Cystic fibrosis survival outcomes following second lung transplant: The north American experience.

INTRODUCTION: Re-transplant is an option for those who develop end-stage lung disease due to rejection; however, little data exist following re-transplantation in cystic fibrosis (CF). METHODS: Data from the Canadian CF Registry and US CF Foundation Patient Registry supplemented with data from United Network for Organ Sharing were used. Individuals who underwent a 2nd lung transplant between 2005 and 2019 were included. The Kaplan-Meier method was used to estimate the probability of survival post-second transplant at 1, 3, and 5-years. RESULTS: Of those people who were waitlisted for a second transplant (N = 818), a total of 254 (31%) died waiting, 395 (48%) were transplanted and 169 (21%) people were alive on the waitlist. Median survival time after 2nd lung transplant was 3.3 years (95% CI: 2.8-4.1). The 1-, 3- and 5-year survival rates were 77.4% (95% CI: 73.1-82%), 52% (95% CI: 46.7-58%) and 39.4% (95% CI: 34.1-45.6%). CONCLUSIONS: Survival following second lung transplant in CF patients is lower than estimates following the first transplant. Over half of subjects who are potentially eligible for a second transplant die without receiving a second organ. This warrants further investigation.

Neuromuscular blocking agents in acute respiratory distress syndrome: updated systematic review and meta-analysis of randomized trials.

PURPOSE: Existing clinical practice guidelines support the use of neuromuscular blocking agents (NMBA) in acute respiratory distress syndrome (ARDS); however, a recent large randomized clinical trial (RCT) has questioned this practice. Therefore, we updated a previous systematic review to determine the efficacy and safety of NMBAs in ARDS. METHODS: We searched MEDLINE, EMBASE (October 2012 to July 2019), the Cochrane (Central) database, and clinical trial registries ( ClinicalTrials.gov , ISRCTN Register, and WHO ICTRP) for RCTs comparing the effects of NMBA as a continuous infusion versus placebo or no NMBA infusion (but allowing intermittent NMBA boluses) on patient-important outcomes for adults with ARDS. Two independent reviewers assessed the methodologic quality of the primary studies and abstracted data. RESULTS: Seven RCTs, including four new RCTs, met eligibility criteria for this review. These trials enrolled 1598 patients with moderate to severe ARDS at centers in the USA, France, and China. All trials assessed short-term continuous infusions of cisatracurium or vecuronium. The pooled estimate for mortality outcomes showed significant statistical heterogeneity, which was only explained by a subgroup analysis by depth of sedation in the control arm. A continuous NMBA infusion did not improve mortality when compared to a light sedation strategy with no NMBA infusion (relative risk [RR] 0.99; 95% CI 0.86-1.15; moderate certainty; P = 0.93). On the other hand, continuous NMBA infusion reduced mortality when compared to deep sedation with as needed NMBA boluses (RR 0.71; 95% CI 0.57-0.89; low certainty; P = 0.003). Continuous NMBA infusion reduced the rate of barotrauma (RR 0.55; 95% CI 0.35-0.85, moderate certainty; P = 0.008) across eligible trials, but the effect on ventilator-free days, duration of mechanical ventilation, and ICU-acquired weakness was uncertain. CONCLUSIONS: Inconsistency in study methods and findings precluded the pooling of all trials for mortality. In a pre-planned sensitivity analysis, the impact of NMBA infusion on mortality depends on the strategy used in the control arm, showing reduced mortality when compared to deep sedation, but no effect on mortality when compared to lighter sedation. In both situations, a continuous NMBA infusion may reduce the risk of barotrauma, but the effects on other patient-important outcomes remain unclear. Future research, including an individual patient data meta-analysis, could help clarify some of the observed findings in this updated systematic review.

Resveratrol inhibits adipocyte differentiation and cellular senescence of human bone marrow stromal stem cells.

Bone marrow adipose tissue (BMAT) is a unique adipose depot originating from bone marrow stromal stem cells (BMSCs) and regulates bone homeostasis and energy metabolism. An increased BMAT volume is observed in several conditions e.g. obesity, type 2 diabetes, osteoporosis and is known to be associated with bone fragility and increased risk for fracture. Therapeutic approaches to decrease the accumulation of BMAT are clinically relevant. In a screening experiment of natural compounds, we identified Resveratrol (RSV), a plant-derived antioxidant mediating biological effects via sirtuin- related mechanisms, to exert significant effects of BMAT formation. Thus, we examined in details the effects RSV on adipocytic and osteoblastic differentiation of tolermerized human BMSCs (hBMSC-TERT). RSV (1.0 µM) enhanced osteoblastic differentiation and inhibited adipocytic differentiation of hBMSC-TERT when compared with control and Sirtinol (Sirtuin inhibitor). Global gene expression profiling and western blot analysis revealed activation of a number of signaling pathways including focal adhesion kinase (FAK). Pharmacological inhibition of FAK using (PF-573228) and AKT inhibitor (LY-294002) (5µM), diminished RSV-induced osteoblast differentiation. In addition, RSV reduced the levels of senescence-associated secretory phenotype (SASP), gene markers associated with senescence (P53, P16, and P21), intracellular ROS levels and increased gene expression of enzymes protecting cells from oxidative damage (HMOX1 and SOD3). In vitro treatment of primary hBMSCs from aged patients characterized with high adipocytic and low osteoblastic differentiation ability with RSV, significantly enhanced osteoblast and decreased adipocyte formation when compared to hBMSCs from young donors. RSV targets hBMSCs and inhibits adipogenic differentiation and senescence-associated phenotype and thus a potential agent for treating conditions of increased BMAT formation.

Work-Related Musculoskeletal Symptoms among Building Construction Workers in Riyadh, Saudi Arabia.

OBJECTIVES: To investigate the work-related musculoskeletal symptoms among building construction workers. METHODS: Total 389 apparently healthy, male volunteers were selected with mean age 34.56±8.33 years and a mean working duration in building construction as 5.76±2.68 years. Musculoskeletal complaints were recorded through a detailed clinical interview and comprehensive questionnaire. RESULTS: Substantial number of building construction workers developed musculoskeletal symptoms including neck pain 29 (7.5%), shoulder pain 41(10.5%), upper back pain 24(6.2%), lower back pain 64 (16.5%), legs pain 93 (23.9%), feet pain 52 (13.4%), head heaviness 44 (11.3%) and whole body fatigue 78 (20.1%). These complaints were significantly associated with long-term duration-response in building construction industry. Furthermore, cigarette smokers had little higher percentage of musculoskeletal complaints compared to non-smoker companions. CONCLUSIONS: Building construction occupation is a prolific source of musculoskeletal ailments and complaints were significantly increased with long-term working duration in building construction industry.