Dofetilide for the treatment of premature ventricular complexes and ventricular tachycardia in patients with structural heart disease.

BACKGROUND: Dofetilide is a class III antiarrhythmic agent approved for the treatment of atrial fibrillation and atrial flutter. Given the efficacy of other class III agents, it has been used off-label for the treatment of premature ventricular complexes (PVCs) and ventricular tachycardias (VTs). OBJECTIVE: The purpose of this study was to determine the efficacy and safety of dofetilide for ventricular arrythmias (VAs). METHODS: In this retrospective cohort study, 81 patients (59 men; age = 60 ± 14 years; LVEF = 0.34 ± 0.16) were admitted for dofetilide initiation to treat PVCs (29), VTs (42) or both (10). A ≥ 80% decrease in PVC burden was defined as a satisfactory response. An ICD was present in 72 patients (89%). Another antiarrhythmic was previously used in 50 patients (62%). Prior catheter ablation had been performed in 33 patients (41%). RESULTS: During intitiation, dofetilide was discontinued in 12 patients (15%) due to QT prolongation (8) and inefficacy to suppress VAs (4). Among the 32 patients with PVCs who successfully started dofetilide, the mean PVC burden decreased from 20 ± 10% to 8 ± 8% at a median follow-up of 2.6 months (p < .001). PVC burden was reduced by ≥80% in only 11/32 patients (34%). During 7 ± 1 years of follow-up, 41/69 patients (59%) continued to have VAs and received appropriate ICD therapies for monomorphic VTs (35) and polymorphic VT/VF (6) at a median of 8.0 (IQR 2.6-33.2) months. Dofetilide had to be discontinued in 50/69 patients (72%) due to inefficacy or intolerance. The composite outcome of VT/VF recurrence, heart transplantation, or death occurred in 6/12 patients (50%) without dofetilide and 49/69 patients (71%) with dofetilide. The event free survival was similar between patients treated with and without dofetilide (log-rank p = .55). CONCLUSIONS: Treatment with dofetilide was associated with a decrease in PVCs, however clinically significant suppression occurred in a minority of patients. Dofetilide failed to suppress the occurrence of VTs in a majority of patients.

Efficacy of a Multimodal Surgical Site Injection for Postoperative Pain Control in Pediatric Patients With Cerebral Palsy Undergoing Hip Reconstruction: A Randomized Controlled Trial.

BACKGROUND: One in 4 children with cerebral palsy (CP) will undergo orthopaedic surgery during their childhood. Despite its ubiquity, postoperative pain control has been poorly studied in this patient population. Moreover, poor pain management has been associated with adverse surgical outcomes. Multimodal analgesic injections have been well studied in the adult population, demonstrating safety and efficacy in reducing postoperative pain and narcotic consumption, but this modality has not been studied in pediatric patients undergoing similarly complex procedures. The objective of this study was to evaluate the efficacy of a multimodal surgical site injection for postoperative pain control following operative management of hip dysplasia in patients with CP. METHODS: After obtaining IRB approval, a multicenter, randomized double-blind placebo control trial was completed. Patients below 18 years old with a diagnosis of CP who were scheduled for varus derotation osteotomy (VDRO) of the proximal femur were randomized to receive a surgical-site injection with either a combination of ropivacaine (3 mg/kg), epinephrine (0.5 mg), and ketorolac (0.5 mg/kg) (experimental group) or normal saline (control). All included patients had identical postoperative care, including immobilization, physical therapy, and standardized, multimodal postoperative pain control. Pain scores and narcotic consumption were recorded at regular intervals and compared between groups utilizing two-tailed t test or a nonparametric Mann-Whitney test for quantitative variables and a Fischer exact test for categorical variables. RESULTS: Thirty-four patients were included, evenly divided between study arms. There were no significant differences in demographic variables, gross motor function classification system (GMFCS), comorbidities, preoperative radiographic parameters, or concomitant surgeries between groups. Patients in the experimental group required significantly lower narcotic medications at all postoperative time points from PACU until hospital discharge compared with controls (0.41 ± 0.42 vs. 1.87 ± 2.05 total morphine mEQ/kg, P=0.01). Similarly, patients in the experimental group were found to have significantly lower pain scores throughout their hospital stays compared with controls (1.0 ± 0.6 vs. 2.4 ± 1.1 mean pain score, P<0.001). There were no significant differences in operative time, OR time, blood transfusion requirements or hospital length of stay between groups. There were no adverse medication reactions or injection site complications in either group. CONCLUSIONS: In patients with CP undergoing hip reconstruction, surgical-site injection with a multimodal analgesic combination improves pain control and reduces narcotic consumption in the early postoperative period with no observed adverse effects. SIGNIFICANCE: Local multimodal analgesic injections should be adopted as part of standard multimodal pain control in this patient population for all osseous surgeries. LEVEL OF EVIDENCE: Level I-therapeutic.

Cardiac Involvement and Arrhythmias Associated with Myotonic Dystrophy.

