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.

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.

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.

A rare case of Pseudomonas aeruginosa enteritis induced by pembrolizumab.

A 72-year-old male had pseudomonal enteritis related to pembrolizumab. Chemotherapy for hypopharyngeal carcinoma with lung metastasis comprised cisplatin, 5-FU, and pembrolizumab. On day 14 of chemotherapy treatment he had a sudden prominent abdominal bulge, decreased consciousness, and drop in blood pressure in septic shock. CT scan showed marked intestinal gas through to intrahepatic bile ducts. Pseudomonas aeruginosa was simultaneously detected in both blood and stool cultures. Intestinal endoscopy revealed ulcerative lesions from the transverse colon to the rectum. Pathological investigations indicated apoptosis of the villus. The patient was diagnosed with pseudomonal enteritis induced by immune-related adverse events from the use of pembrolizumab. Treatment by corticosteroid and meropenem were subsequently switched to cefepime and metronidazole, and this successfully improved his colitis. In this new era of biological-targeted drugs and as clinical experience grows, we recommend a high level of alertness for potential diagnosis of infectious complications.

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.

The Roles of Transient Receptor Potential Vanilloid 1 and 4 in Pneumococcal Nasal Colonization and Subsequent Development of Invasive Disease.

Transient receptor potential (TRP) channels, neuronal stimulations widely known to be associated with thermal responses, pain induction, and osmoregulation, have been shown in recent studies to have underlying mechanisms associated with inflammatory responses. The role of TRP channels on inflammatory milieu during bacterial infections has been widely demonstrated. It may vary among types of channels/pathogens, however, and it is not known how TRP channels function during pneumococcal infections. Streptococcus pneumoniae can cause severe infections such as pneumonia, bacteremia, and meningitis, with systemic inflammatory responses. This study examines the role of TRP channels (TRPV1 and TRPV4) for pneumococcal nasal colonization and subsequent development of invasive pneumococcal disease in a mouse model. Both TRPV1 and TRPV4 channels were shown to be related to regulation of the development of pneumococcal diseases. In particular, the influx of neutrophils (polymorphonuclear cells) in the nasal cavity and the bactericidal activity were significantly suppressed among TRPV4 knockout mice. This may lead to severe pneumococcal pneumonia, resulting in dissemination of the bacteria to various organs and causing high mortality during influenza virus coinfection. Regulating host immune responses by TRP channels could be a novel strategy against pathogenic microorganisms causing strong local/systemic inflammation.

Non-ellipsometric detection of terahertz radiation using heterodyne EO sampling in the Cherenkov velocity matching scheme.

A new electro-optic (EO) sampling scheme, which we refer to as "heterodyne EO sampling", for detection of pulsed terahertz (THz) waves is proposed and experimentally demonstrated. In this heterodyne EO sampling scheme, the intensity change in the optical probe pulse induced by a THz field in a nonlinear crystal is measured without any polarization optics. Applied in combination with the non-collinear Cherenkov velocity matching technique, this method allows one to detect pulsed THz waves efficiently and easily using a simpler optical setup as compared to the conventional ellipsometric EO sampling method.

Efficient electro-optic sampling detection of terahertz radiation via Cherenkov phase matching.

We experimentally demonstrate an efficient electro-optic sampling scheme based on Cherenkov phase matching of broadband terahertz radiation with 800-nm femtosecond probe beam in a 0.5 mm-thick LiNbO3 crystal coupled to a Si prism. The electro-optic signal from a Cherenkov-phase-matched LiNbO3 crystal is found to be comparable to that with a 4 mm-thick ZnTe crystal using a collinear phase matching. The Cherenkov phase matching technique can be achieved with any probe wavelength and hence has an advantage over the collinear phase matching method.

Magnetic resonance and computed tomography-based scoring system for the differential diagnosis of vertebral fractures caused by osteoporosis and malignant tumors.

