Use of a haired angularis oris axial pattern flap in a dog to correct a large oronasal fistula secondary to resection of a hard palate multilobular osteochondrosarcoma.

A 6-year-old neutered male mixed-breed dog underwent curative-intent surgical resection of a hard palatal multilobular osteochondrosarcoma and closure of the defect using bilateral buccal mucosal flaps. However, failure of the flaps resulted in a massive hard palatal defect that was subsequently repaired using a haired skin angularis oris axial pattern flap. This report describes the clinical outcome using this surgical approach and novel complications encountered. Key clinical message: The haired skin angularis oris axial pattern flap appears to be a suitable and robust option for reconstruction of large palatal defects.

Utilisation d'un lambeau cutanée poilus avec rotation axiale au niveau de l'artère angularis oris chez un chien pour corriger une fistule oronasale volumineuse secondaire à la résection d'un ostéochondrosarcome multilobulaire du palais dur. Un chien croisé mâle castré de 6 ans a subi une résection chirurgicale à visée curative d'un ostéochondrosarcome multilobulaire du palais dur et une fermeture de l'anomalie par des lambeaux de la muqueuse buccale. Cependant, la défaillance des lambeaux a entraîné un défaut important du palais dur qui a ensuite été réparé à l'aide d'un lambeau de peau avec poils avec rotation axiale au niveau de l'artère angularis oris. Ce rapport décrit les résultats cliniques de cette approche chirurgicale et les nouvelles complications rencontrées.Message clinique clé :L'utilisation d'un lambeau de peau avec poils avec rotation axiale au niveau de l'artère angularis oris semble être une option appropriée et robuste pour la reconstruction des défauts importants du palais.(Traduit par Dr Serge Messier).

Minimally invasive splenectomy is associated with a low perioperative complication rate and short operative time in cats.

OBJECTIVE: To report the perioperative outcome and complications in cats undergoing minimally invasive splenectomy. ANIMALS: 17 client-owned cats. METHODS: Perioperative data were collected from cats undergoing minimally invasive splenectomy from September 2010 to June 2023. Data included history, signalment, preoperative examination and diagnostic testing results, operative technique and time, perioperative outcomes, complications, hospitalization duration, histopathological diagnosis, and outcome. RESULTS: 13 spayed females and 4 neutered males were included, with a median age of 144 months (48 to 196 months). Seven cats underwent total laparoscopic splenectomy (TLS), with 1 cat requiring conversion from TLS to laparoscopic-assisted splenectomy (LAS) due to splenomegaly and an additional cat requiring conversion from TLS to open splenectomy due to uncontrollable splenic capsular hemorrhage. Ten cats underwent LAS, with 1 cat requiring conversion to open splenectomy due to splenomegaly. Additional procedures were performed in 13 cats, with the most common being liver biopsy in 10 cats. Median operative times were 50 minutes (45 to 90 minutes) for TLS and 35 minutes (25 to 80 minutes) for LAS. An intraoperative complication occurred in 1 cat. All but 1 cat survived to discharge. Median follow-up time was 234 days (18 to 1,761 days), with 15 of 16 cats confirmed alive at 30 days and 9 of 16 cats alive at 180 days postoperatively. CLINICAL RELEVANCE: Minimally invasive splenectomy in this cohort of cats was associated with short operative times and a low perioperative complication rate. Veterinary surgeons may consider minimally invasive splenectomy as an efficient and feasible technique in the treatment of splenomegaly or modestly sized splenic masses for diagnostic and therapeutic purposes in cats.

Identifying important predictors of adolescent suicide ideation, planning, and attempt in low- and middle-income countries.

INTRODUCTION: Over 90% of all adolescent suicides occur in low- and middle-income countries (LMIC), yet the majority of suicide research has focused on primarily high-income countries (HIC). METHOD: Using nationally representative data on 82,494 adolescents from thirty-four LMIC, this research employed machine learning to compare the predictive effects of multiple determinants of suicidal behaviors previously identified in the literature. RESULTS: Results indicate that distinct predictors are present for suicidal ideation, suicidal planning, and suicide attempts in youth living in LMIC as well as shared predictors common to all three behaviors. CONCLUSION: These findings provide insights into the unique needs in global mental health policy and efforts within and across adolescents in LMIC.

