Traditional Japanese herbal medicine Hochuekkito protects development of sepsis after nasal colonization in mice.

INTRODUCTION: Streptococcus pneumoniae, a commensal in the nasopharynx, can cause invasive pneumococcal diseases (IPDs). To prevent the aggravation of IPDs, it is important to enhance host immune defense against S. pneumoniae. Hochuekkito (HET) is expected to have an immunostimulatory effect against infections. METHODS: HET was administrated by gavage to adult BALB/cA mice before and after intranasal inoculation of S. pneumoniae. We evaluated the effect of HET on pneumococcal nasal colonization and subsequent development of lethal pneumococcal infections. RESULTS: No effect on nasal colonization was observed, but HET significantly reduced bacterial count in the blood, decreased the incidence of bacteremia, and improved survival. HET also reduced nasal tissue damage 3 days after intranasal infection. Neutrophils from HET-treated mice showed significantly higher bactericidal activity against S. pneumoniae in the presence of the serum from the HET group compared with from the control group. CONCLUSIONS: The non-specific immunostimulatory effect of HET is suggested by this study to be effective in preventing the progression in IPDs and provided insights into novel strategy in the post-pneumococcal vaccine era.

Factors affecting the antimicrobial changes during treatment for acute otitis media in Japan: A retrospective cohort study using classification and regression trees (CART) analysis.

OBJECTIVES: Factors that affect the change of first-line antimicrobial agents were investigated to further promote their appropriate use. METHODS: This descriptive study used an electronic medical records database. Total 16,353 of the 199,896 patients enrolled between 1996 and 2019 met the inclusion criteria and formed the overall pediatric acute otitis media (AOM) cohort. The factors leading to the change in first-line antimicrobial agents within 14 days were analyzed using classification and regression trees (CART) analysis. RESULTS: This antimicrobial treatment cohort, involved 4860 cases of AOM alone and 9567 cases of AOM with other diseases. The size of the medical facility based on number of beds and historical duration of patient registration impacted on antimicrobial changes. CONCLUSIONS: The current results show that hospital-wide or nation-wide antimicrobial stewardship promotion could be the most influencing factor for antimicrobial changes. Particularly in cases of AOM where other diseases coexist, a more accurate diagnosis and definition of treatment failure of first-line drug are suggested to be important while establishing future treatment strategies. The current study is important to promote appropriate antimicrobial use for AOM treatment.

A rapid simultaneous antigen detection of Haemophilus influenzae and Streptococcus pneumoniae for predicting the prognosis of acute otitis media.

BACKGROUND: Rapid identification of causative bacteria in treatment of acute otitis media (AOM) is of paramount importance for appropriate antibiotic use. MATERIALS AND METHODS: This prospective observational study was conducted in 15 hospitals and clinics in Japan between 2018 and 2020. A new rapid antigen test kit (AOS-116), which simultaneously detects antigens for Streptococcus pneumoniae (Sp) and Haemophilus influenzae (Hi), was applied for middle ear fluids (MEFs) and nasopharyngeal secretions (NPSs) in patients with moderate to severe AOM. We investigated relationship between the results of rapid test, severity at initial visit, and clinical course. RESULTS: Regarding performance accuracy based on culture results, AOS-116 showed 1) high (>80%) sensitivity, specificity, and negative predictive value (NPV) in MEFs for both antigens, 2) high sensitivity, specificity, and positive predictive value (PPV) in NPSs for Hi antigen, and 3) high specificity, and PPV in NPSs for Sp antigen. Regarding predictive value of nasopharyngeal culture and antigen detection for causative middle ear pathogens, similar results were observed between AOS-116 and culture, which was characterized with high sensitivity and NPV for both pathogens. MEFs/NPSs positive for Hi antigen were significantly associated with eardrum findings, and severity. MEFs/NPSs positive for pneumococcal antigen were significantly associated with severity of otalgia, fever, and otorrhea. Among patients with prior antimicrobial treatment, improvement tended to be slower in cases positive for Hi than in cases negative. CONCLUSION: The rapid antigen detection test is useful as a decision-making tool for prescribing antimicrobial agents and may play an important role in promoting appropriate antimicrobial use.

The Roles of Transient Receptor Potential Vanilloid 1 and 4 in Olfactory Regeneration.

