Clustered circulating tumor cells as a predictor of adjuvant-chemotherapy efficacy in lung cancer.

BACKGROUND: Surrogate markers of minimal residual disease primarily include cell-free tumor deoxyribonucleic acid and circulating tumor cells. Cell-free tumor DNA might aid precise decision making regarding who should receive adjuvant chemotherapy. However, there are no relevant reports on circulating tumor cells. Therefore, we aimed to verify whether perioperative clustered circulating tumour cells identification is a predictor of therapeutic efficacy in non-small cell lung cancer adjuvant chemotherapy. METHODS: Circulating tumor cells were diagnosed under light microscopy using a size selection method in 128 patients with clinical stage I/II non-small cell lung cancer around surgery. The main endpoint was recurrence-free survival, and the effect of adjuvant chemotherapy was verified in both groups based on perioperative clustered circulating tumor cell identification. RESULTS: In total, 49 and 79 patients were included in the clustered circulating tumor cell-positive and clustered circulating tumor cell-negative patient groups, respectively. In the clustered circulating tumor cell-positive patient group, adjuvant chemotherapy was performed in 18 patients (2-year recurrence-free survival rate, 71.8%). However, the 2-year recurrence-free survival rate was 36.3% in 31 patients who did not receive adjuvant chemotherapy (p<0.01). In the clustered circulating tumor cell-negative patient group, adjuvant chemotherapy was provided in 11 patients (2-year recurrence-free survival rate, 90.9%). However, 68 patients did not receive adjuvant chemotherapy (2-year recurrence-free survival rate, 94.9%) (not significant). CONCLUSIONS: In surgical cases of clinical stage I/II non-small cell lung cancer, patients with perioperative clustered circulating tumor cells had a poor prognosis, but adjuvant chemotherapy improved their prognosis.

Human granulocytic anaplasmosis with rash and rhabdomyolysis: A case report.

Human granulocytic anaplasmosis (HGA) is a tick-borne infection caused by Anaplasma phagocytophilum. Only seven cases of HGA have been reported in Japan to date. We report the case of a 61-year-old female farmer who developed HGA with rash and rhabdomyolysis. The patient had fever and erythema covering the entire body, including the palms. An induration with an eschar was observed on the right leg, indicating that the patient had been bitten by a tick. Elevated serum creatinine and creatinine kinase levels and hematuria indicated rhabdomyolysis. We suspected Japanese spotted fever, a tick-borne illness caused by Rickettsia Japonica, and administered minocycline and ciprofloxacin for a week. Transient neutropenia and thrombocytopenia were observed, but the symptoms improved. Polymerase chain reaction (PCR) and antibody tests for R. japonica and Orientia tsutsugamushi, which causes scrub typhus, were both negative. The PCR test for severe fever with thrombocytopenia syndrome virus was also negative. Antibodies against A. phagocytophilum-related proteins were detected by western blotting, indicating seroconversion of IgG with paired serum samples, and the patient was diagnosed with HGA. HGA should be suspected in acute febrile patients with a history of outdoor activity and cytopenia, with or without a rash. A testing system and the accumulation of cases in Japan are necessary for the early diagnosis and appropriate treatment of HGA.

Numerous multinucleated giant cells in cutaneous epithelioid angiosarcoma and pulmonary metastasis: A unique observation with potential diagnostic pitfalls.

The histopathologic diagnosis of poorly differentiated cutaneous angiosarcoma can be challenging. We report a case of cutaneous epithelioid angiosarcoma with numerous multinucleated giant cells (MGCs) developing pulmonary metastasis. A 79-year-old man presented with a red-purple plaque on the scalp. A skin biopsy revealed epithelioid cell proliferation, admixed with numerous MGCs, and background hemorrhage. Vascular spaces were focally present and lined by atypical endothelial cells, including MGCs. Immunohistochemically, tumor cells, including MGCs, were positive for CD31, D2-40, and ERG. The patient received radiation therapy and chemotherapy, after which a follow-up CT scan revealed symptomless pneumothorax and pulmonary metastases. The patient received palliative partial lung resection, and the specimen revealed histopathological and immunohistochemical features similar to the primary cutaneous lesion. Our report expands the morphologic spectrum of cutaneous epithelioid angiosarcoma. Cutaneous angiosarcoma is an aggressive neoplasm; thus, awareness of this rare manifestation is important.

