Immune profiling after minimally invasive lobectomy

Open in a separate window OBJECTIVESWhether acute phase and immune responses are minimally affected following minimally invasive lung surgery needs further investigation. We performed a pilot study to evaluate the immune profile of patients who underwent video-assisted thoracoscopic surgery or robot-assisted thoracic surgery lobectomies for the treatment of suspicious or known stage I non-small-cell lung cancer.METHODSBlood samples were taken preoperatively and 3 and 24 h postoperatively were analysed for C-reactive protein, glucose, cortisol, tumour necrosis factor alpha (TNF-α), interleukin 8 (IL-8) and interleukin 10 (IL-10) levels. TNF-α, IL-8 and IL-10 were also measured in lung tissues. T (CD4, CD8), B (CD19) and natural killer (CD56, CD16) cell counts and natural killer cell functions were analysed using a flow cytometry-based assay before and after surgery.RESULTSMinimally invasive surgery (robot-assisted thoracic surgery + video-assisted thoracoscopic surgery) significantly decreased IL-10 (P = 0.016) levels after surgery. No significant differences were detected in TNF-α (P = 0.48) and IL-8 (P = 0.15) levels before and after surgery. C-reactive protein (P < 0.001), cortisol (P < 0.001) and glucose levels (P < 0.001) increased significantly after surgery. Lymphocyte, total T cell, CD3⁺CD4⁺ and CD3⁺CD8⁺ CD16⁺CD56⁺ cell counts were significantly lower on postoperative day 1.CONCLUSIONThere seems to be a dynamic balance between pro- and anti-inflammatory cytokines and immune cells following minimally invasive lobectomy.     

A case of uncontrolled severe asthma patient with coexisting carcinoid tumor presenting as pneumomediastinum

Introduction: Patients with inadequately controlled or uncontrolled asthma are at a greater risk of attacks for asthma requiring emergency room visits or hospital admissions. There is a significant correlation between the severity of the disease and the severity of exacerbations. Patients with poorly controlled asthma are at a higher risk for complications. Case study: We present a 24-year-old aspirin-intolerant, uncontrolled asthma patient with the complication of pneumomediastinum. Results: Severe symptoms persisted after the resolution of the pneumomediastinum despite intense anti-inflammatory and anti-obstructive therapy. A bronchoscopy revealed an endobronchial lesion and she was diagnosed with a carcinoid tumor. Conclusion: This case is an example of the importance of re-evaluating asthma patients who do not respond to standard medical treatment. Clinicians should be aware of the complications associated with asthma attacks such as pneumomediastinum and the possibility of a differential diagnosis that worsen asthma symptoms such as a carcinoid tumor.     

Spatial Patterns of Structural Brain Changes in Type 2 Diabetic Patients and Their Longitudinal Progression With Intensive Control of Blood Glucose

OBJECTIVE

Understanding the effect of diabetes as well as of alternative treatment strategies on cerebral structure is critical for the development of targeted interventions against accelerated neurodegeneration in type 2 diabetes. We investigated whether diabetes characteristics were associated with spatially specific patterns of brain changes and whether those patterns were affected by intensive versus standard glycemic treatment.

RESEARCH DESIGN AND METHODS

Using baseline MRIs of 488 participants with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes (ACCORD-MIND) study, we applied a new voxel-based analysis methodology to identify spatially specific patterns of gray matter and white matter volume loss related to diabetes duration and HbA_1c. The longitudinal analysis used 40-month follow-up data to evaluate differences in progression of volume loss between intensive and standard glycemic treatment arms.

RESULTS

Participants with longer diabetes duration had significantly lower gray matter volumes, primarily in certain regions in the frontal and temporal lobes. The longitudinal analysis of treatment effects revealed a heterogeneous pattern of decelerated loss of gray matter volume associated with intensive glycemic treatment. Intensive treatment decelerated volume loss, particularly in regions adjacent to those cross-sectionally associated with diabetes duration. No significant relationship between low versus high baseline HbA_1c levels and brain changes was found. Finally, regions in which cognitive change was associated with longitudinal volume loss had only small overlap with regions related to diabetes duration and to treatment effects.

CONCLUSIONS

Applying advanced quantitative image pattern analysis methods on longitudinal MRI data of a large sample of patients with type 2 diabetes, we demonstrate that there are spatially specific patterns of brain changes that vary by diabetes characteristics and that the progression of gray matter volume loss is slowed by intensive glycemic treatment, particularly in regions adjacent to areas affected by diabetes.     

Out of pocket health expenditures in Turkey following introduction of co-payments along with improved primary care services

In 2002, Turkey started to implement reforms in health care aiming to improve access and increase efficiency. Reforms increased health insurance coverage and resulted in higher number of outpatient and inpatient treatments at both public and private hospitals. Later, to change preference towards the use of secondary and tertiary care over primary care and rein in increasing health expenditures, a series of co-payments were instituted along with an extension of primary care services through a family-medicine system that provided free access to all. This work aims to measure the impact of these two simultaneous policy measures on out-of-pocket expenditures. We find that while contributory payments resulted in higher OOP health expenditures, especially for lower income households, the impact was small. We also observe that inability to consult a physician and to visit a hospital, especially for monetary reasons, was reduced after the policy change.     

