Impact of sex on ventral hernia repair outcomes: A systematic review and meta-analysis.

BACKGROUND: Given the variability in abdominal physiology and hernia presentation between sexes, better comprehension of sex-related differences in outcomes would tailor surgical approach and counseling regarding postoperative outcomes. This meta-analysis aims to appraise the effect of sex on the outcomes of ventral hernia repair. METHODS: A literature search in PubMed, EMBASE and Cochrane selected studies comparing outcomes of ventral hernia repair between sexes. Postoperative outcomes were assessed by pooled and meta-analysis. Statistical analysis was performed using RevMan 5.4. RESULTS: We screened 3128 studies, reviewed 133, and included 18 observational studies, which encompassed 220,799 patients following ventral hernia repair. Postoperative chronic pain was significantly higher in female (OR 1,9; 95% CI 1,64-2,2; p â€‹< â€‹0,001). There were no significant differences in complications, readmission, or recurrence rates between females and males. CONCLUSION: Female sex is associated with a higher risk of postoperative chronic pain following ventral hernia repair.

A Systematic Review and Meta-analysis of Antibiotic Resistance of Foodborne Pathogenic Bacteria in West Africa Between 2010 and 2020.

OBJECTIVE: In the past, studies on antimicrobial resistance were carried out on pathogens in the clinical areas. However, since then, this phenomenon has become a general case both in the environment and in the food sector. This systematic review aimed to review the various scientific publications on the resistance of bacteria to antibiotics in foods in West Africa. METHODS: An extensive literature search was carried out through an electronic database including PubMed, Google Scholar, Research Gate, and African Journals Online (AJOL). Articles published from fifteen countries of the Economic Community of West African States (ECOWAS) between 2010 and 2020 on antibiotic resistance of foodborne pathogens were included in the study. The titles and abstracts of the retrieved articles and then the full texts of the selected articles were reviewed. RESULTS: Out of the 565 articles found in our initial research, 149 publications (26.55%) were considered suitable for inclusion in this review. Globally, 2018, 2019, and 2020 had more included papers (n = 21 to 25) than the other years. Of the 149 publications analyzed, four types of food commodities were identified as products of high consumption based on the number of publications in the field such as poultry (39/149), read-to-eat food (22/149), meat, and animal products (20/149). Most studies have shown that E. coli has the highest prevalence followed by Salmonella and Staphylococcus. Only 33 (22.14%) of the 149 publications were based on further molecular characterization of the isolates. Publications analyzed showed that the most prevalent detected genes were tet(A), tet(B), tet(C), tet(K) blaTEM, catA1, catA2, cmlA, blaCTXM and qnrA, qnrB, qnrS, parC, and qepA4. CONCLUSION: From these results, antibiotic use in the food areas must be strongly regulated, especially in developing countries, particularly in Africa. This highlights the need to implement suitable and appropriate control strategies to reduce complications and prevent the dissemination of resistant bacteria isolates in foods. One health antimicrobial resistance surveillance system in the region must be a great concern.

CT characteristics of uterine and vaginal mesenchymal tumours in dogs.

OBJECTIVES: To describe the CT characteristics of uterine and vaginal mesenchymal tumours in dogs and to discuss imaging findings of the tumour types encountered. MATERIALS AND METHODS: Retrospective study on female dogs with confirmed histological diagnosis of uterine and vaginal mesenchymal tumours and available CT images. RESULTS: 120 records obtained through a medical record search were manually evaluated for eligibility, and 11 dogs presenting masses associated with the genital tract were identified. Of these 11 dogs, 7 dogs met the inclusion criteria and were included in the study. A clear degree of overlap was present between measurements of maximal diameter of benign and malignant tumours; however, malignant neoplasms tended to occupy a larger portion of the pelvic canal. Objective measurements of length suggest that malignant tumours were longer than benign forms. Bone involvement was only observed with malignancy. CLINICAL SIGNIFICANCE: Although CT is likely to play a limited role in the advanced workup of uterine and vaginal mesenchymal neoplasms, CT may represent a more accessible diagnostic tool than MRI and results of this study may help imagers familiarise themselves with their appearances.

Treatment of cervical cancer metastatic to the abdominal wall with reconstruction using a composite myocutaneous flap: A case report.