Bilateral, single-session, laparoscopic adrenalectomy was associated with favorable outcomes in a cohort of dogs.

OBJECTIVE: To report perioperative characteristics and outcome following bilateral, single-session, laparoscopic adrenalectomy (BSSLA) in dogs. ANIMALS: Client-owned dogs (n = 6). CLINICAL PRESENTATION AND PROCEDURES: Medical records were reviewed and perioperative data collected, including preoperative diagnostic imaging, operative details, complications, and need for conversion to open laparotomy. Bilateral, single-session, laparoscopic adrenalectomy was performed on the right or left side with a standard 3- or 4-portal transperitoneal technique. The dog was repositioned to contralateral recumbency, and laparoscopic adrenalectomy was repeated. Follow-up information was collected by telephone interviews with the owners and/or referring veterinarian. RESULTS: Median age and weight of dogs were 126 months and 14.75 kg, respectively. Contrast-enhanced CT (CECT) was performed in all dogs. Median maximal tumor diameter was 2.6 and 2.3 cm for the right and left-sided tumors, respectively. Median surgical and anesthesia times were 158 and 240 minutes, respectively. Conversion to open laparotomy was performed in 1 dog following renal vein laceration during initial adrenalectomy. Left adrenalectomy and ureteronephrectomy were performed, and the right adrenal tumor was left in situ. Cardiac arrest occurred in 1 dog following initial adrenalectomy (left); however, the dog was resuscitated successfully, and contralateral laparoscopic adrenalectomy was performed without complication. All dogs survived to hospital discharge. Follow-up ranged from 60 to 730 days (median, 264 days) for dogs that successfully underwent BSSLA. CLINICAL RELEVANCE: BSSLA was associated with favorable outcomes in this cohort of dogs. Laparoscopy may be considered in dogs with bilateral, modestly sized, noninvasive adrenal tumors.

Treatment of myeloid neoplasia with doxorubicin and cytarabine in 11 dogs.

Myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) are primary myeloid neoplasms in dogs generally considered to have a poor outcome. In this study, we assessed toxicity, efficacy and outcome of concurrent administration of doxorubicin and cytarabine in 11 dogs with myeloid neoplasia. Bone marrow specimens were reviewed by three pathologists and classified as either MDS (n = 2), high grade MDS/early AML (MDS/AML; n = 4) or AML (n = 5). The median number of treatment cycles was 5 (range 1-9) and resolution of cytopenia was reported in 7 of 11 dogs including 2 dogs with MDS, 2 dogs with MDS/AML, and 3 dogs with AML. The median duration of remission in the seven responders was 344 days (range 109-1428) and the median overall survival for all dogs was 369 days. Adverse events consisted of predominantly low-grade gastrointestinal illness and myelosuppression. Three dogs developed grade V toxicity manifesting with heart failure (n = 2) at 369 and 1170 days after diagnosis and acute gastrointestinal side effects (n =1). Despite a limited sample size, these results suggest that a doxorubicin and cytarabine protocol may be considered as a therapeutic option in dogs with myeloid neoplasia. Protocol safety, in particular regarding myocardial toxicity, and efficacy should be further investigated.

Clinical validation of a next-generation sequencing-based multi-cancer early detection "liquid biopsy" blood test in over 1,000 dogs using an independent testing set: The CANcer Detection in Dogs (CANDiD) study.

