Use of Biologics for the Treatment of Inflammatory Conditions of the Pouch: A Systematic Review.

BACKGROUND: Patients with medically-refractory ulcerative colitis or advanced neoplasia are often offered an ileal-pouch-anal anastomosis to restore bowel continuity. However, up to 50% of patients can suffer from inflammatory conditions of the pouch, some of which require biological therapy to treat. The aim of this study was to determine the efficacy of each biological agent for the treatment of inflammatory conditions of the pouch. MATERIALS AND METHODS: A comprehensive literature search was performed in the major databases from inception through February 11, 2020, for studies assessing the efficacy of biologics in chronic antibiotic-refractory pouchitis (CARP) and Crohn's disease (CD) of the pouch. Both prospective and retrospective studies were included. The primary outcomes of interest were complete and partial responses were defined within each study. χ 2 test was used to compare variables. RESULTS: Thirty-four studies were included in the systematic review and meta-analysis. Sixteen studies (N=247) evaluated the use of infliximab (IFX), showing complete response in 50.7% and partial response in 28.1% for CARP, and complete response in 66.7% and partial response in 20% for CD of the pouch. Seven studies (n=107) assessed the efficacy of adalimumab. For CARP, 33.3% of patients had a complete response, and 38.1% had a partial response, whereas for CD of the pouch, 47.7% experienced a complete response, and 24.6% had a partial response. Three studies (n=78) reported outcomes with the use of ustekinumab, showing 50% complete response and 3.8% partial response for CARP. For the CD of the pouch, 5.8% had a complete response and 78.8% had a partial response. Seven studies (n=151) reported the efficacy of vedolizumab, showing 28.4% complete response and 43.2% partial response in patients with CARP, whereas 63% of patients experienced partial response in CD of the pouch. IFX had higher rates of complete response in CARP compared with adalimumab ( P =0.04) and compared with vedolizumab ( P =0.005), but not compared with ustekinumab ( P =0.95). There were no new safety signals reported in any of the studies. CONCLUSIONS: Biologics are safe and efficacious in the treatment of chronic, refractory inflammatory conditions of the pouch. IFX seems to be more efficacious than adalimumab and vedolizumab for CARP. Further prospective, head-to-head evaluations are needed to compare biological therapies in the treatment of CARP and CD of the pouch.

A Novel Patient-like Swine Model of Perianal Crohn's Disease.

