Epidemiology of endemic human coronavirus infection during the COVID-19 pandemic.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the coronavirus family that also includes endemic human coronaviruses (HCoVs) types OC43, HKU1, 229E, and NL63. HCoVs share extensive sequence homology with SARS-CoV-2. It has been assumed that HCoV infection occur primarily in winter and spring in Japan before the coronavirus disease 2019 (COVID-19) pandemic and that its frequency is the same for all age groups. METHODS: Nasopharyngeal swab samples were collected for HCoVs and SARS-CoV-2. All medical data were retrospectively analyzed. Our primary objective was to describe the epidemiology of HCoV in the Furano, Japan during the COVID-19 pandemic. Our secondary objective was to compare the prevalence of HCoV with that of SARS-CoV-2. RESULTS: From September 2020 to August 2022, 113 (6.2 %) of 1823 cases were positive for any HCoV. The HCoV-NL63 activity peaked in January-March 2021. The HCoV-OC43 activity peaked in June-August 2021. HCoVs were mostly detected at age ≤11 years and most frequently at age ≤2 years. HCoVs showed high detection in 2021, while SARS-CoV-2 showed moderate detection in 2020-2021, but significantly increased in 2022. CONCLUSIONS: During the COVID-19 pandemic, HCoV-OC43 activity peaked in the summer. The frequency of HCoV infection varied widely by age group and was higher among those aged ≤11 years. These were different from those reported before the COVID-19 pandemic. These findings suggest that the disease dynamics of HCoVs remain unclear and that continued surveillance is essential in the post-COVID-19 pandemic.

Clinical effectiveness of baloxavir marboxil against influenza in three seasons.

BACKGROUND: Previous reports have not clarified the difference in clinical efficacy between baloxavir and oseltamivir against influenza. METHODS: A prospective observational study was performed during 2017-2018, 2018-2019, and 2019-2020 influenza seasons. The primary endpoint of this study was to compare the duration of fever between patients who received baloxavir and those who received oseltamivir. RESULTS: A total of 235 influenza-infected patients (3-18 years of age), including 91 who received oseltamivir and 144 who received baloxavir, were enrolled. The proportions of influenza A(H3N2) virus, influenza A(H1N1)pdm09 virus, and influenza B virus-infected patients were 31.5%, 42.6%, and 26.0%, respectively. Patients who received oseltamivir were significantly younger than those who received baloxavir. Univariate analyses showed that the duration of fever was shorter with baloxavir than with oseltamivir against influenza virus overall, influenza A virus, influenza B virus, and influenza A(H1N1)pdm09 virus, but not for influenza A(H3N2) virus. In multivariate analyses, hazard ratios for influenza virus overall (0.53 [95% CI, 0.38-0.73]), influenza B virus (0.16 [95% CI, 0.07-0.41]), and influenza A(H1N1)pdm09 virus (0.55 [95% CI, 0.32-0.93]) were significantly lower in the patients who received baloxavir than those who received oseltamivir. However, the differences between influenza A virus and influenza A(H3N2) virus were not significant between the two groups. CONCLUSION: For influenza virus overall, influenza B virus, and influenza A(H1N1)pdm09 virus, baloxavir treatment resulted in shorter duration of fever than oseltamivir treatment, but not for influenza A virus and influenza A(H3N2) virus.

Comparison of Oropharyngeal and Nasopharyngeal Swab Specimens for the Detection of Mycoplasma pneumoniae in Children with Lower Respiratory Tract Infection.

The oropharyngeal swab specimen was superior to the nasopharyngeal swab specimen for the detection of Mycoplasma pneumoniae in children with lower respiratory tract infection. The oropharyngeal loop-mediated isothermal amplification had 100% sensitivity and specificity compared with polymerase chain reaction testing, whereas the oropharyngeal rapid antigen detection test using immunochromatographic assay had relatively low sensitivity (66%) and reasonable specificity (90.7%).

Clinical findings in 10 children with H275Y influenza A(H1N1)pdm09 virus infection.

