The 2023 top 10 list of endoscopy topics in medical publishing: an annual review by the American Society for Gastrointestinal Endoscopy Editorial Board.

Using a systematic literature search of original articles published during 2023 in Gastrointestinal Endoscopy (GIE) and other high-impact medical and gastroenterology journals, the GIE Editorial Board of the American Society for Gastrointestinal Endoscopy compiled a list of the top 10 most significant topic areas in general and advanced GI endoscopy during the year. Each GIE Editorial Board member was directed to consider 3 criteria in generating candidate topics-significance, novelty, and impact on global clinical practice-and subject matter consensus was facilitated by the Chair through electronic voting and a meeting of the entire GIE Editorial Board. The 10 identified areas collectively represent advances in the following endoscopic spheres: GI bleeding, endohepatology, endoscopic palliation, artificial intelligence and polyp detection, artificial intelligence beyond the colon, better polypectomy and endoscopic mucosal resection, how to make endoscopy units greener, high quality upper endoscopy, endoscopic tissue apposition/closure devices, and endoscopic submucosal dissection. Each board member was assigned a topic area around which summarized relevant important articles, thereby generating this overview of the "top 10" endoscopic advances of 2023.

Patient Outcomes of Definitive Diverticular Hemorrhage After Colonoscopic, Medical, Surgical, or Embolization Treatment.

BACKGROUND: There are few reports of clinical outcomes or the natural history of definitive diverticular hemorrhage (DDH). AIMS: To describe 1-year clinical outcomes of patients with documented DDH treated with colonoscopic hemostasis, angioembolization, surgery, or medical treatment. METHODS: DDH was diagnosed when active bleeding or other stigmata of hemorrhage were found in a colonic diverticulum during urgent colonoscopy or extravasation on angiography or red blood cell (RBC) scanning. This was a retrospective analysis of prospectively collected data of DDH patients from two referral centers between 1993 and 2022. Outcomes were compared for the four treatment groups. The Kaplan-Meier analysis was for time-to-first diverticular rebleed. RESULTS: 162 patients with DDH were stratified based on their final treatment before discharge-104 colonoscopic hemostasis, 24 medical treatment alone, 19 colon surgery, and 15 angioembolization. There were no differences in baseline characteristics, except for a higher Glasgow-Blatchford score in the angioembolization group vs. the colonoscopic group. Post-treatment, the colonoscopic hemostasis group had the lowest rate of RBC transfusions and fewer hospital and ICU days compared to surgical and embolization groups. The medical group had significantly higher rates of rebleeding and reintervention. The surgical group had the highest postoperative complications. CONCLUSIONS: Medically treated DDH patients had significantly higher 1-year rebleed and reintervention rates than the three other treatments. Those with colonoscopic hemostasis had significantly better clinical outcomes during the index hospitalization. Surgery and embolization are recommended as salvage therapies in case of failure of colonoscopic and medical treatments.

Cytoplasmic TDP-43 accumulation drives changes in C-bouton number and size in a mouse model of sporadic Amyotrophic Lateral Sclerosis.

An altered neuronal excitability of spinal motoneurones has consistently been implicated in Amyotrophic Lateral Sclerosis (ALS) leading to several investigations of synaptic input to these motoneurones. One such input that has repeatedly been shown to be affected is a population of large cholinergic synapses terminating mainly on the soma of the motoneurones referred to as C-boutons. Most research on these synapses during disease progression has used transgenic Superoxide Dismutase 1 (SOD1) mouse models of the disease which have not only produced conflicting findings, but also fail to recapitulate the key pathological feature seen in ALS; cytoplasmic accumulations of TAR DNA-binding protein 43 (TDP-43). Additionally, they fail to distinguish between slow and fast motoneurones, the latter of which have more C-boutons, but are lost earlier in the disease. To circumvent these issues, we quantified the frequency and volume of C-boutons on traced soleus and gastrocnemius motoneurones, representing predominantly slow and fast motor pools respectively. Experiments were performed using the TDP-43ΔNLS mouse model that carries a transgenic construct of TDP-43 devoid of its nuclear localization signal, preventing its nuclear import. This results in the emergence of pathological TDP-43 inclusions in the cytoplasm, modelling the main pathology seen in this disorder, accompanied by a severe and lethal ALS phenotype. Our results confirmed changes in both the number and volume of C-boutons with a decrease in number on the more vulnerable, predominantly fast gastrocnemius motoneurones and an increase in number on the less vulnerable, predominantly slow soleus motoneurones. Importantly, these changes were only found in male mice. However, both sexes and motor pools showed a decrease in C-bouton volume. Our experiments confirm that cytoplasmic TDP-43 accumulation is sufficient to drive C-bouton changes.

