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Rapid qualitative antigen testing is essential in the clinical management of COVID-19. However, most evaluations of antigen tests have been performed before the emergence of the Omicron variant.This prospective observational study evaluated QuickNavi-COVID19 Ag, a rapid antigen detection test between December 2021 and February 2022 in Japan, using real-time reverse transcription (RT)-PCR as a reference. Two nasopharyngeal samples were simultaneously collected for antigen testing and for RT-PCR. Variant analysis of the SARS-CoV-2 genomic sequencing was also performed.In total, nasopharyngeal samples were collected from 1073 participants (417 positive; 919 symptomatic; 154 asymptomatic) for analysis. Compared with those of RT-PCR, the sensitivity, specificity, positive predictive value, and negative predictive value were 94.2% (95% CI: 91.6%-96.3%), 99.5% (95% CI: 98.7%-99.9%), 99.2% (95% CI: 97.8%-99.8%), and 96.5% (95% CI: 94.8%-97.7%), respectively. The sensitivity among symptomatic individuals was 94.3% (95% CI: 91.5%-96.4%). Overall, 85.9% of sequences were classified as Omicron sublineage BA.1, 12.4% were Omicron sublineage BA.2, and 1.6% were Delta B.1.617.2. (Delta variant). Most of the samples (87.1%) had Ct values of25, and the sensitivity was 47.4% for low viral load samples (Ct ≥ 30); a similar trend has been observed in both symptomatic and asymptomatic groups.The QuickNavi-COVID19 Ag test showed sufficient diagnostic performance for the detection of the SARS-CoV-2 Omicron sublineages BA.1 and BA.2 from nasopharyngeal samples. However, the current study was mainly performed in symptomatic patients and the results are not sufficiently applicable for asymptomatic patients.

Since respiratory sample collection is an uncomfortable experience, simultaneous detection of pathogens with a single swab is preferable. We prospectively evaluated the clinical performance of a newly developed antigen test QuickNavi-Flu+COVID19 Ag (Denka Co., Ltd., Tokyo, Japan) which can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses at the same time with a single testing device.We included those who were suspected of contracting coronavirus disease 2019 (COVID-19) and were referred to a PCR center at Ibaraki prefecture in Japan, between August 2, 2021 to September 13, 2021, when the variant carrying L452R spike mutation of SARS-CoV-2 were prevalent. Additional nasopharyngeal samples and anterior nasal samples were obtained for the antigen test and were compared with a reference real-time reverse transcription PCR (RT-PCR) using nasopharyngeal samples.In total, 1510 nasopharyngeal samples and 862 anterior nasal samples were evaluated. During the study period, influenza viruses were not detected by QuickNavi-Flu+COVID19 Ag and reference real-time RT-PCR. For SARS-CoV-2 detection in nasopharyngeal samples, the sensitivity and specificity of the antigen test were 80.9% and 99.8%, respectively. The sensitivity and specificity using anterior nasal samples were 67.8% and 100%, respectively. In symptomatic cases, the sensitivities increased to 88.3% with nasopharyngeal samples and 73.7% with anterior nasal samples. There were three cases of discrepant results between the antigen test and the real-time RT-PCR. All of them were positive with the antigen test but negative with the real-time RT-PCR in SARS-CoV-2 detection.A combo kit, QuickNavi-Flu+COVID19 Ag, showed an acceptable sensitivity and sufficient specificity for SARS-CoV-2 detection, especially using nasopharyngeal sample collected from symptomatic patients.

Introduction Smart Gene is a point-of-care (POC)-type automated molecular testing platform that can be performed with 1 min minute of hands-on-time. Smart Gene SARS-CoV-2 is a newly developed Smart Gene molecular assay for the detection of SARS-CoV-2. The analytical and clinical performance of Smart Gene SARS-CoV-2 has not been evaluated. Methods Nasopharyngeal and anterior nasal samples were prospectively collected from subjects referred to the local PCR center from March 25 to July 5, 2021. Two swabs were simultaneously obtained for the Smart Gene SARS-CoV-2 assay and the reference real-time RT-PCR assay, and the results of Smart Gene SARS-CoV-2 were compared to the reference real-time RT-PCR assay. Results Among a total of 1150 samples, 68 of 791 nasopharyngeal samples and 51 of 359 anterior nasal samples were positive for SARS-CoV-2 in the reference real-time RT-PCR assay. In the testing of nasopharyngeal samples, Smart Gene SARS-CoV-2 showed the total, positive and negative concordance of 99.2% (95% confidence interval [CI]: 98.4–99.7%), 94.1% (95% CI: 85.6–98.4%) and 99.7% (95% CI: 99.0–100%), respectively. For anterior nasal samples, Smart Gene SARS-CoV-2 showed the total, positive and negative concordance of 98.9% (95% CI: 97.2–99.7%), 98.0% (95% CI: 89.6–100%) and 99.0% (95% CI: 97.2–99.8%), respectively. In total, 5 samples were positive in the reference real-time RT-PCR assay and negative in the Smart Gene SARS-CoV-2 assay, whereas 5 samples were negative in the reference real-time RT-PCR assay and positive in the Smart Gene SARS-CoV-2 assay. Conclusion Smart Gene SARS-CoV-2 showed sufficient analytical performance for the detection of SARS-CoV-2 in nasopharyngeal and anterior nasal samples.

Antigen tests for severe acute respiratory coronavirus 2 sometimes show positive lines earlier than their specified read time, although the implication of getting the results at earlier time is not well understood. This study aimed to evaluate the clinical utility of an antigen test by evaluating the time period to get positive results and by comparing the test sensitivity with that of a digital immunoassay (DIA) test.We prospectively collected additional nasopharyngeal samples from patients who had already tested positive for SARS-CoV-2 by reverse transcription PCR. The additional swab was used for an antigen test, QuickNavi™-COVID19 Ag, and the time periods to get positive results were measured. The sensitivity of QuickNavi™-COVID19 Ag was also compared with that of a DIA.In 84 of 96 (87.5%) analyzed cases, the results of QuickNavi™-COVID19 Ag were positive. The time to obtain positive results was 15.0 seconds in median (inter quartile range: 12.0-33.3, range 11-736), and was extended in samples with higher cycle thresholds (Ct) (p32.QuickNavi™-COVID19 Ag immediately showed positive results in most cases, and the time to a positive reaction may have indicated the viral load. In addition, the sensitivity of the test was comparable to the DIA.

