Utility of interferon-gamma releasing assay for the diagnosis of active tuberculosis in children: A systematic review and meta-analysis.

INTRODUCTION: The accurate diagnosis of tuberculosis (TB) in children is essential for its effective management and control. Reliable diagnostic tools that are currently available for identifying TB infection include the in vivo tuberculosis skin test (TST) and ex vivo interferon-gamma release assays (IGRAs). This systematic review and meta-analysis aimed to evaluate the diagnostic accuracy of IGRAs in children. METHODS: Of the 768 screened studies, 47 met the eligibility criteria. Data from 9065 patients, including 1086 (12.0 %) with confirmed TB, were included in the analysis. The overall quality of the included studies, assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, was unclear. RESULTS: The calculated pooled sensitivity and specificity of IGRAs in children were 0.85 (95 % confidence interval [CI]: 0.79-0.89) and 0.94 (95 % CI: 0.88-0.97), respectively. Subpopulation analysis revealed that the sensitivities and specificities were as follows: QuantiFERON tests: 0.83 (95 % CI: 0.74-0.89) and 0.93 (95 % CI: 0.87-0.96), T-SPOT: 0.87 (95 % CI: 0.79-0.91) and 0.99 (95 % CI: 0.85-1.00), IGRAs in children under 15 years: 0.77 (95 % CI: 0.43-0.94) and 0.96 (95 % CI: 0.84-0.97), and IGRAs in children under 5 years: 0.85 (95 % CI: 0.52-0.97) and 0.94 (95 % CI: 0.90-0.99), respectively. CONCLUSIONS: This study demonstrated that the sensitivity and specificity of the IGRAs in children were moderate and high, respectively. Therefore, the IGRAs may be useful for detecting TB infection in children. CLINICAL TRIAL REGISTRATION: The review protocol was prospectively registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000046737).

The first case of Veillonella atypica bacteremia in a patient with renal pelvic tumor.

We report the first case of bacteremia caused by Veillonella atypica in a morbid elderly female patient who developed obstructive pyelonephritis. She was treated with ceftriaxone and ureteral stenting; this is the first report of V. atypica infection in humans. Species identification was performed by multiplex PCR and sequencing of rpoB. The strain was susceptible to metronidazole and clindamycin but resistant to benzylpenicillin, ampicillin, ampicillin/sulbactam, and moxifloxacin.

Comparison of hepatitis B virus genotypes B and C among chronically hepatitis B virus-infected patients who received nucleos(t)ide analogs: A multicenter retrospective study.

AIM: Hepatitis B virus genotype B (HBV/B) has been reported to have less risk of liver cirrhosis and hepatocellular carcinoma (HCC), but long-term observation has rarely been reported. We aimed to clarify the characteristics of HBV/B in nucleos(t)ide analog-treated patients in an area where HBV/B is more prevalent than in other areas of Japan. METHODS: A total of 498 chronically HBV-infected patients treated with nucleos(t)ide analog (lamivudine, entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate) for >6 months (mean 70.6 months) were included from nine hospitals in northeast Japan. The frequencies of hepatitis B surface antigen loss and HCC occurrence were analyzed. RESULTS: Among 427 patients whose genotype could be determined, 34.0% and 64.4% were infected with HBV/B and genotype C (HBV/C), respectively. The age of patients with HBV/B was significantly older than those with HBV/C (57.7 vs. 48.1). The cumulative rate of hepatitis B surface antigen loss was significantly higher in HBV/B than in HBV/C (3.6% vs. 0.7% at 10 years). Among 480 patients without HCC history, HCC occurrence was found in 40 patients (13.4% at 10 years). There was no cumulative rate difference of HCC occurrence among the genotypes, but after propensity score matching for age/sex, it was significantly lower in HBV/B than in HBV/C (5.3% vs. 18.5% at 10 years). CONCLUSIONS: Although a lower rate of HCC occurrence in HBV/B was shown by an age/sex-matched analysis than that in HBV/C, patients with HBV/B were significantly older and had a comparative risk of HCC occurrence in nucleos(t)ide analog-treated patients.

Comparison of Dopamine D3 and D2 Receptor Occupancies by a Single Dose of Blonanserin in Healthy Subjects: A Positron Emission Tomography Study With [11C]-(+)-PHNO.