Olfactory disorders, which are closely related to cognitive deterioration, can be caused by several factors, including infections, such as COVID-19; aging; and environmental chemicals. Injured olfactory receptor neurons (ORNs) regenerate after birth, but it is unclear which receptors and sensors are involved in ORN regeneration. Recently, there has been great focus on the involvement of transient receptor potential vanilloid (TRPV) channels, which are nociceptors expressed on sensory nerves during the healing of damaged tissues. The localization of TRPV in the olfactory nervous system has been reported in the past, but its function there are unclear. Here, we investigated how TRPV1 and TRPV4 channels are involved in ORN regeneration. TRPV1 knockout (KO), TRPV4 KO, and wild-type (WT) mice were used to model methimazole-induced olfactory dysfunction. The regeneration of ORNs was evaluated using olfactory behavior, histologic examination, and measurement of growth factors. Both TRPV1 and TRPV4 were found to be expressed in the olfactory epithelium (OE). TRPV1, in particular, existed near ORN axons. TRPV4 was marginally expressed in the basal layer of the OE. The proliferation of ORN progenitor cells was reduced in TRPV1 KO mice, which delayed ORN regeneration and the improvement of olfactory behavior. Postinjury OE thickness improved faster in TRPV4 KO mice than WT mice but without acceleration of ORN maturation. The nerve growth factor and transforming growth factor ß levels in TRPV1 KO mice were similar to those in WT mice, and the transforming growth factor ß level was higher than TRPV4 KO mice. TRPV1 was involved in stimulating the proliferation of progenitor cells. TRPV4 modulated their proliferation and maturation. ORN regeneration was regulated by the interaction between TRPV1 and TRPV4. However, in this study, TRPV4 involvement was limited compared with TRPV1. To our knowledge, this is the first study to demonstrate the involvement of TRPV1 and TRPV4 in OE regeneration.

Bactericidal effect of lascufloxacin on HEp-2 cell-internalized group A Streptococcus.

INTRODUCTION: Although amoxicillin (AMPC) is recommended as first-line therapy for acute pharyngotonsillitis caused by group A streptococci (GAS), it often fails to eradicate infections. Internalization and subsequent intracellular survival of GAS are considered major mechanisms for penicillin therapeutic failure. It is, therefore, desirable to administer drugs that exert bactericidal effects on extracellular and intracellular GAS. In this study, we aim to investigate the bactericidal effects of lascufloxacin (LSFX) on internalized GAS in HEp-2 cells. MATERIALS AND METHODS: The GAS strain M1 and clinical isolate strain #2 were used in this study. Following treatment of GAS-infected human pharyngeal carcinoma epithelial HEp-2 cells with LSFX or AMPC, internalized GAS cells were recovered. The concentrations of LSFX and AMPC were equivalent to 1 × and 2 × MIC for strain M1. Culture medium was used as a control. Time-lapse and fluorescence images of GAS invading HEp-2 cell were obtained. LIVE/DEAD fluorescence staining was used to confirm the viability of internalized GAS. RESULTS: LSFX significantly reduced the number of cell-internalized M1 and #2 GAS strains compared to the control (p < 0.01) in a dose-dependent manner. However, AMPC did not reduce this in both strains. Both live and dead intracellular GAS were confirmed in HEp-2 cells exposed to LSFX. In contrast, intracellular GAS survived in HEp-2 cells exposed to AMPC and in the control. CONCLUSION: LSFX elicits significant bactericidal effects on cell-internalized GAS, hence it may represent a potent therapeutic option for patients with acute pharyngotonsillitis in whom AMPC treatment has failed.

Improvement of Surgical View and Working Space at the Lower Pole by Three-Dimensional Exoscope-Assisted Coblation Tonsillectomy: A Case Series.

Advantages of hot devices for tonsillectomy, represented by coblation, have been highlighted in recent years. During hot technique tonsillectomy it is important to identify and coagulate the vessels of the tonsillar capsule, especially at the lower pole of the tonsil. Hot technique tonsillectomy under microscope or endoscope has therefore been recommended to achieve accurate identification of the microstructure of the surgical field. We have applied ORBEYE, a three-dimensional surgical exoscope system, to coblation tonsillectomy. Advantages of using ORBEYE include high definition and high magnification images, and flexibility of camera position and angle. This means there is an improved surgical view and working space, particularly at the lower pole during performance of coblation tonsillectomy. Here, we demonstrate that ORBEYE can be an effective surgical instrument in coblation tonsillectomy.

Chondroma Arising from the Temporomandibular Joint: A Case Report.

