Mast cells are upregulated in hidradenitis suppurativa tissue, associated with epithelialized tunnels and normalized by spleen tyrosine kinase antagonism.

Mast cells have traditionally been associated with allergic inflammatory responses; however, they play important roles in cutaneous innate immunity and wound healing. The Hidradenitis Suppurativa tissue transcriptome is associated with alterations in innate immunity and wound healing-associated pathways; however, the role of mast cells in the disease is unexplored. We demonstrate that mast cell-associated gene expression (using whole tissue RNAseq) is upregulated, and in-silico cellular deconvolution identifies activated mast cells upregulated and resting mast cells downregulated in lesional tissue. Tryptase/Chymase positive mast cells (identified using IHC) localize adjacent to epithelialized tunnels, fibrotic regions of the dermis and at perivascular sites associated with Neutrophil Extracellular Trap formation and TNF-alpha production. Treatment with Spleen Tyrosine Kinase antagonist (Fostamatinib) reduces the expression of mast cell-associated gene transcripts, associated biochemical pathways and the number of tryptase/chymase positive mast cells in lesional hidradenitis suppurativa tissue. This data indicates that although mast cells are not the most abundant cell type in Hidradenitis Suppurativa tissue, the dysregulation of mast cells is paralleled with B cell/plasma cell inflammation, inflammatory epithelialized tunnels and epithelial budding. This provides an explanation as to the mixed inflammatory activation signature seen in HS, the correlation with dysregulated wound healing and potential pathways involved in the development of epithelialized tunnels.

Habitat and climate influence hybridization among three genetically distinct Canada jay (Perisoreus canadensis) morphotypes in an avian hybrid zone complex.

Examining the frequency and distribution of hybrids across contact zones provide insights into the factors mediating hybridization. In this study, we examined the effect of habitat and climate on hybridization patterns for three phenotypically, genetically, and ecologically distinct groups of the Canada jay (Perisoreus canadensis) in a secondary contact zone in western North America. Additionally, we tested whether the frequency of hybridization involving the three groups (referred to as Boreal, Pacific and Rocky Mountain morphotypes) is similar across the hybrid zones or whether some pairs have hybridized more frequently than others. We reanalyzed microsatellite, mtDNA and plumage data, and new microsatellite and plumage data for 526 individuals to identify putative genetic and phenotypic hybrids. The genetically and phenotypically distinct groups are associated with different habitats and occupy distinct climate niches across the contact zone. Most putative genetic hybrids (86%) had Rocky Mountain ancestry. Hybrids were observed most commonly in intermediate climate niches and in habitats where Engelmann spruce (Picea engelmannii) overlaps broadly with boreal and subalpine tree species. Our finding that hybrids occupy intermediate climate niches relative to parental morphotypes matches patterns for other plant and animal species found in this region. This study demonstrates how habitat and climate influence hybridization patterns in areas of secondary contact and adds to the growing body of research on tri-species hybrid zones.

Imaging in neonatal respiratory disease.

The purpose of this review is to describe the current state of the art in clinical imaging for NICU patients, divided into major areas that correspond to likely phenotypes of neonatal respiratory disease: airway abnormalities, parenchymal disease, and pulmonary vascular disease. All common imaging modalities (ultrasound, X-ray, CT, and MRI) are discussed, with an emphasis on modalities that are most relevant to the individual underlying aspects of disease. Some promising aspects of dynamic and functional imaging are included, where there may be future clinical applicability.

The COVANOS trial - insight into post-COVID olfactory dysfunction and the role of smell training.

BACKGROUND: Olfactory dysfunction is a cardinal symptom of COVID-19 infection, however, studies assessing long-term olfactory dysfunction are limited and no randomised-controlled trials (RCTs) of early olfactory training have been conducted. METHODOLOGY: We conducted a prospective, multi-centre study consisting of baseline psychophysical measurements of smell and taste function. Eligible participants were further recruited into a 12-week RCT of olfactory training versus control (safety information). Patient-reported outcomes were measured using an electronic survey and BSIT at baseline and 12 weeks. An additional 1-year follow-up was open to all participants. RESULTS: 218 individuals with a sudden loss of sense of smell of at least 4-weeks were recruited. Psychophysical smell loss was observed in only 32.1%; 63 participants were recruited into the RCT. The absolute difference in BSIT improvement after 12 weeks was 0.45 higher in the intervention arm. 76 participants completed 1-year follow-up; 10/19 (52.6%) of participants with an abnormal baseline BSIT test scored below the normal threshold at 1-year, and 24/29 (82.8%) had persistent parosmia. CONCLUSIONS: Early olfactory training may be helpful, although our findings are inconclusive. Notably, a number of individuals who completed the 1-year assessment had persistent smell loss and parosmia at 1-year. As such, both should be considered important entities of long-Covid and further studies to improve management are highly warranted.

