Approaches to neuropathic amputation-related pain: narrative review of surgical, interventional, and medical treatments.

BACKGROUND/IMPORTANCE: Neuropathic amputation-related pain can consist of phantom limb pain (PLP), residual limb pain (RLP), or a combination of both pathologies. Estimated of lifetime prevalence of pain and after amputation ranges between 8% and 72%. OBJECTIVE: This narrative review aims to summarize the surgical and non-surgical treatment options for amputation-related neuropathic pain to aid in developing optimized multidisciplinary and multimodal treatment plans that leverage multidisciplinary care. EVIDENCE REVIEW: A search of the English literature using the following keywords was performed: PLP, amputation pain, RLP. Abstract and full-text articles were evaluated for surgical treatments, medical management, regional anesthesia, peripheral block, neuromodulation, spinal cord stimulation, dorsal root ganglia, and peripheral nerve stimulation. FINDINGS: The evidence supporting most if not all interventions for PLP are inconclusive and lack high certainty. Targeted muscle reinnervation and regional peripheral nerve interface are the leading surgical treatment options for reducing neuroma formation and reducing PLP. Non-surgical options include pharmaceutical therapy, regional interventional techniques and behavioral therapies that can benefit certain patients. There is a growing evidence that neuromodulation at the spinal cord or the dorsal root ganglia and/or peripheral nerves can be an adjuvant therapy for PLP. CONCLUSIONS: Multimodal approaches combining pharmacotherapy, surgery and invasive neuromodulation procedures would appear to be the most promising strategy for preventive and treating PLP and RLP. Future efforts should focus on cross-disciplinary education to increase awareness of treatment options exploring best practices for preventing pain at the time of amputation and enhancing treatment of chronic postamputation pain.

Literature review of spinal hematoma case reports: causes and outcomes in pediatric, obstetric, neuraxial and pain medicine cases.

BACKGROUND: The risk of spinal epidural hematoma (SEH) has been described in the literature but the impact in various patient populations has not been assessed in the same study. We identified the risk factors for SEH and calculated the OR for recovery in the pediatric, adult and obstetric (OB) patients based on the degree of neurological deficit before surgery. METHODS: Adult non-OB cases were categorized whether they were on anticoagulants or not; SEH was related to neuraxial or pain procedure; or whether there was adherence to the American Society of Regional Anesthesia (ASRA) guidelines. Eligible cases were identified through PubMed and Embase searches in the English literature from 1954 to July 2022. RESULTS: A total of 940 cases were evaluated. In the pediatric cases, SEH was typically spontaneous, related to coagulopathy or athletic trauma. OB cases were spontaneous or related to neuraxial injections. Among adults on anticoagulant(s), SEH was mostly spontaneous with no related etiology or related to neuraxial procedure. SEH occurred despite adherence to the ASRA guidelines. Among non-OB adults not on anticoagulants, SEH was due to trauma, neuraxial injections, surgery or other causes. Neurological recovery was related to the degree of neurological deficit before surgery. CONCLUSIONS: Our data show a preponderance of spontaneous SEH in all patient populations. SEH developed even though the ASRA guidelines were followed, especially in patients on multiple anticoagulants. Patients with less impairment prior to surgery had a higher likelihood of complete recovery, regardless of the interval between surgery and onset of symptoms.

A Pharmacological Evaluation of the Analgesic Effect and Hippocampal Protein Modulation of the Ketamine Metabolite (2R,6R)-Hydroxynorketamine in Murine Pain Models.

