Cardiovascular magnetic resonance imaging in hypertrophic cardiomyopathy: Current state of the art

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy with a prevalence of 1:500 (0.2%) in the general population. Sudden cardiac death (SCD) is the most feared presentation of HCM. Therefore, it is essential to identify individuals at high risk in order to prevent SCD. The absence of conventional risk factors does not nullify the risk of HCM related SCD. Although echocardiography is currently the most widely used imaging modality, cardiac magnetic resonance (CMR) allows detailed characterization of the HCM phenotype, which makes it possible to differentiate HCM from other causes of left ventricular hypertrophy. CMR has the potential to further refine risk stratification. Late gadolinium enhancement (LGE) on CMR is a high-risk feature and there is emerging data to suggest that the presence of LGE should be employed as a marker for major adverse outcomes such as SCD, arrhythmias, systolic and diastolic heart failure. Hence, LGE on CMR may be considered an additional risk factor for SCD in HCM patients and should be incorporated in decision-making for implant­able cardioverter defibrillator implantation to aid primary prevention. Novel markers such as the extent of myocardial fibrosis on CMR must be accounted for comprehensive risk stratifica­tion of HCM patients. The purpose of this review is to discuss the current status and emerging role of CMR in HCM

Healthcare expenditures among community-dwelling adults with thyroid cancer in the United States: A propensity score matched analysis

Objective: This study assessed the excess healthcare expenditures and factors associated with it among community-dwelling adults with thyroid cancer compared to non-cancer controls in the United States. Method: A retrospective, cross-sectional, matched case-control study design was used by pooling multiple years of Medical Expenditure Panel Survey (MEPS) data (2002-2012). The eligible study sample comprised of adults (age >= 18 years), who were alive during the calendar year and reported positive healthcare expenditure. The case group consisted of adults with thyroid cancer only while the control group consisted of adults who did not have any form of cancer. Total and subtypes of mean annual healthcare expenditures comprised the main study outcome. We also calculated the total and subtypes of out-of-pocket (OOP) expenditures as well as OOP as a percentage of household income. Ordinary Least Square (OLS) regressions on log-transformed expenditures were conducted to elucidate the influence of different factors on healthcare expenditures among adults with thyroid cancer. Results: The yearly average total healthcare expenditures among adults with thyroid cancer was significantly higher compared to propensity score matched controls ($9,585 vs.$5,830, p < 0.001). Similar observations were found in terms of inpatient, and outpatient expenditures. Functional status as well as comorbid conditions were significantly associated with excess expenditures. The yearly average total OOP expenditure for adults with thyroid cancer was significantly higher compared to matched controls ($1,425 vs.$974, p < 0.001), with major differences observed in inpatient OOP ($178 vs.$24, p = 0.003), outpatient OOP ($435vs.$256, p < 0.001), and prescription OOP ($554 vs.$423, p < 0.001) expenditures. There was a significant (p < 0.001) difference between the average OOP as a percentage of household income between adults with thyroid cancer (Mean: 7.54%, S.E: 1.52%) and matched controls (Mean: 5.80%, S.E: 0.47%). Conclusions: Our findings suggest that holistic care approach could be helpful to significantly reduce the economic burden in this population. Viable strategies such as limits on OOP costs are required to minimize this high OOP burden among cancer survivors and their families.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

A Systematic Review on Predisposition to Lymphoid (B and T cell) Neoplasias in Patients With Primary Immunodeficiencies and Immune Dysregulatory Disorders (Inborn Errors of Immunity)

Primary immunodeficiencies and immune dysregulatory disorders (PIDDs; now referred to as inborn errors in immunity) are rare disorders with a prevalence of 41. 4 or 50.5 per 100,000 persons (1). The incidence of malignancy in PIDD patents is the second-highest cause of death in children as well as adults, after infection, and is higher in certain PIDDs compared to others. We performed a systematic review of the literature to identify reports of B cell and T cell neoplasias in PIDDs and clustered them based on their classification in the IUIS schema. As would be expected, higher susceptibility to malignancies are typically reported in patients with Common Variable Immunodeficiency (CVID), combined immunodeficiencies affecting cellular immunity, in particular, DNA repair defects, or in the context of impaired immune regulatory control. There is not much evidence of increased risk for cancer in patients with innate immune defects, indicating that not all types of infection or genetic susceptibility predispose equally to cancer risk. Viral infections, in particular EBV, HHV and HPV, have been shown to increase susceptibility to developing cancer, but also patients with defects in immune regulation, such as Autoimmune Lymphoproliferative Syndrome (ALPS), activated p110delta syndrome (APDS type 1) and IL-10 receptor deficiency among others have a higher incidence of neoplastic disease, particularly lymphomas. In fact, lymphomas account for two-thirds of all malignancies reported in PIDD patients (2), with either a combined immunodeficiency or DNA repair defect predominating as the underlying immune defect in one registry, or antibody deficiencies in another (3). The vast majority of lymphomas reported in the context of PIDDs are B cell lymphomas, though T cell lymphomas have been reported in a few studies, and tend to largely be associated with chromosomal breakage disorders (4) or Cartilage Hair Hypoplasia (5). There appears to be a much higher prevalence of T cell lymphomas in patients with secondary immunodeficiencies (6), though this could reflect treatment bias. We reviewed the literature and summarized the reports of B and T cell lymphoma in PIDD patients to survey the current state of knowledge in this area

