Squamous cell carcinoma of the anal sac in two cats.

This report describes two cases of feline anal sac squamous cell carcinoma. Cat 1 was managed with a multimodal approach combining surgical resection, radiation therapy and systemic therapy (toceranib phosphate; Palladia™) until local recurrence was identified at 236 days postsurgery. At that time, the cat received carboplatin. With the tumour being progressive, the cat was euthanased 552 days post initial surgery. Cat 2 was managed palliatively with a non-steroidal anti-inflammatory (meloxicam) and supportive medications. Unfortunately, with further decline in quality of life following initial diagnosis, the cat was euthanased 28 days later. Squamous cell carcinoma should be considered as a possible differential diagnosis when a cat is presented for investigation of an anal sac mass.

Assessment of the cost-effectiveness of alternative bovine tuberculosis surveillance protocols in French cattle farms using the mixed interferon gamma test.

Periodic screening in farms, using intradermal cervical comparative tuberculin test (ICCT), is a component of the French ante mortem surveillance of bovine tuberculosis (bTB). Previous studies have estimated the cost-effectiveness of the French mandatory bTB screening protocols. In these protocols, a second ICCT (ICCT2) is performed 42 days after the first one (ICCT1), either on the entire herd (strict protocol) or in series on animals with non-negative results (reactors) to ICCT1 (compliant protocol). The 42-days interval reduced protocols' cost-effectiveness. To minimize this interval, we suggested two alternative protocols, in which a mixed interferon gamma test (IFNMIX), with better sensitivity than ICCT2 and comparable specificity, replaces the ICCT2, and is carried out directly after the ICCT1. In the strict alternative protocol, reactors to ICCT1 are culled to perform laboratory analyses (PCR, bacteriology). Negative results to these analyses imply the IFNMIX testing of the entire herd. In the compliant alternative protocol, only reactor(s) to ICCT1 are tested with IFNMIX, and animals with positive results to IFNMIX are culled for laboratory analyses. We evaluated these protocols through scenario tree modelling. The estimated cost-effectiveness indexes showed that the compliant alternative protocol was the most efficient. The strict protocols (mandatory and alternative) were never the most efficient, but were the most effective. Therefore, using IFNMIX instead of ICCT2 may be useful in reducing the costs of the compliant protocol used when the probability of infection is considered low. The strict alternative protocol may become more attractive would IFNMIX's price decreased.

First results from five multidisciplinary diagnostic centre (MDC) projects for non-specific but concerning symptoms, possibly indicative of cancer.

BACKGROUND: Patients with non-specific symptoms often experience longer times to diagnosis and poorer clinical outcomes than those with site-specific symptoms. This paper reports initial results from five multidisciplinary diagnostic centre (MDC) projects in England, piloting rapid referral for patients with non-specific symptoms. METHODS: The evaluation covered MDC activity from 1st December 2016 to 31st July 2018, with projects using a common dataset. Logistical regression analyses were conducted, with a diagnosis of any cancer as the dependent variable. Exploratory analysis was conducted on presenting symptoms and diagnoses of cancer, and on comparisons within these groupings. RESULTS: In total, 2961 patients were referred into the MDCs and 241 cancers were diagnosed. The pathway detected cancers across a broad range of tumour sites, including several rare and less common cancers. An association between patient age and cancer was identified (p < 0.001). GP 'clinical suspicion' was identified as a strong predictor of cancer (p = 0.006), with a reduced association with cancer observed in patients with higher numbers of GP consultation before referral (p = 0.008). CONCLUSIONS: The MDC model diagnoses cancer in patients with non-specific symptoms, with a conversion rate of 8%, demonstrating the diagnostic potential of a non-site-specific symptomatic referral pathway.

Integrating data of veterinarians' practices in assessing the cost effectiveness of three components of the bovine tuberculosis surveillance system by intradermal tuberculin testing in French cattle farms through a scenario-tree approach.

