Case report: Successful combination therapy with isavuconazole and amphotericin B in treatment of disseminated Candida tropicalis infection.

Disseminated candidiasis is a severe complication in patients with hematological malignancies who have undergone chemotherapy or hematopoietic stem cell transplantation. It has a high mortality rate. When disseminated candidiasis caused by Candida tropicalis involves either the brain or heart, the prognosis is extremely poor. Traditional methods such as cultures are limited in diagnosing disseminated candidiasis. We describe a case report of a 55-year-old man with acute myeloid leukemia who developed candidemia caused by Candida tropicalis after chemotherapy, which disseminated extensively to the heart, brain, skin, liver, spleen and kidneys. In this instance, the patient was rapidly diagnosed with candida infection by metagenomic next generation sequencing, and successfully treated with combination therapy of isavuconazole and amphotericin B. The patient continued with treatment of leukemia while simultaneously receiving antifungal therapy, and both leukemia and disseminated candidiasis were effectively controlled. This case report provides real-world experience for treatment of patients with leukemia complicated by disseminated candidiasis.

Clinical Significance of Circulating Cell-Free DNA Detection in Multiple Myeloma: A Meta-Analysis.

Circulating cell-free DNA (cfDNA) detection, a non-invasive method, appears promising for genetic analyses as well as quantitative assessment of tumor burden in patients with cancer. Although the analysis of cfDNA for clinical prognosis and monitoring disease burden in multiple myeloma (MM) has been recently studied, the results are unclear. In this meta-analysis, we explored the clinical significance of circulating cfDNA detection in patients with MM. We searched PubMed, Embase, and the Cochrane Library for eligible studies published up until July 25, 2021. Diagnostic accuracy variables were calculated and analyzed using Meta-Disc, and prognostic data were analyzed using Review Manager. Overall, seven studies comprising 235 myeloma patients met our inclusion criteria. The overall sensitivity and specificity of cfDNA to detect minimal residual disease (MRD) were 0.58 and 0.91, respectively. Moreover, higher levels of cfDNA were associated with worse progression-free survival as well as with poor overall survival. Our meta-analysis revealed that ctDNA detection has an obvious advantage in terms of MRD detection specificity, but it showed no superiority over bone marrow assessment in terms of MRD detection sensitivity, and higher levels of cfDNA were indicative of worse prognosis in patients with MM. cfDNA detection is a non-invasive method and thus shows promise as a good alternative to BM biopsies for monitoring clonal evolution and tumor burden so as to guide the treatment of patients with MM.

High-dose methotrexate-based regimens and post-remission consolidation for treatment of newly diagnosed primary CNS lymphoma: meta-analysis of clinical trials.

With the exception of high-dose methotrexate (HD-MTX), there is currently no defined standard treatment for newly diagnosed primary central nervous system lymphoma (PCNSL). This review focused on first-line induction and consolidation treatment of PCNSL and aimed to determine the optimal combination of HD-MTX and the long-term beneficial consolidation methods. A comprehensive literature search of MEDLINE identified 1407 studies, among which 31 studies met the inclusion criteria. The meta-analysis was performed by using Stata SE version 15. Forest plots were generated to report combined outcomes like the complete response rate (CRR), overall survival, and progression-free survival. We also conducted univariate regression analyses of the baseline characteristics to identify the source of heterogeneity. Pooled analysis showed a CRR of 41% across all HD-MTX-based regimens, and three- and four-drug regimens had better CRRs than HD-MTX monotherapy. In all combinations based on HD-MTX, the HD-MTX + procarbazine + vincristine (MPV) regimen showed pooled CRRs of 63% and 58% with and without rituximab, respectively, followed by the rituximab + HD-MTX + temozolomide regimen, which showed a pooled CRR of 60%. Pooled PFS and OS showed that post-remission consolidation with autologous stem cell transplantation (ASCT) was associated with the best survival outcome, with a pooled 2-year OS of 80%, a 2-year PFS of 74%, a 5-year OS of 77%, and a 5-year PFS of 63%. Next, whole-brain radiation therapy (WBRT) + chemotherapy showed a pooled 2-year OS of 72%, 2-year PFS of 56%, 5-year OS of 55%, and 5-year PFS of 41%, with no detectable CR heterogeneity throughout the entire treatment process. In HD-MTX-based therapy of newly diagnosed PCNSL, MPV with or without rituximab can be chosen as the inductive regimen, and the rituximab + HD-MTX + temozolomide regimen is also a practical choice. Based on our study, high-dose chemotherapy supported by ASCT is an efficacious approach for consolidation. Consolidation with WBRT + chemotherapy can be another feasible approach.

