Citations

Objective To report a retrospective analysis of patients with migraine headaches treated with rimabotulinumtoxin B as preventive treatment, investigating an association between clinical responsiveness with migraine directionality and migrainous aura. Background The P hase III R esearch E valuating M igraine P rophylaxis T herapy studies demonstrated onabotulinumtoxin A is effective in the preventive management of chronic migraine headaches. J akubowski et al reported greater response to onabotulinumtoxin A in migraine patients reporting inward‐directed head pain (imploding or ocular) compared with outward‐directed head pain (exploding), suggesting subpopulations of patients may be better candidates for its use. No correlation was found between those reporting migrainous aura and onabotulinumtoxin A responsiveness. Methods One hundred twenty‐eight migraine patients were identified who had received rimabotulinumtoxin B injections over an average of 22 months, or 7 injection cycles. Migraine directionality was reported as inward directed (imploding, n = 72), eye centered (ocular, n = 28), outward directed (exploding, n = 16), and mixed (n = 12). Results One hundred two out of one hundred twenty‐eight patients (80%) improved; of these, 58 (57%) demonstrated a >75% reduction in monthly headache frequency (“>75%‐responders”), 76% of which noted sustained benefits >12 months with repeated injections every 10‐12 weeks. Those reporting ocular‐ and imploding‐directed headaches were significantly more likely to be >75%‐responders, compared with exploding‐ and mixed‐directed headaches ( P < .0025). Patients with ocular‐directed headaches were most likely to be sustained >75%‐responders. Patients reporting migrainous aura were more likely to be >75%‐responders ( P = .0007). Those reporting exploding‐ and mixed‐directed headaches were more likely to be nonresponders ( P < .0001). Conclusions Reported migraine directionality and presence of migrainous aura predict migraine headache responsiveness to rimabotulinumtoxin B injections.

Objective Emerging off-pump beating heart valve repair techniques offer patients less invasive alternatives for mitral valve (MV) repair. However, most of these techniques rely on the limited spatial and temporal resolution of transesophageal echocardiography (TEE) alone, which can make tool visualization and guidance challenging. Methods Using a magnetic tracking system and integrated sensors, we created an augmented reality (AR) environment displaying virtual representations of important intracardiac landmarks registered to biplane TEE imaging. In a porcine model, we evaluated the AR guidance system versus TEE alone using the transapically delivered NeoChord DS1000 system to perform MV repair with chordal reconstruction. Results Successful tool navigation from left ventricular apex to MV leaflet was achieved in 12 of 12 and 9 of 12 (P = 0.2) attempts with AR imaging and TEE alone, respectively. The distance errors of the tracked tool tip from the intended midline trajectory (5.2 ± 2.4 mm vs 16.8 ± 10.9 mm, P = 0.003), navigation times (16.7 ± 8.0 seconds vs 92.0 ± 84.5 seconds, P = 0.004), and total path lengths (225.2 ± 120.3 mm vs 1128.9 ± 931.1 mm, P = 0.003) were significantly shorter in the AR-guided trials compared with navigation with TEE alone. Furthermore, the potential for injury to other intracardiac structures was nearly 40-fold lower when using the AR imaging for tool navigation. The AR guidance also seemed to shorten the learning curve for novice surgeons. Conclusions Augmented reality–enhanced TEE facilitates more direct and safe intracardiac navigation of the NeoChord DS tool from left ventricular apex to MV leaflet. Tracked tool path results demonstrate fourfold improved accuracy, fivefold shorter navigation times, and overall improved safety with AR imaging guidance.

Background Two recent studies identified a mutation (p.Asp620Asn) in the vacuolar protein sorting 35 gene as a cause for an autosomal dominant form of Parkinson disease . Although additional missense variants were described, their pathogenic role yet remains inconclusive. Methods and results We performed the largest multi-center study to ascertain the frequency and pathogenicity of the reported vacuolar protein sorting 35 gene variants in more than 15,000 individuals worldwide. p.Asp620Asn was detected in 5 familial and 2 sporadic PD cases and not in healthy controls, p.Leu774Met in 6 cases and 1 control, p.Gly51Ser in 3 cases and 2 controls. Overall analyses did not reveal any significant increased risk for p.Leu774Met and p.Gly51Ser in our cohort. Conclusions Our study apart from identifying the p.Asp620Asn variant in familial cases also identified it in idiopathic Parkinson disease cases, and thus provides genetic evidence for a role of p.Asp620Asn in Parkinson disease in different populations worldwide.

Endoscopic ultrasonography (EUS) is the most sensitive imaging method for diagnosis of pancreatic tumors. However, it still has limits in the differentiation between pancreatic cancers and inflammatory tumor-like masses. A novel technology, contrast-enhanced harmonic EUS (CH-EUS), has been developed recently. It can visualize both parenchymal perfusion and microvasculature in pancreas without Doppler-related artifacts. Therefore, it is superior to EUS and CT in detecting small pancreatic masses and differential diagnosis of pancreatic masses. CH-EUS could be used for adequate sampling of pancreatic tumors and may predict the pathological features of the pancreatic solid lesions but still cannot replace EUS-FNA now.

