Infectious virus shedding duration reflects secretory IgA antibody response latency after SARS-CoV-2 infection.

Infectious virus shedding from individuals infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is used to estimate human-to-human transmission risk. Control of SARS-CoV-2 transmission requires identifying the immune correlates that protect infectious virus shedding. Mucosal immunity prevents infection by SARS-CoV-2, which replicates in the respiratory epithelium and spreads rapidly to other hosts. However, whether mucosal immunity prevents the shedding of the infectious virus in SARS-CoV-2-infected individuals is unknown. We examined the relationship between viral RNA shedding dynamics, duration of infectious virus shedding, and mucosal antibody responses during SARS-CoV-2 infection. Anti-spike secretory IgA antibodies (S-IgA) reduced viral RNA load and infectivity more than anti-spike IgG/IgA antibodies in infected nasopharyngeal samples. Compared with the IgG/IgA response, the anti-spike S-IgA post-infection responses affected the viral RNA shedding dynamics and predicted the duration of infectious virus shedding regardless of the immune history. These findings highlight the importance of anti-spike S-IgA responses in individuals infected with SARS-CoV-2 for preventing infectious virus shedding and SARS-CoV-2 transmission. Developing medical countermeasures to shorten S-IgA response time may help control human-to-human transmission of SARS-CoV-2 infection and prevent future respiratory virus pandemics.

Predictive factors for transition to conversion therapy in hepatocellular carcinoma using atezolizumab plus bevacizumab.

BACKGROUND: To identify predictive factors associated with successful transition to conversion therapy following combination therapy with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC). METHODS: In total, 188 patients with HCC, who received atezolizumab plus bevacizumab combination therapy as the first-line chemotherapy, were studied. Patients who achieved complete response (CR) with systemic chemotherapy alone were excluded. Clinical factors possibly linked to successful transition to conversion therapy and the achievement of cancer-free status were identified. RESULTS: Fifteen (8.0%) patients underwent conversion therapy. In the conversion group, there was a significantly higher proportion of patients with Barcelona Clinic Liver Cancer (BCLC) stage A or B (73.3% versus [vs.] 45.1%; p = .03) and tended to have lower Child-Pugh scores and alpha-fetoprotein levels. Multivariate analysis revealed that BCLC stage was a predictive factor for the implementation of conversion therapy (A or B; odds ratio 3.7 [95% CI: 1.1-13]; p = .04). Furthermore, 10 (66.7%) patients achieved cancer-free status and exhibited a smaller number of intrahepatic lesions at the start of treatment (3.5 vs. 7; p < .01), and a shorter interval between systemic chemotherapy induction and conversion therapy (131 vs. 404 days; p < .01). In addition, the rate of achieving cancer-free status by undergoing surgical resection or ablation therapy was significantly higher (p = .03). CONCLUSION: BCLC stage was the sole predictive factor for successful transition to conversion therapy when using combination therapy with atezolizumab and bevacizumab to treat HCC. Furthermore, a small number of intrahepatic lesions and early transition to conversion therapy were associated with the achievement of cancer-free status.

Different psychopathological courses between chronic interictal psychosis and schizophrenia.

OBJECTIVE: The clinical course of interictal psychosis (IIP) has not yet been investigated. We aimed to compared the psychopathology and time-relevant indices between chronic IIP (CIIP) and schizophrenia (SC) METHODS: In this comprehensive psychopathological study, patients with chronic psychosis with and without epilepsy (127 with CIIP and 187 with SC) were compared. Psychopathology was measured using the Brief Psychiatric Rating Scale (BPRS): total, negative symptoms (NSs), positive symptoms (PSs), and anxiety-depressive symptoms (ADSs). Time-relevant indices included age at the time of evaluation, age at the onset of psychosis, and duration of psychosis. The psychopathology of psychosis types and time-relevant indices were analyzed using Pearson's correlation coefficient analysis of covariance. RESULTS: 　Age at the time of evaluation was significantly correlated with NS, and ADS scores. Age-relevant trajectories significantly interacted with psychosis types. As age advanced, patients with SC exhibited increased scores, whereas patients with CIIP often exhibited decreased (or unchanged) scores. Age at onset of psychosis was significantly correlated with NS and ADS outcomes in patients with CIIP, whereas it was not correlated in patients with SC. There were significant interactions between age at onset and psychosis types. Patients with early-onset CIIP exhibited higher NS and lower ADS scores, whereas patients with SC exhibited no particular trajectory. The duration of psychosis significantly interacted with the psychosis types in the BPRS total, NSs and PSs. As duration increased, patients with CIIP exhibited no significant relationship, whereas patients with SC exhibited significantly higher psychotic scores. CONCLUSION: Psychopathological courses differ between patients with CIIP and SC. Although patients with SC often exhibit deteriorations in psychotic symptoms, patients with CIIP exhibit no distinct deterioration. These findings can contribute psychiatric nosology, treatment strategies, and prediction outcomes.

Phase I/IIa trial of 18F-prostate specific membrane antigen (PSMA) 1007 PET/CT in healthy volunteers and prostate cancer patients.