Cancer is the leading cause of death in dogs, yet there are no established screening paradigms for early detection. Liquid biopsy methods that interrogate cancer-derived genomic alterations in cell-free DNA in blood are being adopted for multi-cancer early detection in human medicine and are now available for veterinary use. The CANcer Detection in Dogs (CANDiD) study is an international, multi-center clinical study designed to validate the performance of a novel multi-cancer early detection "liquid biopsy" test developed for noninvasive detection and characterization of cancer in dogs using next-generation sequencing (NGS) of blood-derived DNA; study results are reported here. In total, 1,358 cancer-diagnosed and presumably cancer-free dogs were enrolled in the study, representing the range of breeds, weights, ages, and cancer types seen in routine clinical practice; 1,100 subjects met inclusion criteria for analysis and were used in the validation of the test. Overall, the liquid biopsy test demonstrated a 54.7% (95% CI: 49.3-60.0%) sensitivity and a 98.5% (95% CI: 97.0-99.3%) specificity. For three of the most aggressive canine cancers (lymphoma, hemangiosarcoma, osteosarcoma), the detection rate was 85.4% (95% CI: 78.4-90.9%); and for eight of the most common canine cancers (lymphoma, hemangiosarcoma, osteosarcoma, soft tissue sarcoma, mast cell tumor, mammary gland carcinoma, anal sac adenocarcinoma, malignant melanoma), the detection rate was 61.9% (95% CI: 55.3-68.1%). The test detected cancer signal in patients representing 30 distinct cancer types and provided a Cancer Signal Origin prediction for a subset of patients with hematological malignancies. Furthermore, the test accurately detected cancer signal in four presumably cancer-free subjects before the onset of clinical signs, further supporting the utility of liquid biopsy as an early detection test. Taken together, these findings demonstrate that NGS-based liquid biopsy can offer a novel option for noninvasive multi-cancer detection in dogs.

Outcome in dogs with curative-intent treatment of localized primary pulmonary histiocytic sarcoma.

Primary pulmonary histiocytic sarcoma (PHS) is a rare form of dendritic cell or macrophage neoplasia originating within the pulmonary parenchyma. There is limited literature describing prognosis in dogs with PHS receiving curative-intent treatment consisting of surgical excision and adjuvant chemotherapy. The primary objective of this study was to report outcomes in dogs with localized PHS treated with standardized local and systemic therapy. A secondary objective was to identify prognostic factors in this population. A multi-institutional retrospective study was performed and medical records including all surgical and histopathologic reports were retrospectively reviewed. For inclusion, dogs were required to have confirmed localized PHS and they must have undergone curative-intent surgery with resection of all gross primary tumour and enlarged tracheobronchial lymph nodes; additionally, they must have received curative-intent treatment with adjuvant single-agent CCNU chemotherapy. Twenty-seven dogs from six veterinary teaching hospitals and five private practices treated from 2008-2019 were included. The overall median survival time was 432 days. Higher CCNU dose was demonstrated to have a negative impact on survival on univariate, but not multivariable, analysis. Factors that were not found to be associated with survival on univariate analysis included body weight, breed, clinical signs at the time of diagnosis, hypoalbuminaemia, tumour size, lung lobe affected, lymph node metastasis, surgical margins and CCNU dose reductions. This study supports a favourable prognosis for dogs diagnosed with localized PHS treated with curative-intent surgery in addition to adjuvant CCNU chemotherapy and suggests that multimodal treatment may be advisable to attempt to prolong survival.

Understanding Somatic Symptoms Associated with South Korean Adolescent Suicidal Ideation, Depression, and Social Anxiety.

Korea's suicide rate has increased steadily in recent years and it has become the leading cause of death among Korean youth. This paper aims to propose suicide risk identification strategies for South Korean youth by identifying profiles of suicide risk alongside reported somatic complaints. For several reasons, somatic complaints are more commonly reported than mental health concerns in Korea, where somatic complaints are likely to be representative of larger mental health worries. Nationally representative data of Korean first-year middle school students were used to identify mental health profiles by examining reported suicidal ideation, depression, and social anxiety and the prediction effect of reported somatic symptoms within these profiles. Results indicated that female students reported a greater level of suicidal ideation, depression, and social anxiety compared to male students. Each gender (females and males) exhibited five different mental health profile groups, which ranged from low risk to high risk. Somatic symptoms (sleep, stomach ache, tiredness, breathing, appetite, headache, fever, nausea) significantly predicted each profile group, with sleep issues serving as the strongest predictor for risk across both genders and all groups. Therefore, for mental health professionals working with Korean youth, it is encouraged to identify and recognize somatic complaints as potentially representative of mental health concerns and suicidality risk.

