Citations

Over 20 years of research has led to the now widely accepted role of cardiac resynchronization therapy (CRT) in medically refractory, mild to severe systolic heart failure (HF) with increased QRS duration. In addition to conferring a mortality benefit, CRT has been shown to reduce HF hospitalization rates and improve functional status in this population. However, not all patients consistently demonstrate a positive response to CRT. Efforts to improve response to CRT have focused on improving patient selection and optimizing device implantation and follow-up, thereby correcting electrical and mechanical dyssynchrony. In this article we review the pathobiology of cardiac dyssynchrony, the rationale for the use of CRT, the history and the state of the art of CRT, and guidelines and recommendations for CRT, while also focusing on the areas of controversy and potential future applications.

Abstract The proliferation of cardiac-related biomarkers and advocacy for their use has often come without adequate discussion of limitations in the interpretation of values and their best use in heart failure (HF) patients to provide a balanced assessment of how cardiac biomarkers are advocated for use in HF and areas where we would argue there are no gaps in knowledge. We include suggestions to address these issues. We have focused on peer-reviewed publications over the period 2000 to present. Most studies have used samples at one or at most two points in time to define risk. Although biomarkers might add to the magnitude of risk, it is unclear how often they lead to changes in treatment. We suggest that defining the use of serial biomarker testing over time would be more helpful. To do this, it is necessary to take into account the biomarker's analytical and biological variability in addition to its ability to define and monitor therapy. These factors are often overlooked leading to conclusions that may be statistically significant but not clinically or analytically robust. An appreciation of the value and limitations of biomarker use is important to all clinicians who manage HF patients. If the proper studies are done so that biomarkers are used optimally, they will likely be helpful in defining when and how to intervene. If we continue as we have, we will continue to have ambiguity about the use of these valuable probes in the assessment and management of HF.

Background and Purpose— Vertebrobasilar, nonsaccular, and dolichoectatic aneurysms generally have a poor natural history. We performed a study examining the natural history of vertebrobasilar, nonsaccular, and dolichoectatic aneurysms receiving serial imaging and studied imaging characteristics associated with growth and rupture. Methods— We included all vertebrobasilar dolichoectatic, fusiform, and transitional aneurysms with serial imaging follow-up seen at our institution over a 15-year period. Two radiologists and a neurologist evaluated aneurysms for size, type, mural T1 signal, mural thrombus, daughter sac, mass effect, and tortuosity. Primary outcomes were aneurysm growth or rupture. Univariate analysis was performed with chi-squared tests for categorical variables and Student’s t test or analysis of variance for continuous variables. Multivariate logistic regression analysis was performed to identify variables independently associated with aneurysm growth or rupture. Results— One hundred and fifty-two patients with 542 patient-years (mean 3.6±3.5 years) of imaging follow-up were included. Aneurysms were fusiform in 45 cases (29.6%), dolichoectatic in 75 cases (49.3%), and transitional in 32 cases (21.1%). Thirty-five aneurysms (23.0%) grew (growth rate=6.5%/year). Eight aneurysms (5.3%) ruptured (rupture rate=1.5%/year). Variables associated with growth and rupture on univariate analysis were size >10 mm (57.6% versus 16.0%, P <0.0001), mural T1 signal (39.7% versus 16.3%, P =0.001), daughter sac (56.3% versus 21.3%), and mural thrombus (45.5% versus 13.4%, P <0.0001). 26.7% of fusiform aneurysms, 9.3% of dolichoectatic aneurysms, and 59.4% of transitional aneurysms grew or ruptured ( P <0.0001). The only variable independently associated with rupture was transitional morphology ( P =0.003). Conclusions— Vertebrobasilar, nonsaccular, and dolichoectatic aneurysms are associated with a poor natural history with high growth and rupture rates. Further research is needed to determine the best treatments for this disease.

ObjectiveThe aim of this work was to evaluate the preprogressive phase in subjects with radiologically isolated syndrome (RIS) who evolve to primary progressive multiple sclerosis (PPMS).MethodsA multicenter RIS cohort was previously established. Demographic, clinical, and radiological characteristics of subjects with RIS that evolved directly to PPMS were compared to those that developed a relapsing disease course from onset (clinically isolated syndrome [CIS] or relapsing‐remitting MS) and were also compared to two other population‐ and clinic‐based PPMS cohorts.ResultsOf the 453 subjects with RIS, 128 evolved to symptomatic MS during the follow‐up (113 developed a first acute clinical event consistent with CIS/MS, 15 evolved to PPMS). PPMS prevalence (11.7%) and onset age (mean ± standard deviation; 49.1 ± 12.1) in the RIS group were comparable to other PPMS populations (p > 0.05). Median time to PPMS was 3.5 years (range, 1.6–5.4). RIS evolved to PPMS more commonly in men (p = 0.005) and at an older age (p < 0.001) when compared to CIS/MS, independent of follow‐up duration. Subjects who evolved to PPMS had more spinal cord lesions (100%) before symptomatic evolution than those that developed CIS/MS (64%) and those that remained asymptomatic (23%) within the follow‐up period (P = 0.005). Other MRI characteristics in the preprogressive phase of PPMS were indistinguishable from CIS/MS.InterpretationSubjects with RIS evolve to PPMS at the same frequency as expected from general MS populations in an age‐dependent manner. Besides age, unequivocal presence of spinal cord lesions and being male predicted evolution to PPMS. Our findings further suggest that RIS is biologically part of the MS spectrum. Ann Neurol 2016;79:288–294

