Synovial calprotectin in prosthetic joint infection. A systematic review and meta-analysis of the literature.

INTRODUCTION: Calprotectin is a protein endowed with antimicrobial properties, rendering it a distinctive marker for infection. Two methods are currently available for the assay of calprotectin: the enzyme-linked immunosorbent assay (ELISA) and the lateral flow test (LFT). We aimed to assess the diagnostic accuracy of synovial fluid calprotectin and to compare the accuracy of the laboratory-based test and the qualitative assessment for the diagnosis of hip and knee prosthetic infection. MATERIALS AND METHODS: We searched (from inception to November 2023) MEDLINE, Scopus, EMBASE, Web of Science, and Cochrane for studies on calprotectin in the diagnosis of periprosthetic joint infection (PJI). Sensitivity, specificity, positive and negative likelihood ratio (LR), and diagnostic odds ratio were analyzed. The receiver-operating curve for each method was calculated. RESULTS: We included 14 articles in our meta-analysis, including 902 patients who underwent total hip and knee arthroplasties revision; 331 (37%) had a joint infection according to MSIS, MSIS-modified criteria, ICM 2018 and EBJIS 2021. Considering the false-positive result rate of 6% and false-negative result rate of 7%, pooled sensitivity and specificity were 0.92 (95% CI 0.89-0.94) and 0.93 (0.91-0.95), respectively. The area under the curve (AUC) was 0.93 (95% CI 0.91-0.94). No statistical differences in terms of sensitivity and specificity were found between ELISA and LFT. The pooled sensitivity and specificity of the two calprotectin assessment methods were: LFT 0.90 (95% CI 0.869-0.935) and 0.92 (95% CI 0.894-0.941), respectively; ELISA 0.96 (95% CI 0.914-0.986) and 0.97 (95% CI 0.934-0.988), respectively. The diagnostic odds ratio of the ELISA was superior to that of the LFT (906.6667, 95% CI 271.2686-3030.3712 versus 113.8886, 95% CI 70.4001-184.2414; p < 0.001). The AUC for ELISA and LFT was 0.968 (95% CI 0.944-0.984) and 0.915 (95% CI 0.895-0.933), respectively. CONCLUSIONS: Detection of synovial calprotectin is an accurate test for diagnosis of hip and knee prosthetic infections. The diagnostic accuracy of the two calprotectin assessment methods is almost comparable. The LFT is a valid, rapid, and more available diagnostic tool, particularly to rule out PJI.

Articulating spacers in elderly patients affected by periprosthetic knee infection: clinical findings and outcome.

OBJECTIVE: Although the two-stage technique is a validated strategy in periprosthetic joint infections, there is a lack of data on the patients' clinical outcomes after the spacer placement. This study aims at evaluating the quality of life, joint function, and pain in patients over 70 years affected by periprosthetic joint infection treated with a two-stage exchange using metal on polyethylene spacers. PATIENTS AND METHODS: We conducted a follow-up study to evaluate the quality of life and functionality of consecutive patients over 70 years treated for PJI at our institution using a validated assessment set including the Western Ontario and Mac Master University (WOMAC) score, Knee Society Score (KSS), numerical rating scale (NRS). Knee Range of Movement (ROM) before and after the surgery was also analyzed. RESULTS: Forty-five patients with a mean age of 76 ± 5.3 years were included. Coagulase-negative staphylococci were the most isolated microorganisms. In the preoperative study group, the WOMAC score was 48.4 ± 18.9, and the KSS objective and functional scores were 37.6 ± 17.3 and 27.6 ± 22.3, respectively. NRS was 7.3 ± 1.8. After three months of follow-up, we found better results than preoperative clinical evaluation. We retrieved similar results comparing our post-operative PROMS (WOMAC and KSS scores) with published thresholds for treatment success two months after primary total knee arthroplasty. The infection eradication rate was 87%. CONCLUSIONS: The two-stage technique confirmed its efficacy in the treatment of PJI. Patients over 70 years who had undergone the first stage of the two-stage technique for PJI showed a good quality of life and knee function.

