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1.
Cardiol Young ; : 1-9, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38682563

ABSTRACT

OBJECTIVE: Challenges to communication between families and care providers of paediatric patients in intensive care units (ICU) include variability of communication preferences, mismatched goals of care, and difficulties carrying forward family preferences from provider to provider. Our objectives were to develop and test an assessment tool that queries parents of children requiring cardiac intensive care about their communication preferences and to determine if this tool facilitates patient-centred care and improves families' ICU experience. DESIGN: In this quality improvement initiative, a novel tool was developed, the Parental Communication Assessment (PCA), which asked parents with children hospitalised in the cardiac ICU about their communication preferences. Participants were prospectively randomised to the intervention group, which received the PCA, or to standard care. All participants completed a follow-up survey evaluating satisfaction with communication. MAIN RESULTS: One hundred thirteen participants enrolled and 56 were randomised to the intervention group. Participants who received the PCA preferred detail-oriented communication over big picture. Most parents understood the daily discussions on rounds (64%) and felt comfortable expressing concerns (68%). Eighty-six percent reported the PCA was worthwhile. Parents were generally satisfied with communication. However, an important proportion felt unprepared for difficult decisions or setbacks, inadequately included or supported in decision-making, and that they lacked control over their child's care. There were no significant differences between the intervention and control groups in their communication satisfaction results. CONCLUSIONS: Parents with children hospitalised in the paediatric ICU demonstrated diverse communication preferences. Most participants felt overall satisfied with communication, but individualising communication with patients' families according to their preferences may improve their experience.

2.
Vet Comp Oncol ; 21(4): 665-672, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37604645

ABSTRACT

Published radiotherapy data for canine intraventricular tumours are limited. In this retrospective, longitudinal study (9/2011-2018), 11 dogs with intraventricular masses were treated with stereotactic radiotherapy (SRT). Pathologic diagnosis was available from surgery or necropsy in 6/11 cases, revealing choroid plexus papilloma (3) or carcinoma (2), and ependymoma (1). The remainder were magnetic resonance imaging (MRI)-diagnosed as suspected choroid tumours or ependymomas. Tumours were located in the third or lateral ventricle (8), fourth ventricle (2), and cerebellopontine angle (1). Surgery was performed in three dogs prior to radiotherapy, and all showed gross residual/recurrent disease at treatment. Dogs received 8 Gray × 3 fractions (7), or 15 Gray × 1 fraction (4). Ten dogs were deceased at analysis, and one was living. The estimated median overall survival time (OS) from first SRT treatment was 16.9 months (515 days, 95% CI 33-1593 days). The survival time for two pathology-diagnosed carcinoma dogs were 24 and 133 days, respectively, and survival time for dogs with moderate to marked ventriculomegaly (4/11) ranged from 24 to 113 days. A total of 10/11 showed clinical improvement per owner or clinician, but two had short-lived benefits and were euthanized within 6 weeks of SRT. Limited conclusions on radiation-specific complications are possible due to the small dataset and limited follow-up imaging. This study provides preliminary evidence that radiotherapy outcomes are variable with intraventricular tumours, and some long-term survivors are noted.


Subject(s)
Carcinoma , Cerebral Ventricle Neoplasms , Dog Diseases , Dogs , Animals , Retrospective Studies , Longitudinal Studies , Dog Diseases/radiotherapy , Cerebral Ventricle Neoplasms/veterinary , Carcinoma/veterinary
3.
Pediatr Cardiol ; 44(7): 1599-1604, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37432410

