The Role of Uric Acid in Preeclampsia: Is Uric Acid a Causative Factor or a Sign of Preeclampsia?

Purpose of Review

Because of the significant discrepancies on this topic, this review will focus on the role of uric acid in PE, uric acid as a predictor of preeclampsia and fetal growth retardation. We considered eligible review and original articles relevant to the research question.

Recent Findings

Hypertensive disorders of pregnancy such as preeclampsia (PE) are a major cause of both maternal and fetal morbidity and mortality worldwide. Uric acid has been reported as a key factor contributing to the pathogenesis of PE. Some studies have indicated that serum uric acid levels increase with the severity of PE, while several studies have shown contradictory results. Some studies suggested high uric acid levels lead to PE, while others state that PE causes an increase in uric acid levels.

Summary

Despite the strong association of uric acid in the pathogenesis of preeclampsia, current data is still contradictory hence genetic and high-end laboratory investigations may clarify this enigma.

     

Sex-Specific Contributions of Endothelin to Hypertension

Purpose of Review

Men and women differ in the prevalence, pathophysiology and control rate of hypertension in an age-dependent manner. The renal endothelin system plays a central role in sex differences in blood pressure regulation by control of sodium excretion and vascular function. Improving our understanding of the sex differences in the endothelin system, especially in regard to blood pressure regulation and sodium homeostasis, will fill a significant gap in our knowledge and may identify sex-specific therapeutic targets for management of hypertension.

Recent Findings

The current review will highlight evidence for the potential role for endothelin system in the pathophysiology of hypertension within three female populations: (i) postmenopausal women, (ii) women suffering from preeclampsia, or (iii) pulmonary arterial hypertension.

Summary

Clinical trials that specifically address cardiovascular and renal diseases in females under different hormonal status are limited. Studies of the modulatory role of gonadal hormones and sex-specific mechanisms on critically important systems involved, such as endothelin, are needed to establish new clinical practice guidelines based on systematic evidence.

     

Identifying and Managing Hibernating Myocardium: What’s New and What Remains Unknown?

Purpose of Review

Hibernation is an important and reversible cause of myocardial dysfunction in ischaemic heart failure.

Recent Findings

Hibernation is an adaptive process that promotes myocyte survival over maintaining contractile function. It is innate to mammalian physiology, sharing features with physiological hibernation in other species. Advanced imaging methods have reasonable accuracy in identifying hibernating myocardium. Novel superior hybrid methods may provide diagnostic potential. New evidence supports the role of surgical revascularisation in ischaemic heart failure, but the role of viability tests in planning such procedures remains unclear. Research to date has exclusively involved patients with ambulatory heart failure: Investigating the role of hibernation in ADHF is a key avenue for the future.

Summary

Whilst our understanding of hibernation pathophysiology has improved dramatically, the clinical utility of identifying and targeting hibernation remains unclear.

     

Human infectious diseases and risk of preeclampsia: an updated review of the literature

Background

Preeclampsia (PE) is one of the major causes of maternal and perinatal morbidity and mortality, especially in low- and middle-income countries. In recent years, a growing body of literatures suggests that infections by bacteria, viruses, and parasites and their related inflammations play an important role in the pathogenesis of PE.

Methods

We searched PubMed, Google scholar, and Cochrane databases using the following search words: “infection and preeclampsia,” “bacterial infection and preeclampsia,” “viral infection and preeclampsia” and “parasitic infection and preeclampsia.”

Results

The literature review revealed that many bacteria including Helicobacter pylori, Chlamydia pneumonia, and those are involved in periodontal disease or urinary tract infections (UTIs) and some viral agents such as Cytomegalovirus, herpes simplex virus type-2, human immunodeficiency virus, and some parasites especially Plasmodium spp. and Toxoplasma gondii can be effective in development of PE. Inflammation responses against infections has major role in the inducement of PE. The shift of immunological cytokine profile of Th2 toward Th1 and high levels of pro-inflammatory cytokines (TNF-ɑ, IL-12, IFN-γ, etc.), increase of oxidative stress, increase of anti-angiogenic proteins, increase of vascular endothelial growth factor receptor 1 (sVEGFR1), and complement C5a are the main potential mechanisms related to infections and enhanced development of PE.

