Diagnostic Value and Safety of Addition of Transbronchial Needle Aspiration to Transbronchial Biopsy Through Endobronchial Ultrasonography Using a Guide Sheath Under Virtual Bronchoscopic Navigation for the Diagnosis of Peripheral Pulmonary Lesions.

BACKGROUND: The diagnostic yield of peripheral pulmonary lesions (PPLs) through endobronchial ultrasonography with a guide sheath transbronchial biopsy (EBUS-GS TBB) under virtual bronchoscopic navigation is unsatisfactory because radial EBUS probe is not always located within the lesion. Transbronchial needle aspiration with a guide sheath (GS-TBNA) has the potential to overcome the lower diagnostic yield by improving the relationship between the probe and the lesion and enabling repeated sampling while maintaining the location of a GS near the lesion. However, there are few data regarding the diagnostic yield and safety for diagnosing PPLs in this procedure. METHODS: We retrospectively analyzed consecutive 363 lesions (83 lesions underwent GS-TBNA/EBUS-GS TBB and 280 lesions underwent EBUS-GS TBB) at our institution between April 1, 2019 and March 31, 2022. We investigated the diagnostic efficacy and complications of GS-TBNA/EBUS-GS TBB and compared them with those of EBUS-GS TBB. RESULTS: The lesion size, distance from the hilum, presence of bronchus leading to the lesion, and EBUS images during the examination differed significantly between the two procedures. Logistic regression analysis adjusted for these 4 covariates revealed that GS-TBNA/EBUS-GS TBB was a significant factor affecting the diagnostic success of PPLs compared with EBUS-GS TBB (odds ratio=2.43, 95% CI=1.16-5.07, P=0.018). Neither procedure differed significantly in terms of complications (6.0% vs. 5.7%, P>0.999). CONCLUSION: GS-TBNA performed in addition to EBUS-GS TBB might be a promising sampling method for improving the diagnostic yield for PPLs without increasing the incidence of complications.

Effects of KRAS, STK11, KEAP1, and TP53 mutations on the clinical outcomes of immune checkpoint inhibitors among patients with lung adenocarcinoma.

BACKGROUND: This study aimed to identify the associations between individual KRAS, STK11, KEAP1, or TP53 mutations, as well as the comutation status of these genes, and the tumor mutation burden (TMB) with clinical outcomes of lung adenocarcinoma patients treated with immune checkpoint inhibitors (ICIs). METHODS: We collected data from patients with lung adenocarcinoma treated with ICIs from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database between June 2019 and August 2023. The main endpoints were the treatment response and overall survival (OS). RESULTS: Among 343 patients with lung adenocarcinoma, 61 (18%), 69 (20%), 41 (12%), and 222 (65%) patients had KRAS, STK11, KEAP1, and TP53 mutations, respectively. An overall objective response was observed in 94 of 338 patients (28%), including 2 (1%) who achieved a complete response and 92 (27%) who achieved a partial response. Patients with STK11, KEAP1, or TP53 mutations had a significantly greater TMB (P<0.001). According to the univariate analysis, the treatment response was significantly correlated with TP53 mutation in both the general (P = 0.041) and KRAS wild-type (P = 0.009) populations. KEAP1 and TP53 mutations were associated with worse OS among assessable patients (hazard ratio (HR) = 2.027, P = 0.002; HR = 1.673, P = 0.007, respectively) and among patients without KRAS mutations (HR = 1.897, P = 0.012; HR = 1.908, P = 0.004, respectively). According to the multivariate analysis, KEAP1 (HR = 1.890, P = 0.008) and TP53 (HR = 1.735, P = 0.011) mutations were found to be independent factors for OS. CONCLUSIONS: STK11, KEAP1, and TP53 mutations are significantly associated with a high TMB. TP53 mutation could affect the treatment response to some degree, and both KEAP1 and TP53 mutations resulted in inferior OS in the general patient population and in those with KRAS-wild-type lung adenocarcinoma, indicating that KEAP1 and TP53 mutations might act as prognostic factors for ICI treatment in lung adenocarcinoma patients.