Impaired Ventilatory Efficiency, Dyspnea, and Exercise Intolerance in Chronic Obstructive Pulmonary Disease: Results from the CanCOLD Study.

Rationale: Impaired exercise ventilatory efficiency (high ventilatory requirements for CO2 [[Formula: see text]e/[Formula: see text]co2]) provides an indication of pulmonary gas exchange abnormalities in chronic obstructive pulmonary disease (COPD). Objectives: To determine 1) the association between high [Formula: see text]e/[Formula: see text]co2 and clinical outcomes (dyspnea and exercise capacity) and its relationship to lung function and structural radiographic abnormalities; and 2) its prevalence in a large population-based cohort. Methods: Participants were recruited randomly from the population and underwent clinical evaluation, pulmonary function, cardiopulmonary exercise testing, and chest computed tomography. Impaired exercise ventilatory efficiency was defined by a nadir [Formula: see text]e/[Formula: see text]co2 above the upper limit of normal (ULN), using population-based normative values. Measurements and Main Results: Participants included 445 never-smokers, 381 ever-smokers without airflow obstruction, 224 with Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 COPD, and 200 with GOLD 2-4 COPD. Participants with [Formula: see text]e/[Formula: see text]co2 above the ULN were more likely to have activity-related dyspnea (Medical Research Council dyspnea scale ⩾ 2; odds ratio [5-95% confidence intervals], 1.77 [1.31 to 2.39]) and abnormally low peak [Formula: see text]o2 ([Formula: see text]o2peak below the lower limit of normal; odds ratio, 4.58 [3.06 to 6.86]). The Kco had a stronger correlation with nadir [Formula: see text]e/[Formula: see text]co2 (r = -0.38; P < 0.001) than other relevant lung function and computed tomography metrics. The prevalence of [Formula: see text]e/[Formula: see text]co2 above the ULN was 24% in COPD (similar in GOLD 1 and 2 through 4), which was greater than in never-smokers (13%) and ever-smokers (12%). Conclusions: [Formula: see text]e/[Formula: see text]co2 above the ULN was associated with greater dyspnea and low [Formula: see text]o2peak and was present in 24% of all participants with COPD, regardless of GOLD stage. The results show the importance of recognizing impaired exercise ventilatory efficiency as a potential contributor to dyspnea and exercise limitation, even in mild COPD.

Exertional dyspnoea in patients with mild-to-severe chronic obstructive pulmonary disease: neuromechanical mechanisms.

In patients with chronic obstructive pulmonary disease (COPD), exertional dyspnoea generally arises when there is imbalance between ventilatory demand and capacity, but the neurophysiological mechanisms are unclear. We therefore determined if disparity between elevated inspiratory neural drive (IND) and tidal volume (VT ) responses (neuromechanical dissociation) impacted dyspnoea intensity and quality during exercise, across the COPD severity spectrum. In this two-centre, cross-sectional observational study, 89 participants with COPD divided into tertiles of FEV1 %predicted (Tertile 1 = FEV1 = 87 ± 9%, Tertile 2 = 60 ± 9%, Tertile 3 = 32 ± 8%) and 18 non-smoking controls, completed a symptom-limited cardiopulmonary exercise test (CPET) with measurement of IND by diaphragm electromyography (EMGdi (%max)). The association between increasing dyspnoea intensity and EMGdi (%max) during CPET was strong (r = 0.730, P < 0.001) and not different between the four groups who showed marked heterogeneity in pulmonary gas exchange and mechanical abnormalities. Significant inspiratory constraints (tidal volume/inspiratory capacity (VT /IC) ≥ 70%) and onset of neuromechanical dissociation (EMGdi (%max):VT /IC > 0.75) occurred at progressively lower minute ventilation ( V ̇ E ${\dot{V}}_{{\rm{E}}}$ ) from Control to Tertile 3. Lower resting IC meant earlier onset of neuromechanical dissociation, heightened dyspnoea intensity and greater propensity (93% in Tertile 3) to select qualitative descriptors of 'unsatisfied inspiration'. We concluded that, regardless of marked variation in mechanical and pulmonary gas exchange abnormalities in our study sample, exertional dyspnoea intensity was linked to the magnitude of EMGdi (%max). Moreover, onset of critical inspiratory constraints and attendant neuromechanical dissociation amplified dyspnoea intensity at higher exercise intensities. Simple measurements of IC and breathing pattern during CPET provide useful insights into mechanisms of dyspnoea and exercise intolerance in individuals with COPD. KEY POINTS: Dyspnoea during exercise is a common and troublesome symptom reported by patients with chronic obstructive pulmonary disease (COPD) and is linked to an elevated inspiratory neural drive (IND). The precise mechanisms of elevated IND and dyspnoea across the continuum of airflow obstruction severity in COPD remains unclear. The present study sought to determine the mechanisms of elevated IND (by diaphragm EMG, EMGdi (%max)) and dyspnoea during cardiopulmonary exercise testing (CPET) across the continuum of COPD severity. There was a strong association between increasing dyspnoea intensity and EMGdi (%max) during CPET across the COPD continuum despite significant heterogeneity in underlying pulmonary gas exchange and respiratory mechanical impairments. Critical inspiratory constraints occurred at progressively lower ventilation during exercise with worsening severity of COPD. This was associated with the progressively lower resting inspiratory capacity with worsening disease severity. Earlier critical inspiratory constraint was associated with earlier neuromechanical dissociation and greater likelihood of reporting the sensation of 'unsatisfied inspiration'.

