Blood and synovial fluid calprotectin as biomarkers to diagnose chronic hip and knee periprosthetic joint infections.

AIMS: Calprotectin (CLP) is produced in neutrophils and monocytes and released into body fluids as a result of inflammation or infection. The aim of this study was to evaluate the utility of blood and synovial CLP in the diagnosis of chronic periprosthetic joint infection (PJI). METHODS: Blood and synovial fluid samples were collected prospectively from 195 patients undergoing primary or revision hip and knee arthroplasty. Patients were divided into five groups: 1) primary total hip and knee arthroplasty performed due to idiopathic osteoarthritis (OA; n = 60); 2) revision hip and knee arthroplasty performed due to aseptic failure of the implant (AR-TJR; n = 40); 3) patients with a confirmed diagnosis of chronic PJI awaiting surgery (n = 45); 4) patients who have finished the first stage of the PJI treatment with the use of cemented spacer and were qualified for replantation procedure (SR-TJR; n = 25), and 5) patients with rheumatoid arthritis undergoing primary total hip and knee arthroplasty (RA; n = 25). CLP concentrations were measured quantitatively in the blood and synovial fluid using an immunoturbidimetric assay. Additionally, blood and synovial CRP, blood interleukin-6 (IL-6), and ESR were measured, and a leucocyte esterase (LE) strip test was performed. RESULTS: Patients with PJI had higher CLP concentrations than those undergoing aseptic revision in blood (median PJI 2.14 mg/l (interquartile range (IQR) 1.37 to 3.56) vs AR-TJR 0.66 mg/l (IQR 0.3 to 0.83); p < 0.001) and synovial fluid samples (median PJI 20.46 mg/l (IQR 14.3 to 22.36) vs AR-TJR 0.7 mg/l (IQR 0.41 to 0.95); p < 0.001). With a cut-off value of 1.0 mg/l, blood CLP showed a sensitivity, specificity, positive predictive value, and negative predictive value of 93.3%, 87.5%, 89.4%, and 92.1%, respectively. For synovial fluid with a cut-off value of 1.5 mg/l, these were 95.6%, 95%, 95.5%, and 95%, respectively. CONCLUSION: This small study suggests that synovial and blood CLP are useful markers in chronic PJI diagnosis with similar or higher sensitivity and specificity than routinely used markers such as CRP, ESR, IL-6, and LE. CLP was not useful to differentiate patients with PJI from those with rheumatoid arthritis. Cite this article: Bone Joint J 2021;103-B(1):46-55.

Elevated plasma D-dimer concentration has higher efficacy for the diagnosis of periprosthetic joint infection of the knee than of the hip-A single-center, retrospective study.

The aim of this study is to evaluate the value of D-dimers in the diagnosis of periprosthetic joint infection (PJI). The analysis was performed for revision total hip (rTHA) and revision total knee arthroplasty (rTKA) together and separately with two thresholds, one calculated by statistical methods and the second adopted from the ICM 2018 definition. The study group comprised 133 patients who underwent rTHA or rTKA: 68 patients diagnosed according to the ICM 2018 definition (PJI group) and 65 with aseptic implant loosening, instability, malposition, or implant failure with the exclusion of infection (aseptic revision total joint arthroplasty or arTJA group). Mean D-dimer concentrations were 0.36 ± 0.25 µg/ml in the arTJA group and 0.87 ± 0.78 µg/ml in the PJI group (p < .001). For rTHA and rTKA together, the sensitivity and specificity of the evaluation were 75% and 73.8% according to the calculated cut-off value (0.45 µg/ml), and 33.8% and 95.4% based on the ICM 2018 threshold (0.85 µg/ml). Separately, for rTHA, sensitivity and specificity were 62.5% and 62.1% for the calculated value (0.43 µg/ml) and 6.3% and 96.6% for the ICM 2018 threshold; for rTKA, sensitivity was 86.1% and specificity was 88.9% for the calculated threshold (0.48 µg/ml) and 58.3% and 94.4% for the ICM 2018 value. Our findings indicate that plasma D-dimers have potential as markers of knee PJI, but moderate to low value for hip PJI.

Plasma Cell Leukemia - Facts and Controversies: More Questions than Answers?

Plasma cell leukemia (PCL) is an aggressive hematological malignancy characterized by an uncontrolled clonal proliferation of plasma cells (PCs) in the bone marrow and peripheral blood. PCL has been defined by an absolute number of circulating PCs exceeding 2.0 × 109/L and/or >20% PCs in the total leucocyte count. It is classified as primary PCL, which develops de novo, and secondary PCL, occurring at the late and advanced stages of multiple myeloma (MM). Primary and secondary PCL are clinically and biologically two distinct entities. After the diagnosis, treatment should be immediate and should include a proteasome inhibitor and immunomodulator-based combination regimens as induction, followed by stem cell transplantation (SCT) in transplant-eligible individuals who have cleared the peripheral blood of circulating PCs. Due to the rarity of the condition, there have been very few clinical trials. Furthermore, virtually all of the myeloma trials exclude patients with active PCL. The evaluation of response has been defined by the International Myeloma Working Group and consists of both acute leukemia and MM criteria. With conventional chemotherapy, the prognosis of primary PCL has been ominous, with reported overall survival (OS) ranging from 6.8 to 12.6 months. The use of novel agents and autologous SCT appears to be associated with deeper response and an improved survival, although it still remains low. The PCL prognostic index provides a simple score to risk-stratify PCL. The prognosis of secondary PCL is extremely poor, with OS of only 1 month.