Comparison of Central and Peripheral Arterial Blood Pressure Gradients in Critically Ill Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: Measurement of blood pressure taken from different anatomical sites, are often perceived as interchangeable, despite them representing different parts of the systemic circulation. We aimed to perform a systematic review and meta-analysis on blood pressure differences between central and peripheral arterial cannulation in critically ill patients. DATA SOURCES: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase from inception to December 26, 2023, using Medical Subject Headings (MeSH) terms and keywords. STUDY SELECTION: Observation study of adult patients in ICUs and operating rooms who underwent simultaneous central (femoral, axillary, or subclavian artery) and peripheral (radial, brachial, or dorsalis pedis artery) arterial catheter placement in ICUs and operating rooms. DATA EXTRACTION: We screened and extracted studies independently and in duplicate. We assessed risk of bias using the revised Quality Assessment for Studies of Diagnostic Accuracy tool. DATA SYNTHESIS: Twenty-four studies that enrolled 1598 patients in total were included. Central pressures (mean arterial pressure [MAP] and systolic blood pressure [SBP]) were found to be significantly higher than their peripheral counterparts, with mean gradients of 3.5 and 8.0 mm Hg, respectively. However, there was no statistically significant difference in central or peripheral diastolic blood pressure (DBP). Subgroup analysis further highlighted a higher MAP gradient during the on-cardiopulmonary bypass stage of cardiac surgery, reperfusion stage of liver transplant, and in nonsurgical critically ill patients. SBP or DBP gradient did not demonstrate any subgroup specific changes. CONCLUSIONS: SBP and MAP obtained by central arterial cannulation were higher than peripheral arterial cannulation; however, clinical implication of a difference of 8.0 mm Hg in SBP and 3.5 mm Hg in MAP remains unclear. Our current clinical practices preferring peripheral arterial lines need not change.

Anxiety evaluated by the Hospital Anxiety and Depression Scale as a predictor of postoperative nausea and vomiting: a pilot study.

The incidence of postoperative nausea and vomiting (PONV) remains high, and improving the accuracy of PONV prediction remains challenging. The primary aim of this study is to examine the impact of anxiety scores evaluated using the Hospital Anxiety and Depression Scale (HADS) on the PONV prediction model. We hypothesized that anxiety and depression, quantified using the HADS, could improve the accuracy of the PONV predictive model. This pilot study evaluated 100 patients. The HADS was conducted by a self-evaluation method before thoracoscopic surgery for lung tumors, and the anesthesia method was standardized. The criterion was whether the nurse in charge of the patient who complained of PONV assessed that drug administration was necessary. As the main analysis, the odds ratio of the HADS score for predicting PONV was evaluated using multivariable logistic regression models. Further, the receiver operating characteristic (ROC) curves of the model with the HADS score added to the variables of without-anxiety predictors and the model with the variables of without-anxiety predictors only were compared. The anxiety score was significantly higher in the PONV group than in the no PONV group (P = 0.021). For predictive accuracy, the model that included age, sex, smoking history, history of PONV, and anxiety score had a higher area under the ROC curve than did the model excluding the anxiety score (P = 0.021). In conclusion, the findings indicate that the HADS is worth investigating as a predictor of PONV.

Evaluation of 4D Flow MRI-Derived Relative Residence Time as a Marker for Cirrhosis Associated Portal Vein Thrombosis.