BACKGROUND: The ketamine metabolite (2R,6R)-hydroxynorketamine ([2R,6R]-HNK) has analgesic efficacy in murine models of acute, neuropathic, and chronic pain. The purpose of this study was to evaluate the α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) dependence of (2R,6R)-HNK analgesia and protein changes in the hippocampus in murine pain models administered (2R,6R)-HNK or saline. METHODS: All mice were CD-1 IGS outbred mice. Male and female mice underwent plantar incision (PI) (n = 60), spared nerve injury (SNI) (n = 64), or tibial fracture (TF) (n = 40) surgery on the left hind limb. Mechanical allodynia was assessed using calibrated von Frey filaments. Mice were randomized to receive saline, naloxone, or the brain-penetrating AMPA blocker (1,2,3,4-Tetrahydro-6-nitro-2,3-dioxobenzo [f]quinoxaline-7-sulfonamide [NBQX]) before (2R,6R)-HNK 10 mg/kg, and this was repeated for 3 consecutive days. The area under the paw withdrawal threshold by time curve for days 0 to 3 (AUC 0-3d ) was calculated using trapezoidal integration. The AUC 0-3d was converted to percent antiallodynic effect using the baseline and pretreatment values as 0% and 100%. In separate experiments, a single dose of (2R,6R)-HNK 10 mg/kg or saline was administered to naive mice (n = 20) and 2 doses to PI (n = 40), SNI injury (n = 40), or TF (n = 40) mice. Naive mice were tested for ambulation, rearing, and motor strength. Immunoblot studies of the right hippocampal tissue were performed to evaluate the ratios of glutamate ionotropic receptor (AMPA) type subunit 1 (GluA1), glutamate ionotropic receptor (AMPA) type subunit 2 (GluA2), phosphorylated voltage-gated potassium channel 2.1 (p-Kv2.1), phosphorylated-calcium/calmodulin-dependent protein kinase II (p-CaMKII), brain-derived neurotrophic factor (BDNF), phosphorylated protein kinase B (p-AKT), phosphorylated extracellular signal-regulated kinase (p-ERK), CXC chemokine receptor 4 (CXCR4), phosphorylated eukaryotic translation initiation factor 2 subunit 1 (p-EIF2SI), and phosphorylated eukaryotic translation initiation factor 4E (p-EIF4E) to glyceraldehyde 3-phosphate dehydrogenase (GAPDH). RESULTS: No model-specific gender difference in antiallodynic responses before (2R,6R)-HNK administration was observed. The antiallodynic AUC 0-3d of (2R,6R)-HNK was decreased by NBQX but not with pretreatment with naloxone or saline. The adjusted mean (95% confidence interval [CI]) antiallodynic effect of (2R,6R)-HNK in the PI, SNI, and TF models was 40.7% (34.1%-47.3%), 55.1% (48.7%-61.5%), and 54.7% (46.5%-63.0%), greater in the SNI, difference 14.3% (95% CI, 3.1-25.6; P = .007) and TF, difference 13.9% (95% CI, 1.9-26.0; P = .019) compared to the PI model. No effect of (2R,6R)-HNK on ambulation, rearing, or motor coordination was observed. Administration of (2R,6R)-HNK was associated with increased GluA1, GluA2, p-Kv2.1, and p-CaMKII and decreased BDNF ratios in the hippocampus, with model-specific variations in proteins involved in other pain pathways. CONCLUSIONS: (2R,6R)-HNK analgesia is AMPA-dependent, and (2R,6R)-HNK affected glutamate, potassium, calcium, and BDNF pathways in the hippocampus. At 10 mg/kg, (2R,6R)-HNK demonstrated a greater antiallodynic effect in models of chronic compared with acute pain. Protein analysis in the hippocampus suggests that AMPA-dependent alterations in BDNF-TrkB and Kv2.1 pathways may be involved in the antiallodynic effect of (2R,6R)-HNK.

Effects of Adding Intrathecal Epinephrine to Spinal Anesthesia on Anesthesia-Related Cesarean Delivery Outcomes: Should We Reconsider Its Use?

BACKGROUND:  Intrathecal epinephrine is used to increase the duration of spinal anesthesia for amenable surgical procedures anticipated to require additional time; however, in the ambulatory setting, it is associated with a prolonged time to post-anesthesia care unit (PACU) discharge. The current study's authors hypothesized that adding intrathecal epinephrine to spinal anesthesia for cesarean delivery would be associated with a dose-dependent prolonged post-anesthesia unit length of stay. METHODS: A single-center, retrospective study of patients undergoing repeat cesarean delivery under spinal anesthesia from 2011 to 2015 was conducted. Patients received spinal bupivacaine 12 mg, morphine 150 mcg, and fentanyl 15 mcg with no-epinephrine, 100 mcg, or 200 mcg of epinephrine. The primary outcome was recovery room length of stay. Secondary outcomes were surgical duration, intraoperative vasopressor use, perioperative opioids, and antiemetic use. RESULTS:  Data were analyzed for 1,362 patients. Median recovery room stay was 123 min (interquartile range, 100 to 150) and was not different among groups. More women receiving epinephrine 200 mcg had ≥2 prior cesarean deliveries compared with no-epinephrine or 100 mcg. No significant differences in surgical duration or intraoperative opioids were identified among the groups. Median intraoperative vasopressor use was increased by 225 mcg of phenylephrine equivalents (99% CI, 25 mcg to 430 mcg) in the 100 mcg group and 250 mcg of phenylephrine equivalents in the 200 mcg group (99% CI, 75 mcg to 500 mcg) compared to no-epinephrine (P<0.001). Recovery room antiemetic and opioid analgesic administration were not different among groups. CONCLUSIONS:  Based on the results of this study, the addition of intrathecal epinephrine for women undergoing cesarean delivery increases intraoperative vasopressor use but does not prolong PACU length of stay, reduce intraoperative opioids, or increase antiemetic requirements postoperatively. The current study also demonstrated that surgical duration times were not different among the no-epinephrine, 100 mcg, and 200 mcg epinephrine groups.

