99mTc-HMPAO-WBC SPECT/CT versus 18F-FDG-WBC PET/CT in chronic prosthetic joint infection: a pilot study.

PURPOSE: The aim of this study was to compare 99mTc-HMPAO-WBC-SPECT/CT combined with 99mTc-nanocollloid SPECT/CT and 18F-FDG-WBC-PET/CT combined with 99mTc-Nanocollloid SPECT/CT for the diagnosis and treatment evaluation of chronic prosthetic joint infection (PJI). METHODS: Patients with suspected chronic PJI were examined with 99mTc-HMPAO-WBC SPECT/CT, 18F-FDG-WBC PET/CT, and 99mTc-nanocolloid SPECT/CT (to visualize bone marrow). The location and patterns of uptake were noted and compared between the two leukocyte examinations. Both leukocyte examinations were evaluated visually for infection. The PET examinations were also evaluated semiquantitatively. Chronic PJI was verified clinically by microbial culture and successfully treated PJI was confirmed by 12 months symptom-free follow-up after cessation of antibiotics. RESULTS: Nineteen patients were included with 10 hip prostheses and nine knee prostheses. Fourteen were diagnosed with chronic PJI and five with successfully treated PJI. The sensitivity of visual evaluation of 99mTc-WBC-HMPAO SPECT/CT for all joints was 0.31 and for 18F-FDG-WBC PET/CT 0.38. The specificity was 0.80 and 0.83, respectively. All patients with a true-positive SPECT examination had a false-negative PET examination and vice versa. Semiquantitative evaluation of the hips gave an area under the curve of 0.905 using the iliac crest as the background. Semiquantitative evaluation of the knees did not produce significant results. CONCLUSION: This pilot study showed no difference in the sensitivity or specificity of 99mTc-HMPAO-WBC SPECT/CT and 18F-FDG-WBC PET/CT when combined with 99mTc-nanocollloid SPECT/CT in the diagnosis or treatment evaluation of suspected late chronic PJI.

Dual-tracer approach vs. dual time-point approach in leukocyte scintigraphy in treatment evaluation of persistent chronic prosthetic joint infection.

BACKGROUND: Both dual time-point 99mTc-hexamethylpropylene amine oxime (HMPAO)-leukocyte scintigraphy and dual-tracer 99mTc-HMPAO-leukocyte scintigraphy (with the addition of 99mTc-nanocolloid bone marrow scintigraphy) have been used to diagnose prosthetic joint infection (PJI). A treatment evaluation of persistent PJI using these imaging protocols has yet to be presented. OBJECTIVE: The purpose of this study was to compare the accuracy of dual time-point 99mTc-HMPAO-leukocyte scintigraphy to the dual-tracer alternative of single time-point 99mTc-HMPAO-leukocyte scintigraphy or single-photon emission computed tomography/computed tomography (SPECT/CT) combined with a 99mTc-nanocolloid bone marrow scintigraphy or SPECT/CT, for treatment evaluation of PJI. MATERIAL AND METHODS: Thirty-one PJI patients under antibiotic treatment were included in this retrospective study. Examinations were organized into three settings. Setting one used dual time-point approach with delayed (2 h) and late (24 h) planar 99mTc-HMPAO-leukocyte scintigraphy, including both visual and semiquantitative analysis. Setting two used delayed (2 h) planar 99mTc-HMPAO-leukocyte scintigraphy combined with 99mTc-nanocolloid bone marrow scintigraphy and for setting three SPECT/CT replaced planar imaging. RESULTS: Accuracy was 0.68 for visual evaluation and 0.55 for semiquantitative evaluation of setting one; 0.71 for setting two; and 0.68 for setting three. Sensitivity was 0.54 for visual evaluation and 0.31 for semiquantitative evaluation of setting one; 0.38 for setting two; and 0.46 for setting three. Specificity was 0.78 for visual evaluation and 0.72 for semiquantitative evaluation of setting one; 0.94 for setting two; and 0.83 for setting three. CONCLUSION: No significant difference in accuracy, sensitivity, or specificity between the approaches for treatment evaluation of suspected persistent PJI in the hip or knee was observed.

