Background Arrhythmogenic cardiomyopathy (AC) is tightly associated with desmosomal mutations in the majority of patients. Arrhythmogenesis in AC patients is likely related to remodeling of cardiac gap junctions and increased levels of fibrosis. Recently, using experimental models, we also identified sodium channel dysfunction secondary to desmosomal dysfunction. The aim of the present study was to assess the immunoreactive signal levels of the sodium channel protein NaV1.5, as well as Connexin43 and Plakoglobin, in myocardial specimens obtained from AC patients. Methods Left and right ventricular free wall (LVFW/RVFW) post-mortem material was obtained from 5 AC patients and 5 age and sex-matched controls. RV septal biopsies (RVSB) were taken from another 15 AC patients. All patients fulfilled the 2010 revised Task Force Criteria for AC diagnosis. Immunohistochemical analyses were performed using antibodies against Connexin43 (Cx43), Plakoglobin, NaV1.5, Plakophilin-2 and N-Cadherin. Results N-Cadherin and Desmoplakin immunoreactive signals and distribution were normal in AC patients compared to control. Plakophilin-2 signals were unaffected unless a PKP2 mutation predicting haploinsufficiency was present. Distribution was unchanged compared to control. Immunoreactive signal levels of PKG, Cx43 and NaV1.5 were disturbed in 74%, 70% and 65% of the patients, respectively. Conclusions Reduced immunoreactive signal of PKG, Cx43 and NaV1.5 at the intercalated disks can be observed in a large majority of the patients. Decreased levels of Nav1.5 might contribute to arrhythmia vulnerability and, in the future, potentially could serve as a new clinically relevant tool for risk assessment strategies.

Purpose To assess the standardized implementation and reporting of surveillance [F]fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scan of the neck in locoregionally advanced head-and-neck squamous cell carcinoma (LAHNSCC) after concurrent chemoradiotherapy (CCRT). Patients and Methods We performed a prospective multicenter study of FDG-PET/CT scanning 12 weeks after CCRT in newly diagnosed patients with LAHNSCC (stage IVa/b) that used standardized reconstruction and Hopkins reporting criteria. The reference standard was histology or > 12 months of clinical follow-up. The primary outcome measure was the negative predictive value (NPV) of FDG-PET/CT scans and other supporting diagnostic test characteristics, including time dependency with increasing follow-up time. Results Of 152 patients, 125 had adequate primary tumor control after CCRT and entered follow-up (median, 20.4 months). Twenty-three (18.4%) had residual neck disease. Overall, NPV was 92.1% (95% CI, 86.9% to 95.3%; null hypothesis: NPV = 85%; P = .012) with sensitivity of 65.2% (95% CI, 44.9% to 81.2%), specificity of 91.2% (95% CI, 84.1% to 95.3%), positive predictive value of 62.5% (95% CI, 45.5% to 76.9%), and accuracy of 86.4% (95% CI, 79.3% to 91.3%). Sensitivity was time dependent and high for residual disease manifesting up to 9 months after imaging but lower (59.7%) for disease detected up to 12 months after imaging. Standardized reporting criteria reduced the number of equivocal reports (95% CI for the difference, 2.6% to 15.0%; P = .003). Test characteristics were not improved with the addition of lymph node CT morphology criteria. Conclusion FDG-PET/CT surveillance using Hopkins criteria 12 weeks after CCRT is reliable in LAHNSCC except for late manifesting residual disease, which may require an additional surveillance scan at 1 year after CCRT to be detected.

Pressure-induced RVF is associated with electrophysiologic remodeling of the atrophic LV.

The (18) F-FDG-PET-CT parameters are lower in HPV-positive than in HPV-negative patients. Low pretreatment SUV values in HPV-positive oropharyngeal SCC may be at least partly explained by HPV-induced tumor changes.

Sensory neurons and immune cells share a common microenvironmental niche for surveying tissue integrity. The immune and nervous systems both sense deviations in homeostasis and initiate protective responses and, upon malfunction, also jointly contribute to disease. Barrier tissues are heavily innervated by nociceptors, the sensory neurons that detect noxious stimuli, leading to pain and itch. The same tissues are also home to diverse immune cells that respond to infections and injury. The physical proximity of nociceptors and immune cells allows for direct local interactions between the two, independent of the CNS. We discuss in this study their ligand–receptor–based interactions and propose the need to shift from studying individual neuroimmune interactions to exploring the reciprocal neuroimmune interaction network in its entirety: the “neuroimmune interactome.” Identification of the nature of the interactome in health and its plasticity in disease will unravel the functional consequences of interactions between nociceptors and immune cells.