ABSTRACT

Flexibility is important for range of motion, muscular performance, and injury prevention with exercise. Promoting exercise is important for patients with congenital and pediatric acquired heart disease (CHD), yet there are a paucity of data addressing flexibility in this population. We hypothesized that flexibility was worse in pediatric patients with CHD than the general population but could be improved with directed training. Patients at Boston Children's Hospital who participated in the pediatric Cardiac Fitness Program between 09/2016 and 11/2022 were retrospectively analyzed. Flexibility was assessed via sit-and-reach (SaR) box. Data from baseline and 60 days into the fitness program intervention were compared to age-matched population norms, and changes over time were assessed. Analyses were also stratified by sex and history of sternotomy. Patients with paired baseline and 60-day data were analyzed (n = 46, age 8-23 years old, 52% male). The mean SaR at baseline for CHD patients was 24.3 cm, significantly lower than the population norm (p = 0.002). The mean for male (n = 24, 21.2 cm) and female (n = 22, 27.2 cm) CHD patients was significantly lower than their respective population norms (p = 0.017 and p = 0.026, respectively). After the fitness intervention, flexibility in CHD patients significantly improved to normal, including patients with a history of sternotomy. Flexibility was significantly lower in CHD patients than the general population, but normalized with training. Further research is warranted to investigate associations of flexibility with other measures of fitness, cardiovascular status, and quality of life, as well as benefits gained with training.


Subject(s)
Heart Defects, Congenital , Quality of Life , Humans , Child , Male , Female , Adolescent , Young Adult , Adult , Retrospective Studies , Heart Defects, Congenital/surgery , Heart Defects, Congenital/complications , Exercise , Morbidity
4.
J Am Vet Med Assoc ; 261(11): 1-8, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37524353

ABSTRACT

OBJECTIVE: To describe radiotherapy outcomes for canine infiltrative lipomas and provide detailed radiotherapy planning data. ANIMALS: 24 dogs from 2000 to 2020. METHODS: In this retrospective study, dogs received 1 to 3 surgeries prior to conventionally fractionated radiotherapy for gross (18) or microscopic (8) infiltrative lipomas. Dogs received 45 to 51 Gray (Gy) in 15 to 20 daily fractions, with 71% of dogs receiving 48 Gy in daily 3-Gy fractions. RESULTS: Masses were regionally located as follows: limbs (7), trunk (13), head/neck (4). At analysis, 16/24 dogs were deceased, 5/24 were alive (median follow-up for alive dogs: 1,216 days [range, 741 to 1,870 days]), and 3/24 were lost to follow-up. One living dog had progressive disease 923 days after completing conventionally fractionated radiotherapy and received another surgery. The estimated median overall survival (OS) after completing radiotherapy was 4.8 years (1,760 days; 95% CI, 1,215 to 2,777 days; range, 23 to 3,499 days) for any cause of death, and no patients were reported to have been euthanized or died from their tumor. No statistically significant difference was found for dogs based on gross versus microscopic disease (gross OS, 4.8 years vs microscopic OS, 3.6 years; P = .45). Furthermore, the number of surgeries before radiotherapy did not impact survival (P = .96). The survival difference between females (median OS, 7.6 years; 95% CI, 963 days to not reached) versus males (median OS, 4.6 years; 95% CI, 335 to 2,245 days; P = .05) was statistically significant, although 4/5 living dogs were female. CLINICAL RELEVANCE: This study demonstrates lengthy survivals with radiotherapy, even with gross disease, for dogs with infiltrative lipomas.


Subject(s)
Dog Diseases , Lipoma , Male , Dogs , Animals , Female , Retrospective Studies , Lipoma/radiotherapy , Lipoma/veterinary , Dog Diseases/radiotherapy
5.
Front Cardiovasc Med ; 10: 1155861, 2023.
Article in English | MEDLINE | ID: mdl-37332590

ABSTRACT

Many children and adolescents with congenital and acquired heart disease (CHD) are physically inactive and participate in an insufficient amount of moderate-to-vigorous intensity exercise. Although physical activity (PA) and exercise interventions are effective at improving short- and long-term physiological and psychosocial outcomes in youth with CHD, several barriers including resource limitations, financial costs, and knowledge inhibit widespread implementation and dissemination of these beneficial programs. New and developing eHealth, mHealth, and remote monitoring technologies offer a potentially transformative and cost-effective solution to increase access to PA and exercise programs for youth with CHD, yet little has been written on this topic. In this review, a cardiac exercise therapeutics (CET) model is presented as a systematic approach to PA and exercise, with assessment and testing guiding three sequential PA and exercise intervention approaches of progressive intensity and resource requirements: (1) PA and exercise promotion within a clinical setting; (2) unsupervised exercise prescription; and (3) medically supervised fitness training intervention (i.e., cardiac rehabilitation). Using the CET model, the goal of this review is to summarize the current evidence describing the application of novel technologies within CET in populations of children and adolescents with CHD and introduce potential future applications of these technologies with an emphasis on improving equity and access to patients in low-resource settings and underserved communities.

