Neurons limit angiogenesis by titrating VEGF in retina.

Vascular and nervous systems, two major networks in mammalian bodies, show a high degree of anatomical parallelism and functional crosstalk. During development, neurons guide and attract blood vessels, and consequently this parallelism is established. Here, we identified a noncanonical neurovascular interaction in eye development and disease. VEGFR2, a critical endothelial receptor for VEGF, was more abundantly expressed in retinal neurons than in endothelial cells, including endothelial tip cells. Genetic deletion of VEGFR2 in neurons caused misdirected angiogenesis toward neurons, resulting in abnormally increased vascular density around neurons. Further genetic experiments revealed that this misdirected angiogenesis was attributable to an excessive amount of VEGF protein around neurons caused by insufficient engulfment of VEGF by VEGFR2-deficient neurons. Moreover, absence of neuronal VEGFR2 caused misdirected regenerative angiogenesis in ischemic retinopathy. Thus, this study revealed neurovascular crosstalk and unprecedented cellular regulation of VEGF: retinal neurons titrate VEGF to limit neuronal vascularization. PAPERFLICK:

Diaphragm Ultrasonography: Reference Values and Influencing Factors for Thickness, Thickening Fraction, and Excursion in the Seated Position.

INTRODUCTION: Measurements of diaphragm function by ultrasonography are affected by body position, but reference values in the seated position have not been established for an Asian population. This study aimed to determine reference values for diaphragm thickness, thickening fraction, and dome excursion by ultrasonography and to investigate the effects of sex, height, and body mass index. METHODS: Diaphragm ultrasonography was performed on 109 seated Japanese volunteers with normal respiratory function who were enrolled between March 2022 and January 2023. Thickness, thickening fraction, and excursion were measured. Reference values and the measurement success rate were calculated. Multivariate analysis adjusted for sex, height, and body mass index was performed. RESULTS: The measurement success rate was better for thickness than for excursion. The mean (lower limit of normal) values on the right/left sides were as follows. During quiet breathing, thickness at end expiration(mm) was 1.7 (0.9)/1.6 (0.80), thickening fraction(%) was 50 (0.0)/52 (0.0), and excursion(cm) was 1.7 (0.5)/1.9 (0.5). During deep breathing, the thickening fraction was 111 (24)/107 (22), and the excursion was 4.4 (1.7)/4.1 (2.0). In multivariate analysis, body mass index was positively associated with thickness but not with the thickening fraction. CONCLUSION: The reference values in this study were smaller than those in previous reports from Europe. Considering that thickness is influenced by body mass index, using Western reference values in Asia, where the average body mass index is lower, might not be appropriate. The thickening fraction in deep breathing is unaffected by other items and can be used more universally.

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.

Postoperative Prognosis According to Pathologic Categorization of Desmoplastic Reaction in Patients with Extrahepatic Cholangiocarcinoma.

BACKGROUND: Recent studies have demonstrated the importance of desmoplastic reaction (DR) in predicting postoperative prognosis for patients with colorectal carcinoma. However, the impact of DR on the prognosis of extrahepatic cholangiocarcinomas (EHCCs) is not established. This study aimed to clarify the associations of pathologic DR categories with clinicopathologic factors and postoperative prognosis of perihilar cholangiocarcinoma (PHCC) and distal cholangiocarcinoma (DCC). METHODS: A pathologic review of 174 patients with PHCC and 109 patients with DCC who underwent surgical resection was performed. The patients were classified into three DR categories (immature, intermediate, and mature) based on the histologic features within the fibrotic stroma in the invasive front. The association between DR categories and the distribution of fibroblasts with anti-α-smooth muscle actin (SMA) expression, seeming to be tumor-promoting cancer-associated fibroblasts (CAFs), was evaluated in 191 tissue microarray specimens of EHCCs. RESULTS: Intermediate/immature DR categories were significantly associated with a more invasive nature, including higher pT and pN stages and more tumor buds than the mature category in both PHCC and DCC. The DR categories could stratify overall survival (OS) and relapse-free survival (RFS) in both PHCC and DCC patients. In the multivariate analysis, the DR category was an independent prognostic factor for OS and RFS in both PHCC and DCC (p < 0.001). The mature and immature DR categories were significantly associated respectively with the confined and pervasive distribution of fibroblasts with α-SMA expression. CONCLUSION: In patients with EHCCs, DR categorization was an independent prognostic factor reflecting the distribution of tumor-promoting CAFs in the invasive front.

