Using qualitative methods to inform the design of a decision aid for people with advanced cystic fibrosis: The InformedChoices CF patient decision aid

ObjectiveTo assess information needs of adults with Cystic Fibrosis and their families toward designing a patient decision aid about invasive mechanical ventilation (IMV) and lung transplant.MethodsFocus groups and in-depth interviews explored participants’ knowledge, prior clinical conversations, and decisions about IMV and lung transplant. Interviews and focus groups were recorded and transcribed for analysis.ResultsN = 24 participants were recruited. Themes identified were: prior communication with clinicians, decision-making process, and living with CF. Participants having prior conversations with CF clinicians regarding: lung transplant (N = 17/74%), and IMV (N = 3/13%). Most 15(65%) felt it was important to hear patients’ real-life experience, others (3/13%) relied on their CF doctors for information. Most people (16/70%) believed hearing prognosis was helpful, but 5(22%) found this information frightening. High degrees of social isolation and a desire for more interaction with other CF adults were found.ConclusionsQualitative methods helped identify areas important for decision making about IMV and LT for CF adults. Future directions include usability and feasibility testing of the decision aid.Practice implicationsBecause IMV is rarely discussed with CF adults, clinicians might approach this topic, as with transplant, as lung function begins to decline. CF-care teams should also foster CF patient-level information exchange.     

Macrophages in metabolic associated fatty liver disease

Metabolic associated fatty liver disease(MAFLD), formerly named non-alcoholic fatty liver disease is the most common liver disorder in many countries. The inflammatory subtype termed steatohepatitis is a driver of disease progression to cirrhosis, hepatocellular carcinoma, liver transplantation, and death, but also to extrahepatic complications including cardiovascular disease, diabetes and chronic kidney disease. The plasticity of macrophages in response to various environmental cues and the fact that they can orchestrate cross talk between different cellular players during disease development and progression render them an ideal target for drug development. This report reviews recent advances in our understanding of macrophage biology during the entire spectrum of MAFLD including steatosis, inflammation, fibrosis, and hepatocellular carcinoma, as well as for the extra-hepatic manifestations of MAFLD. We discuss the underlying molecular mechanisms of macrophage activation and polarization as well as cross talk with other cell types such as hepatocytes, hepatic stellate cells, and adipose tissue. We conclude with a discussion on the potential translational implications and challenges for macrophage based therapeutics for MAFLD.     

Cardiac remodeling and physical training post myocardial infarction

After myocardial infarction(MI), the heart undergoes extensive myocardial remodeling through the accumulation of fibrous tissue in both the infarcted and noninfarcted myocardium, which distorts tissue structure, increases tissue stiffness, and accounts for ventricular dysfunction. There is growing clinical consensus that exercise training may beneficially alter the course of post-MI myocardial remodeling and improve cardiac function. This review summarizes the present state of knowledge regarding the effect of post-MI exercise training on infarcted hearts. Due to the degree of difficulty to study a viable human heart at both protein and molecular levels, most of the detailed studies have been performed by using animal models. Although there are some negative reports indicating that post-MI exercise may further cause deterioration of the wounded hearts, a growing body of research from both human and animal experiments demonstrates that post-MI exercise may beneficially alter the course of wound healing and improve cardiac function. Furthermore, the improved function is likely due to exercise training-induced mitigation of reninangiotensin-aldosterone system, improved balance between matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1, favorable myosin heavy chain isoform switch, diminished oxidative stress, enhanced antioxidant capacity, improved mitochondrial calcium handling, and boosted myocardial angiogenesis. Additionally, meta-analyses revealed that exercise-based cardiac rehabilitation has proven to be effective, and remains one of the least expensive therapies for both the prevention and treatment of cardiovascular disease, and prevents re-infarction.     