Severe Upper Gastrointestinal Hemorrhage Caused by Reflux Esophagitis.

BACKGROUND: There are few reports about reflux esophagitis (RE) as a cause of severe upper gastrointestinal bleeding (UGIB). AIMS: This study aims to evaluate (1) changes in its prevalence over the last three decades and (2) clinical and endoscopic characteristics and 30-day outcomes among RE patients with and without focal esophageal ulcers (EUs) and stigmata of recent hemorrhage (SRH). METHODS: A retrospective study of prospectively collected data of esophagitis patients hospitalized with severe UGIB between 1992 and 2020. Descriptive analysis and statistical comparisons were performed. RESULTS: Of 114 RE patients, the mean age was 61.1 years and 76.3% were males. 38.6% had prior gastroesophageal reflux disease (GERD) symptoms; overall 36% were on acid suppressants. Over three consecutive decades, the prevalence of RE as a cause of severe UGIB increased significantly from 3.8 to 16.7%. 30-day rebleeding and all-cause mortality rates were 11.4% and 6.1%. RE patients with focal EUs and SRH (n = 23) had worse esophagitis than those with diffuse RE (n = 91) (p = 0.012). There were no differences in 30-day outcomes between RE patients with and without EUs and SRH. CONCLUSIONS: For patients with severe UGIB caused by RE, (1) the prevalence has increased significantly over the past three decades, (2) the reasons for this increase and preventive strategies warrant further study, (3) most patients lacked GERD symptoms and did not take acid suppressants, and (4) those with focal ulcers and SRH had more severe esophagitis and were treated endoscopically.

Outcomes of patients with ischemic colitis causing severe hematochezia managed medically or surgically.

PURPOSE: To compare short- and long-term outcomes of hospitalized patients with ischemic colitis (IC) presenting with severe hematochezia and treated medically or colectomy and also those with inpatient vs. outpatient start of hematochezia. METHODS: A retrospective analysis of prospectively collected data for IC patients hospitalized for severe hematochezia from two teaching hospitals was done from 1994 to 2020, with the diagnosis of IC made colonoscopically and confirmed histologically. RESULTS: Ninety-seven patients initially all had medical management for IC. Seventy-two (74.2%) were stable and had no further bleeding; 17 (17.5%) had colon resection; and 8 were critically ill and not surgical candidates. Surgical patients and non-surgical candidate had higher comorbidity scores; received more red blood cell (RBC) transfusion (median (IQR) 5 (3-10) vs. 4.5 (3-6.5) vs. 1 (0-4) units, p < 0.001); had significantly longer hospital and ICU days; had higher severe complication rates (35.3% vs. 100%. vs. 5.6%, p < 0.001); and had higher 30-day all-cause mortality rates (23.5% vs. 87.5% vs. 0, p < 0.001). Inpatients developing IC hemorrhage had more RBC transfusions, more complications, longer hospital stays, and higher mortality than patients whose IC bleeding started as outpatients. CONCLUSIONS: The majority of IC patients hospitalized for severe hematochezia were successfully treated medically. Patients who were not surgical candidate had the highest rates of severe complications and mortality. Surgical patients and those who were not surgical candidate had worse outcomes than the medical group. Patients with inpatient start of bleeding from IC had significantly worse outcomes than those with outpatient start of bleeding.

