Review series: What goes around, comes around: childhood influences on later lung health? Long-term follow-up of infants with lung disease of prematurity

The incidence of live preterm birth is increasing and concomitantly the survival of preterm babies has increased over the last 30 years due to advances in neonatal care. Bronchopulmonary dysplasia (BPD) is a chronic respiratory disease that develops as a consequence of perinatal and/or neonatal lung injury following preterm birth and the pathology has also changed with changes in neonatal care. There are data suggesting that there is increased respiratory morbidity of ex-preterm subjects in childhood. It is only now that large populations of preterm subjects are reaching adulthood and may be at risk of persistent respiratory morbidity. This review will summarize the current knowledge in adulthood of respiratory sequelae following preterm birth; specifically it will review respiratory symptoms, pulmonary function, exercise capacity and structural lung disease as determined by high resolution computed tomography scans in ex-preterm survivors with and without BPD. Whether prematurity-related lung disease is associated with chronic obstructive airways disease will be discussed.     

Additional complex fractionated atrial electrogram ablation does not improve the outcomes of non-paroxysmal atrial fibrillation: A systematic review and meta-analysis of randomized controlled trials

BackgroundNon-paroxysmal atrial fibrillation (AF) has a complex pathophysiological process. The standard catheter ablation approach is pulmonary vein isolation (PVI). The additional value of complex fractionated electrogram (CFAE) ablation is still unclear. We aimed to investigate the additional value of CFAE ablation for non-paroxysmal AF.MethodsWe performed a systematic review and meta-analysis of randomized controlled studies up to May 2020. Articles comparing pulmonary vein isolation (PVI) plus CFAE ablation and PVI alone for AF were obtained from the electronic scientific databases. The pooled mean difference (MD) and pooled risk ratio (RR) were assessed.ResultsA total of 8 randomized controlled trials (RCTs) including 1034 patients were involved. Following a single catheter ablation procedure, the presence of any atrial tachyarrhythmia (ATA) with or without the use of antiarrhythmic drugs (AADs) between both groups were not significantly different (RR = 1.1; 95% confidence interval [CI] = 0.97–1.24; p = 0.13). Similar results were also obtained for the presence of any ATA without the use of AADs (RR = 1.08; 95% CI = 0.96–1.22; p = 0.2). The additional CFAE ablation took longer procedure times (MD = 46.95 min; 95% CI = 38.27–55.63; p = < 0.01) and fluoroscopy times (MD = 11.69 min; 95% CI = 8.54–14.83; p = < 0.01).ConclusionAdditional CFAE ablation failed to improve the outcomes of non-paroxysmal AF patients. It also requires a longer duration of procedure times and fluoroscopy times.     

Integrating health interventions for women, newborn babies, and children: a framework for action

For women and children, especially those who are poor and disadvantaged, to benefit from primary health care, they need to access and use cost-effective interventions for maternal, newborn, and child health. The challenge facing weak health systems is how to deliver such packages. Experiences from countries such as Iran, Malaysia, Sri Lanka, and China, and from projects in countries like Tanzania and India, show that outcomes in maternal, newborn, and child health can be improved through integrated packages of cost-effective health-care interventions that are implemented incrementally in accordance with the capacity of health systems. Such packages should include community-based interventions that act in combination with social protection and intersectoral action in education, infrastructure, and poverty reduction. Interventions need to be planned and implemented at the district level, which requires strengthening of district planning and management skills. Furthermore, districts need to be supported by national strategies and policies, and, in the case of the least developed countries, also by international donors and other partners. If packages for maternal, newborn and child health care can be integrated within a gradually strengthened primary health-care system, continuity of care will be improved, including access to basic referral care before and during pregnancy, birth, the postpartum period, and throughout childhood.     

Combination of alpha-1-acid glycoprotein and alpha-fetoprotein as an improved diagnostic tool for hepatocellular carcinoma

BACKGROUND: To evaluate the diagnostic value of alpha-1-acid glycoprotein (AAG) and the combination with alpha-fetoprotein (AFP) in hepatocellular carcinoma (HCC) patients. METHODS: AAG was measured in serum of 65 HCC patients and 54 chronic liver diseases (CLD) patients by using proteomic approach. Sensitivity and specificity of AAG and its combination with AFP were determined and compared with AFP alone for the diagnosis of HCC. RESULTS: The expression concentration of AAG was significantly higher in HCC patients than chronic liver disease with sensitivity (77%) and accuracy (83%). Receiver operating characteristic analysis yielded the following AUC: AFP 0.750 (CI 95% 0.663-0.837), AAG 0.907 (CI 95% 0.855-0.960) and AFP+AAG 0.943 (CI 95% 0.897-0.988). At a specificity of 90%, the combination of AFP+AAG had sensitivity 89% and accuracy 90%, which was higher than sensitivity (52.3%) and accuracy (70%) when using AFP alone. CONCLUSION: The combination of AAG and AFP shows high sensitivity and improves the accuracy of HCC diagnosis.     