Evidence-based treatment during the SARS-CoV-2 pandemic: Identifying the knowns and unknowns of nebulization.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus 19 (COVID-19), has resulted in a worldwide pandemic and currently represents a major public health issue. Among the considerations for patients with respiratory disease is the optimal delivery of inhaled bronchodilators to maximize patient care. Despite the lack of evidence, there is heightened concern about the potential risk for transmission of SARS-CoV-2 in the form of aerosolized respiratory droplets during the nebulized treatment of patients with COVID-19. In this commentary, the lack of evidence regarding nebulization and transmission of coronaviruses are discussed.

Applying Best Practices from Health Communication to Support a University's Response to COVID-19.

Higher education institutions face profound communication challenges managing risks for university communities during the ongoing pandemic. This commentary shares 1) findings from our study involving analysis of 17 focus groups of students, faculty, staff, and parents of students to explore effective COVID-19 messages about campus safety, and 2) insights into the process of integrating the expertise of a university health communication center into campus-wide responses to COVID-19. Key focus group takeaways highlight the importance of communicating empathetically, acknowledging those who are made vulnerable through their work on campus, and that promises to return to normal would be perceived as unrealistic. Bringing the evidence base of health communication to the typical work of professional communicators on campus allowed us to create a communication toolkit for consistent messaging, and in turn, learn about the vital role health communication scholars can play in university crisis messaging.

Spontaneous Magnetic Superdomain Wall Fluctuations in an Artificial Antiferromagnet.

Collective dynamics often play an important role in determining the stability of ground states for both naturally occurring materials and metamaterials. We studied the temperature dependent dynamics of antiferromagnetically ordered superdomains in a square artificial spin lattice using soft x-ray photon correlation spectroscopy. We observed an exponential slowing down of superdomain wall motion below the antiferromagnetic onset temperature, similar to the behavior of typical bulk antiferromagnets. Using a continuous time random walk model we show that these superdomain walls undergo low-temperature ballistic and high-temperature diffusive motions.

RNA disruption indicates CHOP therapy efficacy in canine lymphoma.

BACKGROUND: Assessment of the efficacy of a multi-agent chemotherapy protocol in which cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) are administered in canine lymphoma is generally performed by physical measurement of lymph node diameter. However, no consistent correlation has been made with prognostic indicators and the length or absence of clinical remission based on lymph node size. RNA disruption measured mid-therapy has been correlated with increased disease-free survival in recent studies of human cancer and was assessed in this study of canine lymphoma patients. Fine needle aspirate samples were taken before treatment and at weeks 3, 6, and 11 of CHOP therapy. RNA was isolated from these samples and assessed using an Agilent Bioanalyzer. RNA disruption assay (RDA) analysis was performed on the data from the resulting electropherograms. RESULTS: An increased RNA disruption index (RDI) score was significantly associated with improved progression-free survival. CONCLUSIONS: Predicting the risk of early relapse during chemotherapy could benefit veterinary patients by reducing ineffective treatment and could allow veterinary oncologists to switch earlier to a more effective drug regimen.

Electron microscopy and tomography reveal that sodium 2-naphthalene sulfonate incorporated into perming solutions swells and tilts trichocyte intermediate filaments causing straightening of curly Japanese human hair.

