Allergic Fungal Rhinosinusitis and Contralateral Chronic Granulomatous Invasive Fungal Sinusitis: A Case Report.

This case report describes rare concomitant allergic fungal rhinosinusitis (AFRS) and chronic granulomatous invasive fungal sinusitis (CGIFS) in a 34-year-old woman with acute lymphoblastic leukemia and graft-versus-host disease (GVHD) post bone marrow transplantation. Initially presenting with rhinorrhea and nasal obstruction, the patient was diagnosed with AFRS in the right maxillary sinus, followed by a postoperative course of CGIFS in the left nasal cavity, showcasing the unique occurrence. She was not immunocompromised during diagnosis. CGIFS may have occurred because of surgery; however, voriconazole led to significant improvement. This case highlights noninvasive and invasive fungal infections in patients with chronic rhinosinusitis and a history of GVHD and underscores the complexity of diagnosing and managing such cases.

In vivo study on the repair of rat Achilles tendon injury treated with non-thermal atmospheric-pressure helium microplasma jet.

Non-thermal atmospheric-pressure plasma (NTAPP) has been widely studied for clinical applications, e.g., disinfection, wound healing, cancer therapy, hemostasis, and bone regeneration. It is being revealed that the physical and chemical actions of plasma have enabled these clinical applications. Based on our previous report regarding plasma-stimulated bone regeneration, this study focused on Achilles tendon repair by NTAPP. This is the first study to reveal that exposure to NTAPP can accelerate Achilles tendon repair using a well-established Achilles tendon injury rat model. Histological evaluation using the Stoll's and histological scores showed a significant improvement at 2 and 4 weeks, with type I collagen content being substantial at the early time point of 2 weeks post-surgery. Notably, the replacement of type III collagen with type I collagen occurred more frequently in the plasma-treated groups at the early stage of repair. Tensile strength test results showed that the maximum breaking strength in the plasma-treated group at two weeks was significantly higher than that in the untreated group. Overall, our results indicate that a single event of NTAPP treatment during the surgery can contribute to an early recovery of an injured tendon.

Anatomic Variation of the Hamate Hook as a Potential Risk in Endoscopic Carpal Tunnel Release.

Purpose: The purpose of this study was to investigate the incidence of anomalies in patients who underwent endoscopic carpal tunnel release and their relationship with clinical outcomes. Methods: This retrospective study included 65 hands of 57 patients (8 men and 49 women; mean age, 64.9 years) who underwent endoscopic carpal tunnel release for carpal tunnel syndrome at our hospital between March 2016 and April 2022. The patients were diagnosed with carpal tunnel syndrome based on clinical observations and electrophysiological studies. On T2-weighted magnetic resonance axial images, the height of the hook of the hamate was measured from the bottom to the tip of the hook, and the total height of the hamate was measured from the dorsal surface of the hamate to the tip of the hook. A hook-to-height ratio of less than 0.34 was defined as hypoplastic, and its incidence was investigated. In addition, electrodiagnostic testing of sensory and motor nerve conduction of the median nerve and patient-reported outcome measurements, including Quick Disabilities of the Arm, Shoulder and Hand score, Boston carpal tunnel questionnaire, and visual analog scale score, were investigated at 6 months after surgery. Adverse events were collected from patient records. Results: The mean hook-to-height ratio was 0.40. Hypoplasia with a ratio ≤0.34 was observed in seven hands (10.8%), and adverse events were observed only in the two cases that had a hypoplastic hook of the hamate (3.07%). The patient-reported outcome measurements and the result of electrodiagnostic testing at 6 months after surgery did not correlate with the height of the hook of the hamate. Conclusions: The incidence of a hypoplastic hook of the hamate is common in patients with carpal tunnel syndrome, and preoperative evaluation of the morphology of the hooks and indications for endoscopic carpal tunnel release in cases of hypoplastic hooks may help predict adverse events. Type of study/level of evidence: Therapeutic Ⅳ.

Fracture healing on non-union fracture model promoted by non-thermal atmospheric-pressure plasma.

