Balancing Antibiotic Perfusion and Tourniquet Usage

Antibiotics are an integral part of infection prophylaxis in orthopaedic surgery, and tourniquets are widely used during many of those same surgeries. The timing of antibiotic administration in relation to tourniquet use has long been debated. Hanberg et al. explore this “balancing act” in the November 4, 2020 issue of The Journal in a carefully performed animal study.

The researchers anesthetized 24 female pigs and surgically exposed both of their hind calcanei. They then placed microdialysis catheters through drill holes in each calcaneus and also into the subcutaneous adipose tissue in the hind feet. Tourniquets were applied to one hind leg on each animal, and each pig was then randomized into 1 of 3 groups, based on when the animal received 1.5 gm of cefuroxime intravenously:

  • Group A –15 minutes prior to tourniquet inflation
  • Group B – 45 minutes prior to tourniquet inflation
  • Group C – At the time of tourniquet release

Hanberg et al. inflated the tourniquets for 90 minutes in all 3 groups, and then they measured the concentrations of cefuroxime and ischemic markers at regular intervals between the time of tourniquet inflation and up to 480 minutes afterward.

The authors found that in both Groups A and B, cefuroxime concentrations were maintained above the minimum inhibitory concentration (MIC) for Staphylococcus aureus in cancellous bone and adipose tissue throughout the 90 minutes of tourniquet inflation. In addition, injecting cefuroxime at the time of tourniquet deflation (Group C) kept the tissue-antibiotic levels above the MIC on the tourniquet side for 3.5 hours after tourniquet release.

There were no differences in the time above MIC in bone or adipose tissue between the 3 groups, but the researchers noted a trend toward shorter time above MIC in bone in Group A vs. Group C (p=0.08). There was also a tendency toward higher time above MIC in bone on the tourniquet side compared to no-tourniquet side in Group B (p=0.08) and Group C (p=0.06). The researchers also found that, in all the animals, tissue ischemia persisted for 2.5 hours after tourniquet deflation in bone, while the adipose tissue recovered immediately.

This animal study provides useful data and prompts us to ponder ideas for further investigation regarding the interplay between tourniquets and antibiotic perfusion. For example, I think the prolonged ischemia in cancellous bone is a topic that warrants further investigation, and I am also curious whether adding antibiotics at the time of tourniquet release might help combat the potentially negative effects of that ischemia.

Matthew R. Schmitz, MD
JBJS Deputy Editor for Social Media

Seeking Molecular Signatures of Ectopic Bone Formation

OrthoBuzz occasionally receives posts from guest bloggers. This guest post comes from Impact Science, in response to an article in the November 4, 2020 JBJS.

Among military personnel who sustain blast-related injuries, physicians have observed a dramatic increase in the incidence of heterotopic ossification (HO), a pathology in which bone grows abnormally within soft tissues. This condition is frequently observed in association with burns and nonmilitary orthopaedic trauma, and combat-related HO is now occurring at an exceptionally high frequency of approximately 60%.

HO can range from an asymptomatic, incidental finding to a debilitating condition causing chronic pain and impaired movement. Although symptomatic HO is usually treated with surgical excision, identifying HO early in its development could go a long way toward improving quality of life for those with combat injuries.

Previous studies have suggested that certain microRNAs (miRNAs) play an important role in the formation of post-traumatic HO. A group of US researchers recently hypothesized that specific miRNA “signatures” might be present in the tissues of military personnel soon after a blast injury.

The authors collected 10 tissue samples from injured servicemembers during the surgical debridement of their wounds, about 8 days after the initial injuries occurred. The miRNA profiling of the samples, performed using a real-time polymerase chain reaction array, revealed that the tissues from patients who developed HO had upregulated levels of 6 miRNAs previously thought to take part in various bone-formation processes. Moreover, when some of those miRNAs were introduced into cultures of mesenchymal progenitor cells, the researchers found that 2 specific miRNAs (miR-1 and miR-206) were the most robust osteogenic “enhancers.” Interestingly, those same 2 miRNAs were found to target the downstream transcription factor SOX9, a deficiency of which can lead to a skeletal malformation syndrome.

These findings show that there are indeed early molecular signatures in the tissues of patients whose injuries progress to HO. While these novel insights into the molecular mechanisms underlying the development of HO may open doors to new therapeutic possibilities, Takamitsu Maruyama, PhD, in a commentary on the findings, cautions that modulating miR-1 and miR-206 “could affect not only HO formation but also the bone-healing process.”

