Clinical practice guidelines for molecular tumor marker, 2nd edition review part 2.

In recent years, rapid advancement in gene/protein analysis technology has resulted in target molecule identification that may be useful in cancer treatment. Therefore, "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" was published in Japan in September 2021. These guidelines were established to align the clinical usefulness of external diagnostic products with the evaluation criteria of the Pharmaceuticals and Medical Devices Agency. The guidelines were scoped for each tumor, and a clinical questionnaire was developed based on a serious clinical problem. This guideline was based on a careful review of the evidence obtained through a literature search, and recommendations were identified following the recommended grades of the Medical Information Network Distribution Services (Minds). Therefore, this guideline can be a tool for cancer treatment in clinical practice. We have already reported the review portion of "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" as Part 1. Here, we present the English version of each part of the Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition.

The quality of life outcome in patients with head and neck squamous cell cancer treated using chemoradiotherapy.

OBJECTIVE: Organ preservation is a goal of head and neck squamous cell cancer (HNSCC) treatment. chemoradiotherapy remains one of the main treatment options and is widely recognized as a method with organ-preserving potential and outcomes comparable to those of surgery. However, few studies have investigated the quality of life (QOL) of patients with HNSCC treated using chemoradiotherapy, therefore, we aimed to retrospectively evaluate how QOL changes pre and post-chemoradiotherapy. METHODS: We evaluated QOL outcomes in patients who underwent initial radical chemoradiotherapy for HNSCC at the Department of Otolaryngology and Head and Neck Surgery Kitasato University Hospital from 2018 to 2021. We used the Cancer Fatigue Scale (CFS) and the combined European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-H&N35 questionnaires at pre-treatment, three months and six months post-treatment. RESULTS: We obtained 37 and 29 responses from the CFS and EORTC QLQ-C30/H&N35 questionnaire, respectively. From the CFS, the physical fatigue score at three months post-treatment deteriorated more than that at pre-treatment, and significantly improved by six months post-treatment. The total score worsened significantly at three months and there was a trend toward improvement at six months. In the EORTC QLQ-C30, physical and social functioning declined in three months and did not improve within six months. Fatigue was substantially worse at three months and significantly improved at six months but did not reach the same level as that before treatment. Appetite loss was also significantly worse at three months. In the QLQ-H&N35 questionnaire, sensory issues, trouble with social contact, and dry mouth were significantly worse at three months and did not improve within six months. Sticky saliva also worsened at three months and significantly improved at six months. CONCLUSION: There were some problems associated with chemoradiotherapy. Some patients showed an improvement, while others continued to have challenges. In Japan, chemoradiotherapy was shown to have a long-term impact on the patient's life.

Suppression of the TGF-ß signaling exacerbates degeneration of auditory neurons in kanamycin-induced ototoxicity in mice.

Transforming growth factor-ß (TGF-ß) signaling plays a significant role in multiple biological processes, including inflammation, immunity, and cell death. However, its specific impact on the cochlea remains unclear. In this study, we aimed to investigate the effects of TGF-ß signaling suppression on auditory function and cochlear pathology in mice with kanamycin-induced ototoxicity. Kanamycin and furosemide (KM-FS) were systemically administered to 8-week-old C57/BL6 mice, followed by immediate topical application of a TGF-ß receptor inhibitor (TGF-ßRI) onto the round window membrane. Results showed significant TGF-ß receptor upregulation in spiral ganglion neurons (SGNs) after KM-FA ototoxicity, whereas expression levels in the TGF-ßRI treated group remained unchanged. Interestingly, despite no significant change in cochlear TGF-ß expression after KM-FS ototoxicity, TGF-ßRI treatment resulted in a significant decrease in TGF-ß signaling. Regarding auditory function, TGF-ßRI treatment offered no therapeutic effects on hearing thresholds and hair cell survival following KM-FS ototoxicity. However, SGN loss and macrophage infiltration were significantly increased with TGF-ßRI treatment. These results imply that inhibition of TGF-ß signaling after KM-FS ototoxicity promotes cochlear inflammation and SGN degeneration.