IntroductionWe newly designed and developed two types of hydrogen fuel cell (HFC) buses (motorcoach type and minibus type) with a mobile laboratory system. Feasibility studies have been performed for mobile laboratory testing, especially for the laboratory performance of COVID-19 RT-PCR (PCR).MethodsWe evaluated the driving range capability, PCR sample size capacity, turn-around time (TAT), and analytical performance for the detection of SARS-CoV-2. Saliva samples were used for the current research and the analytical performance was compared with reference PCR.ResultsThe estimated driving range and sample size capacity were 432 km and 3,258 samples, respectively for the HFC motorcoach and 313 km and 2,146 samples for the HFC minibus, respectively. For the TAT, the median time between the sample submission and the completion of PCR were 86 min for the motorcoach and 76 min for the minibus, and the median time between sample submission and the electronic reporting of the result to each visitor were 182 min for the motorcoach and 194 min for the minibus. A secondary analysis of 1,574 HFC mobile laboratory testing samples was conducted and all negative samples were negative by reference PCR. Furthermore, all positive samples were confirmed as positive by reference PCR or other molecular examinations.ConclusionWe confirmed the feasibility of HFC mobile laboratory systems for achieving the rapid reporting of highly accurate PCR results.

IntroductionRapid qualitative antigen testing has been widely used for the laboratory diagnosis of COVID-19 with nasopharyngeal samples. Saliva samples have been used as alternative samples, but the analytical performance of those samples for qualitative antigen testing has not been sufficiently evaluated.MethodsA prospective observational study evaluated the analytical performance of three In Vitro Diagnostics (IVD) approved COVID-19 rapid antigen detection kits for saliva between June 2022 and July 2022 in Japan using real-time reverse transcription polymerase chain reaction (RT-PCR) as a reference. A nasopharyngeal sample and a saliva sample were simultaneously obtained, and RT-PCR was performed.ResultsIn total, saliva samples and nasopharyngeal samples were collected from 471 participants (140 RT-PCR-positive saliva samples and 143 RT-PCR-positive nasopharyngeal samples) for the analysis. The median Ct values were 25.5 (interquartile range [IQR]: 21.9-28.8) for saliva samples and 17.1 (IQR: 15.5-18.7) for nasopharyngeal samples (p90% for saliva samples with a moderate-to-high viral load (CtConclusionCOVID-19 rapid antigen detection kits with saliva showed high specificities, but the sensitivities varied among kits, and the analytical performance of saliva qualitative antigen detection kits was much worse than that of kits using nasopharyngeal samples.

Molecular tests are the mainstay of detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, their accessibility can be limited by the long examination time and inability to evaluate multiple samples at once. This study evaluated the analytical performance of the newly developed rapid molecular assays GENECUBE® HQ SARS-CoV-2 and GENECUBE® FLU A/B. This prospective study was conducted between 14 December 2020 and 9 January 2021 at a polymerase chain reaction (PCR) center. Samples were collected from the nasopharynx with flocked swabs. Molecular tests were performed with the GENECUBE® system and reference reverse transcription (RT)-PCR, and the results of the two assays were compared. Among 1065 samples, 81 (7.6%) were positive for SARS-CoV-2 on the reference RT-PCR. Three showed discordance between GENECUBE® HQ SARS-CoV-2 and the reference RT-PCR; the total, positive, and negative samples of concordance for the two assays were 99.7%, 100%, and 99.7%, respectively. All discordant cases were positive with GENECUBE® HQ SARS-CoV-2 and negative with the reference RT-PCR. SARS-CoV-2 was detected in all three samples using another molecular assay for SARS-CoV-2. For GENECUBE® FLU A/B, the total, positive, and negative samples of concordance for the two assays were 99.5%, 100%, and 99.1%. The GENECUBE® HQ SARS-CoV-2 and GENECUBE® FLU A/B demonstrated sufficient analytical performance to detect SARS-CoV-2 and influenza virus A/B.

Objective To evaluate the opioid-induced constipation burden in the subgroup of patients with lung cancer who participated in the observational Opioid-Induced Constipation in Patients with Cancer Pain in Japan (OIC-J) study. Methods The prospective, observational study, OIC-J, included 212 patients with various tumour types, 33% of whom had lung cancer. The incidence of opioid-induced constipation was evaluated using several diagnostic criteria, as well as the physician’s diagnosis and patient’s subjective assessment. Following initiation of opioids, patients recorded details of bowel movements (i.e. date/time, Bristol Stool Scale form, sensations of incomplete evacuation or anorectal obstruction/blockage and degree of straining) in a diary for 2 weeks. Relationships between patient characteristics and opioid-induced constipation onset and effects of opioid-induced constipation on quality of life were explored. Results In total, 69 patients were included in this post hoc analysis. The incidence of opioid-induced constipation varied (39.1–59.1%) depending on which diagnostic criteria was used. Diagnostic criteria that included a quality component or a patient’s feeling of bowel movement as an evaluation item (i.e. Rome IV, physician’s diagnosis, Bowel Function Index, patient’s assessment) showed higher incidences of opioid-induced constipation than recording the number of spontaneous bowel movements alone. Opioid-induced constipation occurred rapidly after initiating opioids and had a significant impact on Patient Assessment of Constipation Symptoms total score (P = 0.0031). Patient baseline characteristics did not appear to be predictive of opioid-induced constipation onset. Conclusions In patients with lung cancer, opioid-induced constipation can occur quickly after initiating opioids and can negatively impact quality of life. Early management of opioid-induced constipation, with a focus on quality-of-life improvement and patient’s assessments of bowel movements, is important for these patients., In lung cancer patients, opioid-induced constipation can occur quickly after initiating opioids and can negatively impact quality of life. Treatment with a focus on quality of life and patient’s assessments of bowel movements is important.

