Update About the Management of Low-Density Lipoprotein Cholesterol and Hypertriglyceridemia in Lower Extremity Peripheral Artery Disease Patients: Consensus of the French Society of Vascular Medicine and the French Society for Vascular and Endovascular Surgery.

BACKGROUND: A French intersociety consensus on behalf the Société Française de Médecine Vasculaire and the Société de Chirurgie Vasculaire et Endovasculaire was proposed in 2021 for the management of patients with lower extremity peripheral artery disease (LEAD). Recent studies have been published and an update of this consensus about the management of low-density lipoprotein cholesterol (LDLc) and hypertriglyceridemia was required. METHODS: A steering committee of 12 vascular physicians and surgeons defined questions of interest about LDLc and hypertriglyceridemia management. A French expert panel voted the proposals. Consensus was considered to have been achieved if more than 80% of the responses corresponded to either "Agreement" or "Disagreement". RESULTS: Among the 56 experts who were asked to participate, 46 (82%) accepted. After the first round of the Delphi procedure, the 4 proposals reached consensus. The following suggestions and recommendations were approved: 1. For LEAD patients treated by the highest tolerated statin dose ± ezetimibe and who have an LDLc ≥0.70 g/L, we recommend adding a proprotein convertase subtilisin/kexin type 9 inhibitor. 2. For LEAD patients treated by statin and who have elevated triglyceride level between ≥150 mg/dL and ≤500 mg/dL, we suggest adding Icosapent Ethyl. 3. Before adding Icosapent Ethyl in LEAD patients treated with statin, we suggest looking for symptoms that may suggest atrial fibrillation. 4. For LEAD patients treated by Icosapent Ethyl and who have symptoms that suggest atrial fibrillation, we recommend performing an electrocardiogram. CONCLUSIONS: This update will help clinicians to improve LEAD patient management.

Long-term outcome in dogs with cranial cruciate ligament disease evaluated using the canine orthopaedic index.

BACKGROUND: Cranial cruciate ligament disease (CCLD) is common in dogs, but studies on the long-term treatment outcome are scarce. METHODS: The long-term outcome in a cohort of 71 dogs with CCLD treated with tibial plateau levelling osteotomy (TPLO, n = 18), tibial tuberosity advancement (TTA, n = 23) or lateral fabellotibial suture (LFS, n = 30) was evaluated using the canine orthopaedic index. RESULTS: The risk of stiffness and lameness was increased in dogs treated with TPLO (stiffness: incidence rate ratio [IRR] 1.33, p = 0.015; lameness: IRR 1.34, p = 0.020) or TTA (stiffness: IRR 1.26, p = 0.035; lameness: IRR 1.31, p = 0.026) when compared to LFS at a median follow-up time of 4.6 years. LIMITATIONS: No follow-up veterinary examination was performed. Data were collected from only two university animal hospitals, and thus, a referral bias towards more complicated cases is possible, which may limit the generalisability of the results. CONCLUSION: Clinicians can use the results to inform dog owners about the expected long-term outcome in dogs with CCLD.

Degree of osteophyte formation seen on radiographs provides useful prognostic information for dogs with cruciate ligament disease.

BACKGROUND: Concurrent osteoarthritis is generally present in the stifle joints of dogs with cranial cruciate ligament disease (CCLD), but it is not known if the degree of osteoarthritis-related changes affects the prognosis. Development of osteophytes is a key radiographic feature of osteoarthritis. The aim of this study was to evaluate the association between the degree of osteophyte formation seen on radiographs and CCLD-related euthanasia in dogs with CCLD. METHODS: A retrospective cohort study including 226 dogs treated for CCLD at two university animal hospitals was performed. Clinical and follow-up information was retrieved, and stifle radiographs taken during the 31 days before treatment for the CCLD were graded for osteophyte formation by three veterinary radiologists. A multivariable Cox proportional hazards model was applied to assess the association between the degree of osteophyte formation and CCLD-related euthanasia. RESULTS: An association between the degree of osteophyte formation and CCLD-related euthanasia was found, with increased osteophyte formation associated with an increased hazard of CCLD-related euthanasia (hazard ratio 1.06, 95% confidence interval 1.01-1.11, p = 0.01). LIMITATIONS: No clinical assessment of the outcome was performed. CONCLUSION: The findings suggest that evaluation of stifle radiographs for osteophyte formation could provide useful prognostic information for dogs with CCLD.

Perinatal exposure to a human relevant mixture of persistent organic pollutants: Effects on mammary gland development, ovarian folliculogenesis and liver in CD-1 mice.