Hyperviscosity syndrome is clinically manifested by oronasal bleeding, retinal hemorrhages, and variable neurological symptoms. It occurs when resistance to flow of blood increases sharply, resulting in impaired transit through the microcirculatory system. The most common cause of hyperviscosity is increased concentrations of gamma globulins, either monoclonal in malignant disease or polyclonal, usually seen with rheumatic disorders. Increased numbers of red blood cells, as in polycythemia vera, can result in viscous blood. Extreme increases in concentrations of mature and immature white blood cells can also produce hyperviscosity. Treatment with plasma exchange is required when the clinical syndrome is symptomatic. Although plasma exchange is not a completely benign procedure, it represents the most effective method of controlling hyperviscosity.

Background: A previously published study found positive outcomes for a novel technique for ultrasound-guided percutaneous ultrasonic tenotomy, showing good tolerability, safety, and early efficacy within an office setting. Purpose: In this follow-up study, all 20 members of the original cohort were contacted after 3 years to explore the sustainability of symptomatic relief, functional improvement, and sonographic soft tissue response for percutaneous ultrasonic tenotomy. Study Design: Case series; Level of evidence, 4. Methods: All 20 subjects of the clinical trial that was performed from June to November 2011 were further assessed at 36 months after the procedure in terms of visual analog scale for pain, Disabilities of the Arm, Shoulder and Hand (DASH)–Compulsory/Work scores, need for adjunct procedures, and overall satisfaction. Importantly, all 20 were reassessed with ultrasound imaging at 36 months, and evidence of the common extensor tendon response was assessed in terms of tendon hypervascularity, tendon thickness, and the progress of the hypoechoic scar tissue. Results: A 100% clinical follow-up was achieved, inclusive of ultrasonographic assessment. None of the subjects required further treatment procedures, and 100% expressed satisfaction. Previous improvements in visual analog scale (current median ± SD, 0 ± 0.9; range, 0-3) and DASH-Work scores (current median, 0 ± 0) were sustained with conformity to a linear pattern on polynomial measures. There was further reduction in DASH-Compulsory scores to a median of 0 ± 0.644 (range, 0-2) with a significant decrease on repeated measures ( P = .008). Tendon hypervascularity was resolved in 94% of patients, and 100% had reduction in tendon thickness. Overall reduction in the hypoechoic scar tissue was observed in all subjects, with a 90% response achieved by 6 months. Between 6 and 36 months, further reduction in the scar was observed in around 60% of patients, with 20% of patients having complete resolution of the hypoechoic scar. Conclusion: Minimally invasive percutaneous ultrasonic tenotomy provided sustained pain relief and functional improvement for recalcitrant tennis elbow at 3-year follow-up. It is one of the few procedures to demonstrate positive sonographic evidence of tissue-healing response and is an attractive alternative to surgical intervention for definitive treatment of recalcitrant elbow tendinopathy.

Abstract Background: The need to develop valid methods for sampling and analyzing fecal specimens for microbiome studies is increasingly important, especially for large population studies. Methods: Some of the most important attributes of any sampling method are reproducibility, stability, and accuracy. We compared seven fecal sampling methods [no additive, RNAlater, 70% ethanol, EDTA, dry swab, and pre/post development fecal occult blood test (FOBT)] using 16S rRNA microbiome profiling in two laboratories. We evaluated nine commonly used microbiome metrics: abundance of three phyla, two alpha-diversities, and four beta-diversities. We determined the technical reproducibility, stability at ambient temperature, and accuracy. Results: Although microbiome profiles showed systematic biases according to sample method and time at ambient temperature, the highest source of variation was between individuals. All collection methods showed high reproducibility. FOBT and RNAlater resulted in the highest stability without freezing for 4 days. In comparison with no-additive samples, swab, FOBT, and 70% ethanol exhibited the greatest accuracy when immediately frozen. Conclusions: Overall, optimal stability and reproducibility were achieved using FOBT, making this a reasonable sample collection method for 16S analysis. Impact: Having standardized method of collecting and storing stable fecal samples will allow future investigations into the role of gut microbiota in chronic disease etiology in large population studies. Cancer Epidemiol Biomarkers Prev; 25(2); 407–16. ©2015 AACR.

Twenty-three patients with clinical signs of adjacent intermetatarsal nerve irritation who underwent adjacent nerve release with single-nerve excision through one incision were studied. Mean follow-up was 11 months. Of 21 patients interviewed, 19 (90%) had resolution of all or most of their pain, 20 (95%) had no or only minimal activity limitation, and 20 (95%) were completely satisfied with their outcome. Of 19 patients examined, none had pain with compression of the interspace of the excised nerve, although two (11%) had discomfort with compression of the interspace of the nerve that was only released. Protective sensation was present postoperatively in all patients except one who had preoperative neuropathy.