Is 99mTc-HMPAO-leukocyte imaging an accurate method in evaluating therapy result in prosthetic joint infection and diagnosing suspected chronic prosthetic joint infection?

BACKGROUND: To investigate the sensitivity and specificity of 99mTc-HMPAO-leukocyte imaging in evaluating therapy result in patients with prosthetic joint infection (PJI) and in diagnosing suspected chronic PJI. METHODS: Sixty-two patients (63 joints) with microbiologically verified PJI were examined by leukocyte imaging to evaluate therapy result during or at the end of antibiotic treatment or if the patient had a chronic PJI after treatment. Group 1 consisted of 49 patients with on-going or within less than 14 days of ending antibiotic treatment examined to evaluate response. Group 2 consisted of 13 patients examined after completed treatment on suspicion of chronic PJI with no or recently initiated renewed antibiotic treatment. This study applied a combination of different imaging approaches of 99mTc-HMPAO-leukocyte scintigraphy: delayed and late planar images, bone marrow imaging and SPECT/CT imaging. All joints were examined with at least two of the approaches and 53 joints with all three approaches. The report was based on the combined results of the approaches used. A chronic PJI was confirmed with a positive microbiological culture. A cured infection was confirmed with either a negative culture or at least 24 months antibiotic-free follow-up with no relapse. RESULTS: In the therapy evaluation group sensitivity was 0.57 and specificity was 0.81. In the suspected chronic infection group sensitivity was 1.00 and specificity 0.91. CONCLUSIONS: 99mTc-HMPAO-leukocyte imaging appears to be an accurate method to diagnose or exclude chronic PJI, but cannot be recommended for therapy evaluation of PJI in patients with on-going antibiotic treatment.

[Treatment of orthopedic implant-associated infections]. / Handläggning av infektioner vid ortopediska implantat en utmaning för vården.

The Swedish National Guidelines for Bone and Joint Infections were revised during 2018. The work was carried out on behalf of the Swedish Society for Infectious Diseases. The study group consists of senior consultants in infectious diseases, supported by specialists in orthopedic surgery, clinical microbiology and allergology when needed. The study group emphasizes that implant associated infections are challenging and requires multidisciplinary cooperation, including, but not limited to, specialists in orthopedic surgery, infectious diseases, clinical microbiology and radiology for optimal treatment results. All aspects of the clinical management are equally important; selecting the optimal antibiotic prophylaxis in arthroplasty as well as fracture surgery, early diagnosis of infection, adequate treatment, follow-up, and finally a structured evaluation of outcome. Profound and updated knowledge of treatment of biofilm related infection is necessary to achieve optimal results in patients with implant-associated infections. Future challenges include improved decision support for combining surgical treatment with selection of proper antibiotics, as well as management of antibiotic resistance, drug-drug interactions and adverse effects of antibiotic treatment.

Multidisciplinary diabetic foot care in Sweden - A national survey.

AIM: To investigate at a national level the multidisciplinary team (MDT) care of patients with diabetes mellitus and foot complications. METHODS: A questionnaire was sent to all 75 Swedish hospitals with emergency departments, which were grouped according to size. RESULTS: The response rate was 92%, 58/69 of the hospitals have a foot team. Most teams have access to an internal medicine specialist/diabetologist, podiatrist and orthotist. Fewer teams reported access to an orthopaedic surgeon and infectious diseases specialist and only half to a vascular surgeon. In joint MDT outpatient evaluations, the majority report the presence of an internal medicine specialist, podiatrist and orthotist, but 50% an infectious disease specialist and orthopaedic surgeon and only a few a vascular surgeon. In hospitalized patients, there is a reduction in the presence of all specialists. The registration of amputation rate and healed foot ulcers is low. CONCLUSIONS: MDT care is mostly adopted among large and medium-sized hospitals in contrast to small ones, which could reflect unequal health care. Vascular surgeons seldom are present at MDT evaluations and there is a reduced regular input of specialists in the evaluation of hospitalized patients. The hospitals' ability to evaluate their work by potential quality control markers is poor.

Diabetic osteoarthropathy care in Sweden - Need for improvement: A national inventory.

