Long-term effect of pulmonary rehabilitation in idiopathic pulmonary fibrosis: a randomised controlled trial.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterised by worsening dyspnoea and exercise intolerance. RESEARCH QUESTION: Does a long-term pulmonary rehabilitation improve exercise tolerance in patients with IPF treated with standard antifibrotic drugs, which are expected to reduce disease progression? METHODS: This open-label randomised controlled trial was performed at 19 institutions. Stable patients receiving nintedanib were randomised into pulmonary rehabilitation and control groups (1:1). The pulmonary rehabilitation group underwent initial rehabilitation which included twice-weekly sessions of monitored exercise training for 12 weeks, followed by an at-home rehabilitation programme for 40 weeks. The control group received usual care only, without pulmonary rehabilitation. Both groups continued to receive nintedanib. The primary and main secondary outcomes were change in 6 min walking distance (6MWD) and change in endurance time (using cycle ergometry) at week 52. RESULTS: Eighty-eight patients were randomised into pulmonary rehabilitation (n=45) and control (n=43) groups. Changes in 6MWD were -33 m (95% CI -65 to -1) and -53 m (95% CI -86 to -21) in the pulmonary rehabilitation and control groups, respectively, with no statistically significant difference (mean difference, 21 m (95% CI -25 to 66), p=0.38). Changes in endurance time were significantly better in the pulmonary rehabilitation (64 s, 95% CI -42.3 to 171)) than in the control (-123 s (95% CI -232 to -13)) group (mean difference, 187 s (95% CI 34 to 153), p=0.019). INTERPRETATION: Although pulmonary rehabilitation in patients taking nintedanib did not improve 6MWD in the long term, it led to prolonged improvement in endurance time. TRIAL REGISTRATION NUMBER: UMIN000026376.

Safety of early oral intake after endoscopic ultrasound-guided hepaticoenterostomy.

BACKGROUND: Techniques and devices for endoscopic ultrasound (EUS)-guided hepaticoenterostomy (EUS-HES) procedures, including EUS-guided hepaticogastrostomy (EUS-HGS) and EUS-guided hepaticojejunostomy (EUS-HJS), have been developed; however, the optimal timing to begin oral intake after EUS-HES remains unknown. This study aimed to evaluate the safety of early oral intake after EUS-HES. METHODS: We retrospectively investigated patients who underwent EUS-HES (EUS-HGS or EUS-HJS) between March 2015 and March 2022. Patients who had no problems with the results of blood tests and computed tomography examinations on the morning of day 1 after EUS-HES were classified as either the early intake group (started oral intake on day 1 after EUS-HES) or the late intake group (started oral intake on day 2 or later after EUS-HES). Patients' characteristics, procedure characteristics, and early postprocedural adverse events (within 14 days after the procedure) were compared between groups. RESULTS: Fifty patients were enrolled in this study. Forty-three patients had no problems with the results of examinations performed on the morning of day 1 after EUS-HES. Twenty-one patients comprised the early intake group and 22 comprised the late intake group. Adverse events that developed within 14 days after EUS-HES were not significantly different between groups (early 4.7% vs. late 9.0%; odds ratio, 0.50; 95% confidence interval, 0.0080-10.49; P = 1.00). CONCLUSIONS: Starting oral intake on day 1 after EUS-HES did not increase postprocedural adverse events compared with starting oral intake on day 2 or later after EUS-HES.

Physical activity in idiopathic pulmonary fibrosis: Longitudinal change and minimal clinically important difference.

BACKGROUND AND OBJECTIVE: Reference values of physical activity to interpret longitudinal changes are not available in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to define the minimal clinical important difference (MCID) of longitudinal changes in physical activity in patients with IPF. METHODS: Using accelerometry, physical activity (steps per day) was measured and compared at baseline and 6-months follow-up in patients with IPF. We calculated MCID of daily step count using multiple anchor-based and distribution-based methods. Forced vital capacity and 6-minute walk distance were applied as anchors in anchor-based methods. Effect size and standard error of measurement were used to calculate MCID in distribution-based methods. RESULTS: One-hundred and five patients were enrolled in the study (mean age: 68.5 ± 7.5 years). Step count significantly decreased from baseline to 6-months follow-up (-461 ± 2402, p = .031). MCID calculated by anchor-based and distribution-based methods ranged from 570-1358 steps. CONCLUSION: Daily step count significantly declined over 6-months in patients with IPF. MCID calculated by multiple anchor-based and distribution-based methods was 570 to 1358 steps/day. These findings contribute to interpretation of the longitudinal changes of physical activity that will assist its use as a clinical and research outcome in patients with IPF.