The Association between Fat-Free Mass and Exercise Test Outcomes in People with Chronic Obstructive Pulmonary Disease: A Systematic Review.

People with chronic obstructive pulmonary disease (COPD) tend to have abnormally low levels of fat-free mass (FFM), which includes skeletal muscle mass as a central component. The purpose of this systematic review was to synthesise available evidence on the association between FFM and exercise test outcomes in COPD. MEDLINE, Cochrane Library, EMBASE, Web of Science, and Scopus were searched. Studies that evaluated exercise-related outcomes in relation to measures of FFM in COPD were included. Eighty-three studies, containing 18,770 (39% female) COPD participants, were included. Considerable heterogeneity was identified in the ways that FFM and exercise test outcomes were assessed; however, higher levels of FFM were generally associated with greater peak exercise capacity. This association was stronger for some exercise test outcomes (e.g. peak rate of oxygen consumption during incremental cycle exercise testing) than others (e.g. six-minute walking distance). This review identified heterogeneity in the methods used for measuring FFM and exercise capacity. There was, in general, a positive association between FFM and exercise capacity in COPD. There was also an identified lack of studies investigating associations between FFM and temporal physiological and perceptual responses to exercise. This review highlights the significance of FFM as a determinant of exercise capacity in COPD.

Randomized Controlled Trial of Over-the-Scope Clip as Initial Treatment of Severe Nonvariceal Upper Gastrointestinal Bleeding.

BACKGROUND AND AIMS: No prior randomized controlled trial (RCT) has reported patient outcomes of large over-the-scope clip (OTSC) compared to standard hemostasis as initial endoscopic treatment of severe NVUGIB. This was our study aim. METHODS: Patients with bleeding ulcers or Dieulafoy's lesions and major stigmata of hemorrhage - SRH (active spurting bleeding, visible vessel, or clot) - or lesser SRH (oozing bleeding or flat spots - with arterial blood flow by Doppler probe) were randomized to OTSC or standard endoscopic hemostasis (with hemoclips or multipolar electrocoagulation - MPEC). Patients and their healthcare providers were blinded to treatments and made all post-randomization management decisions. Ulcer patients received high dose intravenous infusions of proton pump inhibitors (PPI) for 3 days, then 27 days of oral PPI. 30 day outcomes were prospectively recorded; data management was with SAS; and data analysis was by a statistician. RESULTS: 53 patients (25 OTSC, 28 Standard) were randomized, with similar baseline risk factors. However, there were significant differences in OTSC vs. Standard groups in rates of rebleeding (4% vs. 28.6%; p = .017; relative risk 0.10, 95% confidence intervals 0.01, 0.91; number needed to treat 4); severe complications (0 % vs. 14.3%); and post-randomization units of red cell transfusions (0.04 vs. 0.68). All rebleeds occurred in patients with major SRH and none with lesser SRH. CONCLUSION: 1. OTSC significantly reduced rates of rebleeding, severe complications, and post-randomization red cell transfusions. 2. Patients with major stigmata benefited significantly from hemostasis with OTSC, but those with lesser stigmata did not. (ClinicalTrials.gov, Number: NCT03065465).

Multidimensional breathlessness assessment during cardiopulmonary exercise testing in healthy adults.

