Spinal Injuries in the Overhead Athlete.

PURPOSE OF REVIEW: Treatment of overhead athletes requires a systematic approach that will make an accurate diagnosis, deliver effective treatment, and make timely and safe return to sport. RECENT FINDINGS: New data has shown success rates and return to play effectiveness after different types of cervical and lumbar surgery. Cervical foraminotomy has been shown to have the highest rate and fastest return to play, but with the highest incidence of need for revision surgery. Cervical artificial disc replacement has shown promising results in the general population and is being done more commonly in elite athletes, but has an unknown risk for failure. Cervical fusion is a well-established and effective treatment, but has the longest healing time and risk for adjacent level pathology. In the lumbar spine, discectomy has a long and proven track record, fusion is rarely performed but can be effective, and artificial disc replacement is extremely rare in an elite athlete. An effective and comprehensive approach can diagnose, treat, and return overhead athletes to competitive play.

Data-Driven Dose-Volume Histogram Prediction.

PURPOSE: To evaluate dose-volume histogram (DVH) prediction from prior radiation therapy data. METHODS AND MATERIALS: An Oncospace radiation therapy database was constructed including images, structures, and dose distributions for patients with advanced lung cancer. DVH data was queried for total lungs, esophagus, heart, and external body contours. Each query returned DVH data for the N-most similar organs at risk (OARs) based on OAR-to-planning-target-volume (PTV) geometry via the overlap volume histogram (OVH). The DVHs for 5, 20, and 50 of the most similar OVHs were returned for each OAR for each patient. The OVH(0cm) is the relative volume of the OAR overlapping with the PTV, and the OVH(2cm) is the relative volume of the OAR 2 cm away from the PTV. The OVH(cm) and DVH(%) queried from the database were separated into interquartile ranges (IQRs), nonoutlier ranges (NORs) (equal to 3 × IQR), and the average database DVH (DVH-DB) computed from the NOR data. The ability to predict the clinically delivered DVH was evaluated based on percentiles and differences between the DVH-DB and the clinical DVH (DVH-CL) for a varying number of returned patient DVHs for a subset of patients. RESULTS: The ability to predict the clinically delivered DVH was excellent in the lungs and body; the IQR and NOR were <4% and <16%, respectively, in the lungs and <1% and <5%, respectively, in the body at all distances less than 2 cm from the PTV. For 21/23 patients considered, the differences in lung DVH-DB and DVH-CL were <4.6% and in 14/23 cases, <3%. In esophagus and heart, the ability to predict DVH-CL was weaker, with mean DVH differences >10% for 12/23 esophagi and 10/23 hearts. In esophagus and heart queries, the NOR was often 10% to 100% volume in dose ranges between 0% and 50% of prescription, independent of the number of patients queried. CONCLUSIONS: Using prior data to predict clinical dosimetry is increasingly of interest, but model- and data-driven methods have limitations if based on limited data sets. This study's results showed that prediction may be reasonable in organs containing tumors with known overlap, but for nonoverlapped OARs, planning preference and plan design may dominate the clinical dose.

Cervical Disc Herniations, Radiculopathy, and Myelopathy.

The key to successful treatment of elite athletes is optimizing the medical care at every step: injury prevention and sport-specific training; comprehensive history and physical examination; high-quality and complete diagnostic studies; accurate diagnosis; control and completion of rehabilitation program; minimally invasive, safe, and effective surgeries; risk assessment for return to sport; guided and gradual return to sport; and continued rehabilitation and exercise program after return to sport.

Asymptomatic Spinal Cord Compression: Is Surgery Necessary to Return to Play.

Advising athletes with asymptomatic cervical canal stenosis on their return to active play is a topic of considerable debate, with no definitive guidelines in place. Once cervical canal stenosis is identified, often through imaging following other injuries, it is difficult to predict the risk of future injury upon return to play in both contact and collision sports. Consequently, the decision can be a complicated one for the athlete, family, and physician alike. In this article, we identify radiographical and magnetic resonance imaging (MRI)-based criteria that may distinguish athletes "at-risk" for more severe consequences due to asymptomatic cervical canal stenosis from those who are safe to return to play. Using a Torg-Pavlov ratio <0.7 and MRI metrics, namely a minimal disc-level canal diameter <8 mm, a cord-to-canal area ratio >0.8, or space available for the cord <1.2 mm, can help when making these difficult decisions. Counseling can be a critical asset to patients with cervical stenosis who have had a previous episode of cervical cord neuropraxia, especially when they are involved in high-risk sports such as American football and rugby. We believe that while this remains an area of continued concern and controversy, improved MRI criteria will be a useful springboard for further studies, especially in the elite athlete population.

