Circulating MicroRNAs: a Potential Biomarker for Cardiac Damage,Inflammatory Response,and Left Ventricular Function Recovery in Pediatric Viral Myocarditis

Viral myocarditis (VM) can be a life-threatening event resulting in cardiac failure, chronic cardiomyopathy, and death. VM typically includes three phases, i.e., acute, subacute, and resolution/chronic. We prospectively investigated cardiac- and inflammatory-associated plasma-circulating miRNA levels in eight pediatric patients with VM during the three stages of the disease. The level of cardiac-associated miR-208a was significantly elevated during the acute phase compared with the subacute and resolution/chronic phases. The level of cardiac- and inflammatory-associated miR-21 was significantly elevated during the acute phase compared to the resolution/chronic phase. Moreover, cardiac-associated miR-208b levels during the subacute phase correlated with systolic left ventricular function recovery as measured during the resolution/chronic phase. The findings of our study demonstrate an association between cardiac damage and the inflammatory response and the expression of miR-208a and miR-21 during the pathological progression of myocarditis. We also found that miR-208b levels exhibit a prognostic significance for left ventricular functional recovery.     

Hoarding: A meta‐analysis of age of onset

Hoarding disorder is present in 2–6% of the population and can have an immense impact on the lives of patients and their families. Before its inclusion the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, pathological hoarding was often characterized as a symptom of obsessive–compulsive disorder, and several different diagnostic assessment methods were used to identify and characterize it. Although the age of onset of pathological hoarding is an important epidemiological measure, as clarifying the age of onset of hoarding symptoms may allow for early identification and implementation of evidence‐based treatments before symptoms become clinically significant, the typical age of onset of hoarding is still uncertain. To that end, this study is a systematic review and meta‐analysis of research published in English between the years 1900 and 2016 containing information on age of onset of hoarding symptoms. Twenty‐five studies met inclusion criteria. The mean age of onset of hoarding symptoms across studies was 16.7 years old, with evidence of a bimodal distribution of onset. The authors conclude by discussing practice implications for early identification and treatment.     

Outcomes of Superficial and Deep Irrigation and Debridement in Total Hip and Knee Arthroplasty

BackgroundFollowing total knee arthroplasty and total hip arthroplasty, wound-related problems and deep periprosthetic joint infection may present in a similar fashion. Irrigation and debridement (I&D) has a great role in management of patients with early infection. The question that often arises is how to tell the difference between superficial and deep infection. This study evaluated the role and outcomes of both superficial and deep I&D in patients with wound-related issues and/or suspected periprosthetic joint infection.MethodsA retrospective study was conducted evaluating patients who underwent I&D within 28 days of total joint arthroplasty. A total of 176 cases with a minimum of 1-year follow-up were identified, and clinical records were reviewed in detail. Reoperations included superficial (fascia not opened) or deep (fascia opened) I&D. Failure was defined as the need for further surgical intervention within 1 year of initial I&D.ResultsThe overall success for superficial I&D was 84.28% vs 68.86% for deep I&D. The success of both deep and superficial I&D was higher if the I&D was performed closer to the index surgery. Superficial I&D in patients with a positive joint aspiration or evidence of intraoperative purulence or those in whom had no subcutaneous fluid had higher failure rates.ConclusionSuperficial I&D is a viable option in patients with wound-related issues as long as joint aspiration is performed to rule out infection involving the prosthesis. If there are findings of no fluid or purulence, fascia may need to be opened and the deeper tissues explored.     

Serum free immunoglobulin light chain fingerprint identifies a subset of newly diagnosed multiple myeloma patients with worse outcome

