Correlation of the Commercial Anti-SARS-CoV-2 Receptor Binding Domain Antibody Test with the Chemiluminescent Reduction Neutralizing Test and Possible Detection of Antibodies to Emerging Variants.

Serological tests are beneficial for recognizing the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). To identify protective immunity, optimization of the chemiluminescent reduction neutralizing test (CRNT) is critical. Whether commercial antibody tests have comparable accuracy is unknown. Serum samples were obtained from COVID-19 patients (n = 74), SARS-CoV-2 PCR-negative (n = 179), and suspected healthy individuals (n = 229) before SARS-CoV-2 variants had been detected locally. The convalescent phase was defined as the period after day 10 from disease onset or the episode of close contact. The CRNT using pseudotyped viruses displaying the wild-type (WT) spike protein and a commercial anti-receptor-binding domain (RBD) antibody test were assayed. Serology for the B.1.1.7 and B.1.351 variants was also assayed. Both tests concurred for symptomatic COVID-19 patients in the convalescent phase. They clearly differentiated between patients and suspected healthy individuals (sensitivity: 95.8% and 100%, respectively; specificity: 99.1% and 100%, respectively). Anti-RBD antibody test results correlated with neutralizing titers (r = 0.31, 95% confidence interval [CI] 0.22-0.38). Compared with the WT, lower CRNT values were observed for the variants. Of the samples with ≥100 U/mL by the anti-RBD antibody test, 77.8% and 88.9% showed ≥50% neutralization against the B.1.1.7 and the B.1.351 variants, respectively. Exceeding 100 U/mL in the anti-RBD antibody test was associated with neutralization of variants (P < 0.01). The CRNT and commercial anti-RBD antibody test effectively classified convalescent COVID-19 patients. Strong positive results with the anti-RBD antibody test can reflect neutralizing activity against emerging variants. IMPORTANCE This study provides a diagnostic evidence of test validity, which can lead to vaccine efficacy and proof of recovery after COVID-19. It is not easy to know neutralization against SARS-CoV-2 in the clinical laboratory because of technical and biohazard issues. The correlation of the quantitative anti-receptor-binding domain antibody test, which is widely available, with neutralizing test indicates that we can know indirectly the state of acquisition of functional immunity against wild and variant-type viruses in the clinical laboratory.

Primary human herpesvirus 8-negative effusion-based lymphoma: a large B-cell lymphoma with favorable prognosis.

Primary effusion-based lymphoma (EBL) presents as a malignant effusion in a body cavity. The clinicopathologic features and prognosis of primary human herpesvirus 8 (HHV8)-negative EBL remain unclear. We therefore conducted a retrospective study of 95 patients with EBL, regardless of HHV8 status, in Japan. Of 69 patients with EBL tested for HHV8, a total of 64 were negative. The median age of patients with primary HHV8-negative EBL at diagnosis was 77 years (range, 57-98 years); all 58 tested patients were negative for HIV. Primary HHV8-negative EBL was most commonly diagnosed in pleural effusion (77%). Expression of at least 1 pan B-cell antigen (CD19, CD20, or CD79a) was observed in all cases. According to the Hans algorithm, 30 of the 38 evaluated patients had nongerminal center B-cell (non-GCB) tumors. Epstein-Barr virus-encoded small RNA was positive in 6 of 45 patients. In 56 of 64 HHV8-negative patients, systemic therapy was initiated within 3 months after diagnosis. Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) or CHOP-like regimens with or without rituximab (n = 48) were the most common primary treatments. The overall response and complete response rates were 95% and 73%, respectively. Three patients did not progress without systemic treatment for a median of 24 months. With a median 25-month follow-up, the 2-year overall survival and progression-free survival rates were 84.7% and 73.8%. Sixteen patients died; 12 were lymphoma-related deaths. Thus, most EBL cases in Japan are HHV8-negative and affect elderly patients. The non-GCB subtype is predominant. Overall, primary HHV8-negative EBL exhibits a favorable prognosis after anthracycline-based chemotherapy.

[Hyperpigmentation due to Vitamin B12 Deficiency].

Vitamin B12 deficiency is associated with mucocutaneous symptoms, such as glossitis and hyperpigmentation, as well as megaloblastic anemia and neuropathy. These are reversible conditions, and the symptoms improve with early detection and treatment. Whenever anemia is encountered in routine practice, vitamin B12 deficiency should be considered and the presence of skin symptoms should be investigated.

