Antibody levels following vaccination of beef calves with a tetanus toxoid.

Tetanus is a preventable, yet often fatal, disease affecting many species, including beef cattle. Vaccination for tetanus is recommended for calves at high risk of disease, but typical beef cattle management practices often make adherence to vaccine manufacturers' guidance for a second (booster) dose of vaccine difficult. This study examined the antibody response following a single dose of tetanus toxoid, as well as following booster vaccination at various intervals. Anti-tetanus IgG antibodies were detectable 25 days (D25) after a single dose, and rose following booster at either D25 D109 after initial vaccination. Antibody levels then declined numerically from D109 to D179 for calves boostered at D25 but rose on D179 for those receiving a second dose on D109. The relatively rapid response in IgG production, even in the absence of a booster vaccine, may suggest value in vaccinating calves for tetanus at time of greatest risk, even if a booster cannot be administered. The study also provides support for priming of the immune response lasting at least until D109 after primary immunization.

Analysis of adverse events with lumen apposing metal stents for drainage of pancreatic fluid collections.

Background and study aims Innovations in endoscopic management of pancreatic fluid collections (PFCs) using lumen apposing metal stents (LAMS) have rendered it a preferred approach for drainage of PFCs. These advances have not come without concern for adverse events (AEs). We present our experience with LAMS for drainage of PFCs and analyze factors that contribute to LAMS-related AEs. Patients and methods From November 2015 to October 2021, a retrospective analysis was performed of patients undergoing endoscopic management of PFCs using LAMS. All AEs were classified as either early (<48 hours) or late (>48 hours). Univariate and multivariate analysis were performed using logistic regression to assess the relationship between independent variables and AEs. Results A total of 119 patients with symptomatic PFCs underwent endoscopic drainage with LAMS. There were 16 AEs (12.4%). These included systemic inflammatory response syndrome (SIRS) (n=2), stent occlusion (n=5), bleeding (n=7), and stent migration (n=2). Univariate analysis of risk of AEs showed that no variables approached statistical significance. Of the seven patients who developed bleeding, five had pseudoaneurysms following LAMS placement and underwent angioembolization by an interventional radiologist. The average time to bleeding was 9.3 days (standard deviation 7.3) with all bleeding events occurring within 3 weeks. In a multivariate model, pseudocysts and presence of paracolic gutter extension were associated with an increased risk of bleeding. Conclusions Endoscopists should be aware of the risk factors for LAMS-related bleeding and tailor their drainage strategy, including utilization of plastic stents for drainage of pseudocysts and adherence to a strict imaging interval and follow-up protocol.

Immune Responses to Influenza D Virus in Calves Previously Infected with Bovine Viral Diarrhea Virus 2.

Bovine viral diarrhea virus (BVDV) induces immunosuppression and thymus depletion in calves. This study explores the impact of prior BVDV-2 exposure on the subsequent immune response to influenza D virus (IDV). Twenty 3-week-old calves were divided into four groups. Calves in G1 and G3 were mock-treated on day 0, while calves in G2 and G4 received BVDV. Calves in G1 (mock) and G2 (BVDV) were necropsied on day 13 post-infection. IDV was inoculated on day 21 in G3 calves (mock + IDV) and G4 (BVDV + IDV) and necropsy was conducted on day 42. Pre-exposed BVDV calves exhibited prolonged and increased IDV shedding in nasal secretions. An approximate 50% reduction in the thymus was observed in acutely infected BVDV calves (G2) compared to controls (G1). On day 42, thymus depletion was observed in two calves in G4, while three had normal weight. BVDV-2-exposed calves had impaired CD8 T cell proliferation after IDV recall stimulation, and the α/ß T cell impairment was particularly evident in those with persistent thymic atrophy. Conversely, no difference in antibody levels against IDV was noted. BVDV-induced thymus depletion varied from transient to persistent. Persistent thymus atrophy was correlated with weaker T cell proliferation, suggesting correlation between persistent thymus atrophy and impaired T cell immune response to subsequent infections.

