Cellulitis with bacteremia due to multidrug-resistant Campylobacter jejuni in a case of agammaglobulinemia and bronchiectasis.

This case report demonstrates successful treatment outcomes without recurrence using fosfomycin for cellulitis with bacteremia caused by Campylobacter jejuni resistant to macrolides, fluoroquinolones, and tetracyclines in agammaglobulinemia and bronchiectasis. Whole-genome sequencing indicated the presence of ST137 harboring bla OXA-61 and tet(O), with mutations in the 23S rRNA and gyrA genes.

Analgesic effect of a lidocaine-ropivacaine mixture for extraction of impacted mandibular third molars: a randomized controlled trial.

OBJECTIVES: The painless postoperative period can be significantly prolonged by using long-acting local anesthetics such as ropivacaine, though these local anesthetics are known for their slower onset of action. To compensate for this, a mixture of short-onset (e.g., lidocaine) and long-acting local anesthetics is used. However, the efficacy of such an anesthetic cocktail has not been elucidated in the field of oral and maxillofacial surgery. MATERIALS AND METHODS: To address the research purpose, this prospective randomized controlled trial included 56 patients scheduled for impacted mandibular third molar extraction. All patients received the inferior alveolar nerve block (IANB) using either 2% lidocaine with epinephrine or a 1:1 mixture of 2% lidocaine with epinephrine and 0.75% ropivacaine. RESULTS: Patients anesthetized using the lidocaine-ropivacaine mixture showed significantly prolonged postoperative analgesia and pain control than those anesthetized using lidocaine only. CONCLUSIONS: IANB using a lidocaine-ropivacaine mixture can provide prolonged postoperative anesthesia and pain control with extraction of mandibular third molars. CLINICAL RELEVANCE: This method can be a noteworthy addition to existing methods of local anesthesia for the extraction of mandibular third molars. Trial registration number University Hospital Medical Information Network (No. UMIN000044315).

Evaluation of an immunochromatography-based rapid antigen test, Inspecter Kowa® SARS-CoV-2, using saliva specimens for the detection of SARS-CoV-2.

BACKGROUND: In the context of the coronavirus disease 2019 (COVID-19) pandemic, a rapid and reliable point-of-care test is an essential tool for controlling the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In particular, an immunochromatography test (ICT) that uses saliva specimens for rapid antigen detection not only reduces the risk of secondary infections but also reduces the burden on medical personnel. METHODS: The newly developed salivary antigen test kit "Inspecter Kowa® SARS-CoV-2" is an ICT to which saliva specimens can be directly applied. We evaluated its usefulness in comparison with reverse transcription quantitative PCR (RT-qPCR) and the Espline® SARS-CoV-2 Kit for the detection of SARS-CoV-2 using nasopharyngeal swab specimens. In this study, 140 patients with suspected symptomatic COVID-19 who visited our hospital were enrolled, and nasopharyngeal swab and saliva specimens were collected after they consented to participate in the study. RESULTS: Inspector Kowa SARS-CoV-2 was positive in 45 of 61 (73.8%) saliva that were positive by RT-qPCR and the Espline® SARS-CoV-2 Kit was also positive in 56 of 60 (93.3%) Np swabs that were positive by RT-qPCR. Good antigen detection was achieved by ICT with saliva and nasopharyngeal swab specimens when viral load was ≥105 copies/mL, whereas detection sensitivity was low when viral load was <105 copies/mL, especially in saliva specimens. CONCLUSION: This ICT for the detection of SARS-CoV-2 salivary antigen is an attractive tool that does not require specialized equipment and allows patients to perform the entire process from sample collection to self-diagnose and to reduce the burden on medical care during a pandemic.

DNA amplification tests at universal pre-admission screening with enhanced precaution strategies for asymptomatic patients with COVID-19.