BACKGROUND: Portal vein thrombosis (PVT) is thought to arise from stagnant blood flow, yet conclusive evidence is lacking. Relative residence time (RRT) assessed using 4D Flow MRI may offer insight into portal flow stagnation. PURPOSE: To explore the relationship between RRT values and the presence of PVT in cirrhotic participants. STUDY TYPE: Prospective. POPULATION: Forty-eight participants with liver cirrhosis (27 males, median age 67 years [IQR: 57-73]) and 20 healthy control participants (12 males, median age 45 years [IQR: 40-54]). FIELD STRENGTH/SEQUENCE: 3 T/4D Flow MRI. ASSESSMENT: Laboratory (liver and kidney function test results and platelet count) and clinical data (presence of tumors and other imaging findings), and portal hemodynamics derived from 4D Flow MRI (spatiotemporally averaged RRT [RRT-mean], flow velocity, and flow rate) were analyzed. STATISTICAL TESTS: We used multivariable logistic regression, adjusted by selected covariates through the Lasso method, to explore whether RRT-mean is an independent risk factor for PVT. The area under the ROC curve (AUC) was also calculated to assess the model's discriminative ability. P < 0.05 indicated statistical significance. RESULTS: The liver cirrhosis group consisted of 16 participants with PVT and 32 without PVT. Higher RRT-mean values (odds ratio [OR] 11.4 [95% CI: 2.19, 118]) and lower platelet count (OR 0.98 per 1000 µL [95% CI: 0.96, 0.99]) were independent risk factors for PVT. The incorporation of RRT-mean (AUC, 0.77) alongside platelet count (AUC, 0.75) resulted in an AUC of 0.84. When including healthy control participants, RRT-mean had an adjusted OR of 12.4 and the AUC of the combined model (RRT-mean and platelet count) was 0.90. DATA CONCLUSION: Prolonged RRT values and low platelet count were significantly associated with the presence of PVT in cirrhotic participants. RRT values derived from 4D Flow MRI may have potential clinical relevance in the management of PVT. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Docetaxel, cisplatin, and fluorouracil with pegfilgrastim on day 3 as neoadjuvant chemotherapy for esophageal cancer.

PURPOSE: A high risk of febrile neutropenia (FN) from neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer has been reported. The optimal timing of prophylactic use of pegfilgrastim remains to be elucidated. To evaluate the effect of pegfilgrastim administered on day 3, we conducted a feasibility study. METHODS: Chemotherapy consisted of intravenous administration of docetaxel (70 mg/m2 per day) and cisplatin (70 mg/m2 per day) on day 1 and continuous infusion of 5-fluorouracil (750 mg/m2 per day) on days 1-5. Pegfilgrastim was given as a single subcutaneous injection at a dose of 3.6 mg on day 3 during each treatment course. This regimen was repeated every 3 weeks for up to a maximum of three courses. Prophylactic antibiotics were not needed but were allowed to be given at the discretion of the physician. The primary endpoint was the incidence of FN. RESULTS: Twenty-six patients were administered DCF in combination with pegfilgrastim on day 3. After the first course of DCF, 10 out of 26 patients (38.5%) experienced grade 4 neutropenia, and two patients (7.7%) experienced FN. Of the 14 patients who did not receive prophylactic antibiotics, four had grade 4 neutropenia, including two who developed FN. On the contrary, of the 12 patients who received prophylactic levofloxacin, six had grade 4 neutropenia, but no cases of FN were observed. CONCLUSION: Administration of pegfilgrastim on day 3 was not sufficient to prevent FN due to DCF treatment, and prophylactic administration of both pegfilgrastim and antibiotics could be a solution.

Efficacy of intraoperative irrigation with artificial cerebrospinal fluid in chronic subdural hematoma surgery: study protocol for a multicenter randomized controlled trial.

BACKGROUND: The surgical techniques for treatment of chronic subdural hematoma (CSDH), a common neurosurgical condition, have been discussed in a lot of clinical literature. However, the recurrence proportion after CSDH surgery remains high, ranging from 10 to 20%. The standard surgical procedure for CSDH involves a craniostomy to evacuate the hematoma, but irrigating the hematoma cavity during the procedure is debatable. The authors hypothesized that the choice of irrigation fluid might be a key factor affecting the outcomes of surgery. This multicenter randomized controlled trial aims to investigate whether intraoperative irrigation using artificial cerebrospinal fluid (ACF) followed by the placement of a subdural drain would yield superior results compared to the placement of a subdural drain alone for CSDH. METHODS: The study will be conducted across 19 neurosurgical departments in Japan. The 1186 eligible patients will be randomly allocated to two groups: irrigation using ACF or not. In either group, a subdural drain is to be placed for at least 12 h postoperatively. Similar to what was done in previous studies, we set the proportion of patients that meet the criteria for ipsilateral reoperation at 7% in the irrigation group and 12% in the non-irrigation group. The primary endpoint is the proportion of patients who meet the criteria for ipsilateral reoperation within 6 months of surgery (clinical worsening of symptoms and increased hematoma on imaging compared with the postoperative state). The secondary endpoints are the proportion of reoperations within 6 months, the proportion being stratified by preoperative hematoma architecture by computed tomography (CT) scan, neurological symptoms, patient condition, mortality at 6 months, complications associated with surgery, length of hospital stay from surgery to discharge, and time of the surgical procedure. DISCUSSION: We present the study protocol for a multicenter randomized controlled trial to investigate our hypothesis that intraoperative irrigation with ACF reduces the recurrence proportion after the removal of chronic subdural hematomas compared with no irrigation. TRIAL REGISTRATION: ClinicalTrials.gov jRCT1041220124. Registered on January 13, 2023.