6.
Front Pediatr ; 11: 1133255, 2023.
Article in English | MEDLINE | ID: mdl-37334214

ABSTRACT

Introduction: Patients with congenital heart disease (CHD) have variable degrees of peak oxygen consumption (VO2) that can be improved with supervised fitness training. The ability to exercise is affected by anatomy, hemodynamics, and motivation. Motivation is in part related to mindset, or personal attitudes and beliefs, and a more positive mindset around exercise has been associated with better outcomes. It is unknown whether variations in measured peak VO2 in patients with CHD are related to having a positive mindset. Methods: Patient's ages 8-17 years with CHD were administered quality of life and physical activity questionnaires at the time of their routine cardiopulmonary exercise test. Those with severe hemodynamic burden were excluded. Patients were grouped based on disease classification. Mindset was evaluated via validated questionnaires including a PROMIS Meaning and Purpose (MaP) survey and an Anxiety survey. Pearson correlation coefficients were calculated to estimate the magnitude of the association between percent predicted peak oxygen consumption (pppVO2) and questionnaire scores overall and within CHD subgroups. Results: Eighty-five patients participated; median age was 14.7 years, 53% were female, 66% had complex CHD, 20% had simple CHD, and 14% had single ventricle heart disease. Mean MaP scores were significantly lower in all CHD groups compared to population norms (p < 0.001). As a group, MaP scores were positively associated with the amount of reported physical activity (p = 0.017). In patients with simple CHD, MaP scores were positively associated with pppVO2 (p = 0.015). The association was even stronger for MaP:Anxiety, with worse ratios associated with lower pppVO2 (p = 0.005). Patients with complex and single ventricle CHD did not show a similar association. Conclusions: Patients with CHD, regardless of severity, had lower meaning and purpose scores than the general population, and these scores were associated with amount of reported physical activity. In the simple CHD subset, having a more positive mindset was associated with higher peak VO2 and a more negative mindset with lower peak VO2. This relationship was not seen with more significant CHD. While underlying CHD diagnoses are not modifiable, mindset and peak VO2 are, and consideration should be given to measuring both as each may be a target for intervention.

7.
Vet Radiol Ultrasound ; 64(4): 768-774, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37335283

ABSTRACT

Canine optic pathway structures are often contoured on CT images, despite the difficulty of visualizing the optic pathway with CT using standard planes. The purpose of this prospective, analytical, diagnostic accuracy study was to examine the accuracy of optic pathway contouring by veterinary radiation oncologists (ROs) before and after training on optic plane contouring. Optic pathway contours used as the gold standard for comparison were created based on expert consensus from registered CT and MRI for eight dogs. Twenty-one ROs contoured the optic pathway on CT using their preferred method, and again following atlas and video training demonstrating contouring on the optic plane. The Dice similarity coefficient (DSC) was used to assess contour accuracy. A multilevel mixed model with random effects to account for repeated measures was used to examine DSC differences. The median DSC (5th and 95th percentile) before and after training was 0.31 (0.06, 0.48) and 0.41 (0.18, 0.53), respectively. The mean DSC was significantly higher after training compared with before training (mean difference = 0.10; 95% CI, 0.08-0.12; P < 0.001) across all observers and patients. DSC values were comparable to those reported (0.4-0.5) for segmentation of the optic chiasm and nerves in human patients. Contour accuracy improved after training but remained low, potentially due to the small optic pathway volumes. When registered CT-MRI images are not available, our study supports routine addition of an optic plane with specific window settings to improve segmentation accuracy in mesaticephalic dogs ≥11 kg.