Objective: To analyse the effect of hospital pre-admission screening and enhanced precaution strategies on the transmission of severe acute respiratory syndrome coronavirus-2. Methods: This retrospective cohort study was conducted over 17 months from 11 May 2020 to 30 September 2021 at a large hospital in Tokyo. Universal DNA amplification tests were conducted during pre-admission screening, and enhanced precaution strategies were implemented for all patients with negative admission tests. The primary outcome was the occurrence of symptomatic coronavirus disease 2019 (COVID-19) in patients after admission. The secondary outcomes were time-series analyses of monthly positive admission test numbers, positive rates, clinical features in positive cases, and clinically confirmed nosocomial transmission. Results: In total, 32,081 patients were screened pre-admission (29,556 asymptomatic patients and 2525 symptomatic patients). Of the asymptomatic patients, 0.11% (n=32) tested positive and were admitted to a designated COVID-19 ward or were not admitted. Among the five inpatients who developed symptomatic COVID-19 during hospitalization, only two cases were related to a single nosocomial transmission. Conclusion: Pre-admission test screening was effective in identifying asymptomatic cases of COVID-19. This allowed administrators to quarantine patients or delay hospital admission. The combination of testing and enhanced precaution strategies for asymptomatic cases of COVID-19 may minimize nosocomial transmission.

Comparison of methylprednisolone pulse vs conventional dexamethasone for adult cases of COVID-19 requiring oxygen; a Japanese retrospective cohort study.

BACKGROUND: Although dexamethasone is an effective treatment in cases of coronavirus disease 2019 (COVID-19) requiring oxygen, the efficacy of methylprednisolone pulse is unclear. We compared the characteristics and outcomes of methylprednisolone pulse to those of dexamethasone. METHODS: We conducted a retrospective cohort study on adult COVID-19 cases requiring oxygen and no invasive mechanical ventilation treated with methylprednisolone pulse (1 g/day for 3 days) or dexamethasone (6 mg/day orally or 6.6 mg/day intravenously for ≥5 days). The primary outcome was intensive care unit (ICU) admission. The secondary outcomes were hospital mortality, length of hospital stay (LoS), duration of oxygen requirement, and requirement for hospital transfer, vasopressor(s), intubation, extracorporeal membrane oxygenation (ECMO), and continuous renal replacement therapy (CRRT). RESULTS: Twenty two cases of methylprednisolone pulse and 77 cases of dexamethasone were included. Mask ventilation was more common in the methylprednisolone pulse group (P < 0.001). The proportion of ICU admissions was similar between both groups (P = 0.635). The secondary outcomes of hospital mortality and the requirement for hospital transfer, vasopressor(s), intubation, and CRRT were similar between groups. No cases received ECMO. Median LoS (P = 0.006) and duration of oxygen requirement (P = 0.004) were longer in the methylprednisolone pulse group. CONCLUSIONS: The proportion of ICU admissions was similar between the methylprednisolone pulse and the dexamethasone group. However, more cases in the methylprednisolone pulse group required mask ventilation than in the dexamethasone group, suggesting that some cases benefited from methylprednisolone pulse.

Case Report: Kampo Medicine for Non-tuberculous Mycobacterium Pulmonary Disease.

Background: While the number of pulmonary tuberculosis cases has decreased, increase in non-tuberculous mycobacterium pulmonary disease (NTM-PD) is a global problem. Guideline-based therapy for NTM-PD sometimes causes complications that prevent treatment completion, and there are many cases of relapse even if the treatment can be completed. In addition to antibacterial treatment, care of host risk factors, such as aging, lean physique and immunosuppressive state, is also very important for the management of NTM-PD. In Japan, Kampo medicine, a traditional Japanese herbal formulation, used alone or in combination with standard multidrug therapy for NTM-PD, has been found to be effective for such cases. Case Presentation: A 77-year-old lean woman had been diagnosed with Mycobacterium intracellulare pulmonary infection 6 years earlier, and had received the standard multidrug treatment 5 years later at a former hospital due to worsening of her symptoms of cough, breathlessness and hemoptysis. However, the treatment was discontinued within a year due to the development of adverse events. She refused the guideline-based antibacterial treatment, and asked for Kampo medicine instead. Bukuryoshigyakuto was subsequently prescribed, which led to cough and sputum, especially hemosputum, being well controlled. With 3 years of Kampo medicine treatment, she gained weight and her hemosputum disappeared. High-resolution computed tomography images showed improvement in her lung condition, and her sputum smear culture was negative for acid-fast bacillus. Conclusion: Various kinds of Kampo medicines have been used empirically for NTM-PD in Japan. A literature review from 1992 to 2020 showed that hozais, in particular, seem to be key drugs for the treatment of host NTM-PD risk factors. Kampo medicines can contribute to comprehensive treatment for NTM-PD management that does not rely solely on antibacterial drugs.