Non-thermal atmospheric-pressure plasma (NTAPP) is attracting widespread interest for use in medical applications. The tissue repair capacity of NTAPP has been reported in various fields; however, little is known about its effect on fracture healing. Non-union or delayed union after a fracture is a clinical challenge. In this study, we aimed to investigate how NTAPP irradiation promotes fracture healing in a non-union fracture model and its underlying mechanism, in vitro and in vivo. For the in vivo study, we created normal and non-union fracture models in LEW/SsNSlc rats to investigate the effects of NTAPP. To create a fracture, a transverse osteotomy was performed in the middle of the femoral shaft. To induce the non-union fracture model, the periosteum surrounding the fracture site was cauterized after a normal fracture model was created. The normal fracture model showed no significant difference in bone healing between the control and NTAPP-treated groups. The non-union fracture model demonstrated that the NTAPP-treated group showed consistent improvement in fracture healing. Histological and biomechanical assessments confirmed the fracture healing. The in vitro study using pre-osteoblastic MC3T3-E1 cells demonstrated that NTAPP irradiation under specific conditions did not reduce cell proliferation but did enhance osteoblastic differentiation. Overall, these results suggest that NTAPP is a novel approach to the treatment of bone fractures.

Interlaboratory evaluation of LC-MS-based biomarker assays.

Validation of biomarker assays is crucial for effective drug development and clinical applications. Interlaboratory reproducibility is vital for reliable comparison and combination of data from different centers. This review summarizes interlaboratory studies of quantitative LC-MS-based biomarker assays using reference standards for calibration curves. The following points are discussed: trends in reports, reference and internal standards, evaluation of analytical validation parameters, study sample analysis and normalization of biomarker assay data. Full evaluation of these parameters in interlaboratory studies is limited, necessitating further research. Some reports suggest methods to address variations in biomarker assay data among laboratories, facilitating organized studies and data combination. Method validation across laboratories is crucial for reducing interlaboratory differences and reflecting target biomarker responses.

Relationship Between the Lipidome Profile and Disease Activity in Patients with Rheumatoid Arthritis.

Lipid mediators have been suggested to play important roles in the pathogenesis of rheumatoid arthritis (RA). Lipidomics has recently allowed for the comprehensive analysis of lipids and has revealed the potential of lipids as biomarkers for the early diagnosis of RA and prediction of therapeutic responses. However, the relationship between disease activity and the lipid profile in RA remains unclear. In the present study, we performed a plasma lipidomic analysis of 278 patients with RA during treatment and examined relationships with disease activity using the Disease Activity Score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR). In all patients, five lipids positively correlated and seven lipids negatively correlated with DAS28-ESR. Stearic acid [FA(18:0)] (r = -0.45) and palmitic acid [FA(16:0)] (r = -0.38) showed strong negative correlations. After adjustments for age, body mass index (BMI), and medications, stearic acid, palmitic acid, bilirubin, and lysophosphatidylcholines negatively correlated with disease activity. Stearic acid inhibited osteoclast differentiation from peripheral blood monocytes in in vitro experiments, suggesting its contribution to RA disease activity by affecting bone metabolism. These results indicate that the lipid profile correlates with the disease activity of RA and also that some lipids may be involved in the pathogenesis of RA.

Identification of kynurenine and quinolinic acid as promising serum biomarkers for drug-induced interstitial lung diseases.

BACKGROUND: Drug-induced interstitial lung disease (DILD) is a lung injury caused by various types of drugs and is a serious problem in both clinical practice and drug development. Clinical management of the condition would be improved if there were DILD-specific biomarkers available; this study aimed to meet that need. METHODS: Biomarker candidates were identified by non-targeted metabolomics focusing on hydrophilic molecules, and further validated by targeted approaches using the serum of acute DILD patients, DILD recovery patients, DILD-tolerant patients, patients with other related lung diseases, and healthy controls. RESULTS: Serum levels of kynurenine and quinolinic acid (and kynurenine/tryptophan ratio) were elevated significantly and specifically in acute DILD patients. The diagnostic potentials of these biomarkers were superior to those of conventional lung injury biomarkers, Krebs von den Lungen-6 and surfactant protein-D, in discriminating between acute DILD patients and patients with other lung diseases, including idiopathic interstitial pneumonia and lung diseases associated with connective tissue diseases. In addition to identifying and evaluating the biomarkers, our data showed that kynurenine/tryptophan ratios (an indicator of kynurenine pathway activation) were positively correlated with serum C-reactive protein concentrations in patients with DILD, suggesting the potential association between the generation of these biomarkers and inflammation. Our in vitro experiments demonstrated that macrophage differentiation and inflammatory stimulations typified by interferon gamma could activate the kynurenine pathway, resulting in enhanced kynurenine levels in the extracellular space in macrophage-like cell lines or lung endothelial cells. Extracellular quinolinic acid levels were elevated only in macrophage-like cells but not endothelial cells owing to the lower expression levels of metabolic enzymes converting kynurenine to quinolinic acid. These findings provide clues about the molecular mechanisms behind their specific elevation in the serum of acute DILD patients. CONCLUSIONS: The serum concentrations of kynurenine and quinolinic acid as well as kynurenine/tryptophan ratios are promising and specific biomarkers for detecting and monitoring DILD and its recovery, which could facilitate accurate decisions for appropriate clinical management of patients with DILD.