BACKGROUND: Previous reports have described magnetic resonance imaging (MRI) findings alleged to be specific for vertebral fractures caused by malignant lesions. Using such findings for differential diagnosis is often difficult, especially during the early phase of the fracture. With the relative inaccuracy of any single imaging finding, a validated scoring system based on a combination of imaging findings might lead to enhanced diagnostic accuracy. The purpose of this study was to establish a diagnostic scoring system for discriminating osteoporotic vertebral fractures from those caused by malignant tumors on the basis of MRI and computed tomography (CT) findings. METHODS: Ten MRI and CT scan findings of 57 osteoporotic vertebral fractures and 43 neoplastic fractures were retrospectively evaluated for their ability to discriminate between malignant and benign vertebral fractures. RESULTS: The following four MRI and two CT findings were selected as the basis for the scoring system: pedicle or other posterior element involvement; extension into the paravertebral region; preservation of normal bone marrow signal; a continuous black line representing the posterior vertebral body margin on T2-weighted MRI images; osteolytic destruction; and distinct fracture lines on CT. CONCLUSION: By combining the findings common to MRI and CT scans of vertebral fractures, a simple scoring system was devised. This scoring system was found to enhance the accuracy of imaging diagnosis of fractures caused by benign or malignant spinal lesions.

Neurogenic bladder in patients with cervical compressive myelopathy.

We examined the urinary disturbances in 56 consecutive patients with cervical compressive myelopathy using the latest International Continence Society classification. Of the 56 patients with cervical compressive myelopathy, 29 (52%) had some urinary subjective complaints, whereas the remaining 27 (48%) had none. Urologic examination indicated that 8 of these 29 (28%) patients with urinary complaints had urologic disorders other than neurogenic bladder. Of the remaining 21 patients, only 6 (25%) were judged to have neurogenic bladder on urodynamic study. Urodynamic study may be of limited value in diagnosing urinary disturbance in cervical myelopathy. Further, four cases (83%) showed underactive bladder activity in voiding phase, and only one case (17%) showed overactive bladder activity in filling phase. These results were contrary to those of previous studies indicating that cervical compressive myelopathy is associated with overactive bladder activity in filling phase. There were no significant differences in motor or sensory Japanese Orthopedic Association scores between the patients with and without urinary complaints. However, the patients with urinary complaints had significantly longer durations of myelopathy and delayed motor evoked potential latencies than those without urinary complaints. After surgery, 19 of the 21 (90%) patients with urinary complaints showed recovery from urinary disturbance. Operations in patients with cervical myelopathy were also effective against urinary disturbance. Urinary complaints may be an indication for surgical treatment despite the results of urodynamic study.

Surgical treatment with instrumentation for severely destructive spondyloarthropathy of cervical spine.

Nine patients with severely destructive spondyloarthropathy and marked neurologic deficits associated with dialysis-related amyloidosis underwent posterior decompression and fusion by means of instrumentation at our institute. All patients showed segmental kyphosis, six patients vertebral ankylosis, and eight patients spondylolisthesis. Spondylolisthesis at two levels was noted in three patients. Of the 11 levels of spondylolisthesis in all, 9 were proximally adjacent and 2 were distally adjacent to vertebral ankylosis. All patients underwent posterior decompression and multisegment fusion with autogenous iliac bone. From three to five spinal segments were fixed. Seven patients underwent posterior fusion by means of a pedicle or lateral mass screw between levels C3 and C7, one patient between C3 and C6, and one between C3 and T1. The clinical rate of improvement at the final follow-up was 74.3%. Though complete stability could not be achieved in three patients, the results were rated as good. No postoperative neurologic deterioration has been observed in this series, nor did any patients die immediately after surgery or during the postoperative follow-up period. As anterior long-span surgery might be too invasive for hemodialysis patients, we think that posterior decompression and fusion may well be a reasonable and effective strategy for severe hemodialysis-associated cervical spondyloarthropathy with neurologic deficits. To achieve complete stability, 360 degrees fusion with both anterior and posterior fixation with instrumentation may be required for these patients.

Enhancement of recombinant human bone morphogenetic protein-2 (rhBMP-2)-induced new bone formation by concurrent treatment with parathyroid hormone and a phosphodiesterase inhibitor, pentoxifylline.