Japanese cedar pollen upregulates the effector functions of eosinophils.

BACKGROUND: Symptoms of rhinitis and asthma can be exacerbated during Japanese cedar pollen (JCP)-scattering season, even in subjects who are not sensitized to JCP, suggesting that innate immune responses may contribute to this process. We previously reported that house dust mite directly activates the effector functions of eosinophils. Similar mechanisms may play roles in the JCP-related aggravation of allergic diseases. OBJECTIVE: To investigate whether JCP or Cry j 1, a major allergen of JCP, can modify the effector functions of eosinophils. METHODS: Eosinophils isolated from the peripheral blood of healthy donors were stimulated with either JCP or Cry j 1, and their adhesion to human intercellular adhesion molecule-1 was measured using eosinophil peroxidase assays. The generation of eosinophil superoxide anion (O2 -) was measured based on the superoxide dismutase-inhibitable reduction of cytochrome C. Concentrations of eosinophil-derived neurotoxin in the cell media were measured by enzyme-linked immunosorbent assay as a marker of degranulation. RESULTS: Both JCP and Cry j 1 directly induced eosinophil adhesiveness, generation of O2 -, and release of eosinophil-derived neurotoxin. Both anti-αM and anti-ß2 integrin antibodies blocked all of these eosinophil functions induced by JCP and Cry j 1. Similarly, PAR-2 antagonists also partially suppressed all of these effector functions induced by JCP and Cry j 1. CONCLUSION: JCP and Cry j 1 directly activate the functions of eosinophils, and both αMß2 integrin and partly PAR-2 are contributed to this activation. Therefore, JCP-induced eosinophil activation may play a role in the aggravation of allergic airway diseases in nonsensitized patients as well as in JCP-sensitized patients.

Predictive Value of the Pneumonia Severity Score on Mortality due to Aspiration Pneumonia.

Objective: Designing an efficient management strategy for aspiration is of high priority in our aging society because of its high incidence. We evaluated the prognostic value of both the A-DROP (age, dehydration, respiratory, disorientation, and pressure) and the modified A-DROP scoring systems (adding respiratory rate and comorbidity to A-DROP) in patients with aspiration pneumonia.Design: This is a retrospective study using electronic medical records at Saitama Medical University (SMU) hospital.Setting: A 965-bed university tertiary medical center in Japan.Participants: Data were extracted from the electronic medical records of patients from SMU hospital.Methods: In-hospital mortality was compared between two groups: (1) those with a 'severe' to 'advanced severe' A-DROP score; and (2) those with a 'low' to 'middle' A-DROP score. Area under the curve (AUC) for mortality for both the A-DROP and modified A-DROP scoring systems were compared.Results: The in-hospital mortality rates for patients with a high and a low A-DROP score were 28.6% and 9.0%, respectively. The mortality rates in the high modified A-DROP score group and in the low modified A-DROP score group were 28.2% and 9.9%, respectively. These differences in the mortality rates between the two groups were statistically significant for both the A-DROP and the modified A-DROP scoring systems. The AUC of the receiver operating characteristics curve for the A-DROP (0.700; 95% confidence interval, 0.608-0.779) was statistically significant.Conclusion: The A-DROP and modified A-DROP scoring systems are associated with in-hospital mortality in patients with aspiration pneumonia. The A-DROP scoring system is easy to use and may be a clinically valuable tool in the management of aspiration pneumonia.

The Seasonality of Peripheral Venous Catheter-Related Bloodstream Infections.