Genetic polymorphisms as predictive biomarkers of adverse events during preoperative chemotherapy in esophageal cancer.

PURPOSE: This study aimed to explore associations between genetic polymorphisms and adverse effects due to preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer. METHODS: Preoperative DCF (docetaxel, 70 mg/m2/day, day 1; cisplatin, 70 mg/m2/day, day 1; fluorouracil, 750 mg/m2/day, days 1-5) was repeated every 3 weeks for up to three cycles. Genotyping of nine candidate genetic polymorphisms was conducted using blood samples from the enrolled patients. RESULTS: According to a multivariable analysis evaluating 50 patients, grade 3 or worse neutropenia was more likely to occur in those with the ABCC2-24C/T or T/T genotype (rs717620) (OR, 5.30, P = 0.013). Additionally, patients with the TYMS 3'-UTR 0 bp/0 bp genotype (rs151264360) showed a trend toward grade 3 or worse hyponatremia (OR, 0.16, P = 0.005). Grade 2 or worse thrombocytopenia was more likely to occur in patients with the TNF-α-1031C/T or T/T genotype (rs1799964) (OR, 6.30, P = 0.016) and IL-6-634C/C genotype (rs1800796) (OR, 0.18, P = 0.034), and grade 2 or worse anemia was more likely to occur in patients with the MCP-1-2518G/G genotype (rs1024611) (OR, 0.19, P = 0.027). CONCLUSIONS: ABCC2-24C > T (rs717620), TYMS 3'-UTR 6-bp indel (rs151264360), TNF-α-1031T > C (rs1799964) as well as IL-6-634G > C (rs1800796), and MCP-1-2518A > G (rs1024611) polymorphisms might serve as independent and predictive biomarkers for neutropenia, hyponatremia, thrombocytopenia, and anemia, respectively, during preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for patients with esophageal cancer.

Total Hydrocortisone Dosage in the Neonatal Period May Be Related to Low Developmental Quotient in Extremely Low Birth Weight Infants: A Retrospective Cohort Study.

INTRODUCTION: The effects of hydrocortisone (HDC) administration to extremely low birth weight (ELBW) infants on later development remain unclear. This study examined the association between HDC dosage during neonatal period and neurodevelopmental outcomes in ELBW infants. METHODS: This study was a retrospective cohort study conducted in eight centers in Japan. The subjects of this study were ELBW infants born between April 2015 and March 2017. The association between postnatal total HDC dosage up to 36 weeks postmenstrual age and the developmental quotient (DQ) at 3 years of age was examined. Multiple linear regression evaluated the association, adjusting for weeks of gestation, birth weight, and the presence of bronchopulmonary dysplasia, late-onset circulatory collapse, intracranial hemorrhage, necrotizing enterocolitis, and sepsis. RESULTS: This study included 218 ELBW infants, of whom 144 underwent a developmental test at 3 years of age. Simple linear regression analysis revealed a significant association between total HDC dosage and DQ at 3 years of age (coefficients: -2.65, 95% CI: -3.73, -1.57). Multiple linear regression analysis adjusted for the presence of bronchopulmonary dysplasia and late-onset circulatory collapse also revealed a significant association between total HDC dosage and DQ at 3 years of age (coefficients: -2.66, 95% CI: -3.89, -1.42). CONCLUSION: Higher total HDC dosage up to 36 weeks postmenstrual age in ELBW infants was associated with impaired neurodevelopmental outcomes. Although HDC is often needed in the treatment of ELBW infants, clinicians should be aware that an increased dose of HDC may be associated with impaired neurodevelopmental outcomes.