Background Constipation is a common side effect of opioid therapy. An observational study of opioid-induced constipation (OIC) in Japanese patients with cancer (OIC-J) included 212 patients with various tumor types. This post hoc analysis of OIC-J evaluated a subgroup of patients with gastrointestinal (GI) cancer. Methods Patients were aged ≥ 20 years, starting strong opioid therapy, had an ECOG PS of ≤ 2, and must have had ≥ 3 bowel movements during the week before enrollment. OIC was evaluated for 2 weeks after opioid initiation using the Rome IV diagnostic criteria for colorectal disorders, as well as physician’s diagnosis, number of spontaneous bowel movements, Bowel Function Index score, and patient’s self-assessment. Relationships between baseline characteristics and OIC incidence, and the effects of OIC on quality of life (QOL) were also explored. Results Fifty patients from OIC-J who had GI cancer [colon (50%), stomach (28%), and esophageal (22%)] were included. OIC incidence varied by which diagnostic criteria were used (46.0–62.0%) and occurred rapidly after initiating opioid therapy. The use of prophylactic laxatives reduced the overall incidence rate of OIC from 71.0% to 47.4%. No baseline characteristics, except comorbidities, were associated with OIC incidence. Change from baseline to day 15 in PAC-SYM total score was significantly greater for patients with OIC versus those without OIC (0.188 versus −0.362; P = 0.0011). Conclusions This post hoc analysis suggests that OIC occurs rapidly in patients with GI cancer after initiating opioid therapy, and negatively impacts QOL. Early and effective intervention strategies may be particularly useful in this group. Additional Information Coauthor Makio Gamoh is deceased.

IntroductionAntigen testing is essential in the clinical management of COVID-19. However, most evaluations of antigen tests have been performed before the emergence of the Omicron variant. Thus, an assessment of the diagnostic performance of antigen tests for the detection of SARS-CoV-2 during the circulation of Omicron variant is required.MethodsThis prospective observational study evaluated QuickNavi-COVID19 Ag, a rapid antigen detection test between December 2021 and February 2022 in Japan, using real-time reverse transcription (RT)-PCR as a reference. Two nasopharyngeal samples were simultaneously collected for antigen testing and for RT-PCR. Variant analysis of the SARS-CoV-2 genomic sequencing was also performed.ResultsIn total, nasopharyngeal samples were collected from 1,073 participants (417 positive; 919 symptomatic; 154 asymptomatic) for analysis. Compared with those of RT-PCR, the sensitivity, specificity, positive predictive value, and negative predictive value were 94.2% (95% CI: 91.6%–96.3%), 99.5% (95% CI: 98.7%–99.9%), 99.2% (95% CI: 97.8%–99.8%), and 96.5% (95% CI: 94.8%–97.7%), respectively. The sensitivity among symptomatic individuals was 94.3% (95% CI: 91.5%–96.4%). Overall, 85.9% of sequences were classified as Omicron sublineage BA.1, 12.4% were Omicron sublineage BA.2, and 1.6% were Delta B.1.617.2. (Delta variant). Most of the samples (87.1%) had Ct values ConclusionsThe QuickNavi-COVID19 Ag test showed high diagnostic performance for the detection of the SARS-CoV-2 Omicron sublineages BA.1 and BA.2 from nasopharyngeal samples.

Point-of-care type molecular diagnostic tests have been used for detecting SARS-CoV-2, although their clinical utility with nasal samples has yet to be established. This study evaluated the clinical performance of the cobas Liat SARS-CoV-2Influenza A/B (Liat) assay in nasal samples.Nasal and nasopharyngeal samples were collected and were tested using the Liat, the cobas 6800 system and the cobas SARS-CoV-2Influenza A/B (cobas), and a method developed by National Institute of Infectious Diseases, Japan (NIID).A total of 814 nasal samples were collected. The Liat assay was positive for SARS-CoV-2 in 113 (13.9%). The total, positive, and negative concordance rate between the Liat and cobas/NIID assays were 99.3%/98.4%, 99.1%/100%, and 99.3%/98.2%, respectively. Five samples were positive only using the Liat assay. Their Ct values ranged from 31.9 to 37.2. The Ct values of the Liat assay were significantly lower (p0.001) but were correlated (p0.001) with those of other molecular assays. In the participants who tested positive for SARS-CoV-2 on the Liat assay using nasopharyngeal samples, 88.2% of their nasal samples also tested positive using the Liat assay.The Liat assay showed high concordance with other molecular assays in nasal samples. Some discordance occurred in samples with Ct values30 on the Liat assay.

Background and ObjectivePoint-of-care type molecular diagnostic tests have been used for detecting SARS-CoV-2, although their clinical utility with nasal samples has yet to be established. This study evaluated the clinical performance of the cobas Liat SARS-CoV-2 & Influenza AB (Liat) in nasal samples.MethodsNasal and nasopharyngeal samples were collected and were tested using the Liat, the cobas 6800 system and the cobas SARS-CoV-2 & Influenza AB (cobas), and a method developed by National Institute of Infectious Diseases, Japan (NIID).ResultsA total of 814 nasal samples were collected. The Liat assay was positive for SARS-CoV-2 in 113 (13.9%). The total, positive, and negative concordance rate between the Liat and cobas/NIID assays were 99.3%/98.4%, 99.1%/100%, and 99.3%/98.2%, respectively. Five samples were positive only using the Liat assay. Their Ct values ranged from 31.9 to 37.2. The Ct values of the Liat assay were significantly lower (p < 0.001) but were correlated (p < 0.001) with those of other molecular assays. In the participants who tested positive for SARS-CoV-2 on the Liat assay using nasopharyngeal samples, 88.2% of their nasal samples also tested positive using the Liat assay.ConclusionThe Liat assay showed high concordance with other molecular assays in nasal samples. Some discordance occurred in samples with Ct values > 30 on the Liat assay.Key PointsThe cobas Liat SARS-CoV-2 & Influenza AB assay showed high concordance with other molecular assays in nasal and nasopharyngeal samples, providing results within 20 minutes.Some discordance occurred in samples with Ct values > 30 on the Liat assay.The Liat assay may be suitable for use in a variety of clinical situations, primarily where accurate detection of SARS-CoV-2 is necessary.

