Neutralizing Antibody Levels and Epidemiological Characteristics of Patients with Breakthrough COVID-19 Infection in Toyama, Japan.

Breakthrough infection (BI) after coronavirus disease 2019 (COVID-19) vaccination has increased owing to the emergence of novel SARS-CoV-2 variants. In this study, we analyzed the epidemiological information and possession status of neutralizing antibodies in patients with BI using SARS-CoV-2 pseudotyped viruses. Analysis of 44 specimens from patients diagnosed with COVID-19 after two or more vaccinations showed high inhibition of infection by 90% or more against the Wuhan strain and the Alpha and Delta variants of pseudotyped viruses in 40 specimens. In contrast, almost no neutralizing activity was observed against the Omicron BA.1 variant. Many patients without neutralizing activity or BI were immunosuppressed. The results of this study show that contact with an infected person can result in BI, even when there are sufficient neutralizing antibodies in the blood. Thus, sufficient precautions must be taken to prevent infection even after vaccination.

[A case of gastric follicular lymphoma resected and diagnosed with laparoscopy and endoscopy cooperative surgery].

A woman in her 70s was diagnosed with a protruding mucosa-associated lymphoid tissue (MALT) lymphoma during a secondary health examination. After eradication of Helicobacter pylori, a biopsy revealed gastric follicular lymphoma (FL) and the lesion was still protruding one year later. 18F-fluorodeoxyglucose positron emission tomography showed focal nodular hypermetabolic activity, suggesting that FL may have transformed into a diffuse large B-cell lymphoma. Upper gastrointestinal endoscopy, colonoscopy, and capsule endoscopy showed no other lesions in the gastrointestinal tract, and bone marrow biopsy showed no permeation into the marrow. Therefore, this lesion, which appeared as a submucosal tumor, was limited to the stomach. Laparoscopy and endoscopy cooperative surgery was performed, because it allows for correct pathological diagnosis while removing only a minimal portion of the stomach wall. Histological findings showed follicular structures consisting of abnormal lymphoid cells. Immunohistochemical analysis revealed that neoplastic cells were positive for CD20, CD79a, Bcl-2, CD10, and c-MYC, but negative for CD3, CD5, and cyclin D1. Finally, we diagnosed this lesion as a primary gastric FL.

Late response to low-dose imatinib in patients with chronic phase chronic myeloid leukemia.

Imatinib was the first BCR-ABL tyrosine kinase inhibitor to become clinically available. In this study, we retrospectively evaluated the long-term efficacy of low-dose imatinib (final maintenance dose <300 mg per day) due to intolerance, in comparison to optimal-dose imatinib (≥300 mg per day) in patients with Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase. The Kaplan-Meier estimates of the median time to complete cytogenetic response, major molecular response, and complete molecular response were longer for 31 patients receiving low-dose imatinib (360, 1360, and 1420 days, respectively) than 74 patients receiving optimal-dose imatinib (170, 420, and 720 days, respectively). However, the differences in response shrank over time and progression-free survival were comparable between the two groups. These findings suggest that long-term treatment with low-dose imatinib is an acceptable alternative for patients with intolerance to the optimal dose.

Encephalopathy, disseminated intravascular coagulation, and hemolytic-uremic syndrome after infection with enterohemorrhagic Escherichia coli O111.

An outbreak of enterohemorrhagic Escherichia coli (EHEC) occurred in Toyama and other prefectures in Japan during 2011. Some patients, including adults, showed complications such as encephalopathy, disseminated intravascular coagulation, and hemolytic-uremic syndrome, and the disease course was extremely aggressive. This report describes the clinical features of four patients infected with Escherichia coli (E. coli) O111 who developed very severe to fatal complications. The initial symptoms in all patients included abdominal pain, diarrhea, and bloody stools, and neurological abnormalities started to appear from 1 to 3 days after admission. Vomiting and pyrexia developed in three patients. Leukocyte counts, lactate dehydrogenase (LDH), and fibrin/fibrinogen degradation products were elevated, and thrombocytopenia was evident. Extremely elevated LDH and severe thrombocytopenia were characteristic at the time encephalopathy became apparent. All patients received oral fosfomycin, intravenous antibiotics, and anticoagulant therapy, three received gamma globulin, plasma exchange, and blood transfusion, and two received steroids and dialysis. Three patients required mechanical ventilation, and two adult patients died. E. coli O111 positive for Shiga toxin 2 was detected in stool culture in two patients, and serological tests for E. coli O111 were positive in the other two patients. In conclusion, EHEC O111 can cause severe illness in children and adults, and the prognosis becomes poorer as the severity of complications increases. Close monitoring including platelet counts and LDH are useful. Once these clinical parameters change, intensive treatment should be provided to prevent the development of severe complications.

Efficacy and safety of micafungin as an empirical therapy for invasive fungal infections in patients with hematologic disorders: a multicenter, prospective study.

