Radiofrequency Catheter Ablation of Hemodynamically Unstable Ventricular Tachycardia Associated with Systemic Sclerosis

Systemic sclerosis (SS) is a connective tissue disease and cardiac involvement is common. Primary cardiac involvement such as conduction system disturbances and arrhythmias can also occur. However, reports of sustained ventricular tachycardia (VT) are rare. We report a case of catheter ablation of sustained ventricular tachycardia in a patient with systemic sclerosis using a conventional mapping system. A 64-yr-old woman with a 10-yr history of SS was referred for management of her ventricular tachycardia. There was no structural abnormality in cardiac chambers. However, electrophysiologic study revealed electrical substrate of ventricular tachycardia which could be ablated with pacemapping and substrate mapping. This case demonstrated successful conventional mapping and catheter ablation in a hemodynamically unstable patient with SS

Activated mutant NRasQ61K drives aberrant melanocyte signaling, survival, and invasiveness via a rac1-Dependent mechanism

Around a fifth of melanomas exhibit an activating mutation in the oncogene NRas that confers constitutive signaling to proliferation and promotes tumor initiation. NRas signals downstream of the major melanocyte tyrosine kinase receptor c-kit and activated NRas results in increased signaling via the extracellular signal–regulated kinase (ERK)/MAPK/ERK kinase/mitogen-activated protein kinase (MAPK) pathways to enhance proliferation. The Ras oncogene also activates signaling via the related Rho GTPase Rac1, which can mediate growth, survival, and motility signaling. We tested the effects of activated NRasQ61K on the proliferation, motility, and invasiveness of melanoblasts and melanocytes in the developing mouse and ex vivo explant culture as well as in a melanoma transplant model. We find an important role for Rac1 downstream of NRasQ61K in mediating dermal melanocyte survival in vivo in mouse, but surprisingly NRasQ61K does not appear to affect melanoblast motility or proliferation during mouse embryogenesis. We also show that genetic deletion or pharmacological inhibition of Rac1 in NRasQ61K induced melanoma suppresses tumor growth, lymph node spread, and tumor cell invasiveness, suggesting a potential value for Rac1 as a therapeutic target for activated NRas-driven tumor growth and invasiveness

Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study

In the LYM-3002 study, the efficacy and safety of frontline bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were compared in transplant-ineligible patients with untreated, newly diagnosed, mantle cell lymphoma. We report the final overall survival and safety outcomes for patients in the long-term follow-up phase after the primary progression-free-survival endpoint was met.LYM-3002 was a randomised, open-label, phase 3 study done at 128 clinical centres in 28 countries in Asia, Europe, North America, and South America. Adult patients with confirmed stage II-IV previously untreated mantle cell lymphoma, Eastern Cooperative Oncology Group performance status score of 2 or less, who were ineligible for bone marrow transplantation, were randomly assigned (1:1) to receive six or eight 21-day cycles of VR-CAP (intravenous rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and bortezomib 1·3 mg/m2, plus oral prednisone 100 mg/m2) or R-CHOP (intravenous vincristine 1·4 mg/m2 [2 mg maximum], rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, and doxorubicin 50 mg/m2, plus oral prednisone 100 mg/m2). Randomisation was done according to a computer-generated randomisation schedule prepared by the sponsor; permuted blocks central randomisation was used (block size of 4), and was stratified by International Prognostic Index score and disease stage at diagnosis. The primary endpoint of this final analysis was overall survival, which was analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00722137, and is closed to new participants with follow-up completed.Between May 22, 2008, and Dec 5, 2011, 487 patients were enrolled and randomly assigned. 268 patients (140 in the VR-CAP group and 128 in the R-CHOP group) were included in the follow-up analysis, which included patients with data available after the primary analysis clinical cutoff date of Dec 2, 2013. After median follow-up of 82·0 months (IQR 74·1-94·2), median overall survival was significantly longer in the VR-CAP group than in the R-CHOP group (90·7 months [95% CI 71·4 to not estimable] vs 55·7 months [47·2 to 68·9]; hazard ratio 0·66 [95% CI 0·51-0·85]; p=0·001). Three new adverse events were reported since the primary analysis cutoff (one each of grade 4 lung adenocarcinoma and grade 4 gastric cancer in the VR-CAP group, and one case of grade 2 pneumonia in the R-CHOP group). 103 (42%) of 243 patients in the VR-CAP group, and 138 (57%) of 244 in the R-CHOP group died; the most common cause of death was progressive disease.Compared with R-CHOP, VR-CAP was associated with significantly longer survival, and had a manageable and expected safety profile. Our results support further assessment of VR-CAP in patients with previously untreated mantle cell lymphoma.Janssen Research & Development