Oral and IV Varespladib Rescue Experiments in Juvenile Pigs with Weakness Induced by Australian and Papuan Oxyuranus scutellatus Venoms.

Antivenom is currently the standard-of-care treatment for snakebite envenoming, but its efficacy is limited by treatment delays, availability, and in many cases, species specificity. Many of the rapidly lethal effects of envenoming are caused by venom-derived toxins, such as phospholipase A2 (sPLA2); therefore, small molecule direct toxin inhibitors targeting these toxins may have utility as initial and adjunct therapies after envenoming. Varespladib (intravenous, IV) and varespladib-methyl (oral) have been shown to potently inhibit sPLA2s from snake venoms in murine and porcine models, thus supporting their further study as potential treatments for snakebite envenoming. In this pilot study, we tested the ability of these compounds to reverse neurotoxic effects of venom from the Australian and Papuan taipan (Oxyuranus scutellatus) subspecies in juvenile pigs (Sus domesticus). The mean survival time for control animals receiving Australian taipan venom (0.03 mg/kg, n = 3) was 331 min ± 15 min; for those receiving Papuan taipan venom (0.15 mg/kg, n = 3) it was 178 ± 31 min. Thirteen pigs received Australian taipan venom and treatment with either IV or oral varespladib (or with IV to oral transition) and all 13 survived the duration of the study (≥96 h). Eight pigs received Papuan taipan venom followed by treatment: Briefly: Two animals received antivenom immediately and survived to the end of the study. Two animals received antivenom treatment delayed 45 min from envenoming and died within 4 h. Two animals received similarly delayed antivenom treatment and were rescued by varespladib. Two animals were treated with varespladib alone after a 45-min delay. Treatment with varespladib only was effective but required repeat dosing over the course of the study. Findings highlight both the importance of early treatment and, as well, a half-life for the investigational inhibitors now in Phase II clinical trials for snakebite. Varespladib rapidly reversed weakness even when administered many hours post-envenoming and, overall, our results suggest that varespladib and varespladib-methyl could be efficacious tools in the treatment of sPLA2-induced weakness from Oxyuranus envenoming. Further clinical study as initial therapy and as potential method of rescue from some types of antivenom-resistant envenomings are supported by these data.

Test-retest reliability and construct validity of trunk extensor muscle force modulation accuracy.

Low back pain is associated with changes in trunk muscle structure and function and motor control impairments. Voluntary force modulation (FM) of trunk muscles is a unique and under-investigated motor control characteristic. One of the reasons for this paucity of evidence is the lack of exploration and publication on the reliability and validity of trunk FM protocols. The purpose of this study was to determine the within- and between-day test-retest reliability and construct validity for trunk extensor muscle FM. Twenty-nine healthy participants were tested under three FM conditions with different modulation rates. Testing was performed on a custom-built apparatus designed for trunk isometric force testing. FM accuracy relative to a fluctuating target force (20-50%MVF) was quantified using the root mean square error of the participant's generated force relative to the target force. Reliability and precision of measurement were assessed using the Intraclass Correlation Coefficient (ICC), standard error of measurement (SEM), minimal detectable difference (MDD95), and Bland-Altman plots. In a subset of participants, we collected surface electromyography of trunk and hip muscles. We used non-negative matrix factorization (NNMF) to identify the underlying motor control strategies. Within- and between-day test-retest reliability was excellent for FM accuracy across the three conditions (ICC range: 0.865 to 0.979). SEM values ranged 0.9-1.8 Newtons(N) and MDD95 ranged from 2.4-4.9N. Conditions with faster rates of FM had higher ICCs. NNMF analysis revealed two muscle synergies that were consistent across participants and conditions. These synergies demonstrate that the muscles primarily involved in this FM task were indeed the trunk extensor muscles. This protocol can consistently measure FM accuracy within and between testing sessions. Trunk extensor FM, as measured by this protocol, is not specific to any trunk muscle group but is the result of modulation by all the trunk extensor muscles.

