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Abstract Background Pemetrexed is an efficacious multi-targeted antifolate with acceptable toxicity for non-squamous non-small cell lung cancer (non-Sq NSCLC) and malignant pleural mesothelioma. Vitamin B12 and folic acid as premedication can reduce the frequency of severe toxicities of pemetrexed chemotherapy. However, adverse effects are frequent in clinical settings. In this study, we aimed to identify the clinical factors and single-nucleotide polymorphisms (SNPs) associated with the toxicity and efficacy of pemetrexed chemotherapy. Methods This observational study was conducted from October 2012 to December 2019; we evaluated the toxicities and efficacies of pemetrexed chemotherapy using multivariate logistic or Cox regression analysis. In total, 106 patients received pemetrexed chemotherapy. SNPs were analyzed for four patients with malignant pleural mesothelioma and 67 with non-Sq NSCLC. Results The median progression-free survival (PFS) and overall survival of 63 patients with non-Sq NSCLC, excluding four in the adjuvant setting, were 6.8 and 33.3 months, respectively. Per propensity-score-adjusted multivariate Cox analyses, favorable factors for PFS were folic acid level ≥ 9.3 ng/mL before premedication, platinum combination, bevacizumab combination, vitamin B12 level A), and A/A + A/C of DHFR (680 C > A). Favorable prognostic factors included good performance status, low smoking index, body mass index ≥ 20.66 kg/m2, folic acid level ≥ 5.55 ng/mL before premedication, higher retinol-binding protein before chemotherapy, and A/G of MTRR (66 A > G). Among the 71 patients who were analyzed for SNPs, the frequencies of hematologic toxicities and non-hematologic toxicities in Grades 3–4 were 38% and 36.6%, respectively. Per propensity-score-adjusted multivariate logistic analyses, risk factors for Grades 3–4 hematologic toxicities were vitamin B12 level T). Risk factors for Grades 2–4 non-hematologic toxicities were homocysteine levels ≥ 11.8 nmol/mL before premedication, transthyretin level T), and A/A + G/G of SLC19A1 [IVS2 (4935) G > A]. Conclusion The information on metabolites and SNPs of the folate and methionine cycle will help predict the toxicities and efficacies of pemetrexed. Trial registration This trial was retrospectively registered with the University hospital Medical Information Network (UMIN000009366) on November 20, 2012.

Abstract Introduction This study aimed to evaluate the correlation and agreement between end‐tidal CO2 (EtCO2) measured with the novel portable capnometer (CapnoEye®) and partial pressure of arterial carbon dioxide (PaCO2) levels in patients with respiratory diseases and to compare the efficacy of EtCO2 and PvCO2 in predicting PaCO2 levels. Methods We analyzed the correlation and the agreement between EtCO2 and PaCO2 and between PvCO2 and PaCO2 using Pearson's moment correlation coefficient in patients with type 1 and type 2 respiratory failure and both groups overall. Results A total of 100 samples were included that comprised 67 men (67%). The mean age of the subjects was 77 ± 13 years. Chronic obstructive pulmonary disease (COPD) (43%) was the most common disease. There was a high correlation between EtCO2 and PaCO2 (r = 0.88; p < 0.0001). Sixty‐six PvCO2 samples were obtained, and there was a high correlation between PvCO2 and PaCO2 (r = 0.81; p < 0.0001). Regarding type 2 respiratory failure, there was a high correlation between EtCO2 and PaCO2 (r = 0.81). The Bland–Altman analysis between PaCO2 and EtCO2 revealed a bias of 5.7 mmHg, with limits of agreement ranging from −5.1 mmHg to 16.5 mmHg. In contrast, the analysis between PaCO2 and PvCO2 revealed a bias of −6.8 mmHg, and the limits of agreement ranged from −22.13 mmHg to 8.53 mmHg. Conclusion EtCO2 measured by CapnoEye® was significantly correlated to PaCO2 levels in patients with respiratory diseases. Moreover, CapnoEye® may be more useful for predicting hypercapnia conditions in which respiratory diseases are compared with measure PvCO2.

