Analysis of Suspected Measles Cases with Discrepant Measles-Specific IgM and rRT-PCR Test Results, Japan.

We investigated clinically suspected measles cases that had discrepant real-time reverse transcription PCR (rRT-PCR) and measles-specific IgM test results to determine diagnoses. We performed rRT-PCR and measles-specific IgM testing on samples from 541 suspected measles cases. Of the 24 IgM-positive and rRT-PCR--negative cases, 20 were among children who received a measles-containing vaccine within the previous 6 months; most had low IgG relative avidity indexes (RAIs). The other 4 cases were among adults who had an unknown previous measles history, unknown vaccination status, and high RAIs. We detected viral nucleic acid for viruses other than measles in 15 (62.5%) of the 24 cases with discrepant rRT-PCR and IgM test results. Measles vaccination, measles history, and contact history should be considered in suspected measles cases with discrepant rRT-PCR and IgM test results. If in doubt, measles IgG avidity and PCR testing for other febrile exanthematous viruses can help confirm or refute the diagnosis.

Low blood level of tumour suppressor miR-5193 as a target of immunotherapy to PD-L1 in gastric cancer.

BACKGROUND: Recent studies have identified that low levels of some tumour suppressor microRNAs (miRNAs) in the blood contribute to tumour progression and poor outcomes in various cancers. However, no study has proved these miRNAs are associated with cancer immune mechanisms. METHODS: From a systematic review of the NCBI and miRNA databases, four tumour suppressor miRNA candidates were selected (miR-5193, miR-4443, miR-520h, miR-496) that putatively target programmed cell death ligand 1 (PD-L1). RESULTS: Test-scale and large-scale analyses revealed that plasma levels of miR-5193 were significantly lower in gastric cancer (GC) patients than in healthy volunteers (HVs). Low plasma levels of miR-5193 were associated with advanced pathological stages and were an independent prognostic factor. Overexpression of miR-5193 in GC cells suppressed PD-L1 on the surface of GC cells, even with IFN-γ stimulation. In the coculture model of GC cells and T cells stimulated by anti-CD3/anti-CD28 beads, overexpression of miR-5193 increased anti-tumour activity of T cells by suppressing PD-L1 expression. Subcutaneous injection of miR-5193 also significantly enhanced the tumour-killing activity and trafficking of T cells in mice. CONCLUSIONS: Low blood levels of miR-5193 are associated with GC progression and poor outcomes and could be a target of nucleic acid immunotherapy in GC patients.

Enhanced measures, including PCR-based screening and syndromic surveillance for nosocomial outbreaks of the COVID-19 Omicron variant, using descriptive epidemiology and whole-genome sequencing in a Japanese tertiary care hospital.

INTRODUCTION: In this study, we aimed to analyze the effectiveness of enhanced preventive measures against nosocomial COVID-19 Omicron outbreaks based on those encountered. METHODS: We introduced PCR-based screening and syndromic surveillance, in addition to standard and transmission-based precautions, during a COVID-19 outbreak in three wards of Kagoshima University Hospital, a Japanese tertiary care hospital, in February 2022, amid the Omicron variant endemic. Furthermore, we analyzed the descriptive epidemiology and whole-genome sequencing (WGS) of positive SARS-CoV-2 PCR samples from this outbreak. RESULTS: PCR-based screening tests were conducted following the identification of three cases through syndromic surveillance. As a result, 30 individuals tested positive for SARS-CoV-2, including 13 inpatients, five attendant family members, and 12 healthcare workers across the three wards. Notably, no new infections were observed within eight days following the implementation of preventive measures. Among the SARS-CoV-2 genomes analyzed (n = 16; 53.3%), all strains were identified as belonged to BA.1.1 variant. Detailed analysis of descriptive and molecular epidemiology, incorporating single-nucleotide polymorphism analysis of WGS and clarification of transmission links, considering two potential entry routes to the hospital. CONCLUSIONS: Introduction of additional preventive measures, including PCR-based screening and syndromic surveillance, in addition to WGS and descriptive epidemiology, is useful for the early intervention of nosocomial outbreaks and for revealing the transmission route of the COVID-19 Omicron variant.