Optimal D-Dimer Cutoff Values for Diagnosing Deep Vein Thrombosis in Patients with Comorbid Malignancies.

BACKGROUND: Patients with malignancy are at high risk of venous thromboembolism, and early diagnosis is important. The Khorana score is known as a risk assessment for cancer-related thrombosis during chemotherapy, but there are still few reports on its diagnostic potential, the optimal D-dimer cutoff values for indications other than chemotherapy and the use of the Khorana score in combination with D-dimers. In this study, we examined the clinical appropriateness of increasing the D-dimer cutoff value. METHODS: We retrospectively studied 208 malignancies out of 556 patients who underwent lower extremity venous ultrasonography at our hospital over a 2-year period from January 2018 to December 2019. The optimal D-dimer cutoff value for predicting deep vein thrombosis (DVT) in patients with malignancy was calculated by the Youden index. The usefulness of the Khorana score alone and the model combining the Khorana score with D-dimer for predicting DVT diagnosis was compared using receiver operating characteristic analysis. RESULTS: Of 208 eligible patients, 59 (28.4%) had confirmed DVT. The optimal D-dimer cutoff value for predicting DVT comorbidity in patients with malignancy was 3.96 µg/mL. When the new D-dimer cutoff value was set at 4.0 µg/mL, the odds ratio (OR) for DVT diagnosis was 4.23 (95% confidence interval (CI) 2.10-8.55, P < 0.001), which was higher than the OR of 1.33 (95% CI: 0.98-1.81, P = 0.064) for the Khorana score. The area under the curve for the Khorana score and D-dimer was 0.714, which was significantly higher than the 0.611 for the Khorana score alone, with the difference being significantly higher at 0.103 (P = 0.004, 95% CI: 0.033-0.173). CONCLUSIONS: The optimal D-dimer cutoff value for the diagnosis of DVT in patients with malignancy was 4.0 µg/mL. It was also suggested that the combination of the Khorana score with the D-dimer level was more accurate in diagnosing DVT than the Khorana score alone.

Phase 1b study on the repurposing of meclizine hydrochloride for children with achondroplasia.

Achondroplasia (ACH) is a common skeletal dysplasia characterized by a disproportionately short stature. We found that meclizine, which is an over-the-counter drug for motion sickness, inhibited the fibroblast growth factor receptor 3 (FGFR3) gene using a drug repositioning strategy, and meclizine 1 and 2 mg/kg/day promoted bone growth in a mouse model of ACH. A previous phase 1a clinical trial for children with ACH demonstrated that a single dose of meclizine 25 and 50 mg was safe and that the simulated plasma concentration achieved steady state approximately 10 days after the first dose. The current study aimed to evaluate the safety and pharmacokinetics (PK) of meclizine in children with ACH after a 14-day-repeated dose of meclizine. Twelve patients with ACH aged 5-10 years were enrolled. Meclizine 12.5 (cohort 1) and 25 mg/day (cohort 2) were administered after meals for 14 days, and adverse events (AEs) and PK were evaluated. No patient experienced serious AEs in either group. The average (95% confidential interval [CI]) maximum drug concentration (Cmax), peak drug concentration (Tmax), area under the curve (AUC) from 0 to 24 h, and terminal elimination half-life (t1/2) after a 14-day-repeated administration of meclizine (12.5 mg) were 167 (83-250) ng/mL, 3.7 (3.1-4.2) h, 1170 (765-1570) ng·h/mL, and 7.4 (6.7-8.0) h, respectively. The AUC0-6h after the final administration was 1.5 times that after the initial dose. Cmax and AUC were higher in cohort 2 than in cohort 1 in a dose-dependent manner. Regarding the regimen of meclizine 12.5 and 25 mg in patients < 20 kg and ≥ 20 kg, respectively, the average (95% CI) AUC0-24h was 1270 (1100-1440) ng·h/mL. Compartment models demonstrated that the plasma concentration of meclizine achieved at a steady state after the 14th administration. Long-term administration of meclizine 12.5 or 25 mg/day is recommended for phase 2 clinical trials in children with ACH.

Pelvic morphologies of developmental dysplasia and primary osteoarthritis on range of motion after total hip arthroplasty.