Differences in muscle magnetic resonance imaging findings between anti-signal recognition particle antibody-positive myopathy and anti-aminoacyl-tRNA synthetase antibody-positive myositis.

OBJECTIVES: To compare the findings of muscle magnetic resonance imaging (MRI) between anti-signal recognition particle antibody-positive myopathy (anti-SRP myopathy) and anti-aminoacyl-tRNA synthetase antibody-positive myositis (anti-ARS myositis). METHODS: Of the patients newly diagnosed with polymyositis (PM)/dermatomyositis (DM) and immune-mediated necrotising myopathy (IMNM) admitted to our Department between April 2012 and December 2021, those who met the eligibility criteria of positive for anti-SRP or anti-ARS antibodies and thigh MRI at the time of diagnosis were included. We compared the lesion sites and MRI findings of the thigh muscles that were classified into oedema, fascial oedema, fatty replacement, and muscle atrophy between the three groups of anti-SRP myopathy, anti-Jo-1 antibody-positive myositis, and non-Jo-1 antibody-positive myositis. RESULTS: Of the 98 PM/DM and IMNM patients, five anti-SRP myopathy patients and 11 anti-Jo-1-positive and 22 non-Jo-1 antibody-positive patients with myositis were included. The SRP group showed significantly higher blood levels of myogenic enzymes such as serum creatinine kinase (CK) than the other groups (p=0.01). In thigh MRI findings, despite oedema in most cases in anti-SRP and anti-ARS groups, fascial oedema was identified only in the ARS group, frequently in Jo-1 positive patients in particular. Moreover, gluteus maximus muscle lesions occurred more frequently in the SRP group than in the ARS group (p=0.008). CONCLUSIONS: A comparison of thigh MRI between anti-SRP myopathy and anti-ARS myositis showed different findings and lesion sites reflecting the different pathophysiology that may contribute to their diagnosis.

Luteibacter jiangsuensis blood stream infection: a first case report.

BACKGROUND: Luteibacter jiangsuensis is a gram-negative aerobic bacillus that was first isolated from soil samples at a pesticide factory in China and reported in 2011. Here, we describe the first case of L. jiangsuensis infection in human. CASE PRESENTATION: A 59-year-old Japanese woman undergoing treatment for Crohn's disease was admitted to our hospital with fever. Clinical examination indicated catheter-related bloodstream infection. The catheter was removed and meropenem was initiated. Morphologically identical glucose non-fermentative gram-negative bacilli were detected from two sets of aerobic blood culture and catheter-tip cultures. MALDI-TOF mass spectrometry failed to identify the bacterium, which was later identified as L. jiangsuensis by 16 S rRNA gene sequencing. Antimicrobial susceptibility test revealed that the isolate was resistant to carbapenem, therefore meropenem was switched to intravenous levofloxacin (500 mg/day). After 14 days of treatment with levofloxacin, the patient was discharged. CONCLUSIONS: This is the first case of L. jiangsuensis infection in human. The strain was identified by 16 S rRNA gene sequence analysis.

Coronavirus disease 2019 in a patient with pulmonary fibrosis and emphysema: An autopsy report.