Impact Science is a team of highly specialized subject-area experts (Life Sciences, Physical Sciences, Medicine & Humanities) who collaborate with authors, societies, libraries, universities, and various other stakeholders for services to enhance research impact. Through research engagement and science communication, Impact Science aims at democratizing science by making research-backed content accessible to the world.

Elite Reviewer Spotlight: Brian Werner

JBJS is pleased once again to highlight our Elite Reviewers. The Elite Reviewers Program recognizes our best reviewers for their outstanding efforts. All JBJS reviewers help us maintain the highest standards for quality orthopaedic publishing.

Name:

Brian C. Werner, MD

Affiliation:

 University of Virginia, Charlottesville, VA, USA

Years in practice: 5

How did you begin reviewing for other journals and for JBJS in particular?

I perform a lot of research and felt that reviewing for journals would be a good way to give back to the journals and other researchers who review for me and stay abreast of the newest research in orthopaedics.  I was invited to give my first review for JBJS by Dr. Robert Marx, one of my fellowship mentors.

What is your top piece of advice for those reviewers who aspire to reach Elite status?

Treat each manuscript you review as an opportunity to learn about new research in orthopaedics and give constructive feedback that will help the authors, even if it does not ultimately end up being published in JBJS.  Also understand the importance of timely feedback – I make sure to do my initial review of every manuscript within a day or two of receiving the invite.

Aside from orthopaedic manuscripts, what have you been reading lately?

Born to Run

Learn more about the JBJS Elite Reviewers program.

History Counts–And It Needs to Be Complete

Joel L. Boyd, MD

It has often been shown that those who do not study history are doomed to repeat its mistakes. The Journal of Bone & Joint Surgery has a >130-year history, which we must continue to review. Understanding our history is so important that JBJS staff and trustees have invested in a 6-month project to get our history encapsulated and published on our website for continuous reference and reflection. The history of our journal contains mistakes—one stark example of which is promulgating the use of metal-on-metal arthroplasty.

But history is not complete until all the stories are told. Incomplete history is particularly evident with our North American native populations and individuals of African heritage. Here history is recorded with formerly conscious and now primarily unconscious (I hope) bias against accurately detailing the important contributions of native and Black citizens.

In the November 4, 2020 issue of The Journal, Dr. Joel Boyd does us great service by setting the record straight regarding the contributions of Black Canadians and Americans to the sport of ice hockey. (Our collective history in orthopaedics has particular relevance in sports.) Black athletes were on the ice at the sport’s very inception and in the early formation of competitive leagues. Dr. Boyd’s history, which focuses on the Black Hockey League of the Maritimes and  Willie O’Ree, the “Jackie Robinson of hockey,” is replete with bias against acknowledging these contributions and against allowing non-Whites to compete for the sport’s highest trophies.

Let us all study these contributions, recognize their importance, and vow to be ever-vigilant for any bias, conscious or unconscious, in our thinking and conduct. May Dr. Boyd’s important exercise in completing this bit of history repeat itself in sport, science, and medicine across the board.

Marc Swiontkowski, MD
JBJS Editor-in-Chief

Elite Reviewer Spotlight: Paul Levin

JBJS is pleased once again to highlight our Elite Reviewers. The Elite Reviewers Program recognizes our best reviewers for their outstanding efforts. All JBJS reviewers help us maintain the highest standards for quality orthopaedic publishing.

Name:

Paul Levin

Affiliation:

 Montefiore Medical Center/Albert Einstein College of Medicine

Bronx, NY

Years in practice: 34

How did you begin reviewing for other journals and for JBJS in particular?

It is difficult to recall how I became involved. I believe that I received a letter inquiring if I had an interest in reviewing manuscripts. I thought it was a great opportunity to be able to participate in a process which is critical in introducing clinical and basic scientific research to allow practicing orthopaedic surgeons to remain up to date in their patient care.

What is your top piece of advice for those reviewers who aspire to reach Elite status?

Critically analyze every assertion and statement made in the entire manuscript and be prepared to consult the original reference when an assertion seems overarching or unlikely substantiated. Be wary of the conclusion of “trend or trending”. If the investigation failed to demonstrate a statistically significant finding this should be stated, and possible further investigation is warranted.

Aside from orthopaedic manuscripts, what have you been reading lately?

  • The Hastings Center Report: Excellent source of bioethical analysis of a gamut of current challenges in caring for individuals and the public
  • Sapiens: A Brief History of Humankind; Yuval Harari
  • 21 Lessons for the 21st Century; Yuval Harari
  • Thinking, Fast and Slow; Daniel Kahneman

Learn more about the JBJS Elite Reviewers program.

Elite Reviewer Spotlight: Edward Schwarz

JBJS is pleased once again to highlight our Elite Reviewers. The Elite Reviewers Program recognizes our best reviewers for their outstanding efforts. All JBJS reviewers help us maintain the highest standards for quality orthopaedic publishing.