OBJECTIVE: 18F-PSMA 1007 is a promising PET tracer for prostate cancer. We aimed to examine the safety, biodistribution, radiation dosimetry, and clinical effectiveness in Japanese healthy volunteers and patients with prostate cancer. METHODS: Part A evaluated the pharmacokinetics and exposure doses in three healthy volunteers. Part B evaluated the diagnostic accuracy in patients with untreated preoperative prostate cancer (Cohort 1, n = 7) and patients with biochemical recurrence (Cohort 2, n = 3). All subjects received a single dose of 3.7 MBq/kg 18F-PSMA 1007. Results: 18F-PSMA 1007 was found to be safe and well tolerated in all subjects. No serous AEs or drug-related AEs were identified during the present study. The average blood radioactivity concentration reached a maximum of 47.87 ± 1.05 (percentage of injected dose [%ID]/ml) at 5 min and then decreased to 1.60 ± 0.78 in 6 h. The systemic radioactivity reached a maximum of 211.05 ± 6.77 (%ID$\times$103) at 5 min and decreased to 7.18 ± 3.91 in 6 h. The sensitivity and positive predictive value were 100% and 100% based on both pathologic and imaging confirmation as gold standard. In Cohort 1, 15 primary foci (11.9%) were >5 mm in the largest diameter and identified in 39 of 126 segments (30.1%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for 60 min uptake time acquisition were 80.0, 96.5, 91.4, 91.2 and 91.3%, respectively. CONCLUSIONS: Our study revealed that 18F-PSMA 1007 was safe, well tolerated and showed high accuracy in the diagnosis of prostate cancer.

Human mpox presenting with penile edema and ulcer: A case report.

Human mpox, which has spread worldwide since May 2022, is characterized by symptoms involving the genital area; however, its treatment methods and clinical course are not completely understood. Furthermore, penile swelling in human mpox can be difficult to differentiate from cellulitis and antibiotic use has been reported in such cases. Herein, we report a case of human mpox in Japan with prominent penile swelling and persistent penile ulcers that improved without specific treatment. The patient was a Japanese man in his 20s with a history of having sexual intercourse with men frequently. He visited Tokyo Metropolitan Toshima Hospital because of a fever and rash in the genital area. Physical examination revealed vesicles on the limbs, penile pigmentation, and significant penile swelling and redness. There were no signs of cellulitis and symptomatic treatment was initiated with outpatient follow-up. After 7 days, an improving trend in penile swelling, redness, and pain was observed. However, a partially black skin ulcer with exudate was observed at the left coronal sulcus of the penis. Therefore, the symptomatic treatment was continued. On illness day 28, the penile swelling completely improved; however, the penile ulcer and pain persisted, and the exudate was observed again. By illness day 63, the pain in his anogenital area had disappeared, and the penile skin ulcer had healed. The following observations were noted in this case: (i) human mpox can improve without specific treatment such as tecovirimat administration and (ii) skin lesions in the genital area may change over time.

Assessment of clinical relevance of antigen improves diagnostic accuracy of hypersensitivity pneumonitis.

BACKGROUND: Exposure assessment is integral to the diagnosis of hypersensitivity pneumonitis (HP). Although the clinical relevance of exposed antigens is essential for the assessment, many of the previous guidelines or reports have only evaluated simple exposure histories or immunological tests. To overcome this problem, the Exposure Assessment Form (EAF) was developed as an assessment tool for classifying the exposure grade from G0 to G4. The EAF was modified from the description in the Japanese clinical practice guide 2022 for HP published by the Japanese Respiratory Society. METHODS: One hundred and seventy-two consecutive patients with interstitial lung disease who underwent multidisciplinary discussion (MDD) at our hospital were retrospectively examined. We assessed whether the use of the EAF improved the diagnostic performance of the international guideline of HP. We also evaluated whether the exposure grade affected the prognosis of HP. RESULTS: Even when a HP diagnosis was made with a confidence of 70% or higher according to the international guideline, less than half of these cases resulted in a final diagnosis of HP when the exposure grades were lower than G3. When the result of the EAF was integrated into the exposure definition of the international guideline, the specificity of the diagnostic performance improved, while sensitivity was maintained. Furthermore, HP patients with an exposure grade of G3 or higher showed a tendency to take a longer time to initiate medication. CONCLUSIONS: This is the first study to evaluate the clinical relevance of possible antigens using the EAF. Assessing the exposure grade prevents overdiagnosis and improves the diagnostic performance of the international guideline.

Correlation between pretreatment and follow-up infarct volume using CT perfusion imaging: the Bayesian versus singular value decomposition method.

