Priming of the autonomic nervous system after an experimental human pain model.

Modulated autonomic responses to noxious stimulation have been reported in experimental and clinical pain. These effects are likely mediated by nociceptive sensitization, but may also, more simply reflect increased stimulus-associated arousal. To disentangle between sensitization- and arousal-mediated effects on autonomic responses to noxious input, we recorded sympathetic skin responses (SSRs) in response to 10 pinprick and heat stimuli before (PRE) and after (POST) an experimental heat pain model to induce secondary hyperalgesia (EXP) and a control model (CTRL) in 20 healthy females. Pinprick and heat stimuli were individually adapted for pain perception (4/10) across all assessments. Heart rate, heart rate variability, and skin conductance level (SCL) were assessed before, during, and after the experimental heat pain model. Both pinprick- and heat-induced SSRs habituated from PRE to POST in CTRL, but not EXP (P = 0.033). Background SCL (during stimuli application) was heightened in EXP compared with CTRL condition during pinprick and heat stimuli (P = 0.009). Our findings indicate that enhanced SSRs after an experimental pain model are neither fully related to subjective pain, as SSRs dissociated from perceptual responses, nor to nociceptive sensitization, as SSRs were enhanced for both modalities. Our findings can, however, be explained by priming of the autonomic nervous system during the experimental pain model, which makes the autonomic nervous system more susceptible to noxious input. Taken together, autonomic readouts have the potential to objectively assess not only nociceptive sensitization but also priming of the autonomic nervous system, which may be involved in the generation of distinct clinical pain phenotypes.NEW & NOTEWORTHY The facilitation of pain-induced sympathetic skin responses observed after experimentally induced central sensitization is unspecific to the stimulation modality and thereby unlikely solely driven by nociceptive sensitization. In addition, these enhanced pain-induced autonomic responses are also not related to higher stimulus-associated arousal, but rather a general priming of the autonomic nervous system. Hence, autonomic readouts may be able to detect generalized hyperexcitability in chronic pain, beyond the nociceptive system, which may contribute to clinical pain phenotypes.

Short Sequence Aligner Benchmarking for Chromatin Research.

Much of today's molecular science revolves around next-generation sequencing. Frequently, the first step in analyzing such data is aligning sequencing reads to a reference genome. This step is often taken for granted, but any analysis downstream of the alignment will be affected by the aligner's ability to correctly map sequences. In most cases, for research into chromatin structure and nucleosome positioning, ATAC-seq, ChIP-seq, and MNase-seq experiments use short read lengths. How well aligners manage these reads is critical. Most aligner programs will output mapped reads and unmapped reads. However, from a biological point of view, reads will fall into one of three categories: correctly mapped, incorrectly mapped, and unmapped. While increased sequencing depth can often compensate for unmapped reads, incorrectly and correctly mapped reads appear algorithmically identical but can produce biologically significant alterations in the results. For this reason, we are benchmarking various alignment programs to determine their propensity to incorrectly map short reads. As short-read alignment is an important step in ATAC-seq, ChIP-seq, and MNase-seq experiments, caution should be taken in mapping reads to ensure that the most accurate conclusions can be made from the data generated. Our analysis is intended to help investigators new to the field pick the alignment program best suited for their experimental conditions. In general, the aligners we tested performed well. BWA, Bowtie2, and Chromap were all exceptionally accurate, and we recommend using them. Furthermore, we show that longer read lengths do in fact lead to more accurate mappings.

A game-theoretic model of rabies in domestic dogs with multiple voluntary preventive measures.

Game theory is now routinely applied to quantitatively model the decision making of individuals presented with various voluntary actions that can prevent a given disease. Most models consider only a single preventive strategy and the case where multiple preventative actions are available is severely understudied. In our paper, we consider a very simple SI compartmental model of rabies in the domestic dog population. We study two choices of the dog owners: to vaccinate their dogs or to restrict the movements of unvaccinated dogs. We analyze the relatively rich patterns of Nash equilibria (NE). We show that there is always at least one NE at which the owners utilize only one form of prevention. However, there can be up to three different NEs at the same time: two NEs at which the owners use exclusively only the vaccination or movement restriction, and the third NE when the owners use both forms of prevention simultaneously. However, we also show that, unlike the first two types of NEs, the third kind of NE is not convergent stable.