Name:

Edward M. Schwarz, Ph.D.

Affiliation:

University of Rochester, Rochester, NY, USA

Years in practice: 23

How did you begin reviewing for other journals and for JBJS in particular?

I have published over 300 peer reviewed articles.  I published my first JBJS paper in 2001.  I started reviewing papers for many journals, including JBJS, shortly after that.

What is your top piece of advice for those reviewers who aspire to reach Elite status?

If you publish peer reviewed articles, have research grants, and/or are a member of AAOS, you have an obligation to review JBJS papers in your field.  If you are a thought leader in your field, you are obligated to reach Elite status.

Aside from orthopaedic manuscripts, what have you been reading lately?

I am an expert in the fields of Orthopaedics, Immunology, Bone Biology and Rheumatology, and try to stay current with JBJS, CORR, JOR, A&R, AR&T and JBMR.  For leisure I read biographies and Wine Spectator.

Learn more about the JBJS Elite Reviewers program.

What’s New in Shoulder and Elbow Surgery 2020

Every month, JBJS publishes a review of the most pertinent and impactful studies published in the orthopaedic literature during the previous year in 13 subspecialties. Click here for a collection of all such OrthoBuzz specialty-update summaries.

This month, Matthew R. Schmitz, MD, JBJS Deputy Editor for Social Media, selected the most clinically compelling findings from the >40 studies summarized in the October 21, 2020 “What’s New in Shoulder and Elbow Surgery.

Rotator Cuff Repair
–A prospective randomized study compared operative and nonoperative treatment of small and medium-sized chronic full-thickness rotator cuff tears. At 10 years, the outcomes of primary repair were superior to those of nonoperative treatment, but both groups improved significantly over time.

Anterior Shoulder Instability
–A randomized trial compared arthroscopic Bankart repair to arthroscopic washout in the treatment of a first-time anterior dislocation. Bankart repair was associated with lower recurrence rates, fewer revisions, and better maintenance of functional outcomes.

–A prospective study evaluated the amount of glenoid bone loss associated with a single instability event in young athletes (average age of 20 years).1 A first-time dislocation was associated with a 6.8% bone loss. In the setting of recurrent instability, total bone loss averaged 10.2% at the time of enrollment and 22.8% after a subsequent instability event.

Proximal Humeral Fractures in the Elderly
–A randomized controlled trial compared locking-plate fixation with reverse total shoulder arthroplasty in treating intra-articular displaced proximal humeral fractures in patients 65 to 85 years of age. At 2 years, Constant-Murley scores were significantly better in the reverse total shoulder arthroplasty group.

“Little League” Elbow
–A prospective MRI-based study of Little League baseball players aged 12 to 15 years2 found that 58% of the players had abnormal upper-extremity MRI findings, and that in 80% of those players, the MRI findings worsened with continued baseball play. The authors suggest that surgeons discourage year-round play in young baseball players.

References

  1. Dickens JF, Slaven SE, Cameron KL, Pickett AM, Posner M, Campbell SE, Owens BD. Prospective evaluation of glenoid bone loss after first-time and recurrent anterior glenohumeral instability events. Am J Sports Med.2019 Apr;47(5):1082-9.
  2. Holt JB, Pedowitz JM, Stearns PH, Bastrom TP, Dennis MM, Dwek JR, Pennock AT. Progressive elbow magnetic resonance imaging abnormalities in Little League baseball players are common: a 3-year longitudinal evaluation. Am J Sports Med.2020 Feb;48(2):466-72. Epub 2019 Dec 4.

PROMs Analyzed after Aseptic Revision TKA

The current literature about revision total knee arthroplasty (rTKA) for aseptic causes is focused mainly on “doctorly” data such as complication rates and implant survivorship. Taking a different tack in the October 21, 2020 issue of JBJS, Siddiqi et al. report findings from a comprehensive evaluation of patient-reported outcome measures (PROMs) at baseline and 1 year following rTKA. The PROMs evaluated included KOOS-Pain, KOOS-Physical Function, KOOS-QOL, and Veterans Rand-12.

Here is a general summary of the findings:

  • Patients undergoing aseptic rTKA had overall improvements in pain and function scores at 1 year postoperatively.
  • Knee-related QOL improved nearly 30 points, but >50% of patients did not report improvement in their overall global health at 1 year.
  • Predictors of improved 1-year pain scores were older age, baseline arthrofibrosis, lower baseline pain, and non-Medicare/Medicaid insurance.
  • Predictors of improved 1-year function scores were baseline arthrofibrosis and female sex.
  • Larger mean pain-score improvements occurred in patients undergoing rTKA for implant failure and aseptic loosening; pain-score improvements were lower in patients undergoing rTKA for instability.