BACKGROUND: Little is known about the clinical effectiveness of neuraminidase inhibitors against H275Y influenza A(H1N1)pdm09 virus. A cluster of H275Y influenza A(H1N1)pdm09 virus with cross-resistance to oseltamivir and peramivir was detected among untreated community patients in Hokkaido, Japan, during the 2013-2014 influenza season. METHODS: This was a retrospective observational study. Specimens from nasopharyngeal swabs underwent rapid testing and single-nucleotide polymorphism identification on real-time polymerase chain reaction. We collected clinical data from the H275Y group and a 275H wild-type comparison group. All children were given one of four neuraminidase inhibitors. RESULTS: Twenty-eight children infected with influenza A(H1N1)pdm09 virus were analyzed. Ten viruses had the H275Y substitution, while the other 18 had wild-type 275H. Mean fever duration after treatment and after onset was 25.3 h (95%CI: 14.1-36.5) and 48.9 h (95%CI: 34.4-63.3) in the H275Y group, respectively, and 26.1 h (95%CI: 18.7-33.6) and 46.3 h (95%CI: 35.7-56.8) in the 275H group, respectively. In the H275Y group, three patients were treated with oseltamivir, one with peramivir, five with zanamivir, and one with laninamivir. All of them had mild symptoms and received only outpatient care. Fever duration was 7.5-21.0 h and 18.0-66.0 h after treatment and after onset, respectively, in the patients treated with oseltamivir and peramivir, and 20.5-42.0 h and 42.0-88.0 h, respectively, in those treated with zanamivir and laninamivir. CONCLUSION: Fever in the H275Y children treated with oseltamivir and peramivir resolved rapidly during the 2013-2014 influenza season.

Prevalence of human T-lymphotropic virus type 1 carriers among pregnant women in Hokkaido, Japan.

As there is a risk of MTCT of HTLV-1, the HSGP HTLV-1 MTCT was organized in 2011. To determine how many pregnant women are infected with HTLV-1 in Hokkaido, which is the northernmost and the second largest island in Japan with a population of 5,467,000 and 39,392 newborns in 2011, the HSGP HTLV-1 MTCT asked all facilities that may care for pregnant women in Hokkaido in July 2013 to provide information on the number of pregnant women who underwent screening for anti-HTLV-1 antibody using particle agglutination or chemiluminescent enzyme immunoassay, and the numbers of those with positive, equivocal, and negative test results in the screening and confirmation tests using western blotting or PCR methods in 2012, respectively. A total of 111 facilities participated in this study and provided information on 33,617 pregnant women who underwent screening in 2012, corresponding to approximately 85% of all pregnant women who gave birth in Hokkaido in 2012. Of 81 candidates for a confirmation test because of positive (n = 77) or equivocal (n = 4) results on screening, 63 (78%) underwent the confirmation test and, finally, 34 (0.1%) and 33,563 (99.8%) women were judged to be HTLV-1 carriers and non-carriers, respectively. It was concluded that the prevalence rate of HTLV-1 carriers was low, one per 1000 pregnant women in Hokkaido. Approximately 40 infants are born yearly to mothers infected with HTLV-1 in Hokkaido.

Risk factors for human herpesvirus 6 reactivation and its relationship with syndrome of inappropriate antidiuretic hormone secretion after stem cell transplantation in pediatric patients.

There have been several reports on the reactivation of human herpesvirus 6 (HHV6) after stem cell transplantation (SCT) in adults, which sometimes induces severe illness. Few reports exist on pediatric patients; therefore, we retrospectively examined HHV6 reactivation after SCT in children. We reviewed 80 patients with a median age of 6 years. We analyzed HHV6 DNA serum samples from the patients before SCT and at 20 and 40 days after SCT using polymerase chain reaction. We also analyzed the relationship between HHV6 reactivation and the syndrome of inappropriate antidiuretic hormone secretion (SIADH). At 20 days after SCT, 35.0% of serum samples were positive for HHV6 DNA. The median viral load was 3.1×10 copies/mL serum. Multivariate analysis showed cord blood transplantation as the only risk factor for HHV6 reactivation. HHV6 reactivation occurs in 59.4% of 32 patients who underwent cord blood transplantation and in 18.8% of 48 patients who underwent SCT from other sources. Among the 14 patients with SIADH, 78.6% experienced HHV6 reactivation. Among the 66 patients without SIADH, only 25.8% had HHV6 reactivation. This result was statistically significant (P<0.001). This analysis revealed that HHV6 reactivation occurs in many children. In addition, HHV6 reactivation plus SIADH should prompt evaluation for central nervous system disease.