Purpose: Intensity-modulated radiotherapy (IMRT) is currently used more commonly than 3-dimensional conformal radiation for definitive thoracic radiation. We examined the efficacy profiles of concurrent chemoradiotherapy (CCRT) with IMRT after durvalumab became clinically available. Methods: We reviewed the clinical records of patients with stage III non-small cell lung cancer (NSCLC) treated with CCRT and IMRT at seven centers in Japan and investigated relapse and survival from May 2018 to December 2019. The primary endpoint of this report was progression-free survival (PFS). Results: Among 107 patients enrolled in the study, 87 were sequentially administered durvalumab. From CCRT commencement, patients were followed up for a median period of 29.7 months. The median PFS at the end of the CCRT was 20.7 months. Among the 87 patients, 58 experienced disease relapses, of whom 36 (62.1 %) had distant metastases. Multivariate Cox regression analysis revealed that a favorable response to CCRT, a radiation dose ≥ 62 Gy, and stage IIIA NSCLC were associated with prolonged PFS (all P = 0.04). Multivariate logistic regression by landmark analysis revealed that mortality risk factors were durvalumab treatment duration ≤ 11.7 months, a lower maximum grade of immune-related adverse events, FEV1

Pulmonary hamartomas are common benign lung tumors; however, endobronchial hamartomas are relatively rare. We report a case of asymptomatic endobronchial hamartoma in a 51-year-old man. Chest computed tomography revealed a 10-mm protrusion in the right main bronchus. Preoperative virtual bronchoscopy (VBS) was performed; subsequently, minimally invasive bronchoscopic resection was safely performed under local anesthesia. The use of VBS is a useful treatment strategy and follow-up modality.

Abstract A 62‐year‐old woman with rheumatoid arthritis and a history of receiving immunosuppressant therapy had a recurrence of lung adenocarcinoma with EGFR L858R mutation. Following 14 months of treatment with erlotinib, computed tomography (CT) findings revealed the presence of small diffuse nodules. Bronchoscopy was performed as metastasis was suspected; however, this was not detected on lung biopsy with forceps. Transbronchial lung cryobiopsy (TBLC) succeeded in detecting metastatic adenocarcinoma, and T790M and L858R gene mutations. Pathological examination revealed a cluster of tumor cells in the intralobular interstitial areas, which was consistent with the CT findings. This report provides important information regarding the role of TBLC in diagnosing metastatic cancer, such as diffuse small miliary nodules, and its genetic mutations.

Abstract Background Osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), can be used as second-line treatment for lung cancer patients harboring the T790M substitution. Although osimertinib is more effective than the first-generation EGFR-TKIs used for first-line treatment, its efficacy with respect to long-term patient survival remains unclear even upon the administration of a complete sequence of EGFR-TKI therapy. Moreover, limited information is available regarding genetic diagnostic approaches after the treatment of EGFR-TKI–naïve patients. This study investigated the clinical characteristics of EGFR-mutated lung cancer patients harboring the T790M substitution resistant to EGFR-TKIs, as well as the advantages of rebiopsy and liquid biopsy for these patients. Methods The medical records of patients screened for EGFR mutations were reviewed. Upon failure of naïve treatment with EGFR-TKIs, except for osimertinib, single-plexus cobas version 2 was repeatedly used to detect the T790M substitution in EGFR via tissue or liquid biopsy. Results From April 2016 through May 2019, 113 patients were found to harbor EGFR mutations. Sixty patients were treated with EGFR-TKIs, among whom 46 underwent tissue or liquid biopsy. Twenty-nine of these 46 (63%) patients harbored the T790M substitution. In total, 141 rebiopsies were performed. The T790M substitution was detected in 24 of 43 tissue biopsies and 11 of 98 liquid biopsies. If patients displayed an EGFR exon 19 deletion, had a new lesion, and were administered gefitinib as first-line therapy, they were suspected to harbor the T790M substitution. Furthermore, the T790M substitution was detected through rebiopsy in patients with coexisting original mutations, brain metastases, tumor enlargement by ≥12 mm, or metastases at minor sites. Conclusion Among patients with positive factors associated with the T790M mutation, repeated tissue or liquid biopsies are useful to maximize the detection rate of the T790M substitution. Furthermore, these biopsies need to be repeated numerous times in order to reduce “detection overlook” among such patients.