IMPORTANCE Endoscopic surgical decompression of the supratrochlear nerve (STN) and supraorbital nerve (SON) is a new treatment for patients with frontal chronic headache who are refractory to standard treatment options. OBJECTIVE To evaluate and compare treatment outcomes of oral medication, botulinum toxin type A (BoNT/A) injections, and endoscopic decompression surgery in frontal secondary headache attributed to STN and supraorbital SON entrapment. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of 22 patients from a single institution (Diakonessen Hospital Utrecht) with frontal headache of moderate-to-severe intensity (visual analog scale [VAS] score, 7-10), frontally located, experienced more than 15 days per month, and described as pressure or tension that intensifies with pressure on the area of STN and SON. A screening algorithm was used that included examination, questionnaire, computed tomography of the sinus, injections of local anesthetic, and BoNT/A in the corrugator muscle. INTERVENTIONS Different oral medication therapy for headache encountered in the study cohort, as well as BoNT/A injections (15 IU) into the corrugator muscle. Surgical procedures were performed by a single surgeon using an endoscopic surgical approach to release the supraorbital ridge periosteum and to bluntly dissect the glabellar muscle group. MAIN OUTCOMES AND MEASURES Headache VAS intensity after oral medication and BoNT/A injections. Additionally, early postoperative follow-up consisted of a daily headache questionnaire that was evaluated after 1 year. RESULTS In total, 22 patients (mean [SD] age, 42.0 [15.3] years; 7 men and 15 women) were included in this cohort study. Oral medication therapy reduced the headache intensity significantly (mean [standard error of the mean {SEM}] VAS score, 6.45 [0.20] [95% CI, 0.34-3.02; P < .001] compared with mean [SEM] pretreatment VAS score, 8.13 [0.22]). Botulinum toxin type A decreased the mean (SEM) headache intensity VAS scores significantly as well (pretreatment, 8.1 [0.22] vs posttreatment, 2.9 [0.42]; 95% CI, 3.89-6.56; P < .001). The mean (SEM) pretreatment headache intensity VAS score (8.10 [0.22]) decreased significantly after surgery at 3 months (1.30 [0.55]; 95% CI, 5.48-8.16; P < .001) and 12 months (1.09 [0.50]; 95% CI, 5.71-8.38; P < .001). There was a significant decrease of headache intensity VAS score in the surgical group over the BoNT/A group (mean [SEM] VAS score, 2.90 [0.42]) after 3 months (mean [SEM] VAS score, 1.30 [0.55]; 95% CI, 0.25-2.93; P < .001) and 12 months (mean [SEM] VAS score, 1.09 [0.50]; 95% CI, 0.48-3.16; P < .001) after surgery. CONCLUSIONS AND RELEVANCE Endoscopic decompression surgery had a long-lasting successful outcome in this type of frontal secondary headache. Even though BoNT/A had a positive effect, the effect of surgery was significantly higher. LEVEL OF EVIDENCE 3.

The management of patients with isolated congenital complete atrioventricular block (CCAVB) has changed during the last decades. The current policy is to pace the majority of patients based on a variety of criteria, among which is limited exercise capacity. Data regarding exercise capacity in this population stems from previous publications reporting small case series of unpaced patients. Therefore, we have investigated the exercise capacity of a group of contemporary children with CCAVB. Sixteen children (mean age 11.5 ± 4; seven boys, nine girls) with CCAVB were tested. In 13 patients, a median number of three pacemakers were implanted, whereas in three patients no pacemaker was given. All patients had an echocardiogram and completed a cardiopulmonary cycle exercise test. Exercise parameters were determined and compared with reference values obtained from healthy Dutch peers. The peak oxygen uptake/body mass was reduced to 34.4 ± 9.5 ml kg−1 min−1 (79 ± 24% of predicted) and the ventilatory threshold was reduced to 52 ± 17% of peak oxygen uptake (78 ± 21% of predicted), whereas the peak work load/body mass was 2.8 ± 0.6 W/kg (91 ± 24% of predicted), which was similar to controls. Importantly, 25% of the paced patients showed upper rate restriction by the pacemaker. In conclusion, children with CCAVB show a reduced peak oxygen uptake and ventilatory threshold, whereas they show normal peak work rates. This indicates that they generate more energy during exercise from anaerobic energy sources. Paced children with CCAVB do not perform better than unpaced children.

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