The Effect of Conditioned Pain Modulation on Tonic Heat Pain Assessed Using Participant-Controlled Temperature.

OBJECTIVE: Descending pain modulation can be experimentally assessed by way of testing conditioned pain modulation. The application of tonic heat as a test stimulus in such paradigms offers the possibility of observing dynamic pain responses, such as adaptation and temporal summation of pain. Here we investigated conditioned pain modulation effects on tonic heat employing participant-controlled temperature, an alternative tonic heat pain assessment. Changes in pain perception are thereby represented by temperature adjustments performed by the participant, uncoupling this approach from direct pain ratings. Participant-controlled temperature has emerged as a reliable and sex-independent measure of tonic heat. METHODS: Thirty healthy subjects underwent a sequential conditioned pain modulation paradigm, in which a cold water bath was applied as the conditioning stimulus and tonic heat as a test stimulus. Subjects were instructed to change the temperature of the thermode in response to variations in perception to tonic heat in order to maintain their initial rating over a two-minute period. Two additional test stimuli (i.e., lower limb noxious withdrawal reflex and pressure pain threshold) were included as positive controls for conditioned pain modulation effects. RESULTS: Participant-controlled temperature revealed conditioned pain modulation effects on temporal summation of pain (P = 0.01). Increased noxious withdrawal reflex thresholds (P = 0.004) and pressure pain thresholds (P < 0.001) in response to conditioning also confirmed inhibitory conditioned pain modulation effects. CONCLUSIONS: The measured interaction between conditioned pain modulation and temporal summation of pain supports the participant-controlled temperature approach as a promising method to explore dynamic inhibitory and facilitatory pain processes previously undetected by rating-based approaches.

Acceptance and Commitment Therapy Delivered via a Mobile Phone Messaging Robot to Decrease Postoperative Opioid Use in Patients With Orthopedic Trauma: Randomized Controlled Trial.

BACKGROUND: Acceptance and commitment therapy (ACT) is a pragmatic approach to help individuals decrease avoidable pain. OBJECTIVE: This study aims to evaluate the effects of ACT delivered via an automated mobile messaging robot on postoperative opioid use and patient-reported outcomes (PROs) in patients with orthopedic trauma who underwent operative intervention for their injuries. METHODS: Adult patients presenting to a level 1 trauma center who underwent operative fixation of a traumatic upper or lower extremity fracture and who used mobile phone text messaging were eligible for the study. Patients were randomized in a 1:1 ratio to either the intervention group, who received twice-daily mobile phone messages communicating an ACT-based intervention for the first 2 weeks after surgery, or the control group, who received no messages. Baseline PROs were completed. Two weeks after the operative intervention, follow-up was performed in the form of an opioid medication pill count and postoperative administration of PROs. The mean number of opioid tablets used by patients was calculated and compared between groups. The mean PRO scores were also compared between the groups. RESULTS: A total of 82 subjects were enrolled in the study. Of the 82 participants, 76 (38 ACT and 38 controls) completed the study. No differences between groups in demographic factors were identified. The intervention group used an average of 26.1 (SD 21.4) opioid tablets, whereas the control group used 41.1 (SD 22.0) tablets, resulting in 36.5% ([41.1-26.1]/41.1) less tablets used by subjects receiving the mobile phone-based ACT intervention (P=.004). The intervention group subjects reported a lower postoperative Patient-Reported Outcome Measure Information System Pain Intensity score (mean 45.9, SD 7.2) than control group subjects (mean 49.7, SD 8.8; P=.04). CONCLUSIONS: In this study, the delivery of an ACT-based intervention via an automated mobile messaging robot in the acute postoperative period decreased opioid use in selected patients with orthopedic trauma. Participants receiving the ACT-based intervention also reported lower pain intensity after 2 weeks, although this may not represent a clinically important difference. TRIAL REGISTRATION: ClinicalTrials.gov NCT03991546; https://clinicaltrials.gov/ct2/show/NCT03991546.

Pathobiont release from dysbiotic gut microbiota biofilms in intestinal inflammatory diseases: a role for iron?

