Long-term Exercise After Pulmonary Rehabilitation (LEAP): a pilot randomised controlled trial of Tai Chi in COPD.

Mind-body modalities are promising strategies to maintain the benefits gained after completion of conventional pulmonary rehabilitation in persons with COPD. In this pilot randomised controlled study we examined Tai Chi in persons with COPD after completing pulmonary rehabilitation. Participants were randomised 2:2:1 to Tai Chi (TC), usual care (UC) or group walking (GW) for 24 weeks. We assessed feasibility; primary outcome was exercise capacity measured by 6-min walk test (6MWT) distance at 24 weeks. Secondary outcomes included health-related quality of life measured by Chronic Respiratory Questionnaire (CRQ), dyspnoea, mood, stress, social support, self-efficacy, physical activity and exercise engagement. Effect size estimates and estimates from generalised estimating equations were calculated. Ninety-one persons (36 TC, 37 UC, 18 GW) were enrolled, with mean age 69±6 years, 59% male, and forced expiratory volume in 1 s % predicted (FEV1 % pred) 48±19%. There was no difference in adherence and adverse events between groups. There was a small between-group effect size (ES=0.25) in change in 6MWT distance favouring TC compared to UC; 24-week comparison was nonsignificant (p=0.10). There were no differences in secondary outcomes. In exploratory analyses, there was a greater percentage of participants in TC who improved 6MWT distance at 24 weeks, compared to UC, 64% versus 39%, p=0.05. There were higher percentages of participants in TC who improved CRQ Fatigue (59% versus 31%, p=0.02) and CRQ Mastery (47% versus 20%, p=0.01) domain scores, compared to UC. For GW, there were no differences compared with TC. Tai Chi may be a feasible option to maintain the benefits gained after completing conventional pulmonary rehabilitation.

Exploring Tai Chi Exercise and Mind-Body Breathing in Patients with COPD in a Randomized Controlled Feasibility Trial.

In this pilot feasibility randomized controlled trial, participants with moderate to severe COPD were randomized to a 12-week tai chi or MBB intervention. Participants were assessed at baseline, 12 weeks, and 24 weeks. Feasibility, as assessed by intervention adherence, was the primary outcome. We also estimated preliminary between-group differences in COPD symptoms and health-related quality of life, cognitive-emotional function, and functional status across three timepoints: baseline, 12, and 24 weeks. A total of 92 participants were randomized 2:1 to tai chi (n = 61) or MBB (n = 31). The overall group adherence in the first 12 weeks was 62% in tai chi and 75% in MBB. From baseline to 12 weeks, tai chi demonstrated greater improvements in depressive symptoms (Cohen's d effect size (ES) = -.53; adj mean diff = -2.31 [-5.7, 1.07]), 6-minute walk test distance (ES = .47; adj mean diff = 62.04 [2.85, 121.22]), social support (ES = .36; adj mean diff = .19 [-0.11, 0.49]) and chair stand (ES = .44; adj mean diff = .91 [-0.05, 1.86]). Only improvements in social support were maintained at 24-week follow-up. Tai chi and MBB are feasible for individuals with COPD. Preliminary effects suggest that while our mindful breathing intervention may not be sufficient to impact outcomes, tai chi may result in short-term benefits in mood, social support and functional capacity. More work is needed to better understand mindful breathing for COPD and to examine methods for maintaining improvements from tai chi over time.Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2021.1928037 .

BEAM study (Breathing, Education, Awareness, Movement): a randomised controlled feasibility trial of tai chi exercise in patients with COPD.