We investigated the enhancement of new bone |formation elicited ectopically by recombinant human bone morphogenetic protein-2 (rhBMP-2), using parathyroid hormone (PTH) and a phosphodiesterase inhibitor (PDEi), pentoxifylline (PTX), in an animal model. Collagen sponge sheet discs containing rhBMP were implanted onto the back muscles of mice. PTX alone (200 mg/kg body weight [BW]), PTH(1-34) (10 microg/kg BW), PTX plus PTH (200 mg/kg BW and 10 microg/kg BW, respectively), or vehicle (control) were injected subcutaneously daily for 3 weeks after implantation. At the end of this period, rhBMP-2-induced ectopic ossicles were harvested from each group of animals. Ossicles from the PTX-treated group were significantly larger in size, with unchanged bone mineral density (BMD), as compared with the ossicles from the controls. In contrast, the ossicles from the PTH-treated group had significantly higher BMD, but showed no difference in size when compared with those from the control animals. The ossicles of the PTX + PTH treatment group were significantly larger than those of the control and PTH treatment groups. In addition, the BMD of the harvested tissues from the PTX + PTH treatment group was signifi-cantly higher than that of tissues from the control and PTX treatment groups. Although the calcium content of ossicles was significantly higher in the PTX-, PTH-, and PTX + PTH-treated groups than in the control group, the Ca content of ossicles from the PTH + PTX-treated group was highest (two times that of controls), followed by the PTH- and PTX-treated groups.

Anterior thoracic spinal fusion in dogs by injection of recombinant human bone morphogenetic protein-2 and a synthetic polymer.

The purpose of this study was to achieve spinal fusion in the absence of bone graft material using a new, injectable, and semi-liquid synthetic polymer (polylactic acid polyethylene glycol [PLA-PEG] block copolymer) containing recombinant human bone morphogenetic protein-2 (rhBMP-2). Twenty-seven skeletally mature beagles underwent anterior thoracic spinal fusion at T9-T10. Group I (n = 9) was injected with 1 mL of PLA-PEG block copolymer carrier alone into space under the vertebral pleura and the anterior longitudinal ligament. Group II (n = 9) was injected with 1 mL of PLA-PEG carrier containing 500 microgram of rhBMP-2. Group III (n = 9) was injected with 1 mL of PLA-PEG carrier containing 1000 microgram of rhBMP-2. In the Group I animals, no evidence of new bone formation was noted at the implanted sites both radiographically and histologically. In contrast, all of the nine animals in Group III showed new bone formation in 12 weeks, and four of the nine animals in Group II showed bony mass at the injected sites. However, vertebral bony fusion was incomplete despite the significant amount of new bone formation in both groups that showed new bone formation. In addition to resulting in improvements in the surgical procedure, injection of rhBMP-2 and a synthetic polymer is useful for bone formation for spinal fusion.

Multilevel subtotal corpectomy and interbody fusion using a fibular bone graft for cervical myelopathy due to ossification of the posterior longitudinal ligament.

A retrospective study of the outcomes of multilevel anterior decompression and interbody fusion for cervical myelopathy due to ossification of the posterior longitudinal ligament (OPLL) was performed to both investigate the long-term results and assess the cause of late deterioration. Twenty-seven patients (mean age, 58.1 years) underwent this procedure and were followed for at least 5 years. The severity of the clinical symptoms was described using the scoring system for cervical myelopathy proposed by the Japanese Orthopaedic Association (JOA score). The average preoperative JOA score was 7.7, and the score at final follow-up was 13.4 with a recovery rate of 62.0%. A delayed deterioration was attributed to a thoracolumbar lesion other than a compromising alteration of the cervical spine. Consequently, this method of treatment for OPLL could stop the progress of ossification and keep a physiological cervical alignment and thus provide good long-term results.

Clinical outcome and survival after palliative surgery for spinal metastases: palliative surgery in spinal metastases.

