What constitutes an Internet Consult?   For no fee, the physicians at REOrthpaedics will do all they can to help you and your family both understand your condition and receive appropriate care.  In the process, we may ask you questions about your health, previous/current care and current status (i.e.; weight-bearing capacity, wound healing and current disabilities).  If you can send your clinical photographs and plain x-rays over the Internet (as jpeg files), we will be happy to review and comment on them, as well.  If, however, your medical condition proves too complex to comfortably manage on the Internet, a formal consultation may be necessary and a $200 fee generated.  For this, we will offer an opinion based on a detailed review of medical records, pathology slides, x-rays and/or discs of other, radiographic studies (MRI scans, CT scans, bone scans, etc).  If, on completion, we feel our services will not help you, the $200 will be returned, in full.

In accordance with laws stipulating we practice medicine only in states in which we are licensed, no prescriptions or treatment will be offered until you are seen in San Diego, as a patient.  If we do, indeed, provide your care and offer definitive treatment, REOrthopaedics will reimburse your airfare for the initial office visit.   In most instances, it will be necessary to see a patient before insurance coverage can be pre-certified and surgery scheduled in the operating room; for those patients coming from countries outside the United States, special arrangements are made in lew of same.   

Our curriculum vitae and scientific work are posted on the Internet for review.  We are experts with over 30 years of experience in the fields of musculoskeletal infection, musculoskeletal oncology, deformity correction and complex orthopaedic reconstructions.  As such, our opinions are  meant not to set community “standards of care” but, rather, as a source of evidence-based information to help patients and providers make wise choices.  GC  11/23/09

Patient Selection: The treatment of adult, chronic osteomyelitis is directed by the careful consideration of anatomic, physiologic and socioeconomic parameters: the site and extent of involvement, the degree of functional impairment caused by disease, the condition of the host, physician experience and institutional resources.         ( CLICK ON IMAGE TO ENLARGE )

  The complex interplay of these factors will  determine treatment to be palliative or curative, simple or complex, limb-sparing or ablative.

The A-Host and B-Host differentiation:  In the Cierny/Mader classification system for adult osteomyelitis, the host status was added to the anatomic type of infection to articulate the biology of the disease to its treatment (see illustration)  This likens our conceptualization of infection to that of the oncologist treating musculoskeletal tumors: treatment and therapeutic outcomes are scaled to grade (biologic activity): A-hosts /low grade tumors need conservative margins and have high success rates; B-hosts /high grade cancers call for radical/wide margins and have lower success rates despite more aggressive treatment.  The difference between the two disease states (tumor vs infection) is that the genetic makeup of the tumor cell, itself, determines tumor grade (low vs high) whereas, in chronic osteomyelitis, it is the capacity of the host immune and defense systems (grade of response) that determines outcomes. Yes, there are deadly, resistant and docile bacteria but, even here, treatment and outcomes will, again, be determined more or less determined by the capacity of the host (A vs B). 

The biologic grade of the disease can be used to: 1) guide patient selection(table 1; page 4);  2) scrutinize treatment options (article);  3) bring objectivity to with holding treatment either because the patient can function safely with their disease or because treatment, if undertaken, will cause more danger/stress to the patient than no treatment, at all.  In the staging system, this later scenario defines the  C-Host.  A healthy or compromised patient can opt out of treatment to be classified a C-host  but revert to an A-host or a B-host status when and if they later become a surgical candidate.  

The Clinical Staging system is about the disease, not the healthcare provider, the type of implant, the pathogen or the antibiotic.   Yes, there are bad implants, toxic drugs /bugs and inexperienced surgeons ………..but, these, too, are circumstances for which the Staging System was designed to differentiate rather than categorize.   In this context, providers, pathogens and post-surgical risks are numerators, not denominators.

Comment:  if you now look at our recent outcomes, the discrepancies between A- and B-hosts are shrinking with each year that passes.  Why? Because we no longer offer these two cohorts the same treatment —- instead, each treatment is individualized —-  options are matched to the physiologic capacity of the host.

I agree there are degrees of compromise just as there are differences in the sweetness of grapes.   But, over the years,  I have stopped trying to sort “bad” factors from the “not so bad”.  To me, anything less than normal is a compromise worthy of an effort to counter or negate its affect(s) on wound healing ———– I know that a reversed compromise will improve outcomes (somewhere, sometime).   GC 11/19/09

How does malnutrition affect outcomes of patients with musculoskeletal infection?”     Good nutrition is essential for normal wound healing and host defense against infection.  A lack of proteins, fats, vitamins and minerals creates a welcome environment for invading bacteria:  1) decreased production of new blood vessels to heal wounds, potentiate antimicrobial effectiveness and thereby prevent infection; 2) lack of proteins to seal and heal wounds, stop bleeding and kill bacteria (antibodies against bacteria and viruses);  3) impotent white blood cells (natural  killer cells ) to destroy invaders.   In our protocols and staging system, patients with obesity and/or mal-nutrition are considered B-hosts with co-morbidities affecting wound healing and treatment outcomes.