Subject(s)
Magnetic Resonance Imaging , Tomography, X-Ray Computed , Humans , Animals , Dogs , Prospective Studies , Reactive Oxygen Species , Tomography, X-Ray Computed/veterinary , Tomography, X-Ray Computed/methods , Magnetic Resonance Imaging/veterinary , Magnetic Resonance Imaging/methods , Eye , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy Planning, Computer-Assisted/veterinary
8.
Vet Comp Oncol ; 21(3): 419-426, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37188527

ABSTRACT

Published radiotherapy results for spinal nephroblastomas in dogs are limited. In this retrospective longitudinal study (1/2007-1/2022), five dogs with a median age of 2.8 years received post-operative 3D conformal, conventional fractionated radiotherapy (CFRT) with 2-4 fields (parallel-opposed with or without two hinge-angle fields), for an incompletely resected nephroblastoma. Clinical findings prior to surgery included one or more of the following: pelvic limb paresis (5), faecal incontinence (2), flaccid tail (1), non-ambulatory (2) and deep pain loss (1). All masses were located between T11 and L3 and surgically removed via hemilaminectomy. Dogs received 45-50 Gray (Gy) in 18-20 fractions, and no dogs received chemotherapy post-radiation. At analysis, all dogs were deceased, with none lost to follow-up. The median overall survival (OS) from first treatment to death of any cause was 3.4 years (1234 days; 95% CI 68 days-upper limit not reached; range: 68-3607 days). The median planning target volume was 51.3 cc, with a median PTV dose of 51.4 Gy and median D98 = 48.3 Gy. Late complications or recurrence was difficult to fully determine in this small dataset; however, some degree of ataxia persisted throughout life in all dogs. This study provides preliminary evidence that post-operative radiotherapy may result in prolonged survival times dogs with spinal nephroblastomas.

9.
Pediatr Cardiol ; 44(3): 631-639, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35953605

ABSTRACT

Recommendations for management of patients with Kawasaki disease (KD) and coronary artery aneurysms (CAA) include physical activity (PA) promotion. This study aimed to characterize self-reported practices of KD providers to evaluate practice variation in use of cardiopulmonary exercise testing (CPET) and PA recommendations. We developed a REDCap survey with different clinical scenarios of KD patients. It was completed by members of the International Kawasaki Disease Registry (IKDR) and community pediatric cardiologists. Twenty-eight physicians responded; 63% practiced in the US, 63% practiced in an academic setting, 48% were general pediatric cardiologists, and 55% were IKDR members. Most respondents (69%) followed < 50 KD patients. The great majority (93%) agreed that patients with no CAA do not require CPET and could be cleared for all PA. For patients with small CAA, 43% of respondents recommended CPET and 75% cleared for all PA if CAAs regressed completely, but only 32% cleared if CAA persisted. For patients with medium CAA, 66% respondents cleared for PA if CAA regressed, and only 7% if CAA persisted; with 66% and 75% recommending CPET, respectively. For patients with large/giant CAA, 81% of respondents recommended CPET. No respondents felt comfortable clearing their patients with persistent large/giant CAA for PA and 19% would restrict from the entire physical education program. There is practice variation in use of CPET in KD patients with CAAs. Providers are hesitant to promote PA in KD patients with CAA despite known benefits and current guidelines.


Subject(s)
Coronary Aneurysm , Mucocutaneous Lymph Node Syndrome , Physicians , Child , Humans , Infant , Exercise Test , Self Report , Exercise
10.
ACS Chem Biol ; 17(7): 1824-1830, 2022 07 15.
Article in English | MEDLINE | ID: mdl-35730734

ABSTRACT

Fungus-growing ants are defended by antibiotic-producing bacterial symbionts in the genus Pseudonocardia. Nutrients provisioned by the ants support these symbionts but also invite colonization and competition from other bacteria. As an arena for chemically mediated bacterial competition, this niche offers a window into ecological antibiotic function with well-defined competing organisms. From multiple colonies of the desert specialist ant Trachymyrmex smithi, we isolated Amycolatopsis bacteria that inhibit the growth of Pseudonocardia symbionts under laboratory conditions. Using bioassay-guided fractionation, we discovered a novel analog of the antibiotic nocamycin that is responsible for this antagonism. We identified the biosynthetic gene cluster for this antibiotic, which has a suite of oxidative enzymes consistent with this molecule's more extensive oxidative tailoring relative to similar tetramic acid antibiotics. High genetic similarity to globally distributed soil Amycolatopsis isolates suggest that this ant-derived Amycolatopsis strain may be an opportunistic soil strain whose antibiotic production allows for competition in this specialized niche. This nocamycin analog adds to the catalog of novel bioactive molecules isolated from bacterial associates of fungus-growing ants, and its activity against ant symbionts represents, to our knowledge, the first putative ecological function for the widely distributed enoyl tetramic acid family of antibiotics.


