Short-term Success in Treatment of an Acute Hematogenous Periprosthetic Hip Joint Infection with Debridement, Antibiotics, and Implant Retention.

Introduction: Periprosthetic joint infection (PJI) is an unfortunate but frequent complication following total hip arthroplasty, with an incidence of 1%. Debridement, antibiotics, and implant retention is a treatment option for acute hematogenous PJI, with success rates reported up to 70%. Here, we present a case demonstrating short-term success using this treatment approach in a 74-year-old medically infirm patient. Case Report: The patient - a 74-year-old male with well-functioning bilateral total hip arthroplasties performed 14 years prior - presented to a rural emergency department with an acute onset of right groin pain and dizziness. The patient was found to have sepsis, a right hip joint effusion, and periarticular abscesses on assessment. Synovial fluid aspiration from the right hip grew methicillin-sensitive Staphylococcus aureus. The patient was transferred to an outside hospital for limited debridement of the right hip joint, followed by transfer to our tertiary hospital. On arrival, consideration was given to performing an exchange arthroplasty. However, given the patient's medical frailty, it was felt that the risks were prohibitive, as supported by the presence of ileus, severe electrolyte imbalance, anemia requiring transfusion, anasarca, and vancomycin-resistant Enterococcus faecium infection of a sacral wound. The patient underwent surgery utilizing an established protocol of aggressive debridement and cleaning of the hip space, exchange of the modular arthroplasty components, and placement of antibiotic calcium sulfate beads for local delivery. The patient was treated with parenteral antibiotics followed by chronic oral antimicrobial suppression for 10 months after the final surgery. During treatment, the patient's inflammatory markers have normalized. The patient is ambulatory without assistive devices but uses an ankle orthosis due to a post-operative foot drop that did not resolve. The patient has regained satisfactory mobility with an Oxford hip score of 27. Conclusion: This case demonstrates short-term success in the treatment of acute hematogenous PJI in a medically infirm patient utilizing debridement, antibiotics, and implant retention and may serve to inform future patient counseling.

High-density cortical µECoG arrays concurrently track spreading depolarizations and long-term evolution of stroke in awake rats.

Spreading depolarizations (SDs) are widely recognized as a major contributor to the progression of tissue damage from ischemic stroke even if blood flow can be restored. They are characterized by negative intracortical waveforms of up to -20 mV, propagation velocities of 3 - 6 mm/min, and massive disturbance of membrane ion homeostasis. High-density, micro-electrocorticographic (µECoG) epidural electrodes and custom, DC-coupled, multiplexed amplifiers, were used to continuously characterize and monitor SD and µECoG cortical signal evolution in awake, moving rats over days. This highly innovative approach can define these events over a large brain surface area (~ 3.4 × 3.4 mm), extending across the boundaries of the stroke, and offers sufficient electrode density (60 contacts total per array for a density of 5.7 electrodes / mm2) to measure and determine the origin of SDs in relation to the infarct boundaries. In addition, spontaneous ECoG activity can simultaneously be detected to further define cortical infarct regions. This technology allows us to understand dynamic stroke evolution and provides immediate cortical functional activity over days. Further translational development of this approach may facilitate improved treatment options for acute stroke patients.

Epinephrine-induced Effects on Cerebral Microcirculation and Oxygenation Dynamics Using Multimodal Monitoring and Functional Photoacoustic Microscopy.

BACKGROUND: The administration of epinephrine after severe refractory hypotension, shock, or cardiac arrest restores systemic blood flow and major vessel perfusion but may worsen cerebral microvascular perfusion and oxygen delivery through vasoconstriction. The authors hypothesized that epinephrine induces significant microvascular constriction in the brain, with increased severity after repetitive dosing and in the aged brain, eventually leading to tissue hypoxia. METHODS: The authors investigated the effects of intravenous epinephrine administration in healthy young and aged C57Bl/6 mice on cerebral microvascular blood flow and oxygen delivery using multimodal in vivo imaging, including functional photoacoustic microscopy, brain tissue oxygen sensing, and follow-up histologic assessment. RESULTS: The authors report three main findings. First, after epinephrine administration, microvessels exhibited severe immediate vasoconstriction (57 ± 6% of baseline at 6 min, P < 0.0001, n = 6) that outlasted the concurrent increase in arterial blood pressure, while larger vessels demonstrated an initial increase in flow (108 ± 6% of baseline at 6 min, P = 0.02, n = 6). Second, oxyhemoglobin decreased significantly within cerebral vessels with a more pronounced effect in smaller vessels (microvessels to 69 ± 8% of baseline at 6 min, P < 0.0001, n = 6). Third, oxyhemoglobin desaturation did not indicate brain hypoxia; on the contrary, brain tissue oxygen increased after epinephrine application (from 31 ± 11 mmHg at baseline to 56 ± 12 mmHg, 80% increase, P = 0.01, n = 12). In the aged brains, microvascular constriction was less prominent yet slower to recover compared to young brains, but tissue oxygenation was increased, confirming relative hyperoxia. CONCLUSIONS: Intravenous application of epinephrine induced marked cerebral microvascular constriction, intravascular hemoglobin desaturation, and paradoxically, an increase in brain tissue oxygen levels, likely due to reduced transit time heterogeneity.

