Facilitators, barriers, and changes in POCUS use: longitudinal follow-up after participation in a national point-of-care ultrasound training course in Japan.

BACKGROUND: POCUS training courses are effective at improving knowledge and skills, but few studies have followed learners longitudinally post-course to understand facilitators, barriers, and changes in POCUS use in clinical practice. We conducted a prospective observational study of physicians who attended 11 standardized POCUS training courses between 2017 and 2019 in Japan. Physicians who attended a standardized POCUS course were surveyed about their current frequency of POCUS use of the heart, lung, abdomen, and lower extremity veins, and perceived barriers and facilitators to POCUS use in clinical practice. RESULTS: Data were analyzed from 112 completed surveys (response rate = 20%). A majority of responding physicians were faculty (77%) in internal medicine (69%) affiliated with community hospitals (55%). The mean delay between course attendance and survey response was 50.3 months. A significant increase in POCUS use from < 1 to ≥ 1 time per week was seen for all organ systems after 50 months post-course (p < 0.01). Approximately half of course participants reported an increase in the frequency of cardiac (61%), lung (53%), vascular (44%), and abdominal (50%) ultrasound use. General facilitators of POCUS use were easy access to ultrasound machines (63%), having a colleague with whom to learn POCUS (47%), and adequate departmental support (46%). General barriers included lack of opportunities for POCUS training (47%), poor access to ultrasound machines (38%), and limited time for POCUS training (33%). In the group with increased POCUS usage, specific facilitators reported were enhanced POCUS knowledge, improved image acquisition skills, and greater self-confidence in performing POCUS. Conversely, the group without increased POCUS usage reported lack of supervising physicians, low confidence, and insufficient training opportunities as specific barriers. CONCLUSIONS: Approximately half of physicians reported an increase in cardiac, lung, vascular, and abdominal POCUS use > 4 years after attending a POCUS training course. In addition to improving access to ultrasound machines and training opportunities, a supportive local clinical environment, including colleagues to share experiences in learning POCUS and local experts to supervise scanning, is important to foster ongoing POCUS practice and implementation into clinical practice.

Discovery and Hit to Lead Optimization of Macrocyclic Peptides as Novel Tropomyosin Receptor Kinase A Antagonists.

Tropomyosin receptor kinases (Trks) are receptor tyrosine kinases activated by neurotrophic factors, called neurotrophins. Among them, TrkA interacts with the nerve growth factor (NGF), which leads to pain induction. mRNA-display screening was carried out to discover a hit compound 2, which inhibits protein-protein interactions between TrkA and NGF. Subsequent structure optimization improving phosphorylation inhibitory activity and serum stability was pursued using a unique process that took advantage of the peptide being synthesized by translation from mRNA. This gave peptide 19, which showed an analgesic effect in a rat incisional pain model. The peptides described here can serve as a new class of analgesics, and the structure optimization methods reported provide a strategy for discovering new peptide drugs.

Conversion surgery for gastric remnant cancer with liver metastasis after nivolumab combination chemotherapy achieving pathological complete response: a case report and literature review.

BACKGROUND: Nivolumab combination chemotherapy has recently emerged as a potential first-line treatment for patients with unresectable or metastatic gastric cancer (GC). Further research has indicated that R0 resection by conversion surgery could be an effective treatment strategy to improve overall survival. However, there have been limited reports on the successful application of conversion surgery following combination chemotherapy achieving pathological complete response (pCR) in cases of advanced gastric remnant cancer with liver metastasis. Here, we present a case of long-term survival in a patient who underwent this treatment. CASE PRESENTATION: A 54-year-old man was initially referred to our department for treatment of stage III (cT3N1M0) gastric cancer where he underwent laparoscopic distal gastrectomy and D2 lymph node dissection. After a year of uneventful follow-up, the patient was diagnosed with a tumor in the gastric remnant combined with liver metastasis, resulting in a diagnosis of stage IV (cT3N0M1) gastric remnant cancer. Subsequently, the patient was treated with four cycles of TS-1, Oxaliplatin, and Nivolumab as the first-line regimen. Remarkably, both the remnant tumor and liver metastasis exhibited significant shrinkage, and no new lesions were found. Given this response, conversion surgery was performed to achieve complete resection of the remnant gastric cancer and liver metastasis, followed by laparoscopic remnant gastrectomy and partial hepatectomy. Pathological examination revealed the absence of residual carcinoma cells and lymph node metastases. Postoperatively, the patient was treated with adjuvant chemotherapy with S-1 for 1 year, and survived without recurrence for 18 months after conversion surgery. CONCLUSIONS: Nivolumab combination chemotherapy shows promise as a clinically beneficial treatment approach for gastric remnant cancer with liver metastasis, particularly when pCR can be achieved following conversion surgery.