Association between breakthrough labor pain, patient-controlled epidural analgesia use, and numeracy: A pilot observational study.

OBJECTIVE: Labor analgesia can be maintained with a continuous epidural infusion, supplemented by patient-controlled epidural boluses. patient-controlled epidural boluses use and timing require numeric understanding, as patients need to understand when they can administer supplemental boluses, lockout intervals, and total doses. We hypothesized that women with lower numeric literacy have a higher rate of provider-administered supplemental boluses for breakthrough pain because they do not understand the concept behind patient-controlled epidural boluses. DESIGN: Pilot observational study SETTING: Labor and Delivery Suite PARTICIPANTS: Nulliparous, English-speaking patients with singleton, vertex pregnancies admitted for postdates (gestational age ≥ 41 weeks) induction of labor requesting neuraxial labor analgesia. INTERVENTIONS: Combined spinal-epidural labor analgesia was initiated with intrathecal fentanyl and epidural analgesia was maintained using continuous epidural infusion with patient-controlled epidural boluses. MEASUREMENTS AND FINDINGS: Numeric literacy was assessed using the Lipkus 7-item expanded numeracy test. Patients were stratified by whether or not they required supplemental provider-administered analgesia and patient-controlled epidural boluses use patterns were evaluated. A total of 89 patients completed the study. There were no demographic differences between patients who required supplemental analgesia compared with those who did not. Patients that required supplemental analgesia were more likely to request and receive patient-controlled epidural boluses (P<0.001). Hourly bupivacaine requirement was higher in women with breakthrough pain. There were no differences in numeric literacy between the two groups. KEY CONCLUSIONS: Patients who required treatment of breakthrough pain had higher patient-controlled epidural boluses demands-to-delivery ratio. Numeric literacy was not correlated with the need for provider-administered supplemental boluses. IMPLICATIONS FOR PRACTICE: Easy to understand scripts on how to use patient-controlled epidural boluses allows for understanding of patient-controlled epidural boluses use.

Predicting chronic postsurgical pain: current evidence and a novel program to develop predictive biomarker signatures.

ABSTRACT: Chronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. Biomarkers are used to diagnose, track, and treat other diseases, but no validated clinical biomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fund launched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop them into biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discusses candidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic, neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generatedby A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPS's initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.

Efficacy and Safety of Cervical and High-Thoracic Dorsal Root Ganglion Stimulation Therapy for Complex Regional Pain Syndrome of the Upper Extremities.

OBJECTIVES: The purpose of this study was to evaluate analgesic and safety considerations for high thoracic and cervical dorsal root ganglion (DRG) neuromodulation for complex regional pain syndrome (CRPS). We hypothesized that DRG neuromodulation would provide sustained analgesia with complications like that of low thoracic or lumbar electrode implantation. MATERIALS AND METHODS: A single-center, retrospective study was conducted of patients with CRPS I or II of the upper extremities, refractory to previous therapies, who were treated with DRG neuromodulation in the upper thoracic and cervical spine. The primary outcome was successful DRG therapy, defined as ≥ 50% pain relief on a Numeric Rating Scale (NRS) 0 to 10 pain scale at six months after implantation. A secondary outcome was a reduction in daily opioid use after DRG therapy. RESULTS: After a DRG stimulation trial, 17 of 20 patients (85%) had ≥ 50% improvement in NRS pain and underwent a permanent pulse generator implant, with 100% endorsing ≥ 50% pain relief at six months. Mean NRS pain scores before DRG neuromodulation were 9.3 ± 1.1, with a mean reduction of 5.5 (95% CI, 4.5-6.6; p < 0.001) at six months. Ten patients were taking opioids at baseline; the median (interquartile range) dose was 45 mg (23 to 120) morphine equivalents (MME), which was reduced to 20 MME (15 to 40) at six months. The median reduction in daily MME use was -25 (95% CI, -100 to 20; p = 0.099). Six of 20 patients (30%) experienced a complication: three had lead migration; two experienced paresthesias; and one had a reduction in shoulder mobility. One patient had symptoms of a reversible spinal cord compression immediately after implant, requiring emergent electrode removal. CONCLUSIONS: DRG neuromodulation for patients with CRPS of the upper extremities produced clinically important analgesia and reduced opioid use for ≥ six months but was associated with one serious complication.