BACKGROUND: Perianal Crohn's disease is associated with poor outcomes and high medical costs. It is notoriously difficult to treat despite therapeutic advancements for luminal disease. A large animal model that mimics human perianal disease is needed to test innovative therapies. OBJECTIVE: This study aimed to create a swine model that replicates the inflammatory component and therapeutic challenges found in patients with perianal Crohn's disease. DESIGN: This was an animal preclinical study. SETTINGS: The experiments were performed at the animal laboratory at the Johns Hopkins University. PATIENTS: Four sus scrufus female pigs were included in the study. INTERVENTIONS: Four female pigs underwent creation of 3 surgical perianal fistulas each, 1 rectovaginal and 2 perianal. Size 24 French setons were placed to maintain patency of the fistula tracts for 4 weeks. After removal of the setons, trinitrobenzene sulfonic acid was administered into the fistula tract to create and maintain local inflammation mimicking perianal Crohn's disease. MAIN OUTCOMES MEASURES: An MRI was obtained to assess the fistulas and the pigs were euthanized to review histopathology. RESULTS: Three inflammatory chronic fistula tracts were successfully created in each pig as confirmed by MRI and examination under anesthesia. This is the first report of maintaining patent fistulas in swine 2 weeks after removal of setons. For the first time, we reported that 2 pigs developed branching fistulas and small abscesses reminiscent of human perianal Crohn's disease. The corresponding histopathologic examination found significant chronic active inflammation on standard hematoxylin and eosin staining. LIMITATIONS: The fistulas were surgically induced and did not occur naturally. CONCLUSIONS: A chronic perianal fistula model in pigs that strongly resembles human perianal Crohn's disease was successfully created. This model can be used to test novel therapeutics and techniques to pave the path for human trials. See Video Abstract at http://links.lww.com/DCR/B969 . UN NUEVO MODELO PORCINO SIMILAR A UN PACIENTE DE LA ENFERMEDAD DE CROHN PERIANAL ANTECEDENTES: La enfermedad de Crohn perianal se asocia con malos resultados y altos costos médicos. Es notoriamente difícil de tratar a pesar de los avances terapéuticos para la enfermedad luminal. Se precisa de un modelo animal grande que imite la enfermedad perianal humana para probar terapias innovadoras.OBJETIVO:Nuestro objetivo de este estudio fue crear un modelo porcino que replique el componente inflamatorio y los desafíos terapéuticos que se encuentran en los pacientes con enfermedad de Crohn perianal.DISEÑO:Este fue un estudio preclínico en animales.AJUSTES:Los experimentos se realizaron en el laboratorio de animales de la Universidad Johns Hopkins.PACIENTES:Se incluyeron en el estudio cuatro cerdas sus scrofa.INTERVENCIONES:Cuatro cerdas fueron sometidas a la creación de 3 fístulas perianales quirúrgicas cada una: 1 recto vaginal y 2 perianales. Se colocaron sedales de 24 French para mantener la permeabilidad de los trayectos fistulosos durante 4 semanas. Tras el retiro de los sedales, se administró ácido trinitrobenceno sulfónico en el trayecto de la fístula para crear y mantener la inflamación local simulando la enfermedad de Crohn perianal.PRINCIPALES MEDIDAS DE RESULTADOS:Se obtuvo una resonancia magnética para evaluar las fístulas y los cerdos fueron sacrificados para revisar la histopatología.RESULTADOS:Se crearon de manera exitosa tres trayectos fistulosos inflamatorios crónicos en cada cerdo, confirmados por imágenes de resonancia magnética y examen bajo anestesia. Este es el primer informe de preservación de fístulas permeables en cerdos 2 semanas tras el retiro de los setones. Por primera vez, informamos que dos cerdos desarrollaron fístulas ramificadas y pequeños abscesos que recuerdan a la enfermedad de Crohn perianal humana. El examen histopatológico correspondiente encontró una significativa inflamación crónica activa en la tinción estándar de hematoxilina y eosina.LIMITACIONES:Las fístulas se indujeron quirúrgicamente y no se produjeron de forma natural.CONCLUSIONES:Se logro recrear con éxito un modelo de fístula perianal crónica en cerdos que se asemeja mucho a la enfermedad de Crohn perianal humana. Este modelo se puede utilizar para probar nuevas terapias y técnicas para allanar el camino para los ensayos en humanos. Consulte Video Resumen en http://links.lww.com/DCR/B969 . (Traducción-Dr Osvaldo Gauto).

Regulatory Light-Chain Phosphorylation During Weightlifting Training: Association With Postactivation Performance Enhancement.

ABSTRACT: Chiu, LZF, Fry, AC, Galpin, AJ, Salem, GJ, and Cabarkapa, D. Regulatory light-chain phosphorylation during weightlifting training: association with postactivation performance enhancement. J Strength Cond Res 37(10): e563-e568, 2023-Postactivation performance enhancement has been reported for multijoint resistance exercise, with both neural and intrinsic muscle mechanisms suggested as contributing factors. The purpose of this investigation was to examine whether regulatory light-chain (RLC) phosphorylation in a primary mover is associated with enhanced weightlifting performance. Nine male athletes performed 15 sets of 3 repetitions of a multijoint weightlifting activity (clean pull) at 85% 1 repetition maximum. Measures of performance, peak barbell velocity (PV), and average barbell power (AP) were determined by video analysis. Muscle biopsies were taken within 30-60 seconds of completion of the previous lifting set from the vastus lateralis before (PRE), during (MID), and after (POST) a training session. AP was significantly greater for sets 3, 4, and 5 compared with set 1, with large effect sizes (0.8-1.0). Increases in PV did not reach significance; however, the effect size increase for sets 3 and 4 versus set 1 was moderate (0.4). Relative change scores for AP and RLC phosphorylation were positively and negatively correlated at MID (r = 0.60; p = 0.05) and POST (r = -0.74; p = 0.01) exercise, respectively. These data suggest that RLC phosphorylation initially may be associated with postactivation performance enhancement during repeated multijoint exercise.

Advances in Imaging of Inflammation, Fibrosis, and Cancer in the Gastrointestinal Tract.

