Infection following total joint replacement remains a major problem that has not been solved during the last thirty years. The prevalence of infection at the Mayo Clinic between 1969 and 1996 was 1.7 per cent of 30,680 total hip arthroplasties and 2.5 per cent of 18,749 total knee arthroplasties. After primary operations, the rate of infection was 1.3 per cent of 23,519 hips and 2.0 per cent of 16,035 knees. After revision operations, the rate was 3.2 per cent of 7161 hips and 5.6 per cent of 2714 knees (Table I). The rate of infection has been remarkably constant despite the use of different regimens of antibiotic prophylaxis, operating-room configurations, operative techniques, and modes of fixation of the implant. Factors leading to deep infection must be considered with respect to the host, wound, operative technique, operating-room environment, and microbiological characteristics of the infecting organisms. A prompt diagnosis of infection will facilitate treatment and minimize morbidity.

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TABLE I PREVALENCE OF INFECTION AFTER TOTAL JOINT ARTHROPLASTY FOR THE YEARS 1969 THROUGH 1996



As stated, in discussing the etiology of infection, the host, wound, operating-room environment, operative technique, and microbiological characteristics of the infecting organisms must be considered. The patient as host is an important risk factor for infection. The operative wound is contaminated to some extent in all procedures, but the immune-defense mechanisms of the host prevent infection in most instances. Immunocompromised patients are clearly at increased risk for deep infection as are patients who have rheumatoid arthritis110,140. In a series of 4171 total knee replacements, an infection developed after sixteen (0.9 per cent) of 1854 replacements in patients who had osteoarthrosis compared with forty-five (2.2 per cent) of 2076 replacements in those who had rheumatoid arthritis140. In a series of 4240 total hip, knee, and …

Evaluation and treatment of infection at the site of a total hip or knee arthroplasty.

Background: Despite the widespread use of several diagnostic tests, there is still no perfect test for the diagnosis of infection at the site of a total knee arthroplasty. The purpose of this study was to evaluate the diagnostic test characteristics of the erythrocyte sedimentation rate and C-reactive protein level for the assessment of infection in patients presenting for revision total knee arthroplasty.

Methods: One hundred and fifty-one knees in 145 patients presenting for revision total knee arthroplasty were evaluated prospectively for the presence of infection with measurement of the erythrocyte sedimentation rate and the C-reactive protein level. The characteristics of these tests were assessed with use of two different techniques: first, receiver-operating-characteristic curve analysis was performed to determine the optimal positivity criterion for the diagnostic test, and, second, previously accepted criteria for establishing positivity of the tests were used.

Results: A diagnosis of infection was established for forty-five of the 151 knees that underwent revision total knee arthroplasty. The receiver-operating-characteristic curves indicated that the optimal positivity criterion was 22.5 mm/hr for the erythrocyte sedimentation rate and 13.5 mg/L for the C-reactive protein level. Both the erythrocyte sedimentation rate (sensitivity, 0.93; specificity, 0.83; positive likelihood ratio, 5.81; accuracy, 0.86) and the C-reactive protein level (sensitivity, 0.91; specificity, 0.86; positive likelihood ratio, 6.89; accuracy, 0.88) have excellent diagnostic test performance.

Conclusions: The erythrocyte sedimentation rate and the C-reactive protein level provide excellent diagnostic test information for establishing the presence or absence of infection prior to surgical intervention in patients with pain at the site of a knee arthroplasty.

Level of Evidence: Diagnostic Level I. See Instructions to Authors for a complete description of levels of evidence.

Use of erythrocyte sedimentation rate and C-reactive protein level to diagnose infection before revision total knee arthroplasty. A prospective evaluation.

