81.8% (95% CI %.78.1-85.0). The 10-year freedom from cardiac death was 98.6% (95% CI 96.9-99.4). There were 27 post radiation cardiac events including 5 cardiac deaths and 19 cases of acute myocardial infarction. 265 (53%) had at least one cardiac risk factor. Twenty five of the 27 patients with a cardiac event had cardiac risk factors. On univariate and multivariate analysis, fractionation schedule was not significantly associated with a post radiation ischaemic event, however, there was a significant relationship with age and the presence of a cardiac risk factor. The standardised mortality ratio was 0.89 (95% CI: 0-3.13). CONCLUSIONS: Our study has shown a low rate of ischaemic cardiac disease for both CFRT and HFRT in women treated for breast cancer with no evidence of an effect with fractionation schedule. Coexisting cardiac risk factors are common in the population.

Complications of curative radiation treatment for early prostate cancer.

AIM: To report the incidence of urological complications following curative radiation treatment for early prostate cancer, including minimally invasive urological procedures (MUIP), hospital admissions and open surgical procedures. Second malignancies following radiation are also reported and compared with patients undergoing a prostatectomy. METHODS: Included were patients receiving curative intent external beam radiation treatment for early prostate cancer between January 1, 2002, and December 31, 2009. Medical records were reviewed for baseline characteristics, treatment details and outcomes. Kaplan-Meier methods were used to derive the 5-year cumulative incidence of the urological outcomes and second malignancy. RESULTS: There were 439 patients identified. The median follow-up was 6.96 years. The median age was 69. A total of 56 patients developed a radiation related urological complication, 25 requiring hospital admission. The 5-year cumulative incidence for an MIUP and admission was 3.95% (95% confidence interval (CI), 2.47-6.28) and 2.24% (95% CI, 1.17-4.27), respectively. There were no open surgical procedures. Further malignancy developed in 27 patients during the 5- to 9-year posttreatment period with a cumulative incidence of 10.7% (95% CI, 7.31-15.51). Of the comparator prostatectomy group, of the 265 eligible patients analyzed, 19 patients developed a second malignancy with a cumulative incidence of 9.92% (95% CI, 6.28-15.48). On log-rank testing, there was no difference in the cumulative incidence rates of second malignancy between 5 and 9 years, following respective treatments (P  =  0.8554). CONCLUSIONS: The incidence of MUIP, hospital admissions and open surgical procedures following radiation is reassuringly low. The second malignancy rates are also low and similar to the rates in patients treated with a prostatectomy.

The Utility of Contrast Medium Fractional Flow Reserve in Functional Assessment Of Coronary Disease in Daily Practice.

BACKGROUND: Adenosine induced hyperaemic fractional flow reserve (aFFR) is a validated predictor of clinical outcome and part of routine interventional practice. Protocol issues associated with the adenosine infusion limit the use of aFFR in clinical practice. Contrast medium induced hyperaemic FFR (cFFR) is a simpler procedure from a practical standpoint. We compared the two in a real world setting. METHODS: We analysed 76 patients that had both cFFR and aFFR assessment of 100 angiographically indeterminate coronary stenosis. cFFR was performed with intracoronary contrast medium injections (10ml for left coronary lesions and 8ml for right coronary lesions). The diagnostic performance of cFFR was analysed and compared to the gold standard aFFR. RESULTS: Mean cFFR was 0.87 (±0.07) and mean aFFR was 0.84 (±0.08). Bland-Altman analysis revealed a close agreement between cFFR and aFFR (0.035±0.032; 95% CI: -0.028 to 0.098) and good linear correlation (r=0.92, r2=0.86; p<0.0001). Using cFFR cut-off values of ≤0.83 in predicting an aFFR value of ≤0.80 or a cFFR value ≥0.88, predicting an aFFR value of >0.80 yielded a sensitivity of 100%, specificity of 96.1%, positive predictive value of 92.3%, negative predictive value of 100% and diagnostic accuracy of 96%. Only 24% of cFFR values were in the 0.84 to 0.87 range. CONCLUSION: Contrast medium induced hyperaemic FFR as an initial assessment may limit the need for adenosine to when cFFR falls in the 0.84 to 0.87 range. The use of adenosine infusion potentially could have been avoided in the majority of patients in this study.

Small Numbers, Big Challenges: Adolescent and Young Adult Cancer Incidence and Survival in New Zealand.

PURPOSE: This study was undertaken to determine cancer survival and describe the unique spectrum of cancers diagnosed among New Zealand's adolescents and young adult (AYA) population. METHODS: Registrations for 1606 15-24 year olds diagnosed with a new primary malignant tumor between 2000 and 2009 were obtained from the New Zealand Cancer Registry and classified according to AYA diagnostic group and subgroup, age, sex, and prioritized ethnicity. Age-standardized incidence rates (IRs) per million person years and 5-year relative survival ratios were calculated. RESULTS: Cancer incidence was 228.6 per million for adolescents aged 15-19 years and 325.7 per million for young adults aged 20-24 years. Overall IRs were consistent across all ethnic groups but there were unique ethnic differences by tumor group including a higher incidence of bone tumors, carcinoma of the gastrointestinal tract, and gonadal germ cell tumors among Maori, a higher incidence of leukemia among Pacific peoples, and a higher incidence of melanoma among non-Maori/non-Pacific peoples. Five-year relative survival for adolescents (75.1%) and AYA overall (80.6%) appeared poorer than had been achieved in other high-income countries. Maori (69.5%) and Pacific (71.3%) AYA had lower 5-year survival compared to non-Maori/non-Pacific peoples (84.2%). CONCLUSION: The survival disparities observed require further investigation to identify and address the causes of these inferior outcomes. The newly established AYA Cancer Network Aotearoa has been tasked with improving cancer survival and care and ensuring equality of access for New Zealand AYAs with cancer.

Long-term outcomes of hepatic resection for colorectal liver metastases at a New Zealand tertiary level public hospital.

BACKGROUND: Colorectal cancer is common with half of all patients developing metastases to the liver. The aim of this study was to document the survival for patients undergoing liver resection for colorectal cancer metastases. METHOD: A review of all patients undergoing hepatic resection for colorectal liver metastases at a New Zealand tertiary level public hospital over a 9-year period was performed. RESULTS: Primary survival outcomes assessed were overall survival (OS) and disease-free survival (DFS). Of the 116 patients followed-up with a median (range) of 53 (10-116) months, the OS at 5 years was 53%. Median survival was 6.5 years. At end of follow-up, 57% of patients were alive and 49% were alive without recurrence. The overall rate of recurrence was 39%. CONCLUSION: This study confirms that excellent long term survival can be achieved with hepatic resection for colorectal liver metastases.