Unilateral lymphadenitis caused by community-associated methicillin-resistant Staphylococcus aureus ST834 strain.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a global concern, primarily as a cause of skin and soft tissue infections, particularly in young people. Here, we describe a case of unilateral multiple lymphadenitis caused by the CA-MRSA sequence type (ST) 834 strain. A previously healthy 15-year-old girl was referred to our hospital with fever and swollen lymph nodes in the right axillary, cubital, and groin regions. Imaging examinations revealed enlargement of the lymph nodes in these areas but no swelling in any other lymph nodes. The patient had self-destructive lymph nodes in her groin. MRSA was detected in all swollen lymph node samples. Antimicrobial susceptibility tests showed that MRSA was susceptible to clindamycin and levofloxacin, leading to the suspicion of CA-MRSA. Genetic analysis revealed that all strains were ST834 and carried the staphylococcal cassette chromosome mec IV and the toxic shock syndrome toxin-1 gene but not the Panton-Valentine leukocidin gene. The patient was treated with linezolid followed by oral clindamycin. This was a rare case of unilateral multiple lymphadenitis caused by ST834 CA-MRSA. Although ST834 strains are rarely reported, lymphadenitis has been frequently reported and is considered more likely to cause lymphadenitis than other CA-MRSA strains.

[Management of iron overload during pregnancy and childbirth in a patient with ferroportin disease].

An asymptomatic woman in her early 40s with a history of hyperferritinemia (5,412 ng/ml) was referred to our hospital after repeated phlebotomy for hemosiderosis. She had unexplained hyperferritinemia, low-normal transferrin saturation, and high hepcidin levels, in the absence of iron overload-induced organ injury. She was diagnosed with ferroportin disease based on detection of the SLC40A1 variant SLC40A1 c.485_487del (p.Val162del) on genetic analysis. Her ferritin levels remained stable during pregnancy, and postpartum anemia was successfully treated with 2-week oral iron therapy. Ferroportin disease is characterized by impaired iron export and preferential iron trapping in tissue macrophages. To reduce risk of anemia, a non-aggressive phlebotomy regimen is recommended in patients with ferroportin disease, which shows a milder clinical course compared with other classical hemochromatosis subtypes.

COVID-19 Cluster in the Hematology/Respirology Ward of a University Hospital during the Seventh Wave of the SARS-CoV-2 Pandemic in Japan: A Descriptive Study.

Objective Patients with hematological malignancies and solid organ tumors reportedly tend to have a more severe coronavirus disease 2019 (COVID-19) trajectory than do those with other diseases. We studied the clinical features and outcomes of nosocomial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the seventh wave of the pandemic. Methods This study retrospectively described the characteristics of COVID-19 clusters involving patients in the hematology/respirology ward of Kochi Medical School Hospital during the seventh wave of the pandemic of SARS-CoV-2. Patients A total of 40 individuals, including 25 patients and 15 healthcare workers, were studied. The diagnosis of SARS-CoV-2 infection was based on reverse transcription polymerase chain reaction performed on nasopharyngeal samples. Results Eleven patients had hematological diseases, and 14 had respiratory diseases. Most patients presented with a fever (n=19) and/or sore throat (n=10). Lower respiratory tract symptoms and pneumonia were rather infrequent, occurring in two patients. All patients received antivirals. The maximal severities were mild in 21 patients and moderate in 2. Two asymptomatic patients with SARS-CoV-2 infection did not develop symptoms of COVID-19. Cycle threshold values in nasopharyngeal samples were significantly lower in patients with COVID-19 than in those who were asymptomatic at the time of the diagnosis with SARS-CoV-2 infection. All SARS-CoV-2-infected inpatients recovered or did not develop symptoms of COVID-19. Conclusion COVID-19 vaccination, early or preemptive treatment with antivirals, and intrinsic changes in SARS-CoV-2 may have contributed to the more favorable outcomes in our series than in previously reported nosocomial clusters.

Psoas and Mediastinal Abscesses during Intravenous Tocilizumab Treatment in Multicentric Castleman Disease.