Subject(s)
Ants , Animals , Anti-Bacterial Agents/pharmacology , Ants/microbiology , Bacteria , Fungi , Polyketides , Soil , Symbiosis
11.
Pediatrics ; 149(2)2022 02 01.
Article in English | MEDLINE | ID: mdl-34984466

ABSTRACT

BACKGROUND AND OBJECTIVES: Adolescents with cardiac disease are at risk for life-changing complications and premature death. The importance of advance care planning (ACP) in adults with congenital heart disease and in pediatric patients with HIV and cancer has been demonstrated. ACP preferences of adolescents with heart disease have not been evaluated. We describe ACP preferences of adolescents with heart disease and compare with those of their caregivers. METHODS: Outpatient adolescents aged 12 to 18 years with heart failure, cardiomyopathy, heart transplantation, or who were at risk for cardiomyopathy, as well as their caregivers, completed self-administered questionnaires which evaluated participants' opinions regarding content and timing of ACP discussions, preferences for end-of-life communication, and emotional responses to ACP. RESULTS: Seventy-eight adolescents and 69 caregivers participated, forming 62 adolescent-caregiver dyads. Adolescents and caregivers reported that adolescent ACP discussions should occur early in the disease course (75% and 61%, respectively). Adolescents (92%) wanted to be told about terminal prognosis, whereas only 43% of caregivers wanted the doctor to tell their child this information. Most adolescents (72%) and caregivers (67%) anticipated that discussing ACP would make the adolescent feel relieved the medical team knew their wishes. Most caregivers (61%) believed that adolescents would feel stress associated with ACP discussions, whereas only 31% of adolescents anticipated this. CONCLUSIONS: Adolescents and their caregivers agree that ACP should occur early in disease course. There are discrepancies regarding communication of prognosis and perceived adolescent stress related to ACP discussions. Facilitated conversations between patient, caregiver, and providers may align goals of care and communication preferences.


Subject(s)
Advance Care Planning/trends , Caregivers/psychology , Caregivers/trends , Heart Diseases/psychology , Patient Preference/psychology , Surveys and Questionnaires , Adolescent , Adult , Advance Care Planning/standards , Child , Cross-Sectional Studies , Female , Heart Diseases/therapy , Humans , Male , Middle Aged , Patient Transfer/standards , Patient Transfer/trends , Surveys and Questionnaires/standards
12.
Curr Opin Cardiol ; 37(1): 91-98, 2022 Jan 01.
Article in English | MEDLINE | ID: mdl-34608879

ABSTRACT

PURPOSE OF REVIEW: Historically, children with congenital heart disease have been restricted from exercise, contributing to a sedentary lifestyle as well as increased cardiovascular risk factors. Given the large benefits and small risks of exercise in this population, guidelines have recently shifted towards exercise promotion. However, these recommendations have yet not gained traction and children with congenital heart disease continue to live sedentary lives. The purpose of this review is to summarize the current literature on exercise and exercise promotion in this population. RECENT FINDINGS: New literature reinforces the importance of recommending exercise and improving exercise capacity both in congenital heart disease in general and for specific lesions. Exercise recommendations should be individualized based on functional parameters using a structured methodology to approach the evaluation, risk classification, and prescriptions of exercise and physical activity. SUMMARY: Regular exercise is essential for children with congenital heart disease and providers must take an active role in providing exercise recommendations for their patients. Exercise promotion remains a challenge, necessitating novel approaches to promote exercise. Further studies are needed to improve the risk stratification of patients with congenital heart disease, assess the long-term outcomes of specific exercise interventions, and inform individualized recommendations to encourage children with congenital heart disease to safely engage in exercise and establish healthy lifelong habits that will decrease their cardiovascular risk.