PURPOSE: This study explored if healthy adults could discriminate between different breathlessness dimensions when rated immediately one after another (successively) during symptom-limited incremental cardiopulmonary cycle exercise testing (CPET) using multiple single-item rating scales. METHODS: Fifteen apparently healthy adults (60% male) aged 22 ± 2 years performed six incremental cycle CPETs separated by ≥ 48 h. During each CPET (at rest, every 2-min and at end exercise), participants rated different breathlessness sensations using the 0-10 modified Borg scale using one of six assessment protocols, randomized for order: (1) 'BREATHLESSALL' = breathlessness sensory intensity (SI), breathlessness unpleasantness (UN), work/effort of breathing (SQW/E), and unsatisfied inspiration (SQUI) assessed; (2) SI and UN assessed; and (3-6) SI, UN, SQW/E, and SQUI each assessed alone. Physiological responses to CPET were also evaluated. RESULTS: Physiological and breathlessness responses to CPET were comparable across the six protocols, with the exception of SI rated lower at the highest submaximal power output (220 ± 56 watts) during the BREATHLESSALL protocol (0-10 Borg units 4.2 ± 1.7) compared to SI + UN (5.2 ± 2.1, p = 0.03) and SI alone (5.1 ± 1.9, p = 0.04) protocols. Ratings of SI and SQW/E were not significantly different when assessed in the same protocol, and were significantly higher than UN and SQUI, which were comparable. CONCLUSION: In healthy younger adults, use of two separate single-item rating scales to assess breathlessness during CPET is feasible and enables the distinct sensory intensity and affective dimensions of exertional breathlessness to be assessed.

Research and Healthcare Priorities of Individuals Living with COPD.

This study describes the research and healthcare priorities of individuals living with COPD. On an online survey, individuals living with COPD assigned a percentage of funding to 22 research priorities and a percentage of time spent communicating with a healthcare provider to 24 healthcare priorities, indicating which topics were most important. For each research and healthcare priority, we examined the selection frequency of the priority and used chi-square analyses to examine differences in priority selection by quartiles of airflow obstruction (percent predicted forced expiratory volume in 1-sec (FEV1%predicted)) and breathlessness burden and exacerbation risk. Based on participants' responses (N = 148, 47% women; Mean ± Standard Deviation age = 68 ± 9 yrs) relief of breathlessness was the most often selected research (76% of respondents) and healthcare priority (61% of respondents). It was selected most often, regardless of disease severity or breathlessness burden and exacerbation risk. We found differences for disease severity and breathlessness burden and exacerbation risk in some research priorities (e.g., to improve the maximal amount of exercise of adults living with COPD in and out of the home (χ2(3) = 9.97, Cramer's V =.28) and healthcare priorities (e.g., increase your ability to exercise (χ2(3) = 9.72, Cramer's V =.27)). This study provides empirical evidence that relief of breathlessness is a top research and healthcare priority for individuals living with COPD. Future healthcare and research activities should align with the priorities of individuals with COPD to improve their care by minimizing disease/symptom burden and optimizing health-related quality of life.

Spinal motoneurones are intrinsically more responsive in the adult G93A SOD1 mouse model of amyotrophic lateral sclerosis.

KEY POINTS: Although in vitro recordings using neonatal preparations from mouse models of amyotrophic lateral sclerosis (ALS) suggest increased motoneurone excitability, in vivo recordings in adult ALS mouse models have been conflicting. In adult G93A SOD1 models, spinal motoneurones have previously been shown to have deficits in repetitive firing, in contrast to the G127X SOD1 mouse model. Our in vivo intracellular recordings in barbiturate-anaesthetized adult male G93A SOD1 mice reveal that the incidence of failure to fire with current injection was equally low in control and ALS mice (∼2%). We show that failure to fire repetitively can be a consequence of experimental protocol and should not be used alone to classify otherwise normal motoneurones as hypo-excitable. Motoneurones in the G93A SOD1 mice showed an increased response to inputs, with lower rheobase, higher input-output gains and increased activation of persistent inward currents. ABSTRACT: In vitro studies from transgenic amyotrophic lateral sclerosis models have suggested an increased excitability of spinal motoneurones. However, in vivo intracellular recordings from adult amyotrophic lateral sclerosis mice models have produced conflicting findings. Previous investigations using barbiturate anaesthetized G93A SOD1 mice have suggested that some motoneurones are hypo-excitable, defined by deficits in repetitive firing. Our own previous recordings in G127X SOD1 mice using different anaesthesia, however, showed no repetitive firing deficits and increased persistent inward currents at symptom onset. These discrepancies may be a result of differences between models, symptomatic stage, anaesthesia or technical differences. To investigate this, we repeated our original experiments, but in adult male G93A SOD1 mice, at both presymptomatic and symptomatic stages, under barbiturate anaesthesia. In vivo intracellular recordings from antidromically identified spinal motoneurones revealed that the incidence of failure to fire with current injection was equally low in control and G93A SOD1 mice (∼2%). Motoneurones in G93A SOD1 mice fired significantly more spontaneous action potentials. Rheobase was significantly lower and the input resistance and input-output gain were significantly higher in both presymptomatic and symptomatic G93A SOD1 mice. This was despite a significant increase in the duration of the post-spike after-hyperpolarization in both presymptomatic and symptomatic G93A SOD1 mice. Finally, evidence of increased activation of persistent inward currents was seen in both presymptomatic and symptomatic G93A SOD1 mice. Our results do not confirm previous reports of hypo-excitability of spinal motoneurones in the G93A SOD1 mouse and demonstrate that the motoneurones show an increased response to inputs.