A 43-year-old woman treated with radical hysterectomy 1 year ago for cervical cancer presented with a suprapubic abdominal mass. A 15 cm necrotic mass from the abdominal wall along with 2 small bowel loops and the dome of the bladder were resected. The peritoneal defect was reconstructed with a pedicled anterolateral thigh and Vastus Lateralis muscle composite flap. Pathology showed invasive non-keratinizing moderately differentiated squamous cell carcinoma, consistent with metastatic cervical cancer, involving urinary bladder, bowel and soft tissue. With advancement in reconstructive surgery, extensive resection with defect closure in properly selected cases of metastatic cervical cancer to the abdominal wall may be considered in an attempt at improving quality of life and overall survival.

Prevalence of proteinuria in a canine oncology population.

OBJECTIVE: To evaluate the point prevalence of proteinuria in dogs presenting to the University of Georgia Oncology Service for the first time. MATERIALS AND METHODS: In this prospective study, 60 client-owned dogs with a confirmed cancer diagnosis were included but those with lower urinary tract neoplasia were excluded. Each dog's signalment, cancer diagnosis, previous cancer treatments, current medications and travel history were recorded. Renal values, electrolytes, packed cell volume, total solids, systolic blood pressure, urinalysis, urine protein:urine creatinine and retinal examinations were recorded. Non-proteinuric, borderline proteinuria and overt proteinuria were defined as urine protein:urine creatinine <0·2, ≥0·2 but <0·5, and ≥0·5, respectively. Urine culture was performed in dogs with active urine sediments or overt proteinuria. RESULTS: Twenty-nine dogs were non-proteinuric (48·3%), 22 (36·7%) borderline proteinuric and nine (15%) overtly proteinuric. None were azotaemic. Hypertension (systolic blood pressure ≥160 mmHg) was detected in 18 (30%) dogs. Of these, six were non-proteinuric, nine borderline proteinuric, and three overtly proteinuric. Proteinuria was detected in 51% of dogs presented to our oncology service, the majority of which were classified as borderline. CLINICAL SIGNIFICANCE: The high proportion of proteinuria in dogs in this study suggests that screening for proteinuria in dogs with cancer may be prudent. Larger studies are required to correlate specific cancer types and the impact of treatment with the development, magnitude and persistence of proteinuria.

Rabacfosadine for relapsed canine B-cell lymphoma: Efficacy and adverse event profiles of 2 different doses.

Rabacfosadine (RAB), a novel double prodrug of the acyclic nucleotide phosphonate PMEG, preferentially targets neoplastic lymphocytes with reduced off target toxicity. Historical studies have suggested that every 21-day dosing is effective with acceptable toxicity. The purpose of this study was to evaluate RAB's safety and efficacy at 2 different doses every 21 days in dogs with relapsed B-cell lymphoma. Dogs that had failed 1 doxorubicin-based chemotherapy protocol were eligible for inclusion in this prospective trial. Once enrolled, dogs were randomized to receive RAB at either 0.82 mg/kg or 1.0 mg/kg as a 30-minute IV infusion every 21 days for up to 5 treatments. Response assessment and adverse event (AE) evaluation were performed every 21 days via VCOG criteria. Fifty dogs were enrolled, with 16 treated at 0.82 mg/kg and 34 treated at 1.0 mg/kg. The overall response rate was 74%, with 45% of dogs experiencing a complete response (CR). The median progression free intervals (PFIs) were 108 days, 172 days and 203 days for all dogs, all responders, and all CRs, respectively. Response rates and PFIs were similar in both treatment groups. The incidence of AEs, dose delays, dose reductions and withdrawals were not statistically different between the 2 groups. The AEs observed were similar to those previously reported and included hematologic, gastrointestinal, dermatologic and pulmonary AEs. One dog had grade 5 pulmonary fibrosis; otherwise, AEs resolved with supportive treatment. Rabacfosadine is a generally well tolerated, effective chemotherapy option for dogs with relapsed B-cell lymphoma.

Characterization of a low expression haplotype in canine glutathione S-transferase (GSTT1) and its prevalence in golden retrievers.