Conclusion

Thus, early diagnosis and treatment of bacterial, viral, and parasitic infections could be an effective strategy to reduce the incidence of PE.

     

Biologics and Small Molecule Agents in Allergic and Immunologic Skin Diseases

Purpose of Review

Biologics and small molecules are key therapeutic options in the treatment of chronic immunologic and allergic skin conditions. By directly targeting innate and inflammatory responses within the skin, including pro-inflammatory cytokines and cellular signaling pathways, these new agents have the potential to counteract the inflammatory cascade responsible for various conditions, including psoriasis and atopic dermatitis. Over the past decade, groundbreaking research identifying key cytokines and receptors involved in the pathogenesis of these diseases has allowed for the development of highly efficacious biologics and small molecules that are associated with unprecedented rates of skin clearance and favorable adverse event profiles.

Recent Findings

This narrative review evaluates new and upcoming biologic and small molecule agents for the treatment of two allergic/immunologic skin diseases—atopic dermatitis and psoriasis. Numerous small molecules and biologics targeting TNF-α, IL-12/23, IL-17 and IL-17R, and IL-23 are commercially available for the treatment of psoriasis, and newer agents are in various stages of development. Currently, dupilumab, a monoclonal antibody that blocks IL-4R∝, is the only approved biologic for atopic dermatitis. Antibodies targeting IL-13 and IL-31 and small molecules that inhibit Janus kinase and pruritus-mediating receptors are currently being studied in clinical trials. Further investigations into the pathophysiology of atopic dermatitis will likely yield additional therapeutic options in the future.

Summary

This article reviews recent literature on small molecules and biologics for the treatment of atopic dermatitis and psoriasis.

     

Die Rolle der Selbsthilfegruppen in der Onkologie

Background

Little is known about self-help associations and their possibilities. Obstacles often prevent early contacts between affected people.

Objectives

The psychosocial support given by self-help associations in different phases is evaluated.

Materials and methods

Based on the experience of the Deutsche ILCO and from cooperation with other organizations and institutions, various dimensions of self-help groups are investigated.

Results

On the professional side, there is a lack of knowledge and of attitude. Suitable structures are rare.

Conclusions

The removal of barriers and development of effective structures are overdue.

     

Phosphodiesterase Inhibition in the Treatment of Preeclampsia: What Is New?

Purpose of Review

The present study intends to review the possibility of using phosphodiesterase inhibitors as a treatment option for preeclampsia, addressing potential risks and benefits.

Recent Findings

Preeclampsia is the most common hypertensive disorder of pregnancy, often responsible for severe maternal and fetal complications, which can lead to early pregnancy termination and death. Despite the numerous studies, its pathophysiology is still unclear, although it seems to involve a multiplicity of complex factors related to angiogenesis, ineffective vasodilation, oxidative stress, inflammatory cytokines, and endothelial dysfunction. It has been hypothetically suggested that the use of phosphodiesterase inhibitors is capable of improving placental and fetal perfusion, contributing to gestational scenario, by decreasing the symptomatology and severity of this syndrome. In this literature review, it has been found that most of the studies were conducted in animal models, and there is still lack of evidence supporting its use in clinical practice. Research in human indicates conflicting findings; randomized controlled trials were scarce and did not demonstrate any benefit in morbidity or mortality. Data regarding to pathophysiological and interventional research are described and commented in this review.

Summary

The use of phosphodiesterase inhibitors in the treatment of preeclampsia is controversial and should not be encouraged taking into account recent data.

     

The Complement Alternative Pathway and Preeclampsia

Purpose of Review

Significant and intricate immune adaptations are essential for the establishment and maintenance of normal pregnancy. Preeclampsia is a morbid, potentially life-threatening disease for both mother and neonate that occurs uniquely in pregnancy, at least in part, due to maternal immune maladaptation. We aim to review the literature that focuses on case reports, diagnostic approaches, and treatment strategies for disorders of the complement alternative pathway (CAP) as related to preeclampsia.

Recent Findings

There is evidence of complement dysregulation in preeclampsia and HELLP syndrome, similar to that observed in a few rare types of thrombotic microangiopathies. Complement dysregulation may be identified with functional laboratory testing as well as genetic testing.