Tocilizumab has been used to treat idiopathic multicentric Castleman disease (iMCD). As tocilizumab prevents interleukin-6 from exerting pro-inflammatory effects, there is some concern about a delayed diagnosis of severe infections during tocilizumab treatment. Although serious infections during tocilizumab therapy have been previously described in patients with rheumatoid arthritis, they have not been reported in iMCD. We herein report a case of disseminated Staphylococcus aureus infection after a superficial skin wound followed by psoas and mediastinal abscesses with pyogenic spondylodiscitis in an iMCD patient with diabetes. Physicians should be alert for the occurrence of disseminated S. aureus infection after even minor skin injury during tocilizumab therapy.

[Diagnostic efficacy of WT1 expression in asymptomatic acute promyelocytic leukemia].

We report a case of early asymptomatic acute promyelocytic leukemia (APL) with leukopenia as the only hematologic abnormality. A 55-year-old woman was referred to our hospital with leukopenia (white blood cell [WBC] count of 1,500/µl with 36% neutrophils), which was incidentally determined during an annual medical checkup. Two months before the presentation, her WBC was 3,400/µl with 60% neutrophils. A WBC count was 1,200/µl with 40% neutrophils. Immature myeloid cells were not observed. Her hemoglobin level and platelet count were normal. Moreover, no clinical or laboratory evidence was suggestive of disseminated intravascular coagulation or infection. The peripheral blood WT1 mRNA level was increased to 26,000 copies/µg RNA. The bone marrow aspirate smear revealed 40% myeloperoxidase-positive promyelocytes with occasional Auer rods and faggots; however, circulating leukemia cells were not revealed by cell morphology or flow cytometry analysis. Quantitative reverse-transcription polymerase chain reaction analysis revealed WT1 and PML-RARA fusion transcripts in both the peripheral blood and bone marrow samples. Thus, the determination of peripheral blood WT1 expression may be sufficiently sensitive for detecting a small number of circulating APL cells.

Targeting VEGF with bevacizumab inhibits malignant effusion formation of primary human herpesvirus 8-unrelated effusion large B-cell lymphoma in vivo.

Primary human herpesvirus 8 (HHV8)-unrelated effusion large B-cell lymphoma (ELBCL) is recognized as a new clinical entity, but its pathogenesis and therapeutic strategies remain largely unknown. We have generated two mouse models with profuse lymphomatous effusions that resemble HHV8-unrelated ELBCL occurring in humans, by grafting the cell lines designated as Pell-1 and Pell-2. Using these in vivo models, we evaluated the potential role of vascular endothelial growth factor (VEGF) in the pathogenesis of HHV8-unrelated ELBCL. Both Pell-1 and Pell-2 cells consistently produced very high levels of VEGF in mice, in contrast to in vitro findings of relatively low VEGF production in culture medium by HHV8-unrelated ELBCL cells, especially Pell-1 cells. Conversely, returning Pell-1 cells grown in mice to culture medium markedly suppressed VEGF production to the original in vitro level. These findings suggest that the tumour microenvironment plays a role in the steady production of VEGF. We also found that the interaction between HHV8-unrelated ELBCL cells and peritoneal mesothelial cells increased the production of VEGF in vitro. Finally, we found that bevacizumab significantly suppressed effusion formation and lymphoma cell growth in both mouse models. These results suggest that bevacizumab is a rational approach to the treatment of HHV8-unrelated ELBCL.

Glucocorticoid-induced redistribution lymphocytosis in mantle cell lymphoma with hyaline vascular Castleman disease-like features.

We report a case of mantle cell lymphoma mimicking Castleman disease. A 76-year-old man presented with generalized lymphadenopathy, splenomegaly, anemia, polyclonal gammopathy, and pulmonary infiltrations. Lymph node biopsy revealed histological features of hyaline vascular Castleman disease. Treatment with prednisolone induced lymphocytosis with immunophenotypic and genetic features of mantle cell lymphoma. A detailed immunohistochemical study of the lymph node demonstrated a mantle cell lymphoma-mantle zone growth pattern. Glucocorticoid-induced distribution lymphocytosis has not been reported in mantle cell lymphoma. Careful observation of circulating lymphocytes during steroid treatment may enable diagnosis of the underlying occult lymphoma in a subset of patients exhibiting clinical manifestations of Castleman disease.

Development of a novel cell line-derived xenograft model of primary herpesvirus 8-unrelated effusion large B-cell lymphoma and antitumor activity of birabresib in vitro and in vivo.