IntroductionSince respiratory sample collection is an uncomfortable experience, simultaneous detection of pathogens with a single swab is preferable. We prospectively evaluated the clinical performance of a newly developed antigen test QuickNavi-Flu+COVID19 Ag (Denka Co., Ltd., Tokyo, Japan) which can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses at the same time with a single testing device.MethodsIncluded were those who were suspected of contracting coronavirus disease 2019 (COVID-19) and referred to a PCR center at Ibaraki prefecture in Japan, between August 2, 2021 to September 13, 2021, when the L452R mutant strains of SARS-CoV-2 were prevalent. Additional nasopharyngeal samples and anterior nasal samples were obtained for the antigen test and were compared with a reference reverse transcription PCR (RT-PCR) using nasopharyngeal samples.ResultsIn total, 1510 nasopharyngeal samples and 862 anterior nasal samples were evaluated. For SARS-CoV-2 detection in nasopharyngeal samples, the sensitivity and specificity of the antigen test were 80.9% and 99.8%, respectively. The sensitivity and specificity using anterior nasal samples were 67.8% and 100%, respectively. In symptomatic cases, the sensitivities increased to 88.3% with nasopharyngeal samples and 73.7% with anterior nasal samples. There were three cases of discrepant results between the antigen test and the real-time RT-PCR. All of them were positive with the antigen test but negative with the real-time RT-PCR in SARS-CoV-2 detection. During the study period, influenza viruses were not detected.ConclusionA combo kit, QuickNavi-Flu+COVID19 Ag, showed an acceptable sensitivity and sufficient specificity for SARS-CoV-2 detection, especially using nasopharyngeal sample collected from symptomatic patients.

Immune checkpoint inhibitors (ICIs) have markedly changed the treatment landscape for melanoma; however, their efficacy and applications are currently limited and medical requirements remain unmet. The present case study reports on a 85-year-old female patient who visited our outpatient clinic with a 1-month history of a buccal mucosa mass and was diagnosed with locally advanced mucosal melanoma of the head and neck. The patient's tumor progressed right after the administration of nivolumab, compromising oral intake. Palliative debulking surgery was performed. Subsequently, the other part of the melanoma on the hard palate slightly decreased in size without forming new lesions for more than one year after surgery. The present case exemplifies that tumor volume reduction surgery may increase the response to ICI and may prolong the duration of response. This combination therapy may be more effective in patients whose tumors increase in size after administration of ICIs or whose tumor is already large at the beginning of treatment. The combination of ICIs and debulking surgery may become an important treatment option in the future for locally advanced mucosal melanoma.

The diagnostic accuracy of antigen testing of anterior nasal (AN) samples for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has not been evaluated in the Japanese population. This study assessed the diagnostic accuracy of the Roche SARS-CoV-2 rapid antigen test (rapid antigen test) using AN samples.Two AN samples and one nasopharyngeal (NP) sample were collected from individuals undergoing screening for SARS-CoV-2 infection. The results of the rapid antigen test and the reverse-transcription polymerase chain reaction (RT-PCR) test using AN samples were compared to those of RT-PCR tests using NP samples.Samples were collected from 800 participants, 95 and 110 of whom tested positive for SARS-CoV-2 on RT-PCR tests of AN and NP samples, respectively. The overall sensitivity/specificity of the AN rapid antigen test and AN RT-PCR were 72.7%/100% and 86.4%/100%, respectively. In symptomatic cases, the sensitivities of the AN rapid antigen test and AN RT-PCR were 84.7% and 94.9%, respectively. In asymptomatic cases, the sensitivities of the AN rapid antigen test and AN RT-PCR were 58.8% and 76.5%, respectively. The sensitivity of the AN rapid antigen test was over 80% in cases with cycle threshold (Ct) values 25; it significantly decreased with an increase in the Ct values (p 0.001).The rapid antigen test with AN samples had a favorable sensitivity, especially in symptomatic cases or in cases with Ct values 25. It gave no false-positive results. Compared with AN-RT PCR, the AN rapid antigen test had a modestly lower sensitivity in asymptomatic cases.

Introduction Digital immunoassays are generally regarded as superior tests for the detection of infectious disease pathogens, but there have been insufficient data concerning SARS-CoV-2 immunoassays. Methods We prospectively evaluated a novel digital immunoassay (RapidTesta SARS-CoV-2). Two nasopharyngeal samples were simultaneously collected for antigen tests and Real-time RT-PCR. Results During the study period, 1127 nasopharyngeal samples (symptomatic patients: 802, asymptomatic patients: 325) were evaluated. For digital immunoassay antigen tests, the sensitivity was 78.3% (95% CI: 67.3%–87.1%) and the specificity was 97.6% (95% CI: 96.5%–98.5%). When technicians visually analyzed the antigen test results, the sensitivity was 71.6% (95% CI: 59.9%–81.5%) and the specificity was 99.2% (95% CI: 98.5%–99.7%). Among symptomatic patients, the sensitivity was 89.4% (95% CI; 76.9%–96.5%) with digital immunoassay antigen tests, and 85.1% (95% CI; 71.7%–93.8%) with visually analyzed the antigen test, respectively. Conclusions The sensitivity of digital immunoassay antigen tests was superior to that of visually analyzed antigen tests, but the rate of false-positive results increased with the introduction of a digital immunoassay device.

Tumour burden (TB) is implicated in resistance to programmed cell death-1/PD-L1 inhibitor (immune checkpoint inhibitor [ICI]) therapy. However, whether TB contributes to such resistance in non-small-cell lung cancer (NSCLC) has remained unknown.A total of 260 treatment-naïve patients with advanced NSCLC who started ICI monotherapy (ICI cohort), platinum-doublet therapy (Chemo cohort) or ICI and platinum-doublet therapy (ICI+Chemo cohort) as first-line treatment were consecutively included. TB was estimated on the basis of the sum of the diameters of measurable target lesions as per Response Evaluation Criteria in Solid Tumours. Progression-free survival (PFS) in the ICI cohort was evaluated as per TB as a preplanned primary objective, with the analysis based on propensity score-weighted survival curves and estimation of restricted mean survival time (RMST). The Chemo cohort served as a control to determine whether TB is predictive of ICI treatment outcomes. The ICI+Chemo cohort was exploratory. The relation of TB to tumour immune status was assessed by immune-related gene expression profiling (irGEP) of pretreatment tumour tissue.In the ICI cohort, patients with a low TB showed a significantly longer PFS than did those with a high TB (median, 17.9 vs 4.3 months; weighted hazard ratio, 0.32 [95% confidence interval, 0.19-0.53]). No such difference was apparent in the other cohorts. A significant difference in overall survival was also observed only in the ICI cohort. RMST-based analysis confirmed these results. The irGEP analysis implicated M2-type macrophages, angiogenesis and transforming growth factor-β as well as protumourigenic signalling pathways in ICI resistance conferred by a high TB.A high TB was associated with a poor outcome of ICI therapy for advanced NSCLC as a result of immunosuppressive phenotypes. Development of combination or novel treatment strategies for such disease is thus warranted.