Abstract Immune checkpoint inhibitors (ICIs) are reportedly effective against many kinds of neoplasm, but may be responsible for several kinds of immune‐related adverse events (irAEs). Among these irAEs, the incidence of myelosuppression due to ICIs is relatively low. Corticosteroids are needed to control most cases of myelosuppression. Here, we report an 88‐year‐old woman with squamous cell lung cancer who was administered pembrolizumab. After five cycles of pembrolizumab, she developed severe pancytopenia. The pancytopenia improved under observation without steroid administration after cessation of pembrolizumab. During recovery from this irAE, the patient also maintained long‐term antitumor efficacy. Key points Significant findings of the study There are several kinds of immune‐related adverse events. We encountered a case of pembrolizumab‐induced pancytopenia with squamous cell lung cancer. What this study adds Corticosteroids are needed to control most cases of myelosuppression induced by ICIs, but pancytopenia induced by pembrolizumab in our case improved without steroids.

Abstract Background 4′-[Methyl-11C] thiothymidine (4DST) PET/CT provides DNA synthesis imaging, which represented a higher correlation with the proliferation in advanced non-small cell lung cancer (NSCLC) than that from imaging with FDG. The aim of this prospective study was to evaluate the potential of 4DST in early therapy monitoring for advanced NSCLC, and to compare the results with those from CT and FDG PET/CT. Results Patients who had been pathologically diagnosed with advanced NSCLC and were scheduled to receive platinum-doublet chemotherapy (PT-DC) were eligible. PET/CT imaging with 4DST and with FDG, and CT were performed at baseline and after 2 cycles of PT-DC (interim). Patients were evaluated semi-quantitatively after the 2 cycles of PT-DC using several PET parameters, response evaluation criteria in solid tumors (RECIST) 1.1 based on CT measurements, European Organization for Research and Treatment of Cancer (EORTC) criteria and PET Response Criteria in Solid Tumors (PERCIST) 1.0 based on PET/CT measurements. Baseline measurement data and metabolic response were compared between patients with progression-free survival (PFS) > 4 months and ≤ 4 months, and PFS and overall survival (OS) were compared between patients with and without metabolic response measured with each of the different parameters, using Kaplan-Meier statistics and log-rank testing. A total of 22 patients were included in this study. For predicting PFS > 4 months and ≤ 4 months, metabolic tumor volume (MTV) of baseline 4DST showed the highest area under the curve (0.73), positive predictive value (80.0%), negative predictive value (66.7%), and accuracy (72.7%) among baseline measurement data and metabolic responses from 4DST PET/CT, FDG PET/CT, and CT. Kaplan-Meier curves and log-rank tests for PFS with MTV of baseline FDG and baseline 4DST, and for OS with MTV of baseline FDG and baseline TLG, and MTV of baseline 4DST revealed significant results. Conclusions MTV of baseline 4DST PET/CT along with MTV of baseline FDG PET/CT represent promising predictors of PFS, and MTV of baseline 4DST PET/CT along with MTV and TLG of baseline FDG PET/CT are possible predictors of OS in patients with advanced NSCLC.