Glutathione S-transferase-theta (GSTT1) is a carcinogen detoxification enzyme, and low activity variants are associated with lymphoma in humans. We recently found a variant in the 3' untranslated region (UTR) of canine GSTT1, *101_102insT, which was predicted to change miRNA binding and was found in 5 of 17 golden retriever (GR) dogs with lymphoma but none of 14 healthy GRs. The aim of this study was to determine whether this variant led to decreased GSTT1 expression and was a discernible risk factor for lymphoma within the GR breed. On resequencing, *101_102insT appeared to be in complete linkage disequilibrium with 3 additional 3'UTR variants, leading to the inferred haplotype *3T>C; *101_102insT; *190C>A; *203T>C. In canine livers that were heterozygous for this variant haplotype, GSTT1 protein expression was significantly lower compared to the reference haplotype (densitometry .40 vs .64, P = .022), and GSTT1 transcript levels by qPCR were also significantly lower (fold difference .52, P = .012), without evidence of substantial allelic expression imbalance. The variant haplotype led to >50% decrease in expression in vitro (.31 ± .07 vs .64 ± .19; P = .019). We found no significant difference in minor allele frequencies between 71 GR dogs with lymphoma (MAF .162) and 33 healthy age-matched controls (MAF .136, P = .69). Our results indicate that the variant GSTT1 3'UTR haplotype containing *101_102insT reduces gene expression, which could lead to impaired carcinogen detoxification, but was not a detectable risk factor for lymphoma in GR dogs.

Geographical differences in survival of dogs with non-Hodgkin lymphoma treated with a CHOP based chemotherapy protocol.

BACKGROUND: In humans geographical differences in the incidence and presentation of various cancers have been reported. However, much of this information has not been collected in veterinary oncology. AIM: The purpose of this study was to determine if a geographic difference in progression free survival exists for dogs with lymphoma treated within the US. MATERIALS AND METHODS: Medical records of 775 cases of canine lymphoma from 3 US regions (west, south and north), treated with CHOP chemotherapy, were retrospectively evaluated. Cases were collected from referral institutions and were required to have received at least one doxorubicin treatment and have follow up information regarding time to progression. RESULTS: Significant differences in sex (p = 0.05), weight (p = 0.049), stage (p < 0.001), immunophenotype (p = <0.001), and number of doxorubicin doses (p = 0.001) were seen between regions. Upon univariate analysis, progression free survival (PFS) differed by region (p = 0.006), stage (p = 0.009), sub-stage (p = 0.0005), and immunophenotype (p = 0.001). A multivariable Cox regression model showed that dogs in the western region had a significantly shorter PFS when compared to the south and east. CONCLUSION: PFS was significantly affected by stage, sub-stage and phenotype.

Anti-proliferative effect of metformin on a feline injection site sarcoma cell line independent of Mtor inhibition.

Metformin is an oral hypoglycemic drug that has been shown to inhibit cancer cell proliferation via up-regulation of AMPK (AMP-activated protein kinase), and possibly inhibition of mTOR (mammalian target of rapamycin). The purpose of this study was to evaluate the effects of metformin on a feline injection site sarcoma cell line. Cells from a feline injection site sarcoma cell line were treated with metformin at varied concentrations. A dose-dependent decrease in cell viability following metformin treatment was observed, with an IC50 of 8.0mM. Using flow cytometry, the mechanism of cell death was determined to be apoptosis or necrosis. To evaluate the role of mTOR inhibition in metformin-induced cell death, Western blot was performed. No inhibition of mTOR or phosphorylated mTOR was found. Although metformin treatment leads to apoptotic or necrotic cell death in feline injection site sarcoma cells, the mechanism does not appear to be mediated by mTOR inhibition.

Febrile neutropenia in cats treated with chemotherapy.

The purpose of this study was to describe the clinical presentation, potential causative agents, treatment and outcome of febrile neutropenia (FN) in chemotherapy-treated cats. Medical records from eight institutions were retrospectively reviewed. A total of 22 FN events in 20 cats were evaluated. Lymphoma was the most common cancer diagnosis; lomustine and vinca alkaloids were the most frequently implicated causative agents. Presenting clinical signs included decreased appetite, lethargy, vomiting and diarrhoea. Median body temperature and absolute neutrophil count at presentation were 104.1 °F; 40 °C (range: 103.1-105.1 °F; 39.5-40.6 °C) and 246 mL-1 (range: 0-1600 mL-1 ), respectively. Median number of days between chemotherapy administration and FN onset was 5 (range: 4-25 days). All but one cat were treated with intravenous fluids and broad spectrum antibiotics. Fevers resolved in all cases and absolute neutrophil counts returned to normal in 19 cats. Clinical presentation of cats with FN appears similar to that of dogs.