Effectiveness of clip-and-thread traction-assisted duodenal endoscopic submucosal dissection: a propensity score-matched study (with video).

BACKGROUND AND AIMS: The indications for endoscopic submucosal dissection (ESD) in superficial nonampullary duodenal epithelial tumors (SNADETs) remain controversial because the procedure is technically challenging. Moreover, the effectiveness of clip-and-thread traction-assisted ESD (TA-ESD) for SNADETs has not been assessed. The aim of the current study was to compare the effectiveness of duodenal TA-ESD and conventional ESD for SNADETs. METHODS: SNADETs treated with conventional ESD or TA-ESD between April 2017 and March 2021 at Saitama Medical University International Medical Center were evaluated retrospectively. RESULTS: There were 49 cases of conventional ESD and 32 cases of TA-ESD for SNADETs. Using a propensity score-matched design, we selected 26 pairs of cases with conventional ESD and TA-ESD. In the unmatched cohort, patients treated with TA-ESD were characterized by a higher R0 (no tumor identified at the lateral or vertical margins) resection rate (P = .004), more frequent poor submucosal lifting because of fibrosis (P = .014), and shorter follow-up period (P = .0004) than patients treated with conventional ESD. In the propensity score-matched pairs, patients treated with TA-ESD were characterized by a higher rate of R0 resection (P = .021) and a shorter follow-up period (P = .0061). The findings regarding R0 resection rates were confirmed by multivariate logistic regression models, which found a higher odds ratio (OR) for R0 resection in patients who underwent TA-ESD than in patients who underwent conventional ESD both in the unmatched cohort (OR, 17.0; 95% confidence interval, 1.6-178.8; P = .018) and in the propensity score-matched pairs (OR, 26.7; 95% confidence interval, 1.5-460.2; P = .024). CONCLUSIONS: Our findings suggest TA-ESD may increase the rate of R0 resection in patients with SNADETs in comparison with conventional ESD.

Efficacy and factors affecting procedure results of short-type single-balloon enteroscopy-assisted ERCP for altered anatomy: a multicenter cohort in Japan.

BACKGROUND AND AIMS: Although single-balloon enteroscopy (SBE)-assisted or short-type SBE (short SBE)-assisted ERCP has been reported as useful in patients with surgically altered anatomy, most studies had small sample sizes or single-center designs. This study aimed to evaluate the efficacy and factors affecting the procedure results of short SBE-assisted ERCP in patients with surgically altered anatomy. METHODS: This multicenter, retrospective study was conducted at 8 tertiary referral care centers in Japan. The data of patients who underwent ERCP-related procedures using short SBE between September 2011 and August 2019 at each facility were analyzed. RESULTS: Overall, 1318 patients were included in this analysis. The enteroscopy (reaching the target site), cannulation, and total procedural success rates were 87.9% (95% confidence interval [CI], 86.1%-89.6%), 87.0% (95% CI, 84.9%-88.8%), and 74.9% (95% CI, 72.5%-77.2%), respectively. Adverse events occurred in 7.7% of patients (95% CI, 6.4%-9.3%). Multiple logistic regression analysis indicated that age (≥75 years), Roux-en-Y reconstruction, pancreatic indication, and malignancy were factors affecting the total procedural failure. CONCLUSIONS: This large-scale study proved that short SBE-assisted ERCP in patients with surgically altered anatomy was effective. Moreover, it clarified factors affecting procedure results. Proficiency with alternative treatment techniques is required in difficult cases. (Clinical trial registration number: UMIN00004045.).

Factors affecting complete stone extraction in the initial procedure in short type single-balloon enteroscopy-assisted endoscopic retrograde cholangiography for patients with Roux-en-Y gastrectomy.

