Citations

Key Points Using the largest set of patients with newly diagnosed myeloma, we identified 63 mutated driver genes. We identified oncogenic dependencies, particularly relating to primary translocations, indicating a nonrandom accumulation of genetic hits.

Abstract Neuromuscular choristoma (NMC) is a rare congenital nerve lesion that is classified by the presence of heterotopic muscle fibers intercalated within nerve fascicles. 1 The presence of NMC typically causes progressive neuropathy and bony/soft tissue undergrowth, often leading to a shortened atrophic limb. 2,3 The typical appearance of NMC on magnetic resonance imaging is an enlarged fusiform nerve that exhibits minimal gadolinium enhancement. 4 While there is increasing documentation of pathognomonic clinical and radiographic features for various diffuse fusiform peripheral nerve lesions, nerve biopsy is still occasionally required for some patients given the rarity of these diseases and progressive neuropathic features. The intraoperative appearance of NMC and its unique electrical stimulation properties are quite interesting. Intrafascicular replacement of nerve by skeletal muscle gives the nerve a red beefy color and causes the fascicles to contract with electrical stimulation. 5 In this video, we demonstrate the intraoperative appearance and contractile properties of NMC in a 60-yr-old woman with progressive sciatic neuropathy. Histologic and immunohistochemical studies identified a gradient of intralesional mature skeletal muscle within the NMC, with substantially fewer desmin-positive skeletal muscle fibers in the distal aspect. A gradient of contractility with intraoperative stimulation seemed to correlate with this pathology. These findings suggest that the lesional extent of NMC may not be clinically or grossly evident, reflecting a varying distribution of skeletal muscle within the affected nerve. The Mayo Clinic Institutional Review Board Office for Human Research Protection does not require approval for single participant case studies. The subject involved in this study was not identifiable and the general surgical consent form included permission for intraoperative photos and video.

Abstract Aims Type 2 diabetes (T2D) is strongly associated with cardiovascular morbidity and mortality in patients. Vascular large conductance Ca2+-activated potassium (BK) channels, composed of four pore-forming α subunits (BK-α), and four regulatory β1 subunits (BK-β1), are densely expressed in coronary arterial smooth muscle cells (SMCs) and play an important role in regulating vascular tone and myocardial perfusion. However, the role of BK channels in coronary microvascular dysfunction of human subjects with diabetes is unclear. In this study, we examined BK channel function and protein expression, and BK channel-mediated vasodilation in freshly isolated coronary arterioles from T2D patients. Methods and results Atrial tissues were obtained from 16 patients with T2D and 25 matched non-diabetic subjects during cardiopulmonary bypass procedure. Microvessel videomicroscopy and immunoblot analysis were performed in freshly dissected coronary arterioles and inside-out single BK channel currents was recorded in enzymatically isolated coronary arteriolar SMCs. We found that BK channel sensitivity to physiological Ca2+ concentration and voltage was downregulated in the coronary arteriolar SMCs of diabetic patients, compared with non-diabetic controls. BK channel kinetics analysis revealed that there was significant shortening of the mean open time and prolongation of the mean closed time in diabetic patients, resulting in a remarkable reduction of the channel open probability. Functional studies showed that BK channel activation by dehydrosoyasaponin-1 was diminished and that BK channel-mediated vasodilation in response to shear stress was impaired in diabetic coronary arterioles. Immunoblot experiments confirmed that the protein expressions of BK-α and BK-β1 subunits were significantly downregulated, but the ratio of BK-α/BK-β1 was unchanged in the coronary arterioles of T2D patients. Conclusions Our results demonstrated for the first time that BK channel function and BK channel-mediated vasodilation were abnormal in the coronary microvasculature of diabetic patients, due to decreased protein expression and altered intrinsic properties of BK channels.