PCSK9 inhibitors and ezetimibe with or without statin therapy for cardiovascular risk reduction: a systematic review and network meta-analysis.

OBJECTIVE To compare the impact of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on cardiovascular outcomes in adults taking maximally tolerated statin therapy or who are statin intolerant. DESIGN Network meta-analysis. DATA SOURCES Medline, EMBASE, and Cochrane Library up to 31 December 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Randomised controlled trials of ezetimibe and PCSK9 inhibitors with ≥500 patients and follow-up of ≥6 months. MAIN OUTCOME MEASURES We performed frequentist fixed-effects network meta-analysis and GRADE (grading of recommendations, assessment, development, and evaluation) to assess certainty of evidence. Results included relative risks (RR) and absolute risks per 1000 patients treated for five years for non-fatal myocardial infarction (MI), non-fatal stroke, all-cause mortality, and cardiovascular mortality. We estimated absolute risk differences assuming constant RR (estimated from network meta-analysis) across different baseline therapies and cardiovascular risk thresholds; the PREDICT risk calculator estimated cardiovascular risk in primary and secondary prevention. Patients were categorised at low to very high cardiovascular risk. A guideline panel and systematic review authors established the minimal important differences (MID) of 12 per 1000 for MI and 10 per 1000 for stroke. RESULTS We identified 14 trials assessing ezetimibe and PCSK9 inhibitors among 83 660 adults using statins. Adding ezetimibe to statins reduced MI (RR 0.87 (95% confidence interval 0.80 to 0.94)) and stroke (RR 0.82 (0.71 to 0.96)) but not all-cause mortality (RR 0.99 (0.92 to 1.06)) or cardiovascular mortality (RR 0.97 (0.87 to 1.09)). Similarly, adding PCSK9 inhibitor to statins reduced MI (0.81 (0.76 to 0.87)) and stroke (0.74 (0.64 to 0.85)) but not all-cause (0.95 (0.87 to 1.03)) or cardiovascular mortality (0.95 (0.87 to 1.03)). Among adults with very high cardiovascular risk, adding PCSK9 inhibitor was likely to reduce MI (16 per 1000) and stroke (21 per 1000) (moderate to high certainty); whereas adding ezetimibe was likely to reduce stroke (14 per 1000), but the reduction of MI (11 per 1000) (moderate certainty) did not reach MID. Adding ezetimibe to PCSK9 inhibitor and statin may reduce stroke (11 per 1000), but the reduction of MI (9 per 1000) (low certainty) did not reach MID. Adding PCSK9 inhibitors to statins and ezetimibe may reduce MI (14 per 1000) and stroke (17 per 1000) (low certainty). Among adults with high cardiovascular risk, adding PCSK9 inhibitor probably reduced MI (12 per 1000) and stroke (16 per 1000) (moderate certainty); adding ezetimibe probably reduced stroke (11 per 1000), but the reduction in MI did not achieve MID (8 per 1000) (moderate certainty). Adding ezetimibe to PCSK9 inhibitor and statins did not reduce outcomes beyond MID, while adding PCSK9 inhibitor to ezetimibe and statins may reduce stroke (13 per 1000). These effects were consistent in statin-intolerant patients. Among moderate and low cardiovascular risk groups, adding PCSK9 inhibitor or ezetimibe to statins yielded little or no benefit for MI and stroke. CONCLUSIONS Ezetimibe or PCSK9 inhibitors may reduce non-fatal MI and stroke in adults at very high or high cardiovascular risk who are receiving maximally tolerated statin therapy or are statin-intolerant, but not in those with moderate and low cardiovascular risk

PCSK9 inhibitors and ezetimibe for the reduction of cardiovascular events: a clinical practice guideline with risk-stratified recommendations.