Outcomes after transperitoneal laparoscopic ureteronephrectomy for the treatment of primary renal neoplasia in seven dogs.

OBJECTIVE: To describe the perioperative characteristics and outcomes in dogs that underwent transperitoneal laparoscopic ureteronephrectomy (TLU) for primary renal neoplasia. STUDY DESIGN: Short case series. ANIMALS: Seven client-owned dogs. METHODS: Medical records were reviewed and data extracted regarding perioperative characteristics and animal outcomes. TLU was performed using a single-port + 1 or multiple port techniques. Hemostatic clips or a vessel-sealing device were used for occlusion of renal hilar vessels. The ureter was occluded and transected close to the ureterovesicular junction and the tumor was placed in a specimen retrieval bag for extraction from the abdomen. RESULTS: Preoperative contrast enhanced computed tomography (CECT) was performed in 6/7 dogs. Median estimated tumor volume measured from abdominal CECT removed by TLU was 32.42 cm3 (interquartile range [IQR] 14.76-94.85). Median surgery time for TLU was 90 minutes (IQR 85-105). In one dog, elective conversion to open laparotomy was performed due to large tumor size. Median time to discharge was 31 hours (IQR 24-48). No major perioperative complications occurred and all dogs survived to discharge. Progression free survival in four dogs was 422 days (IQR 119-784). CONCLUSION: TLU was performed for the extirpation of modest sized primary renal tumors with acceptable perioperative outcomes and a low complication rate. CLINICAL RELEVANCE: TLU may be considered for the treatment of selected cases of primary renal neoplasia in dogs.

Primary bone marrow T-cell lymphoma in a Golden Retriever.

A 6.2-year-old 28-kg (61.7 lb) intact female Golden Retriever was referred due to persistent and multiple cytopenias noted on a routine CBC prior to a mature ovariohysterectomy procedure. The patient's physical examination was unremarkable, and staging of the thorax and abdomen identified no abnormalities. At the referral hospital, moderate hypercalcemia, borderline anemia, and neutropenia were noted. Assessment of bone marrow samples by cytology, histology, immunohistochemistry, and flow cytometry indicated a T-cell neoplasm. The patient was treated with a multi-agent chemotherapy protocol for 6 months, which induced remission. Nine months after diagnosis, she relapsed with recurrence of hypercalcemia, cytopenias, and clinical illness. Single-agent anthracycline (mitoxantrone) in combination with prednisone therapy was initiated for 3 months. Two months after completion, the patient relapsed again, and palliative therapy with prednisone was elected. The patient was euthanized 16 months after diagnosis due to progressive disease. Post-mortem histopathologic evaluation showed extensive replacement of bone marrow by neoplastic cells, and infiltrates in multiple organs. The neoplasm was diagnosed as lymphoma rather than leukemia due to the lack of abnormal circulating cells throughout the course of disease. The neoplasm was detected only in marrow at the time of initial diagnosis, and the marrow was the most extensively effaced organ at the time of death. Therefore, leukemia or stage V lymphoma was considered unlikely. In patients with a cytopenia and lack of neoplastic leukocytosis or solid tissue masses, primary bone marrow lymphoma should be considered among the differential diagnoses.

Soft tissue sarcoma at the site of a previous laparoscopic-assisted gastropexy in a dog.