Gut microbiota interacting with an intact mucosal surface are key to the maintenance of homeostasis and health. This review discusses the current state of knowledge of the biofilm mode of growth of these microbiota communities, and how in turn their disruptions may cause disease. Beyond alterations of relative microbial abundance and diversity, the aim of the review is to focus on the disruptions of the microbiota biofilm structure and function, the dispersion of commensal bacteria, and the mechanisms whereby these dispersed commensals may become pathobionts. Recent findings have linked iron acquisition to the expression of virulence factors in gut commensals that have become pathobionts. Causal studies are emerging, and mechanisms common to enteropathogen-induced disruptions, as well as those reported for Inflammatory Bowel Disease and colo-rectal cancer are used as examples to illustrate the great translational potential of such research. These new observations shed new light on our attempts to develop new therapies that are able to protect and restore gut microbiota homeostasis in the many disease conditions that have been linked to microbiota dysbiosis.

Factor VIII and vWF deficiency in STT3A-CDG.

STT3A-CDG (OMIM# 615596) is an autosomal recessive N-linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern. All previously reported cases (n = 6) have been attributed to a homozygous pathogenic missense variant c.1877C>T (p.Val626Ala) in STT3A. We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures. VWF in our patient's plasma is present in a mildly hypoglycosylated form. FVIII antigen levels were too low to quantify in our patient. Functional studies with STT3A-/- HEK293 cells showed severely reduced FVIII antigen and activity levels in conditioned media <10% expected, but normal intracellular levels. We also show decreased glycosylation of STT3A-specific acceptors in fibroblasts from our patient, providing a mechanistic explanation for how STT3A deficiency leads to a severe defect in FVIII secretion. Our results suggest that certain STT3A-dependent N-glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level. Our report expands both the genotype and phenotype of STT3A-CDG; demonstrating, as in most types of CDG, that there are multiple disease-causing variants in STT3A.

Taking a step back: Self-distancing dynamics in adolescent writing about peer problems.

Can the retelling of an unpleasant experience help adolescents cope with that experience? This study answers that question by looking at the role of psychological self-distancing when adolescents write about recently untold stressful events with peers using either a traditional expressive writing (EW) intervention or a cognitively oriented expressive writing (CEW) intervention. Extent of self-distancing (i.e., low and high) as well as its variability (i.e., increasing or stable) were taken into account. Data, obtained from 292 written essays from 78 Italian adolescents (mean age was 12.9; 50% was female), were collected longitudinally on four occasions. Group-based trajectory modeling determined the extent and variability in self-distancing for the two writing interventions (i.e., EW and CEW) and two baseline peer problem conditions (i.e., low and high). Findings indicate that, for adolescents who experience high peer problems at baseline, CEW intervention fosters meaning-making through self-distancing, resulting in being more beneficial than traditional EW.

Astrocytic IP3 Rs: Contribution to Ca2+ signalling and hippocampal LTP.

Astrocytes regulate hippocampal synaptic plasticity by the Ca2+ dependent release of the N-methyl d-aspartate receptor (NMDAR) co-agonist d-serine. Previous evidence indicated that d-serine release would be regulated by the intracellular Ca2+ release channel IP3 receptor (IP3 R), however, genetic deletion of IP3 R2, the putative astrocytic IP3 R subtype, had no impact on synaptic plasticity or transmission. Although IP3 R2 is widely believed to be the only functional IP3 R in astrocytes, three IP3 R subtypes (1, 2, and 3) have been identified in vertebrates. Therefore, to better understand gliotransmission, we investigated the functionality of IP3 R and the contribution of the three IP3 R subtypes to Ca2+ signalling. As a proxy for gliotransmission, we found that long-term potentiation (LTP) was impaired by dialyzing astrocytes with the broad IP3 R blocker heparin, and rescued by exogenous d-serine, indicating that astrocytic IP3 Rs regulate d-serine release. To explore which IP3 R subtypes are functional in astrocytes, we used pharmacology and two-photon Ca2+ imaging of hippocampal slices from transgenic mice (IP3 R2-/- and IP3 R2-/- ;3-/- ). This approach revealed that underneath IP3 R2-mediated global Ca2+ events are an overlooked class of IP3 R-mediated local events, occurring in astroglial processes. Notably, multiple IP3 Rs were recruited by high frequency stimulation of the Schaffer collaterals, a classical LTP induction protocol. Together, these findings show the dependence of LTP and gliotransmission on Ca2+ release by astrocytic IP3 Rs. GLIA 2017;65:502-513.

A Case of Ovarian Hyperthecosis in a Postmenopausal Woman.