Disease surveillance systems' effectiveness relies on participants following prescribed practices. We developed a general method to improve a previous cost-effectiveness evaluation of three French screening program protocols for bovine tuberculosis (bTB) to account for the practices of participants by scenario tree modelling. This method relies on: 1) semi-directive interviews of participants to identify the variability of practices and potentially influential factors, and to understand the sociological context; 2) a quantitative survey, based on multiple-choice questions, to quantify various practices and identify significantly influential factors by multivariable regression analyses; 3) addition of the scenario-tree nodes corresponding to the practices and their influential factors and configuration of the new limbs according to the data of the quantitative survey. We used this approach to integrate data concerning veterinary practices and identify some failures to conform to regulatory guidelines regarding intradermal cervical comparative tuberculin test (SICCT) (testing and notification of non-negative results). Such nonconformities appeared to be mainly caused by cattle restraint issues and the perception of veterinarians of the bTB control program. Indeed, their perception of that program significantly influenced veterinarians' practices. We modelled the influence of the SICCT practices on the SICCT results. The incorporation of these data led to a major decrease of the herd sensitivity estimations relative to the previous assessments that did not incorporate data of practices (15% to 42% decrease). This result shows the important impact of veterinarians' practices and their influencing factors (such as perception of the bTB control program) on the effectiveness of the surveillance system.

Cost-effectiveness of two different protocols for animal tracing investigations of bovine tuberculosis outbreaks in France.

In the French bovine tuberculosis (bTB) surveillance program, tracing-on and back investigations have a major importance as, in 2016, they represented about 21 % of the detected outbreaks. Building on our previous work on the other surveillance system components (Poirier et al., 2019), we evaluated for the first time the sensitivity and the cost of the two existing protocols of bTB's tracing-on investigations trough scenario tree modelling with a stochastic approach. We used French databases (national database for bovine identification and database recording all bTB surveillance and control results) and direct and indirect costs collected in a previous study. These assessments allowed us to calculate the cost-effectiveness index (cost/sensitivity) of each tracing-on protocol. In the first protocol (trace-and-cull protocol), the animal(s) linking the farm to an outbreak are systematically culled for bacteriology, PCR and histology testing. In the second protocol (trace-and-test protocol), the traced animal is culled only if it had non-negative result to an intradermal cervical comparative tuberculin test (ICCT). We estimated herd sensitivity of the two tracing-on protocols for 12 herd types defined by their production type, size and herd turnover. For the trace-and-cull protocol, mean herd sensitivity was estimated between 67.3 % [66.8-67.7]CI95 % and 89.2 % [88.7-89.7]CI95 % and between 51.2 % [50.8-51.5]CI95 % and 73.1 % [72.6-73.6]CI95 % for the trace-and-test protocol, depending on herd type. The trace-and-cull protocol was between 278 €/herd and 717 €/herd more expensive than the trace-and-test protocol, depending on herd type. Regardless of herd type, the trace-and-cull protocol had the smaller cost/sensitivity ratio and was therefore the most cost-effective protocol. That work showed that systematically culling traced animals to perform bacteriology and PCR on them (trace-and-cull protocol) is associated with a better herd sensitivity and is more cost-effective for all herd types. That is consistent with French veterinary authorities' recommendations but does not account for sociological aspects such as the bond between the farmer and his animals. Yet, cost-effectiveness difference was minor in small dairy and beef herds with a low turnover, suggesting the protocol could be chosen depending on the epidemiological context in those herds.

Cost-effectiveness assessment of three components of the bovine tuberculosis surveillance system by intradermal tuberculin testing in French cattle farms by a scenario tree approach.