BACKGROUND: Despite therapeutic advances, the management of chronic obstructive pulmonary disease (COPD) remains complex. There is growing interest in multidimensional, mind-body exercises to improve both physical and psychosocial aspects of COPD burden. Few US data are available in this population on tai chi (TC) a mind-body exercise incorporating physical activity, breathing and mindful awareness. We explored feasibility and preliminary efficacy of TC in COPD in an US academic medical setting. METHODS: Patients with COPD Global Obstructive Lung Disease (GOLD) stages 2-4 were randomised to a 12-week TC programme or education control. At 12 weeks, those in TC were randomised again to continue in maintenance classes or not to further explore optimal duration. All groups were followed to 24 weeks. Feasibility/safety parameters were analysed descriptively. Preliminary between-group differences were estimated in symptoms (dyspnoea, fatigue), health-related quality-of-life (Chronic Respiratory Questionnaire CRQ), cognitive-emotional measures (mood, COPD self-efficacy) and functional status (6 min walk test, lower body strength, flexibility, physical activity). RESULTS: Ninety-two subjects were randomised (N=61 TC, N=31 education). Mean age was 68±8 years, 66% male, mean forced expiratory volume in 1 s % predicted 57±13, 28% were GOLD stage 3-4. Overall retention was 85%. Nineteen adverse events occurred, most being study-unrelated COPD exacerbations. From baseline to 12 weeks, there were between-group improvements favouring TC, in CRQ-total (Cohen's d effect size (ES)=0.46; adj mean diff (AMD)=0.31), CRQ-emotion (ES=0.54; AMD=0.49), Centre for Epidemiologic Studies Depression (ES=-0.37; AMD=2.39) and Patient-Reported Outcome Measurement Information System (PROMIS)-fatigue (ES=-0.34; AMD=-0.17). From baseline to 24 weeks, there was an improvement favouring TC in CRQ-dyspnoea (ES=0.41; AMD=0.46). Among TC participants, there was a positive effect of maintenance classes on self-efficacy (ES=-0.69; AMD=-0.40), 6 min walk (ES=0.56; AMD=49.26 feet), PROMIS-fatigue (ES=-0.41; AMD=-0.28) and chair stand (0.43; AMD=0.56). CONCLUSION: TC in patients with COPD is feasible and safe. Preliminary analyses support a potential modest role in improving quality-of-life, cognitive-emotional health and function that should be further studied. TRIAL REGISTRATION NUMBER: NCT01551953. IRB REFERENCE: BIDMC 2010P-000412; VA 2540.

Outcomes of front-line ibrutinib treated CLL patients excluded from landmark clinical trial.

Ibrutinib demonstrated superior response rates and survival for treatment-naïve chronic lymphocytic leukemia (CLL) patients in a pivotal study that excluded patients younger than 65 (<65) and/or with chromosome 17p13 deletion (del[17p13]). We examined outcomes and toxicities of CLL patients who would have been excluded from the pivotal study, specifically <65 and/or those with del[17p13]. This multicenter, retrospective cohort study examined CLL patients treated with front-line ibrutinib at 20 community and academic centers, categorizing them based on key inclusion criteria for the RESONATE-2 trial: <65 vs ≥65 and present vs absent del[17p13]. Of 391 included patients, 57% would have been excluded from the pivotal study. Forty-one percent of our cohort was <65, and 30% had del(17p13). Patients <65 were more likely to start 420 mg of ibrutinib daily; those who started at reduced doses had inferior PFS. The most common adverse events were arthralgias, fatigue, rash, bruising, and diarrhea. Twenty-four percent discontinued ibrutinib at 13.8 months median follow-up; toxicity was the most common reason for discontinuation, though progression and/or transformation accounted for a larger proportion of discontinuations in <65 and those with del(17p13). Response rates were similar for <65 and those with del(17p13). However, patients with del(17p13) had inferior PFS and OS. Ibrutinib in the front-line setting has extended beyond the population in which it was initially studied and approved. This study highlights and compares important differences in ibrutinib dosing, treatment interruptions, toxicities, reasons for discontinuation, and survival outcomes in two important patient populations not studied in RESONATE-2.

Long-term Exercise After Pulmonary Rehabilitation (LEAP): Design and rationale of a randomized controlled trial of Tai Chi.