PURPOSE: Pretreatment ischemic core volume is conceptually equal to follow-up infarct volume (FIV) in patients with successful recanalization. However, there is sometimes an absolute volume difference (AD) between pretreatment core volume and FIV. The aim was to compare the AD values between the Bayesian and the singular value decomposition (SVD) methods with time from onset-to-imaging in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy. METHODS: Consecutive AIS patients were included if they had the following: (1) anterior large vessel occlusion (internal carotid or middle cerebral artery); (2) within 24 h of onset; (3) pretreatment CT perfusion (CTP); (4) successful recanalization (mTICI ≥ 2b); and (5) 24-h diffusion-weighted imaging (DWI). FIV was measured on 24-h DWI. The AD value between FIV and the pretreatment core volume was calculated for Bayesian and SVD methods. Spearman's rank correlation coefficient (rho) was calculated as appropriate. RESULTS: In the 47 patients enrolled (25 men; median age 78 years; median baseline National Institutes of Health Stroke Scale, 22), the median time from onset-to-imaging and onset-to-recanalization was 136 and 220 min, respectively. Shorter onset-to-imaging time was correlated with a larger AD value, and more trend was seen in the SVD method (rho = - 0.28, p = 0.05) compared with the Bayesian method (rho = - 0.08). A larger pretreatment core volume was correlated with a larger AD value, and this tendency was slightly stronger for the SVD (rho = 0.63, p < 0.01) than for the Bayesian (rho = 0.32, p = 0.03) method. CONCLUSIONS: The Bayesian method might be more correlated with FIV than the SVD method in patients with a large ischemic lesion immediately after stroke onset, but not perfect.

Disease Progression-Related Markers for Aged Non-Alcoholic Fatty Liver Disease Patients.

Liver fibrosis is an important phenomenon in non-alcoholic fatty liver disease (NAFLD) progression. Standard markers reflecting liver fibrosis, including the FIB-4 index, increase with age. This study aimed to identify fibrosis progression-related markers that are diagnostically beneficial even in aged individuals. Serum levels of pro- and anti-inflammatory cytokines were measured by multiple enzyme-linked immunosorbent assay. Two standard NAFLD or fibrosis progression-related markers - the FIB-4 index and APRI score - were analyzed along with cytokine levels to define the best approach to discriminate advanced fibrosis. Ninety-eight NAFLD patients were enrolled: 59 and 39 patients with fibrosis stages 1-2 and 3-4 respectively. In addition to the FIB-4 index and APRI score, the following factors showed significant differences between stages 1-2 and stages 3-4 in a multivariate analysis: platelet counts, IP-10, and RANTES. The fibrosis stage, FIB-4, APRI, PDGF-BB, and RANTES were related to the prognosis. In aged patients, IP-10, GM-CSF, and RANTES differed between stages 1-2 and stages 3-4. FIB-4 and APRI were beneficial for their correlation with fibrosis. However, to stratify either young or elderly advanced fibrosis patients, and to identify patients likely to have a bad outcome, RANTES was the best marker.

Effects of Denture Treatment on Salivary Metabolites: A Pilot Study.

Symptoms of oral discomfort such as dry mouth are common in older people wearing dentures. Such symptoms are mainly treated symptomatically. Many of these symptoms are related to saliva, and associations with salivary volume have been reported. Although denture treatment improves symptoms by increasing the amount of saliva, the effects on salivary components remain unclear. This study aimed to investigate the effects of denture treatment on salivary metabolite changes based on salivary metabolome analyses. We enrolled 21 patients requiring denture treatment. At the first visit, and after completion of denture treatment, saliva outflow was measured under resting and stimulated conditions, samples for salivary metabolite analysis were collected, and masticatory efficiency was tested. In all participants, masticatory efficiency increased after denture treatment. Moreover, the amounts of resting and stimulated saliva were increased. Using salivary metabolome analysis, 61 salivary metabolites were detected. Substantial concentration changes were observed for 4 and 21 metabolites in resting and stimulated saliva, respectively. The four metabolites common to both saliva tests had significantly lower concentrations after treatment. These results suggest that the improvement in masticatory function by dentures is related not only to salivary secretion volume, but also to salivary metabolite composition.

Imaging-detected bone stress injuries at the Tokyo 2020 summer Olympics: epidemiology, injury onset, and competition withdrawal rate.

BACKGROUND: Prevention and early detection of injuries are essential in optimising sport participation and performance. The aim of this study is to investigate the epidemiology, athlete injury history, and competition withdrawal rate of imaging-detected bone stress injuries during the Tokyo 2020 Olympic Games. METHODS: We collected and analysed imaging and clinical information in athletes with bone stress injuries diagnosed in the Olympic Village polyclinic during the Games. Two physicians independently and retrospectively reviewed all imaging examinations of bone stress injuries. RESULTS: A total of 11,315 individual athletes from 206 National Olympic Committees competed at the Games, during which 567 MRIs and 352 X-rays were performed at the Olympic Village polyclinic. Radiology examinations revealed four stress fractures and 38 stress reactions in 29 athletes (median age 24 years, range 18-35 years). Of these, 72% of athletes (n = 21) had symptoms before entering the Olympic Village. Bone stress injuries were most common in women (55%), the lower extremities (66%), and track and field athletes (45%). Six athletes (21%) did not start or did not finish their competitions. CONCLUSIONS: This study revealed 42 imaging-detected bone stress injuries in the polyclinic of the Tokyo 2020 Olympic Village. The high proportion of athletes with symptoms before entering the village and the high proportion of competition withdrawals suggests the usefulness of an early MRI examination.