OBJECTIVES: This study aimed to evaluate the efficacy and safety of stone extraction in patients who underwent Roux-en-Y gastrectomy using short-type single-balloon enteroscopy (SBE) and to clarify the factors affecting complete stone extraction in the initial procedure. METHODS: The data of patients with Roux-en-Y gastrectomy who underwent endoscopic stone extraction using short SBE between September 2011 and January 2022 was analyzed. RESULTS: Overall, 85 patients were scheduled to undergo stone extraction. 77 patients were intended stone extraction after successful biliary cannulation. The complete stone extraction success in the initial procedure, overall complete stone extraction success including repeated procedures, and adverse event rates were 68.2% (95% confidence interval [CI], 57.2%-77.9%), 87.1% (95% CI, 78.0%-93.4%), and 8.2% (95% CI, 3.4%-16.2%), respectively. Multiple logistic regression analysis indicated that bile duct diameter affected the success of complete stone extraction after successful biliary cannulation in the initial procedure (odds ratio 0.53, 95% CI, 0.30-0.94, p = .03). CONCLUSIONS: Stone extraction in patients with Roux-en-Y gastrectomy using short SBE was effective. Patients with a large diameter bile duct required several sessions for complete stone extraction, suggesting that more dedicated devices are warranted for patients with surgically altered anatomy.

Evaluation of endoscopic ultrasound-guided fine-needle biopsy for preoperative pancreatic solid lesions.

OBJECTIVES: Obtaining an accurate preoperative diagnosis is crucial. This study aimed to evaluate the diagnostic accuracy and utility of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) for preoperative pancreatic solid lesions. MATERIALS AND METHODS: We retrospectively assessed all patients who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or EUS-FNB to evaluate solid pancreatic lesions preoperatively at our center between July 2013 and June 2020. We enrolled 71 patients who underwent EUS-FNA using a 22 G conventional needle (FNA group) and 34 patients who underwent EUS-FNB using a 22 G Franseen needle (FNB group). Overall, 105 patients were analyzed. We employed propensity-matched analysis and adjusted the confounders. RESULTS: No procedural adverse events were encountered. Both groups showed no significant differences in the procedure time, technical success rate, and rate of operator changes from trainee to expert. Regarding diagnostic accuracy, the FNB group (88.2%; 30/34) was higher but not significantly different from the FNA group (85.3%; 29/34) (p > .99). Furthermore, the FNB group (median 2, IQR;2-3) had a significantly lower number of punctures than the FNA group (median 3, IQR; 2-4) (p = .01). CONCLUSIONS: The FNB needle provides higher diagnostic accuracy and requires significantly fewer punctures than conventional needles even at facilities with no available rapid on-site evaluation. Thus, using the FNB needle can be useful for preoperative pancreatic solid lesions.

A retrospective cohort study of factors influencing long procedure times in colorectal endoscopic submucosal dissection.

OBJECTIVE: To evaluate the outcomes and factors influencing colorectal endoscopic submucosal dissection (ESD) with a long procedure time. MATERIALS AND METHODS: In this single-center, retrospective study, we included 1,100 patients with 1,199 lesions who underwent colorectal ESD between April 2016 and December 2020. ESD was performed using an advanced system knife for lesions >20 mm. An S-O clip was used as the traction device. The long-time group (LP; procedure time >120 min) and normal-time group (NP; procedure time <120 min) were compared. RESULTS: The procedure times were 166.86 and 44.72 min in the LP and NP groups, respectively. The completion rate was higher in the NP group (96.5% vs. 83.5%, p = .001); the completed lesions were resected en bloc. Multivariate analysis revealed 18.8% and 7.8% of submucosal fibrosis in the LP and NP groups, respectively (odds ratio [OR] = 2.410, p = .026). Compared to the NP group, the LP group presented larger maximum lesion sizes and higher rates of R1 resection, and traction device use. Time to introduction of traction device use was longer in the LP than in the NP group (126.05 vs. 21.72 min; p < .001). Fibrosis tends to occur cecal lesions (OR 2.436, p = .011) and laterally spreading tumor-non-granular-pseudo-depressed (LST-NG-PD) (OR 2.6181, p = .001). CONCLUSIONS: Lesion size and fibrosis were factors associated with a long procedure time in colonic ESD. For fibrotic lesions (LST-NG-PD and cecal lesions), it is necessary to consider early use of traction devices and advisable to plan a strategy for the use of traction devices.

Cutoff Points for Step Count to Predict 1-year All-Cause Mortality in Patients with Idiopathic Pulmonary Fibrosis.