BACKGROUND: Persons with chronic obstructive pulmonary disease (COPD) have reduced exercise capacity and levels of physical activity. Supervised, facility-based pulmonary rehabilitation programs improve exercise capacity and reduce dyspnea, but novel long-term strategies are needed to maintain the benefits gained. Mind-body modalities such as Tai Chi which combine aerobic activity, coordination of breathing, and cognitive techniques that alleviate the physical inactivity, dyspnea, and anxiety and depression that are the hallmarks of COPD are promising strategies. METHODS/DESIGN: We have designed a randomized controlled study to examine whether Tai Chi will maintain exercise capacity in persons with COPD who have recently completed a supervised pulmonary rehabilitation program, compared to standard care. The primary outcome is 6-min walk test distance at 6 months. Secondary outcomes include health-related quality of life, dyspnea, mood, occurrence of acute exacerbations, engagement in physical activity, exercise self-efficacy, and exercise adherence. Simultaneously, we are conducting a pilot study of group walking. We will enroll 90 persons who will be randomized to one of three arms in a 2:2:1 ratio: Tai Chi, standard care, or group-based walking. DISCUSSION: The Long-term Exercise After Pulmonary Rehabilitation (LEAP) study is a novel and clinically relevant trial. We will enroll a well-characterized cohort of persons with COPD and will comprehensively assess physiological and psychosocial outcomes. Results of this study will provide the evidence base for persons with COPD to engage in Tai Chi as a low-cost, long-term modality to sustain physical activity in persons who have completed a standard short-term pulmonary rehabilitation program. TRIAL REGISTRATION: This trial is registered in Clinical Trials.gov, with the ID number of NCT01998724.

Duplication of chromosome 1 [dup(1)(q21q32)] as the sole cytogenetic abnormality in a patient previously treated for AML.

A nonrandom structural gain of 1q may be seen in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), and often it is due to an unbalanced translocation. Dup(1)(q21q32) as the sole abnormality has only rarely been reported. Reports have suggested that the dup(1)(q21q32) is predictive of a poor prognosis. We describe a case report of a 55 year old male who presented in 2002 with AML-M2, t(8;21)(q22;q22). He underwent induction with "7+3" followed by consolidation chemotherapy resulting in a complete remission. Two years later, his bone marrow revealed a dup(1)(q21q32) as an isolated aberration for the first time. In 2010, cytogenetic analysis of the bone marrow again confirmed this finding and FISH for AML1/ETO t(8;21) remained negative. Dup(1q) developed as an isolated abnormality two years after AML treatment, and to date, there is no evidence of progression to MDS. This is the first report of an acquired dup(1)(q21q32) as the sole abnormality in a patient treated for AML. This suggests that the dup(1q) may not be exclusively associated with a poor prognosis.

Metastatic renal cell carcinoma to the phalanx.

A 79-year-old man presented with a history of clear cell carcinoma of the right kidney, Fuhrman grade 2, 12 years after nephrectomy, and a history of low-risk prostate adenocarcinoma 11 years after brachytherapy. One year before presentation, the renal cell carcinoma had metastasized to his axial skeleton, and temsirolimus was started. Approximately 1 year later, he presented with a new, painful, lytic lesion in a rare site, his middle phalanx, which was biopsy proven to be clear cell carcinoma.

Extrapulmonary small cell: a novel case of small cell carcinoma of the thyroid gland.

