Evaluation of locking compression plate fixation of the distal phalanx to the hoof wall as a potential therapy for laminitis.

BACKGROUND: Surgical stabilisation of the distal phalanx (DP) is a potential therapeutic strategy for severe acute laminitis. OBJECTIVE: To evaluate the effects of locking compression plate (LCP) fixation of the DP to the dorsal hoof wall. STUDY DESIGN: Ex vivo and in vivo experiments. METHODS: A T-shaped LCP was applied to one limb per pair in six pairs of cadaver forelimbs subjected to a combination of thermally induced lamellar failure and vertical load to simulate severe acute laminitis. Standard radiographic measurements were used to compare DP displacement. The LCP was then applied to one forefoot in 12 healthy Standardbred horses either standing (n = 6) or under general anaesthesia (n = 6). Lameness was evaluated daily, then horses were euthanised (day 8) and lamellar tissue analysed using light microscopy, histomorphometery and molecular markers of apoptosis. RESULTS: In the cadaver limb model, LCP fixation prevented the significant changes in hoof-distal phalanx distance, coronary extensor process distance and sole depth that characterised DP displacement in untreated limbs (p < 0.05). Application of the construct in vivo was well tolerated with minimal lameness (10/12 horses were sound at the trot on day 8); however, histology revealed dorsal lamellar pathology consistent with laminitis, but with extensive keratinocyte apoptosis. Adjacent to the LCP, caspase-3 positive cell counts were approximately 20-fold higher than control (p < 0.001). MAIN LIMITATIONS: Pathology was evaluated at a single time point. Microvascular perfusion was not evaluated. CONCLUSIONS: Rigid fixation of the DP to the hoof capsule was achieved with the LCP construct in a cadaver limb laminitis model. In live horses, LCP fixation caused regional lamellar pathology with extensive apoptosis, likely due to disturbed lamellar microvascular perfusion and/or mechanostasis. Understanding these mechanisms is critical for refinement of the technique in order to avoid iatrogenic lamellar damage.

The effect of different grazing conditions on the insulin and incretin response to the oral glucose test in ponies.

BACKGROUND: The oral glucose test (OGT) is a useful tool for diagnosing insulin dysregulation (ID) and is somewhat repeatable in ponies under consistent management. This study aimed to determine whether the insulin and incretin responses to an OGT in ponies differed after short-term access to fertilised pasture, compared to unfertilised pasture, by using a randomised, repeated measures study design. Sixteen mixed-breed ponies were classified as severely insulin-dysregulated (SD; post-prandial insulin ≥80 µIU/mL) or not severely insulin-dysregulated (NSD; post-prandial insulin < 80 µIU/mL) using an OGT prior to the study. The ponies accessed pasture that was fertilised, or unfertilised, for 5 days (4 h/day, with supplemental hay provided at 0.7% bodyweight), with a 10 day period between phases. An OGT was performed after each phase. Glucose, insulin, active glucagon-like peptide-1 (aGLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured in post-prandial blood samples. RESULTS: The volume of fertilised pasture was five-fold greater than unfertilised pasture, with % non-structural carbohydrates (NSC) similar between all forages. Consuming fertilised pasture increased (P = 0.018) the serum insulin response to an OGT, compared to grazing unfertilised pasture. A limitation of the study was that pasture intake was unable to be quantified. Insulin responses were greater in SD, compared to NSD, ponies (P < 0.001) and remained well above the test cut-off at all times. A subset of ponies, initially screened as NSD, became (more) insulin-dysregulated after pasture access. Further, aGLP-1 was a significant predictor of insulin concentration in this cohort. CONCLUSIONS: Whereas some insulin-dysregulated ponies were comparatively resistant to dietary intervention, others showed markedly different OGT responses following subtle changes in their forage-based diet. This implies that mild/early ID might be unmasked by dietary change, and that dietary management is important in these ponies. However, dietary management alone may not be adequate for all cases of ID.

A "modified Obel" method for the severity scoring of (endocrinopathic) equine laminitis.