Although 31% of the 246 eligible patients were lost to follow-up and excluded from the final analysis, the authors say their findings “corroborate the overall quality and, most importantly, the value that aseptic rTKA provides to patients.” Perhaps the findings’ greatest value is their potential application in the shared decision-making process between surgeons and patients pondering an aseptic rTKA, and in helping set realistic patient expectations if the surgery is undertaken.

A Genetic Basis for Adhesive Capsulitis?

This post comes from Fred Nelson, MD, an orthopaedic surgeon in the Department of Orthopedics at Henry Ford Hospital and a clinical associate professor at Wayne State Medical School. Some of Dr. Nelson’s tips go out weekly to more than 3,000 members of the Orthopaedic Research Society (ORS), and all are distributed to more than 30 orthopaedic residency programs. Those not sent to the ORS are periodically reposted in OrthoBuzz with the permission of Dr. Nelson.

Adhesive capsulitis (AC), colloquially known as frozen shoulder, is associated with conditions such as diabetes, cardiopulmonary disorders, stroke, Parkinsonism, and injury. However, many cases are idiopathic. Given the inflammatory nature of the condition, clinicians often administer intra-articular steroid injections in recalcitrant cases where physical therapy alone is too painful or nonproductive. Some cases, particularly in patients with diabetes, may require manipulation, brisement, or arthroscopic release.

To better understand the genetic basis of AC, investigators obtained punch tissue samples from the middle glenohumeral ligament and rotator cuff interval from AC patients undergoing arthroscopic release surgery (mean age of 53 years) and from a comparative group of patients undergoing arthroscopic surgery for shoulder instability (mean age of 24 years).1 The researchers performed RNA sequencing-based transcriptomics on the samples and, after identifying differentially expressed genes, they applied real-time reverse transcription polymerase chain reaction (RT-PCR) to obtain more detailed genetic data.

A total of 545 genes were differentially expressed. The top 50 were associated with extracellular matrix remodeling. Patient age and sex did not have a major influence on gene expression. The genes marked by overexpression (not necessarily protein expression) were genes for matrix metallopeptidase 13 and platelet-derived growth factor subunit B. Other suspects included the gene for metalloprotease 9 and COL18A1.

In the discussion, the authors comment on the association between AC and protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK). FAK activation is particularly sensitive to fibronectin and other integrins. Activated FAK also controls cell migration and focal adhesion assembly. These interesting associations may also shine light onto the etiology of other musculoskeletal diseases.

Reference

  1. Kamal N, McGee SL, Eng K, Brown G, Beattie S, Collier F, Gill S, Page RS.
    Transcriptomic analysis of adhesive capsulitis of the shoulder.
    J Orthop Res. 2020 Oct;38(10):2280-2289. doi: 10.1002/jor.24686. Epub 2020 Apr 17. PMID: 32270543

Elite Reviewer Spotlight: Kerr Graham

JBJS is pleased once again to highlight our Elite Reviewers. The Elite Reviewers Program recognizes our best reviewers for their outstanding efforts. All JBJS reviewers help us maintain the highest standards for quality orthopaedic publishing.

Name:

Professor Kerr Graham

Affiliation:

Royal Children’s Hospital

Murdoch Children’s Research Institute (MCRI)

University of Melbourne

Melbourne, Victoria, Australia.

Years in practice: 43

How did you begin reviewing for other journals and for JBJS in particular?

I think my first invitation to review for JBJS came after my first published paper in JBJS. That has been a similar pattern with other journals.

What is your top piece of advice for those reviewers who aspire to reach Elite status?

I consider reviewing to be a privilege and a serious academic responsibility. I try to give JBJS reviews the first/best part of my working day, after any urgent clinical matters. Early mornings are best when the hospital is quiet and competing demands are fewer. I remember well, being the young researcher avidly checking for a reply and a decision on a submitted paper. So, knowing that I have accepted the responsibility I try to discharge that responsibility as quickly as possible. This is for the efficiency of the journal’s operations and to show the hard-working authors my respect for their efforts.

Aside from orthopaedic manuscripts, what have you been reading lately?

The classics (Shakespeare, Dostoevsky, Dickens, Emerson, Thoreau) and a lot of Poetry (Heaney, Auden, Larkin, Whitman, Eliot, Dickinson). Travel books: anything by Paul Theroux dreaming about being able to travel again, post Covid-19.

Learn more about the JBJS Elite Reviewers program.