Effectiveness of point of care ultrasound (POCUS) simulation course and skills retention for Japanese nurse practitioners.

BACKGROUND: In Japan, the nurse practitioner (NP) system has only been in place for a short time, and there is no ultrasound (US) simulation course for NPs. Therefore, NPs may have to attend US simulation courses for physicians. We evaluated whether US simulation course for physicians lead to improved image acquisition and interpretation amongst NPs and, if so, if these changes would be maintained over time. METHODS: A 2-day point-of-care ultrasound (POCUS) course designed for physicians in cardiac US, lung US, lower extremity deep vein thrombosis (DVT) US, and abdominal US was held for Japanese nurse practitioners (JNP) and JNP trainees in 2018 and 2019. Participants kept a record of the number of US examinations they performed for 3 months before and 3 months after the course. The number of US exams performed was grouped into six categories. All participants underwent pre-course, immediate post-course, and 4-month post-course testing to assess image interpretation skills, image acquisition skills, and confidence. RESULTS: Thirty-three participants from 21 facilities completed the program. Before and immediately after the course, test scores of the image interpretation test, image acquisition test, and confidence increased significantly (37.1, 72.6: P < 0.001), (13.7, 53.6: P < 0.001), and (15.8, 35.7: P < 0.001), respectively. Comparing the follow-up tests immediately after the course and 4 months later, there was no decrease in scores on the image interpretation test, the image acquisition test, or confidence (72.6, 71.8: P = 1.00) (53.6, 52.9: p = 1.00) (35.7, 33.0: P = 0.34). There was a statistically significant increase (P < 0.001) in both the total number of ultrasound examinations and in the number of ultrasound examinations by category (cardiac, lung, lower extremity DVT, and abdominal) in the 3 months before and 3 months after the course. CONCLUSIONS: The POCUS simulation course for physicians is useful for JNPs to acquire US examination skills even if it is not arranged for JNPs. Image interpretation skill, image acquisition skill, and confidence improved significantly and were maintained even after 4 months of the course. It leads to behavioral changes such as increasing the number of US examinations in daily practice after the course.

[A Case of Advanced Gastric Cancer with Pancreatic Invasion Completely Resected after Chemotherapy].

An 80-year-old man with severe anemia was found to have a circumferential type 3 lesion with obstruction in the gastric pylorus during upper gastrointestinal endoscopy. A contrast-enhanced CT scan of the abdomen showed severe invasion of the pancreatic head, and the diagnosis was gastric cancer L, Circ, cType 3, tub2, cT4b, N(+), M0, cStage ⅣA. The patient underwent laparoscopic gastrojejunostomy for gastrointestinal transit obstruction followed by 4 courses of SOX therapy as systemic chemotherapy. After chemotherapy, the invasion to the head of the pancreas was obscured, and pyloric gastrectomy and lymph node dissection were performed. The patient was recurrence-free as of 18 months after surgery. In this case, we performed gastric jejunal bypass surgery followed by chemotherapy with oral anticancer agents to achieve the downstaging of unresectable advanced gastric cancer with pancreatic invasion and pyloric stenosis in patients with poor general condition. As a result, the patient was able to undergo distal gastrectomy, which is one of the recommended multidisciplinary treatments.

Targeted amplicon sequencing for primary tumors and matched lymph node metastases in patients with extrahepatic cholangiocarcinoma.