Characteristics of viral pneumonia in the COVID-19 era: an update.

Influenza virus, rhinovirus, and adenovirus frequently cause viral pneumonia, an important cause of morbidity and mortality especially in the extreme ages of life. During the last two decades, three outbreaks of coronavirus-associated pneumonia, namely Severe Acute Respiratory Syndrome, Middle-East Respiratory Syndrome, and the ongoing Coronavirus Infectious Disease-2019 (COVID-19) were reported. The rate of diagnosis of viral pneumonia is increasingly approaching 60% among children identified as having community-acquired pneumonia (CAP). Clinical presentation ranges from mild to severe pneumonitis complicated by respiratory failure in severe cases. The most vulnerable patients, the elderly and those living with cancer, report a relevant mortality rate. No clinical characteristics can be useful to conclusively distinguish the different etiology of viral pneumonia. However, accessory symptoms, such as anosmia or ageusia together with respiratory symptoms suggest COVID-19. An etiologic-based treatment of viral pneumonia is possible in a small percentage of cases only. Neuraminidase inhibitors have been proven to reduce the need for ventilatory support and mortality rate while only a few data support the large-scale use of other antivirals. A low-middle dose of dexamethasone and heparin seems to be effective in COVID-19 patients, but data regarding their possible efficacy in viral pneumonia caused by other viruses are conflicting. In conclusion, viral pneumonia is a relevant cause of CAP, whose interest is increasing due to the current COVID-19 outbreak. To set up a therapeutic approach is difficult because of the low number of active molecules and the conflicting data bearing supportive treatments such as steroids.

Blood loss and transfusion rate in patients undergoing two-stage exchange in infected total knee arthroplasty.

Two-stage exchange in infected total knee arthroplasty is a reliable technique, but it has a high rate of blood loss. The study aims to compare the pre-operative and post-operative haemoglobin levels, the rate of transfusion, and the blood loss in two-stage exchange. From July 2018 to July 2019, eighteen patients underwent two-stage exchange of their infected total knee arthroplasty. Local and systemic tranexamic acid was administered in both surgical stages. Calculated blood loss was 2246 mL (range 1528 - 2850) in the first stage and 2388 mL (1873 - 2829) during reimplantation, respectively. The corresponding transfusion rate was 55 % and 67%, respectively. With the numbers available, these differences were not significant. In conclusion, this study shows that the blood loss and transfusion rate are similar during the two stages of exchange knee arthroplasty for infection.

Prevention and treatment of peri-prosthetic joint infection using surgical wound irrigation.

Over the past decade, the incidence of revision arthroplasty due to infection has increased substantially, often resulting in multiple surgical interventions with variable success rates and poor clinical outcome. Intraoperative wound irrigation has been proposed to reduce bacterial bioburden and contamination, but currently there is no widely accepted recommendation for the use of topical antiseptics, whether as separate molecules or as a mixed solution. We reviewed studies regarding the use of intraoperative topical antiseptics, their security profile and efficacy in preventing and treating infections of orthopedic implants and introduced a possible combination that may prove valuable in the future.

Clinical and prognostic features of prosthetic joint infections caused by Enterococcus spp.