Periarticular chondromas are common in the humerus and femur but rarely occur in the temporomandibular joint. We report a case of a chondroma in the anterior part of the ear. One year prior to his visit, a 53-year-old man became aware of swelling in the right cheek region which gradually increased in size. In the anterior part of the right ear, there was a palpable 25 mm tumor, elastic and hard, with poor mobility and without tenderness. A contrast-enhanced computed tomography CT showed a mass lesion with diffuse calcification or ossification in the upper pole of the parotid gland and areas of poor contrast within. A magnetic resonance imaging showed a low-signal mass lesion at the parotid gland with some high signals in both T1 and T2. Fine-needle aspiration cytology did not lead to diagnosis. Using a nerve monitoring system, the tumor was resected with normal tissue of the upper pole of the parotid gland in the same way as for a benign parotid tumor. Distinguishing between pleomorphic adenoma, including diffuse microcalcification of the parotid gland and cartilaginous tumors of the temporomandibular joint, may be sometimes difficult. In such cases, surgical resection may be a beneficial treatment option.

A Novel Pneumococcal Surface Protein K of Nonencapsulated Streptococcus pneumoniae Promotes Transmission among Littermates in an Infant Mouse Model with Influenza A Virus Coinfection.

We established an infant mouse model for colonization and transmission by nonencapsulated Streptococcus pneumoniae (NESp) strains to gain important information about its virulence among children. Invasive pneumococcal diseases have decreased dramatically since the worldwide introduction of pneumococcal capsular polysaccharide vaccines. Increasing prevalence of nonvaccine serotypes, including NESp, has been highlighted as a challenge in treatment strategy, but the virulence of NESp is not well understood. Protective strategies against NESp colonization and transmission between children require particularly urgent evaluation. NESp lacks capsules, a major virulence factor of pneumococci, but can cause a variety of infections in children and older people. PspK, a specific surface protein of NESp, is a key factor in establishing nasal colonization. In our infant mouse model for colonization and transmission by NESp strains, NESp could establish stable nasal colonization at the same level as encapsulated serotype 6A in infant mice and could be transmitted between littermates. Transmission was promoted by NESp surface virulence factor PspK and influenza virus coinfection. However, PspK deletion mutants lost the ability to colonize and transmit to new hosts. Promotion of NESp transmission by influenza was due to increased susceptibility of the new hosts. PspK was a key factor not only in establishment of nasal colonization but also in transmission to new hosts. PspK may be targeted as a new candidate vaccine for NESp infection in children.

Impact of the practical guideline on appropriate usage of antimicrobial treatments for surgical site infections in reconstructive surgery of head and neck cancer.

OBJECTIVES: In 2016, Japanese Society of Chemotherapy and Japan Society for Surgical Infection presented the practical guideline for appropriate usage of antimicrobial agents to prevent postoperative infections. This study aims to exhibit the validity of the guideline as a series of effective strategies for prevention of surgical site infections (SSIs) during reconstructive surgery of the head and neck cancer. METHODS: We retrospectively evaluated patients who underwent head and neck reconstructive surgery with free or pedicle flaps in a single institute in Japan between July 2010 and July 2020. We evaluated the incidence of SSIs, patient backgrounds, and microbiological characteristics on the basis of antimicrobial prophylaxis recommended by the guideline. RESULTS: Enrolled in this study were 102 patients in our institution who underwent head and neck reconstructive surgery with free or pedicle flaps between July 2010 and July 2020. In the period between January 2018 to July 2020 after the SSI guideline was advocated (SSI guideline period), the ratio of administration of sulbactam/ampicillin (SBT/ABPC) was significantly higher (P < 0.001) and the duration of prophylactic antimicrobial treatment was significantly shorter than in the period between July 2010 to December 2017 before the SSI guideline was advocated (Pre-SSI guideline period) (P < 0.001). Incidence of SSIs were similar, even when antibiotic use was changed to be short-term single-agent administration in accordance with the practical guideline. CONCLUSIONS: Adherence to the current Japanese practical guideline on appropriate antimicrobial prophylaxis for SSIs can shorten the duration of usage of antimicrobial treatment without increasing the risk for occurrence of SSIs.

Respiratory quinolones can eradicate amoxicillin-induced mature biofilms and nontypeable Haemophilus influenzae in biofilms.