In most officially bovine tuberculosis (bTB)-free countries, bTB has not been fully eradicated. Costly and time-consuming surveillance and control measures are therefore still in place to control this infection. An officially bTB-free status, both at the national and at the herd level, influences whether and when animals can be sold. Thus, this infection is still an economic issue, justifying measures towards its eradication. An evaluation of the cost-effectiveness of such measures would be highly useful, especially to optimise the costs of control measures and their adaptation to a local epidemiological context. We evaluated the cost-effectiveness of three mandatory surveillance protocols currently used in France by herd type (type of production, size, and turnover of the herd) under French field conditions. The first protocol ("strict") implies the direct slaughter and post-mortem analyses of any intradermal cervical tuberculin test (ICT) reactor, and negative results to a second intradermal cervical comparative tuberculin test (ICCT) to regain bTB-free status of the herd. In the second protocol ("compliant quick-path") bTB-free status can be regain if post-mortem analyses of reactors to the first ICT are negative. In the third protocol ("compliant slow-path"), ICCT-reactive animals are tested using the interferon gamma assay; the results of this test influence the path of further investigation. We built scenario trees for each of these protocols at the animal level. They allowed us to estimate herd sensitivity and the total cost of each protocol by herd type. The protocols could be ordered by decreasing herd sensitivity and cost, regardless of the herd type, as follows: strict protocol, compliant quick-path protocol, and compliant slow-path protocol. We calculated a cost-effectiveness index to evaluate the cost-effectiveness of each protocol. The strict protocol was never the most cost-effective, regardless of herd type, due to higher costs relative to the other protocols, despite better herd sensitivity. We found the compliant quick-path to be the most cost-effective protocol for big beef, big dairy, and mixed herds. The compliant slow-path was the most cost-effective for small-scale beef and dairy herds. All differences were significant. This comparison of the cost-effectiveness of the protocols by herd type could help authorities to choose the most suitable protocol in the investigation of suspected cases, depending on the herd type, but could be improved by accounting for important sociological data, such as the acceptability of the protocols.

Outcome of secondary intention healing of full thickness lower eyelid defects in dogs.

OBJECTIVES: To assess healing of the canine lower eyelid without anatomical reconstruction. MATERIALS AND METHODS: Retrospective case series of three client-owned dogs with lower eyelid defects. These dogs that underwent debridement of lower eyelid wounds that were left to heal by secondary intention were assessed for anatomical, functional and aesthetic outcomes. RESULTS: Two of the cases had previously undergone tumour resection with a lip-to-lid reconstruction and, following flap failure, developed a full thickness defect. The third dog presented with a traumatic laceration. Each dog lost approximately 70 to 90% of the lower eyelid margin. Two received topical antimicrobial eye drops after debridement, while the third dog required no further treatment. Follow-up periods of 3 years, 15 months and 4 months were available. All owners were satisfied with the cosmetic outcome and provided pictures. One owner reported epiphora but no other ophthalmic complications occurred. CLINICAL SIGNIFICANCE: The result of this small case series supports the notion that not all lower eyelid injuries or tumour resections require anatomical reconstruction. Selected cases can be left to heal by secondary intention with minimal post-operative complications.

Efficacy of Radiation Therapy for the Treatment of Sialocele in Dogs.

BACKGROUND: Sialocele is a collection of saliva that has leaked from a damaged salivary gland or duct and is surrounded by granulation tissue. Surgery is the recognized first-line treatment. Recurrence rate after surgery is 5-14%. Salivary gland tissue is very sensitive to radiation therapy (RT). HYPOTHESIS/OBJECTIVES: Radiation therapy will be useful for the treatment of sialocele. The aims were to characterize response rate and clinical course of dogs with sialocele treated with RT and to determine a starting dose for clinical use. ANIMALS: Eleven dogs with sialocele. METHODS: Retrospective study of response and outcome after RT. RESULTS: All dogs had cervical sialocele. Seven dogs (63.6%) were treated with 3 weekly fractions of 4 Gray (Gy); (total dose, 12 Gy). Three dogs (27.3%) received 4 fractions of 4 Gy (16 Gy) and 1 dog received 5 fractions of 4 Gy (20 Gy) on a Monday-Wednesday-Friday schedule. Six dogs (54%) achieved a complete response (CR), and 5 dogs (45%) achieved a partial response (PR). Three dogs had progression of their sialocele 2, 3, and 9 months after RT; all three had received 12 Gy initially and 2 received 2 additional fractions of 4 Gy (cumulative total dose, 20 Gy) and subsequently achieved remission for >2 years. CONCLUSIONS AND CLINICAL IMPORTANCE: Radiation therapy is useful for the treatment of recurrent sialocele refractory to surgical management and a minimum total dose of 16 or 20 Gy in 4 Gy fractions appears effective.