Management of Nonvariceal Upper Gastrointestinal Bleeding: Guideline Recommendations From the International Consensus Group.

Description: This update of the 2010 International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding (UGIB) refines previous important statements and presents new clinically relevant recommendations. Methods: An international multidisciplinary group of experts developed the recommendations. Data sources included evidence summarized in previous recommendations, as well as systematic reviews and trials identified from a series of literature searches of several electronic bibliographic databases from inception to April 2018. Using an iterative process, group members formulated key questions. Two methodologists prepared evidence profiles and assessed quality (certainty) of evidence relevant to the key questions according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Group members reviewed the evidence profiles and, using a consensus process, voted on recommendations and determined the strength of recommendations as strong or conditional. Recommendations: Preendoscopic management: The group suggests using a Glasgow Blatchford score of 1 or less to identify patients at very low risk for rebleeding, who may not require hospitalization. In patients without cardiovascular disease, the suggested hemoglobin threshold for blood transfusion is less than 80 g/L, with a higher threshold for those with cardiovascular disease. Endoscopic management: The group suggests that patients with acute UGIB undergo endoscopy within 24 hours of presentation. Thermocoagulation and sclerosant injection are recommended, and clips are suggested, for endoscopic therapy in patients with high-risk stigmata. Use of TC-325 (hemostatic powder) was suggested as temporizing therapy, but not as sole treatment, in patients with actively bleeding ulcers. Pharmacologic management: The group recommends that patients with bleeding ulcers with high-risk stigmata who have had successful endoscopic therapy receive high-dose proton-pump inhibitor (PPI) therapy (intravenous loading dose followed by continuous infusion) for 3 days. For these high-risk patients, continued oral PPI therapy is suggested twice daily through 14 days, then once daily for a total duration that depends on the nature of the bleeding lesion. Secondary prophylaxis: The group suggests PPI therapy for patients with previous ulcer bleeding who require antiplatelet or anticoagulant therapy for cardiovascular prophylaxis.

Description of Participation in Daily and Social Activities for Individuals with COPD.

This study described the participation in daily and social activities and the perceived barriers and facilitators to participation of individuals with chronic obstructive pulmonary disease (COPD). Individuals, recruited from outpatient clinics, responded to a survey on their participation in, and barriers and facilitators towards, 26 daily and social activities, divided into 3 categories: (1) physical activity and movement (PAM); (2) self-care; and (3) social engagement. For each activity, chi-square analyses were used to examine participation differences by individuals': quartiles of airflow obstruction [percent predicted forced expiratory volume in 1 second (FEV1%predicted)] and breathlessness burden and exacerbation risk. Of the 200 participants (47% women; mean ± standard deviation age = 68 ± 9 years), most wanted to increase their participation in PAM activities (range 21-75%) and significant differences were found in 5/10 PAM activities for individuals' breathlessness burden and exacerbation risk (e.g., more individuals than expected in group A (modified Medical Research Council breathlessness score <2 and 0-1 exacerbations in past 12 months) participated in regular exercise as much as they wanted (χ(9)2=20.43, Cramer's V=.23)). Regardless of the degree of airflow obstruction or breathlessness burden and exacerbation risk, the most common barrier to participation was breathlessness (p<.001, η2p=.86) and the most common facilitator was engaging as part of their routine (p<.001, η2p=.75). Individuals with COPD want to increase their participation in daily and social activities but are limited by breathlessness. Strategies to alleviate breathlessness should be identified/prioritized and incorporated into individuals' daily routines to meet their self-reported participation objectives in daily and social activities.

The Subprimary Range of Firing Is Present in Both Cat and Mouse Spinal Motoneurons and Its Relationship to Force Development Is Similar for the Two Species.