AIMS: Osteoarthropathy, a rare foot complication in patients with diabetes mellitus, calls for immediate and optimal management to prevent irreversible bone/joint destruction and risk of amputation. Awareness of the condition and adequate guidelines would minimize the consequences and the costs, both for the patient and for the society. We investigated the diabetic osteoarthropathy care in Swedish orthopedic clinics. METHODS: A questionnaire was distributed to 63 Swedish hospitals with emergency department for orthopedic patients. There was a 95% response rate. RESULTS: Most of the respondents (79%) specified absence of established procedures including guidelines for managing patients with osteoarthropathy. The most common diagnostic method was clinical diagnosis and plain X-ray (95%). MRI or scintigraphy was used by 19% and 10.5% respectively. As treatment method, 84% used a total contact cast, while 38% used orthoses. Treatment duration <3 months was reported in 4%, 3-6 months in 53% and 6-12 months in 28% of the clinics. Four clinics reported treatment duration >12 months and two clinics provided no treatment. CONCLUSION: Our national inventory indicates a need for improvement in knowledge as well as guidance and organization at orthopedic clinics regarding optimal care of patients with diabetic osteoarthropathy.

Fulminant anaplastic large cell lymphoma (ALCL) concomitant with primary cytomegalovirus (CMV) infection, and human herpes virus 8 (HHV-8) infection together with Epstein-Barr-virus (EBV) reactivation in a patient with asymptomatic HIV-infection.

BACKGROUND: Most malignant lymphomas in HIV-patients are caused by reactivation of EBV-infection. Some lymphomas have a very rapid fulminant course. HHV-8 has also been reported to be a cause of lymphoma. The role of CMV in the development of lymphoma is not clear, though both CMV and HHV-8 have been reported in tissues adjacent to the tumour in Burkitt lymphoma patients. Here we present a patient with asymptomatic HIV infection, that contracted a primary cytomegalovirus (CMV) infection and human herpes virus 8 (HHV-8) infection. Three weeks before onset of symptoms the patient had unprotected sex which could be possible source of his CMV and also HHV-8 infection He deteriorated rapidly and died with a generalized anaplastic large cell lymphoma (ALCL). METHODS: A Caucasian homosexual male with asymptomatic human immunodeficiency virus (HIV) infection contracted a primary cytomegalovirus (CMV) infection and human herpes virus 8 (HHV-8) infection. He deteriorated rapidly and died with a generalized anaplastic large cell lymphoma (ALCL). Clinical and laboratory records were compiled. Immunohistochemistry was performed on lymphoid tissues, a liver biopsy, a bone marrow aspirate and the spleen during the illness and at autopsy. Serology and PCR for HIV, CMV, EBV, HHV-1-3 and 6-8 was performed on blood drawn during the course of disease. RESULTS: The patient presented with an acute primary CMV infection. Biopsies taken 2 weeks before death showed a small focus of ALCL in one lymph node of the neck. Autopsy demonstrated a massive infiltration of ALCL in lymph nodes, liver, spleen and bone marrow. Blood samples confirmed primary CMV- infection, a HHV-8 infection together with reactivation of Epstein- Barr-virus (EBV). CONCLUSION: Primary CMV-infection and concomitant HHV-8 infection correlated with reactivation of EBV. We propose that these two viruses influenced the development and progression of the lymphoma. Quantitative PCR blood analysis for EBV, CMV and HHV-8 could be valuable in diagnosis and treatment of this type of very rapidly developing lymphoma. It is also a reminder of the importance of prevention and prophylaxis of several infections by having protected sex.

Epstein Barr virus DNA analysis in blood predicts disease progression in a rare case of plasmablastic lymphoma with effusion.