Subject(s)
Exercise , Heart Defects, Congenital , Child , Health Promotion , Humans , Sedentary Behavior
14.
Vet Comp Oncol ; 19(3): 463-472, 2021 Sep.
Article in English | MEDLINE | ID: mdl-32892513

ABSTRACT

Tumour stage has been demonstrated to have prognostic significance in canine oral malignant melanoma (OMM). Various evaluation techniques of positron emission tomography/computed tomography (PET/CT) have been reported for staging of head-and-neck tumours in people, but canine-specific data are limited, and reports for CT accuracy have been variable. In this prospective study, the head/neck of client-owned dogs with cytologically or histologically diagnosed OMM were imaged with 18 Fluorine-fluorodeoxyglucose (18 F-FDG) PET/ CT. Bilateral mandibular lymphadenectomy was performed for histopathologic assessment. Two evaluation techniques for CT and PET were applied by four independent observers. CT evaluation utilized both a standardized grading scheme and a subjective clinical interpretation. PET evaluation was first performed solely on 18 F-FDG-uptake in lymph nodes compared to background on a truncated scan excluding the oral cavity. Subsequently, the entire head/neck scan and standardized uptake value (SUV) measurements were available. Receiver operating characteristic analysis was performed with histopathology as gold standard. Twelve dogs completed the study and metastatic OMM was identified in six mandibular lymph nodes from five dogs. Of the CT-interpretation techniques, use of clinical grading performed best (sensitivity = 83% and specificity = 94%). Both PET techniques resulted in 100% sensitivity, but primary tumour site evaluation and use of SUV increased specificity from 78% to 94%. The SUVmax cut-point, 3.3, led to 100% sensitivity and 83% specificity. In this population of dogs, PET appeared to be highly sensitive but at risk of being less specific without use of appropriate parameters and thresholds.


Subject(s)
Dog Diseases , Melanoma , Mouth Neoplasms/veterinary , Positron Emission Tomography Computed Tomography , Animals , Dog Diseases/diagnostic imaging , Dogs , Fluorodeoxyglucose F18 , Lymph Nodes/diagnostic imaging , Lymphatic Metastasis/diagnostic imaging , Melanoma/diagnostic imaging , Melanoma/veterinary , Mouth Neoplasms/diagnostic imaging , Positron Emission Tomography Computed Tomography/veterinary , Prospective Studies , Radiopharmaceuticals , Sensitivity and Specificity , Skin Neoplasms , Melanoma, Cutaneous Malignant
15.
Vet Comp Oncol ; 19(1): 191-200, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33135852

ABSTRACT

Published radiotherapy results for suspected heart-based tumours in dogs are limited. In this retrospective longitudinal study (3/2014-2019), eight dogs with either clinical signs attributable to a heart-base mass (6), or asymptomatic with a progressively larger mass on echocardiogram (2), received conventional fractionated radiotherapy (CFRT) or stereotactic body radiotherapy (SBRT). Clinical findings in symptomatic cases included one or more of the following: retching/coughing (4), exercise intolerance (2), collapse (1), pericardial effusion (2), rare ventricular premature contractions (2), abdominal effusion (1), or respiratory distress due to chylothorax (1). CFRT cases received 50 Gray (Gy) in 20 fractions and SBRT cases received 30 Gy in 5 or 24 Gy in three fractions. Two dogs received chemotherapy post-radiation. At analysis, 7/8 dogs were deceased and one was alive 684 days post-treatment. The estimated median overall survival (MOS) from first treatment was 785 days (95% CI 114-868 days, [range 114-1492 days]). Five dogs received CFRT (MOS 817 days; (95% CI 155 days-not reached [range 155-1492 days])). Three dogs received SBRT with one alive at analysis (MOS 414 days, (95% CI, 114 days-not reached [range 114-414 days])). No statistically significant difference was found between survival for CFRT and SBRT. Of the symptomatic patients, 5/6 showed improvement. Mass size reduced in 4/5 cases receiving follow-up ultrasounds. Possible complications included asymptomatic radiation pneumonitis (4), atrial tachycardia/premature beats (4) and pericardial effusion with heart failure coincident with tumour progression (1). This study provides preliminary evidence that radiotherapy may impact clinically relevant or progressively enlarging heart-base masses.