BACKGROUND: The authors sought to identify treatment-related factors that influenced survival after surgical treatment for metastatic spinal tumors and to evaluate the relationship between survival and postoperative ambulation time as a factor related to quality of life. METHODS: The medical records of 81 patients with metastatic spinal tumors who underwent palliative surgery at the study institution were assessed. Univariate analysis for factors influencing survival used the Kaplan-Meier log rank statistic and multivariate analysis used the Cox proportional hazards model. The Spearman correlation test was used to analyze the relationship between postoperative ambulation and survival time. RESULTS: The patients had a median age of 59.9 years and a median survival of 10.6 months after surgery. For patients, postoperative ambulatory median survival was 16.5 months and median ambulation time was 13.8 months. By univariate analysis, anatomic site of the primary tumor, postoperative ambulation, and combined adjuvant therapy (chemotherapy plus radiotherapy) were associated with prolonged survival (P < 0.05). Multivariate analysis identified primary site and postoperative ambulatory function as independent predictors of prolonged survival (P < 0.0001). Significant correlations were found between ambulation time and survival time of patients who were able to walk after surgery (P < 0.0001), even in patients with liver (P < 0.05) or lung carcinoma (P < 0.05). CONCLUSIONS: The anatomic site of primary carcinoma and postoperative ambulation were associated with longer survival after palliative surgery for metastatic spinal tumor. When ambulation is attained after surgery, it can be preserved until late in remaining life even when the primary tumor is unfavorable. Palliative surgery for spinal metastasis can improve the quality and quantity of life.

Pro-inflammatory and anti-inflammatory cytokine increases after spinal instrumentation surgery.

We investigated the effects of instrumentation on postoperative inflammatory reaction and identified standard changes in serum cytokine concentrations after spinal surgery. Pro-inflammatory cytokines [interleukin (IL)-6 and IL-8] and anti-inflammatory cytokines [IL-10, IL-1 receptor antagonist (ra), and soluble tumor necrosis factor receptors (sTNF-R) I and II] were assayed in serum from seven patients with lumbar spinal posterior decompression, six with spinal decompression and posterolateral fusion without instrumentation and seven with spinal decompression and posterolateral fusion with instrumentation. All cytokines after spinal instrumentation increased significantly more than in other groups on postoperative days 0 and 1. Seven days after SI, IL-6, -8, and -10 had normalized, but IL-1ra and sTNF-RI and sTNF-RII remained elevated. Both pro-inflammatory and anti-inflammatory cytokines were enhanced by implants in the acute phase, whereas only anti-inflammatory cytokines were enhanced by instruments in the subacute phase.

Involvement of phosphodiesterase isozymes in osteoblastic differentiation.

The cyclic monophosphate nucleotides (cyclic adenosine monophosphate [cAMP] and cyclic guanosine monophosphate [cGMP]) are found ubiquitously in mammalian cells and act as second messenger transducers to effect the intracellular actions of a variety of hormones, cytokines, and neurotransmitters. In turn, these nucleotides also modulate the signal transduction processes regulated by a range of cytokines and growth factors. Previously, we have reported that pentoxifylline, a nonselective phosphodiesterase (PDE) inhibitor, can promote osteoblastic differentiation by elevating intracellular cAMP levels and, consequently, enhance bone formation in vivo and in vitro. In this study, reverse-transcription polymerase chain reaction (RT-PCR) analysis of the osteoblastic cell lines, MC3T3-E1 and ST2 revealed the presence of PDE1, PDE2, PDE3, PDE4, PDE7, PDE8, and PDE9. We examined the effect of selective inhibitors for a respective PDE isozyme on the capacity of bone morphogenetic protein 4 (BMP-4)-induced alkaline phosphatase (ALP) activity, a cellular differentiation marker, in cells with osteogenetic potential. The results indicate that selective inhibitors for PDE2, PDE3, and PDE4 enhanced the BMP-4-induced ALP activity in a dose-dependent manner in ST2 cells but not in MC3T3-E1 cells. Northern blot analysis also revealed that the selective inhibitors for PDE2, PDE3, and PDE4 enhanced the levels of expression of messenger RNAs (mRNAs) of ALP, osteopontin (OP), and collagen type I in ST2 cells but not in MC3T3-E1 cells except for the treatment with PDE4 inhibitor. Given these data, we conclude that PDE isozymes are involved in the modulation of osteoblastic differentiation mainly at an early stage. Additionally, selective inhibitors for PDE2, PDE3, and PDE4 appear to promote the differentiation of osteogenic precursor cells toward an osteoblastic phenotype.