BACKGROUND: Although physical activity is associated with mortality in patients with idiopathic pulmonary fibrosis (IPF), reference values to interpret levels of physical activity are lacking. OBJECTIVES: This study aimed to investigate the prognostic significance of physical activity assessed by step count and its cutoff points for all-cause mortality. METHODS: We measured physical activity (steps per day) using an accelerometer in patients with IPF at the time of diagnosis. Relationships among physical activity and mortality, as well as cutoff points of daily step count to predict all-cause mortality were examined. RESULTS: Eighty-seven patients (73 males) were enrolled. Forty-four patients (50.1%) died during the follow-up (median 54 months). In analysis adjusting for Gender-Age-Physiology stage and 6-min walk distance, daily step count was an independent predictor of all-cause mortality (hazard ratio (HR) = 0.820, 95% confidence interval (CI) = 0.694-0.968, p = 0.019). The optimal cutoff point (receiving operating characteristic analysis) for 1-year mortality was 3,473 steps per day (sensitivity = 0.818 and specificity = 0.724). Mortality was significantly lower in patients with a daily step count exceeding 3,473 steps than in those whose count was 3,473 or less (HR = 0.395, 95% CI = 0.218-0.715, p = 0.002). CONCLUSIONS: Step count, an easily interpretable measurement, was a significant predictor of all-cause mortality in patients with IPF. At the time of diagnosis, a count that exceeded the cutoff point of 3,473 steps/day more than halved mortality. These findings highlight the importance of assessing physical activity in this patient population.

Long-term Multidisciplinary Rehabilitation Efficacy in Older Patients After Traumatic Brain Injury: Assessed by the Functional Independence Measure.

Instances of traumatic brain injury (TBI) in the elderly have been increasing along with the aging of popula-tions. In the present study, we examined the effect of aging on long-term multidisciplinary in-patient rehabili-tation efficacy after TBI. Sixty-three patients with physical and cognitive impairments after TBI were enrolled in this study. Patients were divided into 4 age groups (≤ 24, 25-44, 45-64, ≥ 65 years) and the clinical charac-teristics and rehabilitation efficacy of each age group were determined. Functional disability was evaluated using motor and cognitive Functional Independence Measure (FIM) scores. Rehabilitation efficacy was assessed by FIM gains during rehabilitation and compared among the groups. There were no statistically significant dif-ferences in motor and cognitive FIM gains among the age groups. However, cognitive FIM gain was limited in a subset of ≥ 65 patients, and initial cognitive measures could not predict cognitive FIM improvement. These results indicate that chronological age is insufficient to accurately predict rehabilitation efficacy in older TBI patients, and that such patients should be considered candidates for intensive rehabilitation programs based on these results. Accurate prognostication of rehabilitation efficacy with continuing data collection is important when using rehabilitation resources for older TBI patients.

Status of single-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography in patients with surgically altered anatomy: Systematic review and meta-analysis on biliary interventions.

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy is still challenging. Usefulness of single-balloon enteroscopy (SBE)-assisted ERCP has been increasingly reported. Short SBE is considered beneficial with a 152-cm working length and a 3.2-mm working channel. This has increased the variety of devices that can be used during ERCP procedures. The aim of this pooled analysis was to evaluate the efficacy of SBE-assisted ERCP in patients with surgically altered anatomy and elucidate the current status. METHODS: This systematic review only involved biliary interventions which excluded pancreatic cases. Studies involving SBE-assisted ERCP in patients with Roux-en-Y gastrectomy, hepaticojejunostomy with Roux-en-Y, pancreaticoduodenectomy (Whipple or Child procedure), or Billroth II gastrectomy were analyzed. Enteroscopy, biliary cannulation, and procedural success were assessed by pooling data in a random-effect model, according to the degree of heterogeneity, to obtain a proportion with 95% confidence interval (CI). The outcomes observed for conventional and short SBE cases were also reported. RESULTS: Overall, 1227 SBE-assisted ERCP procedures from 21 studies were included. The pooled enteroscopy, biliary cannulation, and procedural success rates were 86.6% (95% CI, 82.4-90.3%), 90% (95% CI, 87.1-92.5%), and 75.8% (95% CI, 71.0-80.3%), respectively. Adverse events occurred in 6.6% (95% CI, 5.3-8.2%) of the procedures. Although good outcomes were reported for short SBE-assisted ERCP, these should not be directly compared to the outcomes observed for conventional SBE, as they assume different backgrounds and include confounding variables. CONCLUSIONS: Single-balloon enteroscopy-assisted ERCP in patients with surgically altered anatomy on biliary interventions is effective.

Supplemental oxygen improves exercise capacity in IPF patients with exertional desaturation.

