Abstract Objectives This study sought to compare techniques evaluating cardiac dysautonomia and predicting the risk of death of patients with hereditary transthyretin amyloidosis (mATTR) after liver ...transplantation (LT). Background mATTR is a multisystemic disease involving mainly the heart and the peripheral nervous system. LT is the reference treatment, and pre-operative detection of high-risk patients is critical. Cardiovascular dysautonomia is commonly encountered in ATTR and may affect patient outcome, although it is not known yet which technique should be used in the field to evaluate it. Methods In a series of 215 consecutive mATTR patients who underwent LT, cardiac dysautonomia was assessed by a dedicated clinical score, time-domain heart rate variability,123 -meta-iodobenzylguanidine heart/mediastinum (123 -MIBG H/M) ratio on scintigraphy, and heart rate response to atropine (HRRA). Results Patient median age was 43 years, 62% were male and 69% carried the Val30Met mutation. Cardiac dysautonomia was documented by at least 1 technique for all patients but 6 (97%). In univariate analysis, clinical score,123 -MIBG H/M ratio and HRRA were associated with mortality but not heart rate variability. The123 -MIBG H/M ratio and HRRA had greater area under the curve (AUC) of receiver-operating characteristic curves than clinical score and heart rate variability (AUC: 0.787, 0.748, 0.656, and 0.523, respectively). Multivariate score models were then built using the following variables: New York Heart Association functional class, interventricular septum thickness, and either123- MIBG H/M ratio ( S MIBG ) or HRRA ( S atropine ). AUC of S MIBG and S atropine were greater than AUC of univariate models, although nonsignificantly (AUC: 0.798 and 0.799, respectively). Predictive powers of S MIBG , S atropine , and a reference clinical model (AUC: 0.785) were similar. Conclusions Evaluation of cardiac dysautonomia is a valuable addition for predicting survival of mATTR patients following LT. Among the different techniques that evaluate cardiac dysautonomia,123 -MIBG scintigraphy and heart rate response to atropine had better prognostic accuracy. Multivariate models did not improve significantly prediction of outcome.
By removing the main source of the mutated TTR, liver transplantation (LT) has become the standard treatment for ATTR (1). Because the demand for liver grafts exceeds the number of available organs ...and because new treatments have recently emerged, screening patients at high risk of death after LT is critical (2). The risk score was built from variables that measured the cardiac and neurological status regardless of mutation type. ...our proposed score should be useful to gauge the risk of patients with rare variants of TTR and to take into account the phenotypic variability encountered among patients with a similar mutation.
Background: Spitzoid morphology in familial melanoma has been associated with germline variants in POT1, a telomere maintenance gene (TMG), suggesting a link between telomere biology and spitzoid ...differentiation. Objective: To assess if familial melanoma cases associated with germline variants in TMG (POT1, ACD, TERF2IP, and TERT) commonly exhibit spitzoid morphology. Methods: In this case series, melanomas were classified as having spitzoid morphology if at least 3 of 4 dermatopathologists reported this finding in ≥25% of tumor cells. Logistic regression was used to calculate odds ratios (OR) of spitzoid morphology compared to familial melanomas from unmatched noncarriers that were previously reviewed by a National Cancer Institute dermatopathologist. Results: Spitzoid morphology was observed in 77% (23 of 30), 75% (3 of 4), 50% (2 of 4), and 50% (1 of 2) of melanomas from individuals with germline variants in POT1, TERF2IP, ACD, and TERT, respectively. Compared to noncarriers (n = 139 melanomas), POT1 carriers (OR = 225.1, 95% confidence interval: 51.7-980.5; P < .001) and individuals with TERF2IP, ACD, and TERT variants (OR = 82.4, 95% confidence interval: 21.3-494.6; P < .001) had increased odds of spitzoid morphology. Limitations: Findings may not be generalizable to nonfamilial melanoma cases. Conclusion: Spitzoid morphology in familial melanoma could suggest germline alteration of TMG.
Rationale Adoptive immunotherapy using virus-specific T-lymphocytes (VSTs) has been successful in preventing or treating viral infections after hematopoietic stem cell transplantation (HSCT), and has ...also been safe and effective in a limited number of patients with primary immunodeficiency disorders (PID).
Familial amyloid polyneuropathy (FAP) is an autosomic dominant disease with a high rate of conduction disorders and increased risk of sudden death. Prophylactic cardiac pacing may be considered in ...asymptomatic patients with FAP. However, the potential benefits are unknown.
To document conduction disorders in a large series of FAP and the incidence of high-degree atrioventricular (AV) block in patients with prophylactic pacemaker (PM).
From January 1999 to January 2010, 262 patients with FAP were retrospectively evaluated. Prophylactic PM was implanted in patients with His-ventricular interval ≥ 70 ms, His-ventricular interval >55 ms associated with a fascicular block, a first-degree AV block, or a Wenckebach anterograde point ≤ 100 beats/min. The spontaneous AV conduction was then analyzed by temporarily inhibiting the PM.
As compared with patients with prophylactic PM (n = 100) and patients implanted given a class I/IIa indication (n = 18), the patients who did not require PM (n = 144) were younger and displayed less severe cardiac involvement. Follow-up after prophylactic PM implantation was analyzed in 95 of the 100 patients over 45 ± 35 months, and a high-degree AV block was documented in 24 of the 95 patients (25%). The risk of high-degree AV block was higher in patients with first-degree AV block or Wenckebach anterograde point ≤ 100 beats/min (hazard ratio 3.5; 95% confidence interval 1.2-10) while microvoltage on surface electrocardiogram reduced the risk (hazard ratio 0.2; 95% confidence interval 0.1-0.7).