Bony impingement, especially in the anterior inferior iliac spine (AIIS) after total hip arthroplasty (THA), may cause dislocation. However, the influence of AIIS characteristics on bony impingement after THA is not fully understood. Thus, we aimed to determine the morphological characteristics of AIIS with developmental dysplasia of the hip (DDH) and primary osteoarthritis (pOA) and to evaluate its effect on range of motion (ROM) after THA. Hips from 130 patients who underwent THA, including pOA were analyzed. In total, we had 27 male and 27 female participants with pOA, and 38 male and 38 female participants with DDH. The horizontal distances of AIIS from teardrop (TD) were compared. In the computed tomography simulation, flexion ROM was measured, and its relationship to the distance between TD and AIIS was investigated. DDH had a more medial (male: DDH, 36.9 ± 5.8; pOA, 45.5 ± 6.1; p < 0.001) (female: DDH, 31.5 ± 10.0; pOA, 36.2 ± 4.7; p < 0.001) position of AIIS than pOA. In the male with pOA group, flexion ROM was significantly smaller than that in the other groups, and there was a correlation between flexion ROM and horizontal distances (r = -0.543; 95% confidence interval = -0.765 to -0.206; p = 0.003). AIIS position is a factor that limits ROM during flexion after THA, particularly in males. Further studies are required to develop surgical strategies for cases of impingement at the AIIS site after THA. Level of evidence: Ð¨, retrospective comparative study.

Fixation of intra-articular calcaneal fractures: A comparative study of the postoperative outcome between HA/PPLA screws and locking plates.

Background: Forged unsintered hydroxyapatite and poly l-lactic acid (F-u-HA/PLLA) screw is bioactivite, bioabsorbable, and radiopaque with high mechanical strength. Its efficacy has been previously demonstrated in the treatment of lateral humeral condylar, lateral tibial condylar, ankle, and patellar fractures. However, studies on its efficacy in treatment of calcaneal fractures is lacking. This study aimed to compare the postoperative results of F-u-HA/PLLA screw fixation and locking plate fixation for intra-articular calcaneal fractures. Methods: From January 2013 to December 2019, 47 closed intra-articular fractures treated with either F-u-HA/PLLA screws (group S, 18 feet in 17 patients) or locking plates (group P, 29 feet in 28 patients) in a single trauma center were retrospectively reviewed. The sinus tarsi approach was used in both groups. The time to bone union, step-off, varus deformity, Bohler's angle, and width and height of the calcaneus were assessed after surgery. Ankle joint range of motion (ROM) and postoperative complications were also assessed. Results: All fractures were successfully treated. The Kaplan-Meier curves of the two groups showed similar trends. The log-rank test showed no significant difference in the time to bone union between the two groups (p = 0.48). In the Cox proportional hazards model adjusted for preoperative width and Bohler's angle, the hazard ratio for bone union was not statistically significant (HR: 1.13, 95%CI: 0.50-2.56, p = 0.78). Other variables included step-off (group S: 2.0 vs group P: 2.2 mm, p = 0.84), varus deformity (2.0° vs. 3.0°, p = 0.7), Gissane's angle (103.5° vs 104.0°, p = 0.84), width (38.0 vs 34.8 mm, p = 0.12), height (42.1 vs 44.0 mm, p = 0.07), and ankle ROM degrees (dorsal flexion, 20.0° vs. 20.0°, p = 0.13; plantar flexion 40.0° vs 40.0°, p = 0.56), which were not significantly different between groups P and S. The Bohler's angle was smaller in group S than in group P (20.5° vs 27.0°, p < 0.01). No skin necrosis or infection was observed in either group. Conclusion: Postoperative results of F-u-HA/PLLA screw fixation using the sinus tarsi approach for intra-articular calcaneal fractures were as good as those of locking plate fixation.

Diagnostic Performance of Endocytoscopy for Esophageal Eosinophilia.