Prospective evaluation of the safety of compounded bulk material L-asparaginase in dogs with lymphoma.

Use of compounded L-asparaginase became routine in veterinary oncology when manufacturing of Elspar® was discontinued in 2012. The objective of this study was to evaluate the safety of compounded L-asparaginase (CLASP, KRS Global Biotechnology, Boca Raton, FL, USA) in comparison with Elspar® (Lundbeck LLC, Deerfield, IL, USA). In addition, we documented the response to CLASP in combination with a corticosteroid in this population of dogs with lymphoma. Dogs were prospectively treated with 10 000 IU/m2 CLASP or Elspar® subcutaneously. Corticosteroids were administered concurrently. Adverse events (AE) were assessed according to the Veterinary Cooperative Oncology Group Common Terminology Criteria for Adverse Events v1.1 (VCOG-CTCAE). Response was recorded. Seventy-three dogs received 75 treatments (CLASP, n = 47; Elspar® , n = 28). No AE were attributed to CLASP. Grade I and II AE probably or possibly related to treatment were observed following two Elspar® treatments. The overall response rate to the combination of CLASP and a corticosteroid was 80% (24% CR and 56% PR). In combination with a steroid, the compounded L-asparaginase evaluated in this study is safe and demonstrates activity against canine lymphoma. In the face of the discontinuation of Elspar® , veterinarians should seek compounded LASP products that have been tested for activity, purity, and sterility.

Body adiposity and bone parameters of male rats from mothers fed diet containing flaxseed flour during lactation.

Obesity and osteoporosis may have their origins in early postnatal life. This study was designed to evaluate whether flaxseed flour use during lactation period bears effect on body adiposity and skeletal structure of male rat pups at weaning. At birth, male Wistar rats were randomly assigned to control and experimental (FF) groups, whose dams were treated with control or flaxseed flour diet, respectively, during lactation. At 21 days of age, pups were weaned to assess body mass, length and composition by dual-energy X-ray absorptiometry. The animals were then sacrificed to carry out analysis of serum profile, intra-abdominal adipocyte morphology and femur characteristics. Differences were considered significant when P<0.05. The FF group displayed the following characteristics (P<0.05): higher body mass, length, bone mineral content, bone area and concentrations of osteoprotegerin, osteocalcin and high-density lipoprotein cholesterol; higher levels of stearic, α-linolenic, eicosapentaenoic and docosapentaenoic acids and lower levels of arachidonic acid and cholesterol; smaller adipocyte area; and higher mass, epiphysis distance, diaphysis width, maximal load, break load, resilience and stiffness of femur. Flaxseed flour intake during lactation period promoted adipocyte hypertrophy down-regulation and contributed to pup bone quality at weaning.

Phase II evaluation of VDC-1101 in canine cutaneous T-cell lymphoma.

BACKGROUND: Canine cutaneous T-cell lymphoma (CTCL) is an uncommon disease for which efficacious therapies are lacking. The novel anticancer nucleotide prodrug VDC-1101 (formerly known as GS-9219) has shown efficacy in dogs with multicentric lymphoma. One of the observed adverse effects with this drug was a skin change characterized by hair loss, erythema, and pruritus, implying delivery of VDC-1101 to the skin. HYPOTHESIS/OBJECTIVES: The primary study objective was to identify the objective response rate (ORR) to VDC-1101 in canine CTCL; secondary objectives included characterization of progression-free survival (PFS) and adverse events (AEs). ANIMALS: Twelve dogs with chemotherapy-naïve or relapsed, histologically and immunohistochemically confirmed CTCL. METHODS: Dogs received VDC-1101 as a 30-minute IV infusion once every 21 days. Prednisone (1 mg/kg PO q48h) was administered concurrently. RESULTS: In 11 evaluable patients, responses included 1 complete response (CR), 4 partial responses (PR), 2 stable disease (SD), and 4 progressive disease for an ORR of 45% and biologic response rate (CR/PR/SD) of 64%. The median PFS was 37.5 days (26 to >399 days), which includes 1 durable and ongoing CR (>1 year). Gastrointestinal and hematologic AEs were mild; no dogs developed grade 3 or 4 AEs. Three dogs developed dermatopathies and 1 of these dogs was removed from the study as a result of this AE. CONCLUSIONS AND CLINICAL IMPORTANCE: VDC-1101 has activity against canine CTCL and could provide another treatment option in a disease process with a poor prognosis.