In the motor system, force gradation is achieved by recruitment of motoneurons and rate modulation of their firing frequency. Classical experiments investigating the relationship between injected current to the soma during intracellular recording and the firing frequency (the I-f relation) in cat spinal motoneurons identified two clear ranges: a primary range and a secondary range. Recent work in mice, however, has identified an additional range proposed to be exclusive to rodents, the subprimary range (SPR), due to the presence of mixed mode oscillations of the membrane potential. Surprisingly, fully summated tetanic contractions occurred in mice during SPR frequencies. With the mouse now one of the most popular models to investigate motor control, it is crucial that such discrepancies between observations in mice and basic principles that have been widely accepted in larger animals are resolved. To do this, we have reinvestigated the I-f relation using ramp current injections in spinal motoneurons in both barbiturate-anesthetized and decerebrate (nonanesthetized) cats and mice. We demonstrate the presence of the SPR and mixed mode oscillations in both species and show that the SPR is enhanced by barbiturate anesthetics. Our measurements of the I-f relation in both cats and mice support the classical opinion that firing frequencies in the higher end of the primary range are necessary to obtain a full summation. By systematically varying the leg oil pool temperature (from 37°C to room temperature), we found that only at lower temperatures can maximal summation occur at SPR frequencies due to prolongation of individual muscle twitches.SIGNIFICANCE STATEMENT This work investigates recent revelations that mouse motoneurons behave in a fundamentally different way from motoneurons of larger animals with respect to the importance of rate modulation of motoneuron firing for force gradation. The current study systematically addresses the proposed discrepancies between mice and larger species (cats) and demonstrates that mouse motoneurons, in fact, use rate modulation as a mechanism of force modulation in a similar manner to the classical descriptions in larger animals.

The accuracy of trans rectal ultrasonography (TRUS) in early-stage rectal cancer or benign adenomas.

Background: Screening for colorectal cancer in Denmark has resulted in more patients being diagnosed with benign adenomas and early-stage rectal cancer. In general, TRUS is accepted as a good modality for evaluating the above mentioned before deciding on surgery. Objective: To investigate the accuracy of TRUS in a clinical setting at the Region Hospital in Herning, Denmark. Study design: Retrospective cohort study from January 2016 to June 2018. Methods: Quantitative method. The cohort (117 patients) was recruited by searching for specific procedure codes. Data were collected by going through the electronic patient files. Results: TRUS predicted T0, T1, T2 and T3 with an accuracy of 91%, 35%, 43% and 20% respectively and an overall accuracy of 68%. A weighted Cohens kappa value of 0.30 (p ≤ .05). TRUS differentiated between T0/T1 with a sensitivity of 70%, specificity of 85% and an accuracy of 85% and kappa value of 0.44 (p ≤ .05). Conclusion: TRUS can with great precision establish whether the tumor is benign so correct local treatment can be instituted.

Asia-Pacific working group consensus on non-variceal upper gastrointestinal bleeding: an update 2018.

Non-variceal upper gastrointestinal bleeding remains an important emergency condition, leading to significant morbidity and mortality. As endoscopic therapy is the 'gold standard' of management, treatment of these patients can be considered in three stages: pre-endoscopic treatment, endoscopic haemostasis and post-endoscopic management. Since publication of the Asia-Pacific consensus on non-variceal upper gastrointestinal bleeding (NVUGIB) 7 years ago, there have been significant advancements in the clinical management of patients in all three stages. These include pre-endoscopy risk stratification scores, blood and platelet transfusion, use of proton pump inhibitors; during endoscopy new haemostasis techniques (haemostatic powder spray and over-the-scope clips); and post-endoscopy management by second-look endoscopy and medication strategies. Emerging techniques, including capsule endoscopy and Doppler endoscopic probe in assessing adequacy of endoscopic therapy, and the pre-emptive use of angiographic embolisation, are attracting new attention. An emerging problem is the increasing use of dual antiplatelet agents and direct oral anticoagulants in patients with cardiac and cerebrovascular diseases. Guidelines on the discontinuation and then resumption of these agents in patients presenting with NVUGIB are very much needed. The Asia-Pacific Working Group examined recent evidence and recommends practical management guidelines in this updated consensus statement.

Doppler Endoscopic Probe Monitoring of Blood Flow Improves Risk Stratification and Outcomes of Patients With Severe Nonvariceal Upper Gastrointestinal Hemorrhage.

