Metagenomic next-generation sequencing performed on blood samples for the early recognition of severe Pneumocystis pneumonia in critical hematological patients.

Severe Pneumocystis pneumonia (PCP) has a poor prognosis, and its early and precise diagnosis is difficult in immunocompromised individuals. Therefore, this study explored the diagnostic value of metagenomic next-generation sequencing (mNGS) of peripheral blood in diagnosing severe PCP in patients with hematological diseases. This prospective study analyzed the clinical manifestations, mNGS results (from the peripheral blood), traditional pathogen detection results, laboratory test results, chest computed tomography (CT) images, treatments, and outcomes of severe PCP in hematological patients who were hospitalized in the 2 centers of the Affiliated Hospital of Soochow University between September 2019 and October 2021. A total of 31 cases of hematological diseases complicated with pulmonary infections, including 7 cases of severe PCP diagnosed by mNGS performed on peripheral blood samples, were analyzed. Traditional pathogen detection methods for PCP cannot be used. In contrast, the laboratory readings for Pneumocystis jirovecii (Pj) detected within 48 hours of symptom onset by mNGS on the 7 blood samples ranged from 12 to 5873, with a median value of 43. Under the guidance of the mNGS results, preemptive antimicrobial therapy with trimethoprim/sulfamethoxazole alone or in combination with caspofungin was administered to treat Pj. After treatment, 4 patients recovered, and 3 patients died of acute respiratory failure and acute respiratory distress syndrome (ARDS). MNGS performed on peripheral blood samples is optional but can provide early recognition of severe PCP and help guide empirical treatment in critical hematological patients.

Flexural Behavior of Two-Span Continuous CFRP RC Beams.

This paper investigates the feasibility of replacing steel bars with carbon-fiber-reinforced polymer (CFRP) bars in continuous reinforced concrete (RC) beams. A numerical model is introduced. Model predictions are compared with the experimental results that are available in the literature. A comprehensive numerical investigation is then performed on two-span CFRP/steel RC beams with ρb2 = 0.61-3.03% and ρb1/ρb2 = 1.5, where ρb1 and ρb2 are tensile bar ratios (ratios of tensile bar area to effective cross-sectional area of beams) over positive and negative moment regions, respectively. The study shows that replacing steel bars with CFRP bars greatly improves the crack mode at a low bar ratio. The ultimate load of CFRP RC beams is 89% higher at ρb2 = 0.61% but 7.2% lower at ρb2 = 3.03% than that of steel RC beams. In addition, CFRP RC beams exhibit around 13% greater ultimate deflection compared to steel RC beams. The difference of moment redistribution between CFRP and steel RC beams diminishes as ρb2 increases. ACI 318-19 appears to be conservative, and it leads to more accurate predictions of moment redistribution in CFRP RC beams than that in steel RC beams.

Successful prevention of severe allergic transfusion reactions with omalizumab.

BACKGROUND: Allergic transfusion reactions (ATRs) are a common adverse reaction to transfusion therapy and can be potentially fatal. Washing blood products is the most effective strategy for preventing ATRs; however, washed products, especially platelets, are not available at many blood centers. STUDY DESIGN AND METHODS: A 29-year-old female patient with an advanced myelodysplastic/myeloproliferative neoplasm, unclassifiable, developed severe ATRs after four platelet transfusions in a week. She showed no response to premedication with histamines and steroids and still had severe ATRs with the next three platelet transfusions. A laboratory workup revealed that her IgA level was slightly decreased, while her haptoglobin level was normal. Anti-IgA testing was not available. The patient decided to undergo allogeneic peripheral blood stem cell (PBSC) transplantation. As the onset of symptoms ATR, which were similar to Type 1 hypersensitivity reactions mediated by IgE antibodies, occurred immediately after transfusion and omalizumab is a humanized monoclonal anti-IgE, we elected to offer off-label use of omalizumab before administering the conditioning regimen. RESULTS: Omalizumab was injected subcutaneously at a dose of 150 mg. Surprisingly, transfusion reactions fully resolved within 24 hours. No serious side effects were noticed. Another 150 mg of omalizumab was administered 1 day before PBSC infusion. The patient remained asymptomatic without any signs of ATRs throughout the whole period of transplantation. Seven months after transplantation, the patient was in complete remission without overt complications. CONCLUSION: This case suggests that omalizumab is a promising new alternative treatment for the prevention of severe ATRs.

Reduced urinary corin levels in patients with chronic kidney disease.

Corin is a cardiac protease that regulates BP (blood pressure) by activating natriuretic peptides. Recent animal studies identified corin expression in the kidney where it may regulate renal function. In the present study, we tested the hypothesis that corin may be present in human urine and that urinary corin levels may be altered in patients with kidney disease. We obtained urine and kidney tissue samples from normal individuals and CKD (chronic kidney disease) patients. Using ELISA, we detected corin protein in human urine. In normal individuals, urinary corin levels did not correlate with that of plasma, indicating that urinary corin is probably of kidney origin. Compared with normal controls, CKD patients had markedly reduced urinary corin levels and this reduction correlated with disease severity. By immunostaining, human corin protein was identified on the epithelial cell surface in renal tubules. The renal corin mRNA and protein levels were significantly lower in CKD patients than non-CKD controls. The results indicate that renal tubular corin may be shed into urine and that urinary and renal corin levels were reduced in CKD patients. These data suggest that reduced corin levels in the kidney may reflect the underlying pathology in CKD.

Identification and functional analysis of a novel von Willebrand factor mutation in a family with type 2A von Willebrand disease.

von Willebrand factor (VWF) is essential for normal hemostasis. VWF gene mutations cause the hemorrhagic von Willebrand disease (VWD). In this study, a 9-year-old boy was diagnosed as type 2A VWD, based on a history of abnormal bleeding, low plasma VWF antigen and activity, low plasma factor VIII activity, and lack of plasma high-molecular-weight (HMW) VWF multimers. Sequencing analysis detected a 6-bp deletion in exon 28 of his VWF gene, which created a mutant lacking D1529V1530 residues in VWF A2 domain. This mutation also existed in his family members with abnormal bleedings but not in >60 normal controls. In transfected HEK293 cells, recombinant VWF ΔD1529V1530 protein had markedly reduced levels in the conditioned medium (42±4% of wild-type (WT) VWF, p<0.01). The mutant VWF in the medium had less HMW multimers. In contrast, the intracellular levels of the mutant VWF in the transfected cells were significantly higher than that of WT (174±29%, p<0.05), indicating intracellular retention of the mutant VWF. In co-transfection experiments, the mutant reduced WT VWF secretion from the cells. By immunofluorescence staining, the retention of the mutant VWF was identified within the endoplasmic reticulum (ER). Together, we identified a unique VWF mutation responsible for the bleeding phenotype in a patient family with type 2A VWD. The mutation impaired VWF trafficking through the ER, thereby preventing VWF secretion from the cells. Our results illustrate the diversity of VWF gene mutations, which contributes to the wide spectrum of VWD.