Mind-Body Exercise Performed by Physical Therapists for Reducing Pain and Disability in Low Back Pain: A Systematic Review With Meta-analysis.

OBJECTIVE: To assess the effectiveness of mind-body (MB) exercise interventions provided by physical therapists for reducing pain and disability in people with low back pain (LBP). DATA SOURCES: MEDLINE, Embase, CINAHL, and the Cochrane Library were searched for articles published in English between December 2010 and June 2020. STUDY SELECTION: Randomized controlled trials evaluating the effects of Pilates, yoga, and tai chi interventions performed by physical therapists on pain or disability outcomes in adults with musculoskeletal LBP were included. DATA EXTRACTION: Data were extracted by 2 independent reviewers. Quality of evidence and risk of bias were assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework and Cochrane risk of bias tools, respectively. DATA SYNTHESIS: 21,230 exercise trials were identified; 161 progressed to full-text review. Eight trials, 7 reporting on Pilates and 1 reporting on yoga, were included. Short-term outcomes for pain (SMD: -0.93; 95% confidence interval [CI]: -1.65 to -0.021) and disability (SMD: -0.74 95% CI: -1.36 to -0.012) indicated MB exercise was more effective than control intervention. Tests for subgroup differences between studies with exercise vs non-exercise control groups revealed a moderating effect on short-term outcomes where larger effects were observed in studies with non-exercise comparators. Long-term outcomes for pain (SMD: -0.60; 95% CI:-1.43 to 0.23) and disability (SMD: -1.05; 95% CI:-3.51 to 1.41) suggested that MB exercise is not more effective than control interventions for pain or disability. Quality of the evidence ranged from very low to low. CONCLUSIONS: Physical therapist-delivered MB exercise interventions, which overwhelmingly consisted of Pilates, were more effective than control in the short and long-term for pain and in the short-term for disability, with differences in the short-term effects lessened when compared with an active intervention. Pilates interventions delivered by physical therapists represent a viable tool for the clinical management of chronic LBP.

Delayed endoscopic necrosectomy improves hospital length of stay and reduces endoscopic interventions in patients with symptomatic walled-off necrosis.

Objectives: Advancements in the endoscopic management of walled-off necrosis using lumen apposing metal stents have improved outcomes over its surgical and percutaneous alternatives. The ideal procedural technique and timing of direct endoscopic necrosectomy (DEN) have yet to be clarified. Methods: From November 2015 to June 2021, a retrospective comparative cohort analysis was performed comparing clinical outcomes for patients undergoing immediate DEN (iDEN) versus delayed DEN (dDEN). Subgroups were identified based on the quantification of necrosis. Wilcoxon two-sample tests were used to compare continuous variables and Fisher's exact test was used to compare categorical variables. Results: A total of 80 patients underwent DEN for management of walled-off necrosis (iDEN = 43, dDEN = 37). Technical success was achieved in all patients. Clinical success was seen in 39 (91%) patients in the iDEN group and 34 (92%) in the dDEN group. Amongst iDEN patients, the mean number of necrosectomies was 2.5 (standard deviation [SD] 1.4) in comparison to 1.5 (SD 1.0) for dDEN (p-value = 0.0011). The median index hospital length of stay was longer with iDEN than dDEN (7.5 days vs. 3.0 days respectively, p-value = 0.010). Subgroup analysis was performed based on the percentage of necrosis (<25% vs. >25% necrosis). iDEN was associated with more necrosectomies than dDEN regardless of the percentage of necrosis (p = 0.017 and 0.0067, respectively). Conclusion: Patients undergoing dDEN had a shorter index hospital stay and fewer necrosectomies than iDEN. The large diameter of lumen apposing metal stents permits adequate drainage allowing a less aggressive approach thereby improving clinical outcomes and avoiding unnecessary interventions.

Long-term transmural drainage of pancreatic fluid collections with double pigtail stents following lumen-apposing metal stent placement improves recurrence-free survival in disconnected pancreatic duct syndrome.

