The Effect of Commonly Used Local Anesthetic on Bacterial Growth.

INTRODUCTION: Liposomal bupivacaine (LB) has emerged as a superior form of local anesthetic across numerous surgical subspecialties. The purpose of this study is to evaluate the ex-vivo antimicrobial effects of LB in comparison with traditional local anesthetics. METHODS: A standardized inoculum of bacteria commonly associated with surgical site infection was inoculated into a suspension of 1% lidocaine, 0.25% bupivacaine, Exparel (proprietary liposomally packaged 1.3% bupivacaine), and normal saline as a growth control. RESULTS: In all five bacteria tested, the medium inoculated with traditional local anesthetics reduced growth to a greater degree than LB-inoculated plates. Both conventional local anesthetics reduced the growth of all bacteria when compared with the control with the exception of methicillin-susceptible Staphylococcus aureus growth in bupivacaine. LB-inoculated plates had equivalent growth to the control in all plates with the exception of Escherichia coli plates which demonstrated superior growth. CONCLUSIONS: The results of this simple ex-vivo model suggest that the liposomal packaging of bupivacaine may decrease this local anesthetic's innate antibacterial properties.

Range of Motion Adaptations in Powerlifters.

Gadomski, SJ, Ratamess, NA, and Cutrufello, PT. Range of motion adaptations in powerlifters. J Strength Cond Res 32(11): 3020-3028, 2018-The aim of this study was to investigate range of motion (ROM) and training patterns in powerlifters. Upper- and lower-extremity passive ROMs were assessed through goniometry in 15 male powerlifters (35.3 ± 13.7 years) and 15 age-matched controls (34.9 ± 14.6 years). The Apley scratch test and modified Thomas test were used to assess ROM across multiple joints. Training frequency, stretching frequency, and exercise selection were recorded using questionnaires. Passive glenohumeral (GH) extension, internal rotation, and external rotation ROM were significantly decreased in powerlifters (p < 0.050). Powerlifters displayed decreased ROM in the Apley scratch test in both dominant (p = 0.015) and nondominant (p = 0.025) arms. However, knee extension angle was markedly improved in powerlifters (20.3 ± 7.3°) compared with controls (29.9 ± 6.2°; p < 0.001). Bench press and bench press variations accounted for 74.8% of all upper-body exercises, whereas back squat and deadlift accounted for 79.7% of all lower-body exercises in powerlifters' training programs. To determine whether existing ROM adaptations were seen in elite powerlifters, the powerlifting cohort was split into 3 groups based on Wilks score: <400 (low), 400-500 (intermediate), and >500 (high). GH ROM limitations were more pronounced in elite powerlifters (Wilks >500), who had more powerlifting experience (p = 0.048) and greater lean body mass (p = 0.040). Overall, powerlifters displayed decreased GH ROM, but increased hamstring ROM, after training programs that were heavily focused on the bench press, back squat, and deadlift.

An Evaluation of Agonist: Antagonist Strength Ratios and Posture Among Powerlifters.

Cutrufello, PT, Gadomski, SJ, and Ratamess, NA. An evaluation of agonist:antagonist strength ratios and posture among powerlifters. J Strength Cond Res 31(2): 298-304, 2017-Powerlifters routinely focus on 3 exercises: bench press, squat, and deadlift. This focus may predispose them to the development of muscle imbalances in either the upper or lower extremity which might also influence posture. Therefore, the purpose of the present study was to examine the agonist:antagonist strength ratios and their relationship to postural measures among powerlifters. An ex post facto study design compared 15 male powerlifters (35.3 ± 13.7 years old) and 15 age-matched controls (34.9 ± 14.6 years old). Maximal isometric strength tests were conducted using handheld dynamometry. Posture was evaluated using pectoralis minor length, pelvic tilt, thoracic kyphosis, and lumbar lordosis. Strength imbalances were observed for shoulder horizontal adduction:abduction (2.57 ± 0.58 vs. 1.78 ± 0.28; p < 0.001) and knee flexion:extension (0.61 ± 0.15 vs. 0.50 ± 0.10; p = 0.033). Pectoralis minor length was significantly shorter among the powerlifters (6.1 ± 1.9 vs. 4.2 ± 1.4; p = 0.005); however, there was no statistical difference in thoracic kyphosis (37.7 ± 9.4 vs. 39.1 ± 10.9; p = 0.722), pelvic tilt (10.6 ± 3.6 vs. 11.3 ± 3.7; p = 0.622), or lumbar lordosis (25.0 ± 7.6 vs. 23.0 ± 8.4; p = 0.500) angles. Strength imbalances, including shoulder horizontal adduction:abduction and knee flexion:extension, and a shortened pectoralis minor may evolve as training adaptations among powerlifters, whereas thoracic kyphosis, pelvic tilt, and lumbar lordosis remain unchanged.