OBJECTIVE: Pathogens colonizing the intestinal or urinary tract such as enterococci or Gram-negative bacilli can cause prosthetic joint infection (PJI). PATIENTS AND METHODS: PJI undergoing 2-stage exchange, referred to the Department of Infectious Diseases of the Cotugno Hospital of Naples and the Fondazione Policlinico Gemelli of Rome over a 7-year period (2009-2015) for Infectious Diseases (ID) consultation were included. Demographic data, detailed information about previous or underlying diseases, findings of the clinical examination, and results of laboratory investigations were analyzed. The cure was defined by the disappearance of clinical, laboratory, and radiological evidence of PJI 96 week after the discontinuation of antibiotic treatment. RESULTS: Thirty-one cases of PJI sustained by Enterococci were included (16 early infections, 13 delayed infections, and 2 late infections). Median age was 73 years (range 39-83), 39% were males. Comorbidities related to an increased risk of infection were reported in 17 (55%) cases. Joint pain interfering with daily living was reported in 27 (87%) cases, fever in 7 with early infection and in no case with delayed or late infection (7/17 vs. 0/14, Odds ratio undefined, p=0.01). Local inflammation and joint effusion were reported in 29 (93%) cases, sinus tract in 25 (81%). Enterococcus faecalis was the etiologic agent in 28 (90%) cases, E. faecium in 2 (6%), E. casseliflavus in 1 (3%). Eleven cases were polymicrobial. Favourable outcome was reported in 20 (65%) cases. Patients with comorbidities reported more frequently an unfavourable outcome (9/17 vs. 2/14, Odds ratio 6.7, 95% CI 1.1-39.8; p=0.06). CONCLUSIONS: Comorbidities should arise the suspect of infection by enterococci. Associative protocols, considering drugs active against biofilm should be considered in the cases with enterococcal infection.

Post-arthroscopic septic arthritis of the knee. Analysis of the outcome after treatment in a case series and systematic literature review.

OBJECTIVE: The aim of this study was to review the characteristics of patients with septic arthritis after ACL reconstruction comparing our results with those deriving from the literature review. PATIENTS AND METHODS: Patients with suspected post arthroscopic septic arthritis of the knee occurring within 6 months after surgery were evaluated to be included in the investigation. Septic arthritis was defined by i) clinical evidence; ii) laboratory investigations; iii) synovial fluid leukocyte count of more than 2,5 x 104/µL or positive cultures obtained by synovial fluid aspirate. RESULTS: Thirty-nine patients (median age 25 years, range 17-42) with septic arthritis following ACL reconstruction were enrolled. Staphylococci were the main bacteria identified. Resolution within 4 weeks of local signs was observed more frequently in those receiving arthroscopic debridement and synovectomy coupled with antibiotic therapy (18/21 vs. 9/18, p<0.05). Fever was present in 33 (85%) cases. Fever disappearance and CRP normalization within 4 weeks were reported more frequently in patients receiving intravenous antibiotics (17/20 vs. 9/19, p<0.05). Similar findings were retrieved by literature analysis. CONCLUSIONS: An intravenous antibiotic therapy with surgical debridement is the first-line treatment for septic arthritis. Staphylococci are the main causative agents, justifying an empiric therapeutic approach with an anti-MRSA agent and cephalosporin.

Knee Septic Arthritis after Arthroscopy: Incidence, Risk Factors, Functional Outcome, and Infection Eradication Rate.

Purpose Septic knee arthritis following arthroscopy is a rare but dreaded complication. Definition and management of knee deep infections are quite discussed in literature. In this review, literature regarding infections after knee arthroscopy is analyzed highlighting the incidence, causative bacteria, risk factors as well as clinical outcomes. Methods We performed a review of the literature matching the following key words: "septic arthritis" OR "infection" AND "arthroscopy" AND "knee." Knee arthroscopic procedures, such as debridement, meniscectomy, meniscus repair, synovectomy, microfracture, and lateral release, were considered. Complex procedures, such as ligament reconstruction, fractures, or complex cartilage repair techniques, were not included. Results Thirteen studies were included in this review. Incidence of infection ranged from 0.009 to 1.1% in patients undergoing simple arthroscopic procedures. Staphylococci are the most commonly isolated organisms from postarthroscopy infection. Use of intraoperative intra-articular steroids, smoking, obesity, male sex, diabetes, number of procedures performed during surgery, time of surgery, and tourniquet time of more than 60 minutes have been certified as risk factors for knee infection. Conclusion Postarthroscopy septic arthritis of the knee causes significant morbidity, usually requiring readmission to the hospital, at least one additional operation, and prolonged antibiotic therapy, both intravenous and oral. Prompt diagnosis and treatment are associated with a high success rate. Level of Evidence Level IV, systematic review of I-IV studies.

RELEASE OF GENTAMICIN FROM CEMENT SPACERS IN TWO-STAGE PROCEDURES FOR HIP AND KNEE PROSTHETIC INFECTION: AN IN VIVO PHARMACOKINETIC STUDY WITH CLINICAL FOLLOW-UP.