Background: Blockade of D3 receptor, a member of the dopamine D2-like receptor family, has been suggested as a possible medication for schizophrenia. Blonanserin has high affinity in vitro for D3 as well as D2 receptors. We investigated whether a single dose of 12 mg blonanserin, which was within the daily clinical dose range (i.e., 8-24 mg) for the treatment of schizophrenia, occupies D3 as well as D2 receptors in healthy subjects. Methods: Six healthy males (mean 35.7±7.6 years) received 2 positron emission tomography scans, the first prior to taking blonanserin, and the second 2 hours after the administration of a single dose of 12 mg blonanserin. Dopamine receptor occupancies by blonanserin were evaluated by [11C]-(+)-PHNO. Results: Occupancy of each region by 12 mg blonanserin was: caudate (range 64.3%-81.5%; mean±SD, 74.3±5.6%), putamen (range 60.4%-84.3%; mean±SD, 73.3%±8.2%), ventral striatum (range 40.1%-88.2%; mean±SD, 60.8%±17.1%), globus pallidus (range 65.8%-87.6%; mean±SD, 75.7%±8.6%), and substantia nigra (range 56.0%-88.7%; mean±SD, 72.4%±11.0%). Correlation analysis between plasma concentration of blonanserin and receptor occupancy in D2-rich (caudate and putamen) and D3-rich (globus pallidus and substantia nigra) regions showed that EC50 for D2-rich region was 0.39 ng/mL (r=0.43) and EC50 for D3-rich region was 0.40 ng/mL (r=0.79). Conclusions: A single dose of 12 mg blonanserin occupied D3 receptor to the same degree as D2 receptor in vivo. Our results were consistent with previous studies that reported that some of the pharmacological effect of blonanserin is mediated via D3 receptor antagonism.

[A CASE OF PULMONARY MYCOBACTERIUM ABSCESSUS INFECTION THAT DEVELOPED DURING IMMUNOSUPPRESSIVE THERAPY FOR MYASTHENIA GRAVIS WITH RECURRENT THYMOMA].

A 58-year-old man developed cough, sputum, and low-grade fever during immunosuppressive treatment with corticosteroids and cyclosporine for myasthenia gravis with recurrent thymoma. Since chest CT revealed diffuse nodular opacities in both lung fields, he was referred to our department. Mycobacterium abscessus was repeatedly cultured from his sputum, and he was diagnosed with pulmonary M. abscessus infection. Although both chest radiological findings and clinical symptoms were mild, he required treatment with immunosuppressive agents and systemic anesthesia for resection of the recurrent thymoma. Based on complications and according to the patient's preference, oral treatment with clarithromycin 600 mg/day, levofloxacin 500 mg/day, and faropenem 600 mg/day was initiated on an outpatient basis. Following these treatments, his chest CT findings and clinical symptoms subsided, and the thymoma was successfully resected. Our experience with the present case suggests a possible treatment strategy for M. abscessus infection in immunocompromised and complicated cases.

Molecular analysis of the interspousal transmission of hepatitis B virus in two Japanese patients who acquired fulminant hepatitis B after 50 and 49 years of marriage.

A 71-year-old (C1I) and 69-year-old (C2I) Japanese female contracted fulminant hepatitis B after 50 and 49 years of marriage, respectively. Both index cases exhibited high levels of anti-HBc IgM antibodies (24.2 and 31.5 S/CO, respectively), suggestive of acute hepatitis B virus (HBV) infection, although they had no discernible risk factors for HBV infection, except for chronically HBV-infected spouses with detectable HBV DNA (3.3 log copies/ml [C1S: 72-year-old] and 7.2 log copies/ml [C2S: 71-year-old]). The HBV genotype/subgenotype was identical in each couple (B/B1 or C/C2). The HBV isolates from the index cases and spouses shared a nucleotide sequence identity of 99.5% and 99.7%, respectively, over the entire genome, and these four isolates had the highest nucleotide sequence identity of only 97% to HBV isolates deposited in DNA databases. Phylogenetic trees confirmed a close relationship of the HBV isolates between C1I and C1S and between C2I and C2S, supported by a high bootstrap value of 100% within each couple, indicating the transfer of HBV infection between spouses. These four isolates shared a precore mutation of G1896A known to be associated with fulminant hepatitis B. Although the history of sexual contact within a reasonable incubation period was obscure for one stable, monogamous couple (C1I and C1S), the other couple had a monogamous sexual relationship within six months prior to disease onset. This study indicates that two elderly Japanese patients with fulminant hepatitis B acquired HBV infection via interspousal (most likely sexual) transmission during long-lasting marriages.