Background Peer-to-peer advisory among colleagues in orthopedic surgery is commonplace in academic medical centers. In the private practice setting, however, it becomes more difficult for surgeons to discuss complex cases among peers. Purpose/Questions We sought to study the effect of peer-to-peer mentorship on surgeons’ decision-making and on patient care across academic and private adult joint reconstruction practices via the use of group secured messages. Methods From 2013 to 2016, we established a messaging system that was compliant with the Health Insurance Portability and Accountability Act (HIPAA) among five previous adult hip and knee reconstruction co-fellows in order to discuss complex cases. Data collected from each case included patient demographics (age and sex), history and physical examination, relevant imaging in orthogonal planes, and preliminary diagnosis and treatment plans. Data collected from group responses included nature of additional inquiries, literature citations, operative recommendations, and sample imaging of similar cases previously treated. Results The group consisted of two private practice surgeons and three academic surgeons. Data was collected on 283 cases discussed during the study period. None of the patients had any HIPAA violations. The mean number of reviewers who commented on a case was 2.4, with at least one response in 97% of cases. In 33% of the cases, the peers confirmed the initial treatment plan, and in 67% of the cases, an alternative treatment plan was recommended and executed. The case distribution was 94 primary and 189 revision procedures, including 173 hips, 103 knees, three ankles, two shoulders, and two pelvises. Conclusion In the majority of cases exchanged between young surgeons via a group messaging system, a significant impact on patient care was appreciated. In a technology-driven era, peer-to-peer advisory for difficult cases via a rapid feedback method may allow for substantial improvement in patient care, particularly for surgeons not practicing at a large academic medical center with access to several partners and multiple opinions.

OBJECTIVE The overall risk of ischemic stroke from a chronically occluded internal carotid artery (COICA) is around 5%–7% per year despite receiving the best available medical therapy. Here, authors propose a radiographic classification of COICA that can be used as a guide to determine the technical success and safety of endovascular recanalization for symptomatic COICA and to assess the changes in systemic blood pressure following successful revascularization. METHODS The radiographic images of 100 consecutive subjects with COICA were analyzed. A new classification of COICA was proposed based on the morphology, location of occlusion, and presence or absence of reconstitution of the distal ICA. The classification was used to predict successful revascularization in 32 symptomatic COICAs in 31 patients, five of whom were female (5/31 [16.13%]). Patients were included in the study if they had a COICA with ischemic symptoms refractory to medical therapy. Carotid artery occlusion was defined as 100% cross-sectional occlusion of the vessel lumen as documented on CTA or MRA and confirmed by digital subtraction angiography. RESULTS Four types (A–D) of radiographic COICA were identified. Types A and B were more amenable to safe revascularization than types C and D. Recanalization was successful at a rate of 68.75% (22/32 COICAs; type A: 8/8; type B: 8/8; type C: 4/8; type D: 2/8). The perioperative complication rate was 18.75% (6/32; type A: 0/8 [0%]; type B: 1/8 [12.50%]; type C: 3/8 [37.50%], type D: 2/8 [25.00%]). None of these complications led to permanent morbidity or death. Twenty (64.52%) of 31 subjects had improvement in their symptoms at the 2–6 months’ follow-up. A statistically significant decrease in systolic blood pressure (SBP) was noted in 17/21 (80.95%) patients who had successful revascularization, which persisted on follow-up (p = 0.0001). The remaining 10 subjects in whom revascularization failed had no significant changes in SBP (p = 0.73). CONCLUSIONS The pilot study suggested that our proposed classification of COICA may be useful as an adjunctive guide to determine the technical feasibility and safety of revascularization for symptomatic COICA using endovascular techniques. Additionally, successful revascularization may lead to a significant decrease in SBP postprocedure. A Phase 2b trial in larger cohorts to assess the efficacy of endovascular revascularization using our COICA classification is warranted.

Abstract This Consensus Document is the first of two reports summarizing the views of an expert panel organized by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on the clinical use of intracoronary imaging including intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The first document appraises the role of intracoronary imaging to guide percutaneous coronary interventions (PCIs) in clinical practice. Current evidence regarding the impact of intracoronary imaging guidance on cardiovascular outcomes is summarized, and patients or lesions most likely to derive clinical benefit from an imaging-guided intervention are identified. The relevance of the use of IVUS or OCT prior to PCI for optimizing stent sizing (stent length and diameter) and planning the procedural strategy is discussed. Regarding post-implantation imaging, the consensus group recommends key parameters that characterize an optimal PCI result and provides cut-offs to guide corrective measures and optimize the stenting result. Moreover, routine performance of intracoronary imaging in patients with stent failure (restenosis or stent thrombosis) is recommended. Finally, strengths and limitations of IVUS and OCT for guiding PCI and assessing stent failures and areas that warrant further research are critically discussed.

