Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed >/= 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a >/= 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms >/= 7 weeks from diagnosis may benefit from further delay.

Human myeloma cells from about 10% of cases with multiple myeloma expressed CD33 and had monocytoid morphology with convoluted nuclei, and all these patients had no increase in serum CRP values. In CD33(+) myeloma cells as well as myeloma cell lines, CD33 expression levels were correlated with the increased expression levels of CEBPA (C/EBPalpha). This correlation was confirmed by the finding that transfection with the CEBPA gene induced CD33 expression in a CD33(-) myeloma cell line. As suggested by the lack of an increase in serum CRP values in CD33(+) myelomas, IL-6 down-regulated the expression of CD33 in CD33(+) myeloma cell lines along with the down-regulation of CEBPA gene expression. Cucurbitacin I (STAT3 inhibitor), but not U0126 (MAPK inhibitor), could abolish the effect of IL-6. Furthermore, IL-6 up-regulated the expression of MYC via STAT3 phosphorylation and MYC bound to the promoter region of the CEBPA gene followed by the down-regulation of CEBPA expression. It was confirmed that introduction of shRNA for MYC into a CD33(+) myeloma cell line blocked the IL-6-induced down-regulation of CD33 and CEBPA expression. Therefore, these results indicate that IL-6 can reverse the expression level of CD33 by up-regulating MYC followed by the down-regulation of CEBPA expression.

Multiple myeloma (MM) is a proliferative disorder of monoclonal plasma cells which accumulate in human bone marrow (BM). CD19 is a hallmark differentiation antigen of the B cell lineage and positively regulates antigen receptor signal transduction in mature B cells. We have previously shown that malignant plasma cells (myeloma cells) isolated from the MM patients lack the CD19 expression, while non-malignant plasma cells isolated from the healthy donors do express the CD19 antigens. It is also intriguing that there exists both CD19- and CD19+ plasma cells in some cases in pre-myeloma states including monoclonal gammopathy of undetermined significance (MGUS). It indicates that MGUS is usually composed of phenotypically non-malignant (CD19+) and malignant (CD19-) plasma cells. Furthermore, we recently demonstrate that, expression of the CD19 gene markedly inhibits the proliferation of human myeloma cell lines in vitro, and exhibits the reduced tumorigenicity in vivo and no anchorage-independent growth in vitro of a tumorigenic myeloma cell line. This inhibitory effect might result from the CD19-mediated intracellular signals because it is not observed in cells expressing the mutant CD19, which lacks the cytoplasmic domain. In this review, we suggest that loss of CD19 in MM could contribute to the proliferative advantage of the malignant plasma cell clones in this disease. Furthermore, we propose the usefulness of the phenotypic analysis of plasma cells in human plasma cell dyscrasia as a new diagnostic tool, and the CD19 gene as a potential target for the gene therapy in MM.

In the peripheral blood (PB) we detected so-called early plasma cells that might already be committed to entering the bone marrow (BM). By two-colour staining with FITC-anti-CD38 antibody, their intensity (CD38++) of expression of CD38 antigen was between that of germinal center (GC) B cells (low expression (CD38+)) and that of BM plasma cells (high expression (CD38++), and their phenotype was CD38++ CD19+ CD10- CD20- CD21+ CD24- CD39+ CD5- VLA-4+ VLA-5- MPC-1- without expression of surface membrane IgM (SmIgM). Morphological and immunological examination of the sorted cells confirmed that they were plasmacytoid cells with expression of cytoplasmic IgG (cIgG). Variations of these early plasma cells were examined in various diseases. In active systemic lupus erythematosus, bacterial septicaemia and liver cirrhosis, early plasma cell levels were significantly increased in PB, and after subsidence of such inflammation (inactive states) these cells returned to normal levels. In contrast, normal early plasma cells were significantly suppressed in myelomas, whilst normal or slightly increased numbers of early plasma cells was found in benign monoclonal gammopathy (BMG). In addition, the number of normal early plasma cells returned to a normal level in myeloma cases with complete responses. Therefore, early plasma cells were identified phenotypically, and an increase and decrease in these cells in PB may reflect mobilization and suppression, respectively, of activated B cells into BM plasma cells.

To evaluate nuclear factor-κB (NF-κB) activity in primary myeloma cells from myeloma patients, we confirmed that the expression levels of CD54 showed a good correlation with the levels of DNA binding activity for NF-κB in human myeloma cell lines, and thus analyzed the expression levels of CD54 on CD38(++) plasma cell fractions as one of NF-κB activity. Primary myeloma cells unexpectedly showed constitutively lower expressions of CD54 than normal bone marrow (BM) plasma cells. Furthermore, the expression levels of CD54 on these plasma cells showed a significant correlation with the plasma levels of CXCL12 stromal cell-derived factor-1a (SDF-1a) in their BM aspirates, and the expressions of CXCR4, the receptor for CXCL12, decreased on primary myeloma cells compared with normal BM plasma cells. It was also confirmed that the addition of CXCL12 to the in vitro culture significantly induced the up-regulation of CD54 expression in primary myeloma cells. In addition, myeloma cells with lower expressions of CD54 were more unstable in the in vitro culture, resulting in a marked reduction of the viable cell number. In the immunohistochemical analysis of BM aspirates, myeloma cells with lower CD54 expression resided in the perivascular regions. Therefore, these data suggest that primary myeloma cells exhibit constitutively lower CD54 that might be partially regulated by CXCL12, and their localizations in the BM may be associated with the expression levels of CD54.