IntroductionDigital immunoassays are generally regarded as superior tests for the detection of infectious disease pathogens, but there have been insufficient data concerning SARS-CoV-2 immunoassays.MethodsWe prospectively evaluated a novel digital immunoassay (RapidTesta SARS-CoV-2). Two nasopharyngeal samples were simultaneously collected for antigen tests and RT-PCR. Real-time RT-PCR for SARS-CoV-2, using a method developed by the National Institute of Infectious Diseases, Japan, served as the reference RT-PCR method.ResultsDuring the study period, 1,127 nasopharyngeal samples (symptomatic patients: 802, asymptomatic patients: 325) were evaluated. For digital immunoassay antigen tests, the sensitivity was 78.3% (95% CI: 67.3%–87.1%) and the specificity was 97.6% (95% CI: 96.5%–98.5%). When technicians visually analyzed the antigen test results, the sensitivity was 71.6% (95% CI: 59.9%–81.5%) and the specificity was 99.2% (95% CI: 98.5%–99.7%). Among symptomatic patients, the sensitivity was 89.4% (95% CI; 76.9%–96.5%) with digital immunoassay antigen tests, and 85.1% (95% CI; 71.7%–93.8%) with visually analyzed the antigen test, respectively.ConclusionsThe findings indicated that RapidTesta SARS-CoV-2 analysis with the DIA device had sufficient analytical performance for the detection of SARS-CoV-2 in nasopharyngeal samples. When positive DIA results are recorded without a visually recognizable red line at the positive line location on the test cassette, additional RT-PCR evaluation should be performed.

Opioid-induced constipation (OIC) can limit the clinical benefit of opioid treatment. This post-hoc analysis evaluated the association between the Rome IV diagnostic criteria and other measures for OIC, including the Bowel Function Index (BFI), correlation between demographics and OIC onset, impact of OIC on pain treatment, and impact of patient–healthcare professional (HCP) communication on patient satisfaction. Patients recorded bowel habits in paper diaries for 14 days following opioid initiation. Study-specific questionnaires were used to evaluate patient awareness of OIC and satisfaction. Patients were ≥20 years old, initiating strong opioid therapy for cancer pain, had an ECOG PS ≤ 2, and had no constipation (≥3 bowel movements within 7 days of enrollment). A total of 220 patients were enrolled. The sensitivity and specificity of BFI for identifying OIC were 81.2% and 54.7%, respectively. Age &lt, 65 versus ≥65 years (odds ratio (OR) = 0.510, 95% confidence interval (CI): 0.267–0.977) and the presence or absence of comorbidities (OR = 0.443, 95% CI: 0.221–0.885) were correlated with OIC onset. The proportion of inpatients with sustainable pain control at week 2 was similar in patients with or without OIC (60.0% vs. 67.2%, respectively). By patient assessment, there was a significant correlation between an adequate level of patient–HCP communication and satisfaction with OIC treatment (OR = 9.538 (95% CI: 1.577–57.681)). Using BFI to screen for OIC represents a valid approach in patients with cancer pain. Patient–HCP communication is essential for effective management of OIC in patients with cancer pain.

IntroductionAntigen testing may help screen for and detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in asymptomatic individuals. However, limited data regarding the diagnostic performance of antigen tests for this group are available.MethodsWe used clinical samples to prospectively evaluate the analytical and clinical performance of the antigen test QuickNavi™-COVID19 Ag. This study was conducted at a PCR center between October 7, 2020 and January 9, 2021. Two nasopharyngeal samples per patient were obtained with flocked swabs; one was used for the antigen test, and the other for real-time reverse transcription PCR (RT-PCR). The diagnostic performance of the antigen test was compared between asymptomatic and symptomatic patients, and the RT-PCR results were used as a reference.ResultsAmong the 1,934 collected samples, SARS-CoV-2 was detected by real-time RT-PCR in 188 (9.7%); 76 (40.4%) of these samples were from asymptomatic individuals. Over half of the total samples (1,073; 55.5%) were obtained from asymptomatic volunteers. The sensitivity of the antigen test was significantly lower for asymptomatic group than for symptomatic patients (67.1% vs 89.3%, p < 0.001). The specificity was 100% for both groups, and no false positives were observed among all 1,934 samples. The median Ct value for the asymptomatic group was significantly higher than that of the symptomatic group (24 vs 20, p < 0.001).ConclusionsThe QuickNavi™-COVID19 Ag showed a lower sensitivity for asymptomatic group than for symptomatic patients. However, its specificity was consistently high, and no false positives were found in this study.

We conducted a prospective study in Japan to evaluate the diagnostic performance of the antigen test QuickNavi-COVID19 Ag using anterior nasal samples and to compare the degrees of coughs or sneezes induction and the severity of pain between anterior nasal collection and nasopharyngeal collection. A total of 862 participants were included in the analysis. In comparison to the findings of reverse transcription PCR using nasopharyngeal samples, the antigen test using anterior nasal samples showed 72.5% sensitivity (95% confidence interval [CI]: 58.3%-84.1%) and 100% specificity (95% CI: 99.3%-100%). Anterior nasal collection was associated with a significantly lower degree of coughs or sneezes induction and the severity of pain in comparison to nasopharyngeal collection (p < 0.001). The antigen test using anterior nasal samples showed moderate sensitivity but was less painful and induced fewer coughs or sneezes.