Gastrointestinal disease is prevalent and broad, manifesting itself in a variety of ways, including inflammation, fibrosis, infection, and cancer. However, historically, diagnostic technologies have exhibited limitations, especially with regard to diagnostic uncertainty. Despite development of newly emerging technologies such as optoacoustic imaging, many recent advancements have focused on improving upon pre-existing modalities such as ultrasound, computed tomography, magnetic resonance imaging, and endoscopy. These advancements include utilization of machine learning models, biomarkers, new technological applications such as diffusion weighted imaging, and new techniques such as transrectal ultrasound. This review discusses assessment of disease processes using imaging strategies for the detection and monitoring of inflammation, fibrosis, and cancer in the context of gastrointestinal disease. Specifically, we include ulcerative colitis, Crohn's disease, diverticulitis, celiac disease, graft vs. host disease, intestinal fibrosis, colorectal stricture, gastric cancer, and colorectal cancer. We address some of the most recent and promising advancements for improvement of gastrointestinal imaging, including unique discussions of such advancements with regard to imaging of fibrosis and differentiation between similar disease processes.

Effects of high-intensity interval training on vascular endothelial function and vascular wall thickness in breast cancer patients receiving anthracycline-based chemotherapy: a randomized pilot study.

PURPOSE: The purpose of this study was to determine the effects of an 8-week high-intensity interval training (HIIT) intervention on vascular endothelial function, measured as brachial artery flow-mediated dilation (baFMD), and vascular wall thickness measured by carotid intima media thickness (cIMT) in breast cancer patients undergoing anthracycline-based chemotherapy. METHODS: Thirty women were randomized to either HIIT or non-exercise control groups (CON). The HIIT group participated in an 8-week HIIT intervention occurring three times per week on a cycle ergometer. The CON group was offered the HIIT intervention after 8 weeks. baFMD was measured from the brachial artery diameter at baseline (D0) and 1 min after cuff deflation (D1); percent change was calculated by measuring brachial artery diameter after cuff deflation relative to the baseline [baFMD = (D1 - D0)/D0 × 100]. The cIMT was obtained from the posterior wall of common carotid artery 10 mm below the carotid bulb. Paired t test and repeated measures ANCOVA were performed to assess changes in baFMD and cIMT. RESULTS: At baseline, the HIIT (n = 15) and CON (n = 15) groups did not differ by age (46.9 ± 9.8 years), BMI (31.0 ± 7.5 kg/m2), and blood pressure (123.4 ± 16.8/72.3.9 ± 5.6 mmHg). Post-exercise, baFMD significantly increased [4.3; 95% confidence interval (CI): (1.5, 7.0), p = 0.005] in HIIT versus CON group. cIMT did not significantly change [0.003, 95% CI - 0.004, 0.009), p = 0.40] in HIIT group, while IMT significantly increased from baseline to post-intervention (0.009, 95% CI 0.004, 0.010, p = 0.003) in CON group. CONCLUSION: This study may suggest that HIIT improved vascular endothelial function and maintained wall thickness in breast cancer patients undergoing anthracycline-based chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02454777.

Feasibility of high intensity interval training in patients with breast Cancer undergoing anthracycline chemotherapy: a randomized pilot trial.

BACKGROUND: Anthracycline-based chemotherapy is associated with reduced cardiorespiratory fitness in breast cancer patients. High intensity interval training (HIIT) induces greater benefits on cardiorespiratory fitness than moderate continuous aerobic exercise in patients with heart failure. The study purpose was to determine whether a HIIT intervention is a feasible exercise strategy for breast cancer patients undergoing anthracycline-based chemotherapy. METHODS: Thirty women were randomized to either HIIT or non-exercise control group (CON). Participants performed a maximal cycling fitness test to measure peak power output during maximal oxygen uptake (VO2max). The HIIT group participated in an 8-week HIIT intervention occurring 3 times weekly. Feasibility was calculated by computing (1) the average weekly minutes of HIIT over 8 weeks and (2) the number of sessions attended and multiplied by 100 (percentage of sessions). The intervention was considered feasible if more than 50% of participants completed both an average of 70% of weekly minutes (63/90 min) and attended 70% exercise sessions (17/24 sessions). RESULTS: Participants were 46.9 ± 9.8 (mean ± SD) years old, diagnosed with clinical stage II (30%) or III (63%) breast cancer. The average weekly minutes of exercise completed was 78 ± 5.1 out of 90 min. Twelve of 15 participants met both feasibility criteria, attending 19.2 ± 2.1 out of 24 sessions (82.3%). VO2max was maintained (19.7 ± 8.7 to 19.4 ± 6.6 ml/kg/min) in HIIT group (p = 0.94) while there was a significant decrease in VO2max (18.7 ± 7.1 to 16.1 ± 6.0 ml/kg/min) in CON group from baseline to 8 weeks (p = 0.001). CONCLUSIONS: HIIT is a feasible exercise intervention to maintain VO2max in breast cancer patients receiving anthracycline-based chemotherapy. TRIAL REGISTRATION: The protocol and informed consent were approved by the institutional IRB (HS-12-00227) and registered ( ClinicalTrials.gov NCT02454777; date of registration: May 272,015).