Visual morphometry and three non-invasive markers in the evaluation of liver fibrosis in chronic liver disease

Objective: Liver fibrosis is traditionally graded into categorical stages with cirrhosis as the highest stage. However, cirrhosis stage may vary between individuals widely in terms of the amount of fibrosis which is not assessed by traditional staging systems. We aimed to utilise visual morphometry to quantify the amount of fibrosis in liver biopsy and compare how non-invasive methods of quantifying liver fibrosis correlated with histological measures.

Materials and methods: Liver biopsy specimens from 115 consecutive chronic liver disease patients were assessed by a single pathologist for fibrosis stage by the Clinical Research Network and METAVIR systems as well as percentage fibrosis by visual morphometry. Liver T₁ relaxation times, liver stiffness measurement (LSM) by transient elastography and enhanced liver fibrosis (ELF) score were compared between fibrosis stages. In addition, these parameters were correlated with pathologist’s visual estimate of percentage fibrosis and their predictive ability for advanced fibrosis and cirrhosis assessed by area under receiver operating curve (AUROC).

Results: All four parameters increased sequentially from fibrosis stage F0 to F4 (p<.001 for each). AUROCs for advanced fibrosis and cirrhosis were 0.931 and 1.000 respectively for pathologist’s estimate of fibrosis, 0.707 and 0.926 for ELF score, 0.763 and 0.972 for T₁ and 0.881 and 0.989 for LSM. LSM, ELF score and T₁ correlated significantly with pathologist’s estimate of percentage fibrosis.

Conclusion: Non-invasive markers of fibrosis LSM, ELF and T₁ relaxation time provide continuous surrogates for categorical histopathological staging of fibrosis which can be useful as markers of progression and regression of fibrosis on follow-up.     

Tracking errors related to cardiac cycle: a new approach

One-dimensional manual tracking was investigated in relation to cardiac activity. The task of the subjects was, by means of a joy-stick, to maintain a spotlight between two vertical lines moving horizontally across an oscilloscope screen. Error incidence was time-locked with respect to the cardiac cycle. Error rate was higher for faster (2-s trial periods) than for slower (3-s trial periods) target movement. Using linear-ramp and sinusoidal movements, it was demonstrated that error incidence is associated with positive and negative cardiac acceleration.     

Nitric oxide hinders antibody clearance from the surface of Trypanoplasma borreli and increases susceptibility to complement-mediated lysis

Trypanoplasma borreli is an extracellular blood parasite of carp belonging to the same Order (Kinetoplastida) as African trypanosomes. These mammalian parasites have developed different strategies to evade the host immune system including antigenic variation, immunosuppression and clearance of surface-bound antibodies. The latter mechanism allows trypanosomes to use their swimming movement to cause surface-bound antibodies to ‘sail’ and accumulate at the posterior end of the parasite, to be internalized via the flagellar pocket and be degraded. There is no evidence that T. borreli shows antigenic variation, but during the late phases of infection NO-mediated immunosuppression is observed. High levels of nitric oxide (NO) lead to extensive tissue nitration whereas the parasite itself is not affected. Therefore, the induction of NO has thus far been considered a parasite-driven response with immunosuppressive effects. In the present study, we show that the induction of NO, particularly during the early phase of T. borreli infections, should be re-considered an effective part of the host immune response. We show that T. borreli rapidly removes surface-bound IgM. In addition, moderate concentrations of NO, by hindering surface antibody clearance, maintain high the concentrations of membrane-bound IgM, thereby favoring antibody-dependent complement-mediated parasite lysis. We performed a comprehensive quantitative gene expression analysis of in total seven different complement factors involved in all three activation pathways, differentiating between 1 and 4 isoforms for each complement gene. Our gene expression analysis supports an important role for antibody-dependent complement-mediated lysis of T. borreli in vivo. To our knowledge, NO-dependent inhibition of antibody clearance from the surface of kinetoplastid parasites has not been investigated. Our data support a role for NO as an important player in host–parasite interactions, not only as immune suppressor (late response) but also as immune effector (early response) in infections with bloodstream parasites such as T. borreli.