OBJECTIVE: A new hair-care process has been specifically developed for the straightening of curved Japanese woman's hair . The process included sodium 2-naphthalene sulfonate (SNS) in the reduction and oxidation steps of a conventional perming process. Our objective was to develop an understanding of how this process caused hair straightening by measuring the changes to morphology and ultrastructure between untreated, conventionally permed and SNS permed hair. Untreated and SNS permed Merino wool fibres were used to confirm structural changes. METHODS: Japanese hair samples were measured for single-fibre curvature before and after perming treatments. A silver staining method was developed to stain hair fibres without changing fibre curvature so that transmission electron microscopy could be used to measure changes in the lateral dimensions of all structural components from the cellular to protein filament level. Electron tomography determined intermediate filament slopes and slope changes after SNS perming relative to the central longitudinal axis of the fibre. RESULTS: SNS perming was found to cause greater lateral swelling than conventional perming of: the paracortical cells of wool; the cuticle, the cuticular cell membrane complex and the macrofibrillar centre-to-centre distance of hair; and of the intermediate filaments in wool and hair. In curved hair, SNS perming caused the intermediate filaments of the helical macrofibrils to simultaneously swell and to tilt further, resulting in the slight longitudinal contraction of the macrofibrils. The overall swelling and tilting was greatest in the helical macrofibrils of Type B cortical cells predominately located in the convex fibre half. The presence of a higher percentage of helical macrofibrils in the convex fibre half than in the concave fibre half caused a contraction differential between the two halves leading to straighten of the curved fibre. A mechanical model was proposed to explain how SNS perming straightened curly hair. CONCLUSION: The effects of conventional and SNS perming on the morphological and ultrastructural components of curved Japanese hair and high-curl Merino wool fibres have given clear insights into understanding the mechanism of fibre curvature change.

OBJECTIF: Un nouveau procédé de soin des cheveux a été spécialement conçu pour lisser les cheveux ondulés des Japonaises[1]. Le procédé utilise le sulfonate de naphthalène-2 sodium (SNS) dans les étapes de réduction et d'oxydation du procédé conventionnel de permanente. Notre objectif était de comprendre la façon dont ce procédé induisait le lissage des cheveux en mesurant les différences de changement morphologique et ultrastructural entre les cheveux non traités et ceux soumis à une permanente conventionnelle et une permanente à base de SNS. Des fibres de laine de mérinos non traitées et soumises à une permanente à base de SNS ont été utilisées pour confirmer les changements structurels. MÉTHODES: Des échantillons de cheveux japonais ont été utilisés pour mesurer la courbure d'une fibre isolée avant et après le traitement de permanente. Une méthode de coloration argent a été mise au point pour colorer les fibres de cheveux sans changer la courbure des fibres afin de pouvoir utiliser la microscopie électronique en transmission pour mesurer les modifications des dimensions en largeur de tous les composants structurels du filament, de la cellule aux protéines. Une tomographie électronique a déterminé les pentes intermédiaires et les changements de pente des filaments après permanente à base de SNS par rapport à l'axe longitudinal central de la fibre. RÉSULTATS: On a constaté que la permanente à base de SNS induisait un gonflement en largeur plus important que la permanente classique des cellules paracorticales de la laine; de la cuticule, du complexe de la membrane cellulaire cuticulaire et de la distance centre à centre des macrofibrilles du cheveu; et des filaments intermédiaires dans la laine et les cheveux. Dans les cheveux ondulés, la permanente à base de SNS a provoqué à la fois un gonflement et une inclinaison des filaments intermédiaires des macrofibrilles hélicoïdales, entraînant une légère contraction longitudinale des macrofibrilles. Au total, le gonflement et l'inclinaison étaient plus importants dans les macrofibrilles hélicoïdales des cellules corticales de type B situées principalement dans la moitié convexe de la fibre. La présence d'un pourcentage plus élevé de macrofibrilles hélicoïdales dans la moitié convexe par rapport à la moitié concave de la fibre a entraîné une contraction différentielle entre les deux moitiés qui a entraîné le redressement de la fibre courbée. Un modèle mécanique a été proposé pour expliquer comment la permanente à base de SNS lissait les cheveux bouclés. CONCLUSION: Les effets de la permanente conventionnelle et à base de SNS sur les composants morphologiques et ultrastructuraux des cheveux japonais ondulés et des fibres de laine très frisés de mérinos ont permis de mieux comprendre le mécanisme du changement de courbure des fibres.

Development of a Small Molecule Tubulysin B Conjugate for Treatment of Carbonic Anhydrase IX Receptor Expressing Cancers.