An 8-year-old, spayed female, Doberman pinscher dog was presented to the Ontario Veterinary College Health Sciences Center for evaluation of a large subcutaneous mass on the right cranial ventral abdomen. Computed tomography localized a 6 × 7 cm soft tissue mass to the site of a laparoscopic-assisted gastropexy performed 3 years earlier. Body wall resection with wide surgical margins was performed. Histological evaluation identified the mass as a grade III soft tissue sarcoma with clean surgical margins. To the authors' knowledge, this report is the first to detail a case of a soft tissue sarcoma that is suspected to have originated at and/or infiltrated into tissues that were previously incised during a surgical procedure. Key clinical message: Based on this case, there is a possibility of a clinical correlate to the feline injection site sarcoma in the canine species.

Sarcome des tissus mous au site d'une gastropexie aidée par laparoscopie antérieure chez un chien. Une chienne Doberman pinscher stérilisée âgée de 8 ans fut présentée au Health Sciences Center de l'Ontario Veterinary College pour évaluation d'une large masse sous-cutanée au niveau de l'abdomen ventral crânial droit. Une tomodensitométrie permis de localiser une masse de tissus mous de 6 × 7 cm au site d'une gastropexie aidée par laparoscopie effectuée 3 ans plus tôt. Une résection de la paroi corporelle avec de larges bordures chirurgicales fut réalisée. Une évaluation histologique identifia la masse comme étant un sarcome des tissus mous de grade III avec des bordures chirurgicales nettes. À la connaissance des auteurs ce rapport est le premier à détailler un cas de sarcome des tissus mous qui est suspecté avoir son origine et/ou avoir infiltré des tissus qui furent précédemment incisés durant une procédure chirurgicale.Message clinique clé:Sur la base de ce cas, il y a possibilité d'une relation clinique avec le sarcome du site d'injection chez le chat chez l'espèce canine.(Traduit par Dr Serge Messier).

Composite lymphoma of concurrent T zone lymphoma and large cell B cell lymphoma in a dog.

BACKGROUND: Evolution of indolent to aggressive lymphoma has been described in dogs but is difficult to distinguish from the de novo development of a second, clonally distinct lymphoma. Differentiation of these scenarios can be aided by next generation sequencing (NGS)-based assessment of clonality of lymphocyte antigen receptor genes. CASE PRESENTATION: An 8-year-old male intact Mastiff presented with generalized lymphadenomegaly was diagnosed with nodal T zone lymphoma (TZL) based on cytology, histopathology, immunohistochemistry and flow cytometry. Thirteen months later, the dog re-presented with progressive lymphadenomegaly, and based on cytology and flow cytometry, a large B cell lymphoma (LBCL) was diagnosed. Sequencing-based clonality testing confirmed the de novo development of a LBCL and the persistence of a TZL. CONCLUSIONS: The occurrence of two distinct lymphoid neoplasms should be considered if patient features and tumor cytomorphology or immunophenotype differ among sequential samples. Sequencing-based clonality testing may provide conclusive evidence of two concurrent and distinct clonal lymphocyte populations, termed most appropriately "composite lymphoma".

A pilot study evaluating the effects of prestorage leukoreduction on markers of inflammation in critically ill dogs receiving a blood transfusion.

OBJECTIVES: To compare markers of inflammation after transfusion of leukoreduced (LR) packed RBCs (pRBCs) versus non-LR pRBCs in dogs with critical illness requiring blood transfusion, and to report survival to discharge and rates of transfusion reactions in these dogs. DESIGN: Prospective randomized blinded clinical study June 2014-September 2015. SETTING: University veterinary teaching hospital. ANIMALS: Twenty-three client-owned critically ill dogs, consecutively enrolled. INTERVENTIONS: Dogs requiring a single pRBC transfusion were randomized into the LR or non-LR pRBC group. Exclusion criteria included: requirement for multiple blood products, history of previous blood transfusion, and administration of anti-inflammatory or immunosuppressive medication prior to enrollment. MEASUREMENTS: Blood samples were obtained immediately prior to transfusion, then 2 and 24 hours following transfusion. Parameters measured at each time point included: PCV, WBC count, segmented and band neutrophil counts, fibrinogen, and plasma lactate and C-reactive protein concentrations. Acute patient physiologic and laboratory evaluation fast score was calculated on admission. RESULTS: Eleven dogs were included in the LR group and 12 in the non-LR group; scores of illness severity were not significantly different between groups. Total WBC count was significantly higher in the non-LR versus LR group 24 hours following pRBC transfusion, but this difference was not evident 2 hours following transfusion. No other inflammatory parameters at any time point were significantly different between LR versus non-LR pRBC transfused dogs. Survival rates to discharge for LR and non-LR groups were 8/11 and 9/12, respectively. Acute transfusion reactions were identified in 1/11 and 2/12 dogs in the LR and non-LR group, respectively. All transfused blood was stored ≤12 days. CONCLUSIONS: Most markers of inflammation did not significantly increase following transfusion of LR versus non-LR pRBCs stored ≤12 days in ill dogs. Further prospective, randomized trials are needed in clinically ill dogs to determine the benefit of prestorage leukoreduction.

