Extracorporeal membrane oxygenator as a bridge to successful surgical repair of bronchopleural fistula following bilateral sequential lung transplantation: a case report and review of literature

<p>Abstract</p> <p>Background</p> <p>Lung transplantation (LTx) is widely accepted as a therapeutic option for end-stage respiratory failure in cystic fibrosis. However, airway complications remain a major cause of morbidity and mortality in these patients, serious airway complications like bronchopleural fistula (BPF) are rare, and their management is very difficult.</p> <p>Case presentation</p> <p>A 47-year-old man with end-stage respiratory failure due to cystic fibrosis underwent bilateral sequential lung transplantation. Severe post-operative bleeding occurred due to dense intrapleural adhesions of the native lungs. He was re-explored and packed leading to satisfactory haemostasis. He developed a bronchopleural fistula on the 14^thpost-operative day. The fistula was successfully repaired using pericardial and intercostal vascular flaps with veno-venous extracorporeal membrane oxygenator (VV-ECMO) support. Subsequently his recovery was uneventful.</p> <p>Conclusion</p> <p>The combination of pedicled intercostal and pericardial flaps provide adequate vascular tissue for sealing a large BPF following LTx. Veno-venous ECMO allows a feasible bridge to recovery.</p

HALT (Hernia Active Living Trial): protocol for a feasibility study of a randomised controlled trial of a physical activity intervention to improve quality of life in people with bowel stoma with a bulge/parastomal hernia

Background Parastomal hernia (PSH) can be repaired surgically, but results to date have been disappointing, with reported recurrence rates of 30 to 76%. Other types of intervention are therefore needed to improve the quality of life of people with PSH. One potential intervention is physical activity. We hypothesise that the intervention will increase core activation and control across the abdominal wall at a site of potential weakness and thus reduce the risk of PSH progression. Increases in physical activity will improve body image and quality of life (QoL). Methods Subjects and sample There were approximately 20 adults with a bowel stoma and PSH. People with previous PSH repair will be excluded as well as people who already do core training. Study design This is a feasibility study of a randomised controlled trial with 2 months follow-up, in 2 sites using mixed methods. Stage 1 involves intervention development and in stage 2, intervention and trial parameters will be assessed. Intervention A theoretically informed physical activity intervention was done, targeting people with PSH. Main outcome of feasibility study The main outcome is the decision by an independent Study Steering Committee whether to proceed to a full randomised controlled trial of the intervention. Other outcomes We will evaluate 4 intervention parameters—fidelity, adherence, acceptability and safety and 3 trial parameters (eligible patients’ consent rate, acceptability of study design and data availability rates for following endpoints): I. Diagnosis and classification of PSH II. Muscle activation III. Body composition (BMI, waist circumference) IV. Patient reported outcomes: QoL, body image and physical functioning V. Physical activity; VI. Psychological determinants of physical activity Other data Included are other data such as interviews with all participants about the intervention and trial procedures. Data analysis and statistical power As this is a feasibility study, the quantitative data will be analysed using descriptive statistics. Audio-recorded qualitative data from interviews will be transcribed verbatim and analysed thematically. Discussion The feasibility and acceptability of key intervention and trial parameters will be used to decide whether to proceed to a full trial of the intervention, which aims to improve body image, quality of life and PSH progression. Trial registration ISRCTN1520759

The role of hypothalamic H1 receptor antagonism in antipsychotic-induced weight gain