OBJECTIVES: Disconnected pancreatic duct syndrome (DPDS) is the most common cause of pancreatic fluid collection (PFC) recurrence. While long-term transmural drainage with plastic stents is the preferred endoscopic approach, there is a paucity of literature on patients undergoing initial drainage with lumen-apposing metal stents (LAMS). We describe our experience managing patients with DPDS. METHODS: A retrospective review of a prospectively maintained database (November 2015-September 2020) was performed looking at clinical outcomes and overall survival for patients undergoing endoscopic management of PFCs using LAMS. The primary outcome was to assess recurrence-free survival in PFC patients with DPDS managed with or without double pigtail stents (DPS) replacement after LAMS removal. RESULTS: Of 96 patients with PFCs, 48 with DPDS were included in the study. The median follow-up was 20.1 months. LAMS replacement with DPS was successful in 21/48 (43.8%) patients. Recurrence was seen in 1/21 (5%) patients with DPS replacement and 10/27 (37%) without DPS replacement. In multivariable models, a longer duration of LAMS placement was negatively associated with successful DPS replacement (odds ratio 1.33, 95% confidence interval [CI] 1.11, 1.59, P = 0.0019) and successful LAMS replacement with DPS in patients with DPDS improved recurrence-free survival (hazard ratio 0.09, 95% CI 0.01, 0.83, P = 0.033). CONCLUSION: In patients with PFCs and DPDS, early replacement of LAMS with DPS improves the likelihood of successful long-term transmural drainage and decreases recurrences.

Interventions for the Management of Acute and Chronic Low Back Pain: Revision 2021.

Low back pain (LBP) remains a musculoskeletal condition with an adverse societal impact. Globally, LBP is highly prevalent and a leading cause of disability. This is an update to the 2012 Academy of Orthopaedic Physical Therapy (AOPT), formerly the Orthopaedic Section of the American Physical Therapy Association (APTA), clinical practice guideline (CPG) for LBP. The overall objective of this update was to provide recommendations on interventions delivered by physical therapists or studied in care settings that included physical therapy providers. It also focused on synthesizing new evidence, with the purpose of making recommendations for specific nonpharmacologic treatments. J Orthop Sports Phys Ther 2021;51(11):CPG1-CPG60. doi:10.2519/jospt.2021.0304.

EUS-guided hepaticogastrostomy for management of cholangitis, hepatolithiasis, and anastomotic stricture after Roux-en-Y hepaticojejunostomy.

Video 1EUS-guided hepaticogastrostomy for management of cholangitis, hepatolithiasis, and anastomotic stricture after Roux-en-Y hepaticojejunostomy.

BioSphincters to treat Fecal Incontinence in Nonhuman Primates.

Loss of anorectal resting pressure due to internal anal sphincter (IAS) dysfunctionality causes uncontrolled fecal soiling and leads to passive fecal incontinence (FI). The study is focused on immediate and long-term safety and potential efficacy of bioengineered IAS BioSphincters to treat passive FI in a clinically relevant large animal model of passive FI. Passive FI was successfully developed in Non-Human Primates (NHPs) model. The implantation of autologous intrinsically innervated functional constructs resolved the fecal soiling, restored the resting pressure and Recto Anal Inhibitory Reflex (RAIR) within 1-month. These results were sustained with time, and efficacy was preserved up to 12-months. The histological studies validated manometric results with the regeneration of a well-organized neuro-muscular population in IAS. The control groups (non-treated and sham) remained affected by poor anal hygiene, lower resting pressure, and reduced RAIR throughout the study. The pathological assessment of implants, blood, and the vital organs confirmed biocompatibility without any adverse effect after implantation. This regenerative approach of implanting intrinsically innervated IAS BioSphincters has the potential to offer a better quality of life to the patients suffering from FI.

Delayed LY333013 (Oral) and LY315920 (Intravenous) Reverse Severe Neurotoxicity and Rescue Juvenile Pigs from Lethal Doses of Micrurus fulvius (Eastern Coral Snake) Venom.