BACKGROUND: Lymph node metastasis (LNM) is one of the most adverse prognostic factors in extrahepatic cholangiocarcinoma (EHCC) cases. As next-generation sequencing technology has become more widely available, the genomic profile of biliary tract carcinoma has been clarified. However, whether LNMs have additional genomic alterations in patients with EHCC has not been investigated. Here, we aimed to compare the genomic alterations between primary tumors and matched LNMs in patients with EHCC. METHODS: Sixteen patients with node-positive EHCCs were included. Genomic DNA was extracted from tissue samples of primary tumors and matched LNMs. Targeted amplicon sequencing of 160 cancer-related genes was performed. RESULTS: Among the 32 tumor samples from 16 patients, 91 genomic mutations were identified. Genomic mutations were noted in 31 genes, including TP53, MAP3K1, SMAD4, APC, and ARID1A. TP53 mutations were most frequently observed (12/32; 37.5%). Genomic mutation profiles were highly concordant between primary tumors and matched LNMs (13/16; 81.3%), and an additional genomic mutation of CDK12 was observed in only one patient. CONCLUSION: Genomic mutations were highly concordant between primary tumors and matched LNMs, suggesting that genotyping of archived primary tumor samples may help predict genomic mutations of metastatic tumors in patients with EHCC.

[Staging Laparoscopy in the Treatment of Advanced Gastric Cancer].

OBJECTIVE: We examined the applicability and safety of staging laparoscopy(SL)in the treatment of advanced gastric cancer. METHODS: We retrospectively reviewed the gastric cancer cases that were examined using SL between January 2015 and December 2019 at our hospital. RESULTS: Within this period, 59 gastric cancer patients underwent SL, of whom 53 were diagnosed with SL at first examination. The rare complications of SL were postoperative nausea and vomiting(1 case). In 47.5%(28/59)of patients, we observed peritoneal dissemination including positive lavage cytology. In 2 cases, peritoneal dissemination was found during curative resection despite not being detected by SL. Thus, the false negative rate of peritoneal dissemination discovery was 6.7%(2/30). Among the individuals who were diagnosed as P1 or CY1 at first, subsequent SLs were performed in 6 cases, and 5 patients were re-assigned as P0CY0, of whom 4 underwent conversion surgery. CONCLUSIONS: SL is an essential and safe examination method for defining the treatment strategy in advanced gastric cancer. However, further improvements are needed to reduce the false negative discovery rate and to advance gastric cancer treatment by increasing reliability of diagnosis.

Changes in Maximum Tongue Pressure and Postoperative Dysphagia in Mechanically Ventilated Patients after Cardiovascular Surgery.

Background: There is no objective quantitative parameter for dysphagia, and the relationship between changes in maximum tongue pressure values and dysphagia is unknown. This study aimed to determine whether there is a difference in the change in maximal tongue pressure after extubating patients who were ventilated after cardiovascular surgery, with or without dysphagia. Materials and methods: Adult patients who underwent mechanical ventilation via endotracheal intubation following cardiovascular surgery were included. Tongue pressure was measured before cardiovascular surgery and at 6 hours; 3 and 7 days after extubation. Dysphagia was confirmed by the functional oral intake scale (FOIS) on day 7 after extubation; an FOIS level above or equal to 6 was considered "dysphagia-negative." Results: Of 68 patients, 15 (22.1%) were in the dysphagia-positive group, which significantly showed a history of diabetes mellitus, prolonged mechanical ventilation, and postextubation hospitalization. Additionally, the postoperative C-reactive protein level was significantly higher in the dysphagia-positive group than in the dysphagia-negative group. Maximum tongue pressure was significantly lower in the dysphagia-positive group at 3 and 7 days postextubation. Using a cutoff value of 27.6 kPa in a receiver operating characteristic (ROC) curve for maximum tongue pressure at 3 days after extubation, the area under the curve (AUC) was 0.82, sensitivity was 84.9%, and specificity was 84.2%. Conclusion: Tongue pressure at 3 days after extubation is significantly lower in patients with dysphagia after cardiovascular surgery than in patients without dysphagia. If the maximum tongue pressure value is below 27.6 kPa on the third day following extubation, oral intake should be performed with caution. How to cite this article: Yamada T, Ochiai R, Kotake Y. Changes in Maximum Tongue Pressure and Postoperative Dysphagia in Mechanically Ventilated Patients after Cardiovascular Surgery. Indian J Crit Care Med 2022;26(12):1253-1258.