BACKGROUND: Laminitis is a common equine disease characterized by foot pain, and is commonly diagnosed using a five-grade Obel system developed in 1948 using sepsis-related cases. However, endocrinopathic laminitis is now the most common form of the disease and clinical signs may be mild, or spread across two Obel grades. This paper describes a modified method which assigns scores to discreet clinical signs, providing a wider scale suitable for use in a research setting. METHODS: The "modified Obel" method was developed using an iterative process. First, a prototype method was developed during the detailed observation of 37 ponies undergoing a laminitis induction experiment. The final method was refined and validated using video footage taken during the induction study and from a clinical trial of naturally occurring endocrinopathic laminitis cases. The Obel method was deconstructed and key laminitis signs were evaluated to develop a three-stage, five criteria method that employs a severity scale of 0-12. Veterinarians (n = 28) were recruited to watch and assess 15 video recordings of cases of varying severity, using the Obel and "modified Obel" methods. The inter-observer agreement (reproducibility) was determined using Kendall's coefficient of concordance (Kendall W) and Krippendorf's alpha reliability coefficient. A total of 14 veterinarians repeated the exercise 2-4 weeks after their original assessment, to determine intra-observer agreement (repeatability), assessed using a weighted kappa statistic (kw). Agreement between methods was calculated by converting all "modified Obel" scores to Obel grades and calculating the mean and distribution of the differences. RESULTS: The "modified Obel" and Obel methods showed excellent and similar inter-observer agreement based on the Kendall W value (0.87, P < 0.001 vs. 0.85, P < 0.001) and Krippendorf's alpha (95% CI) value (0.83 [0.53-0.90] vs. 0.77 [0.55-0.85]). Based on the kw value, the "modified Obel" method also had substantial repeatability, although slightly less than the Obel method, (0.80 vs. 0.91). Excellent agreement between the methods was found, with the mean difference (95% CI), comparing the Obel grade, with the "modified Obel" score converted to an Obel grade, being -0.12 (-0.19 to -0.06) grades. The Obel and converted "modified Obel" grades were identical 62% of the time (259/420) and a difference of one grade (higher or lower) occurred in 35% of cases (148/420). CONCLUSION: Both methods show excellent agreement, reproducibility and repeatability when used to diagnose endocrinopathic laminitis. The "modified Obel" method is a three-step examination process for severity-scoring of endocrinopathic laminitis, initially proposed for use within a research setting. When using the modified method a diagnosis of laminitis also requires clinical acumen. The allocation of scores for specific clinical signs should be particularly useful in research trials monitoring laminitis recovery.

Insulin and incretin responses to grazing in insulin-dysregulated and healthy ponies.

BACKGROUND: Supraphysiological insulin and incretin responses to a cereal-based diet have been described in horses and ponies with insulin dysregulation (ID). However, the hormonal responses to grazing have not yet been described. OBJECTIVES: To determine if there is a difference in the insulin and incretin responses to grazing pasture between insulin-dysregulated and healthy ponies. ANIMALS: A cohort of 16 ponies comprising 5 with normal insulin regulation (NIR), 6 with moderate ID (MID), and 5 with severe ID (SID). METHODS: In this case-control study, an oral glucose test (OGT) was used to determine the insulin responsiveness of each pony to PO carbohydrate before grazing pasture (4 hours) for 3 consecutive days. Serial blood samples collected during grazing were analyzed for glucose, insulin, glucose-dependent insulinotropic peptide (GIP) and active glucagon-like peptide-1 (aGLP-1), and compared among pony groups and day of pasture access. RESULTS: The area under the insulin curve when grazing increased with ID severity (P < .03). The median (range) maximal insulin concentration was greater in the MID (72.5 [129] µIU/mL) and SID (255 [338.5] µIU/mL) groups, compared to the NIR (11.7 [24.9] µIU/mL) group (P < .03) and occurred within 2-4 hours of grazing. Postprandial OGT insulin concentration was positively correlated with 2 hours post-grazing insulin across all 3 grazing days (P ≤ .03). The aGLP-1 and GIP concentrations increased in response to grazing but did not differ among groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Grazing pasture provoked an increased insulin and incretin response in insulin-dysregulated ponies within 4 hours of grazing. The pasture and OGT insulin concentrations were correlated.

The sodium-glucose co-transporter 2 inhibitor velagliflozin reduces hyperinsulinemia and prevents laminitis in insulin-dysregulated ponies.

There are no registered veterinary drugs for treating insulin dysregulation and preventing insulin-associated laminitis in horses. Velagliflozin is a sodium-glucose co-transport 2 inhibitor that reduces renal glucose reabsorption, promotes glucosuria, and consequently, decreases blood glucose and insulin concentrations. This study aimed to determine if velagliflozin reduced hyperinsulinemia and prevented laminitis in insulin-dysregulated ponies fed a challenge diet high in non-structural carbohydrates (NSC). An oral glucose test (1 g dextrose/kg BW) was used to screen 75 ponies for insulin dysregulation, of which 49 ponies with the highest insulin concentrations were selected. These animals were assigned randomly to either a treated group (n = 12) that received velagliflozin (0.3 mg/kg BW, p.o., s.i.d.) throughout the study, or a control group (n = 37). All ponies were fed a maintenance diet of alfalfa hay for 3 weeks, before transferring to a challenge diet (12 g NSC/kg BW/d) for up to 18 d. Blood glucose and serum insulin concentrations were measured over 4 h after feeding, on d 2 of the diet. The maximum glucose concentration was 22% lower (P = 0.014) in treated animals, with a geometric mean (95% CI) of 9.4 (8.0-11.0) mM, versus 12.1 (10.7-13.7) mM in the controls. This was reflected by lower (45%) maximum insulin concentrations in the treated group (P = 0.017), of 149 (97-228) µIU/mL, versus 272 (207-356) µIU/mL for controls. The diet induced Obel grade 1 or 2 laminitis in 14 of the 37 controls (38%), whereas no velagliflozin-treated pony developed laminitis (P = 0.011). Velagliflozin was well-tolerated, with no hypoglycemia or any clinical signs of adverse effects. The main limitation of this study was the sample size. Velagliflozin shows promise as a safe and effective compound for treating insulin dysregulation and preventing laminitis by reducing the hyperinsulinemic response to dietary NSC.