Risk factor analysis of bloodstream infection in pediatric patients after hematopoietic stem cell transplantation.

Bloodstream infection (BSI) is a recognized cause of morbidity and mortality in children after hematopoietic stem cell transplantation (HSCT). However, there are limited reports on BSI after HSCT in pediatric patients in multiple centers. This study was a retrospective cohort analysis of consecutive patients who underwent allogeneic and autologous HSCT at the Department of Paediatrics, Hokkaido University Hospital, between 1988 and 2009; the Department of Paediatrics, Sapporo Hokuyu Hospital, between 2007 and 2009; and the Department of Paediatrics, Asahikawa Medical University, between 1989 and 2009. A total of 277 patients underwent HSCT during the study period. In this multicenter analysis, cases of BSI after HSCT were recorded in the early posttransplant period (within the first 100 d), and BSI was observed in 24 of 277 HSCT patients. Multivariate analysis showed that nonmalignant disease was an independent factor associated with BSI after HSCT (hazard ratio 6.3 for aplastic anemia or Wiskott-Aldrich syndrome patients; confidence interval, 1.4-12.8; P = 0.012). We conclude that aplastic anemia and Wiskott-Aldrich syndrome were the novel risk factors for BSI in pediatric patients after HSCT.

[A case of metastatic lung cancer from colon cancer resected successfully after preoperative chemotherapy].

We describe a case of metastatic lung cancer from colon cancer resected successfully after preoperative chemotherapy. A 68-year-old male patient underwent low anterior resection for colon cancer in October 2004 (Stage III a), transcatheteric hepatic arterial embolization (TAE) for liver metastasis (S5) in October 2005, and partial hepatectomy (S5) in February 2006. Forty-seven months after surgery, lung metastases were detected. He was treated with bevacizumab plus FOLFOX/FOLFIRI, but the lung metastases progressed. Panitumumab plus FOLFIRI was performed and a partial response was obtained. Partial pulmonary resection was performed done in June 2011. It is necessary to add many cases to decide the value of prognostic factor, surgical indication and effectiveness of preoperative chemotherapy for lung metastasis of colorectal cancer.

Predictive Factors Among Clinicopathological Characteristics for Sentinel Lymph Node Metastasis in T1-T2 Breast Cancer.

BACKGROUND: The axillary lymph node status is an important prognostic factor of breast cancer. This study explores the predictive factors for sentinel lymph node (SLN) metastasis among the preoperative clinicopathological features, including impaired glucose tolerance (IGT). METHODS: This study comprised patients diagnosed with breast cancer who underwent surgery at Nagasaki Harbor Medical Center between April 2014 and December 2019. The factors assessed using univariate and multivariate analyses were the clinicopathological data of these cancers, including the patient age, gender, menstrual status, breast or ovarian cancer family history, body mass index, glycosylated hemoglobin, clinical tumor size, nipple-tumor distance (NTD), tumor histology, histological grade, node status, estrogen receptor, progesterone receptor, human epidermal growth factor receptor type 2 status, and Ki67 labeling index. RESULTS: In the cohort of 313 cases, the ratio of SLN metastasis was 17.3%. A univariate analysis found that the tumor size, NTD, IGT, and clinical tumor stage were associated with SLN metastasis. In a multivariable analysis, the tumor size, NTD, and IGT were associated with SLN metastasis. The receiver operating characteristic curve showed a sensitivity and specificity of 61.1% and 65.6%, respectively, at a cut-off of 1.7 cm for the tumor size (area under the curve [AUC]: 0.664; 95% confidence interval: 0.592-0.736), and a sensitivity and specificity of 60.4% and 62.9%, respectively, at a cut-off of 2.0 cm for NTD (AUC: 0.651; 95% confidence interval: 0.571-0.731) to predict the risk of SLN metastasis. CONCLUSION: T1 and T2 breast cancer patients with a larger tumor size, tumor located closer to the nipple, and IGT have a higher risk of SLN metastases than others.