We report a case of a 55-year-old postmenopausal woman who presented with symptoms of fatigue, male pattern hair loss, and hirsutism over 3 years. Investigations showed elevated total testosterone levels of 5.0 nmol/L (1.44 ng/mL; range, 0.3-3.1 nmol/L) using Beckman-Unicel-DXI-800 immunoassay. Testosterone levels were repeated by liquid chromatography-tandem mass spectrometry and were found to be elevated at 7.3 nmol/L (2.10 ng/mL). Estradiol was detectable and free androgen index was elevated. Dehydroepiandrosterone sulfate levels and androstenedione were within normal range, suggesting a nonadrenal source. Computed tomography scan of the abdomen showed no evidence of adrenal or adnexal tumor. GnRH analog stimulation test led to reduction of gonadotrophins and normalization of testosterone within 4 weeks. She had a biopsy of a cranial hair follicle, which showed androgenic alopecia. These investigations confirmed an ovarian source of androgens. Subsequently, she underwent bilateral salpingo-oophorectomy. Histological study of gonadal tissue confirmed the diagnosis of ovarian hyperthecosis. Four weeks after oophorectomy, her testosterone levels normalized and clinical symptoms improved. Ovarian hyperthecosis is a rare cause of hyperandrogenism in postmenopausal women and can pose a diagnostic and therapeutic challenge. Careful history and physical examination along with critical analysis of biochemistry and imaging studies is crucial for correct diagnosis.

Biomechanical guidance can improve accuracy of reduction for intra-articular tibia plafond fractures and reduce joint contact stress.

Articular fracture malreduction increases posttraumatic osteoarthritis (PTOA) risk by elevating joint contact stress. A new biomechanical guidance system (BGS) that provides intraoperative assessment of articular fracture reduction and joint contact stress based solely on a preoperative computed tomography (CT) and intraoperative fluoroscopy may facilitate better fracture reduction. The objective of this proof-of-concept cadaveric study was to test this premise while characterizing BGS performance. Articular tibia plafond fractures were created in five cadaveric ankles. CT scans were obtained to provide digital models. Indirect reduction was performed in a simulated operating room once with and once without BGS guidance. CT scans after fixation provided models of the reduced ankles for assessing reduction accuracy, joint contact stresses, and BGS accuracy. BGS was utilized 4.8 ± 1.3 (mean ± SD) times per procedure, increasing operative time by 10 min (39%), and the number of fluoroscopy images by 31 (17%). Errors in BGS reduction assessment compared to CT-derived models were 0.45 ± 0.57 mm in translation and 2.0 ± 2.5° in rotation. For the four ankles that were successfully reduced and fixed, associated absolute errors in computed mean and maximum contact stress were 0.40 ± 0.40 and 0.96 ± 1.12 MPa, respectively. BGS reduced mean and maximum contact stress by 1.1 and 2.6 MPa, respectively. BGS thus improved the accuracy of articular fracture reduction and significantly reduced contact stress. Statement of Clinical Significance: Malreduction of articular fractures is known to lead to PTOA. The BGS described in this work has potential to improve quality of articular fracture reduction and clinical outcomes for patients with a tibia plafond fracture.

Agricultural Trauma Causing Open Fractures: Is Antibiotic Coverage Against Anaerobic Organisms Indicated?

OBJECTIVE: To compare deep infection rate and causative organisms in open fractures of the lower extremity from agricultural trauma with similar injuries in nonagricultural trauma. DESIGN: Retrospective. SETTING: Two tertiary care institutions. METHODS: Open lower extremity fractures sustained between 2003 and 2018 caused by agriculture-related trauma in adult patients were reviewed. A nonagriculture open fracture control group (NAG) was identified for comparison. Patient demographics and injury characteristics were assessed. Outcomes included occurrence of deep infection and causative organisms. RESULTS: One hundred seventy-eight patients were identified in the agriculture (AG) (n = 89) and control (NAG) (n = 89) groups. Among patients with agricultural injury, farm machinery was the most common mechanism in 69 (77.5%) of them. Open injuries of the foot (38.2%) and tibial shaft injuries (25.8%) were the most common in the AG and NAG groups, respectively. Deep infection was seen in 21% of patients in the AG group compared with 10% in the NAG group (P < 0.05). In the AG group, anaerobic infection occurred in 44% of patients with deep infection compared with 9.1% in the NAG group (P < 0.05). The most common anaerobic organisms included enterococci, Pseudomonas aeruginosa, and Clostridium perfringens. CONCLUSIONS: This study supports that open fractures due to agricultural trauma have a high infection rate, with anaerobic infection occurring at higher rates than in injuries due to nonagricultural trauma. Prophylactic treatment with antibiotics directed against anaerobes is indicated in these injuries. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Motor Recovery Depends on Timing of Surgery in Patients With Lumbar Disk Herniation.