Carbonic anhydrase IX (CAIX) is a membrane-spanning zinc metalloenzyme that catalyzes the reversible consumption of CO2 and water to form H+ + HCO3-. Many human cancers upregulate CAIX to help control the pH in their hypoxic microenvironments. The consequent overexpression of CAIX on malignant cells and low expression on normal tissues render CAIX a particularly attractive target for small molecule inhibitors, antibody-drug conjugates, and ligand-targeted drugs. In this study, CAIX-targeted fluorescent reporter molecules were initially exploited to investigate CAIX-specific binding to multiple cancer cell lines, where they were shown to display potent and selective binding to CAIX positive cells. A small molecule CAIX-targeted tubulysin B conjugate was then synthesized and examined for its ability to kill CAIX-expressing tumor cells in vitro. Potent therapeutic conjugates were subsequently tested in vivo and demonstrated to eliminate solid human tumor xenografts in murine tumor models without exhibiting overt signs of toxicity. Because most solid tumors contain hypoxic regions where CAIX is overexpressed, development of a method to selectively deliver drugs to these hypoxic regions could aid in the therapy of otherwise difficult to treat tumors.

Public health investigation and response to a hepatitis A outbreak from imported scallops consumed raw-Hawaii, 2016.

During the summer of 2016, the Hawaii Department of Health responded to the second-largest domestic foodborne hepatitis A virus (HAV) outbreak in the post-vaccine era. The epidemiological investigation included case finding and investigation, sequencing of RNA positive clinical specimens, product trace-back and virologic testing and sequencing of HAV RNA from the product. Additionally, an online survey open to all Hawaii residents was conducted to estimate baseline commercial food consumption. We identified 292 confirmed HAV cases, of whom 11 (4%) were possible secondary cases. Seventy-four (25%) were hospitalised and there were two deaths. Among all cases, 94% reported eating at Oahu or Kauai Island branches of Restaurant Chain A, with 86% of those cases reporting raw scallop consumption. In contrast, a food consumption survey conducted during the outbreak indicated 25% of Oahu residents patronised Restaurant Chain A in the 7 weeks before the survey. Product trace-back revealed a single distributor that supplied scallops imported from the Philippines to Restaurant Chain A. Recovery, amplification and sequence comparison of HAV recovered from scallops revealed viral sequences matching those from case-patients. Removal of product from implicated restaurants and vaccination of those potentially exposed led to the cessation of the outbreak. This outbreak further highlights the need for improved imported food safety.

Impact of distance education via interactive videoconferencing on students' course performance and satisfaction.

The impact of distance education via interactive videoconferencing on pharmacy students' performance in a course was assessed after implementation of a distance campus. Students filled out a "Student Demographic Survey" and a "Precourse Knowledge Assessment" at the start of the course and a "Postcourse Knowledge Assessment" and a "Postcourse Student Perceptions Survey" at the end of the course. The primary end point, a comparison of course grades (%) between the main and distance campuses, was examined using the two-sample t-test. We examined the relationships among demographics, campus location, course grades, grade point average, pre- and postcourse knowledge assessments, and postcourse perceptions as our secondary end points with parametric and nonparametric tests. Data from 93 students were included in the analysis [main campus ( n = 81); distance campus ( n = 12)]. Students on the main campus achieved a significantly higher final course grade (87 vs. 81%; P = 0.02). Scores on the Postcourse Knowledge Assessment were also significantly higher compared with those of students on the distance education campus (77 vs. 68%; P = 0.04). Students on both campuses reported self-perceived improvement in their knowledge base regarding various aspects of infectious diseases. Compared with the students on the distance campus, those on the main campus were more likely to subjectively perceive that they had succeeded in the course ( P = 0.04). Our study suggests that students on the main campus achieved a higher final course grade and were more likely to feel that they had succeeded in the course. Students on both campuses reported improvement in knowledge.

The physical and chemical disruption of human hair after bleaching - studies by transmission electron microscopy and redox proteomics.