Detection of spreading depolarization events and spatiotemporal analysis for advancing stroke therapy.

While the presence of spreading depolarization (SD) and associated spreading depression have been well studied and known to be associated with post-ischemic brain damage, the spatiotemporal spread of these events from the site of injury is not well understood. With the recent development of high-density micro-electrocorticographic (ECoG) electrode arrays, monitoring the spread of the depolarizing events and associated depression is possible. The goal of this work is to define the electrocorticographic features of SD and associated depression across the multichannel array and search for patterns in these features that emerge across both space and time. We present the spatial distribution of features found from chronic ECoG recordings acquired from awake behaving rats induced with a rodent model of stroke. SD events were detected with an unsupervised algorithm that searched for a stereotyped pattern in the first derivative of the ECoG. The algorithm yielded a 58% correct detection rate on average across four rats, and a 36% false positive rate. We defined key electrophysiological features and mapped them onto the physical brain regions using MATLAB, such as the peak-to-peak amplitude of each SD event, the width (or duration) of the SD event, direct current (DC) level, and average rate of decline in the signal baseline. We performed k-means clustering to the activity in this feature space which yielded three contiguous regions in physical space. The elbow optimization method was applied to a distortion metric and indicated that 3 clusters was optimal. These findings motivate us to conduct future studies that would verify whether these 3 clusters in electrode-space correspond to immunohistochemically defined regions of tissue health, namely, infarct, penumbra, and healthy tissue. Clinical Relevance- The extent and severity of damage that stroke ultimately causes is suspected to be related to the progression of spreading depolarization and associated depression. An understanding of how the features of these electrophysiological events progress across the brain and over time is an important step toward eventual development of closed-loop therapies which limit and minimize the long-term effects of stroke.

Development and Evaluation of a Novel Mouse Model of Asphyxial Cardiac Arrest Revealed Severely Impaired Lymphopoiesis After Resuscitation.

Background Animal disease models represent the cornerstone in basic cardiac arrest (CA) research. However, current experimental models of CA and resuscitation in mice are limited. In this study, we aimed to develop a mouse model of asphyxial CA followed by cardiopulmonary resuscitation (CPR), and to characterize the immune response after asphyxial CA/CPR. Methods and Results CA was induced in mice by switching from an O2/N2 mixture to 100% N2 gas for mechanical ventilation under anesthesia. Real-time measurements of blood pressure, brain tissue oxygen, cerebral blood flow, and ECG confirmed asphyxia and ensuing CA. After a defined CA period, mice were resuscitated with intravenous epinephrine administration and chest compression. We subjected young adult and aged mice to this model, and found that after CA/CPR, mice from both groups exhibited significant neurologic deficits compared with sham mice. Analysis of post-CA brain confirmed neuroinflammation. Detailed characterization of the post-CA immune response in the peripheral organs of both young adult and aged mice revealed that at the subacute phase following asphyxial CA/CPR, the immune system was markedly suppressed as manifested by drastic atrophy of the spleen and thymus, and profound lymphopenia. Finally, our data showed that post-CA systemic lymphopenia was accompanied with impaired T and B lymphopoiesis in the thymus and bone marrow, respectively. Conclusions In this study, we established a novel validated asphyxial CA model in mice. Using this new model, we further demonstrated that asphyxial CA/CPR markedly affects both the nervous and immune systems, and notably impairs lymphopoiesis of T and B cells.

Does external fixator pin site distance from definitive implant affect infection rate in pilon fractures?