SARS-CoV-2 Infection in Wrestlers after International Tournaments, April 2021.

Epidemiologic and genomic investigation of SARS-CoV-2 infections in members of Japan's national wrestling team after participation in international tournaments in 2021 revealed multiple lineages of SARS-CoV-2 not reported in Japan. The attack rate among wrestlers was high. Results suggest possible transmission during matches. We recommend early case detection and response practices.

Plasma miR-1254 as a predictive biomarker of chemosensitivity and a target of nucleic acid therapy in esophageal cancer.

This study investigated novel tumor suppressor microRNAs (miRNAs) that decrease in plasma and predict chemosensitivity to neoadjuvant chemotherapy (NAC) for esophageal squamous cell carcinoma (ESCC) and revealed their usefulness as novel therapeutic agents. We selected four miRNA candidates (miR-323, 345, 409, and 1254) based on the microRNA microarray comparing pre-treatment plasma levels in ESCC patients with high and low histopathological responses to NAC and an NCBI database review. Among these miRNA candidates, miR-1254 was more highly elevated in pre-treatment plasma of ESCC patients with a high histopathological response than in those with a low histopathological response (P = 0.0021, area under the receiver-operating characteristic curve 0.7621). High plasma miR-1254 levels tended to correlate with the absence of venous invasion (P = 0.0710) and were an independent factor predicting a higher response to chemotherapy (P = 0.0022, odds ratio 7.86) and better prognosis (P = 0.0235, hazard ratio 0.23). Overexpressing miR-1254 in ESCC cells significantly enhanced chemosensitivity to cisplatin through the transcriptional regulation of ABCC1 in vitro. Moreover, increased plasma miR-1254 levels by subcutaneous injection significantly improved responses to cisplatin in mice. Plasma miR-1254 might be a useful biomarker for predicting responses to NAC, and the restoration of plasma miR-1254 levels might improve chemosensitivity in ESCC.

Emergence of ciprofloxacin- and penicillin-resistant Neisseria meningitidis isolates in Japan between 2003 and 2020 and its genetic features.

Although we previously reported that some meningococcal isolates in Japan were resistant to penicillin (PCG) and ciprofloxacin (CIP), the antibiotic susceptibilities of Neisseria meningitidis isolates obtained in Japan remained unclear. In the present study, 290 N. meningitidis isolates in Japan between 2003 and 2020 were examined for the sensitivities to eight antibiotics (azithromycin, ceftriaxone, ciprofloxacin, chloramphenicol, meropenem, minocycline, penicillin, and rifampicin). All isolates were susceptible to chloramphenicol, ceftriaxone, meropenem, minocycline, and rifampicin while two were resistant to azithromycin. Penicillin- and ciprofloxacin-resistant and -intermediate isolates (PCGR, CIPR, PCGI and CIPI, respectively) were also identified. Based on our previous findings from whole genome sequence analysis, approximately 40% of PCGI were associated with ST-11026 and cc2057 meningococci, both of which were unique to Japan. Moreover, the majority of ST-11026 meningococci were CIPR or CIPI. Sensitivities to PCG and CIP were closely associated with genetic features, which indicated that, at least for Japanese meningococcal isolates, PCGR/I or CIPI/R would be less likely to be horizontally conferred from other neisserial genomes by transferring of the genes responsible (penA and gyrA genes, respectively), but rather that ancestral N. meningitidis strains conferring PCGR/I or CIPI/R phenotypes clonally disseminated in Japan.

Evaluating prognostic value and stage migration effects using a positive lymph node ratio in adenocarcinoma of the esophagogastric junction.