The effect of l-citrulline and watermelon juice supplementation on anaerobic and aerobic exercise performance.

Citrulline has been proposed as an ergogenic aid, leading to an interest in watermelon given its high citrulline concentration. The aim of this study was to determine the effects of a single, pre-exercise dose of l-citrulline, watermelon juice, or a placebo on the total maximum number of repetitions completed over 5 sets, time to exhaustion, maximal oxygen consumption (VO2max), anaerobic threshold, and flow-mediated vasodilation. A randomised double-blind within-participants study design was used to examine these effects among 22 participants (n = 11 males). Supplementation included either a 7.5% sucrose drink containing 6 g of l-citrulline, 710 mL of watermelon juice (~1.0 g citrulline), or a 7.5% sucrose placebo drink. Supplementation was administered 1 or 2 h before exercise testing to investigate a timing effect. There was no significant effect between the three supplements for the total number of repetitions, time to exhaustion, VO2max, anaerobic threshold, or flow-mediated vasodilation. There was also no interaction observed relative to gender or supplement timing (P > 0.05). A single dose of l-citrulline or watermelon juice as a pre-exercise supplement appears to be ineffective in improving exercise performance; however, greater doses of l-citrulline have been shown to be safe and are currently left unexamined.

Handoffs and transitions of care: A systematic review, meta-analysis, and practice management guideline from the Eastern Association for the Surgery of Trauma.

BACKGROUND: The Joint Commission reports that at least half of communication breakdowns occur during handovers or transitions of care. There is no consensus on how best to approach the transfer of care within acute care surgery (ACS). We conduct a systematic review and meta-analysis of the current data on handoffs and transitions of care in ACS patients and evaluate the impact of standardization and formalized communication processes. METHODS: Clinically relevant questions regarding handoffs and transitions of care with clearly defined patient Population(s), Intervention(s), Comparison(s), and appropriately selected Outcomes were determined. These centered around specific transitions of care within the setting of ACS, specifically perioperative interactions, emergency medical services and trauma team interactions, and intra/interfloor and intensive care unit (ICU) interactions. A systematic literature review and meta-analysis were conducted using the Grading of Recommendations Assessment, Development, and Evaluation methodology. RESULTS: A total of 10 studies were identified for analysis. These included 5,113 patients in the standardized handoff group and 5,293 in the current process group. Standardized handoffs reduced handover errors for perioperative interactions and preventable adverse events for intra/interfloor and ICU interactions. There were insufficient data to evaluate outcomes of clinical complications and medical errors. CONCLUSION: We conditionally recommend a standardized handoff in the field of ACS, including perioperative interactions, emergency medical services and trauma team interactions, and intra/interfloor and ICU interactions. LEVEL OF EVIDENCE: Systematic Review/Meta-analysis; Level III.

Time- and cell-specific activation of BMP signaling restrains chondrocyte hypertrophy.

Stem cell therapies for degenerative cartilage disease are limited by an incomplete understanding of hyaline cartilage formation and maintenance. Human bone marrow stromal cells/skeletal stem cells (hBMSCs/SSCs) produce stable hyaline cartilage when attached to hyaluronic acid-coated fibrin microbeads (HyA-FMBs), yet the mechanism remains unclear. In vitro, hBMSC/SSC/HyA-FMB organoids exhibited reduced BMP signaling early in chondrogenic differentiation, followed by restoration of BMP signaling in chondrogenic IGFBP5 + /MGP + cells. Subsequently, human-induced pluripotent stem cell (hiPSC)-derived sclerotome cells were established (BMP inhibition) and then treated with transforming growth factor ß (TGF-ß) -/+ BMP2 and growth differentiation factor 5 (GDF5) (BMP signaling activation). TGF-ß alone elicited a weak chondrogenic response, but TGF-ß/BMP2/GDF5 led to delamination of SOX9 + aggregates (chondrospheroids) with high expression of COL2A1, ACAN, and PRG4 and minimal expression of COL10A1 and ALP in vitro. While transplanted hBMSCs/SSCs/HyA-FMBs did not heal articular cartilage defects in immunocompromised rodents, chondrospheroid-derived cells/HyA-FMBs formed non-hypertrophic cartilage that persisted until at least 5 months in vivo.