[Motivations for a consultation before adoption: A multicenter study]. / Étude multicentrique sur les motivations d'une consultation avant adoption.

INTRODUCTION: While the number of international adoptions in France is decreasing, adopted children are older and in poorer health than they used to be. This phenomenon has resulted in an increase in the demand for preadoption consultations over the past several years. This study analyses the reasons for these consultations. METHOD: Prospective multicenter study conducted from 1 January to 31 December 2013. RESULTS: Ten centers contributed to the study, i.e., 196 preadoption consultations. Seeking medical advice was the reason for 88% of the consultations, whether the advice was based on the study of an identified child's medical file (32%) or a country's healthcare characteristics, whether the country was identified (34%) or not (23%). In 6% of cases, the motive for preadoption consultations was social and familial, and in the last 5% it was to obtain general information about adoption and its procedures. In more than 40% of the cases, whether the child or the country identified, Russia is the subject of the consultation because of the complexity of the files and because of the dreaded but rarely mentioned fetal alcohol syndrome. CONCLUSION: The deterioration of adopted children's health is an additional worry for future adoption applicants. To provide them with the best information possible without making choices for them, specialists should have substantial experience in adoption before going into these preadoption consultations.

Hypofractionated radiation therapy for the treatment of microscopic canine soft tissue sarcoma.

Soft tissue sarcomas (STSs) are locally invasive and surgery with or without radiation therapy is the current standard of care in dogs. Typical protocols for treating incompletely excised STSs involve curative intent radiation with total dose in excess of 50 Gy. Forty-eight dogs with histologically confirmed incomplete or closely excised STSs were treated with a hypofractionated protocol that is typically reserved for palliative radiation therapy (RT) (6-8 Gy/weekly fractions to a total dose of 24-32 Gy). Ten dogs (21%) developed local recurrence, 11 dogs (23%) developed metastasis, and 3 dogs developed both (included in each group). The median progression free survival was 698 days. The local failure-free probability at 1 and 3 years was 81 and 73%. The 1 and 3 years tumour-specific overall survival was 81 and 61%. Long-term local tumour control was achieved in the majority of dogs. This protocol is reasonable to prescribe in older patients or when financial limitations exist.

Transmission of infectious diseases from internationally adopted children to their adoptive families.

Internationally adopted children may suffer from different pathologies, including infectious diseases contracted in the country of origin. We evaluated the frequency of infectious diseases that may disseminate from adoptees to adoptive families on their arrival in France. All children who attended the clinic for international adoption in Clermont-Ferrand from January 2009 through to December 2011 were eligible for inclusion in the study. Standardized medical records dedicated to international adoption were retrospectively reviewed for demographic data, clinical diagnosis, and biological and radiological results. Data were completed by phone interviews with adoptive families after informed consent. One hundred and forty-two medical records were retrospectively reviewed and 86% of families agreed to be interviewed. One hundred and seventy-one potentially transmissible infections were diagnosed in 142 children, 12% (n = 20) of which were transmitted to adoptive families. Most of these infections were benign and transmission was restricted to the close family. Tinea was diagnosed in 44 adoptees and transmitted in 15 cases. Panton Valentine leukocidin producing methicillin-sensitive S. aureus (MSSA) was transmitted to an adoptive father who required hospitalization for bursitis. Transmission also occurred for CMV (n = 1), hepatitis A (n = 1), giardiasis (n = 1), scabies (n = 1), Moluscum (n = 2) and pediculosis (n = 2). Two cases of chronic hepatitis B and latent tuberculosis were diagnosed without subsequent transmission. In conclusion, infectious diseases are common in internationally adopted children and should be detected shortly after arrival to avoid transmission.

Measuring current and future cost of skin cancer in England.