INTRODUCTION: Although the seasonality of infectious diseases has been widely reported, the seasonality of peripheral venous catheter-related bloodstream infection (PV-CRBSI) has not been investigated. This study investigated the seasonality of PV-CRBSI and its relationship with meteorological conditions. METHODS: A retrospective cohort study of PV-CRBSI at Tokyo Medical University Hospital (Tokyo, Japan), from 2009 to 2019, provided the data for descriptive and time series analyses used to evaluate the number of PV-CRBSI cases per 1000 admissions that occurred each month for each causative organism. By performing univariate and multivariate analyses, the researchers investigated the seasonality of cases and the relationships between meteorological conditions, other external factors, and PV-CRBSIs. RESULTS: This study included a total of 184 PV-CRBSI cases. The mean numbers of PV-CRBSI cases per 1000 admissions caused by all organisms, Bacillus cereus, Gram-positive cocci, and Gram-negative rods were 0.67, 0.15, 0.37, and 0.16 per month, respectively, during the study period. The time series analysis showed that the incidences of PV-CRBSI cases associated with B. cereus and Gram-negative rods were significantly different in the winter/spring from those in the summer/autumn (P < 0.05). The incidence of PV-CRBSI cases caused by B. cereus peaked during summer. The incidence of PV-CRBSI cases caused by B. cereus was significantly positively associated with average monthly temperature, whereas the incidence of PV-CRBSIs caused by Gram-negative rods was significantly negatively associated with average daylight hours. CONCLUSION: The incidence of PV-CRBSIs caused by B. cereus showed seasonality, peaking during the summer, and a significant correlation was found between PV-CRBSIs caused by B. cereus and average monthly temperature.

Temperature-dependent fasciation mutants provide a link between mitochondrial RNA processing and lateral root morphogenesis.

Although mechanisms that activate organogenesis in plants are well established, much less is known about the subsequent fine-tuning of cell proliferation, which is crucial for creating properly structured and sized organs. Here we show, through analysis of temperature-dependent fasciation (TDF) mutants of Arabidopsis, root redifferentiation defective 1 (rrd1), rrd2, and root initiation defective 4 (rid4), that mitochondrial RNA processing is required for limiting cell division during early lateral root (LR) organogenesis. These mutants formed abnormally broadened (i.e. fasciated) LRs under high-temperature conditions due to extra cell division. All TDF proteins localized to mitochondria, where they were found to participate in RNA processing: RRD1 in mRNA deadenylation, and RRD2 and RID4 in mRNA editing. Further analysis suggested that LR fasciation in the TDF mutants is triggered by reactive oxygen species generation caused by defective mitochondrial respiration. Our findings provide novel clues for the physiological significance of mitochondrial activities in plant organogenesis.

Predictors of adherence to sublingual immunotherapy for Japanese cedar pollinosis: a prospective analysis.

BACKGROUND: Sublingual immunotherapy (SLIT) often has low adherence rates. OBJECTIVE: To provide effective support for SLIT continuation, we investigated potential predictors of SLIT adherence through a prospective analysis of patient characteristics. We excluded evaluation of treatment effect and symptoms during treatment, aiming instead to identify predictors of later dropout or insufficient adherence due to indolence or forgetfulness using only information obtained at initial examination. METHODS: We provided patients with a questionnaire and monitored self-reported adherence once every 6 months. Cases of dropout for clear reasons were excluded, but cases of dropout or insufficient adherence to SLIT for indolence or forgetfulness were included. RESULTS: Fifty-three patients receiving SLIT were assessed. Nine patients dropped out after providing a clear reason. Thirty-four patients maintained good adherence. Seven patients continued SLIT but with insufficient adherence, while three patients discontinued SLIT for unclear reasons (indolence or forgetfulness) and these ten individuals were classified as the poor-adherence group. Univariate analysis and multivariate logistic regression analysis of the good-adherence and poor-adherence groups showed age to be a significant predictor of SLIT adherence. Based on analysis of a receiver operating characteristic curve, age < 40.5 years was selected as the optimal cutoff value for predicting poor adherence to SLIT. CONCLUSIONS: To prevent treatment SLIT discontinuation on account of indolence or forgetfulness, the necessity of longterm treatment continuity should be communicated clearly prior to commencing treatment, especially for patients under 40 years of age.

First Report of Fatal Infection Caused by Community-acquired Methicillin-resistant Staphylococcus aureus USA300 Clone in a Collegiate Athlete.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is prevalent around the world and is a causative agent of skin and soft tissue infections in healthy individuals. Particularly, Panton-Valentine leukocidin (PVL)-positive CA-MRSA strains occasionally cause life-threatening infections, such as septic pulmonary emboli (SPE) and infectious endocarditis. However, severe infections caused by PVL-positive CA-MRSA strains have rarely been reported in Japan. For the first time, this study reports the case of a 20-year-old Japanese college athlete with life-threatening PVL-positive CA-MRSA USA300 clone infection, including sepsis, SPE, and skin and soft tissue infections with iliofemoral deep venous thrombosis.