BACKGROUND: Primary human herpesvirus 8 (HHV8)-unrelated effusion large B-cell lymphoma is a clinical disease entity distinct from HHV8-positive primary effusion lymphoma (PEL). However, the lack of experimental HHV8-unrelated effusion large B-cell lymphoma models continues to hinder the pathophysiologic and therapeutic investigations of this disorder. METHODS: The lymphoma cells were obtained from the pleural effusion of a patient with primary HHV8-unrelated effusion large B-cell lymphoma and cultured in vitro. RESULTS: We established a novel HHV8-unrelated effusion large B-cell lymphoma cell line, designated Pell-1, carrying a c-MYC rearrangement with features distinct from those of HHV8-positive PEL. Moreover, we developed an HHV8-unrelated effusion large B-cell lymphoma cell line-derived xenograft model. Pell-1 cells induced profuse lymphomatous ascites and subsequently formed intra-abdominal tumors after intraperitoneal implantation into irradiated nonobese diabetic/severe combined immunodeficient mice. Thus, this xenograft mouse model mimicked the clinical phenomena observed in patients and recapitulated the sequential stages of aggressive HHV8-unrelated effusion large B-cell lymphoma. The bromodomain and extraterminal domain (BET) inhibitors JQ1 and birabresib (MK-8628/OTX015) reduced the proliferation of Pell-1 cells in vitro through the induction of cell cycle arrest and apoptosis. The antitumor effect of BET inhibition was also demonstrated in vivo, as birabresib significantly reduced ascites and suppressed tumor progression without apparent adverse effects in the xenografted mice. CONCLUSION: These preclinical findings suggest the therapeutic potential of targeting c-MYC through BET inhibition in HHV8-unrelated effusion large B-cell lymphoma.

[Acquired hypofibrinogenemia in patients with leukemia during steroid therapy].

Acquired hypofibrinogenemia is observed in patients with severe liver disease, disseminated intravascular coagulation, and high-volume perioperative fluid replacement. In lymphoblastic leukemia, hypofibrinogenemia is most frequently caused by the administration of L-asparaginase. Here we report the cases of two patients with acquired hypofibrinogenemia that occurred during steroid-containing chemotherapy treatment against lymphoblastic blast crisis of chronic myeloid leukemia in the first case and acute lymphoblastic leukemia in the second case. Administration of steroids repeatedly and promptly caused hypofibrinogenemia, irrespective of the products (prednisolone, dexamethasone, or methylprednisolone) or routes (oral or intravenous) that were used. Monitoring of the fibrinogen levels, especially during the first course of steroid therapy, would be useful for early diagnosis.

Clinical utility of fractional exhaled nitric oxide and blood eosinophils counts in the diagnosis of asthma-COPD overlap.

Background: Asthma-COPD overlap (ACO) is difficult to diagnose because it is characterized by persistent airflow limitation, and patients present with several manifestations that are usually associated with both asthma and COPD. In this retrospective study, we aimed to evaluate the diagnostic accuracy of fractional exhaled nitric oxide (FeNO) and blood eosinophil counts for the clinical diagnosis of ACO. Patients and methods: A total of 121 patients were divided into two study groups, COPD alone or ACO, which was based on criteria from the joint document by the Global Initiative for Asthma and the Global initiative for chronic Obstructive Lung Disease. From July 2014 to April 2017, FeNO levels and blood eosinophil counts were measured in specimens from patients naïve to inhaled corticosteroids (ICS) and those using ICS. Receiver operating characteristic curve analysis was used to determine the cutoff values of FeNO and blood eosinophil levels that provided the best differential diagnosis between ACO and COPD. Results: Among a total of 121 patients, 65 patients were diagnosed with COPD and 56 patients with ACO. The FeNO level was higher in patients with ACO than in patients with COPD (median 24.5 vs 16.0 ppb, respectively; P<0.01). Among patients naïve to ICS, the area under the receiver operating characteristic curve of FeNO values was 0.726, and the optimal diagnostic cutoff level of FeNO was 25.0 ppb, with 60.6% sensitivity and 87.7% specificity for differentiating ACO from COPD. FeNO (≥25.0 ppb) combined with blood eosinophil counts (≥250/µL) showed 96.1% specificity. Conclusion: These results demonstrate that the FeNO level combined with blood eosinophil count is useful for the differential diagnosis between ACO and COPD.