BACKGROUND: Adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide. Lymph node metastasis is an important clinical issue in AEG patients. This study investigated the usefulness of a positive lymph node ratio (PLNR) to stratify prognosis and evaluate stage migration. METHODS: We retrospectively analysed 117 consecutive AEG patients (Siewert type I or II) who received a lymphadenectomy between 2000 and 2016. RESULTS: A PLNR cut-off value of 0.1 most effectively stratified patient prognosis into two groups (P < 0.001). Also, prognosis could be clearly stratified into four groups: PLNR = 0, 0 < PLNR < 0.1, 0.1 ≤ PLNR < 0.2, and 0.2 ≤ PLNR (P < 0.001, 5-year survival rates (88.6%, 61.1%, 34.3%, 10.7%)). A PLNR ≥ 0.1 significantly correlated with tumour diameter ≥ 4 cm (P < 0.001), tumour depth (P < 0.001), greater pathological N-status (P < 0.001), greater pathological Stage (P < 0.001), and oesophageal invasion length ≥ 2 cm (P = 0.002). A PLNR ≥ 0.1 was a poor independent prognostic factor (hazard ratio 6.47, P < 0.001). The PLNR could stratify prognosis if at least 11 lymph nodes were retrieved. A 0.2 PLNR cut-off value discriminated a stage migration effect in pN3 and pStage IV (P = 0.041, P = 0.015) patients; PLNR ≥ 0.2 might potentially diagnose a worse prognosis and need meticulous follow-up post-surgery. CONCLUSION: Using PLNR, we can evaluate the prognosis and detect higher malignant cases who need meticulous treatments and follow-up in the same pStage.

Haplotype networks of SARS-CoV-2 infections in the Diamond Princess cruise ship outbreak.

The Diamond Princess cruise ship was put under quarantine offshore Yokohama, Japan, after a passenger who disembarked in Hong Kong was confirmed as a coronavirus disease 2019 case. We performed whole-genome sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly from PCR+ clinical specimens and conducted a phylogenetic analysis of the outbreak. All tested isolates exhibited a transversion at G11083T, suggesting that SARS-CoV-2 dissemination on the Diamond Princess originated from a single introduction event before the quarantine started. Although further spreading might have been prevented by quarantine, some progeny clusters could be linked to transmission through mass-gathering events in the recreational areas and direct transmission among passengers who shared cabins during the quarantine. This study demonstrates the usefulness of haplotype network/phylogeny analysis in identifying potential infection routes.

Overexpression of Tetraspanin31 contributes to malignant potential and poor outcomes in gastric cancer.

Tetraspanin has important functions in many cancers by aggregating with various proteins that interact with intracellular signaling proteins. The molecular function of Tetraspanin31 (TSPAN31), located in the 12q14 amplified region in various cancers, remains unclear in gastric cancer (GC). We tested whether TSPAN31 acts as a cancer-promoting gene through its activation or overexpression in GC. We analyzed seven GC cell lines and 189 primary tumors, which were curatively resected in our hospital between 2011 and 2013. Overexpression of the TSPAN31 protein was frequently detected in three GC cell lines (42.9%) and 62 primary GC specimens (32.8%). Overexpression of TSPAN31 was significantly correlated with lymphatic invasion, venous invasion, more advanced pT and pN stages, and a higher recurrence rate. Moreover, TSPAN31 positivity was an independent factor predicting worse patient outcomes (p = 0.0283, hazard ratio 3.97). Ectopic overexpression of TSPAN31 facilitated cell proliferation of GC cells, and knockdown of TSPAN31 inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition of GC cells through the PI3K-Akt pathway and increased cell apoptosis in a TP53 mutation-independent manner. In vivo analysis also revealed knockdown of TSPAN31 suppressed tumor progression. In addition, knockdown of TSPAN31 improved chemosensitivity to cisplatin through the suppression of ABCC2. These findings suggest that TSPAN31 plays a crucial role in tumor-malignant potential through overexpression, highlighting its utility as a prognostic factor and a potential therapeutic target in GC.

The clinical characteristics of pediatric coronavirus disease 2019 in 2020 in Japan.