Background Glaucoma is a nonreversible optic neuropathy that may occur primarily or secondary to ocular pathology. Uveitis is a major etiological factor for secondary glaucoma, arising either owing to the inflammation itself or resulting from therapeutic steroid use. Many patients with uveitic glaucoma ultimately require a surgical intervention to maintain optimal intraocular pressures (IOP), often after treatment failure with multiple ocular antihypertensive agents. A leading surgical option for such patients is trabeculectomy augmented by intraoperative administration of mitomycin C (MMC). However, in the context of uveitic glaucoma, the relative merit of trabeculectomy with MMC compared with alternative surgical techniques, such as valve implantation, remains a subject of debate among ophthalmic surgeons. Study design This is a review of the literature to evaluate the efficacy and safety of trabeculectomy with MMC in uveitic glaucoma. Materials and methods A literature review of the use of trabeculectomy with MMC administration as an initial surgical management for uveitic glaucoma in adults was performed. Articles were identified by searches of PubMed and the Cochrane Library, using a strategy that defined the target condition (uveitis OR uveitic glaucoma OR inflammatory glaucoma) AND the intervention (trabeculectomy); limitation to MMC-augmented trabeculectomy was undertaken at the abstract and full-text stage. Data extracted included age of the patients, nature of the uveitis, preoperative status in terms of IOP and number of ocular hypotensive medications used, outcomes at annual time-points including IOP, number of ocular hypotensive medications, and surgical success (defined in terms of IOP) up to 5 years postoperatively. Adverse events were also recorded. Results The search strategy identified 498 papers, of which 32 were duplicates, 431 were excluded at abstract stage, and 28 were excluded at full-text stage; five of the 28 satisfied the inclusion criteria but were found to contain data that were entirely or largely contained within one of the other included papers. A total of seven studies were included, comprising 300 patients, with a weighted mean age of 45.8 years (range=30.0–56.9 years), and a range of uveitis syndromes including idiopathic (30%), Behcet’s disease (24.3%), Fuchs’ heterochromic uveitis (13.7%), and Vogt-Koyanagi-Harada syndrome (12.3%). Preoperative IOP and number of medications were reported in all studies. The mean (weighted) preoperative IOP was 34.2 mmHg (range=26.8–39.5 mmHg) and the mean (weighted) number of medications was 3.4 (range=2.3–4.5). Postoperative data were variably reported across the studies; the mean IOP at 1 year was reported in five studies (range=13.8–18.5 mmHg), the mean number of medications at 1 year was reported in four studies (range=0.3–2.6), and surgical success was variably defined preventing direct comparison or aggregation. Conclusion There is limited evidence to evaluate trabeculectomy with MMC as an initial surgical intervention for uveitic glaucoma, with the available evidence being derived entirely from retrospective studies, most of which do not have a parallel comparator group. Variation in reporting limits direct comparison and aggregation of these studies. Comparison between before and after intervention provides some limited evidence of effectiveness and safety. So, there is a need for well-designed prospective randomized controlled trials with long-term follow-up to compare interventions in this vulnerable group of patients.

Introduction

Acute myeloid leukemia (AML) is an aggressive disorder characterized by accumulation of blast cells in bone marrow. The heterogeneous phenotype of AML is based on cytogenetic mutations and molecular aberrations. Immunophenotyping is a convenient method for quick and reproducible diagnosis of most hematological malignancies. The higher frequency of aberrant expression of lymphoid markers in AML may be related to environmental changes and accumulation of biological defects. The CD7, a T‑cell antigen, is expressed in a minority of patients with AML, and it is the most common aberrant marker found in AML in most studies.

Aim

We aimed to determine the frequency of CD7 expression in AML and to verify if this aberrant expression is true or false.

Patients and methods

The study included 32 newly diagnosed patients with AML. Detection of CD7 in AML was done by using an independent method to check the gene expression, namely, reverse transcriptase‑PCR, besides the usually used monoclonal antibody‑based flow cytometric measurements.

Results

The study revealed the frequency of CD7 expression in newly diagnosed AML cases to be 18.1% by flow cytometry. The AML cases with positive CD7 expression by flow cytometry were subjected to reverse transcriptase‑PCR to determine gene expression. All cases with positive CD7 expression by flow cytometry were found to be negative for CD7 gene expression by PCR.

Conclusion

This study raises a reasonable possibility of a false‑positive detection of aberrant CD7 expression in AML using immunophenotyping by flow cytometry.