Phase II Study of Low-Dose Afatinib Maintenance Treatment Among Patients with EGFR-Mutated Non-Small Cell Lung Cancer: North Japan Lung Cancer Study Group Trial 1601 (NJLCG1601).

LESSONS LEARNED: Low-dose afatinib maintenance treatment among patients with EGFR-mutated NSCLC achieved long-time to treatment failure with fewer treatment-related AEs without detracting from the therapeutic efficacy. This modified regimen represents a practical usage that balances effectiveness and safety. BACKGROUND: Although afatinib is an effective therapy for patients with EGFR-mutated non-small cell lung cancer (NSCLC), drug-related adverse events (AEs) have often necessitated dose reductions. In a post hoc analysis of the LUX-Lung 3 and 6 trials, there was no difference in median progression-free survival (PFS) between patients who had the dose of afatinib reduced and those who did not. We thus evaluated the efficacy and tolerability of low-dose afatinib maintenance treatment among patients with NSCLC harboring EGFR mutations who had not been previously treated. METHODS: Eligible patients received afatinib 40 mg orally once daily. When prescribed grade ≥ 2 AEs, rash of grade ≥ 3, or unacceptable toxicity occurred, the afatinib dose was reduced from 40 to 30 mg and if needed from 30 to 20 mg. The primary endpoint was the 1-year PFS rate. Secondary endpoints were PFS, overall response rate (ORR), and toxicity. RESULTS: Among 30 patients, 93% had adenocarcinoma, 53% had exon 19 deletion, 37% had L858R, and 10% had minor mutations. The 1-year PFS rate was 50% (95% confidence interval [CI], 31.3-66.1) and the median PFS was 11.8 months (95% CI, 7.1-21.4). The incidence rate of grade ≥ 3 toxicities was 57%, including elevated aspartate aminotransferase/alanine aminotransferase level (13%), diarrhea (10%), and paronychia (10%). CONCLUSION: Low-dose afatinib maintenance treatment reduced treatment-related AEs without detracting from the therapeutic efficacy.

Frailty is a useful predictive marker of postoperative complications after pancreaticoduodenectomy.

BACKGROUND: Frailty results in a high risk for disability, hospitalization, and mortality. This study aimed to investigate perioperative details of frail patients who underwent pancreatectomy and whether frailty can be a predictive factor of postoperative complications, especially of clinically relevant postoperative pancreatic fistula (CR-POPF). METHODS: This retrospective study included patients who underwent pancreatectomy in our hospital between August 2016 and March 2019. The patients were divided into frail and pre-/non-frail groups. The diagnostic criteria were based on the Japanese version of the Cardiovascular Health Study. RESULTS: Of 93 patients, 11 (11.8%) and 82 (88.2%) were frail and pre-/non-frail patients, with median ages of 82 and 72 years, respectively (p = 0.041). Postoperative complications (Clavien-Dindo ≧ IIIa) were found in 8 and 32 patients (p = 0.034), CR-POPF in 3 and 13 patients (p = 0.346), and postoperative hospital stays were 21 and 17 days (p = 0.041), respectively. On multivariate analysis, frailty was an independent predictive factor (odds ratio [OR] 5.604, 95.0% confidence interval [CI] 1.002-30.734; p = 0.047) of postoperative complications (Clavien-Dindo ≧ IIIa) after pancreaticoduodenectomy. On multivariate analysis, a soft pancreas (OR 5.696, 95.0% CI 1.142-28.149; p = 0.034) was an independent and significant predictive factor of CR-POPF after pancreaticoduodenectomy. CONCLUSIONS: Frailty may be a useful predictive factor of postoperative complications in patients undergoing pancreaticoduodenectomy.

[A Case of DIC Following Mixed Acidosis during Laparoscopic Hepatectomy].