BACKGROUND: Although approximately half of the patients undergoing lumbar disk surgery present with motor deficits, timing of surgery for radicular weakness is largely unclear. OBJECTIVE: To evaluate the impact of surgical timing on motor recovery in patients with lumbar disk herniation (LDH) and to identify an ideal time window for intervention. METHODS: In a single-center observational trial, 390 patients with LDH-associated motor deficits were prospectively followed for a minimum of 12 months after nonelective microscopic disk surgery. The duration of motor deficit before surgery was documented. Motor function was graded according to the Medical Research Council (MRC) scale. Statistical analysis of motor recovery applied unbiased recursive partitioning conditional inference tree to determine cutoff times for optimal surgical intervention. The slope of recovery calculated as the change of the MRC grade over time served as the primary outcome. RESULTS: A preoperative motor deficit of MRC ≤2/5 and the duration of paresis were identified as the most important predictors of recovery ( P < .001). Surgery within 3 days was associated with a better recovery for both severe and moderate/mild deficits ( P = .017 for MRC ≤ 2/5; P < .001 for MRC > 2/5; number needed to treat [NNT] <2). A sensitivity analysis in mild motor deficits indicated a cutoff of 8 days. CONCLUSION: Timing of surgery is crucial for motor recovery in LDH-associated deficits. Immediate diagnosis, imaging, and referral should be aimed for to allow disk surgery within 3 days in patients with severe and moderate radicular weakness. If functionally disabling, even mild deficits may warrant decompression within a week.

Draft Genome Sequence of Nereida sp. Strain MMG025, Isolated from Giant Kelp.

Here, we report the draft genome sequence of Nereida sp. strain MMG025, isolated from the surface of giant kelp and assembled and analyzed by undergraduate students participating in a marine microbial genomics course. A genomic comparison suggests that MMG025 is a novel species, providing a resource for future microbiology and biotechnology investigations.

A rare tumour in a rare location: desmoplastic fibroma in a toe.

We report a case of desmoplastic fibroma occurring in the 2nd toe. This lesion most frequently occurs in the long bones or the mandible. This is only the second reported case of desmoplastic fibroma in a toe in the English language. The importance and process of establishing a differential diagnosis in such lesions is highlighted. The similarity between the clinical and histological findings of this tumour and other tumours, both benign and malignant, makes familiarity with the character of desmoplastic fibroma essential for proper treatment.

When Love Just Ends: An Investigation of the Relationship Between Dysfunctional Behaviors, Attachment Styles, Gender, and Education Shortly After a Relationship Dissolution.

Much information is known about the long-term consequences of separation and divorce, whereas there is a paucity of studies about the short-term consequences of such experiences. This study investigates the adoption of dysfunctional behaviors (e.g., insistent telephone calls and text messages, verbal threats, and sending unwanted objects) shortly after a relationship dissolution. A total of 136 participants who declared to have been left by their former partner in the previous 6 months were included in this study (i.e., females: n = 84; males: n = 52; mean age = 30.38; SD = 4.19). Attachment styles were evaluated as explanatory variables when facing a relationship dissolution, in connection with a set of (1) demographic variables (i.e., gender, education, and current marital/relationship status), (2) dysfunctional behaviors, and (3) motivations on the basis of those behaviors. Results showed that a secure or dismissing attachment style, a higher education, and currently married (but awaiting separation) status were the protective factors in adopting such dysfunctional behaviors, while the preoccupied and fearful-avoidant subjects, especially females, tended to adopt dysfunctional behaviors (i.e., communication attempts and defamation) and reported fear of abandonment and need for attention as underlying motivations. Future study on longitudinal aspects of the relationship dissolution processes is required to have deeper insights into this phenomenon. This study sheds light on the relationship between adult attachment styles and the motivations behind the adoption of dysfunctional behaviors after a relationship dissolution.