IntroductionSeveral antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed worldwide, but their clinical utility has not been well established. In this study, we evaluated the analytical and clinical performance of QuickNavi™-COVID19 Ag, a newly developed antigen test in Japan.MethodsThis prospective observational study was conducted at a PCR center between October 7 and December 5, 2020. The included patients were referred from a local public health center and 89 primary care facilities. We simultaneously obtained two nasopharyngeal samples with flocked swabs; one was used for the antigen test and the other for real-time reverse transcription PCR (RT-PCR). Using the results of real-time RT-PCR as a reference, the performance of the antigen test was evaluated.ResultsA total of 1186 patients were included in this study, and the real-time RT-PCR detected SARS-CoV-2 in 105 (8.9%). Of these 105 patients, 33 (31.4%) were asymptomatic. The antigen test provided a 98.8% (95% confident interval [CI]: 98.0%-99.4%) concordance rate with real-time RT-PCR, along with a sensitivity of 86.7% (95% CI: 78.6%-92.5%) and a specificity of 100% (95% CI: 99.7%-100%). False-negatives were observed in 14 patients, 8 of whom were asymptomatic and had a low viral load (cycle threshold (Ct) >30). In symptomatic patients, the sensitivity was 91.7% (95% CI: 82.7%-96.9%).ConclusionQuickNavi™-COVID19 Ag showed high specificity and sufficient sensitivity for the detection of SARS-CoV-2. This test is a promising potential diagnostic modality especially in symptomatic patients.

BackgroundMolecular tests are the mainstay for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, their accessibility can be limited by the long examination time and inability to evaluate multiple samples at once. This study evaluated the analytical performance of the newly developed rapid molecular assays GENECUBE® HQ SARS-CoV-2 and the GENECUBE® FLU A/B.MethodThis prospective study was conducted between December 14, 2020, and January 9, 2021, at a polymerase chain reaction (PCR) center. Samples were collected from the nasopharynx with flocked swabs. Molecular tests were performed with the GENECUBE® system and reference reverse transcription (RT)-PCR, and the results of the two assays were compared.ResultAmong 1065 samples, 81 (7.6%) were positive for SARS-CoV-2 on the reference RT-PCR. Three showed discordance between GENECUBE® HQ SARS-CoV-2 and the reference RT-PCR; the total, positive and negative samples of concordance for the two assays were 99.7%, 100%, and 99.7%, respectively. All discordant cases were positive for GENECUBE® HQ SARS-CoV-2 and negative for the reference RT-PCR. SARS-CoV-2 was detected from all three samples by another molecular assay for SARS-CoV-2. For the GENECUBE® FLU A/B, the total, positive and negative samples of concordance for the two assays were 99.5%, 100%, and 99.1%.ConclusionThe GENECUBE® HQ SARS-CoV-2 and GENECUBE® FLU A/B demonstrated sufficient analytical performance to detect SARS-CoV-2 and influenza virus A/B.Key pointsWe prospectively evaluated the analytical performance of the newly developed rapid molecular assays GENECUBE® HQ SARS-CoV-2 and the GENECUBE® FLU A/B. The two assays showed >99% concordance rate compared with a reference PCR, which indicated their sufficient analytical performance to detect SARS-CoV-2 and influenza virus A/B.

Community-acquired pneumonia (CAP) is a common illness that can lead to mortality. β-lactams are ineffective against atypical pathogen including Mycoplasma pneumoniae. We used molecular examinations to develop a decision tree to predict atypical pathogens with CAP and to examine the prevalence of macrolide resistance in Mycoplasma pneumoniae. We conducted a prospective observational study of patients aged ≥ 18 years who had fever and respiratory symptoms and were diagnosed with CAP in one of two community hospitals between December 2016 and October 2018. We assessed combinations of clinical variables that best predicted atypical pathogens with CAP by classification and regression tree (CART) analysis. Pneumonia was defined as respiratory symptoms and new infiltration recognized on chest X-ray or chest computed tomography. We analyzed 47 patients (21 females, 44.7%, mean age: 47.6 years). Atypical pathogens were detected in 15 patients (31.9%; 12 Mycoplasma pneumoniae, 3 Chlamydophila pneumoniae). Ten patients carried macrolide resistant Mycoplasma pneumoniae (macrolide resistant rate 83.3%). CART analysis suggested that factors associated with presence of atypical pathogens were absence of crackles, age

Background Patients with adenocarcinoma of the lung are routinely screened for anaplastic lymphoma kinase (ALK) rearrangement because they can be treated by ALK-specific targeted therapy. The clinical and molecular characteristics of large-cell neuroendocrine carcinoma (LCNEC) associated with ALK rearrangement are still unclear. Herein, we assessed the ALK status in a series of patients with LCNEC by testing methods commonly used for adenocarcinoma. Materials and methods ALK expression was first examined by immunohistochemistry. For a positively stained tumor, molecular analyses were then conducted. The ALK fusion partner found in a patient with ALK rearrangement was further identified by direct DNA sequencing. Patient clinicopathological features were also analyzed, focusing on the ALK rearrangement-positive case. Results Immunohistochemistry of seven patients identified strong ALK expression in one case of stage IV LCNEC. Molecular analysis identified a novel rearranged gene resulting from the fusion of kinesin family member 5B (KIF5B) exon 17 to ALK exon 20. The patient was treated with ALK-specific inhibitors, crizotinib and later, alectinib, and has remained alive for more than 24 months without disease progression. Three of the remaining six patients without ALK rearrangement had stage IV cancer and received cytotoxic chemotherapies. Their average overall survival was 5.4 months. Conclusion To our knowledge, this is the first report of a KIF5B-ALK fusion gene in LCNEC. The patient was successfully treated with ALK inhibitors, suggesting that sensitivity to ALK inhibitor may define a specific LCNEC subtype. We propose that screening for ALK rearrangement in patients with LCNEC may assist in selecting potential candidates for targeted therapy.

Background Mycoplasma pneumoniae is a common pathogen causing pneumonia; macrolide‐resistant strains are rapidly spreading across Japan. However, the clinical features of macrolide‐resistant M. pneumoniae pneumonia have not been well established. Here, we evaluated the clinical characteristics and seasonal variations in the prevalence of M. pneumoniae with macrolide‐resistant mutations (MRM). Methods The monthly prevalence of MRM in M. pneumoniae strains isolated from May 2016 to April 2017 was retrospectively analyzed, and the clinical characteristics of pneumonia cases with MRM were compared to those of cases without MRM. The M. pneumoniae isolates and point mutations at site 2063 or 2064 in domain V of 23S rRNA were evaluated by the GENECUBE system and GENECUBE Mycoplasma detection kit. Results Mycoplasma pneumoniae infection was identified in 383 cases, including 221 cases of MRM (57.7%). The MRM prevalence was 86.3% (44/51) between May and July 2016, demonstrating an apparent decrease in September 2016, subsequently reaching 43.0% (34/79) in November 2016. Mycoplasma pneumoniae pneumonia was diagnosed in 275 cases, including 222 pediatric and 53 adult cases. Macrolide use preceding evaluation was found to be the only feature of MRM pneumonia cases both in children (odds ratio [OR] 3.86, 95% confidence interval [CI]:1.72–8.66) and in adults (OR 7.43, 95% CI: 1.67–33.1). Conclusions The determination rate of MRM varied widely throughout the year, and our study demonstrated the challenges in predicting M. pneumoniae with MRM based on clinical features at diagnosis. Therefore, continuous monitoring of the prevalence of MRM is warranted, which may help in selecting an effective treatment.