The patient was an 81-year-old man. Laparoscopic sigmoidectomy was performed for a sigmoid colon cancer(S, type 2, pT3[SS], INF a, Ly0, V0, BD1, Pn0, pPM0, pDM0, RM0, pN0, pM0, pStage Ⅲa, R0, Cur A). One year after the surgery, a blood test showed CEA as high as 68.9 ng/mL, and an abdominal enhanced computed tomography revealed a hepatic tumor showing marginal contrast in the 4th liver segment. Positron emission tomography showed an accumulation of SUVmax 19.0 at the same site, and a metastatic liver tumor was diagnosed. A laparoscopic medial hepatectomy was performed. Bleeding from the hepatectomy site increased significantly after completion. Subcutaneous emphysema spreading from the face to the trunk and thigh was observed, and blood tests revealed a pH of 7.172, PaCO2 of 71.0 mmHg, lactate of 67 mg/dL, mixed acidosis, D-dimer of 118 µg/mL, and a disseminated intravascular coagulation(DIC)syndrome was diagnosed. Following the difficulty of hemostasis, the surgery was changed to laparotomy and terminated by gauze packing. We encountered a case of acidosis exacerbated by hypercapnia that progressed to DIC during laparoscopic medial hepatectomy.

[A Case of Ammonium Acid Urate Staghorn Calculi Lost Only in the Drug Therapy].

We report a case of a staghorn stone containing ammonium acid urate that was effectively treated with drug therapy alone. A 46-year-old man had recurring urinary tract stones. He had no previous episode of urinary tract stones that required hospitalization and operation. He received only drug therapy for hyperuricemia in another hospital. Ultrasonography and computed tomography revealed a left staghorn stone measuring 37×34 mm. The kidney-ureter-bladder radiograph did not show any stones. His urine was acidic, and we estimated that the left staghorn stone consisted of urate. Oral administration of sodium hydrogen carbonate was initiated to alkalize the urine, and treatment with transurethral lithotripsy (TUL) was scheduled. Before the TUL, analysis of an excreted stone sample revealed that it consisted of ammonium acid urate. The staghorn stone was completely removed in 10 months after the first medical examination. At present, the patient is free of urinary tract stones.

Genomic characterization of biliary tract cancers identifies driver genes and predisposing mutations.

BACKGROUND & AIMS: Biliary tract cancers (BTCs) are clinically and pathologically heterogeneous and respond poorly to treatment. Genomic profiling can offer a clearer understanding of their carcinogenesis, classification and treatment strategy. We performed large-scale genome sequencing analyses on BTCs to investigate their somatic and germline driver events and characterize their genomic landscape. METHODS: We analyzed 412 BTC samples from Japanese and Italian populations, 107 by whole-exome sequencing (WES), 39 by whole-genome sequencing (WGS), and a further 266 samples by targeted sequencing. The subtypes were 136 intrahepatic cholangiocarcinomas (ICCs), 101 distal cholangiocarcinomas (DCCs), 109 peri-hilar type cholangiocarcinomas (PHCs), and 66 gallbladder or cystic duct cancers (GBCs/CDCs). We identified somatic alterations and searched for driver genes in BTCs, finding pathogenic germline variants of cancer-predisposing genes. We predicted cell-of-origin for BTCs by combining somatic mutation patterns and epigenetic features. RESULTS: We identified 32 significantly and commonly mutated genes including TP53, KRAS, SMAD4, NF1, ARID1A, PBRM1, and ATR, some of which negatively affected patient prognosis. A novel deletion of MUC17 at 7q22.1 affected patient prognosis. Cell-of-origin predictions using WGS and epigenetic features suggest hepatocyte-origin of hepatitis-related ICCs. Deleterious germline mutations of cancer-predisposing genes such as BRCA1, BRCA2, RAD51D, MLH1, or MSH2 were detected in 11% (16/146) of BTC patients. CONCLUSIONS: BTCs have distinct genetic features including somatic events and germline predisposition. These findings could be useful to establish treatment and diagnostic strategies for BTCs based on genetic information. LAY SUMMARY: We here analyzed genomic features of 412 BTC samples from Japanese and Italian populations. A total of 32 significantly and commonly mutated genes were identified, some of which negatively affected patient prognosis, including a novel deletion of MUC17 at 7q22.1. Cell-of-origin predictions using WGS and epigenetic features suggest hepatocyte-origin of hepatitis-related ICCs. Deleterious germline mutations of cancer-predisposing genes were detected in 11% of patients with BTC. BTCs have distinct genetic features including somatic events and germline predisposition.