Remodeling of the pulmonary artery induced by metastatic gastric carcinoma: a histopathological analysis of 51 autopsy cases.

BACKGROUND: Gastric carcinoma remains the second commonest cause of cancer deaths worldwide. Presence of the carcinoma cell in the pulmonary artery is serious condition that might cause remodeling of the pulmonary artery. The present study conducted detailed histopathological analyses to elucidate how gastric carcinoma cells may affect the structure and hemodynamics of pulmonary arteries. METHODS: Remodeling of the pulmonary artery was assessed based on measurements of arterial diameters and stenosis rates from the autopsies, and their correlation were also validated. We additionally calculated 95 percent confidential intervals (CIs) for the rate of stenosis in groups of pulmonary arteries of different caliber zones (under 100, 100 to 300, and over 300 micrometer). The right ventricular thickness was measured and examined whether it correlated with the rate of pulmonary arterial stenosis. RESULTS: A total of 4612 autopsy cases were recorded at our institute, among which 168 had gastric carcinoma. Finally, 51 cases of the gastric carcinoma were employed for the study which had carcinoma cells in the lumen of the pulmonary artery. The mean right ventricular wall thickness of these cases was 3.14 mm. There were significant positive associations between the rates of pulmonary arterial stenosis and right ventricular thickness from pulmonary arteries of diameter under 100, 100 to 300, and over 300 micrometer. In these zones, 31, 31, and 33 cases had rates of pulmonary arterial stenosis that were below the lower limit of the 95 percent CI values, respectively. On the other hand, among cases with significant pulmonary stenosis, 17 of 18 cases with stenosis in the over 300 micrometer zone involved pulmonary arteries of both in the under 100 and 100 to 300 micrometer zones. CONCLUSION: One-third of autopsy with advanced gastric carcinoma had carcinoma cells in lumen of pulmonary artery, but implantation and proliferation may be essential to induce intimal thickening that causes an increasing of pulmonary arterial pressure, because our study revealed a significant positive association between the rate of pulmonary arterial stenosis and right ventricular thickness. In addition, diffuse type gastric carcinoma may be apt to cause the remodeling of the pulmonary artery.

A Perspective on the 6th International Conference on Sports Concussion.

The International Conference on Sports Concussion, held every four years since 2001, has been instrumental in forming the international consensus on sports-related concussions. However, due to the unprecedented global pandemic of COVID-19, not only the Tokyo Olympics 2020, but also the initially scheduled sixth conference was postponed multiple times. Finally, the 6th International Conference on Sports Concussion took place in Amsterdam at the end of October 2022. In July 2023, the Amsterdam Declaration, reflecting the outcomes of this sixth conference, was released. This paper provides an overview of the conference, in which significant updates were revealed and introduced, including revisions to the definition of sports-related concussions, as well as the latest version of the Sports Concussion Assessment Tool (SCAT), known as SCAT6, the Office Assessment Tool (SCOAT), and the updated staged return-to-play protocol.

The emergence of metronidazole-resistant Prevotella bivia harboring nimK gene in Japan.