Evaluation of metronomic cyclophosphamide chemotherapy as maintenance treatment for dogs with appendicular osteosarcoma following limb amputation and carboplatin chemotherapy.

OBJECTIVE To determine the effectiveness of metronomic cyclophosphamide (MC) chemotherapy (primary treatment of interest) with adjuvant meloxicam administration as maintenance treatment for dogs with appendicular osteosarcoma following limb amputation and carboplatin chemotherapy. DESIGN Retrospective case series with nested cohort study. ANIMALS 39 dogs with a histologic diagnosis of appendicular osteosarcoma that underwent limb amputation and completed carboplatin chemotherapy from January 2011 through December 2015. PROCEDURES Dogs were grouped by whether carboplatin chemotherapy had been followed with or without MC chemotherapy (15 mg/m2, PO, q 24 h) and meloxicam (0.1 mg/kg [0.045 mg/lb], PO, q 24 h). The Breslow rank test was used to assess whether MC chemotherapy was associated with overall survival time (OST) and disease progression-free time (PFT) after limb amputation. RESULTS 19 dogs received carboplatin and MC chemotherapy, and 20 dogs received only carboplatin chemotherapy. No differences were identified between these groups regarding age, reproductive status, body weight, serum alkaline phosphatase activity, tumor location, or histologic grade or subtype of osteosarcoma. Median duration of MC chemotherapy for dogs in the carboplatin-MC group was 94 days (range, 7 to 586 days); this treatment was discontinued for 11 (58%) dogs when cystitis developed. Overall, 11 (28%) dogs survived to the time of analysis, for a median follow-up period of 450 days (range, 204 to 1,400 days). No difference in median PFT or OST was identified between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE Maintenance MC chemotherapy following limb amputation and completed carboplatin chemotherapy was associated with no increase in PFT or OST in dogs with appendicular osteosarcoma. Cystitis was common in MC-treated dogs, and prophylactic treatment such as furosemide administration could be considered to reduce the incidence of cystitis in such dogs.

Correlation Between Body Weight and Mitoxantrone-Associated Neutropenia in Dogs.

Thirty-seven dogs with histologically or cytologically confirmed malignant tumors treated with single-agent mitoxantrone at 5 mg/m2 were evaluated in a retrospective study assessing the correlation between body weight and neutropenia associated with a single dose of mitoxantrone in dogs. Overall, eight dogs (21%) experienced grade 3 neutropenia and five dogs (14%) experienced grade 4 neutropenia on day 7 following mitoxantrone chemotherapy. Dogs ≤10 kg body weight were significantly more likely to develop grade 3 or 4 neutropenia (5.8 relative risk; 95% confidence interval, 2.6-12.9; P < .0001) than dogs >10 kg. Dogs ≤15 kg body weight were significantly more likely to develop grade 3 or 4 neutropenia (8.1 relative risk; 95% confidence interval, 2.1-31.3; P < .0001) than dogs >15 kg. Of the 13 patients who developed grade 3 or 4 neutropenia, 6 (46%) were hospitalized for clinical signs related to neutropenia. Based on the severity of neutropenia and the resulting hospitalization seen in dogs ≤10 kg, a dose reduction could be considered for the initial dose of mitoxantrone, and clinicians should be aware of the increased risk of neutropenia in patients 10.1 to ≤15 kg.