BACKGROUND AND OBJECTIVE: The efficacy of supplemental oxygen during exercise remains unclear for patients with IPF, as there have been conflicting results from recent prospective studies with small sample sizes. METHODS: This prospective, single-blind, randomized, crossover trial evaluated the efficacy of supplemental oxygen compared with placebo air during exercise in consecutive patients with IPF without resting hypoxaemia at initial evaluation. Patients with <90% SpO2 in a 6MWT using room air were randomly assigned to a CWRET at 80% of peak work rate with oxygen or placebo air gas via nasal cannula at 4 L/min. The primary endpoint was the effect of supplemental oxygen on endurance time. RESULTS: We recruited 72 consecutive patients (median age: 66.5 years, % FVC: 84.6%, % DLCO : 61.4%). Supplemental oxygen significantly increased the endurance time (340-424 s; P < 0.001) and minimum SpO2 (88.0-94.0%; P < 0.001) compared with placebo air. Furthermore, supplemental oxygen significantly improved dyspnoea and leg fatigue. In a multivariate linear regression analysis, the endurance time on air was an independent explanatory variable of the improvement rate of endurance time (P = 0.02). CONCLUSION: In mild-moderate IPF with exercise-induced hypoxaemia even without resting hypoxaemia, supplemental oxygen during exercise improved the endurance time, desaturation and subjective symptoms. Patients with shorter endurance times with placebo air showed better improvement with supplemental oxygen.

Analysis of the factors involved in procedural failure: Endoscopic retrograde cholangiopancreatography using a short-type single-balloon enteroscope for patients with surgically altered gastrointestinal anatomy.

AIM: To analyze factors involved in procedural failure and to discuss responses to procedural failure by using the outcomes of endoscopic retrograde cholangiopancreatography (ERCP) carried out using a short-type single-balloon enteroscope (short SBE) in patients with surgically altered gastrointestinal anatomy. METHODS: The study sample included patients who underwent ERCP-related procedures using a short SBE between September 2011 and September 2018 at our hospital. Outcomes, including procedural success rate, were studied retrospectively to analyze the factors involved in procedural failure. RESULTS: Analysis included 191 procedures carried out in 121 patients. Procedural success rate was 85.9% with an adverse event rate of 8.4%. Causes of procedural failure included malignant biliary obstruction (odds ratio [OR] 2.89, 95% confidence interval [CI] 1.19-7.25, P = 0.02), first ERCP attempt (OR: 5.32, 95% CI: 1.30-36.30, P = 0.02), and Roux-en-Y reconstruction (OR: 0.08, 95% CI: 0.004-0.39, P < 0.001). With regard to the response to failure, in cases of malignant biliary obstruction, reattempted short SBE-assisted ERCP was difficult because of invasion of the small intestine or papilla. A large number of these cases required alternative treatment (10 of 15 cases, 66.7%) using percutaneous transhepatic biliary drainage (PTBD) or endoscopic ultrasound-guided biliary drainage (EUS-BD). CONCLUSION: Endoscopic retrograde cholangiopancreatography using a short SBE is safe and effective, with malignant biliary obstruction being a specific cause of failure. Technical proficiency with different modalities, such as PTBD and EUS-BD, is necessary to respond to failure in these cases.

Clumps of Mesenchymal Stem Cell/Extracellular Matrix Complexes Generated with Xeno-Free Conditions Facilitate Bone Regeneration via Direct and Indirect Osteogenesis.

Three-dimensional clumps of mesenchymal stem cell (MSC)/extracellular matrix (ECM) complexes (C-MSCs) consist of cells and self-produced ECM. We demonstrated previously that C-MSCs can be transplanted into bone defect regions with no artificial scaffold to induce bone regeneration. To apply C-MSCs in a clinical setting as a reliable bone regenerative therapy, the present study aimed to generate C-MSCs in xeno-free/serum-free conditions that can exert successful bone regenerative properties and to monitor interactions between grafted cells and host cells during bone healing processes. Human bone marrow-derived MSCs were cultured in xeno-free/serum-free medium. To obtain C-MSCs, confluent cells that had formed on the cellular sheet were scratched using a micropipette tip and then torn off. The sheet was rolled to make a round clump of cells. Then, C-MSCs were transplanted into an immunodeficient mouse calvarial defect model. Transplantation of C-MSCs induced bone regeneration in a time-dependent manner. Immunofluorescence staining showed that both donor human cells and host mice cells contributed to bone reconstruction. Decellularized C-MSCs implantation failed to induce bone regeneration, even though the host mice cells can infiltrate into the defect area. These findings suggested that C-MSCs generated in xeno-free/serum-free conditions can induce bone regeneration via direct and indirect osteogenesis.