BACKGROUND: Increasing incidence of and mortality from skin cancer are posing a large financial burden on the NHS in England. Information provided by cost-of-illness (CoI) studies are used in policy making and are particularly useful for measuring the potential savings from averting a case of disease. METHODS: We estimate the cost of skin cancer in England, and model future costs up to 2020. We compare two costing approaches (top-down and bottom-up). RESULTS: We estimate that costs due to skin cancer were in the range of £106-£112 million in 2008. These figures are very closely related to those provided by the Department of Health (estimated to be £104.0 million in 2007-8 and £105.2 million 2008-9). The expected cost per case of malignant melanoma was estimated to be £2607 and £2560, using the bottom-up and top-down approaches, respectively. The mean cost per case of non-melanoma skin cancer was £889 and £1226, respectively. We estimate that the cost to the NHS due to skin cancer will amount to over £180 million in 2020. CONCLUSION: Effective prevention of skin cancer might not only reduce a significant burden of disease but it could also save considerable resources to the NHS.

Contrast harmonic imaging characterization of canine splenic lesions.

BACKGROUND: Although B-mode ultrasound is very sensitive for the detection of splenic lesions, its specificity is low. Contrast harmonic imaging is used successfully to differentiate benign from malignant liver lesions in humans and dogs. HYPOTHESIS: Contrast harmonic imaging could be useful to differentiate benign and malignant splenic lesions in dogs. ANIMALS: Sixty dogs (clinical patients) with splenic abnormalities detected during abdominal ultrasonography. METHODS: A prospective study was performed with a Philips ATL 5000 unit for contrast pulse inversion harmonic imaging (mechanical index: 0.08, contrast medium: SonoVue). Perfusion was assessed subjectively and quantitatively. RESULTS: Cytology or histology identified 27 benign (hyperplasia, extramedullary hematopoiesis, hematoma) and 29 malignant (hemangiosarcoma, malignant lymphoma, malignant histiocytosis, mesenchymal tumors without classification, mast cell tumors, and others) lesions and 4 normal spleens. Except for 1 benign nodule, extensive to moderate hypoechogenicity was only seen in malignant lesions during wash-in, at peak enhancement, and during wash-out (P= .0001, odds ratios: 37.9 [95% CI 4.5-316.5], 66.4 [95% CI 8.0-551.1], and 36.9 [95% CI 4.4-308.4]). Although all but 1 benign lesion enhanced well and were mildly hypo-, iso-, or hyperechoic in comparison with the normal spleen during all blood pool phases, marked enhancement occurred both in benign as well as in malignant splenic lesions. Quantitative perfusion values did not differ significantly between benign and malignant lesions. CONCLUSIONS AND CLINICAL IMPORTANCE: Moderate to extensive hypoechogenicity clearly identifies canine splenic malignant lesions. In nodules with marked enhancement, contrast harmonic ultrasound is of limited value and histology is needed.

HeartMate VE LVAS design enhancements and its impact on device reliability.

OBJECTIVE: The HeartMate VE left ventricular assist system (LVAS) has supported more than 2300 patients and has been shown to be effective for bridge to cardiac transplantation and has demonstrated improved outcomes in survival as a destination therapy. Improvements in device durability are needed as bridge to transplant times increase and as we move into the era of LVAD as destination therapy. The purpose of this study is to determine if design enhancements to the HeartMate LVAS have improved device reliability and durability. METHODS: A retrospective analysis of serious mechanical failures was performed in 1865 devices (1458 VE, 407 XVE). The analysis of data included devices used to support patients from September 1998 for bridge to transplantation and destination therapy. Serious mechanical failures were defined as inflow valve dysfunction, percutaneous lead breaks, diaphragm fractures or punctures, bearing failures, outflow graft erosion and pump disconnects. RESULTS: Median device duration for the VE was 97 days (max 1206 days), and 85 days (max 517 days) for the XVE. A total of 134 serious mechanical failures occurred and included inflow valve dysfunction (5.3% VE, 2.4% XVE) (P = 0.853) percutaneous lead breaks (1.9% VE, 0% XVE) (P < 0.001) diaphragm fractures (0.1% VE, 0% XVE) (P = 0.134) outflow graft erosion (0.2% VE, 0% XVE) (P = 0.1096), pump disconnects (0.1% VE, 0% XVE) (P = 0.1336) and bearing failures (0.6% VE, 0.2% XVE) (P = 0.5538). Of the XVEs 97% were free of serious mechanical failures at 6 months and 82% at 1 year compared to 92 and 73% for the VE, respectively. The 6-month difference between the devices was statistically significant (P = 0.0063) and there was no statistically significant difference at 1 year (P = 0.1492). CONCLUSIONS: Preliminary experience with the HeartMate XVE LVAS demonstrated a significant reduction in percutaneous lead breaks. Early trends indicate positive impact of recent design modifications on XVE performance. These design modifications may improve device durability and reliability, which is crucial as we enter the era of LVADs as an alternative to medical therapy.

