A case of severe pneumonia with viremia caused by adenovirus B7 identified by off-label use of a multiplex PCR system

Severe infection with human adenovirus (HAdV) is uncommon in adults, and the lack of reliable point-of-care testing makes the diagnosis challenging. A 39-year-old immunocompetent Indian man developed severe pneumonia, and his condition became life-threatening despite antimicrobial therapy. While sputum and blood cultures remained negative, a multiplex PCR respiratory panel (Filmarray Respiratory Panel), which is only approved for use with nasopharyngeal samples, detected HAdV in the serum and tracheal aspirates on day 5. We therefore initiated ganciclovir, steroids, and intravenous immunoglobulin. The patient’s respiratory condition improved significantly, and he eventually recovered without complications. We later confirmed that conventional PCR of serum detected HAdV-B7. Our case illustrated that a respiratory panel using multiplex PCR successfully detected HAdV in unapproved samples. Such off-label analyses may support the early diagnosis of infections caused by pathogens that are difficult to identify by routine microbiological examination

Opioid-Induced Constipation in Patients with Cancer Pain in Japan (OIC-J Study): A Post Hoc Analysis

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 <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

Incidence of opioid‐induced constipation in Japanese patients with cancer pain: A prospective observational cohort study

Abstract 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

Evaluation of performance of the GENECUBE assay for rapid molecular identification of Staphylococcus aureus and methicillin resistance in positive blood culture medium.

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

Development of a mobile laboratory system in hydrogen fuel cell buses and evaluation of the performance for COVID-19 RT-PCR testing

Abstract We designed and developed two new types of hydrogen fuel cell (HFC) buses (motorcoach and minibus) with a mobile laboratory system. Feasibility studies have been performed for mobile laboratory testing, particularly for the laboratory performance of COVID-19 RT-PCR (PCR). We evaluated the driving range capability, PCR sample size capacity, turnaround time (TAT), and analytical performance for the detection of SARS-CoV-2. Saliva samples were used for the current study, and the analytical performance was compared with that of the reference PCR. The estimated driving range and sample size capacity of the HFC and HFC minibus were 432 km and 2847 samples, respectively, for the HFC motorcoach and 313 km and 1949 samples for the HFC minibus. For the TAT, the median time between sample submission and completion of PCR was 86 min for the motorcoach and 76 min for the minibus, and the median time between sample submission and electronic reporting of the result to each visitor was 182 min for the motorcoach and 194 min for the minibus. A secondary analysis of 1574 HFC mobile laboratory testing samples was conducted, and all negative samples were found to be negative by reference PCR. Furthermore, all samples were confirmed to be positive by reference PCR or other molecular examinations

Liquid biopsy detects genomic drivers in NSCLC without EGFR mutations by single‐plex testing: WJOG13620L

Abstract Background Actionable tumor genomic alterations, primarily EGFR mutations, occur in nearly 70% of Japanese advanced nonsquamous non‐small cell lung cancer (NSCLC) patients. Standard assessment of tumor tissue includes rapid testing for EGFR mutations, ALK fusions and ROS1 fusions. We conducted a prospective observational study (WJOG13620L) of follow‐on next‐generation sequencing of circulating tumor DNA (ctDNA) in patients without driver alterations after EGFR testing. Methods Patients with untreated advanced (Stage IIIB–IV or relapsed) nonsquamous NSCLC without EGFR mutations according to single‐plex testing of tumor tissue, were enrolled into this study. Patients with other known driver mutations or who underwent comprehensive genomic profiling were excluded. Plasma was analyzed by Guardant360, and the primary endpoint was the proportion of patients with pathogenic gene alterations in at least one of nine genes. Results Among the 72 patients enrolled, ALK and ROS1 fusions were tested in 86.1% and 65.2%, respectively. Alterations in pre‐defined genes were detected in 21 patients (29.2%; 95% confidence interval: 19.0–41.1, p < 0.001 [one‐sided null hypothesis proportion of 10%]), including RET fusion (n = 1) and mutations in KRAS (n = 11), EGFR (n = 5), ERBB2 (n = 3), and BRAF (n = 1). Median time from sample submission to results was 8 days (range, 5–17 days). Conclusion Rapid follow‐on comprehensive testing of ctDNA should be considered prior to first‐line treatment for patients with advanced nonsquamous NSCLC when no alterations are detected after single‐plex tissue testing