Evidence-Based Management of Spinal Conditions in the Elite Athlete.

Spinal injuries are common and are a significant burden in the professional athlete population. From single-level disk herniation to career-ending fractures, the consequences of these conditions vary widely. Both contact and noncontact injuries can substantially affect the health and performance of elite athletes competing in a variety of sports. The nature and severity of these injuries have great influence on the prospects for full recovery and successful return to play. Common spinal injuries, management decisions, and return to play prospects are important considerations in the professional athlete population.

The Management of Acute Lumbar Stress Reactions of the Pedicle and Pars in Professional Athletes Playing Collision Sports.

Acute stress reactions in the lumbar spine most commonly occur in athletes at the pars interarticularis followed by the pedicle. These reactions occur as a result of repetitive microtrauma from supraphysiological loads applied to the lumbar spine. Characteristic motions such as trunk extension and twisting are also thought to play a role and may be sport-specific. Other risk factors include increased lumbar lordosis, hamstring and thoracolumbar fascia tightness, and abdominal weakness. On physical examination, pain is typically reproduced with lumbar hyperextension. Currently, magnetic resonance imaging or nuclear imaging remain the most sensitive imaging modalities for identifying acute lesions. In the elite athlete, management of these conditions can be challenging, particularly in those playing collision sports such as American football, hockey, or rugby. Nonoperative treatment is the treatment of choice with rehabilitation programs focused on pain-free positioning and progressive strengthening. Operative treatment is rare, but may be warranted for patients symptomatic for >12 months. Specialized diagnosis protocols as well as treatment and return to play guidelines from 4 physicians treating elite athletes playing collision sports are presented and reviewed.

Updated Return-to-Play Recommendations for Collision Athletes After Cervical Spine Injury: A Modified Delphi Consensus Study With the Cervical Spine Research Society.

BACKGROUND: Previous studies have attempted to establish return-to-play (RTP) guidelines in collision sport athletes after cervical spine injury; however, recommendations have been limited by scant high-quality evidence and basic consensus survey methodologies. OBJECTIVE: To create relevant clinical statements regarding management in collision sport athletes after cervical spine injury, and establish consensus RTP recommendations. METHODS: Following the modified Delphi methodology, a 3 round survey study was conducted with spine surgeons from the Cervical Spine Research Society and National Football League team physicians in order to establish consensus guidelines and develop recommendations for cervical spine injury management in collision sport athletes. RESULTS: Our study showed strong consensus that asymptomatic athletes without increased magnetic resonance imaging (MRI) T2-signal changes following 1-/2- level anterior cervical discectomy and fusion (ACDF) may RTP, but not after 3-level ACDF (84.4%). Although allowed RTP after 1-/2-level ACDF was noted in various scenarios, the decision was contentious. No consensus RTP for collision athletes after 2-level ACDF was noted. Strong consensus was achieved for RTP in asymptomatic athletes without increased signal changes and spinal canal diameter >10 mm (90.5%), as well as those with resolved MRI signal changes and diameter >13 mm (81.3%). No consensus was achieved in RTP for cases with pseudarthrosis following ACDF. Strong consensus supported a screening MRI before sport participation in athletes with a history of cervical spine injury (78.9%). CONCLUSION: This study provides modified Delphi process consensus statements regarding cervical spine injury management in collision sport athletes from leading experts in spine surgery, sports injuries, and cervical trauma. Future research should aim to elucidate optimal timelines for RTP, as well as focus on prevention of injuries.

Return to Play After Anterior Cervical Discectomy and Fusion in Professional Athletes.