Inhibitor of DNA binding proteins revealed as orchestrators of steady state, stress and malignant hematopoiesis.

Adult mammalian hematopoiesis is a dynamic cellular process that provides a continuous supply of myeloid, lymphoid, erythroid/megakaryocyte cells for host survival. This process is sustained by regulating hematopoietic stem cells (HSCs) quiescence, proliferation and activation under homeostasis and stress, and regulating the proliferation and differentiation of downstream multipotent progenitor (MPP) and more committed progenitor cells. Inhibitor of DNA binding (ID) proteins are small helix-loop-helix (HLH) proteins that lack a basic (b) DNA binding domain present in other family members, and function as dominant-negative regulators of other bHLH proteins (E proteins) by inhibiting their transcriptional activity. ID proteins are required for normal T cell, B cell, NK and innate lymphoid cells, dendritic cell, and myeloid cell differentiation and development. However, recent evidence suggests that ID proteins are important regulators of normal and leukemic hematopoietic stem and progenitor cells (HSPCs). This chapter will review our current understanding of the function of ID proteins in HSPC development and highlight future areas of scientific investigation.

Cholinergic signals preserve haematopoietic stem cell quiescence during regenerative haematopoiesis.

The sympathetic nervous system has been evolutionary selected to respond to stress and activates haematopoietic stem cells via noradrenergic signals. However, the pathways preserving haematopoietic stem cell quiescence and maintenance under proliferative stress remain largely unknown. Here we found that cholinergic signals preserve haematopoietic stem cell quiescence in bone-associated (endosteal) bone marrow niches. Bone marrow cholinergic neural signals increase during stress haematopoiesis and are amplified through cholinergic osteoprogenitors. Lack of cholinergic innervation impairs balanced responses to chemotherapy or irradiation and reduces haematopoietic stem cell quiescence and self-renewal. Cholinergic signals activate α7 nicotinic receptor in bone marrow mesenchymal stromal cells leading to increased CXCL12 expression and haematopoietic stem cell quiescence. Consequently, nicotine exposure increases endosteal haematopoietic stem cell quiescence in vivo and impairs hematopoietic regeneration after haematopoietic stem cell transplantation in mice. In humans, smoking history is associated with delayed normalisation of platelet counts after allogeneic haematopoietic stem cell transplantation. These results suggest that cholinergic signals preserve stem cell quiescence under proliferative stress.

Direct to OR resuscitation of abdominal trauma: An NTDB propensity matched outcomes study.