We present the identification and characterization of the complete genome of metronidazole (MTZ)-resistant Prevotella bivia strain TOH-2715 [minimum inhibitory concentration (MIC): 8 mg/L], isolated from the urine of an elderly Japanese woman, as well as details of its mobile genetic elements (MGEs) containing antimicrobial resistance (AMR) genes and its relationship with other bacterial species determined using whole-genome sequencing (WGS) data. TOH-2715 possessed two chromosomes with putative MGEs containing AMR genes. Two AMR-related MGE regions were present in chromosome 2. MGE-region 1 (7,821 bp) included Tn6456, where nimK was located, and MGE-region 2 (58.8 Kbp) included the integrative and conjugative element (ICE), where tet(Q) and ermF were located. The genetic structure of the ICE of TOH-2715 was similar to that of CTnDOT-family transposons, where ermF and tet(Q) are located. A search of public databases revealed that nimK was present in Prevotella spp., including P. bivia, and was partially composed of a Tn6456-like element lacking the efflux transporter gene qacE and the Crp/Fnr family transcriptional regulator gene in some cases. Core ICE gene analysis showed that ICEs similar to that of TOH-2715 were present in Prevotella spp. and Bacteroides spp., suggesting horizontal gene transfer among anaerobes. This is the report of WGS analysis of an MTZ-resistant clinical strain of P. bivia (TOH-2715) with Tn6456 encoding nimK. Other submitted genomes have described the presence of nimK, but none of them have described MTZ resistance. Additionally, we described putative MGE regions containing the AMR gene within the genus Prevotella and among anaerobes, raising concerns about the future spread of nimK among anaerobes. IMPORTANCE: Metronidazole (MTZ) is an important antimicrobial agent in anaerobic infections and is widely used in clinical settings. The rate of MTZ resistance in anaerobic bacteria has been increasing in recent years, and the nim gene (nitro-imidazole reductase) is one of the resistance mechanisms. Prevotella bivia is found in humans in the urinary tract and vagina and is known to cause infections in some cases. One of the nim genes, nimK, has recently been discovered in this species of bacteria, but there are no reports of antimicrobial resistance (AMR)-related regions in its whole genome level. In this study, we analyzed the AMR region of nimK-positive P. bivia derived from clinical specimens based on comparisons with other anaerobic genomes. P. bivia was found to be engaged in horizontal gene transfer with other anaerobic bacteria, and the future spread of the nimK gene is a concern.

Evaluation of Treatment Strategies for Male Prolactin-Secreting Pituitary Neuroendocrine Tumors.

Prolactin-secreting pituitary neuroendocrine tumors (PitNETs) are more common in women. Male patients may also have few symptoms and have macroadenomas extending outside the sella turcica. This study aimed to report the results of cabergoline treatment in male patients with prolactin-secreting PitNET. The study included nine male patients aged 26-65 years (median, 46 years) diagnosed with prolactin-secreting PitNETs. The age at onset, prolactin values, tumor size, symptoms, and treatment were assessed. The mean prolactin value at the initial presentation was 2734.6 ng/mL, and the mean maximum tumor diameter was 40.4 mm. Visual field disturbance was the most common symptom (44.4%), followed by headaches (33.3%), asymptomatic symptoms (11.1%), and galactorrhea (11.1%). Eight patients responded to cabergoline treatment with normalization of prolactin levels and tumor shrinkage. One patient did not respond to the cabergoline treatment and required surgical intervention. There were no cases of cerebrospinal fluid leakage. Cabergoline was found to be an effective treatment for male prolactin-secreting PitNETs.

Comparative Study of Postmortem MRI and Pathological Findings in Malignant Brain Tumors.

This study compared magnetic resonance imaging (MRI) findings of postmortem brain specimens with neuropathological findings to evaluate the value of postmortem MRI. Postmortem MRI was performed on five formalin-fixed whole brains with malignant tumors. Postmortem T2-weighted images detected all neuropathological abnormalities as high-signal regions but also showed histological tumor invasion in areas without edema. Tumor lesions with high necrosis and edema showed high signal intensity on T2-weighted images; in three cases, lesion enlargement was detected on the final prenatal imaging and postmortem MRI. Disease progression immediately before death may have contributed to this difference. In conclusion, the correlation between MRI and neuropathological findings facilitates understanding of the mechanisms responsible for MRI abnormalities. Increased free water due to edema, necrosis, and brain tissue injury can explain the increased signal intensity observed on T2-weighted images. Postmortem MRI may contribute to effective pathology by identifying subtle abnormalities prior to brain dissection.

Development of a peptide nucleic acid probe to Trichosporon species and identification of trichosporonosis by use of in situ hybridization in formalin-fixed and paraffin-embedded (FFPE) sections.

In order to identify Trichosporon species in formalin-fixed and paraffin-embedded sections from which visual discrimination of non-glabrata Candida species is mostly ineffective but critical for the choice of antifungals, we tested the usefulness of a newly designed peptide nucleic acid probe (PNA) for in situ hybridization (ISH). Results confirmed the usefulness of ISH with our PNA probe in identifying Trichosporon species from Candida albicans.