Myotonic dystrophy is an autosomal dominant genetic disease of nucleotide expansion resulting in neuromuscular disease with two distinct subtypes. There are significant systemic manifestations of this condition including progressive muscular decline, neurologic abnormalities, and cardiac disease. Given the higher prevalence of cardiac dysfunction compared to the general population, there is significant interest in early diagnosis and prevention of cardiac morbidity and mortality. Cardiac dysfunction has an origin in abnormal and unstable nucleotide repeats in the DMPK and CNBP genes which have downstream effects leading to an increased propensity for arrhythmias and left ventricular systolic dysfunction. Current screening paradigms involve the use of routine screening electrocardiograms, ambulatory electrocardiographic monitors, and cardiac imaging to stratify risk and suggest further invasive evaluation. The most common cardiac abnormality is atrial arrhythmia, however there is significant mortality in this population from high-degree atrioventricular block and ventricular arrhythmia. In this review, we describe the cardiac manifestations of myotonic dystrophy with an emphasis on arrhythmia which is the second most common cause of death in this population after respiratory failure.

Low-cost, high-precision micro-lensed optical fiber providing deep-micrometer to deep-nanometer-level light focusing.

A new type of micro-lensed optical fiber through stacking appropriate high-refractive microspheres at designed locations with respect to the cleaved end of an optical fiber is numerically and experimentally demonstrated. This new type of micro-lensed optical fiber can be precisely constructed with low cost and high speed. Deep micrometer-scale and submicrometer-scale far-field light spots can be achieved when the optical fibers are multimode and single mode, respectively. By placing an appropriate teardrop dielectric nanoscale scatterer at the far-field spot of this new type of micro-lensed optical fiber, a deep-nanometer near-field spot can also be generated with high intensity and minimum joule heating, which is valuable in high-speed, high-resolution, and high-power nanoscale detection compared with traditional near-field optical fibers containing a significant portion of metallic material.

A Rapid MRI Protocol for the Evaluation of Acute Pediatric Musculoskeletal Infections: Eliminating Contrast and Decreasing Anesthesia, Scan Time, and Hospital Length of Stay and Charges.

BACKGROUND: Acute musculoskeletal infection affects >1 in 6,000 children in the United States annually. Magnetic resonance imaging (MRI) is the gold standard for the diagnosis of musculoskeletal infection, but it traditionally requires contrast and anesthesia for children, delaying management. A rapid MRI protocol involves MRI without anesthesia and with limited non-contrast sequences optimized for fluid detection and diffusion-weighted images to identify abscesses. We hypothesized that a rapid MRI protocol would improve imaging and treatment efficiency for pediatric patients undergoing musculoskeletal infection evaluation without substantially affecting accuracy. METHODS: This was a single-center, retrospective study of patients undergoing evaluation for musculoskeletal infection before (60 patients in the traditional cohort [TC]) and after (68 patients in the rapid cohort [RC]) implementation of the rapid MRI protocol. Sociodemographic and clinical variables were extracted from electronic health records, and statistical comparisons were performed. RESULTS: The anesthesia rates were 53% for the TC and 4% for the RC, and the contrast administration rates were 88% for the TC and 0% for the RC. The median time to MRI after ordering was 6.5 hours (95% confidence interval [CI], 5.0 to 8.6 hours) for the TC and 2.2 hours (95% CI, 1.4 to 3.6 hours) for the RC (p < 0.01). The median duration of MRI was 63.2 minutes (95% CI, 56.8 to 69.6 minutes) for the TC and 24.0 minutes (95% CI, 21.1 to 29.5 minutes) for the RC (p < 0.01). The median hospital length of stay was 5.3 days (95% CI, 3.7 to 6.9 days) for the TC and 3.7 days (95% CI, 1.9 to 4.1 days) for the RC (p < 0.01). The median hospital charges were $47,309 (95% CI, $39,137 to $58,769) for the TC and $32,824 (95% CI, $22,865 to $45,339) for the RC (p < 0.01). Only 2 positive cases of musculoskeletal infection in the RC were missed on the initial imaging, but these instances were not attributable to the rapid protocol itself. Although 10 of 68 rapid MRI scans resulted in nondiagnostic outcomes due to patient motion, only 6 of 68 required repeat MRI with anesthesia. CONCLUSIONS: In patients evaluated for musculoskeletal infection, the rapid MRI protocol eliminated contrast and minimized anesthesia while improving MRI access and decreased scan and interpretation times, hospital length of stay, and hospital charges. The rapid MRI protocol had high sensitivity for diagnosing musculoskeletal infection and a low rate of imaging failure. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Complications of catheter ablation for ventricular tachycardia.

With the increasing literature demonstrating benefits of catheter ablation for ventricular tachycardia (VT), the number of patients undergoing VT ablation has increased dramatically. As VT ablation is being performed more routinely, operators must be aware of potential complications of VT ablation. This review delves deeper into the practice of VT ablation with a focus on periprocedural complications.

Effect of Transcutaneous Magnetic Stimulation in Patients With Ventricular Tachycardia Storm: A Randomized Clinical Trial.