A risk as an infection route: Nasal colonization of methicillin-resistant Staphylococcus aureus USA300 clone among contact sport athletes in Japan.

Panton-Valentine leukocidin (PVL)-positive USA300 clone is a highly pathogenic and global epidemic community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) clone. Athletes are particularly vulnerable to CA-MRSA infection because of the frequency of skin trauma, close-contact situations, and sharing of equipment that is customary in the athletic setting. We experienced a case of Japanese collegiate football player with septic pulmonary emboli secondary to infectious iliofemoral deep venous thrombosis caused by the USA300 clone. Here, we screened the nasal carriage of USA300 clone colonization among asymptomatic teammate of the patient to elucidate the infection route. Among 69 nasal samples, CA-MRSA strains were found in 5.8% (four samples). Molecular epidemiological analyses showed that three of the CA-MRSA strains were USA300 clone. Furthermore, pulsed-field gel electrophoresis revealed that all nasal USA300 clones showed 100% identity with the USA300 clone isolated from their teammate with critical infection. Our findings indicate that nasal colonization of the PVL-positive CA-MRSA, especially USA300 clone, pose a threat among contact sport athletes in Japan likewise other countries. An immediate infection control strategy for contact sport athletes is necessary to prevent outbreaks of PVL-positive CA-MRSA infections.

Identification of new pentatricopeptide repeat proteins, MREF1 and 2, involved in mitochondrial RNA editing, using computational target RNA prediction.

C-to-U RNA editing has been widely observed in mitochondrial and plastid RNAs in plants. The editing sites are known to be recognized by pentatricopeptide repeat (PPR) proteins, which belong to one of the largest protein families in vascular plants. PPR proteins are sequence-specific RNA-binding proteins that participate in various steps of organelle RNA metabolism, such as cleavage, stabilization, splicing, translation, and editing. Elucidating the underlying mechanisms of sequence-specific RNA recognition by PPR proteins expanded our understanding of the role of PPR proteins in plant organellar RNA editing and enabled the computational prediction of target RNA-editing sites for PPR proteins of interest. Combining computational prediction and experimental verification, we identified three new PPR proteins involved in mitochondrial RNA editing: At1g56570, known as PGN for RNA editing of nad6_leader_-73 and cox2_742, At4g04370 for RNA editing of nad5_242, and At2g41080 for atp1_1292. Therefore, At4g04370 and At2g41080 were designated as mitochondrial RNA-editing factor 1 (MREF1) and MREF2, respectively. This study supports the use of computational prediction in establishing connections between PPR proteins and specific RNA-editing sites, which are important for maintaining various physiological processes, such as plant development, embryogenesis, and biotic- and abiotic-stress responses.

Effects of ß2-adrenergic agonists on house dust mite-induced adhesion, superoxide anion generation, and degranulation of human eosinophils.

BACKGROUND: Even in subjects who are not sensitized to house dust mite (HDM), allergic symptoms can be clinically aggravated by exposure to dust. We previously reported that Dermatophagoides farinae (Df), an important HDM, or Der f 1, a major allergen of Df, induced the effector functions of eosinophils, which may be an important mechanism for HDM-induced symptoms in nonsensitized patients. In a clinical setting, ß2-adrenergic agonists, such as salbutamol and formoterol, are used for the treatment of asthma attacks or exacerbation to release the airway obstruction. Several reports have suggested that some ß2-adrenergic agonists have an anti-inflammatory capacity. OBJECTIVE: In this study, we investigated whether ß2-adrenergic agonist could modify the Df- or Der f 1-induced activation of eosinophils. METHODS: Blood eosinophils obtained from healthy donors were preincubated with either formoterol (1 µM), salbutamol (1 µM), or buffer control and then stimulated with Df extract (1 µg/mL) or Der f 1 (100 pg/mL). Eosinophil adhesion to intercellular adhesion molecule (ICAM)-1 was measured using eosinophil peroxidase assays. Generation of superoxide anion (O2 -) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) concentrations in cell media were measured by enzyme-linked immunosorbent assay. RESULTS: Formoterol, but not salbutamol, suppressed the Df- or Der f 1-induced eosinophil adhesion to ICAM-1. Furthermore, formoterol, but not salbutamol, suppressed Df-induced O2 - generation or EDN release. Neither formoterol nor salbutamol suppressed spontaneous eosinophil adhesion, O2 - generation, or EDN release. CONCLUSION: These findings suggested that formoterol, but not salbutamol, suppressed Df- or Der f 1-induced eosinophil activation when used at the same concentration. Therefore, formoterol could potentially be used for the treatment of bronchial asthma via both bronchodilation and anti-inflammatory effect.