BACKGROUND: The COVID-19 pandemic has affected the lives of people of all ages. Most reports on pediatric cases suggest that children experience fewer and milder symptoms than do adults. This is the first nationwide study in Japan focusing on pediatric cases reported by pediatricians, including cases with no or mild symptoms. METHODS: We analyzed the epidemiological and clinical characteristics and transmission patterns of 840 pediatric (<16 years old) COVID-19 cases reported between February and December 2020 in Japan, using a dedicated database which was maintained voluntarily by members of the Japan Pediatric Society. RESULTS: Almost half of the patients (47.7%) were asymptomatic, while most of the others presented mild symptoms. At the time of admission or first outpatient clinic visit, 84.0% of the cases were afebrile (<37.5°C). In total, 609 cases (72.5%) were exposed to COVID-19-positive household members. We analyzed the influence of nationwide school closures that were introduced in March 2020 on COVID-19 transmission routes among children in Japan. Transmission within households occurred most frequently, with no significant difference between the periods before and after declaring nationwide school closures (70.9% and 74.5%, respectively). CONCLUSIONS: COVID-19 symptoms in children are less severe than those in adults. School closure appeared to have a limited effect on transmission. Controlling household transmission from adult family members is the most important measure for prevention of COVID-19 among children.

Factors associated with knowledges and attitudes about measles and rubella immunization in a non-health care occupational setting in Japan.

INTRODUCTION: Elimination of measles and rubella has been achieved in several countries and some regions. After verified measles elimination, some countries have reported outbreaks among adults in occupational settings such as health care institution and school setting. Studies have reported that knowledge and attitude for measles and/or rubella are significantly associated with immunization uptake in adults, but few studies have been conducted in settings other than health care facilities and schools. METHODS: We conducted a cross-sectional study among 134 office employees during a routine health checkup in June 17-20, 2014, to examine the association between willingness to receive immunization and knowledge and attitudes. RESULTS: Approximately 75% had a protective level of antibody for measles (PA≥1:256) and rubella (HI ≥ 32 IU/mL). After adjustment for sex, age and immune status, the attitudes that immunization prevents measles (adjusted odds ratio [aOR] = 7.8, 95% confidence interval [95%CI]: 2.5-24.7) and prevents infection and transmission to others (aOR = 4.0, 95%CI: 1.4-11.4). Knowing that males are the vulnerable group for rubella infection (aOR = 5.8, 95%CI: 2.4-13.9), attitude that immunization prevents rubella infection (aOR = 7.9, 95%CI: 2.4-26.5), and prevents infection and transmit to others (aOR = 6.7, 95%CI: 2.2-20.1) were significantly associated with willingness to receive immunization after adjustment for sex, age, and immune status. CONCLUSIONS: Studies have shown that physicians and other health care workers are important source of information for promotion of immunization. Thus, we recommend that physicians educate and promote immunization for measles and/or rubella to adults working in offices during routine health checks.

Development of a simple and cost-effective gel-based duplex PCR method to identify both encapsulated and unencapsulated Neisseria meningitidis applicable under resource-limited conditions.

Tens of thousands of cases of invasive meningococcal diseases (IMD) with thousands of deaths are reported annually worldwide; however, only approximately 40 cases occur each year in Japan. Therefore, the majority of medical technologists in Japan have never performed or prepared for analyses of the causative agent, Neisseria meningitidis. Since IMD outbreaks have been reported at mass gathering events, the risk of IMD will increase in Japan in 2021 because of the Olympics. In the present study, we developed a new simple gel-based duplex PCR method that may be employed by the majority Japanese clinical laboratories. It is simple to perform and time- and cost-effectively identifies encapsulated and unencapsulated N. meningitidis by detecting the encapsulated N. meningitidis-specific ctrB and N. meningitidis-specific ggt genes. We consider this simple and cost-effective identification method to compensate for the lack of experience and resource-poor conditions in most Japanese laboratories in which N. meningitidis has rarely been examined.

Environmental Sampling for Severe Acute Respiratory Syndrome Coronavirus 2 During a COVID-19 Outbreak on the Diamond Princess Cruise Ship.

During a COVID-19 outbreak on the Diamond Princess cruise ship we sampled environmental surfaces after passengers and crew vacated cabins. SARS-CoV-2 RNA was detected in 58 of 601 samples (10%) from case cabins 1-17 days after cabins were vacated but not from noncase cabins. There was no difference in detection proportion between cabins of symptomatic (15%, 28/189; cycle quantification [Cq], 29.79-38.86) and asymptomatic cases (21%, 28/131; Cq, 26.21-38.99). No SARS-CoV-2 virus was isolated from any of the samples. Transmission risk of SARS-CoV-2 from symptomatic and asymptomatic patients may be similar and surfaces could be involved in transmission.