OBJECTIVE: There is a clear, unmet need for effective, lightweight, shelf-stable and economical snakebite envenoming therapies that can be given rapidly after the time of a snake's bite and as adjuncts to antivenom therapies in the hospital setting. The sPLA2 inhibitor, LY315920, and its orally bioavailable prodrug, LY333013, demonstrate surprising efficacy and have the characteristics of an antidote with potential for both field and hospital use. METHODS: The efficacy of the active pharmaceutical ingredient (LY315920) and its prodrug (LY333013) to treat experimental, lethal envenoming by Micrurus fulvius (Eastern coral snake) venom was tested using a porcine model. Inhibitors were administered by either intravenous or oral routes at different time intervals after venom injection. In some experiments, antivenom was also administered alone or in conjunction with LY333013. RESULTS: 14 of 14 animals (100%) receiving either LY315920 (intravenous) and/or LY333013 (oral) survived to the 120 h endpoint despite, in some protocols, the presence of severe neurotoxic signs. The study drugs demonstrated the ability to treat, rescue, and re-rescue animals with advanced manifestations of envenoming. CONCLUSIONS: Low molecular mass sPLA2 inhibitors were highly effective in preventing lethality following experimental envenoming by M. fulvius. These findings suggest the plausibility of a new therapeutic approach to snakebite envenoming, in this example, for the treatment of a coral snake species for which there are limitations in the availability of effective antivenom.

Congenital amelanotic melanoma in a crossbred heifer calf.

A large, pedunculated cutaneous mass protruding from the left flank fold and an enlarged left prefemoral lymph node were found on examination of a 3-d-old crossbred Aberdeen Angus heifer. The calf was asymptomatic aside from peripheral lymphadenopathy, and the mass, along with the left prefemoral lymph node, was surgically excised. Histologic examination of the mass and the lymph node revealed a homogeneous population of neoplastic cells that stained positively with immunohistochemical stains S100 and melan A, supporting a diagnosis of congenital amelanotic melanoma with nodal metastasis. Two months later, the calf became acutely recumbent and was euthanized after clinical examination revealed widespread metastasis. Gross autopsy revealed widely disseminated metastases that involved vertebral bodies, spinal cord, heart, kidneys, lungs, oral mucosa, multiple lymph nodes, and the marrow cavity of several long bones. Our case serves as a reminder that, although rare, congenital neoplasms occur in bovids and have the potential for aggressive, metastatic behavior.

Brainstem and Cranial Nerve Disorders of Ruminants.

Asymmetrical signs of brainstem disease occur relatively infrequently in ruminants. The most common differential diagnoses include listeriosis, otitis media/interna, and pituitary abscess syndrome. Although these conditions produce signs of brainstem dysfunction, the diseases can usually be differentiated based on historical findings and subtle clinical differences. Basic laboratory diagnostic tests are often not specific in the definitive diagnosis but may be supportive. Advanced imaging techniques have proven to be useful in the diagnosis of otitis media/interna. Presumptive clinical diagnosis is confirmed at necropsy. Treatment involves a prolonged course of antibiotic therapy but is unrewarding in cases of pituitary abscess syndrome.

Validation of a portable pneumatic captive bolt device as a one-step method of euthanasia for use in depopulation of feedlot cattle.

OBJECTIVE: To validate the effectiveness of a penetrating captive bolt device with a built-in low-pressure air channel pithing mechanism (PCBD) as a 1-step method for euthanasia of cattle. DESIGN: Clinical trial. ANIMALS: 66 feedlot steers and heifers (weight, 227 to 500 kg [500 to 1,100 lb]) that were not expected to survive or finish the feeding period with their cohorts. PROCEDURES: Cattle were transported to a university facility and euthanized with the PCBD. For each calf, clinical variables were monitored and recorded immediately before and for at least 10 minutes after application of the PCBD. Following euthanasia, the head of each calf was removed and trauma to the brain and skull was assessed and scored. RESULTS: Death was successfully achieved with the PCBD without application of an ancillary technique in all 66 cattle; however, 4 (6%) cattle required a second or third shot from the PCBD because of technical errors in its placement. All shots from the PCBD that entered the cranial vault successfully rendered cattle unconscious without a return to sensibility. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the PCBD was an effective 1-step method of euthanasia for use in mass depopulation of feedlot cattle.