Background Patients with acute respiratory tract infections are frequently prescribed antimicrobials despite high rates of virus detection. Physicians may overprescribe antimicrobials owing to the concern of bacterial infections, including those because of atypical pathogens. We investigated the accuracy of clinical predictions concerning atypical pathogen infections. Methods We prospectively enrolled adult patients who presented with a fever and cough in outpatient clinics between December 2016 and August 2018. After taking a history and performing physical examinations, physicians predicted the possibility of respiratory infections because of atypical pathogens. Disease probabilities were categorized into 3 grades (high: ≥50%, intermediate: 20% ≥ and, Our study indicates that while physicians' predictions were associated with the detection of atypical pathogens, overestimation was observed. The criteria for atypical pneumonia did not perform well for accurately diagnosing atypical pathogen infection in patients with a fever and cough.

We retrospectively analyzed adverse effects(AEs), overall survival(OS), and progression-free survival(PFS)in 15 consecutive patients treated with FOLFIRINOX as the first-line treatment for recurrent or unresectable pancreatic ductal adenocarcinoma( PDAC)between February 2014 and December 2017 in our hospital. Eleven patients were treated for unresectable PDAC with distant metastases(UR-M), and 4 were treated for locally advanced unresectable PDAC(UR-LA). The median age was 56(range: 40-75)years. Nine patients were male, and 6 were female. The performance status was 0 or 1 in all patients. Tumors were located in the pancreas head in 8 cases and in the body-tail in 7 cases. Grade 5 AEs were observed in 1 case in which liver abscess causing sepsis resulted in mortality. The response rate was 20.0%, and the disease control rate was 66.7%. Two patients underwent conversion surgery after FOLFIRINOX treatment. Seven patients received a nab-paclitaxel plus gemcitabine regimen as second-line treatment. The median OS and PFS were 17.0 and 8.4 months, respectively, and the 1-year survival rate was 66.7%. FOLFIRINOX for recurrent and unresectable PDAC showed relatively good tumor control. However, strict attention is required for severe AEs. Conversion surgery might be effective in patients who are good responders even if they have metastatic disease.

This multicenter, prospective, observational cohort study assessed opioid induced constipation (OIC) in Japanese patients with cancer. Eligible patients had stable cancer and an ECOG PS of 0‐2. OIC incidence based on the Rome IV diagnostic criteria was determined by patient diary entries during the first 14 days of opioid therapy. The proportion of patients with OIC was calculated for each 1‐week period and the overall 2‐week study period. Secondary measurements of OIC included the Bowel Function Index (BFI) score (patient assessment administered by physician), spontaneous bowel movements (SBMs) per week (patient assessment), and physician assessments. Medication for constipation was allowed. Two hundred and twenty patients were enrolled. The mean morphine‐equivalent dose was 22 mg/day. By Rome IV criteria, the cumulative incidence of OIC was 56% (95% CI: 49.2%‐62.9%); week 1, 48% (95% CI: 40.8%‐54.6%); week 2, 37% (95% CI: 30.1%‐43.9%). The cumulative incidence of OIC was lower in patients who received prophylactic agents for constipation (48% [95% CI: 38.1%‐57.5%]) than in patients who did not (65% [95% CI: 55.0%‐74.2%]). The cumulative incidences of OIC were 59% (95% CI: 51.9%‐66.0%), 61% (95% CI: 54.3%‐68.1%), and 45% (95% CI: 38.0%‐51.8%) based on BFI scores, physician assessments, and SBM frequency, respectively. Frequency of BMs/week before starting opioids was the most influential factor for the occurrence of OIC. Utilization of prophylactic agents for constipation was associated with a modest effect on reducing the incidence of OIC. The incidences of OIC reported were variable depending on the diagnostic tool involved.

Context Many patients who have cancer consider opioid-induced constipation (OIC) to be a burdensome side effect of opioid treatment. Objectives To evaluate patient-reported outcomes in Japanese patients with cancer pain and OIC. Methods This prospective observational study evaluated OIC incidence for two weeks in patients with cancer after they initiated strong opioid therapy. Rome IV diagnostic criteria, a physician's diagnosis, spontaneous bowel movements, Bowel Function Index score, and patients' daily self-assessments were used. Changes from baseline in Patient Assessment of Constipation Symptoms and Patient Assessment of Constipation Quality of Life (PAC-QOL) scores were compared between patients with and without OIC. Patients and health care providers (HCPs) completed study-specific questionnaires regarding OIC burden, treatment satisfaction, and patient-provider communications. Results Among 212 enrolled patients, the incidence of OIC was 47.6% by patients' self-assessments, with a cumulative incidence of 30.2% by Day 3 and 43.5% by Day 7. Patient Assessment of Constipation Symptoms and PAC-QOL overall scores from patients with OIC worsened significantly from baseline compared with patients without OIC by all diagnostic criteria, except for spontaneous bowel movement frequency for PAC-QOL. Patients and HCPs were generally satisfied with OIC treatment; however, 53.5% of patients and approximately 40.0% of HCPs reported that OIC affected pain management. Most patients and HCPs reported that OIC conditions were sufficiently or essentially communicated. Conclusion After starting opioid therapy, patients recognized OIC onset and its impact on cancer pain management, highlighting the need for effective patient-provider communications, diagnosis, and treatment of OIC to improve QOL for patients with cancer receiving opioid analgesics.