BACKGROUND: In HIV-1-infected patients a long lasting CD4+ cell decline influences the host-EBV balance and thereby increases the risk for EBV related malignancies. In spite of a world-wide access to combination antiretroviral therapy (cART) there are still a considerable number of HIV-1-infected patients who will develop severe immunodeficiency. These undiagnosed HIV-1 infected patients, so called late testers, demonstrate an increased lymphoma risk, compared to patients diagnosed early. Consecutive individual screening for EBV DNA-load in late testers might be a useful predictor of emerging EBV-malignancy. METHODS: Patient biopsies and ascites were analyzed morphologically, by immuncyto-histochemistry and in-situ hybridization. Viral DNA and RNA load were quantified by PCR. Cell lines from primary tumor and from ascites, were established in vitro and further analyzed. RESULT: We here report on a case of EBV-positive lymphoma in an AIDS patient, first presenting with pleural effusion and ascites and was thus initially considered a primary effusion lymphoma (PEL) but was later diagnosed as a plasmablastic lymphoma (PBL). The patient had responded to cART with undetectable HIV-RNA and increased CD4 cell count one year prior to lymphoma presentation. At the time of lymphoma diagnosis the HIV-RNA values were <50 RNA-copies per mL blood (undetectable) and the CD4-positive cell count 170 ×106/L. The lymphoma was CD45-negative and weakly CD22- and CD30-positive. The patient had a history of Kaposi sarcoma and HHV-8 seropositivity. The lymphoma biopsies, and three cell lines derived on different occasions from the tumor cell effusion, were all EBV-positive but HHV-8 negative.A noticeable EBV-DNA load decline was observed during the remission of the lymphoma following CHOP-therapy. The EBV-DNA load increased dramatically at the time of recurrence. CONCLUSION: EBV DNA load might be useful in monitoring the effect of lymphoma treatment as well as in estimating the risk of EBV-associated lymphoma in HIV-1 infected patients with pronounced immunosuppression.

Epstein-Barr virus genome load is increased by therapeutic vaccination in HIV-l carriers, and further enhanced in patients with a history of symptomatic primary infection.

OBJECTIVE: Epstein-Barr virus (EBV) infection is an established risk factor for B-cell lymphomas in Human Immunodeficiency virus (HIV)-1 infected patients. A disturbed EBV-host relationship is seen in patient groups with a high risk for EBV-associated lymphomas. We have analysed this relationship by measuring EBV-DNA in the blood of HIV-1 carriers. METHOD: EBV-DNA load in B-cells was monitored by PCR in non- or insufficiently antiretroviral treated and rgp160-vaccinated HIV-patients. RESULTS: Both asymptomatic HIV-infected and AIDS-patients showed a 25-40-fold increase in the number of B cell associated EBV-DNA copies compared to healthy controls. Patients included in a vaccine trial with recombinant HIV gp160 showed a 5-fold increase of EBV load compared to non-immunised patients and a 50-fold increase compared to healthy controls. There was no difference whether they received vaccine or "placebo". Vaccinated patients with a history of symptomatic primary HIV-1 infection (PHI) had a 280-fold increase in median EBV load compared to healthy controls, thus suggesting a synergistic effect between the vaccination and PHI, which hypothetically could affect lymphoma risk. CONCLUSIONS: We recommend analysis of EBV-load and long term follow up of lymphoma risk in all therapeutic HIV-1 vaccination trials.

Host-Epstein-Barr virus relationship affected by immunostimulation in HIV-infected patients representing distinct progressor profile groups.

BACKGROUND: Human immunodeficiency virus (HIV) infection with pronounced immunosuppression disrupts Epstein-Barr virus (EBV)-host balance with increased lymphoma risk. We explored whether different host responses to HIV are reflected in the EBV-host balance. METHODS: Eleven unvaccinated HIV-positive patients and 16 participants in a vaccine trial were included in the study. Blood samples were collected, B cells extracted, and EBV DNA load was determined using a semiquantitative polymerase chain reaction (PCR) method. RESULTS: Treatment-naïve patients with a history of symptomatic primary HIV infection showed non-significant, but higher EBV load compared to untreated long-term non-progressors. A significant difference in HIV RNA titres between these groups correlated weakly to EBV DNA load. Patients in the vaccine trial with recombinant HIV gp160 and/or adjuvant and with a history of symptomatic primary HIV infection, showed a 1-log increase in EBV load compared to patients with long-lasting HIV disease. CONCLUSION: Different host responses to HIV infection, especially in combination with vaccination, can be reflected in the EBV-host balance.

Increased risk of abdominal wall hernia associated with combination anti-retroviral therapy in HIV-infected patients-results from a Swedish cohort-study.