Cytotoxic T Cell Responses Induced by CS1/CRT Fusion DNA Vaccine in a Human Plasmacytoma Model.

To date, multiple myeloma remains an incurable disease. Immunotherapy is an encouraging option in the development of multiple myeloma (MM) therapy. CS1 is a specific myeloma antigen, which is highly expressed in myeloma cells. Calreticulin (CRT) is a key determinant of cell death, which can influence antigen presentation and promote cellular phagocytic uptake. In the current study, we constructed a DNA vaccine encoding both CS1 and CRT. Our results show that the PcDNA3.1-CS1/CRT vaccine was able to induce cytotoxic T cell responses against myeloma cells in vivo, and the tumor growth was significantly suppressed in mice immunized with this vaccine. Therefore, our findings indicate that the CS1/CRT fusion DNA vaccine may represent a promising novel myeloma therapy, and the potential for combining the CS1/CRT vaccine with other myeloma treatments.

Missed diagnosis of oesophageal perforation in ankylosing spondylitis cervical fracture: Two case reports and literature review.

Oesophageal perforation after blunt injury cervical fracture in patients with ankylosing spondylitis (AS) is rarely reported. The early diagnosis of oesophageal perforation is extremely important. We present two cases of patients with AS who sustained cervical fracture dislocation and spinal cord injury. The ossified sharp fragments caused oesophageal perforation, and the delayed diagnoses had serious consequences. Oesophageal perforation should be suspected in patients with AS and cervical fracture if bone fragments are pressing against the oesophagus and a gas shadow is visible around the fracture site on computed tomography imaging.

Maintenance therapy with immunomodulatory drugs after autologous stem cell transplantation in patients with multiple myeloma: a meta-analysis of randomized controlled trials.

BACKGROUND: Although high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) has been confirmed to result in longer remission time than conventional chemotherapy, multiple myeloma (MM) remains incurable. Post-ASCT maintenance is considered as a strategy for obtaining durable remissions and preventing tumor progression. Randomized controlled trials (RCTs) studying maintenance therapy with immunomodulatory drugs (IMiDs) after ASCT have shown some valuable survival improvements. This meta-analysis of RCTs therefore assesses the effect of post-ASCT IMiDs maintenance on MM patients. METHODS: We performed a meta-analysis to evaluate the impact of IMiDs (thalidomide or lenalidomide) as post-ASCT maintenance therapy on the survival of newly diagnosed MM patients. The outcomes for this meta-analysis were progression-free survival (PFS) and overall survival (OS). RESULTS: Eight RCTs enrolling 3514 patients were included for analysis. An obvious improvement in Os (hazard ratio [HR] 0.75) and a significant PFS advantage (HR 0.58) with post-ASCT IMiDs maintenance was revealed. Thalidomide maintenance after ASCT can result in significant benefit in Os (HR 0.72), particularly combined with corticosteroids (HR 0.66). CONCLUSIONS: MM patients after ASCT have a significant overall survival benefit with IMiDs maintenance. IMiDs maintenance was justified for MM patients who received HDT with ASCT.

Platelet-rich plasma promotes healing of osteoporotic fractures.

With an aging population worldwide, the frequency of osteoporotic fractures is increasing. Therefore, biological methods to enhance the internal fixation of osteoporotic fractures becomes more important to reduce the societal burden of care. The purposes of this study were to evaluate the role of platelet-rich plasma (PRP) in the treatment of osteoporotic fractures and to clarify the best concentration of PRP. Bone marrow mesenchymal stem cells isolated from osteoporotic rats were cultured in high- (8.21±0.4×10(9)/mL), medium-(2.65±0.2×10(9)/mL), and low-concentration (0.85±0.16×10(9)/mL) PRP and in platelet-poor plasma (8±0.5×10(6) platelet/mL). The capacities of cell proliferation and osteogenic and adipogenic differentiation were compared. A transverse osteotomy was performed in the middle of the left femoral diaphysis followed by K-wire fixation, and various concentrations of PRP were transplanted into the fracture zone. Radiologic, mechanical, and histologic evaluations were performed at 2, 4, and 8 weeks, respectively. The results indicated that PRP could inhibit adipogenic differentiation and that medium-concentration PRP was effective in inducing the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells derived from osteoporotic bone marrow and in promoting fracture healing, whereas high-concentration PRP inhibited osteogenic differentiation and callus remodeling. Certain concentrations of PRP can effectively enhance the healing of osteoporotic fractures. Medium-concentration PRP is a suitable concentration to use in practice.