BACKGROUND: Data are limited on return to play after anterior cervical discectomy fusion (ACDF) in professional athletes. PURPOSE: To determine the rate and time of return to play among professional athletes after ACDF. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This study involved the prospective and retrospective review of patient charts and diagnostic studies as well as an internet search to collect data on a consecutive series of professional athletes who underwent cervical fusion by 1 of the 2 senior authors between 1982 and 2016. Demographic data included sport, preoperative symptoms and radiologic findings, date of surgery, level of surgery, postoperative symptoms and radiologic findings, and confounding factors (eg, other orthopaedic injuries). An internet search engine was used to determine date of return to play and length of career after surgery. RESULTS: A total of 27 ACDFs were performed on 26 professional athletes: 12 National Football League athletes, 5 National Hockey League athletes, 5 Major League Baseball athletes, 3 National Basketball Association athletes, and 1 Major League Soccer athlete. Twenty-six procedures (96.3%) showed clinical and radiographic evidence of fusion, and 20 of 25 eligible players returned to play (80%). At the conclusion of this study, 2 players were still in the rehabilitation phase and expected to return at the start of the next National Football League season. The mean time to return to play in a professional game was 9.5 months (range, 5.0-20.2 months). Of 15 players who returned to play but had retired by the time of this study, the mean career length after fusion was 3.2 years (range, 0.1-8.0 years). Clinical follow-up ranged from 1 to 96 months, with a mean of 22.1 months and mode of 11 months. CONCLUSION: After single-level ACDF, 80% of professional athletes were able to return to sport at approximately 9 months. The study findings will help athletes, physicians, and teams better predict outcome after ACDF surgery.

Non-union rate with stand-alone lateral lumbar interbody fusion.

Retrospective radiographic analysis.To determine the fusion rate of stand-alone lateral lumbar interbody fusion (LLIF). Biomechanical studies have indicated that LLIF may be more stable than anterior or transforaminal lumbar interbody fusion. Early clinical reports of stand-alone LLIF have shown success in obtaining fusion and indirectly decompressing nerve roots. A consecutive case series of stand-alone LLIF was analyzed with chart and radiographic review. Non-union was determined by symptomatology consistent with non-union and absence of bridging bone on the CT scan. Thirty-nine levels of stand alone LLIF were performed in 23 patients. Eleven patients received 1-level surgery, 7 patients received 2-level surgery, 3 patients received 3-level surgery, and 1 patient received 4-level surgery. Excluding 1 infected case, we analyzed 37 levels of stand alone LLIF in 22 patients. Non-union incidence was 7 levels in 6 patients. Non-union rate was 7/37 (19%) per level and 6/22 (27%) per patient. While our study population was relatively low, a non-union rate of 19% to 27% is concerning for modern spine surgery. Currently in our practice, we occasionally still perform stand-alone LLIF utilizing 22 mm wide grafts in low-demand levels in non-smoking and non-osteoporotic patients. However, in a majority of patients, we provide supplemental fixation: bilateral pedicle screws in most patients and unilateral pedicle screws or spinous process plates in some patients.

Transcription of the Streptococcus pyogenes hyaluronic acid capsule biosynthesis operon is regulated by previously unknown upstream elements.

The important human pathogen Streptococcus pyogenes (group A Streptococcus [GAS]) produces a hyaluronic acid (HA) capsule that plays critical roles in immune evasion. Previous studies showed that the hasABC operon encoding the capsule biosynthesis enzymes is under the control of a single promoter, P1, which is negatively regulated by the two-component regulatory system CovR/S. In this work, we characterize the sequence upstream of P1 and identify a novel regulatory region controlling transcription of the capsule biosynthesis operon in the M1 serotype strain MGAS2221. This region consists of a promoter, P2, which initiates transcription of a novel small RNA, HasS, an intrinsic transcriptional terminator that inefficiently terminates HasS, permitting read-through transcription of hasABC, and a putative promoter which lies upstream of P2. Electrophoretic mobility shift assays, quantitative reverse transcription-PCR, and transcriptional reporter data identified CovR as a negative regulator of P2. We found that the P1 and P2 promoters are completely repressed by CovR, and capsule expression is regulated by the putative promoter upstream of P2. Deletion of hasS or of the terminator eliminates CovR-binding sequences, relieving repression and increasing read-through, hasA transcription, and capsule production. Sequence analysis of 44 GAS genomes revealed a high level of polymorphism in the HasS sequence region. Most of the HasS variations were located in the terminator sequences, suggesting that this region is under strong selective pressure. We discovered that the terminator deletion mutant is highly resistant to neutrophil-mediated killing and is significantly more virulent in a mouse model of GAS invasive disease than the wild-type strain. Together, these results are consistent with the naturally occurring mutations in this region modulating GAS virulence.