Various diseases (e.g., hypertension and diabetes) are risk factors for the exacerbation of coronavirus 2019 (COVID-19). Patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) tend to develop severe COVID-19. Patients with severe COVID-19 present with acute respiratory distress syndrome (ARDS), and many COVID-19-related ARDS survivors eventually develop fibrosis. However, the appropriate management of patients with COVID-19 and ILD and post-COVID-19 ILD remains unclear. Thus, a better understanding of the pathology that exacerbates COVID-19 in patients with ILD is needed. We report the autopsy results of a patient with COVID-19 and combined pulmonary fibrosis and emphysema, whose lung organization and fibrosis progressed after the acute phase of infection. Histopathological findings suggest that fatal pulmonary fibrosis persists after the negative conversion of SARS-CoV-2. Elucidating the cause of death by autopsy may help determine therapeutic strategies in patients with COVID-19 and ILD. Vaccination and early administration of anti-inflammatory drugs or antifibrotic agents may be crucial for preventing disease progression and fatal lung fibrosis. This report aims to clarify the histopathological features of COVID-19 in patients with ILD via autopsy and discuss treatment strategies.

A Novel Filtration Membrane for Clustered Circulating Tumor Cell Extraction: A Prospective Feasibility Study.

BACKGROUND/AIM: Circulating tumor cells (CTCs) have garnered attention as biomarkers for therapeutic response and prognosis in malignant neoplasms. Nonetheless, existing literature predominantly relies on surrogate markers of tumor cells or focuses on single-cell CTC, failing to adequately address the challenge of detecting cluster-forming CTCs, which bear considerable prognostic implications. This prospective study aims to validate the efficacy of a novel filtration membrane, namely Soft Micro Pore Filter (S-MPF®), for rare cell recovery in detecting CTCs through the analysis of clinical samples. PATIENTS AND METHODS: Patients with confirmed lung cancer or highly suspected lung cancer based on specific criteria (solid tumor size >2.0 cm, serum carcinoembryonic level >7.5 ng/ml, maximum standard uptake value derived from fluorodeoxyglucose-position emission tomography >2.9) were included in the study. CTCs were extracted from preoperative peripheral arterial blood samples using S-MPF®, and the validity of the filtration system was positively verified. RESULTS: Out of the 25 enrolled patients, 23 had lung cancer. CTC positivity was observed in 17 cases (73.9%), whereas cluster CTC positivity was observed in 16 cases (69.6%), with a median count of two clusters. Single CTC positivity was observed in 11 cases (52.1%), with a median count of one cell. CONCLUSION: The utilization of the newly developed S-MPF® filtration membrane exhibited a high rate of CTC identification, demonstrating its suitability for clinical applications.

Angiopoietin-like 4 Is a Critical Regulator of Fibroblasts during Pulmonary Fibrosis Development.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible interstitial pneumonia caused by the excessive production and deposition of extracellular matrix components, including type I collagen. Activated fibroblasts, called α-SMA (α-smooth muscle actin)-expressing myofibroblasts, are the major source of type I collagen in pulmonary fibrosis (PF), but the mechanisms underlying disease progression have not been fully elucidated. Here, we obtained lung fibroblasts from patients with IPF from both nonfibrotic and fibrotic areas as determined by a lung computed tomography scan and compared gene expression between these areas by DNA microarray. We found that ANGPTL4 (angiopoietin-like 4) was highly expressed only in fibroblasts from the fibrotic area. ANGPTL4 was selectively expressed in the fibroblastic area of IPF lungs, where the myofibroblast marker α-SMA was also expressed. ANGPTL4 also regulates the gene expression of fibrosis-related markers, cell migration, and proliferation. In addition, ANGPTL4 expression in a murine model of PF induced by treatment with bleomycin was significantly induced in the lungs from the acute to the chronic phase. Single-cell transcriptome analysis during the course of bleomycin-induced PF revealed that Angptl4 was predominantly expressed in the activated fibroblasts and myofibroblasts. Moreover, the administration of recombinant ANGPTL4 to the bleomycin-induced fibrosis model significantly increased collagen deposition and exacerbated the PF. In contrast, the pathogenesis of PF in Angptl4-deficient mice was improved. These results indicate that ANGPTL4 is critical for the progression of PF and might be an early diagnostic marker and therapeutic target for IPF.