Introduction: We examined the long-term efficacy and safety of nivolumab, a human monoclonal antibody that inhibits interactions between the programmed cell death protein-1 receptor and its ligands (programmed death-ligand 1 and programmed death-ligand 2), in Japanese patients with malignant pleural mesothelioma (MPM). Methods: Japanese patients with previously treated MPM (one or two regimens) were enrolled in a single-arm, phase 2 study and received nivolumab intravenously 240 mg every 2 weeks until progressive disease or unacceptable toxicity. The primary end point was the centrally assessed objective response rate. Other end points included overall survival (OS), progression-free survival (PFS), treatment-related adverse events, and patient-reported outcomes (Lung Cancer Symptom Scale for mesothelioma and EuroQOL visual analog scale). Patient enrollment started on June 16, 2016. Here, we report 3-year follow-up data (cutoff date: November 12, 2019). Results: Thirty-four patients were enrolled. The centrally assessed objective response rate was previously reported (29.4%). The 2- and 3-year OS rates were 35.3% and 23.5%, respectively, and the corresponding PFS rates were 17.0% and 12.7%. Median OS and PFS were 17.3 and 5.9 months, respectively. Eight patients were alive at 3 years of follow-up. Nivolumab was well tolerated and no new safety signals were found. The patient-reported outcomes were maintained without marked deteriorations during the study. Conclusions: Our results reveal clinically relevant long-term efficacy and safety of nivolumab for the treatment of MPM.

Lung cancer immunotherapy is an effective treatment option; however, it can be hampered by adverse events, including pancreatitis, associated with excessive immune activation. Here, we report the case of a 70‐year‐old patient who presented with recurrent lung squamous carcinoma and was started with pembrolizumab treatment (200 mg every three weeks). The patient developed pembrolizumab‐induced pancreatitis. After 14 months of pembrolizumab treatment, positron emission tomography–computed tomography showed a tumour‐shaped, highly integrated lesion at the pancreatic head and significantly elevated tumour markers, including carbohydrate antigen 19‐9 (149.3 U/mL), s‐pancreas antigen‐1 (44.7 U/mL), and duke pancreatic monoclonal antigen type 2 (412 U/mL). Pembrolizumab‐induced immune‐related pancreatitis was effectively treated with prednisolone 90 mg (1 mg/kg/day). Four months later, normal levels of the three specific tumour markers were detected, with improved pancreatic enzymes and radiographic findings. To our knowledge, this is the first reported case of immune‐related pancreatitis with elevated pancreatic cancer‐specific markers.

In general, we have to assume tuberculous pleurisy when a patient presents with pleural effusion and elevated adenosine deaminase (ADA). However, other diseases need to be considered, including immunoglobulin (Ig)G4-related disease (IgG4-RD). This case involved a 65-year-old asymptomatic man with right pleural effusion showing elevated ADA. He had no articular findings or rashes. Results were negative for all autoantibodies. Pleura, mediastinal lymph nodes, and areas around the aorta and vertebra showed high uptake of 18F-fluorodeoxyglucose (FDG) on positron-emission tomography-computed tomography (PET-CT). These findings were specific for IgG4-RD. Based on the results of FDG-PET-CT, we performed thoracoscopy under local anesthesia and bronchoscopy. Pleural biopsy and culture, and other examinations including sputum and blood yielded negative findings for tuberculous pleurisy. A pleural biopsy specimen showed IgG4-positive plasma cells and fibrosis without obliterative phlebitis or storiform fibrosis, and serum IgG4 was also high. The ratio of IgG4-to IgG-positive plasma cells was under 40%, and >10 IgG4-positive cells were seen in high-power fields. This case was classed as ‘possible IgG4-RD’ on the comprehensive diagnostic criteria for IgG4-RD, but did not meet the diagnostic criteria for IgG4-related respiratory disease. Prednisolone proved effective against the pleural effusion. We therefore clinically diagnosed IgG4-RD with pleural effusion based on the 2019 classification criteria for IgG4-RD in the United States. Although few cases of IgG4-RD with pleural effusion have been reported, this disease needs to be considered among the differential diagnoses for high-ADA pleural effusion. FDG-PET-CT and thoracoscopy under local anesthesia may be helpful for diagnosis.