Early incident and subsyndromal delirium in older patients undergoing elective surgical procedures: a randomized clinical trial of an avoid delirium protocol.

Background: Pharmacological avoidance guidelines for preventing delirium have been suggested; however, there are limited pragmatic studies of these strategies. Early (<24 h) delirium can be observed in the postoperative care unit and is associated with an increased risk of subsequent delirium. We examined the effectiveness of an avoid delirium protocol (ADP) in older (>65 years) patients undergoing elective surgeries. Methods: The randomized controlled trial assessed an ADP developed using the American Geriatric Society's Clinical Practice Guidelines for Postoperative Delirium in Older Adults, on early (<24 h) incident or subsyndromal delirium. Delirium was assessed using the confusion assessment method before surgery, in the post-anesthesia care unit, and on postoperative day 1. The primary outcome of early delirium was the combined incidence of incident or subsyndromal delirium. Results: Early delirium was identified in 24/235 patients (10.2%) with a risk ratio of 1.27 (95% CI 0.59-2.73, P = 0.667) for patients randomized to the ADP. In cases with protocol adherence and no benzodiazepine use, early delirium was present in 10/ 73 (13.7%) compared to 14/148 (9.5%) in non-adherent cases [risk ratio 1.45 (95% CI 0.57-3.10, P = 0.362)]. Lower American Society of Anesthesiologists physical class [odds ratio 3.31 (95% CI 1.35-8.92, P = 0.008)] and an inpatient admission [odds ratio 2.67 (95% CI 1.55-4.87, P = 0.0002)] were associated with early delirium. Conclusions: Our findings suggest that pharmacological avoidance protocols limiting or avoiding the use of specific classes of medications are not effective in reducing early incident or subsyndromal delirium in older patients undergoing elective surgery.

Analgesic Effectiveness and Dorsal Root Ganglia Protein Modulation of a Peripheral Adenosine Monophosphate Kinase Alpha Activator (O304) Following Lumbar Disk Puncture in the Mouse.

BACKGROUND: Disk herniation is a primary cause of radicular back pain. The purpose of this study was to evaluate the antiallodynic effective dose in 50% of the sample (ED 50 ) and dorsal root ganglion (DRG) protein modulation of a peripheral direct adenosine monophosphate kinase alpha (AMPKα) activator (O304) in a murine model of lumbar disk puncture. METHODS: Male (n = 28) and female (n = 28) mice (C57BL6/J) were assessed for hind paw withdrawal threshold (PWT) and burrowing. Abdominal surgery was performed on all mice, and 48 received a lumbar disk puncture (27-G needle), with 8 serving as nondisk puncture controls. Assessments were repeated at day 7, and mice were then randomized into 5 groups of equal numbers of males and females: O304 at 100 mg/kg (n = 10), 150 mg/kg (n = 10), 200 mg/kg (n = 10), and 250 mg/kg (n = 10) or drug vehicle (n = 8). Starting on day 7, mice received daily gavages of O304 or vehicle for 7 days. On days 14 and 21 PWT and on day 14 burrowing were assessed. The area under the PWT by time curve (AUC) from day 7 to 21 was determined by trapezoidal integration. DRG protein modulation was evaluated in male (n = 10) and female (n = 10) mice (C57BL6/J). Following disk puncture, mice were randomized to receive O304 200 mg/kg or vehicle for 7 days starting on day 7. On day 14, mice were euthanized; the DRG harvested and immunoblot performed for mammalian target of rapamycin (mTOR), transient receptor potential ankyrin 1 (TRPA1), phosphorylated adenosine monophosphate kinase (p-AMPK), phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated eukaryotic translation initiation factor 2 subunit 1 (p-EIF2S1), phosphorylated eukaryotic translation initiation factor 4e (p-EIF4E), and glyceraldehyde 3-phosphate dehydrogenase (GADPH). RESULTS: Disk puncture decreased PWT greater in female mice compared with male mice and decreased burrowing at 7 days. PWTs were increased with increasing doses of O304 from 150 to 250 mg/g on day 14 and sustained through day 21. The ED 50 (95% confidence interval [CI]) for reducing mechanical allodynia was 140 (118-164) mg/kg. Burrowing was not increased at day 14 compared to day 7 by O304 administration. Compared to vehicle-treated animals, O304 increased (95% CI) the p-AMPK/GADPH ratio, difference 0.27 (0.08-0.45; P = . 004) and decreased (95% CI) the ratios of p-TRPA1, p-ERK1/2, pEIF4E, and p-EIF2S1 to GADPH by -0.49 (-0.61 to -0.37; P < . 001), -0.53 (-0.76 to -0.29; P < . 001), -0.27 (-0.42 to 0.11; P = . 001), and -0.21 (-0.32 to -0.08; P = . 003) in the DRG, respectively. CONCLUSIONS: The direct peripheral AMPK activator O304 reduced allodynia in a dose-dependent manner, and immunoblot studies of the DRG showed that O304 increased p-AMPK and decreased TRPA1, p-ERK1/2, as well as translation factors involved in neuroplasticity. Our findings confirm the role of peripheral AMPKα activation in modulating nociceptive pain.