Initial Investigation of Transmission of COVID-19 Among Crew Members During Quarantine of a Cruise Ship - Yokohama, Japan, February 2020.

An outbreak of coronavirus disease 2019 (COVID-19) among passengers and crew on a cruise ship led to quarantine of approximately 3,700 passengers and crew that began on February 3, 2020, and lasted for nearly 4 weeks at the Port of Yokohama, Japan (1). By February 9, 20 cases had occurred among the ship's crew members. By the end of quarantine, approximately 700 cases of COVID-19 had been laboratory-confirmed among passengers and crew. This report describes findings from the initial phase of the cruise ship investigation into COVID-19 cases among crew members during February 4-12, 2020.

Descriptive study of COVID-19 outbreak among passengers and crew on Diamond Princess cruise ship, Yokohama Port, Japan, 20 January to 9 February 2020.

An outbreak of coronavirus disease (COVID-19) occurred on the Diamond Princess cruise ship making an international journey, which led to quarantine of the ship at Yokohama Port, Japan. A suspected COVID-19 case was defined as a passenger or crew member who developed a fever or respiratory symptoms, and a confirmed COVID-19 case had laboratory-confirmation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Between 3 and 9 February 2020, 490 individuals were tested for SARS-CoV-2 and 172 were positive (152 passengers (median age: 70 years; interquartile range (IQR): 64-75; males: 45%) and 20 crew (median age: 40 years; IQR: 35-48.5; males: 80%). Other than the Hong Kong-related index case, symptom onset for the earliest confirmed case was 22 January, 2 days after the cruise ship left port. Attack rates among passengers were similar across the decks, while beverage (3.3%, 2/61) and food service staff (5.7%, 14/245) were most affected. Attack rates tended to increase with age. A comprehensive outbreak response was implemented, including surveillance, provision of essential medical care, food and medicine delivery, isolation, infection prevention and control, sampling and disembarkation.

Characterization of unusual DS-1-like G3P[8] rotavirus strains in children with diarrhea in Japan.

The emergence and rapid spread of novel DS-1-like intergenogroup reassortant rotaviruses having the equine-like G3 genotype (DS-1-like G3P[8] strains) have been recently reported from several countries. During rotavirus surveillance in Japan in 2015-2016, three DS-1-like G3P[8] strains were identified from children with severe diarrhea. In the present study, we sequenced and characterized the full genomes of these three strains. On full-genomic analysis, all three strains showed a unique genotype constellation including both genogroup 1 and 2 genes: G3-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Phylogenetic analysis revealed that each of the 11 genes of the three strains was closely related to that of Japanese DS-1-like G1P[8] and/or Japanese equine-like G3P[4] human strains. Thus, the three study strains were suggested to be reassortants that acquired the G3-VP7 gene from equine G3 rotaviruses on the genetic background of DS-1-like G1P[8] strains. Our observations will provide important insights into the evolutionary dynamics of emerging DS-1-like G3P[8] strains.

[Impact of Muscle Mass Reduction on Postoperative Adjuvant Chemotherapy and Long-Term Prognosis in Patients with Gastric Cancer].

BACKGROUND: Measuring the area of the psoas muscle on computed tomography is useful for the evaluation of skeletal muscle mass. The skeletal muscle is thought to be involved in weight loss after gastric surgery, and weight loss causes a decrease in compliance with chemotherapy continuity. PATIENTS AND METHODS: The psoas muscle index(PMI)was determined in 33 patients undergoing surgery for Stage Ⅱ-ⅢB gastric cancer. The rate of change in PMIwas calculated, and patients were classified into maintained and reduced muscle groups using a cutoff of -0.23 month-1. Relationships between the rate of PMIchanges and prognosis and chemotherapy continuity were examined. RESULTS: The rate of PMIchanges was significantly associated with recurrence-free survival in univariate(maintained vs reduced muscle: p=0.002)and multivariate(p= 0.0018)analyses. A reduction in the muscle mass was associated with dropout from adjuvant chemotherapy and was a predictor of a poor prognosis. CONCLUSION: The rate of PMIchanges is related to the period of adjuvant chemotherapy and is an independent prognostic factor after surgery for StageⅡ-ⅢB gastric cancer.