Consolidation with 90Y ibritumomab tiuxetan radioimmunotherapy in mantle cell lymphoma patients ineligible for high dose therapy: results of the phase II multicentre Polish Lymphoma Research Group trial, after 8-year long follow-up.

Polish Lymphoma Research Group performed a phase-II trial to test whether 90Y ibritumomab tiuxetan radioimmunotherapy (Y90) may constitute an alternative consolidation for mantle cell lymphoma patients unfit for high-dose therapy. Forty-six patients were consolidated with Y90 following response to the 1st (n = 34) or 2nd line (n = 12) (immuno)chemotherapy. Majority of the patients had advanced disease (stage IV and presence of B-symptoms in 85% and 70%, respectively) and high MIPI (5.8, range 4-7). Consolidation with Y90 increased the complete remission (CR) rate obtained by the 1st line therapy from 41% to 91% and allowed for median PFS of 3.3 and OS of 6.5 years. In the first relapse, CR rate increased from 16% to 75%, while median PFS and OS totaled 2.2 and 6.5 years, respectively. At 8 years, 30% of patients, consolidated in the 1st line CR were alive, without relapse. Toxicity associated with Y90 is manageable, more severe after fludarabine-based regimens.

[Hematological toxicity of radioimmunotherpy with 90Y Ibritumomab]. / Toksycznosc hematologiczna radioimmunoterapii z zastosowaniem 90Y Ibritumomabu.

Radioimmunotherapy with 90Y Ibritumomabu (Zevalin, BSP) is a new method of systemic radiotherapy applicable to B-cell lymphoma patients. It may be delivered as a short outpatient procedure, with few adverse effects other than hematological toxicity. In the paper, we present length and depth of cytopenias, together with the results of additional tests performed to reveal the possible pathomechanisms, based on 102 patients treated at the University Hospital in Krakow.

[Beta-carotene regulates the expression of proapoptotic BAX and CAPN2 in HL-60, U-937 and TF-1 - human acute myeloid leukemia cell lines; microarray, RQ-PCR and Western Blot analysis]. / Wplyw beta-karotenu na ekspresje proapoptotycznych genów BAX i CAPN2 w komórkach linii ostrej bialaczki szpikowej HL-60, U-937 i TF-1; analiza technika mikromacierzy, ilosciowej PCR i Western Blot.

Beta carotene (BC) is a nutritional compound widespread in foods which can influence vital cellular functions--differentiation, proliferation and apoptosis of normal and cancer cells. However its role in the carcinogenesis remains controversial. We performed a microarray expression analysis in three human acute leukemia cell lines (HL-60, U937 and TF-1) exposed to 10mM BC and found that BC stimulated the apoptosis in all studied cell lines. This effect was most evident in the HL-60 cell line and correlated with increased expression of proapoptotic BAX and CAPN2 genes. The micro-array findings were replicated by the quantitative BAX and CAPN2 expression analysis using real-time PCR and by Western Blot on protein level. The biological tests (TUNEL method) for apoptosis showed consistent proapoptotic effects in all studied cell lines. In this paper the stimulatory effect of BC on apoptosis (enhanced expression of proapoptotic genes and proteins) in human acute myeloid leukemia cells was confirmed. The most potent activation of apoptosis in the HL-60 cells is in line with other investigators observations suggesting distinct molecular mechanism of apoptosis stimulation by BC in different human acute myeloid leukemia cells.

[High-dose chemotherapy and autologous stem cell transplantation in multiple myeloma patients--single center experience]. / Wysokodawkowana chemioterapia z przeszczepieniem autologicznych komórek macierzystych u chorych na szpiczaka plazmocytowego--wyniki analizy jednoosrodkowej.

Multiple myeloma (MM) is one of the hematologic malignancies in which the impact of dose intensity has been demonstrated. In 2005 it was the most common disease for which autologous stem cell transplantation (ASCT) was performed. However, ASCT is not curative, and most patients relapse within a median of 3 years, the introduction of high-dose therapy resulted in prolonged survival. Novel agents such as thalidomide, bortezomib, or lenalidomide have been introduced to improve high-dose therapy outcome. From April 1998 to December 2008, 65 patients with MM underwent in our Department high-dose chemotherapy supported by autologous transplantation of peripheral blood stem cells (APBSCT). Transplantation of progenitor cells was conducted as consolidation of first line treatment in the majority of patients. Double transplantation was performed in 20 patients (31%). Conditioning regimen consisted of high-dose melphalan (200 mg/m2), in the second procedure the dose of melphalan was reduced to 140 mg/m2. Transplant related mortality was not observed. The duration of hematological recovery after first and second transplantation did not differ significantly. At the time of the analysis (June 2009) 51/65 (78.5%) patients are alive, 14/65 (21.5%) died due to disease progression. Median overall survival (OS) and progression free survival ( PFS) obtained were 86 (range 24-128) and 33 (range 4-110) months respectively. This retrospective analysis confirms the efficacy and safety of APBST in multiple myeloma patients.