Eighteen patients undergoing two-stage exchange arthroplasty for infected total hip or knee arthroplasty using gentamicin-loaded bone cement spacers (80g bone cement, 2 g gentamicin and 2 g clindamycin) were studied. The concentration of gentamicin eluted from the spacers was assessed on samples of blood, urine, and drainage fluid that were collected from each patient at set intervals during the 48 hours following the first-stage surgery. The hip and knee cement spacers showed similar curve of release over the first postoperative hours (early peak followed by slow release), but the mean gentamicin concentration in the drainage fluid was higher in patients with hip spacers compared to patients with knee spacers (30.61±19.47 mg/L vs 17.43±13,63 mg/L, p less than 0.05). In patients with hip spacers, the mean, maximum, and minimum concentration of gentamicin was higher with respect to the minimum inhibitory concentration (MIC) break point for Staphylococcus spp, Pseudomonas Aeruginosa and Enterobacteriaceae throughout the first postoperative 48 h. Conversely, in 25% of patients with a knee spacer a drug concentration below the MIC break point for Gram negative bacteria was found in the drainage fluid after 12 h. Gentamicin levels in the blood samples were negligible over the entire time interval and were steadily well below the renal toxicity reference. The highest urinary concentration of gentamicin was observed between 4 and 9 h postoperatively. Subsequently, it gradually declined until 48 h. Clinically, the rate of cure was 100% at a mean follow-up of 113 weeks (range 90-182). Gentamicin-loaded cement spacers offer the advantage of achieving early high concentrations of the antibiotic directly at the site of infection but especially in the knee a systemic antibiotic therapy must be given as a complement to the spacer implantation to eradicate periprosthetic joint infection (PJI).

Factors related to outcome of early and delayed prosthetic joint infections.

UNLABELLED: In this prospective study, we evaluate the impact of adherence to a diagnostic and therapeutic protocol on prosthetic joint infections (PJI) diagnostic accuracy and outcome. PATIENTS AND METHODS: Patients with early or delayed PJI referred over a 5-year period were included. Diagnosis was based on characteristic clinical signs, radiographic findings and microbiological evidence. Antibiotics were chosen on the basis of microbiological findings, and drugs active against methicillin-resistant staphylococci were administered if no microbiological evidence had been obtained. RESULTS: Inclusion criteria were met in 159 cases (median age 64 years, males 45%). 56 were early infections and 103 delayed infections. Comorbidities were reported in 99 (62%) cases. Positive cultures were obtained in 122/159 (77%), coagulase-negative staphylococci were cultured in 20%, Staphylococcus aureus in 28%, and Pseudomonas aeruginosa in 7%. In early infections, cure rate after debridement and antibiotic therapy was 80%. In delayed infections, cure rate after two-stage exchange was 85%. Of 28 patients with delayed infection treated with antibiotics without surgery, only 8 (29%) infections were suppressed 48 weeks after treatment discontinuation. Rifampin afforded a better outcome. CONCLUSION: Appropriate diagnostic and surgical procedures and microbiologically driven antibiotic therapy including rifampin are recommended to improve diagnostic accuracy and outcome.

Clinical efficacy and tolerability of levofloxacin in patients with liver disease: a prospective, non comparative, observational study.

