Co-infection with Legionella and SARS-CoV-2: a case report.

INTRODUCTION: We report a case of COVID-19 with Legionella co-infection that was treated successfully. CASE REPORT: A 73-year-old man presented to the hospital with symptoms of fatigue that continued for the next 5 days. The patient was receiving docetaxel and prednisolone chemotherapy for prostate cancer. Laboratory findings on admission showed positive urine Legionella antigen test and SARS-CoV-2 test. He was administered antiviral and antibacterial agents, and a corticosteroid. Pneumonia exacerbated on day 2 of hospitalization. The patient underwent tracheal intubation and began receiving multidisciplinary care. On day 8 of hospitalization, his oxygenation improved, and the patient was extubated. He discharged on day 27 of hospitalization. CONCLUSIONS: The patient had a favorable outcome with early diagnosis and early treatment of both diseases. Patients with severe COVID-19 disease need to be evaluated for co-infection. Further, early diagnosis and early treatment of the microbial bacteria causing the co-infection are important.

Rocuronium anaphylaxis in a 7-year-old boy during the induction of anesthesia.

We report a case of rocuronium-induced anaphylaxis in a previously healthy 7-year-old boy. The first presenting sign of anaphylaxis was bronchospasm, appearing 11 min after he received intravenous doses of rocuronium (1 mg/kg) (Eslax®, MSD Co. Ltd., Tokyo, Japan), propofol (2 mg/kg), and cefazolin sodium (25 mg/kg). After the administration of adrenalin and ephedrine hydrochloride, bronchospasm resolved, and the vital signs became stable. Percutaneous pinning of his left humeral supracondylar fracture was performed without problems. The next day, he was successfully liberated from the ventilator support and discharged on the fifth hospital day. On the 76th postoperative day, we performed intradermal tests of rocuronium, propofol, and cefazolin. It showed that diluted rocuronium alone induced 14 mm of flare and 8 mm of wheal within 5 min, both of which disappeared within 15 min after the intradermal injection. The reaction was too quick to mention the possible contribution of rocuronium-specific IgE. His rapid reaction at the rocuronium skin test and anaphylactic reaction upon the first exposure to this drug may highlight the association of rocuronium anaphylaxis with IgE independent mast cell stimulation through mas-related G-protein coupled receptor X2 (MRGPRX2 receptor).

[Positive Effect of an Anesthesia Preoperative Evaluation Clinic in a Small Hospital].

BACKGROUND: We investigated the effect of an anesthetic clinic in a small hospital, with only two anesthesiologists, on operation unit activities and labor burden of the anesthesiologists. METHODS: The number of outpatients visiting the anesthetic clinic during the six month after opening of the clinic was evaluated. The doctor's fee and the number of operations under our anesthetic management were also analyzed. The total time of anesthesiologist's overtime work was compared with that of the corresponding period of the past year. RESULTS: 241 cases (48%) among 502 elective anesthesia cases were examined at the clinic, and 65% of them visited before admission for the surgery and paid for doctor's examination. Although the number of anesthesiologists working at operating rooms decreased 8% after opening of the clinic, the number of operations under the anesthetic management increased 6% compared to the corresponding period of the past year. The overtime work of anesthesiologists decreased drastically probably due to increased efficiency of the operative anesthetic labor resulting from the reduction of anesthesiologist's preoperative duties at bedside. CONCLUSIONS: Establishment of an anesthetic clinic had a positive effect on both hospital-management and anesthesiologist-labor even in a small hospital with a few anesthesiologists.

CCAAT/enhancer-binding protein ß expressed by bone marrow mesenchymal stromal cells regulates early B-cell lymphopoiesis.