Impact of puberty on the evolution of cerebral perfusion during adolescence

Puberty is the defining biological process of adolescent development, yet its effects on fundamental properties of brain physiology such as cerebral blood flow (CBF) have never been investigated. Capitalizing on a sample of 922 youths ages 8–22 y imaged using arterial spin labeled MRI as part of the Philadelphia Neurodevelopmental Cohort, we studied normative developmental differences in cerebral perfusion in males and females, as well as specific associations between puberty and CBF. Males and females had conspicuously divergent nonlinear trajectories in CBF evolution with development as modeled by penalized splines. Seventeen brain regions, including hubs of the executive and default mode networks, showed a robust nonlinear age-by-sex interaction that surpassed Bonferroni correction. Notably, within these regions the decline in CBF was similar between males and females in early puberty and only diverged in midpuberty, with CBF actually increasing in females. Taken together, these results delineate sex-specific growth curves for CBF during youth and for the first time to our knowledge link such differential patterns of development to the effects of puberty.Blood perfusion is one of the fundamental physiologic properties of any organ and is of particular relevance for the human brain, which receives 15% of cardiac output despite only representing 2% of body mass (1). Prior work has shown that cerebral blood flow (CBF) declines markedly throughout childhood and adolescence (2–4). Along with gray matter loss and white matter expansion (5), CBF thus represents one of the most important properties of brain physiology that changes during youth and may be critical for establishing normative growth charts of brain development. CBF is coupled to regional metabolism (6, 7), changes under cognitive demands (8), responds specifically to psychoactive drugs (9), and is abnormal in a variety of psychiatric conditions including schizophrenia (10) and addiction (11). Thus, characterization of normative trajectories of CBF during adolescent development is highly relevant for understanding both normal brain function and its aberrations in psychopathology.Growth curves of height, weight, and head circumference used in typical pediatric practice are separated by sex, because the timing and tempo of growth are different among males and females. One reason for this is the influence of puberty, which is the defining biological process of adolescence. Puberty results in divergent, sex-specific maturation that is driven by the influence of steroid and other metabolic hormones including estrogen and testosterone. Prior work has demonstrated sex differences in patterns of structural brain development (5, 12), and a growing body of literature has begun to establish the influence of puberty on this process (13, 14).In contrast to research on structural brain development, work on cerebral perfusion during development has thus far been relatively sparse. Early research by Kennedy and Sokoloff (15), using a modified Kety–Schmidt nitrous oxide method (16), established that whole-brain CBF was 106 mL⋅100 g⁻¹⋅min⁻¹ in children, compared with 60 mL⋅100 g⁻¹⋅min⁻¹ in adults. Later, CBF was measured on a regional basis using techniques such as ¹³³Xe clearance or ¹⁵O PET. However, sample sizes of these studies were limited by the need for ionizing radiation exposure, which is particularly problematic in pediatric populations. Nonetheless, these studies reliably demonstrated that CBF is elevated during childhood then declines throughout adolescence (3, 17, 18). In adulthood, females have higher CBF than males (8, 19). However, prior nuclear imaging studies in youth were too small (typically n = 20–40) to characterize sex differences during development.Arterial spin labeling (ASL) using MRI permits noninvasive quantification of cerebral perfusion without the use of ionizing radiation (20, 21) but gives comparable gray matter CBF measurements when validated versus PET (22, 23). This feature provides a critical advantage for applications in pediatric populations (4), allowing for a substantial increase in sample size. Using ASL, Taki et al. (24, 25) replicated prior findings of declining perfusion in adolescence and also reported that females had higher perfusion in the posterior cingulate cortex (pCC), owing to a steeper rate of CBF decline in males. However, it is not known whether such effects are limited only to the pCC or whether developmental trajectories of perfusion differ between males and females in other regions, potentially in a complex nonlinear fashion. Divergent trajectories in multiple regions are to be expected, because adult females have higher CBF than males across brain regions beyond the pCC (8, 19, 26, 27). However, it is not yet known when such differences emerge in development.Importantly, no study has investigated whether emerging sex differences in cerebral perfusion seen in adolescence are due to the differential impact of puberty. Studies from both animals and humans provide good reason to suspect that puberty may play a key role in CBF sex differences: Estrogens increase CBF in both animals and humans and also may promote neurogenesis and axonal sprouting (28–31). However, because the progression of age and puberty are correlated, large samples are required to systematically parse the relative influence of each. Here, we investigated developmental patterns of cerebral perfusion in males and females using ASL data from the Philadelphia Neurodevelopmental Cohort (PNC) (32), which constitutes the largest sample of cerebral perfusion yet reported. We hypothesized that differences in cerebral perfusion between males and females would relate to the impact of puberty. As described below, we found pronounced evidence for differential patterns of developmental perfusion in males and females, driven in part by the effects of puberty.