[Effect of Japanese Traditional Medicine, Ninjin-Youei-To(TJ-108), on the Quality of Life of Patients with Non-Small Cell Lung Cancer Receiving Outpatient Chemotherapy].

An increasing number of patients with lung cancer are undergoing outpatient chemotherapy, and thus, it is very important to maintain the quality of life(QOL)of these patients. Ninjin-Youei-To(TJ-108), a Japanese traditional medicine, has been reported to improve the QOL of patients with advanced cancer. However, the effect of TJ-108 in patients with lung cancer undergoing outpatient chemotherapy is unknown. Therefore, we conducted this study. To investigate factors influencing the QOL of these patients, we administered a QOL questionnaire,"The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs"(QOL-ACD)to 15 patients with non-small cell lung cancer. Factors related to the overall QOL scores and other categories indicating"activity","physical condition","psychological condition","social relationship", and"face scale" were analyzed. No significant decrease in each of the evaluated factors was observed in this study.

[Effect of Japanese Traditional Medicine, TJ-48, on the Quality of Life of Patients with Non-Small Cell Lung Cancer Receiving Outpatient Chemotherapy].

An increasing number of patients with lung cancer are undergoing outpatient chemotherapy.It is very important to retain the quality of life (QOL) of these patients.Japanese traditional medicine, TJ-48, has been reported to improve the QOL of patients with advanced cancer. However, the effect of TJ-48 in patients with lung cancer undergoing outpatient chemotherapy is unknown. The present study was conducted to investigate the factors influencing the QOL of these patients. We used "The QOL questionnaire for cancer patients treated with anticancer drugs" (QOL-ACD) with 16 patients with non-small cell lung cancer. The medical factors related to the overall QOL scores and other variables indicating "activity," "physical condition, "psychological condition,""social relationships," "psychological condition," and "face scale" were analyzed. Significant improvement was observed in the total QOL score, mainly owing to the improvement in the patients "physical condition."

[Nab-Paclitaxel with platinum chemotherapy as sixth-line therapy for a non-small cell lung cancer patient].

A 48-year-old woman was admitted to our hospital for sixth-line chemotherapy. A chest X-ray film and computed tomographic (CT) scan revealed a right-sided massive tumor with multiple lung tumors. Repeated treatment with carboplatin (AUC 6) on day 1 and nab-paclitaxel (100mg/m2) on days 1, 8, and 15, every 28 days were effective in this patient. Chemotherapy with nab-paclitaxel may be effective for patients with multi-recurrent adenocarcinoma.

Inferior vena cava thrombosis associated with a distended ileal neobladder.

Venous stasis is generally accepted to be a predisposing factor for venous thrombosis. However, benign causes of inferior vena cava (IVC) obstruction with associated thrombus formation have not been well described. We herein present a case of IVC compression caused by a distended ileal neobladder measuring 2,000 mL in capacity that led to IVC thrombosis. Following transurethral drainage for six weeks and anticoagulation therapy with warfarin for six months, the thrombus completely disappeared. The patient was considered to have a hypercoagulable state resulting from an acute urinary tract infection, a condition that may be associated with an increased risk of thrombosis.

[Analysis of factors associated with the quality of life in patients with non-small cell lung cancer who received outpatient pemetrexed maintenance therapy].

Increasing number of patients with advanced non-small cell lung cancer are receiving outpatient maintenance chemotherapy. It is very important to maintain these patients' quality of life(QOL). Pemetrexed has been reported to be an effective maintenance chemotherapy. However, its effects on the QOL of patients with non-small cell lung cancer who are undergoing outpatient maintenance chemotherapy are unknown; therefore, we conducted this study. To investigate factors that influence the QOL of these patients, we provided a QOL questionnaire,"The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs(QOL-ACD)"to 7 patients with non-small cell lung cancer. The medical factors related to the overall QOL scores, as well as other categories indicating"activity","physical condition","psychological condition","social relationship", and"face scale", were analyzed. No significant reductions in any of the factors were observed in this study.

Low-grade B-cell lymphoma presenting primarily in the bone marrow.