Patient and operative factors associated with unanticipated intensive care admission and outcomes following posterior fossa decompressions in children: A retrospective study.

INTRODUCTION: Posterior fossa decompression for Chiari I Malformation is a common pediatric neurosurgical procedure. We sought to identify the impact of anesthesia-related intraoperative complications on unanticipated admission to the intensive care unit and outcomes following posterior fossa decompression. METHODS: Medical records of all patients <18 years who underwent surgery for Chiari I malformation between 1/1/09 and 1/31/21 at the Ann & Robert H. Lurie Children's Hospital of Chicago were included. Records were reviewed for patient characteristics, anesthesia-related intraoperative complications, postoperative complications, and surgical outcomes. The primary outcome was the incidence of unanticipated admission to the intensive care unit, and the primary variable of interest was an anesthesia-related intraoperative complication. Patient, surgical characteristics, and year of surgery were also compared between patients with and without an unanticipated admission to the intensive care unit, and a multi-variable adjusted estimate of odds of unanticipated admission to the intensive care unit admission following an anesthesia-related intraoperative complication was performed. Secondary outcomes included anesthesia factors associated with an anesthesia-related intraoperative event, and postoperative complications and surgical outcomes between patients admitted to the intensive care unit and those who were not. RESULTS: Two hundred ninety-six patients with Chiari I Malformation were identified. Clinical characteristics associated with an unanticipated admission to the intensive care unit were younger age, American Society of Anesthesiologist (ASA) physical status >2 and an anesthesia-related intraoperative complication. 29 anesthesia-related intraoperative complications were observed in 25 patients (8.4%). Two of 25 patients (8%) with an anesthesia-related intraoperative complication compared with 3 of 271 (1%) patients without anesthesia-related intraoperative complication had an unanticipated admission to the intensive care unit, odds ratio 7.8 (95% CI 1.2-48.8, p = .010). When adjusted for age, sex, ASA physical status, presenting symptoms, concomitant syringomyelia, previous decompression surgery and year of surgery, the odds ratio for an unanticipated admission to the intensive care unit following an anesthesia-related intraoperative complication was 5.9 (95% CI 0.51-59.6, p = .149). There were no differences in surgical outcomes between patients with or without an unanticipated admission to the intensive care unit. CONCLUSION: Our study demonstrates that although anesthesia-related intraoperative complications during posterior fossa decompression are infrequent, they are associated with an increased risk of an unanticipated admission to the intensive care unit.

Multi-Site Observational Study to Assess Biomarkers for Susceptibility or Resilience to Chronic Pain: The Acute to Chronic Pain Signatures (A2CPS) Study Protocol.