How histopathology can contribute to an understanding of defense mechanisms against cryptococci.

Invasive fungal infections, particularly those considered opportunistic, have become a common and significant complication of procedures performed in advanced contemporary medicine. Among such infections, cryptococcosis, which is usually caused by infection with Cryptococcus neoformans and Cryptococcus gattii, is particularly problematic because this fungal infection occurs in immunocompromised and apparently immunocompetent individuals. It has been largely accepted that Cryptococcus species are recognized by cellular receptors and that Th1-type immune responses play an important role in defense mechanisms against the yeast. However, the interaction between the yeast and host tissue varies depending on the characteristics of the yeast and the immune status of the host. To gain a better understanding of the pathophysiology of cryptococcosis, we wish to emphasize the usefulness of histopathological examinations, because it allowed more detailed information of an extremely complex interaction between the causative yeasts and tissue response. In the present review, we describe the pathophysiology of cryptococcosis as largely revealed in our previous histopathological investigations of the experimental infection.

Evaluation of a novel Clostridioides difficile-selective growth broth under aerobic conditions.

A newly developed Clostridioides difficile-selective growth broth, which can be cultured under aerobic conditions, was found to have a sensitivity/specificity (98%/89%) comparable to conventional anaerobic culture methods. This might be a powerful tool for diagnosing Clostridioides difficile infection in resource-limited regions and health care settings in the future.

Traumatic brain injuries caused by knockout in Japanese amateur boxers: A questionnaire-based survey.

The aim of the present study is to conduct a trauma and disability survey in amateur boxers and show the actual conditions of injuries based on the current situations. We have obtained 663 valid responses from male and female boxers. In the questionnaire survey who was carried out on a Web questionnaire form. The questions involve that Face Sheet (gender, height, weight, athletic experience, etc.) and prepared 10 questions about trauma and impairment, 7 questions with concussion or damage on head. and, set 11 self-evaluations, which the boxers assessed their boxing skills. The subjects include amateur boxers who are all high school students (15 years old) and retired boxers. We had analyzed relation between the skills and the injuries. And, main outcome was that make a measure to setting whether or not questionnaires have been knockout (KO) as a variable, we applied a method of multiple logistic regression analysis. Moreover, as for the group who got KO in the past, we have also applied multiple regression analysis by using stepwise regression to factors affecting numbers of symptoms. The number of hits they experienced was smaller in international tournament matches, and the odds rate for KO was 0.669. And, KO experience group was compared with non-KO experience group, and the factors influencing the number of severity symptoms were examined. As a result, 2 factors were selected what "Seriousness in practice" and "Fighting spirit in games". It might be possible that the relation between the experience of being KO and self-assessment of boxing performance.

Gene expression analysis of a murine model with pulmonary vascular remodeling compared to end-stage IPAH lungs.

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) continues to be one of the most serious intractable diseases that might start with activation of several triggers representing the genetic susceptibility of a patient. To elucidate what essentially contributes to the onset and progression of IPAH, we investigated factors playing an important role in IPAH by searching discrepant or controversial expression patterns between our murine model and those previously published for human IPAH. We employed the mouse model, which induced muscularization of pulmonary artery leading to hypertension by repeated intratracheal injection of Stachybotrys chartarum, a member of nonpathogenic and ubiquitous fungus in our envelopment. METHODS: Microarray assays with ontology and pathway analyses were performed with the lungs of mice. A comparison was made of the expression patterns of biological pathways between our model and those published for IPAH. RESULTS: Some pathways in our model showed the same expression patterns in IPAH, which included bone morphogenetic protein (BMP) signaling with down-regulation of BMP receptor type 2, activin-like kinase type 1, and endoglin. On the other hand, both Wnt/planar cell polarity (PCP) signaling and its downstream Rho/ROCK signaling were found alone to be activated in IPAH and not in our model. CONCLUSIONS: Activation of Wnt/PCP signaling, in upstream positions of the pathway, found alone in lungs from end stage IPAH may play essential roles in the pathogenesis of the disease.

Trends in the prevalence of invasive fungal infections from an analysis of annual records of autopsy cases of Toho University.