The Impact on Endoscopic Resource Utilization After a Targeted Intervention for Cost-Minimization of EGD and Colonoscopy.

OBJECTIVES: The need to define the cost of endoscopic procedures becomes increasingly important in an era of providing low-cost, high-quality care. We examined the impact of informing endoscopists of the cost of accessories and pathology specimens as a cost-minimization strategy. METHODS: We conducted a prospective observational cohort study of therapeutic outpatient esophagogastroduodenoscopy (EGD) and colonoscopy. During the pre-intervention phase (phase 1), the endoscopists were not briefed on the cost of accessories or pathology specimens obtained during the procedure. During a 3-week intervention phase and the post-intervention phase (phase 2) endoscopists were informed of the dollar value of accessories and pathology specimens after the completion of all procedures. In all cases the institutional costs (not charges) were used. The endoscopists were blinded to their observation. RESULTS: A total of 969 EGD, colonoscopy, and EGD+colonoscopy performed by 6 endoscopists were reviewed, 456 procedures in phase 1 and 513 procedures in phase 2. There was no significant difference between phases 1 and 2 in total device and pathology cost in dollars (188.8±151.4 vs. 188.9±151.8, P=0.99), total device cost (36.2±107.9 vs. 39.0±95.96, P=0.67) and total pathology cost (152.6±101.3 vs. 149.9±112.5, P=0.70). There was not a significant difference in total device and pathology cost when examined by specific procedures performed, or for any of the endoscopists between phases 1 and 2. CONCLUSIONS: Making endoscopists more cost conscious by informing them of the costs of each procedure during EGD and colonoscopy does not result in lower procedural costs. Analysis of cost-minimization strategies involving procedures in other health-care settings and procedures using high-cost accessories are warranted.

The Influence of a Bout of Exertion on Novice Barefoot Running Dynamics.

Barefoot, forefoot strike (FFS) running has recently risen in popularity. Relative to shod, rear-foot strike (RFS) running, employing a FFS is associated with heightened triceps surae muscle activation and ankle mechanical demand. Novice to this pattern, it is plausible that habitually shod RFS runners exhibit fatigue to the triceps surae when acutely transitioning to barefoot running, thereby limiting their ability to attenuate impact. Therefore, the purpose was to determine how habitually shod RFS runners respond to an exertion bout of barefoot running, operationally defined as a barefoot run 20% of mean daily running distance. Twenty-one RFS runners performed novice barefoot running, before and after exertion. Ankle peak torque, triceps surae EMG median frequency, foot-strike patterns, joint energy absorption, and loading rates were evaluated. Of the 21 runners, 6 maintained a RFS, 10 adopted a mid-foot strike (MFS), and 5 adopted a FFS during novice barefoot running. In-response to exertion, MFS and FFS runners demonstrated reductions in peak torque, median frequency, and ankle energy absorption, and an increase in loading rate. RFS runners demonstrated reductions in peak torque and loading rate. These results indicate that a short bout of running may elicit fatigue to novice barefoot runners, limiting their ability to attenuate impact. Key pointsIn response to exertion, novice barefoot runners demonstrate fatigue to their soleus.In response to exertion, novice barefoot runners demonstrate a reduction in ankle energy absorptionIn response to exertion, novice barefoot runners demonstrate an increase in loading rate.

The Limiting Joint During a Failed Squat: A Biomechanics Case Series.

This investigation examined the characteristics of a failed back squat. Subjects were instructed to perform 3 repetitions of a barbell squat with a 3 repetition maximum load while instrumented for biomechanical analyses and standing atop force platforms. Inverse dynamics calculations were used to determine the net joint moment (NJM) power, work, and energy of the hip, knee, and ankle. Five subjects failed to complete all 3 repetitions, allowing for comparisons between a successful and the failed repetition. Although the NJM power and work were lower at all 3 joints during the failed attempt, the only statistically significant differences were at the hip. These findings suggest that the energy generated by the hip joint NJM limited performance of the task. However, examination of the NJM energy generation over time on an individual basis uncovered some features that were masked by the aggregated group mean data. For some subjects, the knee NJM limited the movement. Additionally, negligible to modest compensations occurred between the hip and knee NJM: a decreased energy generated by one NJM was often accompanied by an increase in energy generated at the other. A limiting joint, or "weak link," may explain the failure to complete a lift. Interventions should address the limiting joint on an individual-specific basis and incorporate assistive exercises that target these deficiencies.