Relationship between airway inflammation and airflow limitation in elderly asthmatics.

BACKGROUND: The prevalence of asthma in elderly population has been increasing. Previous studies have demonstrated clinical characteristics of elderly asthmatics (EA). However, little is known regarding the influence of immunological change on the physiological status of EA. OBJECTIVE: We investigated the relationship between inflammatory mediators and the pulmonary function (PF) of EA. METHODS: Eligible adult asthmatics recruited from the Allergy Center of Saitama Medical University Hospital were classified into a non-EA group (<40 years old, n = 15) and an EA group (≥60 years old, n = 43). Sputum induction and PF tests were performed. Concentrations of an eosinophil-derived neurotoxin (EDN) and neutrophil elastase (NE) in sputum supernatants were measured by enzyme-linked immunosorbent assay and a fluorometric assay using a commercial assay kit, respectively. Cell counts and EDN and NE concentrations in sputum were compared between the 2 groups. The association among those parameters and PF were analyzed in each group. RESULTS: The EA group had a significantly higher severe asthmatics proportion (p = 0.01), a lower current smokers proportion (p = 0.002), lower sensitization rate to aeroallergens (p = 0.012), several PFs deterioration (p < 0.0001) and lower total IgE levels (p = 0.001) than the non-EA group. Sputum neutrophil counts and NE concentrations were significantly higher in the EA group than those in the non-EA group (median neutrophil: 4.11 vs. 2.74 ×105/mL, p = 0.03; NE: 2.0 vs.1.6 µg/mL, p < 0.05, respectively), whereas sputum eosinophil counts and EDN concentrations were not. Sputum EDN concentrations were significantly positively correlated with sputum neutrophil counts (r = 0.39, p = 0.031) and NE concentrations (r = 0.57, p < 0.0001) only in the EA group. Eosinophil-related parameters were negatively correlated with several PFs in the 2 groups. Neutrophil-related parameters were negatively correlated with PFs only in the non-EA group. CONCLUSION: This study determines that in EA, persistent active eosinophilic airway inflammation is accompanied by advanced neutrophilic inflammation, which may contribute to deteriorated PF. This distinct airway inflammation may increase the severity of asthma in EA.

Persistent Legionella contamination of water faucets in a tertiary hospital in Japan.

OBJECTIVE: The feasibility of the decontamination procedure for Legionella pneumophila of water systems in healthcare facilities varies by water purification and disinfection methods in each country. We evaluated the efficacy of feasible decontamination strategies in Japan. METHODS: This study was conducted at Tokyo Medical University Hospital (1015 beds) between 2015 and 2018. Samples from the water system and cooling tower were cultured periodically. Hyper-chlorination of cool tap water (>0.2 ppm), increases in the temperature of hot water (>55 °C), and flushing were used as decontamination strategies. The case of healthcare-associated legionellosis was surveyed. Environmental and clinical isolates were genotyped. RESULTS: 1439 environmental samples were collected; 19 (1.3%) samples tested positive for L. pneumophila from water faucets of patient rooms, toilets, waste rooms, and water sourced from wells. Genotyping of 12 isolates confirmed that the same strains were present in eight environmental isolates and two isolates from patients over three years. Although the environmental contamination of the water system was persistent, the number of positive locations of hospital environments gradually decreased; eight in 2015, four in 2016, three in 2017, and four in 2018, respectively. CONCLUSIONS: Monitoring contamination, hyper-chlorination, controlling temperature, and flushing were effective as a Legionella decontamination strategy.