BACKGROUND: Direct to operating room resuscitation (DOR) is used by some trauma centers for severely injured trauma patients as an approach to minimize time to hemorrhage control. It is unknown whether this strategy results in favorable outcomes. We hypothesized that utilization of an emergency department operating room (EDOR) for resuscitation of patients with abdominal trauma at an urban Level I trauma center would be associated with decreased time to laparotomy and improved outcomes. METHODS: We included patients 15 years or older with abdominal trauma who underwent emergent laparotomy within 120 minutes of arrival both at our institution and within a National Trauma Data Bank sample between 2007 to 2019 and 2013 to 2016, respectively. Our institutional sample was matched 1:1 to an American College of Surgeons National Trauma Databank sample using propensity score matching based on age, sex, mechanism of injury, and abdominal Abbreviated Injury Scale score. The primary outcome was time to laparotomy incision. Secondary outcomes included blood transfusion requirement, intensive care unit (ICU) length of stay (LOS), ventilator days, hospital LOS, and in-hospital mortality. RESULTS: Two hundred forty patients were included (120 institutional, 120 national). Both samples were well balanced, and 83.3% sustained penetrating trauma. There were 84.2% young adults between the ages of 15 and 47, 91.7% were male, 47.5% Black/African American, with a median Injury Severity Score of 14 (interquartile range [IQR], 8-29), Glasgow Coma Scale score of 15 (IQR, 13-15), 71.7% had an systolic blood pressure of >90 mm Hg, and had a shock index of 0.9 (IQR, 0.7-1.1) which did not differ between groups (p > 0.05). Treatment in the EDOR was associated with decreased time to incision (25.5 minutes vs. 40 minutes; p ≤ 0.001), ICU LOS (1 vs. 3.1 days; p < 0.001), transfusion requirement within 24 hours (3 units vs. 5.8 units packed red blood cells; p = 0.025), hospital LOS (5 days vs. 8.5 days, p = 0.014), and ventilator days (1 day vs. 2 days; p ≤ 0.001). There were no significant differences in in-hospital mortality (22.5% vs. 15.0%; p = 0.14) or outcome-free days (4.9 days vs. 4.5 days, p = 0.55). CONCLUSION: The use of an EDOR is associated with decreased time to hemorrhage control as evidenced by the decreased time to incision, blood transfusion requirement, ICU LOS, hospital LOS, and ventilator days. These findings support DOR for patients sustaining operative abdominal trauma. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level III.

A cholinergic neuroskeletal interface promotes bone formation during postnatal growth and exercise.

The autonomic nervous system is a master regulator of homeostatic processes and stress responses. Sympathetic noradrenergic nerve fibers decrease bone mass, but the role of cholinergic signaling in bone has remained largely unknown. Here, we describe that early postnatally, a subset of sympathetic nerve fibers undergoes an interleukin-6 (IL-6)-induced cholinergic switch upon contacting the bone. A neurotrophic dependency mediated through GDNF-family receptor-α2 (GFRα2) and its ligand, neurturin (NRTN), is established between sympathetic cholinergic fibers and bone-embedded osteocytes, which require cholinergic innervation for their survival and connectivity. Bone-lining osteoprogenitors amplify and propagate cholinergic signals in the bone marrow (BM). Moderate exercise augments trabecular bone partly through an IL-6-dependent expansion of sympathetic cholinergic nerve fibers. Consequently, loss of cholinergic skeletal innervation reduces osteocyte survival and function, causing osteopenia and impaired skeletal adaptation to moderate exercise. These results uncover a cholinergic neuro-osteocyte interface that regulates skeletogenesis and skeletal turnover through bone-anabolic effects.

Id1 and Id3 Maintain Steady-State Hematopoiesis by Promoting Sinusoidal Endothelial Cell Survival and Regeneration.

Investigating mechanisms that regulate endothelial cell (EC) growth and survival is important for understanding EC homeostasis and how ECs maintain stem cell niches. We report here that targeted loss of Id genes in adult ECs results in dilated, leaky sinusoids and a pro-inflammatory state that increases in severity over time. Disruption in sinusoidal integrity leads to increased hematopoietic stem cell (HSC) proliferation, differentiation, migration, and exhaustion. Mechanistically, sinusoidal ECs (SECs) show increased apoptosis because of reduced Bcl2-family gene expression following Id gene ablation. Furthermore, Id1-/-Id3-/- SECs and upstream type H vessels show increased expression of cyclin-dependent kinase inhibitors p21 and p27 and impaired ability to proliferate, which is rescued by reducing E2-2 expression. Id1-/-Id3-/- mice do not survive sublethal irradiation because of impaired vessel regeneration and hematopoietic failure. Thus, Id genes are required for the survival and regeneration of BM SECs during homeostasis and stress to maintain HSC development.

Geriatric patients on antithrombotic therapy as a criterion for trauma team activation leads to over triage.