OBJECTIVE: To understand the structural and chemical effects of cosmetic peroxide bleaching on human hair. METHODS: Human hair was progressively bleached using alkaline peroxide-persulphate treatment. Proteins lost through leaching were examined using amino acid analysis and mass spectrometric sequencing. Fibre damage was assessed using transmission electron microscopy, amino acid analysis and redox proteomics. RESULTS: Protein loss through leaching increased with bleaching severity. Leached proteins were not limited to the cuticle, but also included cortical intermediate filaments and matrix keratin-associated proteins. The leached proteins were progressively oxidized as bleaching severity increased. Bleached fibres demonstrated substantial damage to the cuticle layers and to the cortex. Extensive melanin granule degradation was present after the mildest bleach treatment. Protein oxidation in bleached fibres was principally in cortical intermediate filaments - the most abundant hair proteins - and targeted the sulphur-containing amino acids, particularly the conversion of cystine disulphide bonds to cysteic acid. CONCLUSION: Peroxide chemical treatments quickly access the cortex, causing untargeted oxidative damage across the fibre in addition to the desired loss of melanin. Peroxide ingress is likely facilitated by the considerable structural degradation caused to the cuticle layers of hair fibres. The consequences of the peroxide action within the cuticle and cortex are oxidation of the proteins, and subsequent protein loss from the fibre that correlates to bleaching severity.

Pharmacological Characterization of a Novel Beta 3 Adrenergic Agonist, Vibegron: Evaluation of Antimuscarinic Receptor Selectivity for Combination Therapy for Overactive Bladder.

Although the physiologic role of muscarinic receptors in bladder function and the therapeutic efficacy of muscarinic antagonists for the treatment of overactive bladder are well established, the role of ß3-adrenergic receptors (ß3ARs) and their potential as therapeutics is just emerging. In this manuscript, we characterized the pharmacology of a novel ß3AR agonist vibegron (MK-4618, KRP-114V) and explored mechanistic interactions of ß3AR agonism and muscarinic antagonism in urinary bladder function. Vibegron is a potent, selective full ß3AR agonist across species, and it dose dependently increased bladder capacity, decreased micturition pressure, and increased bladder compliance in rhesus monkeys. The relaxation effect of vibegron was enhanced when combined with muscarinic antagonists, but differentially influenced by muscarinic receptor subtype selectivity. The effect was greater when vibegron was co-administered with tolterodine, a nonselective antagonist, compared with coadministration with darifenacin, a selective M3 antagonist. Furthermore, a synergistic effect for bladder strip relaxation was observed with the combination of a ß3AR agonist and tolterodine in contrast to simple additivity with darifenacin. To determine expression in rhesus bladder, we employed a novel ß3AR agonist probe, [3H]MRL-037, that selectively labels ß3 receptors in both urothelium and detrusor smooth muscle. Vibegron administration caused a dose-dependent increase in circulating glycerol and fatty acid levels in rhesus and rat in vivo, suggesting these circulating lipids can be surrogate biomarkers. The translation of our observation to the clinic has yet to be determined, but the combination of ß3AR agonists with M2/M3 antimuscarinics has the potential to redefine the standard of care for the pharmacological treatment of overactive bladder.

A systematic review and critical evaluation of reported pathogenic sequence variants in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a severe chronic inflammatory disorder characterized by recurrent painful deep-seated nodules with a predilection to the apocrine-bearing areas of skin. A minority of cases of HS are due to mutations in the γ-secretase complex. Contention exists surrounding the pathogenicity of sequence variants and their effects upon Notch signalling. This systematic review was registered with PROSPERO (CRD42016041425) and was conducted in line with the PRISMA statement. Eligibility criteria for this review included published case reports, case series and reviews that identified sequence variants or protein or functional studies from patients with HS. Sixty-two articles were identified reporting a total of 41 sequence variants - heterozygous missense (nine), splice site (nine), insertion resulting in frameshift (one), premature termination codon (19) and promoter region PSTPIP1 (three) - with 18 associated protein or functional studies. The American College of Medical Genetics and Genomics standards and guidelines on the interpretation of sequence variants were applied to each identified variant to assess evidence for pathogenicity. Twenty-three variants were assessed as likely pathogenic, 17 of uncertain significance and one benign. The large number of variants of 'uncertain significance' is largely due to the variable number of functional studies. Four studies used Notch as a proxy for γ-secretase function, with conclusions of nonpathogenicity based on the assumption of Notch signalling as the sole pathogenic process. The role of Notch-independent signalling mechanisms requires further research. Limitations to this study include identification of variants of Mendelian inheritance and not complex polygenic traits.