Antibacterial activity of THAM Trisphenylguanide against methicillin-resistant Staphylococcus aureus.

This study investigated the potential antibacterial activity of three series of compounds synthesized from 12 linear and branched polyamines with 2-8 amino groups, which were substituted to produce the corresponding guanides, biguanides, or phenylguanides, against Acinetobacter baumannii, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Antibacterial activity was measured for each compound by determining the minimum inhibitory concentration against the bacteria, and the toxicity towards mammalian cells was determined. The most effective compound, THAM trisphenylguanide, was studied in time-to-kill and cytoplasmic leakage assays against methicillin-resistant Staphylococcus aureus (MRSA, USA300) in comparison to chlorhexidine. Preliminary toxicity and MRSA challenge studies in mice were also conducted on this compound. THAM trisphenylguanide showed significant antibacterial activity (MIC ∼1 mg/L) and selectivity against MRSA relative to all the other bacteria examined. In time-to-kill assays it showed increased antimicrobial activity against MRSA versus chlorhexidine. It induced leakage of cytoplasmic content at concentrations that did not reduce cell viability, suggesting the mechanism of action may involve membrane disruption. Using an intraperitoneal mouse model of invasive MRSA disease, THAM trisphenylguanide reduced bacterial burden locally and in deeper tissues. This study has identified a novel guanide compound with selective microbicidal activity against Staphylococcus aureus, including a methicillin-resistant (MRSA) strain.

The role of innate immunity in promoting SaeR/S-mediated virulence in Staphylococcus aureus.

The ability of Staphylococcus aureus to infect tissues is dependent on precise control of virulence through gene-regulatory systems. While the SaeR/S two-component system has been shown to be a major regulator of S. aureus virulence, the influence of the host environment on SaeR/S-regulated genes (saeR/S targets) remains incompletely defined. Using QuantiGene 2.0 transcriptional assays, we examined expression of genes with the SaeR binding site in USA300 exposed to human and mouse neutrophils and host-derived peptides and during subcutaneous skin infection. We found that only some of the saeR/S targets, as opposed to the entire SaeR/S virulon, were activated within 5 and 10 min of interacting with human neutrophils as well as α-defensin. Furthermore, mouse neutrophils promoted transcription of saeR/S targets despite lacking α-defensin, and the murine skin environment elicited a distinctive expression profile of saeR/S targets. These findings indicate that saeR/S-mediated transcription is unique to and dependent on specific host stimuli. By using isogenic USA300ΔsaeR/S and USA300Δagr knockout strains, we also determined that SaeR/S is the major regulator of virulence factors, while Agr, a quorum-sensing two-component system, has moderate influence on transcription of the saeR/S targets under the tested physiological conditions.

Sagittal alignment after lumbar interbody fusion: comparing anterior, lateral, and transforaminal approaches.

STUDY DESIGN: Retrospective radiographic analysis. OBJECTIVE: To determine which lumbar interbody technique is most effective for restoring lordosis, increasing disk height, and reducing spondylolisthesis. SUMMARY OF BACKGROUND DATA: Lumbar interbody fusions are performed in hopes of increasing fusion potential, correcting deformity, and indirectly decompressing nerve roots. No published study has directly compared anterior, lateral, and transforaminal lumber interbody fusions in terms of ability to restore lordosis, increase disk height, and reduce spondylolisthesis. MATERIALS AND METHODS: Lumbar interbody fusion techniques were retrospectively compared in terms of improvement of lordosis, disk height, and spondylolisthesis between preoperative and follow-up lateral radiographs. RESULTS: A total of 220 consecutive patients with 309 operative levels were compared by surgery type: anterior (184 levels), lateral (86 levels), and transforaminal (39 levels). Average follow-up was 19.2 months (range, 1-56 mo), with no statistical difference between the groups. Intragroup analysis showed that the anterior (4.5 degrees) and lateral (2.2 degrees) groups significantly improved lordosis from preoperative to follow-up, whereas the transforaminal (0.8 degrees) group did not. Intergroup analysis showed that the anterior group significantly improved lordosis more than both the lateral and transforaminal groups. The anterior (2.2 mm) and lateral (2.0 mm) groups both significantly improved disk height more than the transforaminal (0.5 mm) group. All 3 groups significantly reduced spondylolisthesis, with no difference between the groups. CONCLUSIONS: After lumbar interbody fusion, improvement of lordosis was significant for both the anterior and lateral groups, but not the transforaminal group. Intergroup analysis showed the anterior group had significantly improved lordosis compared to both the other groups. The anterior and lateral groups had significantly increased disk height compared to the transforaminal group. All the 3 groups significantly reduced spondylolisthesis, with no difference between the groups.