OBJECTIVES: Biofilm is thought to be involved in the persistent bacterial infections caused by nontypeable Haemophilus influenzae (NTHi). This study aims to evaluate the efficacy of antibiotics against NTHi biofilms. METHODS: A 96-wells pin replicator assay was applied for evaluation of antimicrobial efficacies against NTHi biofilms. The NTHi IH-202 strain for the standard and 10 clinical strains were evaluated, as well as the viability of NTHi in biofilms after antimicrobial exposures. RESULTS: Biofilms formed by IH-202 strain accumulated during incubation. AMPC if not high concentrations, neither reduce or inhibit biofilm formation, nor eradicate matured NTHi biofilms. The NTHi in matured biofilm were alive after exposure to amoxicillin (AMPC). Even high concentration of AMPC produced live NTHi after suspension of exposure, while tosufloxacin and garenoxacin inhibited biofilm formation of NTHi and eradicated matured biofilms. The respiratory quinolones, but not AMPC, killed NTHi in biofilms even at sub-MIC. CONCLUSIONS: NTHi persists in biofilms, even after exposure to AMPC. These findings may eventually lead to a better understanding of effective use of antibiotics to eradicate NTHi growing as biofilms, or even to the development of novel therapeutic agents for treating patients with mucosal NTHi biofilm infections. Meanwhile, respiratory quinolones are attractive agents in reducing NTHi biofilm formation and destroying established biofilm.

Investigation on the virulence of non-encapsulated Streptococcus pneumoniae using liquid agar pneumonia model.

INTRODUCTION: Since the introduction of pneumococcal conjugate vaccine, there have been warnings of an increase in infections caused by non-vaccine type of Streptococcus pneumoniae strains. Among them, nonencapsulated Streptococcus pneumoniae (NESp) has been reported to cause invasive infections, especially in children and the elderly. Due to low virulence, however, basic experimental reports on invasive infections are limited. METHODS: We applied a liquid-agar method to establish a mouse model of invasive NESp infection. Mice were intratracheally administered a bacterial suspension including agar. With this technique, we investigated the pathogenicity of NESp and the effect of Pneumococcal surface protein K (PspK), a specific surface protein antigen of NESp. NESp wild-type strain (MNZ11) and NESp pspK-deleted mutant strain (MNZ1131) were used in this study. The survival rate, number of bacteria, cytokine/chemokine levels in the bronchoalveolar lavage fluid, and histology of the lung tissue were evaluated. RESULTS: Mice that were intratracheally administered MNZ11 developed lethal pneumonia with bacteremia within 48 h. Conversely, MNZ1131 showed predominantly low lethality without significant pro-inflammatory cytokine production. NESp was found to cause severe pneumonia and bacteremia upon reaching the lower respiratory tract, and PspK was a critical factor of NESp for developing invasive infections. CONCLUSIONS: The current study demonstrated the ability of NESp to develop invasive diseases, especially in connection with PspK by use of a mouse pneumonia model.

Pneumococcal capsular phase shift is associated with invasion into cell-to-cell junctions and is inhibited by macrolides.

Streptococcus pneumoniae frequently colonizes the human nasopharynx beginning in the early childhood. Pneumococci exhibit a spontaneous and reversible phase shift between opaque and transparent allowing them to adapt to different environments. This is the first report of the dynamics of pneumococcal phase shift during the course of adhesion and subsequent invasion into epithelial cell monolayers by bacteria-cell co-culture assay with a time-lapse microscopy. The invasion of an inoculum between the human epithelial cells was dependent on the transparent phenotype, but successful replication of the cells within the cell layer was strongly associated with its transformation into an opaque-like variant. We also observed that sub-MIC levels of clarithromycin inhibited the spontaneous pneumococcal phase shift. Our results show that the pneumococcus can modulate its fitness in part because it can switch phenotype in response to the environment during not only inflammation but also during the establishment of colonization. Our current findings provide a more in depth understanding not only of how the pneumococcal phase shift acts to protect pneumococci from commensal flora and the immune status of the host, but also illustrate a novel strategy for antimicrobial treatments to interfere with pneumococcal colonization.

Improvement in the appropriate antimicrobial usage for treating pediatric acute otitis media in Japan: A descriptive study using nation-wide electronic medical record data.