Persistent digital hyperthermia over a 48 h period does not induce laminitis in horses.

Persistent digital hyperthermia, presumably due to vasodilation, occurs during the developmental and acute stages of insulin-induced laminitis. The objectives of this study were to determine if persistent digital hyperthermia is the principal pathogenic mechanism responsible for the development of laminitis. The potent vasodilator, ATP-MgCl(2) was infused continuously into the distal phalanx of the left forefoot of six Standardbred racehorses for 48 h via intra-osseous infusion to promote persistent digital hyperthermia. The right forefoot was infused with saline solution and acted as an internal control. Clinical signs of lameness at the walk were not detected at 0 h, 24h or 48 h post-infusion. Mean ± SE hoof wall temperatures of the left forefoot (29.4 ± 0.25°C) were higher (P<0.05) than those on the right (27.5 ± 0.38°C). Serum insulin (15.0 ± 2.89 µIU/mL) and blood glucose (5.4 ± 0.22 mM) concentrations remained unchanged during the experiment. Histopathological evidence of laminitis was not detected in any horse. The results demonstrated that digital vasodilation up to 30°C for a period of 48 h does not trigger laminitis in the absence of hyperinsulinaemia. Thus, although digital hyperthermia may play a role in the pathogenesis of laminitis, it is not the sole mechanism involved.

Empiric management of cyanide toxicity associated with smoke inhalation.

Enclosed-space smoke inhalation is the fifth most common cause of all unintentional injury deaths in the United States. Increasingly, cyanide has been recognized as a significant toxicant in many cases of smoke inhalation. However, it cannot be emergently verified. Failure to recognize the possibility of cyanide toxicity may result in inadequate treatment. Findings suggestive cyanide toxicity include: (1) a history of an enclosed-space fire scene in which smoke inhalation was likely; (2) the presence of oropharyngeal soot or carbonaceous expectorations; (3) any alteration of the level of consciousness, and particularly, otherwise inexplicable hypotension (systolic blood pressure ≤90 mmHg in adults). Prehospital studies have demonstrated the feasibility and safety of empiric treatment with hydroxocobalamin for patients with suspected smoke inhalation cyanide toxicity. Although United States Food and Drug Administration (FDA)-approved since 2006, the lack of efficacy data has stymied the routine use of this potentially lifesaving antidote. Based on a literature review and on-site observation of the Paris Fire Brigade, emergency management protocols to guide empiric and early hydroxocobalamin administration in smoke inhalation victims with high-risk presentations are proposed.

Field treatment and management of endocrinopathic laminitis in horses and ponies.

Endocrinopathic laminitis in horses and ponies has the potential to cause extensive damage to the feet before clinical signs of laminitis are apparent. Early diagnosis and intervention based on the detection and control of hyperinsulinemia are critical if the crippling changes that are seen in the disease are to be avoided. Preventing endocrinopathic laminitis, rather than treating it, is good practice management benefiting not only equine patients but also their owners.

Laminitis treatment: a personal memoir.

The author has completed 40 years as a veterinarian treating horses with laminitis. The article is a recollection of his experiences with laminitis and the various treatment methods he came across while trying to treat the disease.

Information-sharing in out-of-hospital disaster response: the future role of information technology.

Numerous examples exist of the benefits of the timely access to information in emergencies and disasters. Information technology (IT) is playing an increasingly important role in information-sharing during emergencies and disasters. The effective use of IT in out-of-hospital (OOH) disaster response is accompanied by numerous challenges at the human, applications, communication, and security levels. Most reports of IT applications to emergencies or disasters to date, concern applications that are hospital-based or occur during non-response phases of events (i.e., mitigation, planning and preparedness, or recovery phases). Few reports address the application of IT to OOH disaster response. Wireless peer networks that involve ad hoc wireless routing networks and peer-to-peer application architectures offer a promising solution to the many challenges of information-sharing in OOH disaster response. These networks offer several services that are likely to improve information-sharing in OOH emergency response, including needs and capacity assessment databases, victim tracking, event logging, information retrieval, and overall incident management system support.