INTRODUCTION: Tibial pilon fractures are often treated with initial external fixation followed by delayed definitive fixation. It has been postulated that the external fixator pin site may correlate with infection risk. The purpose of this study was to determine whether external fixator pin-site distance from definitive implants impacts the risk of deep infection in pilon fractures. MATERIALS AND METHODS: A retrospective cohort study was completed at a single level 1 trauma center. All patients ages 15-65 who underwent open reduction and internal fixation (ORIF) of a distal tibial fracture (AO/OTA Classification 43) from 2007 to 2013 were included. The final study population was 133 patients. The impact of external fixation pin location (relative to the definitive implant location) on postoperative infection was measured. RESULTS: As a continuous variable, the distance between the closest pin site and plate was 62.1 ± 44.1 mm in the infected cohort and 62.2 ± 49.7 mm in the non-infected cohort (p = 0.991). Further analysis was performed by grouping the distances into less than 0 mm (i.e. overlapping), >0.0 - 25.0 mm, >25.0 - 50.0 mm, >50.0 - 75.0 mm, >75.0 - 100.0 mm, and >100.0 mm of separation. No significant differences were noted with regards to the risk for infection. CONCLUSIONS: Staged care has been shown to be an effective treatment strategy for AO/OTA type 43 fractures. There are many variables to consider when placing an external fixator construct. In this cohort, pin site distance from definitive implant location was not associated with an increase in deep infections. LEVEL OF EVIDENCE: Level III.

Understanding and Perception of Overlapping Surgery in an Orthopaedic Trauma Population: A Survey Study.

INTRODUCTION: Recently, overlapping surgery has received attention on the national scale. This study quantifies orthopaedic trauma patients' familiarity and concern with overlapping surgery as it relates to their care. METHODS: A 15-question survey was voluntarily completed by 200 orthopaedic trauma patients in the outpatient setting of a level I trauma center. Three domains were evaluated in the survey: demographic data, familiarity with overlapping surgery, and the degree of concern with overlapping surgery. Patients read a position statement explaining the practice of overlapping surgery, and their changes in level of concern were evaluated. Descriptive statistics were used to evaluate the data. RESULTS: A total of 200 patients completed the survey, of which 98 (49%) were male. The age range was broadly distributed. After surgery, 124 patients (62%) were seen for follow up. The remaining 76 patients (38%) did not undergo surgery. Regarding the practice of overlapping surgery, 116 respondents (58%) had no knowledge. There were 127 patients (63%) who reported their concern level as a 1 on an ordinal scale from 1 to 5, corresponding to the lowest possible level. Overall, 182 patients (91%) reported a level of concern of 3 (the median) or less with an average score of 1.7, indicating a low average level of concern. Six patients (3%) reported the maximum level of concern. On the whole, 160 patients (80%) reported either a decreased level of concern or no change after reading our department's position statement on overlapping surgery. Of the 124 patients, 81 (65%) postoperatively reported that they perceived no effect by overlapping surgery. The most common factors cited as areas of concern by patients were the absence of attending physician in the operating room (26%), risk of error by the resident (34%), and risk of a missed step in the surgical procedure (31%). CONCLUSION: These data indicate that most respondents had no previous knowledge of overlapping surgery and had a generally low level of concern with its use as practiced at our institution. Disclosing the use of overlapping surgery and its purpose to patients is an important component of preoperative counseling. LEVEL OF EVIDENCE: Level V.

Primary Total Knee Arthroplasty in Super-obese Patients: Dramatically Higher Postoperative Complication Rates Even Compared to Revision Surgery.

This study utilized a national database to evaluate 90 day postoperative complication rates after total knee arthroplasty (TKA) in super obese (BMI > 50 kg/m(2)) patients (n = 7666) compared to non-obese patients (n = 1,212,793), obese patients (n = 291,914), morbidly obese patients (n = 169,308) and revision TKA patients (n = 28,812). Super obese patients had significantly higher rates of local and systemic complications compared to all other BMI groups as well as those undergoing revision TKA with higher rates of venous thromboembolism (VTE), infection, and medical complications. Super obesity is associated with dramatically increased rates of postoperative complications after TKA compared to non-obese, obese, and morbidly obese patients as well as those undergoing revision TKA.

Arthroscopic suprapectoral and open subpectoral biceps tenodesis: a comparison of restoration of length-tension and mechanical strength between techniques.

PURPOSE: This study aimed to (1) evaluate the ex vivo restoration of the long head biceps length-tension for both arthroscopic suprapectoral biceps tenodesis (ASPBT) and open subpectoral biceps tenodesis (OSPBT) techniques and (2) assess how location in the proximal humerus affects pullout strength for tenodesis using an interference screw implant. METHODS: Eighteen matched cadaveric shoulders were randomized to OSPBT or ASPBT groups (9 each). Tenodesis was performed using clinical techniques. Preoperatively, a metallic bead was placed in the biceps tendon and a fluoroscopic image was obtained. Postoperatively, an image was obtained to evaluate the location of the tenodesis and the metallic bead and determine tensioning. Biomechanical load-to-failure testing was then performed. RESULTS: The ASPBT technique resulted in an average of 2.15 ± 0.62 cm of biceps overtensioning compared with 0.78 ± 0.35 cm (P < .001) in the OSPBT group. The average load to failure in the ASPBT group was 138.8 ± 29.1 N compared with 197 ± 38.6 N (P = .002) in the OSPBT group. Failure caused by implant pullout was significantly more frequent in the ASPBT group (7 of 9) than in the OSPBT group (1 of 9). CONCLUSIONS: The described ASPBT technique using an interference screw implant has the tendency to overtension the biceps and has a significantly decreased ultimate load to failure compared with an open subpectoral technique in matched cadaveric specimens. CLINICAL RELEVANCE: This study shows differences in the biomechanical properties of OSPBT and ASPBT. Modification of currently published ASPBT techniques may be necessary to improve restoration of the physiological length-tension relationship of the biceps. Clinical studies may need to clarify if the lower ultimate load to failure for the ASPBT technique is clinically significant.