[A Case of Cancerous Meningitis in Juvenile Onset Gastric Cancer].

A 30-year-old woman was diagnosed with advanced gastric cancer(MUL, Circ, Type 4, por1+2, T4a, N3a, M1[LYM, P1, CY1, H0], Stage Ⅳ)on delivery. Because of unresectable, she underwent chemotherapy(first-line: S-1 plus CDDP, secondline: PTX plus Rmab, and third-line: Nmab); approximately 10 months later, she started complaining of headache. We performed a close examination, because she also developed resistance to chemotherapy. Contrast-enhanced magnetic resonance imaging of the brain revealed intense and diffuse enhancement on the brain surface, leading to the suspicion of meningeal carcinomatosis. However, hydrocephalus did not occur. She was given steroids to alleviate symptoms, but this treatment did not effective. We used neither intrathecal chemotherapy nor radiation therapy. Her symptoms gradually worsened, and she died approximately 4 weeks after the diagnosis of meningeal carcinomatosis. Meningeal carcinomatosis resulting from gastric cancer is very rare and is often difficult to diagnose. Even though this type of disease is diagnosed correctly, rapid disease progression makes the treatment difficult; therefore, patients with this type of disease have a terribly poor prognosis in daily clinical practice.

[A Study of 15 Patients with Colorectal Cancer Perforation, Kyoto Chubu Medical Center].

In colorectal cancer perforation, selecting the appropriate surgical operation while considering the patient's life and radical treatment is important. We divided 15 patients who underwent surgical intervention at our department into 2 groups, namely, free and covering perforation groups, and conducted a retrospective analysis. In the comparison between the 2 groups (free vs covering), there were 11 vs 4 cases with similar morphology, 2 vs 0 cases of perioperative death, and 3 vs 0 cases of recurrence, respectively. For the 2 groups(free vs covering), the SOFA score was 1.72 vs 1.0, postoperative chemotherapy enforcement rate was 55%vs 75%, start time was 59.4 days vs 40.3 days, and postoperative PMX implementation was 6 vs 0, respectively. All cases of recurrence and perioperative deaths were from the free perforation group. In free perforation, patients have a high risk of sepsis before surgery, and postoperative chemotherapy cannot be performed smoothly and completed. This leads to an increase in the relapse rate. It is important to select the appropriate operative method for curability and to perform postoperative chemotherapy without delay, especially in covering perforation.

Increased Risk for Meningococcal Disease Among Men Who Have Sex With Men in the United States, 2012-2015.

BACKGROUND: Several clusters of serogroup C meningococcal disease among men who have sex with men (MSM) have been reported in the United States in recent years. The epidemiology and risk of meningococcal disease among MSM is not well described. METHODS: All meningococcal disease cases among men aged 18-64 years reported to the National Notifiable Disease Surveillance System between January 2012 and June 2015 were reviewed. Characteristics of meningococcal disease cases among MSM and men not known to be MSM (non-MSM) were described. Annualized incidence rates among MSM and non-MSM were compared through calculation of the relative risk and 95% confidence intervals. Isolates from meningococcal disease cases among MSM were characterized using standard microbiological methods and whole-genome sequencing. RESULTS: Seventy-four cases of meningococcal disease were reported among MSM and 453 among non-MSM. Annualized incidence of meningococcal disease among MSM was 0.56 cases per 100000 population, compared to 0.14 among non-MSM, for a relative risk of 4.0 (95% confidence interval [CI], 3.1-5.1). Among the 64 MSM with known status, 38 (59%) were infected with human immunodeficiency virus (HIV). HIV-infected MSM had 10.1 times (95% CI, 6.1-16.6) the risk of HIV-uninfected MSM. All isolates from cluster-associated cases were serogroup C sequence type 11. CONCLUSIONS: MSM are at increased risk for meningococcal disease, although the incidence of disease remains low. HIV infection may be an important factor for this increased risk. Routine vaccination of HIV-infected persons with a quadrivalent meningococcal conjugate vaccine in accordance with Advisory Committee on Immunization Practices recommendations should be encouraged.