The ability of persistent organic pollutants (POPs) with endocrine disrupting properties to interfere with the developing reproductive system is of increasing concern. POPs are transferred from dams to offspring and the high sensitivity of neonates to endocrine disturbances may be caused by underdeveloped systems of metabolism and excretion. The present study aimed to characterize the effect of in utero and lactational exposure to a human relevant mixture of POPs on the female mammary gland, ovarian folliculogenesis and liver function in CD-1 offspring mice. Dams were exposed to the mixture through the diet at Control, Low or High doses (representing 0x, 5000x and 100 000x human estimated daily intake levels, respectively) from weaning and throughout mating, gestation, and lactation. Perinatally exposed female offspring exhibited altered mammary gland development and a suppressed ovarian follicle maturation. Increased hepatic cytochrome P450 enzymatic activities indirectly indicated activation of nuclear receptors and potential generation of reactive products. Hepatocellular hypertrophy was observed from weaning until 30 weeks of age and could potentially lead to hepatotoxicity. Further studies should investigate the effects of human relevant mixtures of POPs on several hormones combined with female reproductive ability and liver function.

Risk factors for severe postoperative complications in dogs with cranial cruciate ligament disease - A survival analysis.

OBJECTIVE: To analyze the effect of surgical technique and other risk factors on severe postoperative complications in dogs with cranial cruciate ligament disease (CCLD). MATERIALS AND METHODS: A cohort study of 255 dogs (287 stifles) surgically treated for CCLD at two veterinary university hospitals (2011-2016) was performed. The electronic medical records were reviewed and dog owners and referring veterinarians contacted for additional information. The complications were classified as minor, major and catastrophic, where major and catastrophic were considered severe. A multivariable Cox proportional hazards model was applied to assess risk factors for severe postoperative complications. RESULTS: Three surgical techniques were used; lateral fabellotibial suture (LFS, 141 stifles), tibial plateau leveling osteotomy (TPLO, 77 stifles) and tibial tuberosity advancement (TTA, 69 stifles). The most common severe postoperative complications were surgical site infections or complications related to the surgical implant. Severe postoperative complications occurred in 31 % of the stifles treated with TPLO, 22 % of the stifles treated with LFS and 25 % of the stifles treated with TTA. The multivariable Cox proportional hazards model identified surgical technique (p = 0.0258) as a risk factor for severe postoperative complications; TPLO had a significantly lower hazard than LFS (hazard ratio (HR) = 0.37, p = 0.007) when controlling for body weight and age, which also were identified as risk factors (HR = 1.05, p < 0.001 and HR = 0.91, p = 0.047, respectively). CONCLUSION AND CLINICAL RELEVANCE: Although TPLO procedures had the highest occurrence of severe postoperative complications, the hazard was lower than for LFS after adjusting for body weight and age. This implies that it is important to consider potential effect-modifiers when comparing postoperative complications after CCLD surgery.

Disparities Between International Guidelines (AHA/ESC/ESVS/ESVM/SVS) Concerning Lower Extremity Arterial Disease: Consensus of the French Society of Vascular Medicine (SFMV) and the French Society for Vascular and Endovascular Surgery (SCVE).

Several international guidelines concerning lower extremity arterial disease (LEAD) have been published recently, in particular, by the American Heart Association the European Society of Cardiology/European Society for Vascular Surgery, the European Society for Vascular Medicine and the Society for Vascular Surgery. These guidelines differ in some respects and certain issues are not addressed. The objective of this consensus driven by the French Societies of vascular Medicine and surgery was to analyze the disparities between the different guidelines, as well as certain issues not covered, and develop proposals with regard to these points. The following fields of LEAD have been explored: 1) classifications, 2) clinical evaluation, 3) diagnostic criteria, 4) quantification of arterial stenosis using duplex ultrasound, 5) detection of asymptomatic multisite lesions, 6) screening for LEAD in the context of cardiac disease, 7) medical treatment, 8) supervised exercise therapy, 9) revascularization and revascularization of the internal artery stenosis, 10) management of chronic limb ischemia, 11) longitudinal follow-up, and 12) diet.

Prednisolone-induced diabetes mellitus in the cat: a historical cohort.