This case report describes the re-administration of abatacept to successfully reduce the articularsymptoms of a patient with rheumatoid arthritisduring the intensive phase of anti-tuberculous therapy. A 75-year-old man developed active pulmonary tuberculosis during the administration of abatacept for rheumatoid arthritis. The patient experienced a paradoxical reaction and exacerbation of rheumatoid arthritis that caused us to discontinue the abatacept. Later re-administration of abatacept along with anti-tuberculosis treatment led to well-controlled rheumatoid arthritis without exacerbation of the tuberculosis. This case shows that re-administration of abatacept may be much safer than TNF inhibitor to treat patients who are infected with mycobacteria during thetreatment of immunological diseases such asrheumatoid arthritiswith biological agents.

An 80-year-old woman was admitted to our hospital with pneumonia and exacerbation of sinobronchial syndrome (SBS). She presented with yellow discoloration of the nail beds of all fingers and toes, and her nails were recognized as growing slowly. Chest X-ray revealed bronchiectasis in the bilateral lower lobe and bilateral pleural effusion. We diagnosed her as having yellow nail syndrome (YNS), based on the triad of yellow nails, lymphedema, and lung disease. After treatment with antibiotics [ampicillin/sulbactam and clarithromycin (CAM)] for pneumonia and SBS, her general condition improved, and the yellow nails disappeared in some fingers. When she was previously treated with 200 mg CAM for SBS, her yellow nails had not shown improvement. This time, her yellow nails improved after treatment with 400 mg CAM. The literature reports vitamin E, zinc, and topical corticosteroid plus active vitamin D3 to be effective in the treatment of yellow nails. Two studies have reported treatment for YNS using CAM, though they found a lack of efficacy. Thus, the present case is the first to report improved yellow nails using CAM alone. We conclude that not only SBS and lung disease but also YNS were improved by treatment with 400 mg CAM.

Background: Treatment strategy that reduces dependence on long-term medication for chronic asthma is preferable. The purpose of the study is to investigate the efficacy of an early intensive intervention for inducing inactive asthma in adults and identify factors that affect the efficacy. Methods: A prospective study was conducted on subjects who had asthma for two years or less. An intensive intervention consisting of systemic corticosteroid treatment for two weeks followed by inhaled corticosteroid for further 16 weeks with concomitant administration of bronchodilator(s) was administrated on 109 subjects. As a control group, 33 subjects were treated according to the current asthma treatment guidelines for 18 weeks. The primary outcome of the intervention was assessed with symptomatology and use of medication during 12 months after the cessation of treatment period. Results: At one year after the intervention, significantly more patients in the intensive intervention group (41%) than in the control group (24%) had no respiratory symptoms and were medication-free or had experienced minor upper respiratory symptoms (inactive asthma) (P = 0.01). The intensive intervention maintained a significant factor associated with one-year inactive asthma (adjusted odds ratio: 3.61, 95% confidence interval: 1.2010.84; P = 0.02). Infection as onset cause, asthma duration and pre-treatment %FEV1.0 were also identified independently associated with inactive asthma. As the limitation, the study was not randomized trial. Conclusions: Intensive therapy in the early stage is very likely to contribute to increasing one-year asthma inactivity, which may reduce patients' dependence on long-term management by medical treatment.

Molecular iodine catalyzes a cyclization of N-aryl-2-alkynylanilines, which proceeds through the iodocyclization of 2-alkynylanilines followed by the protodeiodination of the iodocyclized intermediates at room temperature. Furthermore, the molecular iodine catalysis can be applied to the cascade cyclization of 2-(enynyl)aniline and to the tandem cyclization-addition reaction of 2-alkynylanilines with a,ß-enones. [ABSTRACT FROM AUTHOR]