Chronic pain has become a global health problem contributing to years lived with disability and reduced quality of life. Advances in the clinical management of chronic pain have been limited due to incomplete understanding of the multiple risk factors and molecular mechanisms that contribute to the development of chronic pain. The Acute to Chronic Pain Signatures (A2CPS) Program aims to characterize the predictive nature of biomarkers (brain imaging, high-throughput molecular screening techniques, or "omics," quantitative sensory testing, patient-reported outcome assessments and functional assessments) to identify individuals who will develop chronic pain following surgical intervention. The A2CPS is a multisite observational study investigating biomarkers and collective biosignatures (a combination of several individual biomarkers) that predict susceptibility or resilience to the development of chronic pain following knee arthroplasty and thoracic surgery. This manuscript provides an overview of data collection methods and procedures designed to standardize data collection across multiple clinical sites and institutions. Pain-related biomarkers are evaluated before surgery and up to 3 months after surgery for use as predictors of patient reported outcomes 6 months after surgery. The dataset from this prospective observational study will be available for researchers internal and external to the A2CPS Consortium to advance understanding of the transition from acute to chronic postsurgical pain.

The effects of sex and neuter status on trauma survival in dogs: A Veterinary Committee on Trauma registry study.

OBJECTIVE: To determine the effect of sex and neuter status on trauma survival in dogs. DESIGN: Multi-institutional prospective case series, September 2013 to March 2019, retrospectively analyzed. SETTING: Level I and II Veterinary Trauma Centers. ANIMALS: Consecutive sample of 2649 dogs in the American College of Veterinary Emergency and Critical Care Veterinary Committee on Trauma patient registry meeting inclusion criteria. For inclusion, dogs had to have complete data entries, be postpubertal (≥7 months age in females and ≥10 months age in males), and have sustained moderate to severe trauma (animal trauma triage [ATT] score ≥5/18). Dogs that were dead upon arrival, euthanized for financial or unknown reasons alone, or that were presented by a Good Samaritan but subsequently humanely euthanized were excluded. MEASUREMENTS AND MAIN RESULTS: Data collected included age, sex, neuter status (intact, neutered), trauma type (blunt, penetrating, both), outcome (survived to hospital discharge, died, euthanized), and reason for euthanasia (grave prognosis, financial reasons, or both). Of 2649 eligible dogs, 56% survived to hospital discharge (n = 1469). Neutered females had a significantly higher survival rate (58.3% vs 51.3%; P = 0.03) compared to intact females, and neutered males had a significantly higher survival rate (56.6% vs 50.7%; P = 0.04) compared to intact males. There was no significant difference in survival between intact females and intact males (P = 0.87) or between neutered females and neutered males (P = 0.46). Mean cumulative ATT score was higher in intact groups and was found to be a significant predictor of survival (P < 0.01). Based on logistic models, overall odds of survival were 20.7% greater in neutered dogs. CONCLUSIONS: Gonadectomy is associated with lower ATT scores and improved survival after moderate to severe trauma in both female and male dogs.

Osteomyelitis in cold-stunned Kemp's ridley sea turtles (Lepidochelys kempii) hospitalized for rehabilitation: 25 cases (2008-2018).

OBJECTIVE: To characterize osteolytic lesions in cold-stunned Kemp's ridley sea turtles (Lepidochelys kempii) hospitalized for rehabilitation and describe methods used for the management of such lesions. ANIMALS: 25 stranded, cold-stunned Kemp's ridley sea turtles hospitalized between 2008 and 2018. PROCEDURES: Medical records of sea turtles with a diagnosis of osteolytic lesions were reviewed retrospectively to obtain the date of diagnosis, clinical signs, radiographic findings, microbial culture results, hematologic and plasma biochemical data, cytologic and histologic findings, antimicrobial history, time to first negative culture result, treatment duration, and outcome. RESULTS: Lesions were identified radiographically a median of 50 days after admission and were located within epiphyses or metaphyses of various appendicular joints. Lesions were associated with periarticular swelling (n = 24), lameness (16), lethargy (2), and hyporexia (2). Bacterial culture yielded growth of single organisms (n = 16), multiple organisms (2), or no growth (6). Significant differences in hematologic and biochemical data were detected between the times of diagnosis and convalescence. Cytologic and histologic findings characterized the lesions as osteomyelitis leading to septic arthritis. Sixteen sea turtles were managed medically, and 8 were managed medically and surgically. Surgery resulted in rapid improvement in joint mobility and overall clinical status. Most (22/25 [88%]) sea turtles survived and were released after long-term management. CONCLUSIONS AND CLINICAL RELEVANCE: During rehabilitation, cold-stunned Kemp's ridley sea turtles may be affected by osteomyelitis. Medical management based on antimicrobial susceptibility testing was effective for most turtles. Long term management efforts in turtles are justified by high survival rate.

Trajectories of opioid consumption from day of surgery to 28 days postoperatively: a prospective cohort study in patients undergoing abdominal, joint, or spine surgery.