Treatment with second generation antipsychotics (SGAs), notably olanzapine and clozapine, causes severe obesity side effects. Antagonism of histamine H1 receptors has been identified as a main cause of SGA-induced obesity, but the molecular mechanisms associated with this antagonism in different stages of SGA-induced weight gain remain unclear. This review aims to explore the potential role of hypothalamic histamine H1 receptors in different stages of SGA-induced weight gain/obesity and the molecular pathways related to SGA-induced antagonism of these receptors. Initial data have demonstrated the importance of hypothalamic H1 receptors in both short- and long-term SGA-induced obesity. Blocking hypothalamic H1 receptors by SGAs activates AMP-activated protein kinase (AMPK), a well-known feeding regulator. During short-term treatment, hypothalamic H1 receptor antagonism by SGAs may activate the AMPK—carnitine palmitoyltransferase 1 signaling to rapidly increase caloric intake and result in weight gain. During long-term SGA treatment, hypothalamic H1 receptor antagonism can reduce thermogenesis, possibly by inhibiting the sympathetic outflows to the brainstem rostral raphe pallidus and rostral ventrolateral medulla, therefore decreasing brown adipose tissue thermogenesis. Additionally, blocking of hypothalamic H1 receptors by SGAs may also contribute to fat accumulation by decreasing lipolysis but increasing lipogenesis in white adipose tissue. In summary, antagonism of hypothalamic H1 receptors by SGAs may time-dependently affect the hypothalamus-brainstem circuits to cause weight gain by stimulating appetite and fat accumulation but reducing energy expenditure. The H1 receptor and its downstream signaling molecules could be valuable targets for the design of new compounds for treating SGA-induced weight gain/obesity

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

BACKGROUND: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. RESULTS: Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. CONCLUSION: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity

NATURALLY BICARBONATED WATER SUPPLEMENTATION DOES NOT IMPROVE ANAEROBIC CYCLING PERFORMANCE IN ACTIVE MEN AND WOMEN

Anthony M. Hagele1, Johnathan L. Boring1, Jessica M. Moon1, Kylie E. Walden1, Kayla M. Ratliff1, Logan Orr1, Connor J. Gaige1, Richard A. Stecker1, Kyle L. Sunderland1, Petey W. Mumford1, Chad M. Kerksick1, FACSM 1Lindenwood University, St. Charles, MO Completion of high-intensity exercise can result in robust perturbations of physiologic homeostasis, challenging the body’s natural buffering systems to mitigate the accumulation of metabolic byproducts. Supplementation with bicarbonate has previously been used to offset metabolic acidosis leading to improvements in anaerobic exercise performance. PURPOSE: The purpose of this study was to investigate the ergogenic properties of a naturally bicarbonated water on anaerobic cycling performance in recreationally active men and women. METHODS: Forty-two healthy, recreationally active men and women (28.1 ± 8.0 yrs, 169.8 ± 11.7 cm, 68.9 ± 10.8 kg, 20.1 ± 7.9 %fat, 42.8 ± 7.6 mL/kg/min) completed two separate testing sessions consisting of 15 cycling sprints (10-s sprint, 20-s active rest) against 7.5% of their body mass. In a randomized, double-blind, placebo controlled fashion, study participants consumed a 10 mL/kg dose of either low mineralized spring water (SW) or mineral water naturally high in bicarbonate (BW) content (35 mg/kg) over a 7 day period. After completion of 15 cycling sprints, averages of peak and mean power for bouts 1-5, 6-10, and 11-15 along with total work for the entire cycling protocol were calculated, then analyzed using mixed factorial ANOVA. RESULTS: pH was found to be significantly higher in BW immediately after (7.17 ± 0.09 mmol vs 7.20 ± 0.11 mmol) and 10-min post exercise (7.21 ± 0.11 mmol vs 7.24 ± 0.09 mmol). A similar pattern of change was observed 5-min post exercises whereby pH levels were lower in the SW group than those observed in the BW group, however this difference was non-significant (p=0.09). A statistical trend (p=0.06) was observed for lactate levels whereby lactate in BW tended to be lower than SW 5-min post exercise. Supplementation resulted in no change over time (p\u3e0.05) for total work, average peak power, or average power. No group x time interactions were observed (p\u3e0.05) for total work, average peak power, or average power. CONCLUSION: One week of consuming water with a naturally high bicarbonate content showed no effect on anaerobic cycling performance. However, BW did significantly decrease post-exercise blood lactate production and increase blood pH. ACKNOWLEDGEMENTS: This study was funded by Borjomi, IDS