Efficacy and toxicity of paclitaxel (Taxol) for the treatment of canine malignant tumors.

Paclitaxel (Taxol) was administered to 25 dogs with histologically confirmed malignant tumors at a dosage of 165 mg/m2 i.v. over 3-6 hours every 3 weeks. Dogs received premedication with antihistimines and corticosteroids to reduce hypersensitivity reactions. However, 64% of the dogs still experienced allergic reactions. Six dogs (24%) had grade 3 or 4 neutropenia, 6 dogs (24%) required hospitalization and 3 dogs (12%) died of sepsis. Five dogs (20%) had a partial response (osteosarcoma [2 dogs] mammary carcinoma [2 dogs] and malignant histiocytosis [1 dog]) for a median duration of 53 days. The overall toxicity was unacceptable at the 165 mg/m2 dose. Therefore, subsequent evaluations of paclitaxel in tumor-bearing dogs should a starting dose of 132 mg/m2 i.v. every 3 weeks.

[Streptococcus pyogenes endocarditis following varicella: a case report]. / Varicelle compliquée d'une endocardite à streptocoque A: à propos d'une observation.

Although varicella is most often a benign and self-limited disease of childhood, it can be associated with a variety of serious and potential lethal complications. Especially, the incidence of severe infectious complications caused by group A streptococci has been increasing over the last years. We report the case of a previously healthy young boy with an aortic bicuspidy who developed a varicella complicated by endocarditis due to group A streptococcus, and a haemophagocytic syndrome. A favorable outcome was obtained after an early valvular replacement and 6 weeks of intravenous antibiotics.

Naloxone for shock.

BACKGROUND: There is pre-clinical evidence, involving several animal species, suggesting that opioid peptides play a role in the physiopathology of shock (endotoxic, hypovolemic, cardiogenic, spinal, anaphylactic). Many case reports have suggested that naloxone (an opiate antagonist) might be an effective treatment for shock in humans, but others have not supported such a point of view. This controversy led us to undertake a meta-analysis of the available evidence on the efficacy of naloxone as a treatment measure of shock in humans. OBJECTIVES: To evaluate the effectiveness and safety of naloxone in human shock and to estimate the methodological quality of the clinical trials. SEARCH STRATEGY: Computerized bibliographic search up to December 2002, review of references of all papers found on the subject and contact with primary investigators of eligible studies. SELECTION CRITERIA: Randomized controlled trials evaluating naloxone in human shock, regardless of the patient's age (adult, child or neonate). DATA COLLECTION AND ANALYSIS: Three independent reviewers extracted data on study design, intervention, outcome and methodological quality. MAIN RESULTS: Three independent readers reviewed 80 human publications and selected six clinical trials. Overall agreement on study selection was perfect (concordance: 100%). This meta-analysis includes six studies involving 126 patients with septic, cardiogenic, hemorrhagic or spinal shock. Naloxone therapy was associated with statistically significant hemodynamic improvement (odds ratio 0.24; 95% confidence interval [95%CI] 0.09-0.68). The mean arterial pressure was significantly higher in the naloxone groups than in the placebo groups (weighted mean difference: +9.33 mmHg; 95%CI 7.07-11.59). No heterogeneity was found for this outcome. The death rate was lower in the naloxone group (odds ratio 0.59; 95%CI 0.21-1.67) but this was consistent with the play of chance. A significant heterogeneity for the latter outcome was detected (p<0.05). REVIEWER'S CONCLUSIONS: Naloxone improves blood pressure, especially mean arterial blood pressure. However, the clinical usefulness of naloxone to treat shock remains to be determined, and additional randomized controlled trials are needed to assess its usefulness.