Summary

Increased utilization of a standardized diagnostic approach to establish whether persistent and/or severe cases of preeclampsia and HELLP syndrome are complement-mediated may lead to development of future treatment strategies, such as complement-targeted therapy.

     

Effects of a Video on Organ Donation Consent Among Primary Care Patients: A Randomized Controlled Trial

BACKGROUND

Low organ donation rates remain a major barrier to organ transplantation.

OBJECTIVE

We aimed to determine the effect of a video and patient cueing on organ donation consent among patients meeting with their primary care provider.

DESIGN

This was a randomized controlled trial between February 2013 and May 2014.

SETTING

The waiting rooms of 18 primary care clinics of a medical system in Cuyahoga County, Ohio.

PATIENTS

The study included 915 patients over 15.5 years of age who had not previously consented to organ donation.

INTERVENTIONS

Just prior to their clinical encounter, intervention patients (n?=?456) watched a 5-minute organ donation video on iPads and then choose a question regarding organ donation to ask their provider. Control patients (n?=?459) visited their provider per usual routine.

MAIN MEASURES

The primary outcome was the proportion of patients who consented for organ donation. Secondary outcomes included the proportion of patients who discussed organ donation with their provider and the proportion who were satisfied with the time spent with their provider during the clinical encounter.

KEY RESULTS

Intervention patients were more likely than control patients to consent to donate organs (22 % vs. 15 %, OR 1.50, 95%CI 1.10–2.13). Intervention patients were also more likely to have donation discussions with their provider (77 % vs. 18 %, OR 15.1, 95%CI 11.1–20.6). Intervention and control patients were similarly satisfied with the time they spent with their provider (83 % vs. 86 %, OR 0.87, 95%CI 0.61–1.25).

LIMITATION

How the observed increases in organ donation consent might translate into a greater organ supply is unclear.

CONCLUSION

Watching a brief video regarding organ donation and being cued to ask a primary care provider a question about donation resulted in more organ donation discussions and an increase in organ donation consent. Satisfaction with the time spent during the clinical encounter was not affected.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT01697137

     

Paricalcitol reduces oxidative stress and inflammation in hemodialysis patients

Background

Treatment with selective vitamin D receptor activators such as paricalcitol have been shown to exert an anti-inflammatory effect in patients on hemodialysis, in addition to their action on mineral metabolism and independently of parathyroid hormone (PTH) levels. The objective of this study was to evaluate the additional antioxidant capacity of paricalcitol in a clinical setting.

Methods

The study included 19 patients with renal disease on hemodialysis, of whom peripheral blood was obtained for analysis at baseline and three months after starting intravenous paricalcitol treatment. The following oxidizing and inflammatory markers were quantified: malondialdehyde (MDA), nitrites and carbonyl groups, indoleamine 2,3-dioxygenase (IDO), tumor necrosis factor alfa (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP). Of the antioxidants and anti-inflammatory markers, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), thioredoxin, and interleukin-10 (IL-10) levels were obtained.

Results

Baseline levels of oxidation markers MDA, nitric oxide and protein carbonyl groups significantly decreased after three months on paricalcitol treatment, while levels of GSH, thioredoxin, catalase and SOD activity significantly increased. After paricalcitol treatment, levels of the inflammatory markers CRP, TNF-α, IL-6 and IL-18 were significantly reduced in serum and the level of anti-inflammatory cytokine IL-10 was increased.

Conclusions

In renal patients undergoing hemodialysis, paricalcitol treatment significantly reduces oxidative stress and inflammation, two well known factors leading to cardiovascular damage.

     

Alterations in Docosahexaenoic Acid-Related Lipid Cascades in Inflammatory Bowel Disease Model Mice

Background

Inflammatory bowel disease (IBD) is an intestinal disorder, involving chronic and relapsing inflammation of the digestive tract. Dysregulation of the immune system based on genetic, environmental, and other factors seems to be involved in the onset of IBD, but its exact pathogenesis remains unclear. Therefore, radical treatments for ulcerative colitis and Crohn’s disease remain to be found, and IBD is considered to be a refractory disease.