Clinical diagnosis of invasive fungal infections (IFIs) is sometimes difficult, and obtaining an accurate assessment of trends concerning the prevalence of IFIs is a challenge. The aim of this study was to determine trends in the prevalence of IFIs from an autopsy survey. The retrospective review of autopsy records stored in Toho University was performed on all documented cases with fungal infection from 1955 to 2006. A total of 411 cases of IFIs were detected among 10 297 autopsies. The prevalence of candidiasis decreased from 3.6% (1981-93) to 2.0% (1994-2006), and that of aspergillosis increased throughout the 52-year period and reached 2.0% (1994-2006). The prevalence of IFIs in the patient group comprising haematological disorders was significantly higher (19.9%) than in other patient groups (2.9%), of which the odds ratio was 18.4 for mucormycosis and 10.0 for aspergillosis. The lung was the most common organ involved irrespective of major fungal species, and most cases with candidiasis showed multiple-organ infection. Results confirmed the increasing prevalence of aspergillosis and high risk of IFIs in the patient group with haematological disorders. IFIs were also detected in an immunocompromised state caused not only by primary disease but also by treatment with anti-tumour drugs and corticosteroids.

Whole-Genome Sequencing Analysis of blaNDM-5/IncX3 Plasmid Estimated to Be Conjugative-Transferred in the Gut.

We characterized plasmids carrying blaNDM-5 detected in Escherichia coli isolated from the infection site and stool sample of a Japanese patient, with no international travel history, by whole-genome sequencing (WGS). WGS was performed using MiSeq and MinlON sequencer followed by hybrid de novo assembly. blaNDM-5 was detected on IncX3 (blaNDM-5/IncX3) plasmids; pMTY18530-4_IncX3 in E. coli TUM18530 isolated from a wound above the pubis; pMTY18780-5_IncX3 and pMTY18781-1_IncX3 in E. coli TUM18780 and TUM18781, respectively, isolated from stool. These three plasmids resembled each other and pGSH8M-2-4, previously detected in E. coli isolated from a Tokyo Bay water sample. E. coli TUM18530 and TUM18780 belonged to sequence type (ST) 1011 and had only two single nucleotide polymorphisms on the core-genome, whereas TUM18781 belonged to ST2040. Three blaNDM-5/IncX3 plasmids (pMTY18530-4_IncX3, pMTY18780-5_IncX3, and pMTY18781-1_IncX3) exhibited conjugative transfer in vitro at an average frequency of 1.71 × 10-3 per donor cell. The transconjugant was resistant to only ß-lactams, including carbapenem, except aztreonam. Similarity of the blaNDM-5/IncX3 plasmids isolated from our patient compared with that isolated from the Tokyo bay water sample suggested that the plasmids may have already spread throughout the Japanese community. The blaNDM-5/IncX3 plasmid exhibited potential for easy transmission to different strains in the patient's intestine.

Identification of Fusarium species in formalin-fixed and paraffin-embedded sections by in situ hybridization using peptide nucleic acid probes.

Fusarium has recently emerged as an opportunistic pathogen of humans, but the histological differentiation of Fusarium from Aspergillus and Scedosporium is particularly difficult because these fungi may induce similar clinical features and exhibit filamentous development in host tissues. Thus, there is a need to establish rapid and reliable methods that are applicable to pathological diagnoses. The aim of this study was to evaluate and establish in situ hybridization (ISH) using peptide nucleic acid (PNA) probes targeting the 28S rRNA to identify Fusarium species in tissue sections. This technique was validated using both formalin-fixed and paraffin-embedded pulmonary tissues from mice infected with seven different species of fungi and cell blocks from fungal cultures of 30 strains. As a result, strong positive signals were observed within fungal organisms present in tissues of the lung from mice infected with Fusarium solani. Furthermore, this probe reacted strongly with both F. solani and Fusarium oxysporum in sections from cell blocks. Although some cross-reactivity occurred with the Pseudallescheria boydii in sections from cell blocks, the signal intensity was low and most hyphae were not reactive. In conclusion, it was confirmed that ISH with PNA probes is accurate and is a valuable tool for identifying Fusarium spp. among organisms that have identical morphological features in formalin-fixed and paraffin-embedded sections.