CLINICAL QUESTION In adults with low density lipoprotein (LDL) cholesterol levels >1.8 mmol/L (>70 mg/dL) who are already taking the maximum dose of statins or are intolerant to statins, should another lipid-lowering drug be added, either a proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor or ezetimibe, to reduce the risk of major cardiovascular events? If so, which drug is preferred? Having decided to use one, should we add the other lipid-lowering drug? CURRENT PRACTICE Most guidelines emphasise LDL cholesterol targets in their recommendations for prescribing PCSK9 inhibitors and/or ezetimibe in adults at high risk of experiencing a major adverse cardiovascular event. However, to achieve these goals in very high risk patients with statins alone is almost impossible, so physicians are increasingly considering other lipid-lowering drugs solely for achieving LDL cholesterol treatment goals rather than for achieving important absolute cardiovascular risk reduction. Most guidelines do not systematically assess the cardiovascular benefits of adding PCSK9 inhibitors and/or ezetimibe for all risk groups across primary and secondary prevention, nor do they report, in accordance with explicit judgments of assumed patients' values and preferences, absolute benefits and harms and potential treatment burdens. RECOMMENDATIONS The guideline panel provided mostly weak recommendations, which means we rely on shared decision making when applying these recommendations. For adults already using statins, the panel suggests adding a second lipid-lowering drug in people at very high and high cardiovascular risk but recommends against adding it in people at low cardiovascular risk. For adults who are intolerant to statins, the panel recommends using a lipid-lowering drug in people at very high and high cardiovascular risk but against adding it in those at low cardiovascular risk. When choosing to add another lipid-lowering drug, the panel suggests ezetimibe in preference to PCSK9 inhibitors. The panel suggests further adding a PCSK9 inhibitor to ezetimibe for adults already taking statins at very high risk and those at very high and high risk who are intolerant to statins. HOW THIS GUIDELINE WAS CREATED An international panel including patients, clinicians, and methodologists produced these recommendations following standards for trustworthy guidelines and using the GRADE approach. The panel identified four risk groups of patients (low, moderate, high, and very high cardiovascular risk) and primarily applied an individual patient perspective in moving from evidence to recommendations, though societal issues were a secondary consideration. The panel considered the balance of benefits and harms and burdens of starting a PCSK9 inhibitor and/or ezetimibe, making assumptions of adults' average values and preferences. Interactive evidence summaries and decision aids accompany multi-layered recommendations, developed in an online authoring and publication platform (www.magicapp.org) that also allows re-use and adaptation. THE EVIDENCE A linked systematic review and network meta-analysis (14 trials including 83 660 participants) of benefits found that PCSK9 inhibitors or ezetimibe probably reduce myocardial infarctions and stroke in patients with very high and high cardiovascular risk, with no impact on mortality (moderate to high certainty evidence), but not in those with moderate and low cardiovascular risk. PCSK9 inhibitors may have similar effects to ezetimibe on reducing non-fatal myocardial infarction or stroke (low certainty evidence). These relative benefits were consistent, but their absolute magnitude varied based on cardiovascular risk in individual patients (for example, for 1000 people treated with PCSK9 inhibitors in addition to statins over five years, benefits ranged from 2 fewer strokes in the lowest risk to 21 fewer in the highest risk). Two systematic reviews on harms found no important adverse events for these drugs (moderate to high certainty evidence). PCSK9 inhibitors require injections that sometimes result in injection site reactions (best estimate 15 more per 1000 in a 5 year timeframe), representing a burden and harm that may matter to patients. The MATCH-IT decision support tool allows you to interact with the evidence and your patients across the alternative options: https://magicevidence.org/match-it/220504dist-lipid-lowering-drugs/. UNDERSTANDING THE RECOMMENDATIONS The stratification into four cardiovascular risk groups means that, to use the recommendations, physicians need to identify their patient's risk first. We therefore suggest, specific to various geographical regions, using some reliable risk calculators that estimate patients' cardiovascular risk based on a mix of known risk factors. The largely weak recommendations concerning the addition of ezetimibe or PCSK9 inhibitors reflect what the panel considered to be a close balance between small reductions in stroke and myocardial infarctions weighed against the burdens and limited harms.Because of the anticipated large variability of patients' values and preferences, well informed choices warrant shared decision making. Interactive evidence summaries and decision aids linked to the recommendations can facilitate such shared decisions. The strong recommendations against adding another drug in people at low cardiovascular risk reflect what the panel considered to be a burden without important benefits. The strong recommendation for adding either ezetimibe or PCSK9 inhibitors in people at high and very high cardiovascular risk reflect a clear benefit.The panel recognised the key uncertainty in the evidence concerning patient values and preferences, namely that what most people consider important reductions in cardiovascular risks, weighed against burdens and harms, remains unclear. Finally, availability and costs will influence decisions when healthcare systems, clinicians, or people consider adding ezetimibe or PCSK9 inhibitors

Disorganized Systematic Reviews and Meta-analyses: Time to Systematize the Conduct and Publication of These Study Overviews