Aims

The aim of this study is to obtain novel insights into IBD via metabolite profiling of interleukin (IL)-10 knockout mice (an IBD animal model that exhibits a dysregulated immune system).

Methods

In this study, the metabolites in the large intestine and plasma of IL-10 knockout mice were analyzed. In our analytical system, two kinds of analysis (gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry) were used to detect a broader range of metabolites, including both hydrophilic and hydrophobic metabolites. In addition, an analysis of lipid mediators in the large intestine and ascites of IL-10 knockout mice was carried out.

Results

The levels of a variety of metabolites, including lipid mediators, were altered in IL-10 knockout mice. For example, high large intestinal and plasma levels of docosahexaenoic acid (DHA) were observed. In addition, arachidonic acid- and DHA-related lipid cascades were upregulated in the ascites of the IL-10 knockout mice.

Conclusions

Our findings based on metabolite profiles including lipid mediators must contribute to development of researches about IBD.

     

Sinus and Upper Airway Surgery in Children

Purpose of Review

Chronic sinus and upper airway disease in children is a common health problem encountered every day. Its pathophysiology is complicated which leads to different treatment options and approaches. We seek to review the current literature and evidence to surgical treatments.

Recent Findings

Medical treatment with antibiotics and topical nasal sprays continues to be the first-line treatment. Surgical interventions include adenoidectomy, balloon catheter sinuplasty (BCS), and endoscopic sinus surgery (ESS). Each modality has proven to be safe; however, its effectiveness is widely variable.

Summary

More research with higher level of evidence is needed to help in choosing the right surgical treatment with optimal benefit.

     

Treatment of acute hepatitis C: recommendations from an expert panel of the Italian Society of Infectious and Tropical Diseases

Aim

This paper is aimed at providing practical recommendations for the management of acute hepatitis C (AHC).

Methods

This is an expert position paper based on the literature revision. Final recommendations were graded by level of evidence and strength of the recommendations.

Results

Treatment of AHC with direct-acting antivirals (DAA) is safe and effective; it overcomes the limitations of INF-based treatments.

Conclusions

Early treatment with DAA should be offered when available.

     

IL-17A Promotes Initiation and Development of Intestinal Fibrosis Through EMT

Background

Intestinal fibrosis is a common complication of Crohn’s disease (CD). Its exact mechanism is still unclear, and effective treatments to control or reverse the fibrosis process are unavailable. Epithelial–mesenchymal transition (EMT) may promote intestinal fibrosis by increasing deposition of extracellular matrix protein. IL-17A is a pro-inflammatory cytokine, and it has been shown as a profibrotic factor as its association with fibrosis of multiple organs was reported.

Aims

To assess the roles of IL-17A and EMT in the initiation and development of intestinal fibrosis and to verify the potential inductive effect of IL-17A on EMT.

Methods

In this study, we evaluated the expression of IL-17A and EMT-related genes in colonic mucosal biopsy tissues of CD patients and control individuals. Then, we examined the changes of EMT-related genes and fibrosis-related genes of IEC-6 cells which cultured for 72 h under increasing concentrations of IL-17A or with TGF-β1, to verify the potential inductive effect of IL-17A on EMT in vitro. We blocked the IL-17A of the mouse model of TNBS-induced experimental intestinal colitis and fibrosis to further verify the potential inductive effect of IL-17A on EMT in vivo.

Results

We found the occurrence of EMT and high-level expression of IL-17A in intestinal mucosa of CD patients. Using IEC-6 cells, we showed that IL-17A may induce EMT in intestinal epithelial cells that come with reduced E-cadherin expression and increased expression of vimentin, snail, and α-SMA. We further found that anti-IL-17A treatment alleviated intestinal fibrosis through reducing EMT in mouse intestine.

Conclusions

Our study confirmed the involvement of IL-17A in the development of intestinal fibrosis through inducing EMT.

     

Diabetes und Depression

Background

One of four patients with type 2 diabetes mellitus (T2DM) has clinically relevant depression. On the other hand, depression increases the risk for T2DM as well as micro- and macrovascular complications.

Objectives

This association may reflect a shared pathophysiology consisting of complex bidirectional interactions, which may influence therapy and prognosis.

Materials and methods

Recent findings, reviews and basic literature are analysed and an update is presented and discussed.

