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There is growing evidence supporting clinically important associations between age at neutering in bitches and subsequent urinary incontinence (UI), although much of this evidence to date is considered weak. Target trial emulation is an innovative approach in causal inference that has gained substantial attention in recent years, aiming to simulate a hypothetical randomised controlled trial by leveraging observational data. Using anonymised veterinary clinical data from the VetCompass Programme, this study applied the target trial emulation framework to determine whether later-age neutering (≥ 7 to ≤ 18 months) causes decreased odds of early-onset UI (diagnosed < 8.5 years) compared to early-age neutering (3 to < 7 months). The study included bitches in the VetCompass database born from January 1, 2010, to December 31, 2012, and neutered between 3 and 18 months old. Bitches were retrospectively confirmed from the electronic health records as neutered early or later. The primary outcome was a diagnosis of early-onset UI. Informed from a directed acyclic graph, data on the following covariates were extracted: breed, insurance status, co-morbidities and veterinary group. Inverse probability of treatment weighting was used to adjust for confounding, with inverse probability of censoring weighting accounting for censored bitches. The emulated trial included 612 early-age neutered bitches and 888 later-age neutered bitches. A pooled logistic regression outcome model identified bitches neutered later at 0.80 times the odds (95% CI 0.54 to 0.97) of early-onset UI compared with bitches neutered early. The findings show that later-age neutering causes reduced odds of early-onset UI diagnosis compared with early-age neutering. Decision-making on the age of neutering should be carefully considered, with preference given to delaying neutering until after 7 months of age unless other major reasons justify earlier surgery. The study is one of the first to demonstrate successful application of the target trial framework to veterinary observational data.

BackgroundDrilling accuracy is essential in the correct positioning of implants and avoidance of iatrogenic damage to surrounding tissues. The use of augmented drilling methods has been documented as an approach to improving the accuracy of drilling. The aim of this study was to compare the accuracy of two augmented drilling methods (fluoroscopically guided and aiming device) to freehand (FH) drilling.MethodsThree experienced specialist surgeons and three veterinary surgeons without primary orthopaedic experience drilled into synthetic bone towards a target using the three different methods at three different angles (0°, 10° and 20°). The duration of drilling was recorded, and the accuracy of drilling was measured using photographs before and after drilling.ResultsThe two augmented methods were more accurate than FH drilling in synthetic bone, with the aiming device producing the greatest accuracy. Increased angulation of drilling decreased the drilling accuracy. Surgeon experience did not impact on drilling accuracy. Surgeon inexperience and augmented drilling methods both increased the time taken to drill.ConclusionThe use of augmented drilling methods improved the accuracy of drilling, and surgeons should consider their use when drilling in anatomical regions where the margin of error is small.

The accuracy of drill hole location is critical for implant placement in orthopaedic surgery. Increasing drill bit size sequentially has been suggested as a method for improving the accuracy of drill hole start location. The aim of this study was to determine whether sequential drilling or drill angulation would alter accuracy of drill hole start location. Three specialist veterinary surgeons drilled holes in synthetic bone models either directly, or with sequentially increasing drill bit sizes. Drilling was performed at 0o, 10o and 20o to perpendicular to the bone models. Three synthetic bone models were used to mimic canine cancellous and cortical bones. Sequential drilling resulted in greater inaccuracy in drill hole location when assessing all drilling angles together. There was no influence of surgeon or synthetic bone density on drilling accuracy. The combination of drill angulation and sequential drilling increased inaccuracy in drill hole start location. We conclude that sequential drilling decreased accuracy of drill hole location in the synthetic bone model when drilling was angled. Inaccuracy associated with the drill hole start location should be taken into account when performing surgery, although the magnitude of inaccuracy is low when compared with other sources of error such as angulation.

Experience in farm animal referral centres in the UK has shown an increase in the number of pigs being presented for age-related problems. These include obesity, arthritis, skin disorders, overgrown tusks and overgrown claws. Seven pigs presented over a 7-year period to two university veterinary teaching hospitals in the UK with clinical signs including behavioural change, abnormal vaginal discharge, inappetence and abdominal distension that was found to localise to the reproductive tract. Histology of the reproductive tract found cystic endometrial hyperplasia (n=7) and uterine tumours (n=4) following ovariohysterectomy (n=4) or postmortem examination (n=3). Tumours identified were leiomyoma (n=1), fibroleiomyoma (n=1) and leiomyosarcoma (n=2).

In hiatal hernia, elements of the abdominal cavity herniate through the oesophageal hiatus into the mediastinum. Although they are uncommon in both human and veterinary medicine, patients can develop significant clinical complications such as severe gastrointestinal signs, gastric dilatation and volvulus syndrome, and in some cases death. The most comprehensive classification scheme recognises four types of hiatal hernia. Herein, the authors describe a first report of a dog with subclinical intermittent type IV paraoesophageal hernia. CT assisted a rapid, definitive diagnosis and illustrated both the dynamic nature of this type of hernia and the potential for it to lead to severe respiratory compromise. It also facilitated rapid surgical planning, increasing the likelihood of a successful surgical outcome.