The aim of this open, non comparative, observational study was to assess the clinical and bacteriological efficacy, the tolerability and safety of levofloxacin for treatment of concurrent bacterial infections in patients with chronic liver disease. Overall, 40 patients (inpatients or outpatients) were recruited to the study (28 with UTI, 6 with pneumonia, and 6 with spontaneous bacterial peritonitis (SBP)). Patients affected by UTI received 250 mg oral levofloxacin once daily for five days; patients with pneumonia or SBP underwent a 10/14-day therapeutic oral regimen with 500 mg b.i.d. Clinical evaluation and possible side effects were monitored daily both in out- and in-patients. For all patients, laboratory tests were performed at baseline and 3-4 days after the end of therapy in order to evaluate levofloxacin tolerability. Statistical analysis was performed by means of Student's t test to show differences between cases; all values are reported as means and standard deviations and p values were considered as significant when p<0.05. After treatment, clinical cure and bacteriological eradication were achieved in all patients (40/40; 100%). Adverse events, mainly gastrointestinal disturbances (e.g. nausea), were observed in 5 out of 40 patients (12.5%) and no neurotoxic effects were registered (e.g. anxiety, hallucinations, convulsions, mental confusion). No significant variation in laboratory tests due to hematic crasis and/or hepatic and renal disorders was observed. Levofloxacin proved to be highly efficacious and safe in the treatment of bacterial infections in patients affected by liver disease.

Premature discontinuation of interferon plus ribavirin for adverse effects: a multicentre survey in 'real world' patients with chronic hepatitis C.

BACKGROUND: Interferon-alpha plus ribavirin therapy for chronic hepatitis C is associated with adverse effects that lead to therapy discontinuation in up to 27% of patients in randomized controlled trials. AIM: To examine the causes and predictive factors for therapy discontinuation in patients treated in current clinical practice. METHODS: We retrospectively enrolled 441 consecutive patients, scheduled to receive interferon-alpha + ribavirin for chronic hepatitis C, in five centres. Patients had been treated with 3 or 6 MU interferon-alpha three times a week plus ribavirin, 800-1200 mg daily, for 6 or 12 months. RESULTS: One hundred and eight [24.5%; confidence interval (CI), 20.5-28.8%] patients failed to finish combination therapy because of adverse events. The discontinuation rate was higher during the first 6 months of treatment; anaemia was an important cause (36.1% of discontinuations); unexplained lipothymia resulted in discontinuation in 11 patients. Female gender [hazard ratio (HR) = 1.85; CI, 1.17-2.92], an interferon-alpha dose > 15 MU/week (HR = 1.79; CI, 1.12-2.86) and no previous interferon-alpha treatment (HR = 1.63; CI, 1.04-2.57) were independent factors associated with discontinuation. The simultaneous presence of these factors identified patients at high risk for discontinuation [odds ratio (OR) = 10; CI, 3.98-25.13]. CONCLUSIONS: The study identified some predictive factors for adverse event-related discontinuation, which may improve the safety profile and effectiveness of interferon-alpha + ribavirin combination therapy in chronic hepatitis C.

Quantitative viremia test for early prediction of a biochemical response in patients with chronic hepatitis C treated with interferon.

To evaluate the importance of the changes in viremia as an early predictor of the outcome of interferon (IFN) therapy, we assayed the levels of hepatitis C virus (HCV)-RNA in stored serum samples obtained from 34 patients with chronic hepatitis C who showed different biochemical responses to therapy. Serum samples obtained before the start of therapy and after 1 and 3 months were used, and viremia levels were determined by "branched DNA (bDNA)" technique. Viremia levels at 1 month of therapy were lower than pre-therapy levels in all 19 patients who had shown a persistent normalization of ALT during therapy (responder patients). The bDNA test was negative, i.e. the levels of viremia were below the sensitivity threshold of the method, in 12 (63.1%) patients at 1 month and in 13 (68.4%) at the 3rd month of therapy, whereas the bDNA test was negative in none of the 15 non-responder patients at the 1st month and in only 2 (13.3%) of them at the 3rd month of therapy. The bDNA test was superior to the ALT test both in predicting the non-response and the biochemical response to IFN after 1 month of therapy. The bDNA test results, instead, were not predictive of the duration of the response to IFN, either at the 1st or 3rd months of therapy. These results seem to indicate the usefulness of measuring the HCV-RNA levels at the beginning and after 1 month of IFN therapy in order to envisage or exclude a possible biochemical response early on in treatment.

Interferon-alpha plus amantadine in chronic hepatitis C resistant to interferon alone: a pilot randomized study.