Dimensional dependence of the Stokes--Einstein relation and its violation

We generalize to higher spatial dimensions the Stokes--Einstein relation (SER) and the leading correction to diffusivity in periodic systems, and validate them using numerical simulations. Using these results, we investigate the evolution of the SER violation with dimension in simple hard sphere glass formers. The analysis suggests that the SER violation disappears around dimension d=8, above which SER is not violated. The critical exponent associated to the violation appears to evolve linearly in 8-d below d=8, as predicted by Biroli and Bouchaud [J. Phys.: Cond. Mat. 19, 205101 (2007)], but the linear coefficient is not consistent with their prediction. The SER violation evolution with d establishes a new benchmark for theory, and a complete description remains an open problem.Comment: 20 pages, 10 figure

Migraine triggers in Asian countries: a narrative review

BackgroundMigraine is one of the most common neurological disorders worldwide. Clinical characteristics of migraine may be somewhat different across ethnic groups. Although factors such as stress, lack of sleep, and fasting are known as migraine triggers, the discussion about geographical differences of migraine triggers in Asia is lacking.MethodsIn this study, we performed a narrative review on migraine triggers in Asia. We searched PubMed for relevant papers published between January 2000 and February 2022.ResultsForty-two papers from 13 Asian countries were included. Stress and sleep are the most frequently reported migraine triggers in Asia. There were some differences in migraine triggers in Asian countries: fatigue and weather common in Eastern Asia and fasting common in Western Asia.ConclusionMajority of the common triggers reported by patients with migraine in Asia were stress and sleep, similar to those reported globally, thus showing they are universally important. Some triggers linked to internal homeostasis are influenced by culture (e.g., alcohol, food/eating habit), and triggers related to environmental homeostasis, such as weather, are highly heterogenous between regions

Calcium phosphate particles stimulate interleukin-1β release from human vascular smooth muscle cells: A role for spleen tyrosine kinase and exosome release

Aims: Calcium phosphate (CaP) particle deposits are found in several inflammatory diseases including atherosclerosis and osteoarthritis. CaP, and other forms of crystals and particles, can promote inflammasome formation in macrophages leading to caspase-1 activation and secretion of mature interleukin-1β (IL-1β). Given the close association of small CaP particles with vascular smooth muscle cells (VSMCs) in atherosclerotic fibrous caps, we aimed to determine if CaP particles affected pro-inflammatory signalling in human VSMCs. Methods and results: Using ELISA to measure IL-1β release from VSMCs, we demonstrated that CaP particles stimulated IL-1β release from proliferating and senescent human VSMCs, but with substantially greater IL-1β release from senescent cells; this required caspase-1 activity but not LPS-priming of cells. Potential inflammasome agonists including ATP, nigericin and monosodium urate crystals did not stimulate IL-1β release from VSMCs. Western blot analysis demonstrated that CaP particles induced rapid activation of spleen tyrosine kinase (SYK) (increased phospho-Y525/526). The SYK inhibitor R406 reduced IL-1β release and caspase-1 activation in CaP particle-treated VSMCs, indicating that SYK activation occurs upstream of and is required for caspase-1 activation. In addition, IL-1β and caspase-1 colocalised in intracellular endosome-like vesicles and we detected IL-1β in exosomes isolated from VSMC media. Furthermore, CaP particle treatment stimulated exosome secretion by VSMCs in a SYK-dependent manner, while the exosome-release inhibitor spiroepoxide reduced IL-1β release. Conclusions: CaP particles stimulate SYK and caspase-1 activation in VSMCs, leading to the release of IL-1β, at least in part via exosomes. These novel findings in human VSMCs highlight the pro-inflammatory and procalcific potential of microcalcification