Cases of low-grade B-cell lymphoma presenting primarily in the bone marrow are rare, and its clinicopathology remains unclear. We retrospectively examined patients with low-grade B-cell lymphoma presenting primarily in the bone marrow. Fourteen patients met the inclusion criteria, including 5 with lymphoplasmacytic lymphoma (LPL), 3 with chronic lymphocytic leukemia/small lymphocytic lymphoma, 2 with follicular lymphoma (FL), and 4 with low-grade B-cell lymphoma not otherwise specified (LGBCL-NOS). The median age was 69.5 years (range, 42-89 years), and a slight male predominance was noted (9 men and 5 women, 1.8: 1). Immunohistochemically, all cases were positive for CD20. One case was positive for CD138. Both cases of FL were positive for CD10 and B-cell lymphoma 2 (BCL-2), and immunoglobulin heavy locus (IgH)/B-cell lymphoma 2 rearrangement was observed by fluorescence in situ hybridization. The myeloid differentiation primary response gene (88) leucine to proline mutation was observed in 3 of 5 LPL, 1 of 2 FL, and 2 of 4 LGBCL-NOS patients. Paraproteinemia was observed in 10 patients; IgM and IgG paraproteinemia were observed in 6 and 3 patients, respectively. In this patient series, 3 patients had died at a median follow-up of 36.5 months; the cause of death of 1 LPL patient was malignant lymphoma itself. Thus, low-grade B-cell lymphoma presenting primarily in the bone marrow has various subtypes, and approximately one-third of the patients had LGBCL-NOS. The immunophenotypic features and myeloid differentiation primary response gene (88) leucine to proline mutation data of LGBCL-NOS suggested that some cases present with characteristics similar to those of LPL or marginal zone lymphoma.

Post-transplantation consolidation and maintenance therapy with lenalidomide for Japanese patients with multiple myeloma.

BACKGROUND: Post-autologous stem cell transplantation (ASCT) consolidation and maintenance therapies in multiple myeloma (MM) have recently been the central focus of studies. However, there have been no reports of Japanese patients with MM treated with post-ASCT consolidation/maintenance therapies. PATIENTS AND METHODS: We retrospectively evaluated eight Japanese patients with newly-diagnosed symptomatic MM who received ASCT after high-dose melphalan, and three to four courses of bortezomib-plus-dexamethasone and two courses of lenalidomide-plus-dexamethasone followed by maintenance lenalidomide for 6-24 months. RESULTS: Four patients achieved complete response (CR) after ASCT, and five patients (63%) achieved stringent CR after the consolidation and maintenance therapy; two out of these five were in molecular CR. At the median follow-up of 38 months, all patients were alive and only one patient had disease progression following post-ASCT therapy. CONCLUSION: Post-ASCT consolidation and maintenance therapy using lenalidomide may be effective in the treatment of Japanese patients with MM.

[Effect of Japanese traditional medicine, TJ-41, on quality of life of patients with non-small cell lung cancer receiving outpatient chemotherapy].

An increasing number of patients with lung cancer are undergoing outpatient chemotherapy. It is very important to maintain good quality of life(QOL)for these patients, and Japanese traditional medicine, TJ-41, has been reported to improve the QOL of patients with advanced cancer. However, the effect of TJ-41 on patients with lung cancer undergoing outpatient chemotherapy is unknown. Therefore, we conducted this study. To investigate the factors influencing the QOL of these patients, we distributed a QOL questionaire,"The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs"(QOL-ACD)to 11 patients with non-small cell lung cancer. The medical factors related to the overall QOL scores and other categories, indicating"activity","physical condition","psychological condition","social relationships","psychological condition"and"face scale"were analyzed. A significant decrease in each of the factors was not observed in this study.

Detection of minimal residual disease in patients with multiple myeloma using clonotype-specific PCR primers designed from DNA extracted from archival bone marrow slides.

Polymerase chain reaction (PCR)-negative molecular complete remission (mCR) can be induced by stem cell transplantation in some patients with multiple myeloma (MM) and is associated with long-term progression-free survival (PFS). The detection of molecular minimal residual disease (MRD), however, requires fresh or frozen materials for designing clone-specific primers, which are not always readily available. In this study, we used DNA extracted from archival bone marrow (BM) slides for PCR to detect MRD in 50 patients with MM who received various induction therapies and autologous peripheral blood stem cell transplantation (ASCT). Clonotype-specific immunoglobulin (Ig) H PCR primers were prepared for 32 of 50 cases (64%) using BM slides, and for 9 of 14 cases (64%) using fresh BM cells. DNA in peripheral blood stem cell autografts of the 22 patients who achieved at least a partial response after ASCT was subjected to PCR to amplify clonotype-specific rearranged IgH gene sequences. The median PFS of the eight patients with MRD-positive autografts was 18 months, whereas that of 14 patients with MRD-negative autografts was not reached at a median follow-up of 27 months (p = 0.012). Post-ASCT PFS of the four patients who achieved mCR was 100% at a median follow-up of 47 months. These results indicate that archival BM slides can serve as a source of DNA for preparing clonotype-specific primers for MRD monitoring in patients with MM whose cryopreserved myeloma cells are not available for DNA preparation. Our results also suggest that patients with MM who received MRD-negative autografts and achieved mCR have a long PFS.