Race/ethnicity difference in the pharmacogenetics of bilirubin-related atazanavir discontinuation.

BACKGROUND: Atazanavir causes plasma indirect bilirubin to increase. We evaluated associations between Gilbert's polymorphism and bilirubin-related atazanavir discontinuation stratified by race/ethnicity. PATIENTS AND METHODS: Patients had initiated atazanavir/ritonavir-containing regimens at an HIV primary care clinic in the southeastern USA, and had at least 12 months of follow-up data. Metabolizer group was defined by UGT1A1 rs887829 C→T. Genome-wide genotype data were used to adjust for genetic ancestry in combined population analyses. RESULTS: Among 321 evaluable patients, 15 (4.6%) had bilirubin-related atazanavir discontinuation within 12 months. Homozygosity for rs887829 T/T was present in 28.1% of Black, 21.4% of Hispanic, and 8.6% of White patients. Among all patients the hazard ratio (HR) for bilirubin-related discontinuation with T/T versus C/C genotype was 7.3 [95% confidence interval (CI): 1.7-31.5; P=0.007]. Among 152 White patients the HR was 14.4 (95% CI: 2.6-78.7; P=0.002), but among 153 Black patients the HR was 0.8 (95% CI: 0.05-12.7; P=0.87). CONCLUSION: Among patients who initiated atazanavir/ritonavir-containing regimens, UGT1A1 slow metabolizer genotype rs887829 T/T was associated with increased bilirubin-related discontinuation of atazanavir in White but not in Black patients, this despite T/T genotype being more frequent in Black patients.

Glucocorticoids Induce Bone and Muscle Atrophy by Tissue-Specific Mechanisms Upstream of E3 Ubiquitin Ligases.

Glucocorticoid excess, either endogenous with diseases of the adrenal gland, stress, or aging or when administered for immunosuppression, induces bone and muscle loss, leading to osteopenia and sarcopenia. Muscle weakness increases the propensity for falling, which, combined with the lower bone mass, increases the fracture risk. The mechanisms underlying glucocorticoid-induced bone and muscle atrophy are not completely understood. We have demonstrated that the loss of bone and muscle mass, decreased bone formation, and reduced muscle strength, hallmarks of glucocorticoid excess, are accompanied by upregulation in both tissues in vivo of the atrophy-related genes atrogin1, MuRF1, and MUSA1. These are E3 ubiquitin ligases traditionally considered muscle-specific. Glucocorticoids also upregulated atrophy genes in cultured osteoblastic/osteocytic cells, in ex vivo bone organ cultures, and in muscle organ cultures and C2C12 myoblasts/myotubes. Furthermore, glucocorticoids markedly increased the expression of components of the Notch signaling pathway in muscle in vivo, ex vivo, and in vitro. In contrast, glucocorticoids did not increase Notch signaling in bone or bone cells. Moreover, the increased expression of atrophy-related genes in muscle, but not in bone, and the decreased myotube diameter induced by glucocorticoids were prevented by inhibiting Notch signaling. Thus, glucocorticoids activate different mechanisms in bone and muscle that upregulate atrophy-related genes. However, the role of these genes in the effects of glucocorticoids in bone is unknown. Nevertheless, these findings advance our knowledge of the mechanism of action of glucocorticoids in the musculoskeletal system and provide the basis for novel therapies to prevent glucocorticoid-induced atrophy of bone and muscle.

Pharmacogenetics of efavirenz discontinuation for reported central nervous system symptoms appears to differ by race.