Possible Transmission of Severe Fever with the Thrombocytopenia Syndrome Virus to an Individual Who Buried an Infected Cat.

Severe fever with thrombocytopenia syndrome (SFTS) is caused by the severe fever with thrombocytopenia syndrome virus (SFTSV). Although SFTS is a fatal tick-borne zoonosis, it can infect humans without tick bite exposure. Recently, direct transmission of SFTSV from companion pets to humans has become a major problem. We present a case of SFTSV transmission from a dead community cat to a woman who buried the cat in Miyazaki Prefecture, Japan. The community cat died without a diagnosis of SFTS, and the woman buried it without taking any precautions. She developed symptoms of SFTS 9 days later. The woman tested positive for SFTS viral RNA and anti-SFTSV antibodies. The cat's carcass was exhumed, and tissue samples were collected to confirm the viral infection. Numerous copies of viral RNA were detected. The SFTSV M segment sequences in the cat and the woman were 100% homologous. The woman claimed that she had touched blood that had leaked from the cat's body while burying it. However, she could have been infected while transporting the cat to the animal hospital. This study highlights the risk of SFTSV infection from contact with sick or dead community cats.

Primary pulmonary diffuse large B-cell lymphoma presenting multiple nodules mimicking metastasis: A case report.

Primary pulmonary diffuse large B-cell lymphoma is a rare entity. We describe a case of pulmonary lymphoma with multiple nodules mimicking metastases in a treated patient with rheumatoid arthritis. A 73-year-old man was diagnosed with rheumatoid arthritis at the age of 30. He was treated with leflunomide. He was followed up for a nontuberculous mycobacterial infection. He underwent percutaneous coronary intervention for acute myocardial infarction at the age of 70. In April 2022, routine follow-up revealed new-onset multiple nodules on chest computed tomography (CT). A position emission tomography/CT scan with 18F-fluorodeoxyglucose showed a low-high maximum standardized uptake value by multiple nodules. Pathologic examination of a video-assisted thoracic surgical biopsy revealed pulmonary diffuse large B-cell lymphoma. Systemic chemotherapy with rituximab, cyclophosphamide, vincristine, and prednisolone reduced and eliminated multiple nodules. Pulmonary lymphoma should be considered as a differential diagnosis in the case of multiple nodules on a chest CT.

HAS-Flow May Be an Adequate Method for Evaluating Human T-Cell Leukemia Virus Type 1 Infected Cells in Human T-Cell Leukemia Virus Type 1-Positive Rheumatoid Arthritis Patients Receiving Antirheumatic Therapies: A Retrospective Cross-Sectional Observation Study.

The study aims to assess the usefulness of human T-cell leukemia virus type 1 (HTLV-1)-infected cell analysis using flow cytometry (HAS-Flow) as a monitoring method for adult T-cell leukemia (ATL) development in HTLV-1-positive patients with rheumatoid arthritis (RA) under treatment with antirheumatic therapies. A total of 13 HTLV-1-negative and 57 HTLV-1-positive RA patients participated in this study, which was used to collect clinical and laboratory data, including HAS-Flow and HTLV-1 proviral load (PVL), which were then compared between the two groups. CADM1 expression on CD4+ cells in peripheral blood (PB) was used to identify HTLV-1-infected cells. The population of CADM1+ CD4+ cells was significantly higher in HTLV-1-positive RA patients compared to HTLV-1-negative RA patients. The population of CADM1+ CD4+ cells was correlated with HTLV-1 PVL values. There were no antirheumatic therapies affecting both the expression of CADM1 on CD4+ cells and PVLs. Six HTLV-1-positive RA patients who indicated both high HTLV-1 PVL and a predominant pattern of CADM1+ CD7neg CD4+ cells in HAS-Flow can be classified as high-risk for ATL progression. HAS-Flow could be a useful method for monitoring high-risk HTLV-1-positive RA patients who are at risk of developing ATL during antirheumatic therapies.