Identifying patients most likely to have a common bile duct stone after a positive intraoperative cholangiogram.

The false-positive rates of a positive intraoperative cholangiogram (IOC) are as high as 60%. Endoscopic retrograde cholangiopancreatography (ERCP) for stone removal is required after a positive IOC. It is unclear which clinical factors identify patients most likely to have a stone after a positive IOC. This study was conducted to identify factors predictive of common bile duct (CBD) stone(s) on ERCP after a positive IOC. A retrospective review of our endoscopic database identified all ERCP and/or endoscopic ultrasound (EUS) procedures performed for a positive IOC between August 2003 and August 2009. Collected data included patient demographics; indication for cholecystectomy; IOC findings; blood tests before and after cholecystectomy, including liver function tests, complete blood count, and amylase and lipase measurements; and ERCP and/or EUS results. Patients who had a negative EUS for CBD stones and no subsequent ERCP were contacted by phone to see if they eventually required an ERCP. Univariate and multi-variable analyses were performed. A total of 114 patients were included in the study. IOC findings included a single stone, multiple stones, nonpassage of contrast into the duodenum, dilated CBD, and poor visualization of the bile duct. Eighty-four percent of patients had ERCP only, 9% had EUS only, and 7% had EUS followed by ERCP. Sixty-five patients (57%) had CBD stones on ERCP or EUS. Older age, multiple stones, dilated CBD on IOC, and elevated postcholecystectomy bilirubin levels were the clinical variables with statistically significant differences on univariate analysis. On multivariable analysis, older age and elevated postcholecystectomy total bilirubin levels correlated with the presence of CBD stones on ERCP. Fifty-seven percent of patients referred for endoscopic evaluation after a positive IOC had CBD stones on ERCP. Patients with CBD stones after a positive IOC were more likely to be older with elevated post-cholecystectomy total serum bilirubin levels.

Pharmacokinetics of florfenicol in serum and synovial fluid after regional intravenous perfusion in the distal portion of the hind limb of adult cows.

OBJECTIVE: To define the pharmacokinetics of florfenicol in synovial fluid (SYNF) and serum from central venous (CV) and digital venous (DV) blood samples following regional IV perfusion (RIVP) of the distal portion of the hind limb in cows. ANIMALS: 6 healthy adult cows. PROCEDURES: In each cow, IV catheters were placed in the dorsal common digital vein (DCDV) and the plantar vein of the lateral digit, and an indwelling catheter was placed in the metatarsophalangeal joint of the left hind limb. A pneumatic tourniquet was applied to the midmetatarsal region. Florfenicol (2.2 mg/kg) was administered into the DCDV. Samples of DV blood, SYNF, and CV (jugular) blood were collected after 0.25, 0.50, and 0.75 hours, and the tourniquet was removed; additional samples were collected at intervals for 24 hours after infusion. Florfenicol analysis was performed via high-performance liquid chromatography. RESULTS: In DV blood, CV blood, and SYNF, mean +/- SD maximum florfenicol concentration was 714.79 +/- 301.93 microg/mL, 5.90 +/- 1.37 microg/mL, and 39.19 +/- 29.42 microg/mL, respectively; area under the concentration versus time curve was 488.14 +/- 272.53 h*microg*mL(1), 23.10 +/- 6.91 h*microg*mL(1), and 113.82 +/- 54.71 h*microg*mL(1), respectively; and half-life was 4.09 +/- 1.93 hours, 4.77 +/- 0.67 hours, and 3.81 +/- 0.81 hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Following RIVP, high florfenicol concentrations were achieved in DV blood and SYNF, whereas the CV blood concentration remained low. In cattle, RIVP of florfenicol may be useful in the treatment of infectious processes involving the distal portion of limbs.