The number of meta-analyses published annually has increased more than 20-fold between 1994 (n = 386) and 2014 (n = 8203). In examining how much of this increase in meta-analysis publication has genuinely represented novel contributions to clinical medicine and public health, it became clear that there was an abundance of redundant and disorganized meta-analyses, creating confusion and generating considerable debate. Ironically, meta-analyses, which should prevent redundant research, have become a victim of it. Recently, 17 meta-analyses were published based on the results of only 3 randomized controlled trials that studied the role of transcatheter closure of patent foramen ovale for prevention of cryptogenic stroke. In our search of the published literature, we identified at least 10 topics that were the subject of 10 meta-analyses. In the context of overlapping meta-analyses, one questions what needs to be done to put this runaway train back on track. In this review we examine the practice of redundant meta-analyses and the reasons for its disturbing popularity. The registration of systematic reviews should be mandatory in prospective registries, such as PROSPERO, and the PRISMA checklist should be updated to incorporate new evidence and mandate the reference of previously published reviews and rationale for any new study

All That Wheezes Is Not Asthma: A Case of Diffuse Large B-Cell Lymphoma of the Larynx

Localized laryngeal lymphoma is a rare entity with an incidence of less than 1% of all laryngeal neoplasms. Diffuse large B-cell lymphoma (DLBCL) is the most common type of laryngeal neoplasms. Here, we describe a case of a young 28-year-old female with large B-cell lymphoma who remained undiagnosed for a long time owing to a myriad of nonspecific presentation including “wheezing.” Although primary laryngeal lymphomas constitute a diagnostic challenge since they are rare, one should have a high index of suspicion for lymphoma of the larynx in patients presenting with unresolved wheezing as it can present catastrophically with acute airway obstruction requiring immediate surgical intervention which was observed in this case. Treatment includes radiotherapy, chemotherapy, immunotherapy, or a combination of these. We hope that the discussions ensuing from case reports regarding uncommon presentations of laryngeal lymphoma may spur the formation of regional/international databases for the description of lymphomas with unusual presentations. This effort can lead to in-depth study of cases and prompt awareness of “rare and subtle presentations” of laryngeal lymphoma

Health Behaviors among Stroke Survivors in the United States: A Propensity Score-Matched Study

Goal: The American Heart Association/American Stroke Association has specific recommendations for secondary stroke prevention. The aim of this study was to compare health behaviors engagement between stroke survivors and propensity score-matched controls. Methods: We conducted a retrospective, cross-sectional, matched case-control study using data from the 2015 Behavioral Risk Factor Surveillance System (BRFSS) survey. We included older adults aged 50 or older who participated in the 2015 BRFSS survey and completed the interview. Each case was matched to 3 controls (1:3) based on propensity scores to increase the power of the analyses. Stroke survivors were compared with controls on their physical activity, smoking, alcohol use, body mass index (BMI), last flu immunization, last physical checkup, last blood cholesterol check, heavy drinking, and vegetable and fruit consumption. We used binomial logistic regression to assess health behaviors among stroke survivors compared with controls. Results: The final study sample consisted of 13,249 stroke survivors and 39,747 controls without stroke after propensity score matching. Multivariable analyses revealed that there were significant differences between stroke survivors and matched controls in terms of BMI, physical activity, smoking status, alcohol consumption, and vegetable and fruit consumption. For example, stroke survivors were 51% more likely to be smokers (adjusted odds ratio [AOR] 1.51, 95% confidence interval [CI], 1.32-1.73) and 14% less likely to consume alcohol (AOR .86, 95% CI .78-.95). Conclusion: Findings from our study indicate that compared with propensity score-matched controls, stroke survivors engage in poorer health behaviors with the exception of alcohol consumption.12 month embargo; published online: 16 April 2018This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Refractory IgD Multiple Myeloma Treated with Daratumumab: A Case Report and Literature Review

Patients with relapsed and refractory multiple myeloma have poor prognosis. A recent analysis of patients with relapsed and refractory multiple myeloma who were refractory to both proteasome inhibitors and immunomodulatory drugs showed the median overall survival of 9 months only. Daratumumab is the first-in-class human monoclonal antibody against CD38 cells which was studied in phase I/II trials for treatment of these patients with relapsed refractory multiple myeloma. It showed an overall response rate of 36% and a median overall survival (OS) of 17 months in these patients. We report a case of 40-year-old man with immunoglobulin D (IgD) multiple myeloma whose disease was refractory to at least 5 different chemotherapy regimens including proteasome inhibitors and immunomodulatory drugs. The clinical studies assessing daratumumab did not include any patients with IgD myeloma which is a rare form of multiple myeloma and to our knowledge is the first study reporting use of daratumumab in IgD myeloma.Open Access Journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]