INTRODUCTION: Descriptions of opioid use trajectories and their association with postsurgical pain and opioid consumption are limited. We hypothesized that trajectories of opioid consumption in the first 28 days following surgery would be associated with unique patterns of pain and duration of opioid use. METHODS: A prospective longitudinal cohort of patients undergoing elective inpatient abdominal, joint, or spine surgery between June 2016 and June 2019 was studied. At hospital discharge and every 7 days for 28 days, patients were assessed for pain, analgesic use, pain interference, satisfaction, and side effects. Duration of opioid use was determined for 6 months. The primary analysis used latent class group modeling to identify trajectories of opioid use. RESULTS: Decreasing, high, and persistent opioid trajectories were identified following joint and spine surgery and a decreasing and persistent trajectory following abdominal surgery. Reported pain was greater in the high and persistent trajectories compared with the decreasing use trajectories. Compared with the decreasing opioid trajectory, the median duration of opioid use was increased by 4.5 (95% CI 1 to 22, p<0.01) weeks in persistent opioid use abdominal and by 6 (95% CI 0 to 6, p<0.01) weeks in the high or persistent use joint and spine groups. The odds (95% CI) of opioid use at 6 months in the high or persistent opioid use trajectory was 24.3 (2.9 to 203.4) for abdominal and 3.7 (1.9 to 7.0) for joint or spine surgery compared with the decreasing use trajectory. Morphine milliequivalent per 24 hours of hospitalization was the primary independent predictor of opioid use trajectories. CONCLUSIONS: We observed distinct opioid use trajectories following abdominal and joint or spine surgery that were associated with different patterns of pain and duration of opioid use postoperatively. Prediction of postoperative opioid use trajectory groups may be clinically important for identifying risk of prolonged opioid use.

Preoperative cognitive-behavioral therapy for reducing pain catastrophizing and improving pain outcomes after total knee replacement: a randomized clinical trial.

INTRODUCTION: Cognitive-behavioral therapy (CBT) can reduce preoperative pain catastrophizing and may improve postsurgical pain outcomes. We hypothesized that CBT would reduce pain catastrophizing more than no-CBT controls and result in improved pain outcomes. METHODS: The study was a randomized controlled trial of patients undergoing elective total knee arthroplasty between January 2013 and March 2020. In phase 1, the change in pain catastrophizing scores (PCS) among 4-week or 8-week telehealth, 4-week in person and no-CBT sessions was compared in 80 patients with a PCS >16. In phase 2, the proportion of subjects that achieved a 3-month decrease in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain subscale >4 following 4-week telehealth CBT with no-CBT controls were compared in 80 subjects. RESULTS: In phase 1, 4-week telehealth CBT had the highest completion rate 17/20 (85%), demonstrated an adjusted median reduction in PCS of -9 (95% CI -1 to -14, p<0.01) compared with no-CBT and was non-inferior to 8-week telehealth CBT at a margin of 2 (p=0.02). In phase 2, 29 of 35 (83%) in the 4-week telehealth CBT and 26 of 33 (79%) subjects in the no-CBT demonstrated a decrease in the WOMAC pain subscale >4 at 3 months, difference 4% (95% CI -18% to 26%, p=0.48), despite a median decrease in the PCS for the 4-week CBT and no-CBT group of -6 (-10 to -2, p=0.02). CONCLUSIONS: Our findings demonstrate that CBT interventions delivered prior to surgery in person or via telehealth can reduced PCS scores; however, this reduction did not lead to improved 3-month pain outcomes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT01772329, registration date 21 January 2013).

Institution of prothrombin complex concentrate protocols is associated with a reduction in plasma administration at a Tertiary Care Hospital.