Endobutton technique for dynamic fixation of traumatic symphysis pubis disruption.

Plate fixation, the conventional treatment for traumatic symphysis pubis disruption, carries the risk of implant failure and demands extensive exposure. The goal of the present study was to evaluate the outcome of dynamic fixation with the Endobutton CL, which has a long successful record in anterior cruciate ligament reconstructions. Twenty-one APC-II injuries were treated from January 2006 to December 2009. The mean duration of follow-up was 23 months (18 to 26). All patients received Endobutton fixation. The incision length was 6.8 +/- 13 cm. The external blood loss was 106 +/- 15 mL. The average surgical time was 63 +/- 12 min. The symphysis distance after reduction was 4.1 +/- 1.2 mm. The symphysis distance at final visit was 4.2 +/- 1.2 mm. Loss of reduction was not significant during bone healing (p = 0.09). The Majeed scoring was excellent in 15 patients, good in 5 patients and fair in 1 patient. One malreduction was seen; there was no implant failure. Our results indicate that Endobutton fixation of the pubic symphysis might be used in the treatment of APC-II injuries.

Lentivirus-mediated RNA interference reversing the drug-resistance in MDR1 single-factor resistant cell line K562/MDR1.

Multidrug-resistance (MDR) is a major hindrance to successful chemotherapy. The emergence of MDR is multi-factorial. Among them, the MDR1 gene/P-glycoprotein (P-gp) is a popular and important reason. In our study, an MDR1 single-factorial drug-resistant leukemia cell line K562/MDR1 was constructed via transferring full-length human MDR1 cDNA into drug-sensitive K562 cells. The short-hairpin RNA (shRNA) targeting MDR1 gene was transfected into K562/MDR1 cell lines by the replication-defective lentiviral vector derived from HIV-1. The efficiency of RNA interference (RNAi) to silence the MDR1 gene and reverse multidrug-resistance in the MDR1 single-factor drug-resistance cell line K562/MDR1 was evaluated. The multi-factor resistant cell line K562/A02, induced by doxorubicin exposure, was used as a control. After RNA interference, the expression of the MDR1 gene and P-gp in K562/MDR1 was markedly down-regulated and the drug sensitivity was restored as IC(50) values became similar to the K562 sensitive cell line. The expression of the MDR1 gene and P-gp in K562/A02 was markedly down-regulated too, and drug-resistance to anticancer drug is reduced to some extent but the IC(50) was significantly higher than that of the sensitive cell line. These results demonstrated that lentivirus-mediated RNAi could efficiently down-regulate the expression of MDR1 and Pgp, and successfully reverse a cell's resistance to chemotherapeutic. Due to only MDR1 resistance, the K562/MDR1 cell showed much high specificity and thus is a better cell model for MDR1/P-gp research.

[Methylation of P15INK4B gene in patients with myelodysplastic syndromes and demethylating effects of drugs].

OBJECTIVES: To detect the methylation of P15INK4B gene in patients with myelodysplastic syndromes (MDS) and to investigate the demethylating effects of decitabine and arsenic trioxide (As2O3). METHODS: The bone marron mononuclear cells from 14 MDS patients were collected. The methylation of P15INK4B gene was detected with restrictive endonucleases combined with PCR technique. The peripheral blood mononuclear cells from one of the patients who had progressed into acute leukemia were treated with decitabine and As2O3 in vitro to test the change of methylation. RESULTS: No methylation of P15INK4B gene was detected in MDS patients with low risk of leukemia. The methylation of P15K4B gene was found in 4 MDS patients with high-risk of leukemia and 4 patients who had progressed from MDS to acute leukemia. After exposed to decitabine or As2O3, the methylation went down by 50%. CONCLUSION: P15INK4B gene hypermethylation is closely associated with MDS pathogenesis. Decitabine and As2O3 have demethylating effect on the cells from the MDS patient.