Impact of serum carbohydrate antigen 19-9 level on prognosis and prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma.

BACKGROUND AND AIM: Lymph node metastasis is an important prognostic factor for intrahepatic cholangiocarcinoma (ICC), but accurate preoperative diagnosis is difficult. The aim of this study was to measure the concentration of serum carbohydrate antigen 19-9 (s-CA19-9) as a preoperative predictor of lymph node metastasis. METHODS: In our department, curative-intent hepatectomy for ICC has been performed only once the absence of metastases in para-aortic lymph nodes (PALN) has been confirmed from intraoperative frozen-section pathological examinations. The present study included 13 non-resected ICC patients with PALN metastasis (PALN group) and 44 resected ICC patients without PALN metastasis (non-PALN group). S-CA19-9 was examined to evaluate predictive performance for PALN metastasis and regional lymph node metastasis (pN1) from analysis of the receiver operating characteristic curve. In the non-PALN group, univariate and multivariate analyses for survival were performed on clinicopathological variables. RESULTS: From receiver operating characteristic curve analysis, s-CA19-9 showed good diagnostic accuracy for PALN metastasis (68%; cut-off, 200 U/mL) and pN1 (77%; cut-off, 100 U/mL). In univariate analysis, age (<65 years), s-CA19-9 (≥100 U/mL), portal vein resection, pN1, and positive resection margin (R1) were all identified as significant negative prognostic factors. Five-year survival rates of patients with high s-CA19-9 and pN1 were 6.9% and 7.3%, respectively. In multivariate analysis, high s-CA19-9 and R1 represented independent predictors of poor prognosis. CONCLUSIONS: Preoperative s-CA19-9 appears useful as a biomarker in patients with ICC, for predicting not only lymph node metastasis but also prognosis after surgical resection with curative intent.

Improving computational accuracy in dissipative particle dynamics via a high order symplectic method.

This study was focused on improving the numerical accuracy of the dissipative particle dynamics simulation via modifying its numerical time integration scheme. Despite the integration of the pairwise Langevin part dealt with by most of the previous studies, we paid attention to the improvement of the standard Liouville part. The numerical accuracy was measured by the configurational temperature in this study. Employing a fourth order symplectic scheme showed a significant improvement of the numerical accuracy for the simulations especially with a large time increment when comparing it with existing schemes, which indicates that enough resolution in time was attained when our modified scheme was employed. In addition, a set of simulations was performed for a wider range of time increments than previous studies. The results showed that the computational error demonstrated different orders of accuracy for different time increment ranges, which led to the fact that the dominant effect on the error is conservative and random forces for the large and small increment ranges.

Skills acquisition for novice learners after a point-of-care ultrasound course: does clinical rank matter?

BACKGROUND: Few studies have compared the effectiveness of brief training courses on point-of-care ultrasound (POCUS) skill acquisition of novice attending physicians vs. trainees. The purpose of this study was to evaluate the change in POCUS image interpretation skills and confidence of novice attending physicians vs. trainees after a 1-day POCUS training course. METHODS: A 1-day POCUS training course was held in March 2017 in Japan. A standardized training curriculum was developed that included online education, live lectures, and hands-on training. The pre-course assessment tools included a written examination to evaluate baseline knowledge and image interpretation skills, and a physician survey to assess confidence in performing specific ultrasound applications. The same assessment tools were administered post-course, along with a course evaluation. All learners were novices and were categorized as trainees or attending physicians. Data were analyzed using two-way analysis of variance. RESULTS: In total, 60 learners attended the course, and 51 learners (85%) completed all tests and surveys. The 51 novice learners included 29 trainees (4 medical students, 9 PGY 1-2 residents, 16 PGY 3-5 residents) and 22 attending physicians (6 PGY 6-10 physicians, and 16 physicians PGY 11 and higher). The mean pre- and post-course test scores of novice trainees improved from 65.5 to 83.9% while novice attending physicians improved from 66.7 to 81.5% (p < 0.001). The post-course physician confidence scores in using ultrasound significantly increased in all skill categories for both groups. Both trainees and attending physicians demonstrated similar improvement in their post-course test scores and confidence with no statistically significant differences between the groups. The course evaluation scores for overall satisfaction and satisfaction with faculty members' teaching skills were 4.5 and 4.6 on a 5-point scale, respectively. CONCLUSIONS: Both novice trainees and attending physicians showed similar improvement in point-of-care ultrasound image interpretation skills and confidence after a brief training course. Although separate training courses have traditionally been developed for attending physicians and trainees, novice learners of point-of-care ultrasound may acquire skills at similar rates, regardless of their ranking as an attending physician or trainee. Future studies are needed to compare the effectiveness of short training courses on image acquisition skills and determine the ideal course design.