Objective Identify novel prognostic factors for patients with peripartum cardiomyopathy (PPCM). Design and setting Prospective cohort study conducted in a single tertiary care centre in South Africa. Patients 176 African women with newly diagnosed PPCM were studied. Interventions Clinical assessment, echocardiography and laboratory results were obtained at baseline and at 6 months. Main outcome measures Poor outcome was defined as the combined end point of death, left ventricular (LV) ejection fraction (LVEF) < 35%, or remaining in New York Heart Association (NYHA) functional class III/IV at 6 months. Complete LV recovery was defined as LVEF ≥55% at 6 months. Results Forty-five (26%) patients had a poor outcome. Multiple logistic regression analysis revealed that, after adjustment for age, NYHA functional class, LVEF and systolic blood pressure, increased left ventricular end systolic dimension (LVESD), lower body mass index (BMI) and lower total cholesterol at baseline were independent predictors of poor outcome (adjusted OR 1.09, 95% CI 1.04 to 1.15, p=0.001; OR 0.89, 95% CI 0.83 to 0.96, p=0.004, and OR 0.50, 95% CI 0.34 to 0.73, p=0.0004, respectively). Thirty (21%) of the 141 surviving patients with echocardiographic follow-up recovered LV function at 6 months. Multiple logistic regression analysis revealed that, after adjustment for NYHA functional class, LVEF and left ventricular end diastolic dimension, older age and smaller LVESD at baseline were predictors of LV recovery (OR 1.08, 95% CI 1.01 to 1.17, p=0.02 and OR 0.92, 95% CI 0.86 to 0.98, p=0.007, respectively). Conclusions This study suggests that increased LVESD, lower BMI and lower serum cholesterol at baseline may be independent predictors of poor outcome in patients with PPCM, while older age and smaller LVESD at baseline appear to be independently associated with a higher chance of LV recovery.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple genetic risk factors, high levels of interferon alpha (IFN- α ), and the production of autoantibodies against components of the cell nucleus. Interferon regulatory factor 5 (IRF5) is a transcription factor which induces the transcription of IFN- α and other cytokines, and genetic variants of IRF5 have been strongly linked to SLE pathogenesis. IRF5 functions downstream of Toll-like receptors and other microbial pattern-recognition receptors, and immune complexes made up of SLE-associated autoantibodies seem to function as a chronic endogenous stimulus to this pathway. In this paper, we discuss the physiologic role of IRF5 in immune defense and the ways in which IRF5 variants may contribute to the pathogenesis of human SLE. Recent data regarding the role of IRF5 in both serologic autoimmunity and the overproduction of IFN- α in human SLE are summarized. These data support a model in which SLE-risk variants of IRF5 participate in a “feed-forward” mechanism, predisposing to SLE-associated autoantibody formation, and subsequently facilitating IFN- α production downstream of Toll-like receptors stimulated by immune complexes composed of these autoantibodies.

Despite advances in contemporary hip and knee arthroplasty, blood loss continues to be an issue. Though blood transfusion has long been used to treat post-operative anemia, the associated risks are well established. The objective of this article is to present two practical and effective approaches to minimising blood loss and transfusion rates in hip and knee arthroplasty: the use of antifibrinolytic medications such as tranexamic acid and the adoption of more conservative transfusion indications.

This conversation represents an attempt by several arthroplasty surgeons to critique several abstracts presented over the last year as well as to use them as a jumping off point for trying to figure out where they fit in into our current understanding of multiple issues in modern hip and knee arthroplasty.

Background Inherent to some immunobullous disorders is potential for intraepidermal or dermal–epidermal junction fragility, a phenomenon that may compromise biopsy specimen integrity and direct immunofluorescence (DIF) interpretation. In these situations, cutaneous adnexal structures (e.g. hair follicles, sweat apparatus) usually remain intact. Whether periadnexal DIF findings are reliable in diagnosing immunobullous conditions is unknown. Methods We evaluated 56 cutaneous specimens with diagnostic immunoglobulin (Ig) deposition patterns that contained adnexal structures. In a corollary study, we examined 145 hematoxylin‐eosin‐stained frozen specimens to determine biopsy factors associated with the presence of adnexal structures. Results Periadnexal DIF findings offered diagnostic sensitivity in conditions with linear or cell‐surface Ig deposition or lupus band. Periadnexal DIF findings were unreliable in dermatitis herpetiformis. Biopsy specimens from scalp and genitalia were most likely to contain folliculosebaceous units and sweat duct apparatus, respectively. Relative depth of biopsy correlated directly with the likelihood of identifying sweat duct apparatus but not folliculosebaceous units. Conclusions Periadnexal DIF findings may add diagnostic sensitivity in DIF evaluation of pemphigoid, pemphigus and lupus erythematosus. Pathologists can guide clinicians to biopsy certain anatomic sites and to obtain sufficient biopsy depth to increase the probability of capturing adnexal structures and, therefore, diagnostic yield from DIF specimens.