Multiple myeloma (MM) is a multi–subclonal malignancy with relatively high heterogeneity. Patients who initially presented with both monoclonal‐protein (MP) and free light chain (FLC) secretion but then relapsed with a light chain escape pattern have been shown to reflect disease clonal evolution and to bare a worse prognosis. We hypothesized that a discordant MP/FLC pattern at diagnosis may reflect a similar clonal evolution that had occurred prior to diagnosis of active myeloma, conferring a worse outcome. We analyzed 255 consecutive newly diagnosed MM patients who received first line bortezomib‐based therapy between 2007 and 2014, hypothesizing that their MP/FLC fingerprint at diagnosis reflects clonal heterogeneity and, therefore, affects outcome. An involved FLC level ≥ 700 mg/L and MP ≥ 2.5 g/L were used as cutoffs for low vs high FLC and MP levels, respectively. Patients were divided into 4 subgroups according to their involved FLC and MP blood levels at diagnosis: HiLC and HiMP for patients with either a predominant FLC or a predominant MP, respectively, and HiLC‐MP and LoLC‐MP when both FLC and MP were increased or decreased, respectively. There were 68 (27%) patients with HiLC, which presented more often with International Staging System‐3 stage (P < .0001). Multivariate analysis showed that HiLC was associated with a 5.1‐fold risk for mortality in a multivariate model (95% confidence interval [CI], 1.34‐19.68). Both HiLC and HiLC‐MP phenotypes were associated with shorter progression‐free survival (hazard ratio of 2.66 [95% CI, 1.33‐5.32] and 2.82 [95% CI, 1.37‐5.83], respectively), independently of other prognostic factors, including the use of autograft. Thus, we identified an LC predominant secretory fingerprint (HiLC phenotype) at diagnosis as a potential independent risk factor that may affect disease control and survival in newly diagnosed MM patients treated with bortezomib‐based induction therapy; this may represent increased subclonal heterogeneity.     

Recommending Unfunded Innovative Cancer Therapies: Ethical vs. Clinical Perspectives among Oncologists on a Public Healthcare System—A Mixed-Methods Study

Over the past decade, there has been a growing development of innovative technologies to treat cancer. Many of these technologies are expensive and not funded by health funds. The present study examined physicians’ perceptions of the ethical and clinical aspects of the recommendation and use of unfunded technologies for cancer treatment. This mixed-methods study surveyed 127 oncologists regarding their perceptions toward using unfunded innovative cancer treatment technologies, followed by in-depth interviews with 16 oncologists. Most respondents believed that patients should be offered all treatment alternatives, regardless of their financial situation. However, 59% indicated that they often face dilemmas regarding recommending new unfunded treatments to patients with financial difficulties and without private health insurance. Over a third (38%) stated that they felt uncomfortable discussing the cost of treatment with patients. A predictive model found that physicians facing patients whose medical condition worsened due to an inability to access new treatments, and who expressed the opinion that physicians can assist in locating funding for patients who cannot afford treatments, were more likely to recommend unfunded innovative therapies to patients (F = 5.22, R² = 0.15, p < 0.001). Subsequent in-depth interviews revealed four key themes: economic considerations in choosing therapy, patient–physician communication, the public healthcare fund, and discussion of treatment costs. Physicians feel a professional commitment to offer patients the best medical care and a moral duty to discuss costs and minimize patients’ financial difficulty. There is a need for careful and balanced use of innovative life-prolonging technologies while putting patients at the center of discourse on this complex and controversial issue. It is essential to develop a psychosocial support program for physicians and patients dealing with ethical and psychosocial dilemmas and to set guidelines for oncologists to conduct a comprehensive and collaborative physician–patient discourse regarding all aspects of treatment.     

Auditory aversive learning increases discrimination thresholds

Animal studies of discriminative fear conditioning traditionally use stimuli that are distant in physical features and thus easily distinguished perceptually. Independently, human studies have shown that training mostly improves discrimination thresholds. We found that aversive learning actually induced an increase in discrimination thresholds in humans and that subjective aversion during conditioning predicted the individual threshold change. This counterintuitive performance deterioration occurred when using odors or sounds as aversive reinforcers and was not a result of attentional distraction or decision bias. In contrast, positive reinforcement or mere exposure induced the typically reported decrease in thresholds. Our findings indicate that aversive outcomes induce wider stimulus generalization by modulating perceptual thresholds, suggesting the engagement of low-level mechanisms. We suggest that for risk- or loss-related stimuli, less specificity could be a benefit, as it invokes the same mechanisms that respond quickly and efficiently in the face of danger.