Arthroscopic suprapectoral and open subpectoral biceps tenodesis: a comparison of minimum 2-year clinical outcomes.

BACKGROUND: While a vast body of literature exists describing biceps tenodesis techniques and evaluating the biomechanical aspects of tenodesis locations or various implants, little literature presents useful clinical outcomes to guide surgeons in their decision to perform a particular method of tenodesis. PURPOSE/HYPOTHESIS: To compare the clinical outcomes of open subpectoral biceps tenodesis (OSPBT) and arthroscopic suprapectoral biceps tenodesis (ASPBT). Our null hypothesis was that both methods would yield satisfactory results with regard to shoulder and biceps function, postoperative shoulder scores, pain relief, and complications. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients who underwent either ASPBT or OSPBT for isolated superior labrum or long head of the biceps lesions with a minimum follow-up of 2 years were evaluated with several validated clinical outcome measures and physical examinations including range of motion and strength. RESULTS: Between 2007 and 2011, a total of 82 patients met all inclusion and exclusion criteria, which included 32 patients with ASPBT and 50 patients with OSPBT; 27 of 32 (84.4%) patients with ASPBT and 35 of 50 (70.0%) patients with OSPBT completed clinical follow-up. Overall outcomes for both procedures were satisfactory. No significant differences were noted in postoperative Constant-Murley (ASPBT: 90.7; OSPBT: 91.8; P = .755), American Shoulder and Elbow Surgeons (ASPBT: 90.1; OSPBT: 88.4; P = .735), Single Assessment Numeric Evaluation (ASPBT: 87.4; OSPBT: 86.8; P = .901), Simple Shoulder Test (ASPBT: 10.4; OSPBT: 10.6; P = .762), long head of the biceps (ASPBT: 91.6; OSPBT: 93.6; P = .481), or Veterans RAND 36-Item Health Survey (ASPBT: 81.0; OSPBT: 80.1; P = .789) scores. No significant range of motion or strength differences was noted between the procedures. CONCLUSION: Both ASPBT and OSPBT yield excellent clinical and functional results for the management of isolated superior labrum or long head of the biceps lesions. No significant differences in clinical outcomes as determined by several validated outcome measures were found between the 2 tenodesis methods, nor were any significant range of motion or strength deficits noted at a minimum 2 years postoperatively.

Enhanced in vitro and in vivo cytotoxicity of umbilical cord blood cells against human breast cancer following activation with IL-15 and colony stimulating factors.

BACKGROUND: Cord blood mononuclear cells (MNC) are a rich source of precursor cytotoxic effector cells. Earlier we have shown that interleukin-2 (IL-2)-activated MNC from cord blood have significant cytotoxic activity against human leukemia and breast cancer cells in vitro and in vivo, compared to MNC from peripheral blood. MATERIALS AND METHODS: In order to further improve the antitumor cytotoxic ability of cord blood MNC, IL-2 was combined with IL-15 and colony stimulating factors GMCSF, G-CSF and M-CSF for the activation. The activated cells were examined for their cytotoxic effects in vitro against human breast cancer cell lines MDA-231, MDA453 and SKB43 and in vivo against MDA-231 grown in SCID mice. Phenotypes of these activated cells were determined using flow cytometry. The expression of immune response related genes in activated cells was measured using RT-PCR techniques. RESULTS: There was a significant increase in cytotoxicity of the effector cells activated with IL-2, IL-15 and some colony stimulating factors compared to cells activated with each of these cytokines alone or other combinations. Our results demonstrated the increase in cytotoxicity appears to be due to: 1) increase in CD56-positive cytotoxic cells; 2) cytokine/cytotoxic factors produced by the effector cells, such as Interferon-7 and Perforin; 3) stimulation by accessory cells, such as dendritic cells. In vivo administration of in vitro-activated cord blood cells into SCID mice bearing MDA-231 tumors reduced the number of metastases and increased survival compared to untreated tumor bearing controls. CONCLUSION: The combination of IL-2 with IL-15 and CSF is better for the activation of cord blood effector cells than to IL-2 alone.