IMPORTANCE: Autonomic neuromodulation provides therapeutic benefit in ventricular tachycardia (VT) storm. Transcutaneous magnetic stimulation (TcMS) can noninvasively and nondestructively modulate a patient's nervous system activity and may reduce VT burden in patients with VT storm. OBJECTIVE: To evaluate the safety and efficacy of TcMS of the left stellate ganglion for patients with VT storm. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, sham-controlled randomized clinical trial took place at a single tertiary referral center between August 2019 and July 2021. The study included 26 adult patients with 3 or more episodes of VT in 24 hours. INTERVENTIONS: Patients were randomly assigned to receive a single session of either TcMS that targeted the left stellate ganglion (n = 14) or sham stimulation (n = 12). MAIN OUTCOMES AND MEASURES: The primary outcome was freedom from VT in the 24-hour period following randomization. Key secondary outcomes included safety of TcMS on cardiac implantable electronic devices, as well as burden of VT in the 72-hour period following randomization. RESULTS: Among 26 patients (mean [SD] age, 64 [13] years; 20 [77%] male), a mean (SD) of 12.7 (10.3) episodes of VT occurred within the 24 hours preceding randomization. Patients had recurrent VT despite taking a mean (SD) of 2.0 (0.6) antiarrhythmic drugs (AADs), and 11 patients (42%) required mechanical hemodynamic support at the time of randomization. In the 24-hour period after randomization, VT recurred in 4 of 14 patients (29% [SD 47%]) in the TcMS group vs 7 of 12 patients (58% [SD 51%]) in the sham group (P = .20). In the 72-hour period after randomization, patients in the TcMS group had a mean (SD) of 4.5 (7.2) episodes of VT vs 10.7 (13.8) in the sham group (incidence rate ratio, 0.42; P < .001). Patients in the TcMS group were taking fewer AADs 24 hours after randomization compared with baseline (mean [SD], 0.9 [0.8] vs 1.8 [0.4]; P = .001), whereas there was no difference in the number of AADs taken for the sham group (mean [SD], 2.3 [0.8] vs 1.9 [0.5]; P = .20). None of the 7 patients in the TcMS group with a cardiac implantable electronic device had clinically significant effects on device function. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, findings support the potential for TcMS to safely reduce the burden of VT in the setting of VT storm in patients with and without cardiac implantable electronic devices and inform the design of future trials to further investigate this novel treatment approach. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04043312.

Investigations of the Y chromosome, male founder structure and YSTR mutation rates in the Old Order Amish.

OBJECTIVES: Using Y chromosome short tandem repeat (YSTR) genotypes, (1) evaluate the accuracy and completeness of the Lancaster County Old Order Amish (OOA) genealogical records and (2) estimate YSTR mutation rates. METHODS: Nine YSTR markers were genotyped in 739 Old Order Amish males who participated in several ongoing genetic studies of complex traits and could be connected into one of 28 all-male lineage pedigrees constructed using the Anabaptist Genealogy Database and the query software Ped-Hunter. A putative founder YSTR haplotype was constructed for each pedigree, and observed and inferred father-son transmissions were used to estimate YSTR mutation rates. RESULTS: We inferred 27 distinct founder Y chromosome haplotypes in the 28 male lineages, which encompassed 27 surnames accounting for 98% of Lancaster OOA households. Nearly all deviations from founder haplotypes were consistent with mutation events rather than errors. The estimated marker-specific mutation rates ranged from 0 to 1.09% (average 0.33% using up to 283 observed meioses only and 0.28% using up to 1,232 observed and inferred meioses combined). CONCLUSIONS: These data confirm the accuracy and completeness of the male lineage portion of the Anabaptist Genealogy Database and contribute mutation rate estimates for several commonly used Y chromosome STR markers.

Osteoporosis-pseudoglioma syndrome: description of 9 new cases and beneficial response to bisphosphonates.

Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive disorder of severe juvenile osteoporosis and congenital blindness, due to mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. Approximately fifty cases of OPPG have been reported. We report 9 new cases of OPPG, in three related nuclear families of Conservative Mennonites in Pennsylvania. All 9 children with OPPG were blind and had osteoporosis. Four of six parents had low bone mineral density (BMD) or osteoporosis; 2 were normal. Sequence analysis from genomic DNA revealed homozygosity for a nonsense mutation of exon 6 of LRP5 (W425X) in four OPPG cases tested in families A and C. In family B, OPPG cases were compound heterozygotes for the exon 6 W425X LRP5 mutation and a second exon 6 mutation (T409A); bone phenotype was milder than in family A. Neither of these mutations was present in an unrelated normal. The four treated OPPG patients all responded to bisphosphonates (duration 1.5-6.5 years) with improvement in Z-scores. One patient had a negligible response to teriparatide. In summary, we report 9 new cases of OPPG due to two novel LRP5 mutations, note a milder bone phenotype but similar ocular phenotype in LRP5 W425X/T409A compound heterozygotes than in W425X homozygotes and describe positive response to bisphosphonate treatment in four cases.