OBJECTIVES: Prednisolone is a commonly used drug in cats and potential adverse effects include hyperglycaemia and diabetes mellitus. The aims of this study were to evaluate the frequency and investigate potential predisposing risk factors for the development of prednisolone-induced diabetes mellitus (PIDM) in cats. METHODS: The electronic records of a tertiary referral centre were searched for cats receiving prednisolone at a starting dose of ⩾1.9 mg/kg/day, for >3 weeks and with follow-up data available for >3 months between January 2007 and July 2019. One hundred and forty-three cats were included in the study. RESULTS: Of the 143 cats, 14 cats (9.7%) were diagnosed with PIDM. Twelve out of 14 cats (85.7%) developed diabetes within 3 months of the initiation of therapy. CONCLUSIONS AND RELEVANCE: Cats requiring high-dose prednisolone therapy should be closely monitored over the first 3 months of therapy for the development of PIDM.

Effects of a human-based mixture of persistent organic pollutants on the in vivo exposed cerebellum and cerebellar neuronal cultures exposed in vitro.

Exposure to persistent organic pollutants (POPs), encompassing chlorinated (Cl), brominated (Br) and perfluoroalkyl acid (PFAA) compounds is associated with adverse neurobehaviour in humans and animals, and is observed to cause adverse effects in nerve cell cultures. Most studies focus on single POPs, whereas studies on effects of complex mixtures are limited. We examined the effects of a mixture of 29 persistent compounds (Cl + Br + PFAA, named Total mixture), as well as 6 sub-mixtures on in vitro exposed rat cerebellar granule neurons (CGNs). Protein expression studies of cerebella from in vivo exposed mice offspring were also conducted. The selection of chemicals for the POP mixture was based on compounds being prominent in food, breast milk or blood from the Scandinavian human population. The Total mixture and sub-mixtures containing PFAAs caused greater toxicity in rat CGNs than the single or combined Cl/Br sub-mixtures, with significant impact on viability from 500x human blood levels. The potencies for these mixtures based on LC50 values were Br + PFAA mixture > Total mixture > Cl + PFAA mixture > PFAA mixture. These mixtures also accelerated induced lipid peroxidation. Protection by the competitive N-methyl-D-aspartate (NMDA) receptor antagonist 3-((R)-2-Carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) indicated involvement of the NMDA receptor in PFAA and Total mixture-, but not Cl mixture-induced toxicity. Gene-expression studies in rat CGNs using a sub-toxic and marginally toxic concentration ((0.4 nM-5.5 µM) 333x and (1 nM-8.2 µM) 500x human blood levels) of the mixtures, revealed differential expression of genes involved in apoptosis, oxidative stress, neurotransmission and cerebellar development, with more genes affected at the marginally toxic concentration. The two important neurodevelopmental markers Pax6 and Grin2b were downregulated at 500x human blood levels, accompanied by decreases in PAX6 and GluN2B protein levels, in cerebellum of offspring mice from mothers exposed to the Total mixture throughout pregnancy and lactation. In rat CGNs, the glutathione peroxidase gene Prdx6 and the regulatory transmembrane glycoprotein gene Sirpa were highly upregulated at both concentrations. In conclusion, our results support that early-life exposure to mixtures of POPs can cause adverse neurodevelopmental effects.

Subjects with venous insufficiency have high risk of obstructive sleep apnea in relationship to fluid shift.

BACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent in conditions characterized by fluid overload. Chronic venous insufficiency (CVI) is associated to fluid overload that might interfere with OSA occurrence and severity. METHODS: A total of 180 patients with symptomatic CVI completed the Berlin questionnaire and were assessed for the presence of symptoms and signs of OSA and fluid shift. RESULTS: According to the Berlin questionnaire, 59 patients (33%) had high risk of OSA. The predictors of having a positive Berlin questionnaire were male sex, body mass index and symptoms possibly related to fluid shift. CONCLUSIONS: Patients with CVI, a disease characterized by fluid overload, present high risk of OSA, which might be related to fluid shift.

Disease-related and overall survival in dogs with cranial cruciate ligament disease, a historical cohort study.

OBJECTIVE: To analyse the effect of treatment method and other risk factors on survival in dogs with cranial cruciate ligament disease (CCLD). METHODS: A historical cohort study of 333 dogs presenting with CCLD at two University Hospitals (2011-2016) was performed. Signalment, history, treatment and follow-up details were retrieved from medical records, dog owners and referring veterinarians. Treatment groups were defined; conservative or surgical with either lateral fabellotibial suture (LFS) or osteotomy procedures. Multivariable Cox proportional hazards models were applied to evaluate risk factors for disease-related and overall survival. RESULTS: Sixty-five dogs were conservatively managed, 125 treated with LFS and 143 with osteotomy techniques. At follow-up (autumn 2018), 164 dogs (49.3 %) were alive and 169 (50.7 %) were dead. Both final Cox proportional hazards models included variables for treatment, age, weight and hospital. In addition, the final disease-related model included a variable for orthopaedic comorbidity, while non-orthopaedic comorbidities and a time-varying effect for age on a linear scale were included in the overall survival model. Treatment method was found to have an effect on both disease-related and overall survival and surgical treatment was associated with a lower hazard than conservative treatment. CONCLUSION: Survival in dogs with CCLD is influenced by treatment strategy, comorbidities, age and weight.