Real-Life Experience With Pirfenidone in Idiopathic Pulmonary Fibrosis in Argentina. A Retrospective Multicenter Study

Introduction

Pirfenidone was the first antifibrotic drug approved in Argentina for idiopathic pulmonary fibrosis (IPF). Outcomes in real life may differ from the results of clinical trials. The primary endpoint was to study the tolerance of pirfenidone in real life. Secondary endpoints were to analyze effectiveness and reasons for discontinuation.

Role of Sprouty1 (Spry1) in the pathogenesis of atrial fibrosis

Atrial fibrosis is the hallmark of atrial fibrillation (AF) dependent structure remodeling. Besides, sprouty 1 (Spry1) plays a key role in the process of fibrosis. In this study, we investigated whether Spry1 could regulate TGF-β1 in atrial fibrosis. Ten dogs or patients were assigned to control (n = 4) and AF group (n = 6). The left atrium of dogs or right atrial appendage of patients was taken. After that, cardiac fibroblasts were treated with or without angiotensin II (Ang II). Furthermore, cardiac fibroblasts were transfected with lentivirus of Spry1 over-expression vector, Spry1 shRNA or negative control (NC). And the protein expression of Spry1 and TGF-β1 was analyzed by western blot and immunohistochemistry. The results showed that TGF-β1 was highly expressed while Spry1 was lowly expressed in the models of human and canine with AF. Besides, the protein expression of TGF-β1 was up-regulated and Spry1 was down-regulated in Ang II stimulated cardiac fibroblasts. Furthermore, when Spry1 was knockdown in Ang II-induced cardiac fibroblasts, the cell proliferation and the TGF-β1 protein expression increased significantly, while Spry1 over-expression showed inverse results. Our results demonstrated that Spry1 may target TGF-β1 in regulating fibrosis. These findings may provide possible therapeutic targets in atrial fibrosis.     

Earlier renal fibrosis aggravates acute kidney injury induced by ischemia reperfusion in mice

Objective To investigate the influence of earlier renal fibrosis on ischemia and reperfusion induced acute kidney injury. Methods Male C57BL/6 mice at eight to twelve weeks old age were divided into 4 groups randomly: (1)Sham (n=3); (2)Unilateral ureter obstruction (UUO, n=6): UUO for 3 days (UUO3d, n=3) and UUO for 5 days (UUO5d, n=3)；(3)Ischemia and reperfusion (IR, n=7): bilateral kidney ischemia for 40 minutes followed by 24 hours of reperfusion; (4)UUO for 3 days plus IR (UUO3d+IR, n=6): bilateral kidney ischemia after UUO 2 days for 40 minutes followed by 24 hours of reperfusion, and the real time for UUO was 3 days. Pathologic analysis for acute or chronic injury was performed on paraffin embedded kidney sections with hematoxylin and eosin (HE) or Masson staining. Apoptosis was detected by immunohistochemistry(IHC) and Western blotting with anti-caspase-3 antibody, and proliferation was observed by IHC with anti-ki67 antibody. Results On kidney sections with HE or Masson staining, it showed that the chronic kidney lesions and fibrosis got more severe as time of UUO prolonged from 3 days to 5 days; the area of matrix deposition increased in UUO5d and UUO3d mice significantly compared to Sham mice (P＜0.05) and was smaller in UUO3d mice compared with UUO5d mice obviously (P＜0.05). Acute kidney injury could be observed in UUO3d+IR mice, such as massive inflammatory cells infiltration, tubules dilation, brush border disappearance, tubular epithelial cells vacuolar degeneration, necrosis, casting formation, coexisting with chronic lesions: thinner cortex, broadened interstitial space, and increased blue stained matrix. Acute kidney injury score in UUO3d+IR mice was higher than that in IR mice significantly (P＜0.05), and serum creatinine level increased significantly in UUO3d+IR mice compared to Sham mice (P＜0.05). Caspase-3 expression increased and ki67 positive tubular cells decreased in UUO3d+IR mice than those in IR mice obviously (P＜0.05). Conclusion Earlier renal fibrosis aggravates acute kidney injury induced by ischemia reperfusion in mice through increasing apoptosis and decreasing proliferation of tubular epithelial cells.