Thalidomide, dexamethasone and lovastatin with autologous stem cell transplantation as a salvage immunomodulatory therapy in patients with relapsed and refractory multiple myeloma.

The treatment of patients with multiple myeloma usually includes many drugs including thalidomide, lenalidomide and bortezomib. Lovastatin and other inhibitors of HMG-CoA reductase demonstrated to exhibit antineoplasmatic and proapoptotic properties in numerous in vitro studies involving myeloma cell lines. We treated 91 patients with relapsed or refractory multiple myeloma with thalidomide, dexamethasone and lovastatin (TDL group, 49 patients) or thalidomide and dexamethasone (TD group, 42 patients). A clinical response defined of at least 50% reduction of monoclonal band has been observed in 32% of TD patients and 44% of TDL patients. Prolongation of overall survival and progression-free survival in the TDL group as compared with the TD group has been documented. The TDL regimen was safe and well tolerated. The incidence of side effects was comparable in both groups. Plasma cells have been cultured in vitro with thalidomide and lovastatin to assess the impact of both drugs on the apoptosis rate of plasma cells. In vitro experiments revealed that the combination of thalidomide and lovastatin induced higher apoptosis rate than apoptosis induced by each drug alone. Our results suggest that the addition of lovastatin to the TD regimen may improve the response rate in patients with relapsed or refractory myeloma.

Transcoronary stem cell delivery using physiological endothelium-targeting perfusion technique: the rationale and a pilot study involving a comparison with conventional over-the-wire balloon coronary occlusions in patients after recent myocardial infarction.

INTRODUCTION: Recent evidence shows poor efficacy of over-the-wire balloon catheter (OTW) coronary occlusive technique adopted widely for intracoronary bone marrow stem cell (BMSC) delivery. The waterfall effect of OTW-balloon inflation/deflation with reactive > or = 2-fold flow velocity increase might be partly responsible for poor BMSC retention. AIM: To evaluate the safety, feasibility and tolerability of perfusion-infusion BMSC delivery with the facilitation of cell rolling in contact with the coronary endothelium (a pre-requisite for downstream transmigration). METHODS: We randomly assigned 11 patients (age 41-72 years) with first anterior myocardial infarction treated with PTCA+stent and LVEF < or =45% at 6-9 days to OTW in-stent occlusive (3 x 3 min.) BMSC delivery or cell infusion via a perfusion catheter with multiple side holes (SH-PC). RESULTS: OTW and SH-PC patients had a similar infarct size (mean peak CK 4361 vs 4717 U/L), LVEF (41.2% vs 40.3%), infused mononuclear cell number (2.99 x 108 range 0.61-7.48 x 108 vs 3.28 x 108 range 1.64-4.39 x 108), CD 34(+) number (1.79 x 106 vs 1.62 x 106), cell viability (91.5% vs 91.8%) and clonogenicity (CFU assay). None of the SH-PC, but 67% of OTW patients, had ST-segment elevation with chest pain (and nsVT in one) that limited OTW occlusion tolerance to 50-110 sec. At 6 months DLVEF in the OTW vs SH-PC patients was +4.2% (2-6) vs +8.8% (5-16) by MRI and +4.8 (2-7) vs +13.8% (2-24) by SPECT. CONCLUSIONS: Our work indicates that the SH-PC technique can be used safely for intracoronary BMSC transplantation. Further research is needed to determine whether the putative advantages of physiological SH-PC delivery translate into enhanced BMSC homing.

The effect of beta-carotene and its derivatives on cytotoxicity, differentiation, proliferative potential and apoptosis on the three human acute leukemia cell lines: U-937, HL-60 and TF-1.

The influence of beta-carotene (BC) and its derivatives on differentiation, proliferation and apoptosis in three human acute leukemia cell lines was studied. We investigated: (i) the cellular uptake of BC, (ii) the cytotoxicity, (iii) the effect on cell cycle progression and/or apoptosis. The dose- and time-dependent pattern of cellular BC uptake in all studied cell lines was seen. We did not observe any cytotoxic effect of BC and ATRA in the chosen concentrations. There was only limited effect of BC on gene expression. The microarrray analysis of U-937 cell line exposed to BC for 72 h showed an increased expression of BAX gene. This finding was confirmed by real-time Q-PCR analysis, and supported by a flow cytometry apoptosis tests. We did not observe any influence of studied components on cellular proliferation. The induction of differentiation after incubation with ATRA in HL-60 cells was noted. The induction of cellular apoptosis by BC was seen in all studied cell lines. We demonstrated that BC used in the concentrations achievable in vivo does not affect the proliferation and differentiation process of the studied leukemic cell lines, but can influence and enhance the apoptosis by modulating the expression of the regulatory genes.