STUDY OBJECTIVE: Explore how the introduction of 4-factor prothrombin complex concentrates (4F-PCC) protocols for reversing anticoagulation and the treatment of critical bleeding influenced blood product utilization. DESIGN: A retrospective analysis of the utilization rate of plasma and 4F-PCC from September 2012 through December 2018. SETTING: Blood bank and pharmacy records of a single large tertiary care medical center. PATIENTS: Admitted patients except obstetric during the study period (n = 283,319). INTERVENTION: Five institutional protocols providing guidelines for 4F-PCC administration were deployed over a 3-year period. MEASUREMENTS: The utilization rate of plasma and 4F-PCC was the primary outcome and analyzed using an interrupted time series analysis. Utilization of platelets and cryoprecipitate as well as the impact of the intervention on the service prescribing the blood products were evaluated as secondary outcomes. Data were evaluated using a segmented time series regression. RESULTS: When adjusted for seasonality, the monthly rate of plasma administration was 24.7 ± 2.0 units per 100 admissions in the 6-month period prior to the 1st intervention (May-October 2013) and decreased to 9.9 ± 2.2 units per 100 admissions in the same six-month period following the 5th intervention (May-October 2018), median difference - 14.5, 95% CI -16.0 to -13.2, P < 0.001. During the 6-month period prior to the 1st intervention (May-October 2013) the monthly rate of 4-F PCC use was 1.2 ± 0.8 doses per 1000 admissions and increased to 2.8 ± 1.0 doses per 1000 admissions 6-months following the 5th intervention (May-October 2018), median difference 1.6, 95% CI 0.3 to 1.9, P = 0.014. The monthly utilization of platelets was decreased and cryoprecipitate slightly increased following the implementation of the PCC protocols. CONCLUSIONS AND RELEVANCE: Our findings demonstrate that establishing institutional protocols for the use of 4F-PCC to reverse the effects of anticoagulation and to treat critical bleeding with associated coagulopathy was associated with reduced plasma utilization.

Ovarian remnant syndrome in a cat with ovarian tissue in the omentum.

CASE DESCRIPTION: A 2-year-old spayed female domestic shorthair cat was evaluated for recurring estrous behavior after ovariohysterectomy and 2 subsequent exploratory laparotomies. CLINICAL FINDINGS: Physical examination revealed no abnormalities. A serum sample tested positive for anti-Müllerian hormone and had a progesterone concentration consistent with the presence of an ovarian remnant. Results of abdominal ultrasonographic examination suggested presence of a slightly hyperechoic mass caudal to the left kidney. TREATMENT AND OUTCOME: Exploratory laparotomy was performed when the cat was showing estrous behavior. Tissues at the right and left ovarian pedicles and the uterine stump appeared grossly normal but were excised and submitted for histologic examination. Two small nodules associated with the omentum were removed, and histologic examination results for one of these nodules indicated ovarian tissue with secondary and graafian follicles. Clinical signs of estrus resolved after surgery, and hormonal assay results were within ranges expected for an ovariectomized cat. CLINICAL RELEVANCE: To the authors' knowledge, the present case represented the first clinical report of ovarian remnant syndrome in a cat or dog in which persistent ovarian tissue was not found at the site of an ovarian pedicle. Our findings emphasized the importance of exploring the entire abdominal cavity when evaluating a patient for possible ovarian remnant tissue and confirming the excision of ovarian remnant tissue by histologic assessment.

Predicting common solid renal tumors using machine learning models of classification of radiologist-assessed magnetic resonance characteristics.

PURPOSE: Solid renal masses (SRM) are difficult to differentiate based on standard MR features. The purpose of this study was to assess MR imaging features of SRM to evaluate performance of ensemble methods of classifying SRM subtypes. MATERIALS AND METHODS: MR images of SRM (n = 330) were retrospectively evaluated for standard and multiparametric (mp) features. Models of MR features for predicting malignant and benign lesions as well as subtyping SRM were developed using a training dataset and performance was evaluated in a test data-set using recursive partitioning (RP), gradient booting machine (GBM), and random forest (RF) methods. RESULTS: In the test dataset, GBM and RF models demonstrated an accuracy of 86% (95% CI 75% to 93%) for predicting benign versus malignant SRM compared to 83% (95% CI 71% to 91%) for the RP model. RF had the greatest accuracy in predicting SRM subtypes, 81.2% (95% CI 69.5% to 89.9%) compared with GBM 73.4% (95% CI 60.9% to 83.7%) or RP 70.3% (95% CI 57.6% to 81.1%). Marginal homogeneity was reduced by the RF model compared with the RP model (P < 0.001), but not the GBM model (P = 0.135). All models had high sensitivity and specificity for clear cell and papillary renal cell carcinomas (RCC), but performed less well in differentiating chromophobe RCC, oncocytomas, and fat-poor angiomyolipomas. CONCLUSION: Ensemble methods for prediction of SRM from radiologist-assessed image characteristics have high accuracy for distinguishing benign and malignant lesions. SRM subtype classification is limited by the ability to categorize chromophobe RCCs, oncocytomas, and fat-poor angiomyolipomas.