A novel processed food classification system applied to Australian food composition databases.

BACKGROUND: The extent of food processing can affect the nutritional quality of foodstuffs. Categorising foods by the level of processing emphasises the differences in nutritional quality between foods within the same food group and is likely useful for determining dietary processed food consumption. The present study aimed to categorise foods within Australian food composition databases according to the level of food processing using a processed food classification system, as well as assess the variation in the levels of processing within food groups. METHODS: A processed foods classification system was applied to food and beverage items contained within Australian Food and Nutrient (AUSNUT) 2007 (n = 3874) and AUSNUT 2011-13 (n = 5740). The proportion of Minimally Processed (MP), Processed Culinary Ingredients (PCI) Processed (P) and Ultra Processed (ULP) by AUSNUT food group and the overall proportion of the four processed food categories across AUSNUT 2007 and AUSNUT 2011-13 were calculated. RESULTS: Across the food composition databases, the overall proportions of foods classified as MP, PCI, P and ULP were 27%, 3%, 26% and 44% for AUSNUT 2007 and 38%, 2%, 24% and 36% for AUSNUT 2011-13. Although there was wide variation in the classifications of food processing within the food groups, approximately one-third of foodstuffs were classified as ULP food items across both the 2007 and 2011-13 AUSNUT databases. CONCLUSIONS: This Australian processed food classification system will allow researchers to easily quantify the contribution of processed foods within the Australian food supply to assist in assessing the nutritional quality of the dietary intake of population groups.

The value of a feasibility study into long-term macrolide therapy in chronic rhinosinusitis.

OBJECTIVES: There is currently conflicting level 1 evidence in the use of long-term antibiotics for chronic rhinosinusitis without nasal polyps. The primary aim of this feasibility study was to optimise future randomised trial design by assessing recruitment and retention of patients alongside providing preliminary data on symptomatic control. DESIGN: Prospective, multicentre feasibility (cohort) study with all patients receiving macrolide therapy for 12 weeks and a further subsequent 12-week follow-up. Participants received a 12-week course of clarithromycin 250 mg alongside twice daily topical mometasone and nasal douching. Primary outcomes focused on recruitment, retention and compliance. Clinical and quality-of-life outcomes measures were also recorded. SETTING: Patients were prospectively recruited from six UK outpatient clinics. PARTICIPANTS: Adult patients with chronic rhinosinusitis without nasal polyps and no prior endoscopic sinus surgery underwent baseline assessment and then follow-up at 3 and 6 months. MAIN OUTCOME MEASURES: Six-month recruitment and retention data. RESULTS: Over 13 months, 55 adults were recruited from five centres. Four patients declined participation. 75% of patients were retained within the study. Dropouts included one medication contraindication, three unable to tolerate medication and 10 not attending full follow-up. Sino Nasal Outcome Test-22 and endoscopic scores showed statistically significant improvement. No other clinical or quality-of-life assessment improvements were seen. CONCLUSION: Retention and recruitment to a trial using long-term clarithromycin to treat chronic rhinosinusitis without nasal polyps is achievable and this data will support a future randomised controlled trial. The study provides vital insight into trial design, thus informing UK research networks and rhinology researchers internationally.

Retrospective evaluation of toceranib (Palladia) treatment for canine metastatic appendicular osteosarcoma.

This retrospective study evaluated the outcomes of dogs with macroscopic pulmonary metastasis of appendicular osteosarcoma (OSA) treated with toceranib. Medical records of 20 dogs with macroscopic pulmonary metastasis of OSA that received toceranib were reviewed. The median dose and duration of toceranib administration were 2.52 mg/kg (range: 2.12 to 2.72 mg/kg) and 60 days (range: 17 to 231 days). The median progression free survival (PFS) and overall survival (OS) were 36 days (range: 17 to 231 days) and 90 days (range: 17 to 433 days), respectively. The clinical benefit rate was 10% (2/20; 1 partial response and 1 stable disease). The longest length of initial pulmonary nodules had significant impact on both PFS (P = 0.01) and OS (P = 0.02). The prognosis for dogs with metastatic OSA was poor with only 10% of dogs showing clinical benefit from toceranib. These results suggest that toceranib may not improve outcome in dogs with macroscopic pulmonary metastasis of OSA.