Association between regional cerebral oxygen saturation and outcome of patients with out-of-hospital cardiac arrest: An observational study.

Aim: This study aimed to evaluate the association between cerebral oxygen saturation (StO2) and return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA). Methods: We retrospectively evaluated the data of patients with OHCA to determine the association between ROSC and various StO2 parameters (initial_StO2, final_StO2, mean_StO2, and Δ_StO2 [=final_StO2-initial_StO2]). Time-domain near-infrared spectroscopy was used to determine absolute StO2 values. Results: Of the 108 patients with OHCA, 23 achieved ROSC. Although initial_StO2 values did not differ between the groups, final_StO2, mean_StO2, and Δ_StO2 were higher in the ROSC group than in the non-ROSC group. The cut-off values for initial_StO2, mean_StO2, and Δ_StO2 as predictors of ROSC were 35%, 30%, and 5%, respectively. The odds ratio for ROSC had markedly increased in the Δ_StO2 ≥ 5% subgroup (19.70 [6.06-64.11], p < 0.001). When the change in StO2 (=d_StO2) at 8 min from the initiation of StO2 measurement was assessed, the d_StO2 ≥ 5% subgroup had a higher odds ratio for ROSC than the d_StO2 < 5% subgroup (5.8 [1.78-18.85], p = 0.002), and this tendency was maintained until 20 min. In the evaluation using a two-by-two contingency table with initial_StO2 and Δ_StO2 as two parameters, 61.9% of the patients fell under the categories of initial_StO2 < 35% and Δ_StO2 < 5% and had the lowest rate of ROSC achievement (4.6%). In the Δ_StO2 ≥ 5% subgroup, approximately-two-thirds of the patients achieved ROSC irrespective of the initial_StO2 (initial_StO2 ≥ 35%, 66.7%; initial_StO2 < 35%, 60.0%). Conclusions: Initial_StO2 and Δ_StO2 were associated with the achievement of ROSC.

Outcome of Resected Lung Cancers with Subcentimeter Solid Component on Computed Tomography.

BACKGROUND: Although the opportunity to treat subcentimeter lung cancers has increased, the optimal surgical methods remain unclear. We performed a retrospective study to examine the clinical outcome of subcentimeter lung cancers. PATIENTS AND METHODS: In total, 118 patients who underwent curative resection for subcentimeter lung cancer from January 2005 to December 2013 were analyzed. Multivariate Cox proportional hazards models were used to calculate the hazard ratio to identify independent predictors of recurrence-free survival (RFS) and overall survival (OS). RESULTS: Anatomical resections were performed for 64 patients (59 lobectomies and 5 segmentectomies) and wedge resections for 54 patients. Recurrence developed in six patients who had consolidation-predominant tumors (consolidation/tumor [C/T] ratio of >0.5) and underwent wedge resections. The first recurrence patterns were regional recurrences in three patients, both regional and distant in one, and distant in two. Seventeen patients died of other causes. The multivariate analysis revealed that the C/T ratio was the independent predictor of RFS (p = 0.008) and OS (p = 0.011). CONCLUSION: Patients with subcentimeter lung cancer rarely developed recurrence. The C/T ratio was the independent prognostic factor, and all relapsed patients received wedge resections. Even for subcentimeter lung cancers, we should select the extent of pulmonary resection after thoroughly considering whether wedge resection (less invasiveness) is a reasonable alternative to anatomical resection (superior oncologic efficacy) considering the C/T ratio of the lesion.

Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome as a Manifestation of Recurrent Ovarian Cancer.

We herein report a case of ovarian cancer recurrence detected every time with symptoms of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. A 46-year-old woman who had a history of ovarian cancer 9 months earlier developed joint pain along with pitting edema in both hands and was diagnosed with RS3PE syndrome. Two and four years after initial surgery for ovarian cancer, symptoms of RS3PE syndrome appeared, and a recurrent site was detected. With resection of the relapsed sites and increased maintenance dose of methylprednisolone, these symptoms improved within a month.