Phase I/IIa study evaluating the safety, efficacy, pharmacokinetics, and pharmacodynamics of lucitanib in advanced solid tumors.

BACKGROUND: Lucitanib is a potent, oral inhibitor fibroblast growth factor receptor types 1 and 2 (FGFR), vascular endothelial growth factor receptor types 1, 2, and 3 (VEGFR), platelet-derived growth factor receptor types α and ß (PGFRα/ß), which are essential kinases for tumor growth, survival, migration, and angiogenesis. Several tumor types, including breast carcinoma, demonstrate amplification of fibroblast growth factor (FGF)-related genes. There are no approved drugs for molecularly defined FGF-aberrant (FGFR1- or FGF3/4/19-amplified) tumors. METHODS: This open-label phase I/IIa study involved a dose-escalation phase to determine maximum tolerated dose (MTD), recommended dose (RD), and pharmacokinetics of lucitanib in patients with advanced solid tumors, followed by a dose-expansion phase to obtain preliminary evidence of efficacy in patients who could potentially benefit from treatment (i.e. with tumors harboring FGF-aberrant pathway or considered angiogenesis-sensitive). RESULTS: Doses from 5 to 30 mg were evaluated with dose-limiting toxic effects dominated by vascular endothelial growth factor (VEGF) inhibition-related toxic effects at the 30 mg dose level (one case of grade 4 depressed level of consciousness and two cases of grade 3 thrombotic microangiopathy). The most common adverse events (all grades, all cohorts) were hypertension (91%), asthenia (42%), and proteinuria (57%). Exposure increased with dose and t½ was 31-40 h, suitable for once daily administration. Seventy-six patients were included. All but one had stage IV; 42% had >3 lines of previous chemotherapy. Sixty-four patients were assessable for response; 58 had measurable disease. Clinical activity was observed at all doses tested with durable Response Evaluation Criteria In Solid Tumors (RECIST) partial responses in a variety of tumor types. In the angiogenesis-sensitive group, objective RECIST response rate (complete response + partial response) was 26% (7 of 27) and progression-free survival (PFS) was 25 weeks. In assessable FGF-aberrant breast cancer patients, 50% (6 of 12) achieved RECIST partial response with a median PFS of 40.4 weeks for all treated patients. CONCLUSION: Lucitanib has promising efficacy and a manageable side-effect profile. The spectrum of activity observed demonstrates clinical benefit in both FGF-aberrant and angiogenesis-sensitive populations. A comprehensive phase II program is planned.

Masitinib mesylate does not enhance sensitivity to radiation in three feline injection-site sarcoma cell lines under normal growth conditions.

Masitinib, a selective tyrosine kinase inhibitor, was investigated as a radiosensitizer in three primary feline injection-site sarcoma (ISS) cell lines. Sensitivity to masitinib was previously assessed via cell growth inhibition assays with mean IC50 values of 5.5-8.6µM. Clonogenic assays were performed to determine the effect of masitinib and radiation on cell survival. Single dose radiation (0-12Gy) experiments were carried out under normal growth conditions in control ISS cells and in cells incubated with 1 or 6µM masitinib for 72h prior to irradiation. Radiation administered either alone or in combination with masitinib induced a dose-dependent reduction in clonogenic survival. Survival from the combined masitinib and radiation treatment was not significantly different from that of radiation alone. Results suggest that masitinib does not directly enhance ISS cell radiosensitivity under normal in vitro conditions, although this does not preclude the utility of further investigations to assess sensitization properties under altered conditions.

Indirect assessment of dihydropyrimidine dehydrogenase activity in cats.