The SaeR/S two-component system induces interferon-gamma production in neutrophils during invasive Staphylococcus aureus infection.

Invasive Staphylococcus aureus (S. aureus) disease is associated with neutrophil activity and pro-inflammatory cytokine expression, including interferon-gamma (IFNγ). Using a mouse model of S. aureus peritonitis, we identify neutrophils as the predominant source of IFNγ and link this induction with the SaeR/S two-component gene regulatory system. Relative to wild-type (BALB/c) mice, IFNγ-deficient mice demonstrated increased bacterial clearance and reduced cellular cytotoxicity following intraperitoneal challenge with S. aureus. Interestingly, bacterial burden and cytotoxicity were similar in BALB/c and IFNγ-deficient mice when infected with an isogenic saeR/S mutant strain. These findings suggest saeR/S-mediated neutrophil-derived IFNγ diminishes innate antibacterial mechanisms against S. aureus.

Staphylococcus aureus nuclease is an SaeRS-dependent virulence factor.

Several prominent bacterial pathogens secrete nuclease (Nuc) enzymes that have an important role in combating the host immune response. Early studies of Staphylococcus aureus Nuc attributed its regulation to the agr quorum-sensing system. However, recent microarray data have indicated that nuc is under the control of the SaeRS two-component system, which is a major regulator of S. aureus virulence determinants. Here we report that the nuc gene is directly controlled by the SaeRS two-component system through reporter fusion, immunoblotting, Nuc activity measurements, promoter mapping, and binding studies, and additionally, we were unable identify a notable regulatory link to the agr system. The observed SaeRS-dependent regulation was conserved across a wide spectrum of representative S. aureus isolates. Moreover, with community-associated methicillin-resistant S. aureus (CA MRSA) in a mouse model of peritonitis, we observed in vivo expression of Nuc activity in an SaeRS-dependent manner and determined that Nuc is a virulence factor that is important for in vivo survival, confirming the enzyme's role as a contributor to invasive disease. Finally, natural polymorphisms were identified in the SaeRS proteins, one of which was linked to Nuc regulation in a CA MRSA USA300 endocarditis isolate. Altogether, our findings demonstrate that Nuc is an important S. aureus virulence factor and part of the SaeRS regulon.

Family practice enhancements for patients with severe mental illness.

Individuals with severe mental health disorders experience difficulty maneuvering the complexity encountered in primary care (PC). This study describes the impact of three components of primary care practice enhancements on: changes in missed appointments, changes in health outcomes, number of ER visits and hospitalization days, and perceptions of integrated care. Missed PC appointments: baseline to post practice enhancement changed from 42 to 11, statistically significant (p < .01). Changes in health outcomes: SF-12 scores had no significant change nor did ER utilization and hospitalization; however, outcomes are low-base rate and assessment period was short. Integration of care: liaison was most helpful in accessing and navigating PC, educating and reconciling medication lists. Behavioral health staff voiced relief regarding access and felt better informed. Strategies focusing on increasing communication, staff education, and reducing barriers to access and receipt of PC may improve integration and continuity of care.

Return-to-play outcomes after microscopic lumbar diskectomy in professional athletes.