First-line chemotherapy regimens that include bevacizumab (Bev) have been hypothesized to improve outcomes in patients with advanced non-squamous non-small cell lung cancer (non-sq NSCLC). Although approved to treat NSCLC in 2009, insufficient data exist on the clinical uses of Bev in Japan. The present study prospectively evaluated the efficacy and safety of Bev-containing combination chemotherapy. Eligible patients exhibited histologically or cytologically documented advanced or recurrent non-sq NSCLC. Patients were administered 15 mg/kg Bev with standard chemotherapy followed by maintenance Bev. The primary endpoints were progression-free survival (PFS) and safety. A total of 102 patients with non-sq NSCLC were enrolled, 44.1% of whose tumor carried epidermal growth factor receptor (EGFR) mutations. The overall response rate to the intervention was 44.1%, and the median PFS was 8.3 months [95% confidence interval (CI)=6.4-10.2 months]. The median overall survival was 26.3 months (95% CI=22.2-30.4 months). The incidence of Bev-associated severe adverse events was similar to those in previous trials, excluding a grade 3-4 hypertension rate of 30.4% in the present study. Multivariate analysis revealed that a higher TNM classification of malignant tumor staging-T factor, adjusted hazard ratio (HR)=1.33 (95% CI=1.10-1.61), and poor performance status [adjusted HR=1.63 (1.02-2.60)] were associated with significantly shorter PFS, whilst the EGFR exon 19 deletion was significantly associated with prolonged PFS [adjusted HR=0.47 (0.25-0.87)]. Bev-containing chemotherapy was safe and effective for patients with non-sq NSCLC in clinical settings in Japan. The EGFR exon 19 deletion was suggested as a positive predictive factor for the efficacy of Bev-containing chemotherapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pneumothorax is one of the most important complications after bronchoscopy. This study was conducted to determine the risk factors for post-bronchoscopy pneumothorax. METHODS: We retrospectively reviewed the medical records of 23 consecutive subjects who were diagnosed with iatrogenic pneumothorax after bronchoscopy between August 2010 and February 2014. Forty-six control subjects who did not develop pneumothorax after bronchoscopy were randomly selected. The factors affecting the occurrence of pneumothorax were determined by univariate and multivariate analyses. RESULTS: Among 991 patients who underwent bronchoscopy during the study period, 23 (2.3%) developed pneumothorax after bronchoscopy. Among these 23 subjects, 13 (57%) required chest tube drainage. Compared with the control group (46 randomly selected from 968 subjects who did not develop pneumothorax), the group that developed pneumothorax had a preponderance of women and had more target lesions located in the subpleural area (odds ratio [OR] 7.8, 95% CI 0.9-64), especially those that were close to the interlobular pleura (OR 5.1, 95% CI 1.6-16.1) and the left lung (OR 3.2, 95% CI 1.1-9.5). Multivariate analysis revealed that a subinterlobular pleural location of a lesion was a risk factor for pneumothorax (OR 4.8, 95% CI 1.1-20.4). CONCLUSIONS: Pneumothorax occurred significantly more frequently when bronchoscopy was performed for subinterlobular pleural lesions. Close attention and care should be taken during bronchoscopy, especially when target lesions are abutting the interlobular pleura. [ABSTRACT FROM AUTHOR]

This report describes a patient with small-cell lung cancer who was infected with both Mycobacterium tuberculosis and non-tuberculous mycobacterium. lie received irinotecan plus cisplatin, with and without rifampin. Rifampin slightly reduced the conversion of irinotecan to 7-ethyl-10-hydroxycamptothecin (SN-38), as determined by pharmacokinetic analysis. Rifampin may influence the metabolism and toxicity of irinotecan to some extent. However, there are possibilities to control M. tuberculosis and Mycobacterium avium complex infections in patients with small-cell lung cancer by using rifampin in combination with irinotecan plus cisplatin. [ABSTRACT FROM AUTHOR]

In this paper, we present a new way of constructing a map from the higher Bloch group to the higher rational K-theory for an algebraic number field. The composition of it with the regulator map is expressed in terms of the polylogarithm function. To do this, we employ exact hermitian cubes and their Bott-Chern forms. [ABSTRACT FROM AUTHOR]