Correction to: Breed susceptibility for common surgically treated orthopaedic diseases in 12 dog breeds.

After publication of our article [1] we were notified that due to an error in the excel formula used to summarise the control population, the ID-registry data from the Swedish county Gävleborg was not included in the calculations. When including Gävleborg, as intended, the numbers in the adjusted Swedish control population change slightly. It does not influence the Norwegian control population.

Cranial cruciate ligament disease in cats: an epidemiological retrospective study of 50 cats (2011-2016).

OBJECTIVES: The aim of this study was to describe the characteristics and long-term outcome of surgically and conservatively treated cats with cranial cruciate ligament disease (CCLD). METHODS: A retrospective cohort study of cats with CCLD, diagnosed at two university animal hospitals between January 2011 and December 2016, was performed. Signalment, history, treatment and follow-up information were retrieved. Cat owners were contacted for additional long-term follow-up information. The cases were divided into two groups: one conservatively managed and one surgically treated with the lateral fabellotibial suture technique. A quality of life questionnaire, the Feline Musculoskeletal Pain Index (FMPI), was distributed to the owners of cats alive at follow-up for assessment of chronic pain as a long-term outcome. Univariable statistical methods were used to evaluate the data. RESULTS: Fifty cats were identified and were followed for a median of 41 months after diagnosis of CCLD. Seven cats (14%) developed bilateral CCLD. Twenty-eight cats (56%) were treated conservatively and 22 (44%) surgically. All surgically treated cats in which arthrotomy was performed (19/22) had total cranial cruciate ligament rupture and 9/19 (47%) had meniscal injuries. Postoperative surgical complications were recorded in 6/22 cats (27%). Owners of 24/29 (83%) cats still alive at follow-up completed the FMPI questionnaire. The conservatively treated cats had a lower FMPI score, indicating less chronic pain, than those cats treated surgically (P = 0.017). CONCLUSIONS AND RELEVANCE: Conservatively treated cats with CCLD experienced less chronic pain at long-term follow-up than surgically treated cats. Bilateral disease is not uncommon in cats with CCLD.

Breed susceptibility for common surgically treated orthopaedic diseases in 12 dog breeds.

BACKGROUND: A retrospective case-control study was conducted to estimate breed predisposition for common orthopaedic conditions in 12 popular dog breeds in Norway and Sweden. Orthopaedic conditions investigated were elbow dysplasia (ED); cranial cruciate ligament disease (CCLD); medial patellar luxation (MPL); and fractures of the radius and ulna. Dogs surgically treated for the conditions above at the Swedish and Norwegian University Animal Hospitals between the years 2011 and 2015 were compared with a geographically adjusted control group calculated from the national ID-registries. Logistic regression analyses (stratified for clinic and combined) were used to calculate odds ratios (OR) and 95% confidence intervals. Mixed breed dogs were used as reference. RESULTS: Breeds found at-risk for ED were the Labrador retriever (OR = 5.73), the Rottweiler (OR = 5.63), the German shepherd dog (OR = 3.31) and the Staffordshire bull terrier (OR = 3.08). The Chihuahua was the only breed where an increased risk for MPL (OR = 2.80) was identified. While the Rottweiler was the only breed predisposed for CCLD (OR = 3.96), the results were conflicting for the Labrador retriever (OR = 0.44 in Sweden, 2.85 in Norway); the overall risk was identical to mixed-breed dogs. CONCLUSIONS: Most results are in concordance with earlier studies. However, an increased risk of CCLD was not identified for the Labrador retriever, the Staffordshire bull terrier was found to have an increased risk of ED and some country-specific differences were noted. These results highlight the importance of utilising large caseloads and appropriate control groups when breed susceptibility is reported.

Reintervention after thoracic endovascular aortic repair of complicated aortic dissection.