BACKGROUND & AIMS: For 4 decades, stigmata of recent hemorrhage in patients with nonvariceal lesions have been used for risk stratification and endoscopic hemostasis. The arterial blood flow that underlies the stigmata rarely is monitored, but can be used to determine risk for rebleeding. We performed a randomized controlled trial to determine whether Doppler endoscopic probe monitoring of blood flow improves risk stratification and outcomes in patients with severe nonvariceal upper gastrointestinal hemorrhage. METHODS: In a single-blind study performed at 2 referral centers we assigned 148 patients with severe nonvariceal upper gastrointestinal bleeding (125 with ulcers, 19 with Dieulafoy's lesions, and 4 with Mallory Weiss tears) to groups that underwent standard, visually guided endoscopic hemostasis (control, n = 76), or endoscopic hemostasis assisted by Doppler monitoring of blood flow under the stigmata (n = 72). The primary outcome was the rate of rebleeding after 30 days; secondary outcomes were complications, death, and need for transfusions, surgery, or angiography. RESULTS: There was a significant difference in the rates of lesion rebleeding within 30 days of endoscopic hemostasis in the control group (26.3%) vs the Doppler group (11.1%) (P = .0214). The odds ratio for rebleeding with Doppler monitoring was 0.35 (95% confidence interval, 0.143-0.8565) and the number needed to treat was 7. CONCLUSIONS: In a randomized controlled trial of patients with severe upper gastrointestinal hemorrhage from ulcers or other lesions, Doppler probe guided endoscopic hemostasis significantly reduced 30-day rates of rebleeding compared with standard, visually guided hemostasis. Guidelines for nonvariceal gastrointestinal bleeding should incorporate these results. ClinicalTrials.gov no: NCT00732212 (CLIN-013-07F).

Cannabis and the Health and Performance of the Elite Athlete.

OBJECTIVE: Cannabis (marijuana) is undergoing extensive regulatory review in many global jurisdictions for medical and nonmedical access. Cannabis has potential impact on the health of athletes as well as on performance in both training and in competition. The aim of this general review is to identify and highlight the challenges in interpreting information with respect to elite athletic performance, and to point to important research areas that need to be addressed. DATA SOURCES: A nonsystematic literature review was conducted using Medline and PubMed for articles related to cannabis/marijuana use and sports/athletic performance; abstracts were reviewed by lead author and key themes identified and explored. MAIN RESULTS: Cannabis may be primarily inhaled or ingested orally for a range of medical and nonmedical reasons; evidence for efficacy is limited but promising for chronic pain management. Although evidence for serious harms from cannabis use on health of athletes is limited, one should be cognizant of the potential for abuse and mental health issues. Although the prevalence of cannabis use among elite athletes is not well-known, use is associated with certain high-risk sports. There is no evidence for cannabis use as a performance-enhancing drug. CONCLUSIONS: Medical and nonmedical cannabis use among athletes reflects changing societal and cultural norms and experiences. Although cannabis use is more prevalent in some athletes engaged in high-risk sports, there is no direct evidence of performance-enhancing effects in athletes. The potential beneficial effects of cannabis as part of a pain management protocol, including reducing concussion-related symptoms, deserve further attention.

Muscle disuse caused by botulinum toxin injection leads to increased central gain of the stretch reflex in the rat.

Botulinum toxin (Btx) is used in children with cerebral palsy and in other neurological patients to diminish spasticity and reduce the risk of development of contractures. We investigated changes in the central gain of the stretch reflex circuitry in response to Btx injection in the triceps surae muscle in rats. Experiments were performed in 21 rats. Eight rats were a control group, and 13 rats were injected with 6 IU of Btx in the left triceps surae muscle. Two weeks after Btx injection, larger monosynaptic reflexes (MSR) were recorded from the left (injected) than the right (noninjected) L4 + L5 ventral roots following stimulation of the corresponding dorsal roots. A similar increase on the left side was observed in response to stimulation of descending motor tracts, suggesting that increased excitability of spinal motor neurons may at least partly explain the increased reflexes. However, significant changes were also observed in postactivation depression of the MSR, suggesting that plastic changes in transmission from Ia afferent to the motor neurons also may be involved. The data demonstrate that muscle paralysis induced by Btx injection is accompanied by plastic adaptations in the central stretch reflex circuitry, which counteract the antispastic effect of Btx.NEW & NOTEWORTHY Injection of botulinum toxin into ankle muscles causes increased gain of stretch reflex. This is caused by adaptive changes in regulation of transmitter release from Ia afferents and increased excitability of spinal motor neurons.