In FAP with conduction disorders, prophylactic PM implantation prevented major cardiac events in 25% of the patients over a 45-month mean follow-up. It is suggested that prophylactic PM implantation prevented symptomatic bradycardia in these patients.
Abstract Objective To make scientifically sound and practical recommendations for daily sleep duration across the life span. Methods The National Sleep Foundation convened a multidisciplinary expert ...panel (“Panel”) with broad representation from leading stakeholder organizations. The Panel evaluated the latest scientific evidence and participated in a formal consensus and voting process. Then, the RAND/UCLA Appropriateness Method was used to formulate sleep duration recommendations. Results The Panel made sleep duration recommendations for 9 age groups. Sleep duration ranges, expressed as hours of sleep per day, were designated as recommended, may be appropriate , or not recommended . Recommended sleep durations are as follows: 14-17 hours for newborns, 12-15 hours for infants, 11-14 hours for toddlers, 10-13 hours for preschoolers, 9-11 hours for school-aged children, and 8-10 hours for teenagers. Seven to 9 hours is recommended for young adults and adults, and 7-8 hours of sleep is recommended for older adults. The self-designated basis for duration selection and critical discussions are also provided. Conclusions Consensus for sleep duration recommendations was reached for specific age groupings. Consensus using a multidisciplinary expert Panel lends robust credibility to the results. Finally, limitations and caveats of these recommendations are discussed.
Abstract Objective The objective was to conduct a scientifically rigorous update to the National Sleep Foundation’s sleep duration recommendations. Methods The National Sleep Foundation convened an ...18-member multidisciplinary expert panel, representing 12 stakeholder organizations, to evaluate scientific literature concerning sleep duration recommendations. We determined expert recommendations for sufficient sleep durations across the lifespan using the RAND/UCLA Appropriateness Method. Results The panel agreed that, for healthy individuals with normal sleep, the appropriate sleep duration for newborns is between 14 and 17 hours, infants between 12 and 15 hours, toddlers between 11 and 14 hours, preschoolers between 10 and 13 hours, and school-aged children between 9 and 11 hours. For teenagers, 8 to 10 hours was considered appropriate, 7 to 9 hours for young adults and adults, and 7 to 8 hours of sleep for older adults. Conclusions Sufficient sleep duration requirements vary across the lifespan and from person to person. The recommendations reported here represent guidelines for healthy individuals and those not suffering from a sleep disorder. Sleep durations outside the recommended range may be appropriate, but deviating far from the normal range is rare. Individuals who habitually sleep outside the normal range may be exhibiting signs or symptoms of serious health problems or, if done volitionally, may be compromising their health and well-being.
Contrast-enhanced ultrasound imaging is a radiation-free diagnostic tool that uses biocompatible ultrasound contrast agents (UCAs) to improve image clarity. UCAs, which do not contain dye, often ...salvage “technically difficult” ultrasound scans, increasing the accuracy and reliability of a front-line ultrasound diagnosis, reducing unnecessary downstream testing, lowering overall health care costs, changing therapy, and improving patient care. Two UCAs currently are approved and regulated by the US Food and Drug Administration. They have favorable safety profiles and risk/benefit ratios in adult and pediatric populations, including compromised patients with severe cardiovascular diseases. Nevertheless, these UCAs are contraindicated in patients with known or suspected right-to-left, bidirectional, or transient right-to-left cardiac shunts. These patients, who constitute 10% to 35% of the general population, typically receive no UCAs when they undergo echocardiography. If their echocardiographic images are suboptimal, they may receive inappropriate diagnosis and treatment, or they may be referred for additional diagnostic testing, including radiation-based procedures that increase their lifetime risk for cancer or procedures that use contrast agents containing dye, which may increase the risk for kidney damage. An exhaustive review of current peer-reviewed research demonstrated no scientific basis for the UCA contraindication in patients with known or suspected cardiac shunts. Initial safety concerns were based on limited rodent data and speculation related to macroaggregated albumin microspheres, a radioactive nuclear imaging agent with different physical and chemical properties and no relation to UCAs. Radioactive macroaggregated albumin is not contraindicated in adult or pediatric patients with cardiac shunts and is routinely used in these populations. In conclusion, the International Contrast Ultrasound Society Board recommends removal of the contraindication to further the public interest in safe, reliable, radiation-free diagnostic imaging options for patients with known or suspected cardiac shunts and to reduce their need for unnecessary downstream testing.
Cardiac resynchronization therapy (CRT) reduces ventricular arrhythmia (VA) burden in some patients with heart failure, but its effect after left ventricular assist device (LVAD) implantation is ...unknown. We compared VA burden in patients with CRT devices in situ who underwent LVAD implantation and continued CRT (n = 39) to those who had CRT turned off before discharge (n = 26). Implantable cardioverter-defibrillator (ICD) shocks were significantly reduced in patients with continued CRT (1.5 ± 2.7 shocks per patient vs 5.5 ± 9.3 with CRT off, p = 0.014). There was a nonsignificant reduction in cumulative VA episodes per patient with CRT continued at discharge (42 ± 105 VA per patient vs 82 ± 198 with CRT off, p = 0.29). On-treatment analysis by whether CRT was on or off identified a significantly lower burden of VA (17 ± 1 per patient-year CRT on vs 37 ± 1 per patient-year CRT off, p <0.0001) and ICD shocks (1.2 ± 0.3 per patient-year CRT on vs 1.7 ± 0.3 per patient-year CRT off, p = 0.018). In conclusion, continued CRT is associated with significantly reduced ICD shocks and VA burden after LVAD implantation.
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