OBJECTIVE: This study assessed predictive factors for reintervention after thoracic endovascular aortic repair (TEVAR) for complicated aortic dissection (C-AD). METHODS: An institutional review of consecutive TEVAR for C-AD was performed. RESULTS: Between 2000 and 2011, 41 patients underwent TEVAR for a C-AD involving the descending thoracic aorta. Primary indications included aneurysm >55 mm in 24, rapid aneurysmal enlargement or impending rupture in 6, saccular aneurysm >20 mm in 1, malperfusion in 1, intractable chest pain in 3, and rupture in 6. Technical success was achieved in 100%. The 30-day mortality rate was 5% (n = 2). Fourteen secondary procedures were performed in 13 patients (32%) for indications of device migration in 2, proximal type I endoleak in 5, distal type I endoleak in 2, type II endoleak in 1, aneurysmal evolution of the descending thoracic aorta in 2, aneurysmal expansion of the dissected abdominal aorta in 1, and retrograde dissection in 1. Multivariate analysis demonstrated that oversizing ≥20% (odds ratio [OR], 16; P = .011), bare-spring stent in the proximal landing zone of the stent graft (OR, 12; P = .032), and anticoagulant therapy (OR, 78; P = .03) were significant factors for reintervention. On univariate analysis, large aneurysm was a risk factor for reintervention (P = .002), whereas complete false lumen thrombosis at the stent graft level was protective (P < .05). CONCLUSIONS: This study confirms the feasibility of TEVAR for C-AD, although the rate of reintervention is high. Excessive oversizing, a bare-spring stent graft in the proximal landing zone, large aortic dilatation, and anticoagulant therapy were factors associated with reintervention. Complete false lumen thrombosis at the stent graft level was protective.

Comparative study on risk factors and early outcome of symptomatic distal versus proximal deep vein thrombosis: results from the OPTIMEV study.

There is a lack of consensus on the value of detecting and treating symptomatic isolated distal deep-vein thrombosis (DVT) of the lower limbs. In our study, we compared the risk factors and outcomes in patients with isolated symptomatic distal DVT with those with proximal symptomatic DVT. We analysed the data of patients with objectively confirmed symptomatic isolated DVT enrolled in the national (France), multicenter, prospective OPTIMEV study. This sub-study outcomes were recurrent venous thromboembolism, major bleeding and death at three months. Among the 6141 patients with suspicion of isolated DVT included between November 2004 and January 2006, DVT was confirmed in 1643 patients (26.8%). Isolated distal DVT was more frequent than proximal DVT (56.8% vs. 43.2%, respectively; p = 0.01). Isolated distal DVT was significantly more often associated with transient risk factors (recent surgery, recent plaster immobilisation, recent travel), whereas proximal DVT was significantly more associated with more chronic states (active cancer, congestive heart failure or respiratory insufficiency, age >75 years). Most patients (96.8%) with isolated distal DVT received anticoagulant therapies. There was no difference in the percentage of recurrent venous thromboembolism and major bleeding in patients with proximal DVT and isolated distal DVT. However, the mortality rate was significantly higher (p < 0.01) in patients with proximal DVT (8.0%) than in those with isolated distal DVT (4.4%). Symptomatic isolated distal DVT differs from symptomatic proximal DVT both in terms of risk factors and clinical outcome. Whether these differences should influence the clinical management of these two events remains to be determined.

Brief report: graduated compression stocking thromboprophylaxis for elderly inpatients: a propensity analysis.

BACKGROUND: Graduated compression stockings (GCS) are often used for deep vein thrombosis prophylaxis in nonsurgical patients, although evidence on their effectiveness is lacking in this setting. OBJECTIVE: To determine whether prophylaxis with GCS is associated with a decrease in the rate of deep vein thrombosis in nonsurgical elderly patients. METHODS: Using original data from 2 multicenter nonrandomized studies, we performed multivariable and propensity score analyses to determine whether prophylaxis with GCS reduced the rate of deep vein thrombosis among 1,310 postacute care patients 65 years or older. The primary outcome was proximal deep vein thrombosis detected by routine compression ultrasonography performed by registered vascular physicians. RESULTS: Proximal deep vein thrombosis was found in 5.7% (21/371) of the GCS users and in 5.2% (49/939) of the GCS nonusers (odds ratio [OR], 1.09; 95% confidence interval [CI], 0.64-1.84). Although adjusting for propensity score eliminated all differences in baseline characteristics between users and nonusers, the OR for proximal deep vein thrombosis associated with GCS remained nonsignificant in propensity-stratified (adjusted OR, 1.11; 95% CI, 0.59-2.10) and propensity-matched (conditional OR, 0.92; 95% CI, 0.42-2.02) analysis. Similar figures were observed for distal and any deep vein thrombosis. The rates of deep vein thrombosis did not differ according to the length of stockings. CONCLUSIONS: Prophylaxis with GCS is not associated with a lower rate of deep vein thrombosis in nonsurgical elderly patients in routine practice. Randomized studies are needed to assess the efficacy of GCS when properly used in this setting.