The association between unilateral heel-rise performance with static and dynamic balance in community dwelling older adults.

As a measure of both strength and muscle endurance of the plantar flexors, the unilateral heel rise (UHR) test has been suggested as a method to evaluate balance capabilities in older adults. Thus, the purpose of this study was to examine the association between UHR performance with biomechanical measures of balance in seniors. Twenty-two older adults completed two testing sessions. The first visit included UHR performance; the second visit included dynamic and static motion analysis. UHR performance was significantly associated with dynamic balance capability as measured by medial-lateral inclination angle during gait. As indicated by an analysis of center of pressure, there were significant associations between UHR performance and measures of static balance. Balance is influenced by plantar flexor performance as measured by the UHR test. We therefore suggest incorporating the UHR test in analyses of balance in seniors.

The biomechanical demands of standing yoga poses in seniors: The Yoga empowers seniors study (YESS).

BACKGROUND: The number of older adults participating in yoga has increased dramatically in recent years; yet, the physical demands associated with yoga performance have not been reported. The primary aim of the Yoga Empowers Seniors Study (YESS) was to use biomechanical methods to quantify the physical demands associated with the performance of 7 commonly-practiced standing yoga poses in older adults. METHODS: 20 ambulatory older adults (70.7+-3.8 yrs) attended 2 weekly 60-minute Hatha yoga classes for 32 weeks. The lower-extremity net joint moments of force (JMOFs), were obtained during the performance of the following poses: Chair, Wall Plank, Tree, Warrior II, Side Stretch, Crescent, and One-Legged Balance. Repeated-measure ANOVA and Tukey's post-hoc tests were used to identify differences in JMOFs among the poses. Electromyographic analysis was used to support the JMOF findings. RESULTS: There was a significant main effect for pose, at the ankle, knee and hip, in the frontal and sagittal planes (p=0.00-0.03). The Crescent, Chair, Warrior II, and One-legged Balance poses generated the greatest average support moments. Side Stretch generated the greatest average hip extensor and knee flexor JMOFs. Crescent placed the highest demands on the hip flexors and knee extensors. All of the poses produced ankle plantar-flexor JMOFs. In the frontal plane, the Tree generated the greatest average hip and knee abductor JMOFs; whereas Warrior II generated the greatest average hip and knee adductor JMOFs. Warrior II and One-legged Balance induced the largest average ankle evertor and invertor JMOFs, respectively. The electromyographic findings were consistent with the JMOF results. CONCLUSIONS: Musculoskeletal demand varied significantly across the different poses. These findings may be used to guide the design of evidence-based yoga interventions that address individual-specific training and rehabilitation goals in seniors. CLINICAL TRIAL REGISTRATION: This study is registered with NIH Clinicaltrials.gov #NCT 01411059.

The physical demands of the tree (vriksasana) and one-leg balance (utthita hasta padangusthasana) poses performed by seniors: a biomechanical examination.

Yoga is considered especially suitable for seniors because poses can be modified to accommodate practitioners' capabilities and limitations. In this study, biomechanical assessments on healthy seniors (n = 20; 70.1 ± 3.8 yr) were used to quantify the physical demands, (net joint moments of force [JMOFs] and muscular activation in the lower extremities) associated with the performance of 3 variations (introductory, intermediate, advanced) of 2 classical Hatha yoga poses - Tree and One-Leg Balance (OLB). ANOVA and Cohen's-d were used to contrast the postural variations statistically. The advanced (single-limb, without additional support) versions were hypothesized to generate the greatest demands, followed by the intermediate (single-limb [Tree] and bilateral-limb [OLB] with support) and introductory (bilateral-limb) versions. Our findings, however, suggest that common, long-held conceptions about pose modifications can be counter-intuitive. There was no difference between the intermediate and advanced Tree variations regarding hip and knee JMOFs in both the sagittal and frontal planes (P = 0.13-0.98). Similarly, OLB introductory and intermediate variations induced sagittal JMOFs that were in the opposite direction of the classic advanced pose version at the hip and knee (P < .001; d = 0.98-2.36). These biomechanical insights provide evidence that may be used by instructors, clinicians and therapists when selecting pose modifications for their yoga participants.