Mycoplasma pneumoniae is a leading causative pathogen of pneumonia among pediatric patients, and its accurate diagnosis may aid in the selection of appropriate antimicrobial agents. We established a rapid reporting system of a polymerase chain reaction (PCR) examination for M. pneumoniae that enables physicians to obtain test results approximately 90 minutes after ordering the test. In this study, we evaluated the impact of this system on antimicrobial prescriptions for pediatric pneumonia patients after its implementation from May 2016 to April 2017. In total, we identified 375 pediatric pneumonia patients, and the results of the rapid PCR examinations for Mycoplasma pneumoniae were reported immediately in 90.7% of patients (340/375), with physicians able to use these results to decide on patients' management before the prescription of antimicrobial agents. Of the 375 pediatric pneumoniae patients, M. pneumoniae was detected in 223 (59.5%). Among the 223 M. pneumoniae-positive pneumonia cases, antimicrobial agents for atypical pathogens (macrolides, tetracyclines or quinolones) were prescribed in 97.3% (217/223) at the initial evaluation, and their prescription rates increased to 99.1% (221/223) during management. In contrast, antimicrobial agents for atypical pathogens were prescribed only in 10.5% of 152 M. pneumoniae-negative pneumonia cases at the initial evaluations, and only 1 additional case was prescribed clarithromycin for persistent symptoms during management. In conclusion, we show that molecular technology could be applicable in the field of point-of-care testing in infectious disease, and its implementation will ensure the correct antimicrobial prescription for pediatric pneumonia patients.

Recently, rapid molecular detection systems have been used for point-of-care testing for the diagnosis of influenza worldwide. Here, we evaluated the performance of the cobas Liat system and the cobas Influenza A/B assay (Liat) using fresh nasopharyngeal samples collected from a Japanese population between December 2017 and February 2018. The performance of the examination was compared with that of antigen testing and a conventional polymerase chain reaction (nested-PCR) method. A total of 159 patients were included in this study, and 77 tested positive using Liat. The concordance rate between Liat and nested PCR was 97.5%. The median time between the ordering of testing and completion of molecular analyses using Liat was 30 min (interquartile range: 28–35 min). The overall sensitivity and specificity of antigen testing were 57.1% and 100%, respectively. The duration from symptom onset to examination did not alter antigen testing sensitivity. The current study demonstrates the high performance of Liat for the rapid molecular identification of the influenza virus.

Rapid identification of causative agents from positive blood culture media is a prerequisite for the timely targeted treatment of patients with sepsis. The GENECUBE (TOYOBO Co., Ltd.) is a novel, fully-automated gene analyzer that can purify DNAs and amplify target DNAs. In this study, we evaluated the ability of two newly developed GENECUBE assays to directly detect the nuc and mecA genes in blood culture medium; nuc is specific to Staphylococcus aureus, and mecA indicates methicillin resistance. We examined 263 positive blood culture samples taken at three hospitals from patients suspected of having staphylococcal bacteremia. The results were then compared with those obtained using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, antimicrobial susceptibility testing (Microscan system or Dry-plate EIKEN), and sequencing analysis. The GENECUBE assays had sensitivity and specificity of 100% in detecting both S. aureus and methicillin resistance in positive blood culture. The turnaround time of the examination was evaluated for 36 positive blood culture samples. The time between the initiation of incubation and completion of the GENECUBE examination was 23 h (interquartile range: IQR 21–37 h); the time between reporting of Gram stain examination and completion of the GENECUBE examination was 52 min (IQR 48–62 min). These findings show that the GENECUBE assays significantly reduce the assay time with no loss of sensitivity or specificity.

Patients with adenocarcinoma of the lung are routinely screened for anaplastic lymphoma kinase (ALK) rearrangement because they can be treated by ALK-specific targeted therapy. The clinical and molecular characteristics of large-cell neuroendocrine carcinoma (LCNEC) associated with ALK rearrangement are still unclear. Herein, we assessed the ALK status in a series of patients with LCNEC by testing methods commonly used for adenocarcinoma.ALK expression was first examined by immunohistochemistry. For a positively stained tumor, molecular analyses were then conducted. The ALK fusion partner found in a patient with ALK rearrangement was further identified by direct DNA sequencing. Patient clinicopathological features were also analyzed, focusing on the ALK rearrangement-positive case.Immunohistochemistry of seven patients identified strong ALK expression in one case of stage IV LCNEC. Molecular analysis identified a novel rearranged gene resulting from the fusion of kinesin family member 5B (KIF5B) exon 17 to ALK exon 20. The patient was treated with ALK-specific inhibitors, crizotinib and later, alectinib, and has remained alive for more than 24 months without disease progression. Three of the remaining six patients without ALK rearrangement had stage IV cancer and received cytotoxic chemotherapies. Their average overall survival was 5.4 months.To our knowledge, this is the first report of a KIF5B-ALK fusion gene in LCNEC. The patient was successfully treated with ALK inhibitors, suggesting that sensitivity to ALK inhibitor may define a specific LCNEC subtype. We propose that screening for ALK rearrangement in patients with LCNEC may assist in selecting potential candidates for targeted therapy.

The association between advanced age and the thiamine concentration has not been conclusively determined. A recent report from Japan showed that more than half of nursing home elderly residents at an institution had a low whole-blood thiamine concentration (

Archival formalin-fixed, paraffin-embedded (FFPE) tumor specimens were collected from advanced NSCLC patients enrolled in LETS phase III trial comparing first-line S-1/carboplatin with paclitaxel/carboplatin and subjected to multiplex genotyping for 214 somatic hotspot mutations in 26 genes (LungCarta Panel) and 20 major variants of ALK, RET, and ROS1 fusion genes (LungFusion Panel) with the Sequenom MassARRAY platform. MET amplification was evaluated by fluorescence in situ hybridization. A somatic mutation in at least one gene was identified in 48% of non–squamous cell carcinoma and 45% of squamous cell carcinoma specimens, with EGFR (17%), TP53 (11%), STK11 (9.8%), MET (7.6%), and KRAS (6.2%). Mutations in EGFR or KRAS were associated with a longer or shorter median overall survival, respectively. The LungFusion Panel identified ALK fusions in six cases (2.5%), ROS1 fusions in five cases (2.1%), and a RET fusion in one case (0.4%), with these three types of rearrangement being mutually exclusive. Nine (3.9%) of 229 patients were found to be positive for de novo MET amplification. This first multiplex genotyping of NSCLC associated with a phase III trial shows that MassARRAY-based genetic testing for somatic mutations and fusion genes performs well with nucleic acid derived from FFPE specimens of NSCLC tissue.