Use of 5-fluoropyridimine antimetabolite drugs, specifically 5-fluorouracil (5-FU), has been discouraged in cats because of adverse events including neurotoxicity and death. Causes of toxicity have never been elucidated. In humans, toxicity has been associated with ineffective metabolism secondary to deficiencies in dihydropyrimidine dehydrogenase (DPD). Direct assessment of DPD activity is challenging; determination of uracil:dihydrouracil (U:UH2 ) in plasma using high performance liquid chromatography (HPLC) has been reported as an indirect measurement. U:UH2 was measured in the plasma of 73 cats. Mean U:UH2 for all cats was 1.66 ± 0.11 (median 1.53, range 0.24-7.00). Seventeen (23%) cats had U:UH2 >2, a value associated with decreased DPD activity in humans. Spayed female cats had significantly lower U:UH2 as compared with intact females, and age and U:UH2 were weakly but significantly negatively correlated (r = -0.26). Studies correlating U:UH2 and 5-FU tolerability are required to further determine the validity and use of this test in cats.

High-fat diets containing soybean or canola oil affect differently pancreas function of young male rats.

The excessive fat intake generally might induce obesity and metabolic disturbances. Thus, the goal of the study was to assess the role of high-fat diets containing soybean or canola oil on intra-abdominal adiposity and pancreatic morphology and function of young rats. After weaning, rats were fed with a control diet (7S) or a high-fat diet containing soybean oil (19S) or canola oil (19C) until they were 60 days old, when they were sacrificed. Food intake (g/day), body mass and length, retroperitoneal and epididymal fat mass, HOMA-IR, HOMA-ß and area of pancreatic islets were assessed. The results were considered different with a significant level of p<0.05. Both 19S and 19C groups showed higher body mass, length, and retroperitoneal fat mass. The 19C group showed higher HOMA-IR (+43% and +78%) and HOMA-ß (+40% and +59%) than 19S and 7S groups, respectively. Both 19S and 19C groups showed lower pancreatic islets area in relation to 7S group. Meantime, 19C presented lower percentage of pancreatic islets area in comparison to 19S (-41%) and 7S group (-70%, p<0.0001). Independent of soybean or canola oil, the high fat diet promoted development of the obesity. Comparing 19C and 19S groups, the higher concentrations of monounsaturated fatty acids, present in the canola oil were worse than higher concentrations of polyunsaturated fatty acids, present in the soybean oil.

Phase I clinical trial of vinorelbine in tumor-bearing cats.

BACKGROUND: Vinorelbine (VRL) has been investigated in dogs, but its use in cats has not been studied. HYPOTHESIS/OBJECTIVES: To determine the maximal tolerated dose (MTD) and dose-limiting toxicity (DLT) of VRL in tumor-bearing cats. ANIMALS: Cats were included in this prospective phase I trial if they had confirmed malignancy, received ≥1 VRL treatment, and had adequate follow-up. Previous treatment was acceptable, but concurrent chemotherapy or radiotherapy was not permitted. METHODS: Using a modified phase I design, cats were enrolled in cohorts of 3 at a starting dosage of 9 mg/m(2) . Cats tolerating the first treatment well were eligible to receive additional VRL treatments at escalating dosages; escalations beyond the perceived MTD were permitted based on individual tolerance. Intended treatment interval was 7 days. Patient histories, physical examinations, and complete blood counts were performed weekly. RESULTS: Nineteen cats were included. Sixty-one VRL treatments were administered. Median number of treatments was 2 (range, 1-9). Starting dosages were 9-12 mg/m(2) . Maximal dosage administered was 15.5 mg/m(2) . The MTD was 11.5 mg/m(2) . Acute DLTs were neutropenia, vomiting, and nephrotoxicity. Other notable toxicities were weight loss and anemia. CONCLUSIONS AND CLINICAL IMPORTANCE: Vinorelbine is tolerated in cats at a weekly interval. Recommended starting dosage is 11.5 mg/m(2) . Neutropenia was transient, lasting <7 days; vomiting was self-limiting in most cases. Although VRL-associated nephrotoxicity has not been reported, potential attribution of this toxicity to VRL must not be discounted. Further investigation of the efficacy of VRL in feline malignancies is warranted.