OBJECTIVES: We investigated changes in prescriptions for antimicrobial agents to treat children with acute otitis media (AOM). METHODS: A descriptive study using an electronic medical record database. Of 199,896 patients enrolled between 2001 and 2019, a total of 10,797 were aged <16 years and had AOM as their first and primary disease (overall pediatric AOM cohort). In addition, 4786 patients with AOM without other comorbidities (pediatric AOM cohort) were included. RESULTS: In the overall pediatric AOM cohort, the age distribution ranged from 11% to 23% for those younger than 2 years and from 66% to 77% for those younger than 6 years, with no change over time. In the pediatric AOM cohort, the antimicrobial prescription rate was 91% in 2001 but declined to 40% by 2019. Antimicrobial use increased from 0% to 75% for penicillins, whereas use of cephalosporins decreased from 84% to 10%. The prescription rate for acetaminophen alone increased from 33% to 58%. There were no differences in the incidence of adverse reactions among the prescribed antimicrobials. CONCLUSIONS: Due to education efforts and promotion of the proper use of antimicrobials through means such as the Clinical practice guidelines for the diagnosis and management of acute otitis media in children (2006) and the Manual of Antimicrobial Stewardship (2016), a change in the use of antimicrobials occurred, leading to a trend to more proper use of these agents.

Features predicting treatment failure in pediatric acute otitis media.

OBJECTIVES: To facilitate better antibiotic stewardship, we conducted this clinical trial to identify the prognostic features of treatment failure in pediatric acute otitis media (AOM). STUDY: Design: This is a randomized, parallel-group, open-label, comparative clinical trial. SUBJECTS AND METHODS: Children with AOM and aged between 1 month and 5 years were enrolled. Patients were randomly assigned to receive either amoxicillin alone (70 mg/kg) for five days, or the same with additional clarithromycin (15 mg/kg) for the initial three days. The clinical course of AOM was evaluated based on tympanic membrane scores. Failure of treatment for AOM was confirmed on day 14. Nasal conditions were also assessed by a clinical scoring system for acute rhinosinusitis. RESULTS: Treatment failures occurred in 25 out of 129 (19.4%) children. The ratio of treatment failures by age was significantly higher in children younger than 2 years than in children older than 2 years. The tympanic membrane scores on day 3 (P = 0.0334) and day 5 (P < 0.0001) and acute rhinosinusitis scores on day 5 (P = 0.0004) were higher in failure cases than in cured cases. Multivariate logistic regression analysis indicated significant associations between the treatment failure with tympanic membrane scores and acute rhinosinusitis scores on day 5, and the antimicrobial treatment regimen. CONCLUSIONS: Improvement of acute rhinosinusitis and tympanic membrane scores on day five were important predictive features in failure of treatment for pediatric AOM. These results will be useful when discussing the treatment decisions with the patient's parents.

Single Cell Bottlenecks in the Pathogenesis of Streptococcus pneumoniae.

Herein, we studied a virulent isolate of the leading bacterial pathogen Streptococcus pneumoniae in an infant mouse model of colonization, disease and transmission, both with and without influenza A (IAV) co-infection. To identify vulnerable points in the multiple steps involved in pneumococcal pathogenesis, this model was utilized for a comprehensive analysis of population bottlenecks. Our findings reveal that in the setting of IAV co-infection the organism must pass through single cell bottlenecks during bloodstream invasion from the nasopharynx within the host and in transmission between hosts. Passage through these bottlenecks was not associated with genetic adaptation by the pathogen. The bottleneck in transmission occurred between bacterial exit from one host and establishment in another explaining why the number of shed organisms in secretions is critical to overcoming it. These observations demonstrate how viral infection, and TLR-dependent innate immune responses it stimulates and that are required to control it, drive bacterial contagion.

Infant Mouse Model for the Study of Shedding and Transmission during Streptococcus pneumoniae Monoinfection.

One of the least understood aspects of the bacterium Streptococcus pneumoniae (pneumococcus) is its transmission from host to host, the critical first step in both the carrier state and the disease state. To date, transmission models have depended on influenza A virus coinfection, which greatly enhances pneumococcal shedding to levels that allow acquisition by a new host. Here, we describe an infant mouse model that can be utilized to study pneumococcal colonization, shedding, and transmission during bacterial monoinfection. Using this model, we demonstrated that the level of bacterial shedding is highest in pups infected intranasally at age 4 days and peaks over the first 4 days postchallenge. Shedding results differed among isolates of five different pneumococcal types. Colonization density was found to be a major factor in the level of pneumococcal shedding and required expression of capsule. Transmission within a litter occurred when there was a high ratio of colonized "index" pups to uncolonized "contact" pups. Transmission was observed for each of the well-colonizing pneumococcal isolates, with the rate of transmission proportional to the level of shedding. This model can be used to examine bacterial and host factors that contribute to pneumococcal transmission without the effects of viral coinfection.