Subject(s)
Dog Diseases/radiotherapy , Dose Fractionation, Radiation , Heart Neoplasms/veterinary , Radiosurgery/veterinary , Animals , Dogs , Female , Male
16.
Materials (Basel) ; 13(5)2020 Feb 27.
Article in English | MEDLINE | ID: mdl-32120834

ABSTRACT

Transition metal nitrides, like titanium nitride (TiN), are promising alternative plasmonic materials. Here we demonstrate a low temperature plasma-enhanced atomic layer deposition (PE-ALD) of non-stoichiometric TiN0.71 on lattice-matched and -mismatched substrates. The TiN was found to be optically metallic for both thick (42 nm) and thin (11 nm) films on MgO and Si <100> substrates, with visible light plasmon resonances in the range of 550-650 nm. We also demonstrate that a hydrogen plasma post-deposition treatment improves the metallic quality of the ultrathin films on both substrates, increasing the ε1 slope by 1.3 times on MgO and by 2 times on Si (100), to be similar to that of thicker, more metallic films. In addition, this post-deposition was found to tune the plasmonic properties of the films, resulting in a blue-shift in the plasmon resonance of 44 nm on a silicon substrate and 59 nm on MgO.

17.
Photochem Photobiol ; 96(5): 1014-1031, 2020 09.
Article in English | MEDLINE | ID: mdl-32221980

ABSTRACT

Psoralen is a furocoumarin natural product that intercalates within DNA and forms covalent adducts when activated by ultraviolet radiation. It is well known that this property contributes to psoralen's clinical efficacy in several disease contexts, which include vitiligo, psoriasis, graft-versus-host disease and cutaneous T-cell lymphoma. Given the therapeutic relevance of psoralen and its derivatives, we attempted to synthesize psoralens with even greater potency. In this study, we report a library of 73 novel psoralens, the largest collection of its kind. When screened for the ability to reduce cell proliferation, we identified two derivatives even more cytotoxic than 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT), one of the most potent psoralens identified to date. Using MALDI-TOF MS, we studied the DNA adduct formation for a subset of novel psoralens and found that in most cases enhanced DNA binding correlated well with cytotoxicity. Generally, our most potent derivatives contain positively charged substituents, which we believe increase DNA affinity and enhance psoralen intercalation. Thus, we provide a rational approach to guide efforts toward further optimizing psoralens to fully capitalize on this drug class' therapeutic potential. Finally, the structure-activity insights we have gained shed light on several opportunities to study currently underappreciated aspects of psoralen's mechanism.


Subject(s)
DNA/drug effects , Furocoumarins/pharmacology , Animals , Cell Line, Tumor , DNA/chemistry , DNA Adducts , Furocoumarins/chemistry , Mice , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Structure-Activity Relationship , Ultraviolet Rays
18.
Vet Comp Oncol ; 18(2): 191-198, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31424596

ABSTRACT

Localized radiation therapy can be an effective treatment for cancer but is associated with localized and systemic side effects. Several studies have noted changes in complete blood count (CBC) parameters including decreases in the absolute lymphocyte count (ALC) and increases in the neutrophil:lymphocyte ratio (NLR). These changes could reflect immunosuppression and may contribute to decreased efficacy of immunotherapies used to treat cancer. We hypothesized that dogs would demonstrate decreased ALCs during a course of radiotherapy. A retrospective study was conducted on 203 dogs receiving definitive-intent radiotherapy. Demographic information, CBC values and details of the radiotherapy protocol were collected. The mean lymphocyte count pre-treatment was 1630.68 cells/µL (SD ± 667.56) with a mean NLR of 3.66 (SD ± 4.53). The mean lymphocyte count mid-treatment was 1251.07 cells/µL (SD ± 585.96) and the mean NLR was 6.23 (SD ± 4.99). There was a significant decrease in the mean lymphocyte count by 351.41 lymphocytes/µL (SD ± 592.32) between pre-treatment and mid-treatment (P < .0001), and a corresponding significant increase in the mean NLR of 0.93 (P = .02). Lymphopenia grade increased in 33.5% of dogs and was significant (P = .03). The ALC decrease was not correlated with the volume irradiated (P = .27), but correlated with the irradiated volume:body weight ratio (P = .03). A subset of patients (n = 35) with additional CBCs available beyond the mid-treatment time point demonstrated significant and sustained downward trends in the ALC compared with baseline. Although severe lymphopenia was rare, these decreases, especially if sustained, could impact adjuvant therapy for their cancer.