BACKGROUND: Efavirenz frequently causes central nervous system (CNS) symptoms. We evaluated genetic associations with efavirenz discontinuation for CNS symptoms within 12 months of treatment initiation. METHODS: Patients had initiated efavirenz-containing regimens at an HIV primary care clinic in the Southeastern United States and had at least 12 months of follow-up data. Polymorphisms in CYP2B6 and CYP2A6 defined efavirenz metabolizer categories. Genome-wide genotyping enabled adjustment for population stratification. RESULTS: Among 563 evaluable patients, 99 (17.5%) discontinued efavirenz within 12 months, 29 (5.1%) for CNS symptoms. The hazard ratio (HR) for efavirenz discontinuation for CNS symptoms in slow versus extensive metabolizers was 4.9 [95% confidence interval (CI): 1.9-12.4; P=0.001]. This HR in Whites was 6.5 (95% CI: 2.3-18.8; P=0.001) and 2.6 in Blacks (95% CI: 0.5-14.1; P=0.27). Considering only slow metabolizers, the HR in Whites versus Blacks was 3.1 (95% CI: 0.9-11.0; P=0.081). The positive predictive value of slow metabolizer genotypes for efavirenz discontinuation was 27% in Whites and 11% in Blacks. CONCLUSION: Slow metabolizer genotypes were associated significantly with efavirenz discontinuation for reported CNS symptoms. This association was considerably stronger in Whites than in Blacks.

Laparoscopic-assisted extirpation of falciform ligament hemangiosarcoma in a dog.

An 8-year-old, spayed female, bichon frisé dog had incidental nodules within its falciform ligament identified on routine abdominal ultrasonography. A laparoscopic-assisted technique provided both a diagnostic and a therapeutic treatment option. A histopathological diagnosis of hemangiosarcoma was made. This is the second case reporting hemangiosarcoma of the falciform fat.

Extraction assistée par laparascopie d'un hémangiosarcome du ligament falciforme chez un chien. Une chienne Bichon frisé stérilisée âgée de 8 ans avait des nodules secondaires dans le ligament falciforme qui ont été identifiés lors d'une échographie abdominale de routine. Une technique assistée par laparascopie a fourni un diagnostic et une option de traitement thérapeutique. Un diagnostic d'hémangiosarcome a été posé à l'histopathologie. Il s'agit du deuxième cas d'hémangiosarcome du gras falciforme signalé.(Traduit par Isabelle Vallières).

Pleiotropic and sex-specific effects of cancer GWAS SNPs on melanoma risk in the population architecture using genomics and epidemiology (PAGE) study.

BACKGROUND: Several regions of the genome show pleiotropic associations with multiple cancers. We sought to evaluate whether 181 single-nucleotide polymorphisms previously associated with various cancers in genome-wide association studies were also associated with melanoma risk. METHODS: We evaluated 2,131 melanoma cases and 20,353 controls from three studies in the Population Architecture using Genomics and Epidemiology (PAGE) study (EAGLE-BioVU, MEC, WHI) and two collaborating studies (HPFS, NHS). Overall and sex-stratified analyses were performed across studies. RESULTS: We observed statistically significant associations with melanoma for two lung cancer SNPs in the TERT-CLPTM1L locus (Bonferroni-corrected p<2.8x10-4), replicating known pleiotropic effects at this locus. In sex-stratified analyses, we also observed a potential male-specific association between prostate cancer risk variant rs12418451 and melanoma risk (OR=1.22, p=8.0x10-4). No other variants in our study were associated with melanoma after multiple comparisons adjustment (p>2.8e-4). CONCLUSIONS: We provide confirmatory evidence of pleiotropic associations with melanoma for two SNPs previously associated with lung cancer, and provide suggestive evidence for a male-specific association with melanoma for prostate cancer variant rs12418451. This SNP is located near TPCN2, an ion transport gene containing SNPs which have been previously associated with hair pigmentation but not melanoma risk. Previous evidence provides biological plausibility for this association, and suggests a complex interplay between ion transport, pigmentation, and melanoma risk that may vary by sex. If confirmed, these pleiotropic relationships may help elucidate shared molecular pathways between cancers and related phenotypes.