Reduction of cortical excitability and increase of thalamic activity in a low-frequency rTMS treatment for chronic tinnitus.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) has received increasing attention for the treatment of tinnitus, but its therapeutic mechanisms are unclear. We performed low-frequency rTMS treatment for a patient with chronic tinnitus and examined changes of cortical excitability and cerebral blood flow using paired-pulse TMS and single-photon emission computed tomography. After the rTMS treatment, tinnitus loudness was decreased, cortical excitability was reduced, and blood flow in the thalamus was increased. Our results suggest that low-frequency rTMS treatment reduces tinnitus loudness by an inhibitory effect on the cortical excitability and a remote activation effect on the thalamus through the corticothalamic networks.

Genetic characteristics of Haemophilus influenzae and Streptococcus pneumoniae isolated from children with conjunctivitis-otitis media syndrome.

Acute conjunctivitis is the most common ocular disorders among children and frequently concomitant with acute otitis media (AOM) as conjunctivitis-otitis syndrome. In this study, we evaluated prevalence of causative pathogens and PCR-based genotypes of Haemophilus influenzae and Streptococcus pneumoniae among children with conjunctivitis-otitis media syndrome. Nontypeable H. influenzae (NTHi) is identified most often at 61.8% in conjunctiva exudates followed by S. pneumoniae at 28.2% and Moraxella catarrhalis at 19.1%. Genetic ß-lactamase nonproducing ampicillin resistant (gBLNAR) strains of NTHi and genetic penicillin resistant S. pneumoniae (gPRSP) were identified at 72.1% and at 74.2% among conjunctiva isolates by polymerase chain reaction (PCR), respectively. Pneumococcal strains having either ermB or mefE genes were identified at 93.5% among conjunctiva isolates. The restriction fragment of patterns of 89.7% pairs of H. influenzae isolates and 100% pairs of pneumococcal isolates from conjunctiva exudates, middle ear fluids (MEFs) and nasopharyngeal swabs were identical. In contrast to the previous reports, most prevalent strains from conjunctivitis-otitis media syndrome was BLNAR H. influenzae in this study. The causative pathogen responsible for acute conjunctivitis will be originated from the nasopharynx. In the absence of MEFs one can possibly rely on the nasopharyngeal culture to guide an appropriate treatment.

Nucleic acid sensing Toll-like receptors 3 and 9 play complementary roles in the development of bacteremia after nasal colonization associated with influenza co-infection.

Streptococcus pneumoniae can cause mortality in infant, elderly, and immunocompromised individuals owing to invasion of bacteria to the lungs, the brain, and the blood. In building strategies against invasive infections, it is important to achieve greater understanding of how the pneumococci are able to survive in the host. Toll-like receptors (TLRs), critically important components in the innate immune system, have roles in various stages of the development of infectious diseases. Endosomal TLRs recognize nucleic acids of the pathogen, but the impact on the pneumococcal diseases of immune responses from signaling them remains unclear. To investigate their role in nasal colonization and invasive disease with/without influenza co-infection, we established a mouse model of invasive pneumococcal diseases directly developing from nasal colonization. TLR9 KO mice had bacteremia more frequently than wildtype in the pneumococcal mono-infection model, while the occurrence of bacteremia was higher among TLR3 KO mice after infection with influenza in advance of pneumococcal inoculation. All TLR KO strains showed poorer survival than wildtype after the mice had bacteremia. The specific and protective role of TLR3 and TLR9 was shown in developing bacteremia with/without influenza co-infection respectively, and all nucleic sensing TLRs would contribute equally to protecting sepsis after bacteremia.

Contrast-Enhanced MRI Is Useful for Prognostic Prediction on Idiopathic Bilateral Simultaneous Facial Nerve Palsy: A Case Report and Literature Review.

Idiopathic bilateral facial nerve palsy is a rare condition and presents a diagnostic and prognostic challenge. Specifically, when bilateral nerves are damaged, it is difficult to predict the prognosis. We showcase the usefulness of contrast-enhanced magnetic resonance imaging (MRI) by providing information about localization and severity of degeneration of facial nerve. A 70-year-old Japanese man presented with bilateral simultaneous facial nerve palsy of House-Brackmann Grade VI on both sides. Contrast-enhanced MRI revealed bilateral intensity enhancement of intratemporal facial nerves. The signal intensity was higher on the left side than on the right side. Facial nerve decompression was performed on the left side. The left facial nerve palsy was finally improved eight months after the onset, while the right side was improved just under two months after the onset. Contrast-enhanced MRI for facial nerve palsy can provide valuable information for the evaluation of damaged facial nerves. In our patient's case, it was useful as a prognostic predictor of bilateral facial nerve palsy.