This study was conducted as a prospective, multicenter trial to evaluate the efficacy and safety of micafungin as an empirical therapy for suspected invasive fungal infections (IFIs), including febrile neutropenia (FN), and to evaluate the usefulness of ß-D: -glucan (BG) and Aspergillus galactomannan (GM) antigen in patients with hematologic diseases. A total of 121 patients were enrolled and assessed for safety, and 119 were examined for clinical efficacy. The main underlying diseases were acute myeloid leukemia (38.0%), acute lymphoblastic leukemia (18.2%), and malignant lymphoma (18.2%). The median initial daily dose and duration of micafungin treatment were 150 mg/day and 13 days, respectively. The overall response rate for suspected IFIs (n = 119), based on four composite endpoints, including baseline IFI, breakthrough IFIs (proven and probable), survival, and premature discontinuation, was 79.0%. In addition, the response rate for FN (n = 81), based on these four endpoints as well as defervescence during neutropenia, was 39.5%. Breakthrough IFIs (proven, probable, and possible) occurred in five patients during micafungin treatment. All of these patients were positive for either BG or GM before the breakthrough IFIs. The incidence of adverse events (AEs) associated with micafungin was 10.7% and most were mild. The majority of AEs were liver dysfunction. These results indicate the effectiveness and safety of micafungin as an empirical therapy for suspected IFIs, including FN, and the usefulness of monitoring both BG and GM to detect breakthrough IFIs.

Pneumothorax associated with malignant lymphoma.

An 82-year-old man was diagnosed with lymphoplasmacytic lymphoma involving multiple lymph nodes and bone marrow. On radiological examinations no involvement of the lung was seen. He was treated with rituximab. Eighteen months later he was complicated with right pneumothorax, and surgery with bullectomy was finally performed. Histological examination disclosed the proliferation of abnormal B lymphocytes near the wall of the bulla and pleura. We conclude that the pneumothorax in this patient was associated with lymphoma. Thus, radiological examination does not disclose lymphomatous lesions, it is possible that lymphoma involves the pleura, and pleural involvement can cause pneumothorax. Surgery is an effective method of treating this rare complication.

Antibiotic treatment for bacterial meningitis caused by Listeria monocytogenes in a patient with multiple myeloma.

Multiple myeloma is a hematolymphoid malignancy, and patients with this disorder are frequently complicated by infection. An 80-year-old woman with multiple myeloma was complicated by bacterial meningitis, and was admitted to our hospital in August 2007. She initially received ceftriaxone, but culture of cerebrospinal fluid detected Listeria monocytogenes. Ampicillin was administered, but headache and pyrexia persisted for 2 weeks, and on cerebrospinal fluid examination, the proliferation of polymorphonuclear leukocytes had not resolved. After medication with meropenem was started, the clinical symptoms completely disappeared, and the abnormalities on cerebrospinal fluid examination resolved. The patient ultimately received meropenem for 27 days, resulting in a cure. In conclusion, meropenem is useful to treat bacterial meningitis caused by L. monocytogenes. This agent is indicated when ampicillin shows inadequate effect or if the patient has an allergy to ampicillin.

[Concurrent chemo-radiotherapy for localized refractory non-Hodgkin's lymphoma--report of two cases].

Localized refractory diffuse large B-cell lymphomas (DLBCL) were treated with concurrent chemo-radiotherapy. Case 1 had right cervical lymphadenopathy. Lymphoma enlarged even after the fourth courses of chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). The second case had a pharyngeal tumor and bilateral cervical lymphadenopathy. A lymphoma enlarged after eighth courses of CHOP. Both cases were treated with concurrent chemo-radiotherapy. Chemotherapy consisted of mitoxantrone, methotrexate, ifosfamide,and prednisolone (MMIP). The dose of radiation to the involved sites was 40 Gy. The first case received chemotherapy three days after radiotherapy was started. The second case was treated with chemotherapy, and radiotherapy was begun one day after. Both cases show mucositis and leukopenia. One case received two courses of chemotherapy after chemo-radiotherapy, and the other received no additional chemotherapy. Both cases achieved complete remission after the combined therapy, however, lymphoma in one case recurred three months after the therapy. It is possible that this concurrent chemo-radiotherapy is effective for localized DLBCL which did not disappear after standard chemotherapy.

Thickening of multiple cranial nerves in a patient with extranodal peripheral T-cell lymphoma.

A 57-year-old male became aware of a subcutaneous tumor in March 2001. Histopathological examination showed peripheral T-cell lymphoma. He achieved complete remission after chemotherapy. Later the lymphoma relapsed in the subcutaneous lesion and chemotherapy was performed again. In April 2003, he developed diplopia, dysarthria, and dysphagia. Abnormal lymphoid cells were found in the cerebrospinal fluid. An immunophenotypical study disclosed that CD2, CD3, CD5, and CD8 were positive. Rearrangement of TCR was detected by Southern blotting. Cranial magnetic resonance imaging did not detect any intraparenchymal lesions, but thickening of multiple cranial nerves was detected. These nerves were homogeneously enhanced by gadolinium-DTPA. After intrathecal chemotherapy, atypical cells disappeared from the cerebrospinal fluid and thickening of the cranial nerves was resolved. Finally, lymphoma spread to the bone marrow, and the patient died in July 2003.