Preference of grade and lymphovascular invasion over invasive size measurement in stage I lung adenocarcinoma.

AIMS: Although it is necessary to measure the invasive size of lung adenocarcinoma with a lepidic component, it is not uncommon to have trouble in measuring the invasive size of lung adenocarcinoma. This study examined whether there were other stronger prognostic factors than invasive size. METHODS: We characterised the clinicopathological features associated with recurrence-free survival (RFS) of 686 patients with the pathological stage (p-Stage) I lung adenocarcinoma. Moreover, we compared the area under the curve (AUC) values for recurrence between various combinations of pathological-baseline (age & sex & p-Stage based on invasive size) (B(i)) and several prognostic factors, and various combinations of p-baseline based on total tumour size (B(t)) and several prognostic factors. RESULTS: AUC showed no significant differences between B(i) & new International Association for the Study of Lung Cancer grade (G) or vascular invasion (V), and B(t) & G or V. AUC was the highest in B & G & lymphatic invasion (L) & V. RFS was significantly shorter in patients with G3 OR L(+) OR V(+) than in those with G≤2 AND L(-) AND V(-) in each p-Stage based on invasive size (p-Stage(i)) and p-Stage based on total tumour size (p-Stage(t)) (p<0.05), and there were no significant differences in RFS between each p-Stage(i) and p-Stage(t). CONCLUSIONS: In any invasive size or total tumour size of p-Stage I lung adenocarcinoma, G, L and V are more powerful prognostic factors than the size criteria of p-Stage. Therefore, pathologists should focus on these pathological findings.

Pure Solid Pattern of Non-Small Cell Lung Cancer and Clustered Circulating Tumor Cells.

There are two solid patterns of non-small cell lung cancer (NSCLC) on computed tomography (CT): pure or mixed with ground-glass opacities (GGOs). They predict the degree of invasiveness, which may suggest the presence of clustered circulating tumor cells (CTCs), a predictor of poor prognosis. In this study, we assessed the implications of the solid patterns on CT and the preoperative clustered CTCs in surgically resected NSCLC. CTCs were detected using a size selection method. The correlation between the presence of preoperative clustered CTCs and the solid pattern and the prognostic implications were evaluated using co-variables from the clinical-pathological findings. Of the 142 cases, pure solid lesions (Group PS) and mixed GGOs (Group G) were observed in 92 (64.8%) and 50 (35.2%) patients, respectively. In Groups PS and G, clustered CTCs were detected in 29 (31.5%) and 1 (2.0%) patient (p < 0.01), respectively. The PS appearance was an independent predictor of preoperative clustered CTCs in the multivariable analysis, and preoperative clustered CTCs were an independent predictor of poor recurrence-free survival; the solid pattern was not an independent variable. Thus, the PS pattern of NSCLC on CT is an indicator of preoperative clustered CTCs, which is an independent poor prognosis predictor.

Verification of A New Filter for Isolation of Circulating Tumor Cells by Only Blood Filtration.

BACKGROUND/AIM: Since circulating tumor cells (CTCs) are precursors of metastatic lesions, extracting CTCs from whole blood is useful in obtaining information for cancer treatment. One of the CTC isolation methods is the size selection method; however, since the conventional methods are expensive and cumbersome, we developed an affordable and simple filter, whose usefulness is verified in this study. MATERIALS AND METHODS: The new filter [hereafter, soft micropore filter (S-MPF)] is made up of a polyethylene film with a thickness of 15 µm and conical pores having a diameter of 8-10 µm, which are opened uniformly (opening rate, 20%). This filter can filter whole blood by free-falling under gravity. The possibilities of the filter's usage for model CTC isolation, immunostaining, short-term cell culture, and gene mutation detection in extracted model CTCs were verified. RESULTS: S-MPF was able to extract model CTCs with an isolation rate of up to 15%. These model CTCs were detected by cytology, immunostaining, and culture by short-term incubation of filtered cells. Furthermore, genetic mutations were identified in the cultured cells. In addition, CTC isolation from the peripheral blood of patients with lung cancer was demonstrated by setting the volume of collected blood to 15 ml to prevent a low recovery rate. CONCLUSION: The S-MPF can be used to extract model CTCs quickly and easily. Moreover, cytological diagnosis, immunostaining, short-term culture, and gene mutation search are possible with this filter. Given its proven applicability in clinical samples, this filter can be used in clinical settings.