Vulnerable Hours of the Day for Severe Iatrogenic Hypoglycaemia in Type 2 Diabetes: A Single-Centre Retrospective Study.

INTRODUCTION: Iatrogenic hypoglycaemia is an event that should be avoided in the treatment of diabetes, but the pathophysiology thereof has been poorly examined and reported. There is no established method for preventing iatrogenic hypoglycaemia and the current approach is a reactive response following onset of the disease. In this study, we aimed to explore the existence of 'hypoglycaemia-vulnerable hours of the day' in patients with type 2 diabetes, with the ultimate goal of preventing the onset of iatrogenic hypoglycaemia by clarifying the time when severe hypoglycaemia is likely to occur. METHODS: Of the 553,201 patients who visited the Critical Care and Emergency Center of Aizawa Hospital between 2008 and 2019, patients with proven hypoglycaemia (blood glucose level <3.0 mmol/L) and those using insulin or oral hypoglycaemic agents for the treatment of type 2 diabetes were included: 146 insulin users and 148 oral hypoglycaemic agent users. Cosinor analysis was employed to identify hypoglycaemia-vulnerable hours of the day. RESULTS: Patients with type 2 diabetes and severe hypoglycaemia had two peaks: at 8:00 and 18:00-19:00. Hypoglycaemia was observed as quadra-peaked in insulin users and double-peaked in oral hypoglycaemic agent users. Single-cosinor analysis revealed that the cycle was 5.83 hours (R=0.417) in insulin users, whereas it was 11.0 hours (R=0.717) in oral hypoglycaemic agent users. In insulin users, a significant periodicity of six hours (P=0.003) was observed in the cosinor detection analysis, and a significant correlation (P<0.05) was present in the cosinor percent rhythmicity analysis. In contrast, in oral hypoglycaemic agent users, a significant periodicity of 11 hours (P=0.03) was ascertained in the cosinor detection analysis, and there was a significant correlation (P<0.001) in the cosinor percent rhythmicity analysis. There were different hypoglycaemia-vulnerable hours of the day in the patients with type 2 diabetes, suggesting an interaction between disease pathophysiology and pharmacology. CONCLUSIONS: These results can help elucidate the trend of the development of iatrogenic hypoglycaemia and contribute to the prevention of the onset thereof.

Effect of statins on hearing outcome in patients with idiopathic sudden sensorineural hearing loss.

Objective: Statins have been reported to improve vascular endothelial function and microcirculation, reduce oxidative stress, and exert anti-inflammatory and protective effects against inner ear damage. Therefore, this study aimed to investigate the effect of statins on hearing prognosis in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). Methods: We reviewed the medical records of 149 patients diagnosed with ISSNHL. Clinical characteristics, hearing thresholds, statin medications, and hematological findings were investigated. First, patients with ISSNHL were assigned to the good and poor outcome groups, and factors influencing their prognosis were analyzed. Furthermore, patients with dyslipidemia were investigated to determine whether statins have therapeutic effects on ISSNHL. Results: Significant differences in age (p = .011), days from the onset of ISSNHL to the initiation of treatment (p = .04), and hematological total cholesterol (TC; p = .015) between the good and poor outcome groups were observed. Furthermore, when hearing outcomes were investigated in patients with dyslipidemia, TC was significantly lower in the good outcome group (p = .03). Although no significant therapeutic effects of statins were observed in participants with dyslipidemia, patients in the statin-treated group were significantly older and experienced more diabetic complications than those in the non-statin-treated group. Conclusion: Although our study showed that dyslipidemia is a poor prognostic factor for ISSNHL, statins had no significant therapeutic effects on hearing recovery in ISSNHL patients with dyslipidemia. The patients that received statin medications were significantly older and experienced more diabetic complications, which may have affected their hearing prognosis. Level of Evidence: Level 4.