INTRODUCTION: Eosinophils in the esophageal epithelium are unevenly distributed in eosinophilic esophagitis (EoE). Esophageal eosinophilia (EE) may be observable by endocytoscopy (EC). This study aimed to evaluate the diagnostic performance of EC for the diagnosis of EE. METHODS: A total of 33 EoE patients underwent EC with methylene blue staining from March 2020 to April 2021. A total of 194 EC images with corresponding biopsies were obtained. Three findings of EC, increased squamous cells (item I), increased inflammatory cells (item II), and cells with bilobed nuclei (item III), were established. These findings were reviewed by two endoscopists to diagnose EE. Another four endoscopists reviewed the images for interobserver agreement. RESULTS: When all three items were met by EC, the sensitivity and the accuracy for the diagnosis of EE were 88% and 76%, respectively. The integrated diagnostic odds ratios (ORs) for the diagnosis of EE of the four endoscopists were significant (OR: 3.98, 95% CI: 2.94-5.40, p < 0.001). The results were similar when only item III was met. Interobserver agreement was good for item III to diagnose EE (kappa value = 0.653). DISCUSSION/CONCLUSION: The diagnostic performance of EC for EE is acceptable and has good interobserver agreement. It may be useful for targeted biopsy in EoE patients.

Impact of Early Ambulation on the Prognosis of Coronary Artery Bypass Grafting Patients.

BACKGROUND: The effect of delayed ambulation on the outcome of coronary artery bypass grafting (CABG) remains to be clarified.Methods and Results: The long-term and in-hospital outcomes of 887 patients who underwent isolated CABG (455 off-pump cases, 135 urgent cases) were evaluated, with a focus on the timing of first ambulation. In-hospital mortality cases were excluded. Early ambulation (first ambulation within 3 days after operation) was achieved in 339 (38%) patients. In the multivariable logistic regression analysis, longer operation time and urgent case, EuroSCORE II, re-thoracotomy, and respiratory time were associated with delayed (≥4 days) ambulation. Delayed ambulation was associated with a high incidence of postoperative complications, such as pneumonia, and stroke (P<0.01). Following discharge, 22.2% of patients experienced major cardiac events and 13.8% died during the follow-up period (median follow-up 60 months). Cox hazards analysis revealed that delayed ambulation was associated with long-term adverse events (hazard ratio 1.04 per day, P<0.001). With adjustment for preoperative factors, the estimated future risk of adverse events was found to be increased day-by-day during the delay until initial ambulation. CONCLUSIONS: In isolated CABG patients, delayed ambulation was associated with poor outcomes, even in the long-term period. The results support the current guideline recommending early ambulation protocol after cardiac surgery.

Scoring system for predicting the prognosis of elderly gastric cancer patients after endoscopic submucosal dissection.

OBJECTIVES: Comprehensive assessments of the long-term outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in the elderly are unavailable. We aimed to create a scoring system to predict the long-term prognosis after ESD for EGC among patients aged ≥75 years. METHODS: We conducted retrospective studies of two cohorts: a single-center cohort (2006-2011) for developing the scoring system, and a multicenter cohort for validating the developed system (2012-2016). In the development cohort, factors related to death after ESD were identified using multivariable Cox regression analysis, and a predictive scoring system was developed. In the validation cohort, the scoring system was validated in 295 patients. RESULTS: In the development cohort, Charlson comorbidity index (CCI) ≥3 (hazard ratio [HR] 3.017), high psoas muscle index (PMI) (HR 2.206), and age ≥80 years (HR 1.978) were significantly related to overall survival after ESD. Therefore, high CCI, low PMI, and age ≥80 years were assigned 1 point each. The patients were categorized into low (≤1 point) and high (≥2 points) score groups based on their total scores. In the validation cohort, 184 and 111 patients were assigned to the low- and high-score groups, respectively. In comparisons based on Kaplan-Meier curves, the 5-year survival rate was 91.5% in the low-score group and 57.8% in the high-score group (log-rank test; P < 0.001). CONCLUSION: Our scoring system including high CCI, low PMI, and age ≥80 years could stratify the long-term prognosis of elderly patients aged ≥75 years after ESD for EGC.

A Diagnostic Predictive Model of Bronchoscopy with Radial Endobronchial Ultrasound for Peripheral Pulmonary Lesions.