PURPOSE: To determine if anti-retroviral therapy (ART) in HIV-infected patients is associated with an increased risk for development of abdominal wall hernia. METHODS: A cohort study of 1072 HIV-infected patients in Sweden. Information was collected by questionnaires to patients and treating physicians, chart reviews by study physicians and regular blood tests for metabolic disorders. Adjusted relative risks were estimated by Cox proportional hazards models. RESULTS: Sixty-three patients (5.9%) developed abdominal wall hernia during the study period, 34 inguinal and 29 midline. Compared to the male general population, inguinal hernia was twice as common in the male study population, standardized incidence ratio (SIR) 2.0 (95% confidence interval (CI) 1.4-2.8). An increased incidence rate of abdominal wall hernia was found in patients exposed to ART, 11.3 per 1000 person-years (PY) compared with therapy naïves, 2.1 per 1000 PY. When adjusting for confounding risk-factors, ART containing protease inhibitors (PIs) during the 2nd and 3rd year of treatment was associated with the development of midline hernia with a hazard ratio (HR) of 10.7 (95%CI 1.3-85.7), and of inguinal hernia with an HR of 4.4 (95%CI 1.1-16.6). Other independent risk factors were age and diabetes/impaired fasting glucose for midline hernia, and age and a previous diagnosis of AIDS for inguinal hernia. CONCLUSIONS: We found an increased risk of developing abdominal wall hernia associated with PI-containing ART. The size of the study-population did not permit any conclusions regarding non-PI-containing ART.

The Effect of Antiretroviral Combination Treatment on Epstein-Barr Virus (EBV) Genome Load in HIV-Infected Patients.

We evaluated the effect of combination anti-retroviral treatment (cART) on the host control of EBV infection in moderately immunosuppressed HIV-1 patients. Twenty HIV-1 infected individuals were followed for five years with repeated measurements of EBV DNA load in peripheral blood lymphocytes in relation to HIV-RNA titers and CD4+ cell counts. Individuals with optimal response, i.e. durable non-detectable HIV-RNA, showed a decline of EBV load to the level of healthy controls. Individuals with non-optimal HIV-1 control did not restore their EBV control. Long-lasting suppression of HIV-replication after early initiation of cART is a prerequisite for re-establishing the immune control of EBV.

Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study.

BACKGROUND: An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons with access to combination antiretroviral therapy (cART) are due to complications of liver diseases. METHODS: We investigated the frequency of and risk factors associated with liver-related deaths in the Data Collection on Adverse Events of Anti-HIV Drugs study, which prospectively evaluated 76 893 person-years of follow-up in 23 441 HIV-infected persons. Multivariable Poisson regression analyses identified factors associated with liver-related, AIDS-related, and other causes of death. RESULTS: There were 1246 deaths (5.3%; 1.6 per 100 person-years); 14.5% were from liver-related causes. Of these, 16.9% had active hepatitis B virus (HBV), 66.1% had hepatitis C virus (HCV), and 7.1% had dual viral hepatitis co-infections. Predictors of liver-related deaths were latest CD4 cell count (adjusted relative rate [RR], 16.1; 95% confidence interval [CI], 8.1-31.7 for <50 vs > or =500/microL), age (RR, 1.3; 95% CI, 1.2-1.4 per 5 years older), intravenous drug use (RR, 2.0; 95% CI, 1.2-3.4), HCV infection (RR, 6.7; 95% CI, 4.0-11.2), and active HBV infection (RR, 3.7; 95% CI, 2.4-5.9). Univariable analyses showed no relationship between cumulative years patients were receiving cART and liver-related death (RR, 1.00; 95% CI, 0.93-1.07). Adjustment for the most recent CD4 cell count and patient characteristics resulted in an increased risk of liver-related mortality per year of mono or dual antiretroviral therapy before cART (RR, 1.09; 95% CI, 1.02-1.16; P = .008) and per year of cART (RR, 1.11; 95% CI, 1.02-1.21; P = .02). CONCLUSIONS: Liver-related death was the most frequent cause of non-AIDS-related death. We found a strong association between immunodeficiency and risk of liver-related death. Longer follow-up is required to investigate whether clinically significant treatment-associated liver-related mortality will develop.