Combined Neurophysiologic and Neuroimaging Approach to Reveal the Structure-Function Paradox in Cervical Myelopathy.

OBJECTIVE: To explore the so-called "structure-function paradox" in individuals with focal spinal lesions by means of tract-specific MRI coupled with multi-modal evoked potentials and quantitative sensory testing. METHODS: Individuals with signs and symptoms attributable to cervical myelopathy (i.e., no evidence of competing neurological diagnosis) were recruited in the Balgrist University Hospital, Zurich, Switzerland between February 2018 and March 2019. We evaluated the relationship between the extent of structural damage within spinal nociceptive pathways (i.e., dorsal horn, spinothalamic tract, anterior commissure) assessed with atlas-based MRI , and 1) the functional integrity of spinal nociceptive pathways measured with contact heat-, cold-, and pinprick- evoked potentials and 2) clinical somatosensory phenotypes assessed with quantitative sensory testing. RESULTS: Sixteen individuals (mean age 61 years) with either degenerative (N=13) or post-traumatic (N=3) cervical myelopathy participated in the study. Most individuals presented with mild myelopathy (modified Japanese Orthopaedic Association score (mJOA)>15; N=13). 71% of individuals presented with structural damage within spinal nociceptive pathways on MRI. Yet, 50% of these individuals presented with complete functional sparing (i.e., normal contact heat-, cold-, and pinprick- evoked potentials). The extent of structural damage within spinal nociceptive pathways was neither associated with functional integrity of thermal (heat: p=0.57; cold: p=0.49) and mechano-nociceptive pathways (p=0.83) nor with the clinical somatosensory phenotype (heat: p=0.16; cold: p=0.37; mechanical: p=0.73). The amount of structural damage to the spinothalamic tract did not correlate with spinothalamic conduction velocity (p>0.05; rho=-0.11). CONCLUSIONS: Our findings provide neurophysiological evidence to substantiate that structural damage in the spinal cord does not equate to functional somatosensory deficits. This study recognizes the pronounced structure-function paradox in cervical myelopathies and underlines the inevitable need for a multi-modal phenotyping approach to reveal the eloquence of lesions within somatosensory pathways.

Minimally Invasive Treatment of Displaced Intra-Articular Calcaneal Fractures.

Minimally invasive surgical techniques are increasingly used for definitive treatment of displaced intra-articular calcaneal fractures. These approaches have been shown to minimize soft tissue injury, preserve blood supply, and decrease operative time. These methods can be applied to all calcaneal fractures and have particular advantages in patients with higher than usual risks to the soft tissues. The literature suggests that results of limited soft tissue dissection approaches provide equivalent outcomes to those obtained with the extensile lateral approach. We predict that as imaging and other techniques continue to improve, more calcaneal fractures will be treated by these appealing safer techniques.

Subsequent Pain or Injury After Foot and Ankle Surgery in Patients Receiving Workers' Compensation.

BACKGROUND: Workers' compensation (WC) has been associated with poor outcomes following a variety of injuries and surgeries, but rates of subsequent pain or injury (SPI) following surgery have not been studied. The purpose of this study was to investigate the rates, locations, and risk factors of SPI in WC patients and non-WC patients who underwent the same surgeries. METHODS: With institutional review board approval, records from foot or ankle surgery performed by author P.P. from 2009 to 2015 were obtained. A retrospective chart review was performed on all WC and non-WC patients with at least 1 Current Procedural Terminology code of interest. SPI was defined as a new injury at a different anatomical location occurring 2 months to 2 years after the index surgery. Chi-square and 2-tailed t tests were used to compare risk factors and rates of SPI in both groups. RESULTS: The WC population had higher rates of SPI than the non-WC population. Specifically, 13 of 56 WC patients (23.2%) vs 12 of 165 non-WC patients (7.3%) reported SPI (P = .001). The hip, knee, and contralateral foot and ankle were common areas of SPI in both groups. Legal representation and increased age were risk factors for SPI in the WC population. Specifically, 10 of 13 WC patients with SPI had legal representation vs 16 of 43 WC patients without SPI (P = .02). Female sex was a risk factor for SPI in the non-WC population. CONCLUSIONS: WC patients had higher rates of subsequent pain or injury than non-WC patients. Legal representation was a risk factor for SPI in the WC population. LEVEL OF EVIDENCE: Level III, comparative series.