BACKGROUND: Several factors have been reported to affect the diagnostic yield of bronchoscopy with radial endobronchial ultrasound (R-EBUS) for peripheral pulmonary lesions (PPLs). However, it is difficult to accurately predict the diagnostic potential of bronchoscopy for each PPL in advance. OBJECTIVES: Our objective was to establish a predictive model to evaluate the diagnostic yield before the procedure. METHOD: We retrospectively analysed consecutive patients who underwent diagnostic bronchoscopy with R-EBUS between April 2012 and October 2015. We assessed the factors that were predictive of successful bronchoscopic diagnosis of PPLs with R-EBUS using a multivariable logistic regression model. The accuracy of the predictive model was evaluated using the receiver operator characteristic area under the curve (ROC AUC). Internal validation was analysed using 10-fold stratified cross-validation. RESULTS: We analysed a total of 1,634 lesions; the median lesion size was 25.0 mm. Of these, 1,138 lesions (69.6%) were successfully diagnosed. In the predictive logistic model, significant factors affecting the diagnostic yield were lesion size, lesion structure, bronchus sign, and visible on chest X-ray. The predictive model consisted of seven factors: lesion size, lesion lobe, lesion location from the hilum, lesion structure, bronchus sign, visibility on chest X-ray, and background lung. The ROC AUC of the predictive model was 0.742 (95% confidence interval: 0.715-0.769). Internal validation using 10-fold stratified cross-validation revealed a mean ROC AUC of 0.734. CONCLUSIONS: The predictive model using the seven factors revealed a good performance in estimating the diagnostic yield.

Impact of Serum Zinc Level and Oral Zinc Supplementation on Clinical Outcomes in Patients Undergoing Infrainguinal Bypass for Chronic Limb-Threatening Ischemia.

BACKGROUND: Zinc (Zn) has been reported to play an important role in wound healing (WH). Nevertheless, the effect of Zn in chronic limb-threatening ischemia (CLTI) patients is unclear. This study investigated the effect of Zn on the clinical outcomes of CLTI patients undergoing bypass surgery.Methods and Results: This study reviewed 111 consecutive patients who underwent an infrainguinal bypass from 2012 to 2020. Patients with Zn deficiency (serum Zn level <60 µg/dL) received oral Zn supplementation and maintained a normal level until WH. This study aimed to explore: (1) the effect of Zn deficiency; and (2) Zn supplementation in Zn-deficient patients on the clinical outcomes of this cohort. Patients with Zn deficiency, Zn supplementation, and no Zn supplementation despite Zn deficiency accounted for 48, 21, and 42 patients, respectively. (1) Zn deficiency was associated with WH (HR, 0.47; 95% CI, 0.29-0.78: P=0.003), major adverse limb events (MALE) (HR, 2.53; 95% CI, 1.26-5.09: P=0.009), and major amputation or death (HR, 3.17; 95% CI, 1.51-6.63: P=0.002). (2) Zn supplementation was positively related to WH (HR, 2.30; 95% CI, 1.21-4.34: P=0.011). This result was confirmed using propensity score matching (HR, 2.24; 95% CI, 1.02-4.87: P=0.043). CONCLUSIONS: The current study revealed that Zn level was associated with clinical outcomes in CLTI patients after bypass surgery. Oral Zn supplementation could improve WH in these patients.

Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade.

Cancer-associated fibroblasts (CAFs) are an integral component of the tumor microenvironment (TME). Most CAFs shape the TME toward an immunosuppressive milieu and attenuate the efficacy of immune checkpoint blockade (ICB) therapy. However, the detailed mechanism of how heterogeneous CAFs regulate tumor response to ICB therapy has not been defined. Here, we show that a recently defined CAF subset characterized by the expression of Meflin, a glycosylphosphatidylinositol-anchored protein marker of mesenchymal stromal/stem cells, is associated with survival and favorable therapeutic response to ICB monotherapy in patients with non-small cell lung cancer (NSCLC). The prevalence of Meflin-positive CAFs was positively correlated with CD4-positive T-cell infiltration and vascularization within non-small cell lung cancer tumors. Meflin deficiency and CAF-specific Meflin overexpression resulted in defective and enhanced ICB therapy responses in syngeneic tumors in mice, respectively. These findings suggest the presence of a CAF subset that promotes ICB therapy efficacy, which adds to our understanding of CAF functions and heterogeneity.