Low SARS-CoV-2 antibody titers may be associated with poor clinical outcomes for patients with severe COVID-19.

Recently, immune response to coronavirus disease (COVID-19) has attracted attention where an association between higher antibody titer and worsening disease severity has been reported. However, our experiences with severe COVID-19 patients with low antibody titers led to hypothesizing that suppressed humoral immune response may be associated with poorer prognosis in severe COVID19. In this study, antibody titers in severe COVID19 patients were measured at 7, 10, 12, and 14 days after onset. Patients were divided into survivors and non-survivors. SARS-CoV-2 IgM in survivors and non-survivors were 0.06 AU and 0.02 AU (P = 0.048) at 10 days, 0.1 AU and 0.03 AU (P = 0.02) at 12 days, and 0.17 AU and 0.06 AU (P = 0.02) at 14 days. IgG in survivors and non-survivors were 0.01 AU and 0.01 AU (P = 0.04) at 7 days, 0.42 AU and 0.01 AU (P = 0.04) at 12 days, and 0.42 AU and 0.01 AU (P = 0.02) at 14 days. Multivariate analysis showed better survival among patients with IgM positivity at 12 days (P = 0.04), IgG positivity at 12 days (P = 0.04), IgM positivity at 14 days (P = 0.008), and IgG positivity at 14 days (P = 0.005). In severe COVID-19, low antibody titers on days 12 and 14 after onset were associated with poorer prognosis.

TAS-Seq is a robust and sensitive amplification method for bead-based scRNA-seq.

Single-cell RNA-sequencing (scRNA-seq) is valuable for analyzing cellular heterogeneity. Cell composition accuracy is critical for analyzing cell-cell interaction networks from scRNA-seq data. However, droplet- and plate-based scRNA-seq techniques have cell sampling bias that could affect the cell composition of scRNA-seq datasets. Here we developed terminator-assisted solid-phase cDNA amplification and sequencing (TAS-Seq) for scRNA-seq based on a terminator, terminal transferase, and nanowell/bead-based scRNA-seq platform. TAS-Seq showed high tolerance to variations in the terminal transferase reaction, which complicate the handling of existing terminal transferase-based scRNA-seq methods. In murine and human lung samples, TAS-Seq yielded scRNA-seq data that were highly correlated with flow-cytometric data, showing higher gene-detection sensitivity and more robust detection of important cell-cell interactions and expression of growth factors/interleukins in cell subsets than 10X Chromium v2 and Smart-seq2. Expanding TAS-Seq application will improve understanding and atlas construction of lung biology at the single-cell level.

Neuropsychiatric Systemic Lupus Erythematosus with Cerebral Vasculitis and Lupus Nephritis Successfully Treated with High-dose Glucocorticoids and Mycophenolate Mofetil.

Neuropsychiatric systemic lupus erythematosus (NPSLE) with cerebral vasculitis is rare, and its prognosis is unfavorable. High-dose glucocorticoids and cyclophosphamide are widely used for the treatment of NPSLE, but cyclophosphamide has a risk of cervical intraepithelial neoplasia and ovarian insufficiency, which may discourage its use in young women. We experienced a case of NPSLE with cerebral vasculitis and lupus nephritis that responded successfully to glucocorticoids and mycophenolate mofetil (MMF). MMF might be a treatment option for NPSLE without concern for reproductive toxicity. However, there are only a few reports on the efficacy of MMF in NPSLE, and further investigations are needed.