Usefulness of Simultaneous Measurement of Plasma Steroids, Including Precursors, for the Evaluation of Drug Effects on Adrenal Steroidogenesis in Rats.

The aim of this study was to evaluate the usefulness of simultaneous measurement of plasma steroids, including precursors, for the evaluation of drug effects on adrenal steroidogenesis in vivo. Plasma concentrations of corticosterone and its precursors were examined in rats dosed with compounds that affect adrenal steroidogenesis via different modes of action as well as the relationships of the changes with blood chemistry and adrenal histopathology. Male rats were dosed with tricresyl phosphate, aminoglutethimide, trilostane (TRL), metyrapone (MET), ketoconazole (KET), or mifepristone for 7 days. In the TRL, MET, and KET groups, precursor levels were markedly increased, while there were no significant changes in the corticosterone level, suggesting that the precursors are more sensitive biomarkers to detect the effect on adrenal steroidogenesis. Also, the precursors with increased levels were those that are normally metabolized by the inhibited enzymes, reflecting the modes of action of the compounds. In addition, different patterns of changes were observed in blood chemistry and histopathology, supporting the mechanism suggested by the steroid changes. These results show that simultaneous measurement of plasma steroids, including precursors, can be a valuable method to sensitively evaluate drug effects on adrenal steroidogenesis and to investigate the underlying mechanisms.

Reliability and acceptability of six station multiple mini-interviews: past-behavioural versus situational questions in postgraduate medical admission.

BACKGROUND: The multiple mini-interview (MMI) is increasingly used for postgraduate medical admissions and in undergraduate settings. MMIs use mostly Situational Questions (SQs) rather than Past-Behavioural Questions (PBQs). A previous study of MMIs in this setting, where PBQs and SQs were asked in the same order, reported that the reliability of PBQs was non-inferior to SQs and that SQs were more acceptable to candidates. The order in which the questions are asked may affect reliability and acceptability of an MMI. This study investigated the reliability of an MMI using both PBQs and SQs, minimising question order bias. Acceptability of PBQs and SQs was also assessed. METHODS: Forty candidates applying for a postgraduate medical admission for 2016-2017 were included; 24 examiners were used. The MMI consisted of six stations with one examiner per station; a PBQ and a SQ were asked at every station, and the order of questions was alternated between stations. Reliability was analysed for scores obtained for PBQs or SQs separately, and for both questions. A post-MMI survey was used to assess the acceptability of PBQs and SQs. RESULTS: The generalisability (G) coefficients for PBQs only, SQs only, and both questions were 0.87, 0.96, and 0.80, respectively. Decision studies suggested that a four-station MMI would also be sufficiently reliable (G-coefficients 0.82 and 0.94 for PBQs and SQs, respectively). In total, 83% of participants were satisfied with the MMI. In terms of face validity, PBQs were more acceptable than SQs for candidates (p = 0.01), but equally acceptable for examiners (88% vs. 83% positive responses for PBQs vs. SQs; p = 0.377). Candidates preferred PBQs to SQs when asked to choose one, though this difference was not significant (p = 0.081); examiners showed a clear preference for PBQs (p = 0.007). CONCLUSIONS: Reliability and acceptability of six-station MMI were good among 40 postgraduate candidates; modelling suggested that four stations would also be reliable. SQs were more reliable than PBQs. Candidates found PBQs more acceptable than SQs and examiners preferred PBQs when they had to choose between the two. Our findings suggest that it is better to ask both PBQs and SQs during an MMI to maximise acceptability.