Neuroendocrine tumors comprise a large group of malignancies which share unique morphological features and are characterized by the presence of neuroendocrine markers such as synaptophysin, chromogranin-A, and CD56 (N-CAM), ranging from indolent tumors, such as carcinoid tumors, to aggressive tumors, such as small cell carcinoma. The lung is the most common site for primary neuroendocrine tumors. Extrapulmonary primary sites of small cell carcinoma are rare but have been documented arising from various sites including esophagus, stomach, colon and rectum, gallbladder, thymus, salivary gland, ovary, cervix, bladder, prostate, and skin. We present a case of small cell carcinoma arising from the thyroid gland, a site not previously described in the literature. A 59-year-old woman presented with a thyroid mass, which, after resection, showed small cell morphology and positive immunostains for TTF-1, synaptophysin, chromogranin-A, CD56, etc. Five months after diagnosis, she had widely metastatic disease. After a near-complete response to the first chemo-treatment, her disease progressed. Following local radiation and more rounds of chemotherapy, she succumbed to the disease, 15 months after diagnosis. Our patient had no pulmonary lesions at the time of diagnosis to suggest metastasis from the lung. Much like its pulmonary counterparts, this small cell carcinoma of primary thyroid origin displayed an aggressive clinical course and poor outcome. Although it shows early sensitivity to chemotherapy, small cell carcinoma remains a difficult-to-treat cancer with a poor prognosis and can rarely be seen originating in organs outside of the lung.

A genome-wide expression analysis in blood identifies pre-elafin as a biomarker in ARDS.

Previous microarray-based studies of acute respiratory distress syndrome (ARDS) were performed using various models to mimic disease pathogenesis. The complexity of the pathophysiologic response to direct or indirect lung injury in ARDS is difficult to reconstruct in experimental conditions. Thus, direct analysis of ARDS patient blood may provide valuable information. We investigated genome-wide gene expression profiles in paired whole blood samples from patients with ARDS (n = 8) during the acute stage (within 3 d of diagnosis) and recovery stage of ARDS (around ICU discharge). Among 126 differentially expressed genes, peptidase inhibitor 3 (PI3, encoding elafin, a potent neutrophil elastase inhibitor) had the largest fold-change (-3-fold changes, acute stage/recovery stage) in expression, indicating down-regulation during the acute stage of ARDS. We further examined plasma PI3 levels in 40 patients with ARDS and 23 at-risk control subjects from the same cohort. There was a coincidence of the microarray findings of lower PI3 gene expression with the lower plasma PI3 during the acute-stage. The plasma PI3 levels were statistically significant different among pre-diagnosis, day of diagnosis, and post-diagnosis groups (ANOVA, P = 0.001), with a trend of decreasing from pre- to post-diagnosis group. The time course of plasma PI3 decrease is well correlated with the course of early ARDS development (Pearson correlation coefficient: -0.52, P = 0.0006). Considering that PI3 can covalently binding to extracellular matrix in lung, circulating PI3 may provide a useful clinical marker for monitoring the early development of ARDS and may have implications for ARDS treatment.

Distinct LIN-10 domains are required for its neuronal function, its epithelial function, and its synaptic localization.

alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors (AMPARs) mediate excitatory neurotransmission at neuronal synapses, and their regulated localization plays a role in synaptic plasticity. In Caenorhabditis elegans, the PDZ and PTB domain-containing protein LIN-10 is required both for the synaptic localization of the AMPAR subunit GLR-1 and for vulval fate induction in epithelia. Here, we examine the role that different LIN-10 domains play in GLR-1 localization. We find that an amino-terminal region of LIN-10 directs LIN-10 protein localization to the Golgi and to synaptic clusters. In addition, mutations in the carboxyl-terminal PDZ domains prevent LIN-10 from regulating GLR-1 localization in neurons but do not prevent LIN-10 from functioning in the vulval epithelia. A mutation in the amino terminus prevents the protein from functioning in the vulval epithelia but does not prevent it from functioning to regulate GLR-1 localization in neurons. Finally, we show that human Mint2 can substitute for LIN-10 to facilitate GLR-1 localization in neurons and that the Mint2 amino terminus is critical for this function. Together, our data suggest that LIN-10 uses distinct modular domains for its functions in neurons and epithelial cells and that during evolution its vertebrate ortholog Mint2 has retained the ability to direct AMPAR localization in neurons.