The optimal therapy for patients with chronic hepatitis C who have not responded to interferon (IFN) is still an unsolved issue. The aim of this study was to evaluate the efficacy and tolerability of a high dose of IFN-alpha2a plus amantadine for chronic hepatitis C patients who were non-responders to a previous course of IFN. Forty consecutive patients with chronic hepatitis C, genotype 1b, who had not responded to IFN-alpha, were randomized to receive: (i) IFN 4.5 MU daily plus amantadine 200 mg/day for 4 weeks and then IFN 6 MU thrice weekly plus amantadine 200 mg/day for an additional 5 months (group A) or (ii) IFN alone at the same dosage and duration (group B). After 1 month of therapy, normal alanine aminotransferase (ALT) values were observed in three of 21 (14.3%) patients in group A and in three of 19 (15.8%) in group B; serum hepatitis C virus (HCV)-RNA clearance was observed in one patient (4.8%) in group A and in six (31.6%) in group B. At the end of treatment, six patients (28.6%) in group A and three (15.8%) in group B had normal ALT levels; however, HCV-RNA in serum was detectable in all of them at levels comparable to the basal values; an ALT relapse occurred within 3 months of stopping therapy. The combination of daily IFN plus amantadine was ineffective in this setting.

Chronic hepatitis D: a vanishing Disease? An Italian multicenter study.

Hepatitis delta virus (HDV) was responsible for a high proportion of cases of acute and chronic liver disease in Southern Europe during the 1970s. Some data suggest that by the 1990s HDV circulation had substantially declined. We have assessed the prevalence of HDV infection and its clinical impact in 834 Italian hepatitis B surface antigen (HBsAg) carriers in 1997. Anti-HDV antibodies were sought in all consecutive chronic HBsAg carriers observed in 14 referral liver units throughout Italy. Risk factors for anti-HDV positivity were evaluated. Anti-HDV antibodies were found in 69 of 834 (8.3%) HBsAg-positive patients. Cohabitation with an anti-HDV-positive subject, intravenous drug addiction, residence in the South of the country, and the presence of cirrhosis were independently associated with the presence of anti-HDV antibodies. The overall prevalence of anti-HDV antibodies was lower than those observed in 2 multicenter surveys performed in 1987 and 1992 (23% and 14%, respectively). By 1997, the percentage of anti-HDV-positive subjects had sharply decreased in the 30 to 50 years age group, whereas it was almost unchanged in subjects over 50 years of age. The highest prevalence of anti-HDV antibodies (11.7%) was found in patients with cirrhosis. This prevalence was as high as 40% in the 1987 study. The circulation of HDV sharply decreased in Italy, by 1.5% per year, from 1987 to 1997. This decrease resulted mainly from the reduction in chronic HDV infections in the young, for whom high morbidity and mortality rates were recorded in the past. The results anticipate the almost complete control of HDV infection in the near future.

[Elevata prevalenza ma bassa incidenza della infezione da HGV in pazienti con epatite cronica C] / Elevata prevalenza ma bassa incidenza della infezione da HGV in pazienti con epatite cronica C.

Objectives To determine 1. The prevalence and incidence of HGV infection in patients with chronic hepatitis C and 2. Its influence on the clinical outcome of chronic hepatitis C. Patients and methods Sixty-five patients with non-parenteral chronic hepatitis C virus infection were investigated for HGV infection using the polymerase chain reaction for HGV-RNA and by detecting serum antibodies against the E2 protein of HGV (anti-E2 antibodies). Results HGV-RNA in serum was found in 12 patients (18.4%) and anti-E2 antibodies in 4 (6.1%). No difference in age, sex, liver histology, basal ALT or ?GT was found between HGV positive and negative cases. Thirty-four patients (6 with HGV-RNA) were followed-up for 4 years; 4 of the 6 lost HGV-RNA, one of whom seroconverted to anti-E2. None of the 28 HGV-RNA negative cases presented HGV infection during the follow-up period. The presence of HGV infection did not influence either basal HCV viremia or the response of HCV to IFN therapy. Conclusions The study demonstrated that HGV had an intense circulation through non-classic parenteral routes, but its impact on HCV replication and liver disease is negligible.