The First Pediatric Patients with Coronavirus Disease 2019 (COVID-19) in Japan: Risk of Co-Infection with Other Respiratory Viruses.

Coronavirus disease 2019 (COVID-19) is a severe infectious disease of the respiratory tract caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2, and has a high mortality rate. The disease emerged from Wuhan, China, in late 2019, and spread to Japan, including Hokkaido, in January 2020. In February 2020, 3 children were diagnosed with COVID-19 in Furano, Hokkaido, Japan. During this period, influenza and human metapneumovirus infections were prevalent among children in the Furano region. Two of the 3 patients experienced co-infection with other respiratory viruses, including influenza virus A or human metapneumovirus. To the authors' knowledge, the cases described in the present report were the first pediatric patients with COVID-19 in Japan. In children with COVID-19, the possibility of co-infection with other respiratory pathogens should be considered.

Acute Pharyngitis Associated With Streptococcus dysgalactiae Subspecies equisimilis in Children.

BACKGROUND AND OBJECTIVES: The importance of Streptococcus dysgalactiae subsp. equisimilis (SDSE) in causing sporadic pharyngitis in children remains controversial. The aims of this study were (1) to report the incidence and (2) to compare the epidemiologic and clinical features of patients with SDSE to those with Streptococcus pyogenes (SP). METHODS: A prospective study was conducted on acute pharyngitis associated with SDSE in children over a 2-year period. SDSE was identified using a phenotypic method, M protein gene (emm) analysis and matrix-assisted laser desorption ionization-time of flight mass spectrometry. Patients with positive SDSE or SP cultures received cephalosporins for 5 days and were followed up. The emm genotyping and specific virulence genes analyses were performed. RESULTS: From 3416 throat cultures, 67 isolates (2.0%) were identified as SDSE and 515 (15.1%) were identified as SP. The mean age of patients with SDSE (8.3 years) was older than those with SP (6.6 years; P < 0.01). There was minimal seasonal variation in the isolation rates of SDSE. The febrile patients' rates, gender distribution, cervical lymph node adenopathy rates, hospitalization rates, eradication and failure rates and the nonsuppurative sequelae between patients with SDSE and SP were similar. All SDSE isolates possessed important virulence genes. The emm genotyping of SDSE showed high strain diversity. CONCLUSIONS: The incidence of acute pharyngitis associated with accurately identified SDSE was 2/15 of that with SP. Epidemiologic and clinical features of acute pharyngitis associated with SDSE are indistinguishable from those with SP, with the exception of age and seasonal variation.

Analysis of the Outcomes in Central Venous Access Port Implantation Performed by Residents via the Internal Jugular Vein and Subclavian Vein.

OBJECTIVE: The central venous access port (CVAP) has played an important role in the safe administration of chemotherapy and parenteral nutrition. The aim of the present study was to clarify the optimal access vein for CVAP implantation when performed by residents rather than attending surgeons. METHODS: A consecutive cases of CVAP implantation via the subclavian vein (SV) using a landmark-guided technique or via the internal jugular vein (JV) using an ultrasound-guided technique were divided into 2 groups according to whether the intervention was performed by a resident or an attending surgeon. Early and late complications were compared retrospectively between the 2 groups, and the outcomes of the CVAPs were compared between those implanted via the SV and those implanted via the JV in resident group. RESULTS: A total of 207 cases of CVAP implantation were performed. Overall, 114 implantations were performed by residents, and another 93 implantations were performed by attending surgeons. Early complications were seen more frequently in the resident group (6.1%) than in the attending-surgeon group (1.1%), but the difference was not significant. No differences in operating time or late complications were observed between the 2 groups. In the resident group, CVAP implantations via the JV using the ultrasound-guided technique were associated with a shorter operating time compared with the SV approach. CONCLUSIONS: Residents can perform CVAP implantations safely using both the SV and JV approaches. However, the JV approach using an ultrasound-guided technique can be performed in less time than the SV approach.

[A case of gallstone ileus which the cholecystoduodenal fistula closed spontaneously after laparoscopic-assisted simple enterolithotomy].