Urinary frequency as a presentation of bulky malignant lymphoma in the pelvis.

Malignant lymphomas may originate from any area of the body and cause a variety of symptoms. However, a malignant lymphoma causing urinary symptoms is uncommon. We report a unique case of a 77-year-old woman who presented with a persistent pollakiuria. Radiographic imaging showed a large pelvic mass (13 × 13 × 11 cm) remarkably compressing and invading the bladder wall and accompanied with bilateral hydronephrosis. Urinary cytology revealed malignant lymphoma, and a final diagnosis of malignant lymphoma was made on the basis of transvaginal needle biopsy. Urinary cytology facilitated the definite diagnosis, following which we initiated a rapid and successful treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab.

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.

[Bevacizumab with platinum chemotherapy as 6th-line treatment in a case of non-small-cell lung cancer].

A 64-year-old man was admitted to our hospital for 6th-line chemotherapy. Chest X-ray film and computed tomographic (CT) scan showed right-sided pleural thickening with multiple lung tumors. Repeated treatment with carboplatin (AUC 6), paclitaxel (200 mg/m(2)) and bevacizumab (150 mg/kg) on day 1 every 21 days was effective for this patient. Chemotherapy with bevacizumab may be effective for patients with multi-recurrent adenocarcinoma.

Disappearance of malignant cells by effusion drainage alone in two patients with HHV-8-unrelated HIV-negative primary effusion lymphoma-like lymphoma.

Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin lymphoma usually confined to the body cavities of predominantly immunosuppressed patients infected with human herpes virus-8 (HHV-8). In PEL, malignant cells are usually negative for B-cell markers, such as CD19, CD20, and CD79a, but are positive for activation and plasma cell-related markers, such as CD30, CD38, and CD138. It has been reported that HHV-8-unrelated PEL shows high expression of B-cell markers, which is referred to as PEL-like lymphoma. Here, we report two cases of HHV-8-unrelated HIV-negative PEL-like lymphoma in which malignant cells regressed spontaneously after effusion drainage alone. These cells expressed B-cell markers, such as CD20. No chemotherapy was given to either patient, as they were of an advanced age, and both achieved a complete response by effusion drainage alone. One showed a complete response for 16 months after effusion drainage, and the other has survived for 11 months with a complete response. This suggests that sufficient drainage of serous effusion may induce and maintain a complete response in some patients with HHV-8-unrelated HIV-negative PEL-like lymphoma, which represents an excellent treatment option for elderly patients with this disease.

[Analysis of factors associated with quality of life for older adult patients with non-small cell lung cancer receiving outpatient gemcitabine therapy as an alternative inpatient therapy].

An increasing number of patients with lung cancer are undergoing outpatient chemotherapy as an alternative to inpatient therapy. To investigate the factors influencing the quality of life (QOL) for these patients, we administered a QOL questionnaire, The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs (QOL-ACD) to 8 older adult patients with non-small cell lung cancer. The medical factors related to the overall QOL scores and other categories indicating activity, physical condition, psychological condition, social relationship, psychological condition and face scale were analyzed. No significant decrease in each factor was observed in this study.

HHV-8/KSHV-negative and CD20-positive primary effusion lymphoma successfully treated by pleural drainage followed by chemotherapy containing rituximab.

The present patient was diagnosed as having human herpes virus-8 (HHV-8)/Kaposi sarcoma herpes virus (KSHV)-negative and CD20-positive primary effusion lymphoma (PEL) of the right-sided pleural effusion. After pleural drainage, malignant cells disappeared spontaneously in a small amount of the remaining pleural effusion without chemotherapy. The patient was treated with six cycles of chemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. He has been in complete remission for more than 22 months. It is suggested that effusion drainage followed by chemotherapy containing rituximab is a potential treatment strategy for patients with HHV-8/KSHV-negative and CD20-positive PEL.