Subject(s)
Dog Diseases/radiotherapy , Dose Fractionation, Radiation , Lymphocyte Count/veterinary , Lymphocytes/physiology , Neoplasms/veterinary , Animals , Combined Modality Therapy/veterinary , Dogs , Female , Lymphocytes/radiation effects , Male , Neoplasms/radiotherapy , Retrospective Studies , Treatment Outcome
19.
Vet Comp Oncol ; 18(3): 381-388, 2020 Sep.
Article in English | MEDLINE | ID: mdl-31811693

ABSTRACT

No standard of care is currently recognized for treatment of canine prostatic carcinoma (PC). This retrospective study assesses outcome following definitive-intent, intensity-modulated radiation therapy (RT) in dogs with PC. Medical records review was performed, including 18 patients from four institutions undergoing definitive-intent intensity-modulated radiotherapy to treat PC. Diagnosis was incidental in 7/18 (39%) patients. Five dogs (28%) had evidence of metastasis to loco-regional lymph nodes at diagnosis. Seventeen patients received concurrent non-steroidal anti-inflammatory drugs; 15/18 (83%) patients received maximally-tolerated dose (MTD) chemotherapy, with variable drugs and protocols employed. Total prescribed radiation dose ranged from 48 to 54 Gy (median 50 Gy) delivered as daily doses of 2.5-2.8 Gy. One patient was euthanized prior to completing radiotherapy. Acute toxicity was observed in nine patients; Grade 1-2 diarrhoea was the most common toxicity observed. Suspected late toxicity (urethral stricture, ureteral stricture and hindlimb oedema) was observed in three patients. Median event-free survival (EFS) following RT was 220 days, and median overall survival was 563 days. Local progression occurred in seven patients at a median of 241 days. Median overall survival was significantly longer in incidentally diagnosed dogs (581 vs 220 days in symptomatic dogs, P = .042). EFS was significantly longer in patients treated with MTD chemotherapy (241 vs 25 days, P < .001), and significantly shorter in patients presenting with evidence of metastatic disease (109 days) vs those without (388 days, P = .008). These findings suggest that definitive-intent radiotherapy is a valuable treatment option for local control of canine PC with moderate risk of toxicity.


Subject(s)
Carcinoma/veterinary , Dog Diseases/radiotherapy , Prostatic Neoplasms/veterinary , Radiotherapy, Intensity-Modulated/veterinary , Animals , Antineoplastic Agents/therapeutic use , Carcinoma/drug therapy , Carcinoma/pathology , Carcinoma/radiotherapy , Dog Diseases/drug therapy , Dogs , Male , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/adverse effects , Retrospective Studies , Treatment Outcome
20.
J Am Anim Hosp Assoc ; 55(4): e55402, 2019.
Article in English | MEDLINE | ID: mdl-31099610

ABSTRACT

An 8 yr old female spayed poodle/terrier mixed-breed dog was referred for evaluation of a recurrent and metastatic ovarian dysgerminoma. A total dose of 20Gy was administered to both the mediastinal metastatic lesion and retroperitoneal recurrent dysgerminoma in five daily fractions of 4Gy. Acute side effects were mild and self-limiting. This was followed by several courses of chemotherapy using a variety of agents. Despite extensive disease, this patient was still alive at the time of publication, 524 days after presentation and 501 days following completion of radiation. This case report demonstrates tolerability and efficacy of palliative radiation and chemotherapy for this rare tumor type.


Subject(s)
Antineoplastic Agents/therapeutic use , Dog Diseases/therapy , Dysgerminoma/veterinary , Ovarian Diseases/veterinary , Radiotherapy/veterinary , Animals , Dogs , Dysgerminoma/pathology , Dysgerminoma/therapy , Female , Ovarian Diseases/pathology , Ovarian Diseases/therapy
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