CD56-positive acute lymphoblastic leukemia.

We report a patient with lung cancer who developed CD56-positive acute lymphoblastic leukemia. He was referred to our hospital for thrombocytopenia. Atypical cells were found in the blood and the bone marrow. These cells were immunophenotypically positive for CD3epsilon, CD56, and terminal deoxynucleotidyl transferase, and negative for surface CD3, CD4, CD19, CD33, and myeloperoxidase. A small proportion of leukemic cells express CD13. There were no rearrangements of T-cell receptor (TCR)-beta, TCR-gamma, or immunoglobulin heavy chain. No Epstein-Barr virus was detected. Systemic examination did not detect any tumors other than pulmonary adenocarcinoma, and the patient was diagnosed as having acute natural killer (NK) cell leukemia. Chemotherapy was effective, and he achieved complete remission. The course of the disease was complicated by a lung abscess, and the patient died 3 months after the diagnosis. We considered that the diagnosis was blastic NK cell lymphoma/leukemia subtype. However, it actually was myeloid/NK cell precursor leukemia subtype that weakly expressed CD13.

Acute parvovirus B19 infection mimicking chronic fatigue syndrome.

A Japanese woman developed prolonged fatigue, neck and shoulder pain, headache, pyrexia, insomnia, anorexia, lymphadenopathy, and diarrhea for two months. She had experienced various stressors before these symptoms developed. Serological test demonstrated that she had acute parvovirus B19 infection. Major depressive disorder was also diagnosed by a psychiatrist. Her symptoms disappeared after administration of selective serotonin reuptake inhibitors and oriental herbs, although human parvovirus B19 viral genome has been present in her serum for nine months. These findings suggest that parvovirus B19 causes clinical features similar to those of chronic fatigue syndrome in cases who have prior life stressors.

Scintigraphic prediction of therapeutic outcomes of splenectomy in patients with thrombocytopenia.

UNLABELLED: In patients with thrombocytopenia, platelet scintigraphy has been used to locate the site of platelet sequestration and destruction and to determine whether splenectomy will be of benefit. However, its efficacy in predicting the outcome of splenectomy is controversial. We assessed the feasibility of platelet scintigraphy in this regard. METHODS: Platelet scintigraphy was performed in five patients (2 women, 3 men, mean age 48 years) before splenectomy. Four patients were diagnosed with idiopathic thrombocytopenic purpura and one with hypersplenism due to portal hypertension caused by intrahepatic chemotherapy against metastatic liver tumors of rectal cancer. Platelets labeled with 37 MBq of In-111 oxine or 1110 MBq of Tc-99m HMPAO were intravenously injected. Anterior images were obtained with a gamma camera 3-5 and 23-29 hours post-injection in five patients. Additional images were obtained 48 hours post-injection in three patients. For the analysis, a spleen/liver ratio (S/L ratio) was calculated using mean counts in regions of interest defined on the spleen and the liver. Serum platelet counts were measured before and after the operation; in three patients, splenectomy effectively resolved the thrombocytopenia (Group A), while it was ineffective in two patients (Group B). RESULTS: The S/L ratios were apparently higher in Group A than in Group B; in Group A, the ratios were 6.05, 6.97 and 3.16 at 3-5 hours, 12.67, 7.48 and 3.46 at 23-29 hours and 17.66 and 8.12 at 48 hours, whereas, in Group B, they were 0.67 and 0.66 at 3-5 hours, 0.52 and 0.54 at 24 hours, and 0.42 at 48 hours. CONCLUSION: The results of this study indicate that platelet scintigraphy is of value in predicting the therapeutic efficacy of splenectomy in patients with thrombocytopenia.

Transient elevation of platelet count in patients with chronic idiopathic thrombocytopenic purpura: association with infection.

Platelet count occasionally increases after infection in patients with chronic idiopathic thrombocytopenic purpura (ITP). We report 5 such patients. Three of them were males. Between November 1992 and December 2001, increased platelet counts were observed 9 times in 5 patients with chronic ITP. Corticosteroids were administered during 7 episodes; splenectomy was performed to treat 3 episodes. Antibiotics were administered in the course of 6 episodes to treat complicating infection. Platelet counts showing 1.4- to 24-fold increases have been observed. Median duration from the onset of infection until peak platelet count was 14 days. However, platelet count finally decreased to the initial level in all episodes. These findings suggest that infection is associated with the elevation of platelet count in some patients with chronic ITP, although this phenomenon is transient.