BACKGROUND: Our institution amended its trauma activation criteria to require a Level II activation for patients ≥65 years old on antithrombotic medication presenting with suspected head trauma. METHODS: Our institutional trauma registry was queried for geriatric patients on antithrombotic medication in the year before and after this criteria change. Demographics, presentation metrics, level of activation, and outcomes were compared between groups. RESULTS: After policy change, a greater proportion of patients received a trauma activation (19.9 vs. 74.9%, P < 0.001) and a greater proportion of these patients were discharged directly home without injury (4.3 vs. 44%, P < 0.001). However, a smaller proportion of patients with a critical Emergency Department disposition or traumatic intracranial hemorrhage failed to receive a trauma activation (65.1 vs. 23.5%, P < 0.001; 70.7% vs. 27.3%, P < 0.001). There was no change in mortality (4.3 vs. 2.0%, P = 0.21). CONCLUSIONS: Implementing new criteria increased overtriage, decreased undertriage, and had little effect on mortality.

Id1 Ablation Protects Hematopoietic Stem Cells from Stress-Induced Exhaustion and Aging.

Defining mechanisms that maintain tissue stem cells during homeostasis, stress, and aging is important for improving tissue regeneration and repair and enhancing cancer therapies. Here, we show that Id1 is induced in hematopoietic stem cells (HSCs) by cytokines that promote HSC proliferation and differentiation, suggesting that it functions in stress hematopoiesis. Genetic ablation of Id1 increases HSC self-renewal in serial bone marrow transplantation (BMT) assays, correlating with decreases in HSC proliferation, mitochondrial biogenesis, and reactive oxygen species (ROS) production. Id1-/- HSCs have a quiescent molecular signature and harbor less DNA damage than control HSCs. Cytokines produced in the hematopoietic microenvironment after γ-irradiation induce Id1 expression. Id1-/- HSCs display a blunted proliferative response to such cytokines and other inducers of chronic proliferation including genotoxic and inflammatory stress and aging, protecting them from chronic stress and exhaustion. Thus, targeting Id1 may be therapeutically useful for improving HSC survival and function during BMT, chronic stress, and aging.

Independent Preoperative Predictors of Prolonged Length of Stay after Laparoscopic Appendectomy in Patients Over 30 Years of Age: Experience from a Single Institution.

Prompt discharge after laparoscopic appendectomy (LA) is a marker of quality of care, fiscally desirable and feasible in select patients. Patients over 30 comprise a more heterogeneous cohort known to experience worse outcomes after LA. We aimed to identify easily available preoperative risk factors portending a postoperative length of stay ≥2 days among patients above age 30. In this investigation, 296 included patients from a single institution who underwent LA for acute appendicitis from 2010 to 2014 were retrospectively reviewed for preoperative demographics, laboratory studies, comorbidities, presentation characteristics, radiographic finding, and other rationally selected factors for association with postoperative length of stay ≥2 days. Bivariate and multivariate analysis was conducted to determine independent risk factors, which were subsequently modeled via receiver-operating characteristic curve generation and Kaplan-Meier analysis. "Classic" presentation [odds ratio (OR) = 0.5, P = .02], elevated red cell distribution width (RDW; OR = 1.5/% increase, P = 0.004) as well as evidence of rupture on CT (OR = 6.9, P < 0.001) were independently associated with postoperative length of stay ≥ 2 days. Modeling length of stay using these factors generated an area under the curve of 0.713 ± 0.037. Kaplan-Meier analysis of "classic" presentation, elevated RDW, and evidence of rupture on CT through the fifth postoperative day generated log-rank P values of 0.02, 0.05, and ≤ 0.001, respectively. In summary, lack of "classic" presentation, elevated RDW, and CT evidence of rupture are novel risk factors for prolonged postoperative length of stay in LA patients over 30. These findings may help target patients most appropriate for prompt discharge.

The influence of VKORC1 and CYP2C9 mutations on warfarin response after total hip and knee arthroplasty.

AIMS: This study characterizes the influence of genotype at two loci on warfarin response after arthroplasty. METHODS: 121 postarthroplasty patients given warfarin thromboprophylaxis were reviewed for international normalized ratio (INR) values on the first three days postoperatively. Significant differences among genotypes in INR values on each of the first three postoperative days were assessed. RESULTS: Wild-type patients at both loci (∼23% of patients) had yet to reach therapeutic INR (1.5-2.0) by postoperative day three more frequently than those with a mutation conferring hyper-responsiveness (61% vs. 30%; P ≤ .01). CONCLUSIONS: Wild-type patients are not anticoagulated in a sufficiently prompt manner after arthroplasty.

Utility of Postoperative Radiographs for Pediatric Scoliosis: Association Between History and Physical Examination Findings and Radiographic Findings.