Background: Heterologous functional validation studies of putative long-QT syndrome subtype 2–associated variants clarify their pathological potential and identify disease mechanism(s) for most variants studied. The purpose of this study is to clarify the pathological potential for rare nonsynonymous KCNH2 variants seemingly associated with sudden infant death syndrome. Methods: Genetic testing of 292 sudden infant death syndrome cases identified 9 KCNH2 variants: E90K, R181Q, A190T, G294V, R791W, P967L, R1005W, R1047L, and Q1068R. Previous studies show R181Q-, P967L-, and R1047L-Kv11.1 channels function similar to wild-type Kv11.1 channels, whereas Q1068R-Kv11.1 channels accelerate inactivation gating. We studied the biochemical and biophysical properties for E90K-, G294V-, R791W-, and R1005W-Kv11.1 channels expressed in human embryonic kidney 293 cells; examined the electronic health records of patients who were genotype positive for the sudden infant death syndrome–linked KCNH2 variants; and simulated their functional impact using computational models of the human ventricular action potential. RESULTS: Western blot and voltage-clamping analyses of cells expressing E90K-, G294V-, R791W-, and R1005W-Kv11.1 channels demonstrated these variants express and generate peak Kv11.1 current levels similar to cells expressing wild-type-Kv11.1 channels, but R791W- and R1005W-Kv11.1 channels accelerated deactivation and activation gating, respectively. Electronic health records of patients with the sudden infant death syndrome–linked KCNH2 variants showed that the patients had median heart rate–corrected QT intervals <480 ms and none had been diagnosed with long-QT syndrome or experienced cardiac arrest. Simulating the impact of dysfunctional gating variants predicted that they have little impact on ventricular action potential duration. Conclusions: We conclude that these rare Kv11.1 missense variants are not long-QT syndrome subtype 2–causative variants and therefore do not represent the pathogenic substrate for sudden infant death syndrome in the variant-positive infants.

AbstractObjectivesBoth projection and dual‐energy (DE)‐based methods have been used for metal artifact reduction (MAR) in CT. The two methods can also be combined. The purpose of this work was to evaluate these three MAR methods using phantom experiments for five types of metal implants.Materials and MethodsFive phantoms representing spine, dental, hip, shoulder, and knee were constructed with metal implants. These phantoms were scanned using both single‐energy (SE) and DE protocols with matched radiation output. The SE data were processed using a projection‐based MAR (iMAR, Siemens) algorithm, while the DE data were processed to generate virtual monochromatic images at high keV (Mono+, Siemens). In addition, the DE images after iMAR were used to generate Mono+ images (DE iMAR Mono+). Artifacts were quantitatively evaluated using CT numbers at different regions of interest. Iodine contrast‐to‐noise ratio (CNR) was evaluated in the spine phantom. Three musculoskeletal radiologists and two neuro‐radiologists independently ranked the artifact reduction.ResultsThe DE Mono+ at high keV resulted in reduced artifacts but also lower iodine CNR. The iMAR method alone caused missing tissue artifacts in dental phantom. DE iMAR Mono+ caused wrong CT numbers in close proximity to the metal prostheses in knee and hip phantoms. All musculoskeletal radiologists ranked SE iMAR > DE iMAR Mono+ > DE Mono+ for knee and hip, while DE iMAR Mono+ > SE iMAR > DE Mono+ for shoulder. Both neuro‐radiologists ranked DE iMAR Mono+ > DE Mono+ > SE iMAR for spine and DE Mono+ > DE iMAR Mono+ > SE iMAR for dental.ConclusionsThe SE iMAR was the best choice for the hip and knee prostheses, while DE Mono+ at high keV was best for dental implants and DE iMAR Mono+ was best for spine and shoulder prostheses. Artifacts were also introduced by MAR algorithms.