Relationship Between Diaphragm Thickness, Thickening Fraction, Dome Excursion, and Respiratory Pressures in Healthy Subjects: An Ultrasound Study.

PURPOSE: Diaphragm ultrasonography is used to identify causes of diaphragm dysfunction. However, its correlation with pulmonary function tests, including maximal inspiratory (MIP) and expiratory pressures (MEP), remains unclear. This study investigated this relationship by measuring diaphragm thickness, thickening fraction (TF), and excursion (DE) using ultrasonography, and their relationship to MIP and MEP. It also examined the influence of age, sex, height, and BMI on these measures. METHODS: We recruited healthy Japanese volunteers and conducted pulmonary function tests and diaphragm ultrasonography in a seated position. Diaphragm ultrasonography was performed during quiet breathing (QB) and deep breathing (DB) to measure the diaphragm thickness, TF, and DE. A multivariate analysis was conducted, adjusting for age, sex, height, and BMI. RESULTS: Between March 2022 and January 2023, 109 individuals (56 males) were included from three facilities. The mean (standard deviation) MIP and MEP [cmH2O] were 72.2 (24.6) and 96.9 (35.8), respectively. Thickness [mm] at the end of expiration was 1.7 (0.4), TF [%] was 50.0 (25.9) during QB and 110.7 (44.3) during DB, and DE [cm] was 1.7 (0.6) during QB and 4.4 (1.4) during DB. Multivariate analysis revealed that only DE (DB) had a statistically significant relationship with MIP and MEP (p = 0.021, p = 0.008). Sex, age, and BMI had a statistically significant influence on relationships between DE (DB) and MIP (p = 0.008, 0.048, and < 0.001, respectively). CONCLUSION: In healthy adults, DE (DB) has a relationship with MIP and MEP. Sex, age, and BMI, but not height, are influencing factors on this relationship.

Impact of Tumor Grade Distribution on Genetic Alterations in Clear Cell Renal Cell Carcinoma and Prostate Cancer.

BACKGROUND/AIM: A genomic analysis based on next-generation sequencing is important for deciding cancer treatment strategies. Cancer tissue sometimes displays intratumor heterogeneity and a pathologic specimen may contain more than two tumor grades. Although tumor grades are very important for the cancer prognosis, the impact of higher tumor grade distribution in a specimen used for a genomic analysis is unknown. PATIENTS AND METHODS: We retrospectively analyzed the data of 61 clear cell carcinoma and 46 prostate cancer patients that were diagnosed between December 2018 and August 2022 using the GeneRead Human Comprehensive Cancer Panel or SureSelect PrePool custom Tier2. Genome annotation and curation were performed using the GenomeJack software. RESULTS: Tumor mutation burden (TMB) was increased in proportion to the higher tumor grade distribution in grade 2 clear cell renal cell carcinoma (ccRCC). In PC, Grade Group 3/4 specimens that included an increased distribution of Gleason pattern 4 had more frequent gene mutations. CONCLUSION: Our results suggest the importance of selecting the maximum distribution of higher tumor grade areas to obtain results on the precise gene alterations for genomics-focused treatments.

Development of a national point-of-care ultrasound training course for physicians in Japan: A 3-year evaluation.

Purpose: Point-of-care ultrasound (POCUS) allows bedside clinicians to acquire, interpret, and integrate ultrasound images into patient care. Although the availability of POCUS training courses has increased, the educational effectiveness of these courses is unclear. Methods: From 2017 to 2019, we investigated the educational effectiveness of a standardized 2-day hands-on POCUS training course and changes in pre- and post-course exam scores in relationship to participants' (n = 571) clinical rank, years of POCUS experience, and frequency of POCUS use in clinical practice. Results: The mean pre- and post-course examination scores were 67.2 (standard deviation [SD] 12.3) and 79.7 (SD 9.7), respectively. Higher pre-course examination scores were associated with higher clinical rank, more years of POCUS experience, and more frequent POCUS use (p < 0.05). All participants showed significant changes in pre- to post-course exam scores. Though pre-course scores differed by clinical rank, POCUS experience, and frequency of POCUS use, differences in post-course scores according to participant baseline differences were non-significant. Conclusion: A standardized hands-on POCUS training course is effective for improving POCUS knowledge regardless of baseline differences in clinical rank, POCUS experience, or frequency of POCUS use. Future studies shall evaluate changes in POCUS use in clinical practice after POCUS training.