The transcription factor CCAAT/enhancer-binding protein ß (C/EBPß) regulates the differentiation of a variety of cell types. Here, the role of C/EBPß expressed by bone marrow mesenchymal stromal cells (BMMSCs) in B-cell lymphopoiesis was examined. The size of the precursor B-cell population in bone marrow was reduced in C/EBPß-knockout (KO) mice. When bone marrow cells from C/EBPß-KO mice were transplanted into lethally irradiated wild-type (WT) mice, which provide a normal bone marrow microenvironment, the size of the precursor B-cell population was restored to a level equivalent to that generated by WT bone marrow cells. In coculture experiments, BMMSCs from C/EBPß-KO mice did not support the differentiation of WT c-Kit(+) Sca-1(+) Lineage(-) hematopoietic stem cells (KSL cells) into precursor B cells, whereas BMMSCs from WT mice did. The impaired differentiation of KSL cells correlated with the reduced production of CXCL12/stromal cell-derived factor-1 by the cocultured C/EBPß-deficient BMMSCs. The ability of C/EBPß-deficient BMMSCs to undergo osteogenic and adipogenic differentiation was also defective. The survival of leukemic precursor B cells was poorer when they were cocultured with C/EBPß-deficient BMMSCs than when they were cocultured with WT BMMSCs. These results indicate that C/EBPß expressed by BMMSCs plays a crucial role in early B-cell lymphopoiesis.

Cyclic AMP responsive element binding proteins are involved in 'emergency' granulopoiesis through the upregulation of CCAAT/enhancer binding protein ß.

In contrast to the definitive role of the transcription factor, CCAAT/Enhancer binding protein α (C/EBPα), in steady-state granulopoiesis, previous findings have suggested that granulopoiesis during emergency situations, such as infection, is dependent on C/EBPß. In this study, a novel lentivirus-based reporter system was developed to elucidate the molecular switch required for C/EBPß-dependency. The results demonstrated that two cyclic AMP responsive elements (CREs) in the proximal promoter region of C/EBPß were involved in the positive regulation of C/EBPß transcription during granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced differentiation of bone marrow cells. In addition, the transcripts of CRE binding (CREB) family proteins were readily detected in hematopoietic stem/progenitor cells. CREB was upregulated, phosphorylated and bound to the CREs in response to GM-CSF stimulation. Retroviral transduction of a dominant negative CREB mutant reduced C/EBPß mRNA levels and significantly impaired the proliferation/differentiation of granulocyte precursors, while a constitutively active form of CREB facilitated C/EBPß transcription. These data suggest that CREB proteins are involved in the regulation of granulopoiesis via C/EBPß upregulation.

C/EBPß is involved in the amplification of early granulocyte precursors during candidemia-induced "emergency" granulopoiesis.

Granulopoiesis is tightly regulated to meet host demands during both "steady-state" and "emergency" situations, such as infections. The transcription factor CCAAT/enhancer binding protein ß (C/EBPß) plays critical roles in emergency granulopoiesis, but the precise developmental stages in which C/EBPß is required are unknown. In this study, a novel flow cytometric method was developed that successfully dissected mouse bone marrow cells undergoing granulopoiesis into five distinct subpopulations (#1-5) according to their levels of c-Kit and Ly-6G expression. After the induction of candidemia, rapid mobilization of mature granulocytes and an increase in early granulocyte precursors accompanied by cell cycle acceleration was followed by a gradual increase in granulocytes originating from the immature populations. Upon infection, C/EBPß was upregulated at the protein level in all the granulopoietic subpopulations. The rapid increase in immature subpopulations #1 and #2 observed in C/EBPß knockout mice at 1 d postinfection was attenuated. Candidemia-induced cell cycle acceleration and proliferation of hematopoietic stem/progenitors were also impaired. Taken together, these data suggest that C/EBPß is involved in the efficient amplification of early granulocyte precursors during candidemia-induced emergency granulopoiesis.

Rapid automated detection of ABL kinase domain mutations in imatinib-resistant patients.

ABL tyrosine kinase inhibitor (TKI), imatinib is used for BCR-ABL(+) leukemias. We developed an automatic method utilizing guanine-quenching probes (QP) to detect 17 kinds of mutations frequently observed in imatinib-resistance. Results were obtained from 100µL of whole blood within 90min by this method. Detected mutations were almost identical between QP method and direct sequencing. Furthermore, the mutation-biased PCR (MBP) was added to the QP method to increase sensitivity, resulting earlier detection of T315I mutation which was insensitive to any ABL TKIs. Thus, the QP and MBP-QP may become useful methods for the management of ABL TKI-treated patients.