BACKGROUND: It has been shown a microscopic lumbar diskectomy (MLD) is effective in getting professional athletes back to their sport after a herniated nucleus pulposus (HNP). There is a need for more information on the time it takes professional athletes to return after surgery. PURPOSE: To determine average time for return to play and success in returning to play for professional athletes undergoing MLD. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between 1996 and 2010, the senior authors treated 171 professional athletes for lumbar HNP. A retrospective review was performed using patient charts, operative reports, team medical records, and internet search. Eighty-five patients were treated with MLD, and 86 patients were treated nonoperatively. This study focused on the return to play of the operatively treated patients. Primary outcome measures were return rate and average return time, considering only patients whose sport is in season at specific postoperative time points. RESULTS: Of surgically treated patients, 89.3% returned to sport. The average time it took operative patients to return to their sport (return time) was 5.8 months. Progressive return data for surgically treated patients showed the percentage of athletes who returned increased from 50% at 3 months to 72% at 6 months to 77% at 9 months and 84% at 12 months. CONCLUSION: The chance a player returns to play after MLD is 50% at 3 months, 72% at 6 months, 77% at 9 months, and 84% at 12 months. The overall chance of returning to play at any point is 89%.

Alpha-toxin induces programmed cell death of human T cells, B cells, and monocytes during USA300 infection.

This investigation examines the influence of alpha-toxin (Hla) during USA300 infection of human leukocytes. Survival of an USA300 isogenic deletion mutant of hla (USA300Δhla) in human blood was comparable to the parental wild-type strain and polymorphonuclear leukocyte (PMN) plasma membrane permeability caused by USA300 did not require Hla. Flow cytometry analysis of peripheral blood mononuclear cells (PBMCs) following infection by USA300, USA300Δhla, and USA300Δhla transformed with a plasmid over-expressing Hla (USA300Δhla Comp) demonstrated this toxin plays a significant role inducing plasma membrane permeability of CD14(+), CD3(+), and CD19(+) PBMCs. Rapid plasma membrane permeability independent of Hla was observed for PMNs, CD14(+) and CD19(+) PBMCs following intoxication with USA300 supernatant while the majority of CD3(+) PBMC plasma membrane permeability induced by USA300 required Hla. Addition of recombinant Hla to USA300Δhla supernatant rescued CD3(+) and CD19(+) PBMC plasma membrane permeability generated by USA300 supernatant. An observed delay in plasma membrane permeability caused by Hla in conjunction with Annexin V binding and ApoBrdU Tunel assays examining PBMCs intoxicated with recombinant Hla or infected with USA300, USA300Δhla, USA300Δhla Comp, and USA300ΔsaeR/S suggest Hla induces programmed cell death of monocytes, B cells, and T cells that results in plasma membrane permeability. Together these findings underscore the importance of Hla during S. aureus infection of human tissue and specifically demonstrate Hla activity during USA300 infection triggers programmed cell death of human monocytes, T cells and B cells that leads to plasma membrane permeability.

The SaeR/S gene regulatory system induces a pro-inflammatory cytokine response during Staphylococcus aureus infection.

Community-associated methicillin-resistant Staphylococcus aureus accounts for a large portion of the increased staphylococcal disease incidence and can cause illness ranging from mild skin infections to rapidly fatal sepsis syndromes. Currently, we have limited understanding of S. aureus-derived mechanisms contributing to bacterial pathogenesis and host inflammation during staphylococcal disease. Herein, we characterize an influential role for the saeR/S two-component gene regulatory system in mediating cytokine induction using mouse models of S. aureus pathogenesis. Invasive S. aureus infection induced the production of localized and systemic pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin (IL)-6 and IL-2. In contrast, mice infected with an isogenic saeR/S deletion mutant demonstrated significantly reduced pro-inflammatory cytokine levels. Additionally, secreted factors influenced by saeR/S elicited pro-inflammatory cytokines in human blood ex vivo. Our study further demonstrated robust saeR/S-mediated IFN-γ production during both invasive and subcutaneous skin infections. Results also indicated a critical role for saeR/S in promoting bacterial survival and enhancing host mortality during S. aureus peritonitis. Taken together, this study provides insight into specific mechanisms used by S. aureus during staphylococcal disease and characterizes a relationship between a bacterial global regulator of virulence and the production of pro-inflammatory mediators.