 How can I be obese and still be malnourished?  Concomitant  obesity and malnutrition can offend occur if the obesity is linked to: 1)  the consumption of empty calories in a diet of processed, fast  foods lacking minerals and containing additives to prolong shelf life; 2) bariatric patients following bariatric surgery where absorption is altered; 3) dietary deficiencies in folate, selenium, zinc and vitamins A, B-12, B-1, C, D and E.  Obesity, for these purposes, is defined as a Mean Body Index (BMI) > 40.   Our treatment center has introduced many innovations in treatment that have improved outcomes for all B-hosts.

How do you diagnose mal-nutrition?  Common measurements of nutritional status include: laboratory tests (serum albumin, transferring, pre-albumin and total lymphocyte count); body measurements such as BMI, tricps skin fold thickness (fat reserves) and a  mid-humeral circumference (protein reserves).  

Can I still be operated if I am malnourished?  In order to prevent post-operative wound complications (healing) and infection (SSI), surgery is often delayed until a mal-nourished patient can first be restored to good health and nutrition.  However, in the case of a serious infection or tumor, when a delay of surgery cannot be advised, alternative and sometimes more circuitous methods must be employed to reach a similar goal (TREATMENT OUTCOMES: slide #4).  

The Clamshell Osteotomy: A New Technique to Correct Complex Diaphyseal Malunions.      The Journal of Bone and Joint Surgery (American). 2009;91:314-324.  George V. Russell, MD¹, Matt L. Graves, MD¹, Michael T. Archdeacon, MD, MSE², David P. Barei, MD, FRCS(C)³, Glenn A. Brien, Jr., MD¹ and Scott E. Porter, MD¹

 Methods: After surgical exposure, the malunited segment is transected perpendicular to the normal diaphysis  (proximally and distally) and then wedged open on its long axis. The proximal and distal segments of the diaphysis are then aligned with use of an intramedullary rod as an anatomic axis template.    The  osteotomy provides a quick, safe, and useful way to correct many forms of diaphyseal malunion.  The technique provides an alternative that decreases preoperative planning time and complexity as well as the need for intraoperative osteotomy precision in a correctly chosen subset of patients (slide #2).

Hypersensitivity reactions: a source of failure following total hip arthroplasty: New-generation metal-on-metal bearings made from cobalt-chromium alloys for use in total hip arthroplasty are now being utilized worldwide.  There is a unique histological response in patients with these implants in which there is a prominent, perivascular and/or diffuse lymphocytic infiltration reminiscent of a delayed type hypersensitivity response (type IV). This response has been termed ALVAL (aseptic lymphocyte dominated vasculitis associated lesion) and it is reported around metal-on-metal implants from various manufacturers (total hip arthroplasties). Degradation products, either in the form of ionic or particulate debris, can complex with local proteins to alter their confirmation and elicit an allergic response.   This type of hypersensitivity is mediated by T-lymphocytes which become reactive to metal ion-modified proteins. In this paradigm, there is co-operation between innate and adaptive immunity to produce antigen-driven clonal proliferation and differentiation.   The cells and byproducts accumulate, locally, to acclude the small vessels, resulting in an early loosening of implants, the accumulation of inflammatory tissues (pseudotumors) and, if prolonged, ischemic death of bone and soft tissues.  Recently, Langton and colleagues in Stockton, England, reviewed 650 metal-on-metal arthroplasties from different manufacturers and observed a 4.4% incidence of ALVAL in one make of joint(500) and a 0% incidence in another(150).  When the lymphocytes of the patients with failure were studied in the lab, they were not hyper-reactive to metal ions, alone.  This made sense: ALVAL is mediated by a local, toxic reaction (primary and secondary). Their study also showed there are specific design, geometric, and manufacturing parameters that contribute to the failures, independent of gender, composition of the bearing couple and positioning of the components, in situ.   Hanseen et al ⁽¹⁾ has reported elevated ESR and CRP levels in a case of ALVAL failure, adding to the difficulty in the making the diagnosis of an aseptic vs septic failure.   

In the last three years, 15% of the peri-prosthetic, total hip infections ( slide #3) treated at our treatment center in San Diego were associated with hyper-sensitivity reactions following metal-on-metal bearing arthroplasties.  