Preoperative Imaging of Sentinel Lymph Nodes in Gastric Cancer Using CT Lymphography

Purpose: Preoperative identification of the sentinel lymph node (SLN) in gastric cancer (GC) patients may have great advantages for the minimally invasive treatment. This study was performed to evaluate the possibility of preoperative SLN detection using CT lymphography. Materials and Methods: Fourteen patients with early GC were enrolled. CT images were obtained before and at 1, 3, and 5 minutes after endoscopic submucosal peritumoral injection of 2 mL iopamidol. For patients with clearly identified SLNs, to make comparisons with the CT lymphography results, intraoperative SLN detection was performed using subserosally injected Indocyanine green (ICG) lymphography and ex vivo ICG and iopamidol lymphography using mammography was also performed. Results: CT lymphography clearly visualized draining lymphatics and SLNs in 4 (28.6%) out of 14 patients. All clearly visualized SLNs (one to three SLNs per patient) under preoperative imaging were detected in the same location by intraoperative ICG lymphography and ex vivo ICG and iopamidol lymphography using mammography. All preoperative SLN detections were observed with the primary tumors in the lower third of the stomach. Conclusion: Although our study demonstrated a SLN detection rate of less than 30%, CT lymphography with radio-contrast showed potential as a method of preoperative SLN detection for GC

Secondary Progressive Multiple Sclerosis: A Review of Clinical Characteristics, Definition, Prognostic Tools, and Disease-Modifying Therapies

Many challenges exist in the precise diagnosis and clinical management of secondary progressive multiple sclerosis (SPMS) because of the lack of definitive clinical, imaging, immunologic, or pathologic criteria that demarcate the transition from relapsing-remitting MS to SPMS. This review provides an overview of the diagnostic criteria/definition and the heterogeneity associated with different SPMS patient populations; it also emphasizes the importance of available prospective/retrospective tools to identify patients with SPMS earlier in the disease course so that approved disease-modifying therapies and nonpharmacological strategies will translate into better outcomes. Delivery of such interventions necessitates an evolving patient-clinician dialog within the context of a multidisciplinary team

CT Findings of Atypical Adenomatous Hyperplasia in the Lung

OBJECTIVE: The aim of this study was to analyze the computed tomographic (CT) findings of atypical adenomatous hyperplasia (AAH) in the lung. MATERIALS AND METHODS: The CT findings of AAHs in eight patients were retrospectively reviewed. The CT findings of each AAH lesion were evaluated for multiplicity, location, shape, size and internal density of the lesion, the interface between the normal lung and the lesion, the internal features within the lesion and any change of the lesion on the follow-up CT scans (range: 33 to 540 days; average: 145.3 days). RESULTS: The eight patients consisted of three men and five women (age range: 43-71 years). Six of eight patients were asymptomatic. Four of them (50%) had synchronous malignancies in the lung: adenocarcinoma of the lung (n = 3), and metastatic squamous cell carcinoma from the uterus (n = 1). We could identify and evaluate eleven AAH nodules in seven patients on the CT scans. Three patients had multiple AAHs. Seven of the 11 lesions (64%) were located in the upper lobe. All the AAHs showed a well-defined oval or round shape and pure ground-glass opacity (GGO) without any solid component (size: 3.9x3 mm to 19x17 mm; internal attenuation: -467 to -785 HU). All the AAHs showed no change of their size and internal density on the follow-up CT scans. CONCLUSION: Atypical adenomatous hyperplasia is often associated with malignancy. This tumor is shown on CT as persistent well-defined oval or round nodular GGOs without solid components, and it does not change on the follow-up CT.This study is supported by KISTEP, Ministry of Science and Technology, Korea