Évaluation rétrospective du traitement avec tocéranib (Palladia) pour l'ostéosarcome appendiculaire métastatique canin. Cette étude rétrospective a évalué les résultats des chiens souffrant de métastase pulmonaire macroscopique de l'ostéosarcome appendiculaire (OSE) traité avec tocéranib. Les dossiers médicaux de 20 chiens atteints de métastase pulmonaire macroscopique d'OSE qui ont reçu tocéranib ont été évalués. La dose médiane et la durée de l'administration de tocéranib étaient de 2,52 mg/kg (étendue de 2,12 à 2,72 mg/kg) et de 60 jours (étendue de 17 à 231 jours). La progression de survie libre (PSL) médiane et la survie totale (ST) étaient de 36 jours (étendue de 17 à 231 jours) et de 90 jours (étendue de 17 à 433 jours), respectivement. Le taux de bienfaits cliniques étaient de 10 % (2/20; 1 réponse partielle et 1 maladie stable). Le plus long intervalle avant l'apparition des nodules pulmonaires initiaux avait un impact important sur la PSL (P = 0,01) et la ST (P = 0,02). Le pronostic pour les chiens atteints d'OSE métastatique était mauvais et seulement 10 % des chiens ont manifesté des bienfaits cliniques lors de l'usage de tocéranib. Ces résultats suggèrent que le tocéranib pourraient ne pas améliorer les résultats cliniques chez les chiens souffrant de métastase pulmonaire macroscopique causée par OSE.(Traduit par Isabelle Vallières).

Evaluation of toxicity of a chronic alternate day metronomic cyclophosphamide chemotherapy protocol in dogs with naturally occurring cancer.

Sterile hemorrhagic cystitis (SHC) is an important complication of cyclophosphamide chemotherapy in dogs as it is reported in up to 23% of cases with various protocols. The current study reports toxicities of a protocol of metronomic cyclophosphamide, and identifies risk factors for development of adverse effects. A retrospective cohort study of dogs treated with metronomic cyclophosphamide at an intended dose of 25 mg/m2 every other day was conducted. Fifty dogs were included with a median length of treatment of 90 days (range: 1 to 1305 days). Treatment was discontinued in 22 dogs (44%) due to adverse effects; 16 dogs (32%) developed SHC after a median time of 127.5 days (range: 54 to 1305 days). Higher cumulative dose was significantly associated with a higher risk of SHC development (P = 0.048). Therefore, close monitoring and/or prophylactic treatments should be considered for patients receiving chronic metronomic cyclophosphamide therapy.

Évaluation de la toxicité du protocole de chimiothérapie prolongée à la cyclophosphamide métronomique tous les deux jours chez les chiens atteints d'un cancer acquis naturellement. La cystite hémorragique stérile (CHS) est une complication importante de la chimiothérapie à la cyclophosphamide chez les chiens car elle est signalée dans jusqu'à 23 % des cas avec divers protocoles. L'étude actuelle signale les toxicités d'un protocole de cyclophosphamide métronomique et identifie les facteurs de risque pour le développement d'effets indésirables. Une étude rétrospective auprès d'une cohorte de chiens traités à l'aide de la cyclosphamide métronomique à une dose prévue de 25 mg/m2 tous les deux jours a été réalisée. Cinquante chiens ont été inclus avec une durée moyenne de traitement de 90 jours (fourchette : de 1 à 1305 jours). Le traitement a été discontinué chez 22 chiens (44 %) en raison des effets indésirables; 16 chiens (32 %) ont développé la CHS après une durée moyenne de 127,5 jours (fourchette : de 54 à 1305 jours). Une dose cumulative supérieure était significativement associée à un risque supérieur de développer la CHS (P = 0,048). Par conséquent, une surveillance étroite et/ou des traitements prophylactiques devraient être considérés pour les patients recevant une thérapie prolongée à la cyclophosphamide métronomique.(Traduit par Isabelle Vallières).