Results

Overall, accumulating evidence indicates a metabolic–mood syndrome with a linkage that includes stress sensitivity, insulin resistance (IR), neurohormonal dysregulation and inflammation. IR alters dopamine turnover and causes depression-like behaviour. Furthermore IR is associated with worse memory performance. Metabolic risk influences neurodevelopment. However, cross-sectional data do not support a genetic association between T2DM and depression.

Conclusions

T2DM may promote depression and interact with neurodevelopment and neurodegeneration. Comorbidity seems to be particularly toxic. Both prevention of T2DM in depressed patients and treatment of depression in T2DM are of considerable significance. Serotonin reuptake inhibition (SSRI) and psychotherapy are effective in the treatment of depression.

     

Cost of Transformation among Primary Care Practices Participating in a Medical Home Pilot

Background

Medical home initiatives encourage primary care practices to invest in new structural capabilities such as patient registries and information technology, but little is known about the costs of these investments.

Objectives

To estimate costs of transformation incurred by primary care practices participating in a medical home pilot.

Design

We interviewed practice leaders in order to identify changes practices had undertaken due to medical home transformation. Based on the principles of activity-based costing, we estimated the costs of additional personnel and other investments associated with these changes.

Setting

The Pennsylvania Chronic Care Initiative (PACCI), a statewide multi-payer medical home pilot.

Participants

Twelve practices that participated in the PACCI.

Measurements

One-time and ongoing yearly costs attributed to medical home transformation.

Results

Practices incurred median one-time transformation-associated costs of $30,991 per practice (range, $7694 to $117,810), equivalent to $9814 per clinician ($1497 to $57,476) and $8 per patient ($1 to $30). Median ongoing yearly costs associated with transformation were $147,573 per practice (range, $83,829 to $346,603), equivalent to $64,768 per clinician ($18,585 to $93,856) and $30 per patient ($8 to $136). Care management activities accounted for over 60% of practices’ transformation-associated costs. Per-clinician and per-patient transformation costs were greater for small and independent practices than for large and system-affiliated practices.

Limitations

Error in interviewee recall could affect estimates. Transformation costs in other medical home interventions may be different.

Conclusions

The costs of medical home transformation vary widely, creating potential financial challenges for primary care practices—especially those that are small and independent. Tailored subsidies from payers may help practices make these investments.

Primary Funding Source

Agency for Healthcare Research and Quality

     

Autosomal-dominante polyzystische Nierenerkrankung

Background

Patients with autosomal dominant polycystic kidney disease (ADPKD) have a varying risk for progression to renal failure and the necessity for dialysis depending on the individual risk profile. This review summarizes the current knowledge on the genetics and pathophysiology relevant for individual disease progression and currently available treatment strategies for ADPKD are assessed.

Methods

Literature search for articles on the pathophysiology and treatment of ADPKD.

Results

Renal scanning with magnetic resonance imaging (MRI) represents the most sensitive tool for establishing both the diagnosis and prognosis for estimation of the risk of progression. Strict blood pressure control, preferably with angiotensin-converting enzyme (ACE) inhibitors, is the most crucial component of treatment. Selected patients with chronic kidney disease (CKD) stages I–III and a high probability of rapid progression to end-stage renal disease can benefit from treatment with tolvaptan, which has been shown to delay cyst growth and to reduce loss of the estimated glomerular filtration rate (eGFR).

Conclusion

In addition to non-specific treatment approaches, tolvaptan represents a treatment option for high risk ADPKD patients to inhibit progression of cyst growth and loss of eGFR.

     

A nationwide passive surveillance on fungal infections shows a low burden of azole resistance in molds and yeasts in Tyrol,Austria

Purpose

To determine the burden of antifungal resistance in fungi over the last 10 years.

Methods

Performance of a semi-nationwide surveillance on antifungal resistance.

Results

We observed a low frequency of azole resistance in Aspergillus fumigatus, a moderate increase of echinocandin resistance in yeasts, and a stable amphotericin B activity in yeasts and molds. Posaconazole resistance in Aspergillus terreus occurred in a few isolates.

Conclusion

The burden of resistance in fungi seems to be low in Tyrol, Austria.