A seven-year-old male neutered labrador weighing 35 kg with a two-week history of left forelimb lameness was diagnosed with osteosarcoma of the third metacarpal bone. No pulmonary metastases were detected and ray amputation (removal of the left third metacarpal bone and third phalanx en bloc) was performed. Circumferential sutures were placed around metacarpals II and IV to realign the adjacent bones and digits during the healing period. The dog received six cycles of single-agent carboplatin (300 mg/m2) postoperatively. Restaging nine months postoperatively revealed no evidence of metastasis or recurrence. Two years postoperatively, the dog has no evidence of complications or lameness. Thoracic limb amputation and postoperative adjunctive therapy are considered the gold standard treatment for appendicular osteosarcoma; however, an oncological compartment excision of this bone tumour was performed with similar outcome for the patient while preserving the limb.

An eight-year-old male entire boxer dog was presented by the owner with a four-week history of haematuria. Abdominal ultrasound identified a moderately dilated left ureter from immediately distal to the renal pelvis to a focal stenosis at the level of L5. Intravenous urography showed a diffusely tortuous proximal left ureter with irregular contrast borders and focal stenosis distally. Left ureteronephrectomy was performed and histology of the left ureter revealed a primary ureteral urothelial (transitional cell) carcinoma infiltrating the ureteral wall. This is the first imaging description of a primary ureteral urothelial carcinoma and only the second description of a primary ureteral urothelial carcinoma in veterinary literature.

Congenital lobar emphysema is a rare condition in dogs. A three-month-old pug presented with acute dyspnoea and radiographic findings diagnosed congenital lobar emphysema. Due to the patient’s rapidly deteriorating ventilation, an emergency right middle lung lobectomy was performed and recovery was uneventful. This case report describes the importance of making a prompt and accurate diagnosis of this condition, based on radiographic findings, to facilitate immediate treatment.

The Atlantic meridional overturning circulation (AMOC) is a system of ocean currents that has an essential role in Earth’s climate, redistributing heat and influencing the carbon cycle 1 , 2 . The AMOC has been shown to be weakening in recent years 1 ; this decline may reflect decadal-scale variability in convection in the Labrador Sea, but short observational datasets preclude a longer-term perspective on the modern state and variability of Labrador Sea convection and the AMOC 1 , 3 – 5 . Here we provide several lines of palaeo-oceanographic evidence that Labrador Sea deep convection and the AMOC have been anomalously weak over the past 150 years or so (since the end of the Little Ice Age, LIA, approximately ad  1850) compared with the preceding 1,500 years. Our palaeoclimate reconstructions indicate that the transition occurred either as a predominantly abrupt shift towards the end of the LIA, or as a more gradual, continued decline over the past 150 years; this ambiguity probably arises from non-AMOC influences on the various proxies or from the different sensitivities of these proxies to individual components of the AMOC. We suggest that enhanced freshwater fluxes from the Arctic and Nordic seas towards the end of the LIA—sourced from melting glaciers and thickened sea ice that developed earlier in the LIA—weakened Labrador Sea convection and the AMOC. The lack of a subsequent recovery may have resulted from hysteresis or from twentieth-century melting of the Greenland Ice Sheet 6 . Our results suggest that recent decadal variability in Labrador Sea convection and the AMOC has occurred during an atypical, weak background state. Future work should aim to constrain the roles of internal climate variability and early anthropogenic forcing in the AMOC weakening described here. Palaeoclimate records show that the Atlantic meridional overturning circulation weakened substantially at the end of the Little Ice Age, probably in response to enhanced freshwater fluxes from the Arctic and Nordic seas.

Bacterial signaling systems are prime drug targets for combating the global health threat of antibiotic resistant bacterial infections including those caused by Staphylococcus aureus. S. aureus is the primary cause of acute bacterial skin and soft tissue infections (SSTIs) and the quorum sensing operon agr is causally associated with these. Whether efficacious chemical inhibitors of agr signaling can be developed that promote host defense against SSTIs while sparing the normal microbiota of the skin is unknown. In a high throughput screen, we identified a small molecule inhibitor (SMI), savirin (S. aureus virulence inhibitor) that disrupted agr-mediated quorum sensing in this pathogen but not in the important skin commensal Staphylococcus epidermidis. Mechanistic studies employing electrophoretic mobility shift assays and a novel AgrA activation reporter strain revealed the transcriptional regulator AgrA as the target of inhibition within the pathogen, preventing virulence gene upregulation. Consistent with its minimal impact on exponential phase growth, including skin microbiota members, savirin did not provoke stress responses or membrane dysfunction induced by conventional antibiotics as determined by transcriptional profiling and membrane potential and integrity studies. Importantly, savirin was efficacious in two murine skin infection models, abating tissue injury and selectively promoting clearance of agr+ but not Δagr bacteria when administered at the time of infection or delayed until maximal abscess development. The mechanism of enhanced host defense involved in part enhanced intracellular killing of agr+ but not Δagr in macrophages and by low pH. Notably, resistance or tolerance to savirin inhibition of agr was not observed after multiple passages either in vivo or in vitro where under the same conditions resistance to growth inhibition was induced after passage with conventional antibiotics. Therefore, chemical inhibitors can selectively target AgrA in S. aureus to promote host defense while sparing agr signaling in S. epidermidis and limiting resistance development.