This report provides a compendium of current information relating to radiation dose to patients, including biokinetic models, biokinetic data, dose coefficients for organ and tissue absorbed doses, and effective dose for major radiopharmaceuticals based on the radiation protection guidance given in Publication 60(ICRP, 1991) These data were mainly compiled from Publications 53, 80, and 106(ICRP, 1987, 1998, 2008), and related amendments and corrections This report also includes new information for 82Rb-chloride, iodide (123I, 124I, 125I, and 131I) and 123I labeled 2s-carbomethoxy 3s-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FPCIT)The coefficients tabulated in this publication will be superseded in due course by values calculated using new International Commission on Radiation Units and Measurements/International Commission on Radiological Protection adult and paediatric reference phantoms and Publication 103 methodology (ICRP,2007) The data presented in this report are intended for diagnostic nuclear medicine and not for therapeutic applications

Radiation Dose to Patients from Radiopharmaceuticals: a Compendium of Current Information Related to Frequently Used Substances.

The spectrum of infectious diseases has changed over the last few years, hence the requirements for radionuclide imaging for the detection of infection are becoming more demanding so that, although gallium-67 and labelled leucocytes remain useful agents, there is currently great interest in the development of new agents especially able to target chronic, non-pyogenic inflammation. Agents can be classified according to the site at which the radiolabel is targeted: pre-endothelial (for example, labelled leucocytes), endothelial (for example, labelled anti-endothelial monoclonal antibodies) or post-endothelial (for example, fluorine-18-fluorodeoxyglucose (FDG)). 67Ga and labelled polyclonal human immunoglobulin (HIG) localize at inflammation initially as a result of increased endothelial permeability, followed by retention of the label through binding to local extravascular receptors. Labelled leucocytes are avidly taken up by acute pyogenic inflammatory foci but perform less well in chronic inflammation. Ot...

The use of nuclear medicine in infections.

Chronic post-traumatic osteomyelitis (OM) represents a particular challenge for nuclear medicine and radiology since clinical and biochemical parameters are frequently unreliable. The aim of this study was to investigate the value of combined bone scan (BS) and immunoscintigraphy (IS) with technetium-99m labelled monoclonal antigranulocyte antibody (MAB) in patients with suspected chronic OM of the appendicular skeleton. Twenty-four patients (17 females and 7 males) with suspected chronic post-traumatic OM were evaluated with three-phase BS/99mTc-MAB-IS. The final diagnosis was established by means of bone culture and histology in 19 cases and clinical follow-up in five cases. The studies were reviewed by two independent and experienced observers; the interobserver agreement was calculated by kappa statistics. The sensitivity, specificity and accuracy of BS alone were 92%, 18% and 58%, respectively. Combined BS/99mTc-MAB-IS. had a sensitivity, specificity and accuracy of 84%, 72% and 79%, respectively. Of 24 studies, 11 were true-positive, two false-negative, eight true-negative and three false-positive. Two patients presented with unexpected ectopic haematopoietic bone marrow in the appendicular skeleton that caused falsepositive results. A high degree of interobserver agreement was found (κ=0.85). It is concluded that combined BS/99mTc-MAB-IS. represents a very sensitive and reproducible method with an acceptable specificity for the investigation of chronic OM. Problems may occur in the differentiation of low-grade OM from aseptic inflammation. Another problem is ectopic marrow that may occur in the appendicular skeleton due to a chronic inflammatory stimulus. A former intramedullary intervention in the femur with displacement of haematopoietic marrow may also lead to an ectopic location.

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Chronic complicated osteomyelitis of the appendicular skeleton: diagnosis with technetium-99m labelled monoclonal antigranulocyte antibody-immunoscintigraphy.

UNLABELLED The purpose of this study was to determine the efficacy of 111In-polyclonal immunoglobulin (IgG) for the diagnosis of infection or inflammation. METHODS Fifty-three patients with suspected infection were prospectively studied. Each underwent an 111In-polyclonal IgG study; biopsy, surgery, additional nuclear medicine scans and radiographic studies were used to confirm the IgG scan results. RESULTS The polyclonal IgG scan had a sensitivity of 97.9% and a specificity of 94% for infection or inflammation. When only infection or severe inflammation such as bowel infarction was considered, the sensitivity remained the same but the specificity fell to 83%. Chronic infections were detected equally as well as acute infections. Antibiotics, steroids, anti-inflammatory agents, diabetes and diminished renal function did not affect scan sensitivity. There were no adverse reactions to the radiopharmaceutical. Three patients underwent extended imaging. Their scans stayed positive for an average of 8 days. Three patients treated for infection had their scans turn negative on repeat study, confirming the efficacy of their antibiotic therapy. CONCLUSION Indium-111-polyclonal IgG is an effective imaging agent of infection and/or inflammation that is useful in a variety of infections and in severe inflammatory diseases. The ease of preparation and safety make it an attractive alternative to labeled leukocytes.