A copper(I) iodide/sodium hydride/ethylene glycol system promoted reaction of aryl- and alkenyldimethylsilanes with C(sp³)-X electrophiles bearing a β-hydrogen produced the crosscoupling products at ambient temperature within a short period of time. [ABSTRACT FROM AUTHOR]

Fluoride-free cross-coupling of aryl- and alkenyldimethylsilanes with organic halides proceeded in the presence of monocopper(I) alkoxide of ethylene glycol. [ABSTRACT FROM AUTHOR]

Background:Papillary thyroid carcinoma (PTC) generally has a good prognosis but may have an aggressive course, particularly in the elderly. Standard treatment consists of radioactive iodine and thyrotropin suppression with superphysiological doses of thyroid hormone. Other modalities are less commonly used. We report perhaps the first patient with PTC who was treated with Mohs chemosurgery.Summary:The patient was a 94-year-old woman who was diagnosed at age 67 with PTC and underwent a near-total thyroidectomy. The PTC recurred in the cervical nodes and reached the size of 8 × 5.5 cm by age 89. The tumor had become exposed and was hemorrhaging. By age 92 it measured 10 cm, encompassed the right common carotid artery, and was invading the trachea and larynx. In order to implement local control, we applied Mohs ointment. She also required blood transfusions. After approximately 1 month, the tumor had flattened, and the hemorrhaging stopped, and the patient was able to be discharged from the hospital to home nursing.Conclusion:Treatment with Mohs chemosurgery should be considered in the rare patient with exposed locally aggressive PTC for palliation and improved quality of life. [ABSTRACT FROM AUTHOR]

Despite various attempts to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients with COVID-19 convalescent plasmas, neither appropriate approach nor clinical utility has been established. We examined the efficacy of administration of highly neutralizing COVID-19 convalescent plasma (hn-plasmas) and such plasma-derived IgG administration using the Syrian hamster COVID-19 model. Two hn-plasmas, which were in the best 1% of 340 neutralizing activity-determined convalescent plasmas, were intraperitoneally administered to SARS-CoV-2-infected hamsters, resulting in a significant reduction of viral titers in lungs by up to 32-fold compared to the viral titers in hamsters receiving control nonneutralizing plasma, while with two moderately neutralizing plasmas (mn-plasmas) administered, viral titer reduction was by up to 6-fold. IgG fractions purified from the two hn-plasmas also reduced viral titers in lungs more than those from the two mn-plasmas. The severity of lung lesions seen in hamsters receiving hn-plasmas was minimal to moderate as assessed using microcomputerized tomography, which histological examination confirmed. Western blotting revealed that all four COVID-19 convalescent plasmas variably contained antibodies against SARS-CoV-2 components, including the receptor-binding domain and S1 domain. The present data strongly suggest that administering potent neutralizing activity-confirmed COVID-19 convalescent plasmas would be efficacious in treating patients with COVID-19. IMPORTANCE Convalescent plasmas obtained from patients who recovered from a specific infection have been used as agents to treat other patients infected with the very pathogen. To treat using convalescent plasmas, despite thatmore than 10 randomized controlled clinical trials have been conducted and more than 100 studies are currently ongoing, the effects of convalescent plasma against COVID-19 remained uncertain. On the other hand, certain COVID-19 vaccines have been shown to reduce the clinical COVID-19 onset by 94 to 95%, for which the elicited SARS-CoV-2-neutralizing antibodies are apparently directly responsible. Here, we demonstrate that highly neutralizing effect-confirmed convalescent plasmas significantly reduce the viral titers in the lung of SARS-CoV-2-infected Syrian hamsters and block the development of virally induced lung lesions. The present data provide a proof of concept that the presence of highly neutralizing antibody in COVID-19 convalescent plasmas is directly responsible for the reduction of viral replication and support the use of highly neutralizing antibody-containing plasmas in COVID-19 therapy with convalescent plasmas. [ABSTRACT FROM AUTHOR]