Ref: 1) Mikhael MM, Hanssen AD, Sierra RJ.  Failure of Metal-on-Metal Total Hip Arthroplasty Mimicking Hip Infection.  Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, MN.  The Journal of Bone and Joint Surgery (American),2009; 91:443-446.   2) Jacobs JJ, Hallab NJ. Loosening and osteolysis associated with metal-on-metal bearings: a local effect of metal hypersensitivity? J Bone Joint Surg Am. 2006;88:1171-2

( CLICK FOR SLIDE SHOW: FIVE FIGURES )

Outcomes for adult patients treated for osteomyelitis over a 20 year period (1986-2006);  methods of reconstruction used to manage 314 consecutively treated segmental osseous defects (2003-2008); results following staged treatment of 194 peri-prosthetic total joint infections; the impact of our center’s innovations on treatment outcomes for patients with wound-healing deficiencies;  long-term treatment results for 2207 patients with all types of osteomyelitis (A-hosts and B-hosts).

BLOOD TESTS TO DIAGNOSE OSTEOMYELITIS / BONE and SOFT TISSUE  INFECTIONS - 

The Erythrocyte Sedimentation Rate (ESR):   When inflammation is present in the body, proteins are produced by the liver and the immune system under many abnormal conditions, such as an infection, an autoimmune disease, and/or cancer.  The increased presence of these proteins will cause red blood cells to stick together in solution (whole blood) and, therefore, settle out of solution more slowly than when these proteins are absent or in lower concentrations.   The Erythrocyte Sedimentation Rate (ESR) is, therefore, a non-specific test to indicate thickening of the blood due and can be used to rule in or rule out disease processes that, when present, stimulate production of these proteins (see below discussion of acute phase proteins).   Since there are many possible causes of an elevated sedimentation rate, this blood test is done with other tests to confirm a diagnosis such as a chronic osteomyelitis.  Once a sed rate (ESR) blood test is conducted, the course of a disease or the effectiveness of treatment can be monitored.

C-reactive protein (CRP): CRP is believed to play another important role in innate immunity, as an early defense system against infection.  It is a protein found in the blood, the levels of which rise in response to inflammation due to trauma, infection or serious illnesses; it is an “acute-phase protein” synthesized by the liver.  It is not related to C-peptide or protein C.   A rise in C-RP is due to a rise in the plasma concentration of IL-6(see below), which is produced predominantly by macrophages and fat cells.   CRP binds to microbes and is thought to enhance the process of phagocytosis (cellular ingestion/digestion) of bacteria by macrophages.  

When signaled, the CRP level rises above normal limits within 6 hours, and peaks at 48 hours.  Thereafter, its level is determined by the rate of production (and hence the severity of the precipitating cause).  Measuring and charting C-reactive protein values can prove useful in determining the presence of disease, disease progress and/or the effectiveness of various treatments.

Acute-phase proteins:  a class of proteins whose plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response is called the acute-phase reaction (also called acute-phase response).  In response to injury, local inflammatory cells (neutrophils, granulocytes and macrophages) secrete a number of cytokines; cytokines are chemical signals between cells that have an effect on other cells, the most most notable of which are the interleukins IL-1, IL-6 and IL-8 and tumor-necrosis factor alpha (TNF- α).   

Interleukin-6 (IL-6) is both a pro-inflammatory and anti-inflammatory cytokine.  It is secreted by T-cells and macrophages to stimulate immune response to trauma, especially burns or other tissue damage leading to inflammation. IL-6 has been shown to be required for resistance against certain bacteria (i.e.; Streptococcus pneumoniae).  IL-6, one of the most important mediators of fever and of the acute phase response, can be secreted in response to specific microbial molecules referred to as pathogen associated molecular patterns (PAMPs).  These PAMPs bind to highly important group of detection molecules of the innate immune system called pattern recognition receptors (PRRs) which signal cascades giving rise to inflammatory cytokine production.

 At our Osteomyelitis Treatment Center in Sand Diego, CA we use the ESR, CRP and IL-6 blood tests in the diagnosis of bone and soft tissue infections as well as in the follow up following treatment results and peri-prosthetic total joint infections.

The Fate of the Unexpected Positive Intraoperative Cultures After Revision Total Knee Arthroplasty.  Robert L. Barrack,  Ajay Aggarwal,  R. Stephen J. Burnett,  John C. Clohisy,  Elie Ghanem,  Peter Sharkey and Javad Parvizi.  Washington University & Barnes-Jewish Hosp., St. Louis, MO;  Thomas Jefferson University & Rothman Inst,  Philadelphia, PA.  Journal of Arthroplasty, 2007; 22(6) pp94-99.