Safety and outcome of three-dimensional transoral videolaryngoscopic surgery.

BACKGROUND: Transoral videolaryngoscopic surgery (TOVS) is widely used in Japan, and conventional two-dimensional (2D) endoscopic methods have been established. Three-dimensional (3D) endoscopic surgery offers superior distance perception because it provides stereoscopic views. Recently, we have developed 3D endoscopy for TOVS (3D TOVS). METHODS: This study included 46 patients with pharyngeal cancer who underwent 3D TOVS. The perioperative complications and survival curves were retrospectively analyzed. RESULTS: One patient with oropharyngeal cancer who underwent neck dissection and transoral resection simultaneously experienced postoperative hemorrhage of the neck. Another patient with oropharyngeal cancer underwent hemostasis for postoperative pharyngeal hemorrhage. There was one case of aspiration pneumonia. One patient developed cervical lymph node recurrence; however, there was no local recurrence or primary mortality. The 2-year overall survival, disease-specific survival, local control rates, locoregional control rate, and invasive disease-free survival were 90.9%, 100%, 100%, 97.4%, and 79.9%, respectively. CONCLUSIONS: Three-dimensional endoscopy can be safely applied to TOVS.

Impact of microsampling on toxicological evaluation in rodent safety studies.

Recently, animal welfare has been attracting worldwide attention, and implementation of 3Rs (replacement, reduction, and refinement) is prioritized in every way possible in the drug development. Microsampling, in which small amounts of blood are collected, is attracting attention in this context. ICH S3A Q&A focused on microsampling was published in November 2017 to help accelerate the application of microsampling for toxicokinetic assessment. The increased sensitivity of drug measurement apparatuses such as mass spectrometers has made it possible to measure drug concentrations with small amounts of blood samples. In this review, we summarized the reports on toxicological influence of microsampling in rodents (rats and mice) with or without drug administration or recovery period after blood collection and influences that may arise from differences in the blood sampling site or blood sampling volume. We also summarized some perspectives on further implementation of microsampling in toxicology studies. The use of microsampling in regulatory toxicology studies has gradually increased, although at a lower rate than in discovery studies. Since more animals are used in GLP toxicology studies than in discovery studies, the effect of reducing the number of animals by microsampling is expected to be greater in the toxicology studies. This report aims to promote the application of microsampling to nonclinical studies, as it is beneficial for improving animal welfare and can contribute to the 3Rs.

Nerve Grafting for Isolated Injury to the Intrinsic Motor Branch of the Ulnar Nerve due to a Stab Injury: A Case Report.

Isolated injury to the deep motor branch of the ulnar nerve caused by stabbing is sporadic, with only one reported case in the English-language literature. We report one such case treated successfully using nerve grafting. A 33-year-old patient had sustained a stab wound to the right hypothenar eminence and showed a claw hand deformity. Needle electromyography study revealed denervation potentials with no voluntary motor unit action potentials (MUAPs) in the first dorsal interosseous (FDI) muscles. Nerve exploration revealed a neuroma-in-continuity in the intrinsic motor branch of the ulnar nerve. Intraoperative nerve stimulation confirmed the absence of compound muscle action potentials in the FDI. The damaged scarred nerve was resected, and the 15-mm defects were reconstructed with cable autografting. Two years and 5 months after the surgery, voluntary MUAPs were observed in the FDI. The pinch strengths recovered. Laceration of the deep branch of the ulnar nerve caused by stabbing can sometimes remain hidden as the hand sensation remains intact. Pre- and intraoperative electrophysiological examination is essential to assess the severity of the injured nerve and determine an appropriate surgical option. Even nerve grafting can facilitate satisfactory results as target intrinsic muscles are quite close to the repair site.