A 47-year-old woman complaining of diarrhea and vomiting was admitted on the suspicion of gallstone ileus 4 days after onset. Upper gastrointestinal radiography by Gastrografin showed a cholecystoduodenal fistula. Laparoscopic-assisted simple enterolithotomy was performed. The omentum was severely adherent to the gall bladder and fistula, though biliary surgery was not performed. Without second look operation, for cholecystoduodenal fistula closed spontaneously.

Detection of serum and intrahepatic hepatocyte growth factor during DEN-induced carcinogenesis in the rat.

We studied changes in serum levels of hepatocytes growth factor (HGF), as well as the levels of HGF expression in the livers, of rats with chemically-induced cancer. Rats were given diethylnitrosamine (DEN) orally in their drinking water. The serum HGF level was measured by enzyme-linked immunosorbent assay. The degree of HGF expression in liver, detected by immunoperoxidase staining, was classified from negative to high. For two DEN-treated rats, the nucleotide sequence of HGF DNA was determined from the livers containing cancerous foci (CA). The serum HGF levels tended to be higher in the DEN-treated rats than in the control rats. In the DEN-treated rats, low to moderate levels of expression of HGF were found in hepatocytes with strong atypia at 8, 12, and 14 weeks. Low levels of HGF expression were found in moderately differentiated cancer cells. The sequence of HGF showed the loss of three nucleotides, in comparison with a sequence reported previously. In conclusion, the results of this study suggest that HGF may contribute to hepatocarcinogenesis in chemically induced cancer in rats.

Spontaneous colon perforations associated with a vascular type of ehlers-danlos syndrome.

Ehlers-Danlos syndrome, vascular type (vEDS) (MIM #130050) is an autosomal dominant disorder caused by mutation in the type III collagen gene, COL3A1, leading to fragility of blood vessels, bowel and uterus that leads to spontaneous rupture. We report a previously undiagnosed vEDS patient with bowel complications. A 20-year-old female patient was referred to our hospital with abdominal pain. Computed tomography showed notable dilatation of the sigmoid colon with intraperitoneal fluid. Laparotomy revealed dilatation of the sigmoid colon, breakdown of serosa and muscularis propria of the sigmoid colon with impending perforation, and intra-abdominal hemorrhage caused by breakdown of the mesenterium. Resection of the sigmoid colon with Hartmann's pouch and an end colostomy were performed. Physical examination showed joint hypermobility, translucent skin with venous prominence and facial structure abnormalities. Genetic analysis using cDNA extracted from the patient's fibroblasts by reverse transcriptase polymerase chain reaction direct sequencing showed a missense mutation within the triple helix region of COL3A1 (c.2150 G>A; Gly717Asp).

Primary malignant fibrous histiocytoma of the ascending colon: report of a case.

We report a rare case of primary malignant fibrous histiocytoma (MFH) of the ascending colon. A 66-year-old man presented to our hospital with epigastralgia, and abdominal ultrasonography and computed tomography showed a large soft-tissue mass in the ascending colon. Barium enema and endoscopic examination showed a huge tumor in the ascending colon. At laparotomy, we found a tumor in the ascending colon and performed a right hemicolectomy with en bloc lymph node dissection. The resected specimen contained a tumor measuring 14.5 x 8.0 x 4.5 cm, the cut surface of which was yellowish. Based on histological and immunohistological studies, the tumor was diagnosed as MFH of the ascending colon. To our knowledge, only 20 cases of colorectal MFH, including our case, have been documented, which we review following this case report.

Chiral recognition in the binding of helicenediamine to double strand DNA: interactions between low molecular weight helical compounds and a helical polymer.

Binding of a helicene, 5,8-bis(aminomethyl)-1,12-dimethylbenzo[c]phenanthrene, to calf thymus DNA was studied using UV, CD, and fluorescence spectroscopy as well as calorimetry. The enantiomeric helicenes strongly bound to the double strand DNA possessing the right-handed helical structure. In addition, chiral recognition was observed in the binding, where the (P)-helicene with the right-handed helicity formed more stable complex than the (M)-helicene with the left-handed helicity. The binding studies of the helicenes and natural nucleosides by 1H NMR spectroscopy also revealed the higher affinity to the (P)-helicene. Both monomeric and polymeric nucleic acids thus turned out to favor the (P)-helicity.