https://jnm.snmjournals.org/content/35/1/74.full.pdf

The Efficacy of Indium-111-Polyclonal IgG for the Detection of Infection and Inflammation

Indium-111-polyclonal IgG is a new imaging agent of infection and inflammation that has been developed as a possible replacement for radiolabeled leukocytes. We undertook a study to determine the safety, biodistribution and dosimetry of the agent in normal subjects. Methods : Twelve normal male volunteers with an average age of 34 yr (range 21-55 yr) were studied. Each was injected with 1.22-1.47 mCi 111 In-labeled polyclonal IgG ; digital whole-body images, in addition to blood, urine and fecal samples, were obtained immediately after injection and at 6, 24, 48, 72, 96 and 120 hr. Whole-body counts, as well as individual organ data obtained by outlining regions of interest, were measured. Blood, urine and fecal counting were done in a well counter and compared to known standards ; dosimetry calculations were performed with the MIRD technique. Results : The mean whole-blood activity had a two-phase disappearance curve : the T 1/2 I was 11.4 hr (61.1%) and the T 1/2 II was 112.5 hr (38%). Twelve percent of the dose was excreted in the urine and 1.14% in the feces. Skeletal muscle had the highest percentage of uptake, followed by the bone marrow, liver and lungs ; the spleen showed less than 1 % uptake. Activity in the lungs varied with time, falling by 37% after 18 hr and by 68% after 72 hr. Dosimetry calculations indicated that the highest absorbed dose was to the liver (1.42 rad/mCi) followed by the testes (1.23 rad/mCi) and red marrow (0.976 rad/mCi). The total-body dose was 0.467 rad/mCi, with an effective dose equivalent of 790.84 mrem. Conclusion The biodistribution of 111 In IgG is similar to that of 99m Tc-HMPAO-labeled leukocytes. Activity in the liver, kidneys and Gl tract may make evaluation of infection in these regions difficult. The dosimetry data indicate that adequate doses can be administered for clinical imaging without exposing the patient to excessive radiation.

https://jnm.snmjournals.org/content/36/12/2372.full.pdf

Biodistribution and dosimetry of indium-111-polyclonal IgG in normal subjects

Aging manifests as progressive deterioration in cellular and systemic homeostasis, requiring systems-level perspectives to understand the gradual molecular dysregulation of underlying biological processes. Here, we report systems-level changes in the molecular regulation of biological processes under multiple lifespan-extending interventions in mice and across age in humans. In mouse cohorts, Differential Rank Conservation (DIRAC) analyses of liver proteomics and transcriptomics show that mechanistically distinct prolongevity interventions tighten the regulation of aging-related biological modules, including fatty acid metabolism and inflammation processes. An integrated analysis of liver transcriptomics with mouse genome-scale metabolic model supports the shifts in fatty acid metabolism. Additionally, the difference in DIRAC patterns between proteins and transcripts suggests biological modules which may be tightly regulated via cap-independent translation. In a human cohort spanning the majority of the adult lifespan, DIRAC analyses of blood proteomics and metabolomics demonstrate that regulation of biological modules does not monotonically loosen with age; instead, the regulatory patterns shift according to both chronological and biological ages. Our findings highlight the power of systems-level approaches to identifying and characterizing the biological processes involved in aging and longevity.

Kelly Crebs

Papers

The Efficacy of Indium-111-Polyclonal IgG for the Detection of Infection and Inflammation

Biodistribution and dosimetry of indium-111-polyclonal IgG in normal subjects

Systems-level patterns in biological processes are changed under prolongevity interventions and across biological age