BACKGROUND: Postoperative radiographs are routinely obtained following surgery for the correction of scoliosis in pediatric patients. The purpose of this study was to comprehensively evaluate the utility of obtaining routine postoperative radiographs in the management of these patients. METHODS: A total of 1969 clinic notes and corresponding radiographs regarding 451 consecutive patients with scoliosis (age range, ten to eighteen years) who had surgical correction over a ten-year period at a single institution were retrospectively reviewed. Curve etiology, preoperative curve characteristics, and surgical procedures performed were recorded. All postoperative clinic notes and radiographs were reviewed for abnormalities and changes in treatment course. It was then determined whether clinical signs and symptoms and/or abnormal radiographic findings led to a change in treatment course, which was defined as a therapeutic intervention or further diagnostic testing. RESULTS: Of the 451 patients in this study (average age [and standard deviation], 14.7 ± 2.4 years), 72.5% had adolescent idiopathic scoliosis, 23.3% had neuromuscular scoliosis, and 4.2% had other underlying causes of scoliosis. A change in treatment course occurred in the cases of forty-two patients, all of whom had symptomatic findings on postoperative history and physical examination and only fifteen of whom had supportive abnormal findings on postoperative radiographs. Curve etiology and surgical procedures performed had no impact on radiographic utility. A significant increase in utility was seen for radiographs obtained at visits one year or more following surgery compared with those obtained at visits less than one year following surgery (1.7% compared with 0.3%, p = 0.001). The overall sensitivity, specificity, positive predictive value, and negative predictive value of routine postoperative radiographs in guiding treatment course were 35.7%, 98.1%, 28.8%, and 98.6%, respectively. CONCLUSIONS: Routine radiographs provide low utility in guiding the course of treatment for asymptomatic pediatric patients following surgery for scoliosis. The results of this study suggest that patient or caregiver complaints, comorbidities, and clinical suspicion should be considered before obtaining radiographs at postoperative visits in order to minimize radiation exposure in pediatric patients and reduce medical costs without compromising care. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Utility of postoperative radiographs for cervical spine fusion: a comprehensive evaluation of operative technique, surgical indication, and duration since surgery.

STUDY DESIGN: A retrospective study. OBJECTIVE: To assess the utility of postoperative radiographs in patients across a spectrum of cervical fusion procedures, surgical indication, and time since surgery. SUMMARY OF BACKGROUND DATA: Postoperative radiographs are routinely obtained after cervical spine fusion despite lack of evidence supporting such practice. Studies assessing postoperative radiographical utility in the cervical spine have been limited. To date, no study has comprehensively evaluated the utility of obtaining such radiographs across multiple cervical fusion procedures. METHODS: A total of 972 clinic notes from 301 patients during a 10-year period at a single institution were retrospectively reviewed. Patients in this study underwent an anterior cervical discectomy and fusion, anterior corpectomy and fusion, a combined anterior cervical discectomy and fusion and anterior corpectomy and fusion (hybrid), posterior spine fusion, or 360° fusion. All postoperative clinic notes and radiographs were reviewed for abnormalities and changes in treatment course. It was determined whether an abnormal radiograph alone led to a change in treatment course among the various operative techniques, surgical indication, or time since surgery. RESULTS: No statistical significant difference in radiograph utility between anterior cervical discectomy and fusion (0 changes in treatment course due to radiograph alone out of 332 clinic notes), anterior corpectomy and fusion (0 of 140), hybrid procedure (1 of 72), posterior spine fusion (5 of 357), and 360° fusion (0 of 71) was found. Surgical indication (trauma vs. degeneration) and duration from surgery yielded no statistical significant difference in radiograph utility. The overall sensitivity, specificity, and positive and negative predictive values of radiographs were 33.8%, 87.6%, 19.0%, and 93.9%, respectively. CONCLUSION: Regardless of operative techniques performed, surgical indication, and time since surgery, routine postoperative radiographs provide low utility in guiding treatment course in asymptomatic patients. Although radiographs may provide important diagnostic utility in certain individual cases, the results of this study provide further evidence that radiographs should not be considered routine during postoperative visits, thus minimizing unnecessary radiation exposure and medical costs.