-Of a consecutive series of 692 revision total knees at 3 centers, intra-operative cultures were unexpectedly found to be positive in 41cases (5.9%). Of the 41, 29 (71%) cases had a single positive intra-operative culture and were determined to be a probable false positive based on absence of any other evidence of infection, of which 5 were treated with extended course of intravenous antibiotics after hospital discharge and the remaining 24 received no further treatment. None of these 24 patients manifested any sign of infection at follow-up, averaging 46 months (range, 24-74 months): Staph. epi (46%); enterococcus (11%); Staph. aureus (14%); Strep (9%); Corynebact. (7%); Diptheroids(7%); Prop. Acne(4%). Twelve patients were determined to have probable type 1 peri-prosthetic infection, 11 of which were treated with a course of antibiotics: Staph. epi.(50%); Enterococcus 29%; Staph. aureus 7%; MRSE (7%); Strep(7%).   Two (18%) of these patients became re-infected within one year.  CONCLUSION: A single positive intra-operative culture after revision total knee arthroplasty does not mandate further treatment in the absence of any other signs of infection.  DR. CIERNY’S COMMENTS: THIS ARTICLE EMPHASIZES TWO VERY IMPORTANT POINTS WHEN SENDING WOUND  CULTURES: 1) ALWAYS SEND MORE THAN ONE SPECIMEN WHEN CULTURING A WOUND. —–  FALSE POSITIVE CULTURES DO OCCUR;  2) BIOPSY WHAT YOU CULTURE AND CULTURE WHAT YOU BIOPSY.  A  POSITIVE CULTURE +  TISSUE WITH NO EVIDENCE OF ACUTE INFLAMMATION = A FALSE POSITIVE CULTURE.  IF, HOWEVER, THERE IS A POSITIVE CULTURE WITH POSITIVE HISTOLOGY IN AN UNEXPECTED SCENARIO FOLLOWING IMPLANTATION OF HARDWARE (SEE PROTOCOL),  AT THE VERY LEAST WE WOULD RECOMMEND OPEN IRRIGATION/DEBRIDEMENT OFTHE WOUND, SYSTEMIC ANTIBIOTICS AND ANTIBIOTIC-DEPOT FILLING OF THE ADJACENT DEAD SPACE. 

Time-related Concordance Between Swab and Biopsy Samples in the Microbiological Assessment of Burn Wounds  Ebrahim Salehifar, PharmD; Ghasemali Khorasani, MD; Shahram Ala, PharmD.  Mazandaran University of Medical Sciences; Emam Square, Valliasr Blvard; Sari, Mazandaran.   Wounds, VOLUME: 21Mar 01 2009.

-The aim of this study was to investigate the concordance between swab and tissue biopsy samples in terms of microbiological isolates and their time-related changes. A total of 156 samples (78 swab and 78 biopsy) were collected from 39 cases of partial- or full-thickness burns and compared at days 7 and 14 after admission regarding the type of microorganisms and their time-related changes. Pseudomonas aeruginosa and Citrobacter freundii were the two most common microorganisms found by both sampling methods. While the majority of swab and biopsy samples were concordant in day 7, the rate of concordance in day 14 was less than day 7—87.1% versus 66.6%, respectively. After comparing the ratio of P aeruginosa and C freundii in positive swab and biopsy cultures on days 7 and 14, unlike the swab samples, the biopsy samples yielded similar results both times (75% P aeruginosa and 25% C freundii, respectively).      DR. CIERNY’S COMMENTS:  THE RESULTS OF THIS STUDY SUGGEST THAT TISSUE SWABS ARE SUFFICIENT FOR WOUND MONITORING ONLY DURING THE ACUTE-PHASE OF AN  INFECTION.  BY THE SECOND WEEK, THE MAJORITY OF THE PATHOGENS ARE SESSILE (WITHIN THE BIOFILM COLONY) AND NO LONGER FREE-SWIMMING (PLANKTONIC) OR AMENABLE TO GROWTH IN STANDARD CULTURE MEDIA.   IN THIS STUDY, AS IN OTHERS DEALING WITH BIOFILM INFECTIONS, DEEP TISSUE SPECIMENS WERE REQUIRED TO HARVEST ENOUGH PLANKTONIC (CULTURABLE) ORGANISMS TO YIELD POSITIVE RESULTS.  HOWEVER,  EVEN THEN, 20-40% OF OUR CULTURES WILL  STILL COME UP  “NO GROWTH”  UNTIL WE DEVELOP METHODS TO FREEING OR INTICE SESSILE ORGANISMS BACK TO  PLANKTONIC PHENOTYPES.