The bisphosphonates alendronate and zoledronate are inhibitors of canine and human osteosarcoma cell growth in vitro.

Bisphosphonates (BPs) are a class of non-hydrolysable analogues of pyrophosphate that have high affinity for bone mineral and are inhibitors of bone resorption. The in vitro effects of two nitrogen-containing BPs, alendronate (ALE) and zoledronate (ZOL), on growth, induction of apoptosis and effects on cell-cycle distribution in two canine and two human osteosarcoma (OSA) cell lines are investigated here. Both significantly (P < 0.001) reduced cell growth in all cell lines, as assessed by a colorimetric assay with IC(50) values in the range of 7.3-61.4 microM and 7.9-36.3 microM for ALE and ZOL, respectively. Both BPs caused a significant (P < 0.001) dose-dependent increase in the proportion of cells undergoing apoptosis, as assessed both by cell-cycle analysis and by annexin-V binding. Both ALE and ZOL altered the proportion of cells in each phase of the cell cycle, but the extent and proportion was both drug and cell line dependent. These data indicate that the nitrogen-containing BPs have direct anti-tumour activity against canine and human OSA cells.

Multicenter clinical evaluation of the HeartMate vented electric left ventricular assist system in patients awaiting heart transplantation.

BACKGROUND: Despite advances in heart transplantation and mechanical circulatory support, mortality among transplant candidates remains high. Better ways are needed to ensure the survival of transplant candidates both inside and outside the hospital. METHODS: In a prospective, multicenter clinical trial conducted at 24 centers in the United States, 280 transplant candidates (232 men, 48 women; median age, 55 years; range, 11-72 years) unresponsive to inotropic drugs, intra-aortic balloon counterpulsation, or both, were treated with the HeartMate Vented Electric Left Ventricular Assist System (VE LVAS). A cohort of 48 patients (40 men, 8 women; median age, 50 years; range, 21-67 years) not supported with an LVAS served as a historical control group. Outcomes were measured in terms of laboratory data (hemodynamic, hematologic, and biochemical), adverse events, New York Heart Association functional class, and survival. RESULTS: The VE LVAS-treated and non-VE LVAS-treated (control) groups were similar in terms of age, sex, and distribution of patients by diagnosis (ischemic cardiomyopathy, idiopathic cardiomyopathy, and subacute myocardial infarction). VE LVAS support lasted an average of 112 days (range, < 1-691 days), with 54 patients supported for > 180 days. Mean VE LVAS flow (expressed as pump index) throughout support was 2.8 L x min(-1) x m(-2). Median total bilirubin values decreased from 1.2 mg/dL at baseline to 0.7 mg/dL (P =.0001); median creatinine values decreased from 1.5 mg/dL at baseline to 1.1 mg/dL (P =.0001). VE LVAS-related adverse events included bleeding in 31 patients (11%), infection in 113 (40%), neurologic dysfunction in 14 (5%), and thromboembolic events in 17 (6%). A total of 160 (58%) patients were enrolled in a hospital release program. Twenty-nine percent of the VE LVAS-treated patients (82/280) died before receiving a transplant, compared with 67% of controls (32/48) (P <.001). Conversely, 71% of the VE LVAS-treated patients (198/280) survived: 67% (188/280) ultimately received a heart transplant, and 4% (10/280) had the device removed electively. One-year post-transplant survival of VE LVAS-treated patients was significantly better than that of controls (84% [158/188] vs 63% [10/16]; log rank analysis P =.0197). CONCLUSION: The HeartMate VE LVAS provides adequate hemodynamic support, has an acceptably low incidence of adverse effects, and improves survival in heart transplant candidates both inside and outside the hospital. The studies of the HeartMate LVAS (both pneumatic and electric) for Food and Drug Administration approval are the only studies with a valid control group to show a survival benefit for cardiac transplantation.