Right ventricular pacing causes electric and mechanical dyssynchrony, which is associated with an increased risk for heart failure and atrial fibrillation. Cardiac resynchronization therapy with ...biventricular pacing reduces ventricular dyssynchrony and results in clinical benefits in subsets of patients with heart failure with QRS prolongation. Recently, His bundle pacing has increased in use as a physiological pacing modality but is limited by difficult implantation, lower success rates in patients with QRS prolongation, and high, often unstable, pacing capture threshold. Thus, the concept of pacing the conduction system distal to the His bundle to bypass the region of conduction block was proposed. Early clinical studies demonstrated the procedural feasibility of left bundle branch pacing using a transventricular septal approach that generates narrow paced QRS duration, fast synchronized left ventricular activation, and correction of left bundle branch block. The current status and future direction of left bundle branch pacing are summarized in this paper.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The B cell antigen receptor (BCR) plays a central role in the self nonself selection of B lymphocytes and in their activation by cognate antigen during the clonal selection process. It was long ...thought that most cell surface receptors, including the BCR, were freely diffusing and randomly distributed. Since the advent of superresolution techniques, it has become clear that the plasma membrane is compartmentalized and highly organized at the nanometer scale. Hence, a complete understanding of the precise conformation and activation mechanism of the BCR must take into account the organization of the B cell plasma membrane. We review here the recent literature on the nanoscale organization of the lymphocyte membrane and discuss how this new information influences our view of the conformational changes that the BCR undergoes during activation.
Background The ideal age to introduce egg into the infant diet has been debated for the past 2 decades in the context of rising rates of egg allergy. Objective We sought to determine whether regular ...consumption of egg protein from age 4 to 6 months reduces the risk of IgE-mediated egg allergy in infants with hereditary risk, but without eczema. Methods Infants aged 4 to 6 months were randomly allocated to receive daily pasteurized raw whole egg powder (n = 407) or a color-matched rice powder (n = 413) to age 10 months. All infants followed an egg-free diet and cooked egg was introduced to both groups at age 10 months. The primary outcome was IgE-mediated egg allergy defined by a positive pasteurized raw egg challenge and egg sensitization at age 12 months. Results There was no difference between groups in the percentage of infants with IgE-mediated egg allergy (egg 7.0% vs control 10.3%; adjusted relative risk, 0.75; 95% CI, 0.48-1.17; P = .20). A higher proportion of participants in the egg group stopped taking the study powder because of a confirmed allergic reaction (25 of 407 6.1% compared with 6 of 413 1.5%). Egg-specific IgG4 levels were substantially higher in the egg group at 12 months (median, 1.22 mgA /L vs control 0.07 mgA /L; P < .0001). Conclusions We found no evidence that regular egg intake from age 4 to 6 months substantially alters the risk of egg allergy by age 1 year in infants who are at hereditary risk of allergic disease and had no eczema symptoms at study entry.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In patients with or without left bundle branch block, left bundle branch pacing (LBBP) can produce near normalization of QRS duration (QRSd). This has recently emerged as an alternative technique to ...His bundle pacing.
The purpose of this study was to characterize a novel approach for LBBP in patients with bradycardia indications for pacing and to assess implant success rate and midterm safety.
Patients with bradycardia indications for pacing underwent LBBP by a trans-ventricular-septal method in the basal ventricular septum. Procedural success, pacing parameters, and complications were assessed at implantation and at 3 months follow-up.
This prospective study evaluated 87 patients (sinus node dysfunction 67.8%; atrioventricular conduction disease 32.2%) undergoing pacemaker implantation. LBBP implantation succeeded in 80.5% (70/87) of patients and the remaining 17 patients received right ventricular septal pacing. The procedure time of LBBP implantation was 18.0 ± 8.8 minutes with a fluoroscopic exposure time of 3.9 ± 2.7 minutes. LBBP produced narrower electrocardiographic QRSd than did right ventricular septal pacing (113.2 ± 9.9 ms vs 144.4 ± 12.8 ms; P < .001). There were no major implantation-related complications. The pacing threshold was low (0.76 ± 0.22 V at implantation and 0.71 ± 0.23 V at 3 months), with no loss of capture or lead dislodgment observed.
This study demonstrates that in patients with standard bradycardia pacing indications, LBBP results in QRSd < 120 ms in most patients and can be performed successfully and safely in the majority of patients.
To evaluate the addition of the humanized monoclonal antiprogrammed death ligand-1 (PD-L1) antibody, atezolizumab, to platinum-based chemotherapy and bevacizumab in newly diagnosed stage III or IV ...ovarian cancer (OC).
This multicenter placebo-controlled double-blind randomized phase III trial (ClinicalTrials.gov identifier: NCT03038100) enrolled patients with newly diagnosed untreated International Federation of Gynecology and Obstetrics (FIGO) stage III or IV OC who either had undergone primary cytoreductive surgery with macroscopic residual disease or were planned to receive neoadjuvant chemotherapy and interval surgery. Patients were stratified by FIGO stage, Eastern Cooperative Oncology Group performance status, tumor immune cell PD-L1 staining, and treatment strategy and randomly assigned 1:1 to receive 3-weekly cycles of atezolizumab 1,200 mg or placebo (day 1, cycles 1-22), with paclitaxel plus carboplatin (day 1, cycles 1-6) plus bevacizumab 15 mg/kg (day 1, cycles 2-22), omitting perioperative bevacizumab in neoadjuvant patients. The co-primary end points were investigator-assessed progression-free survival and overall survival in the intention-to-treat and PD-L1-positive populations.
Between March 8, 2017, and March 26, 2019, 1,301 patients were enrolled. The median progression-free survival was 19.5 versus 18.4 months with atezolizumab versus placebo, respectively (hazard ratio, 0.92; 95% CI, 0.79 to 1.07; stratified log-rank
= .28), in the intention-to-treat population and 20.8 versus 18.5 months, respectively (hazard ratio, 0.80; 95% CI, 0.65 to 0.99;
= .038), in the PD-L1-positive population. The interim (immature) overall survival results showed no significant benefit from atezolizumab. The most common grade 3 or 4 adverse events were neutropenia (21% with atezolizumab
21% with placebo), hypertension (18%
20%, respectively), and anemia (12%
12%).
Current evidence does not support the use of immune checkpoint inhibitors in newly diagnosed OC. Insight from this trial should inform further evaluation of immunotherapy in OC.
The incidence of chronic pain is estimated to be 20-25% worldwide. Few patients with chronic pain obtain complete relief from the drugs that are currently available, and more than half report ...inadequate relief. Underlying the challenge of developing better drugs to manage chronic pain is incomplete understanding of the heterogeneity of mechanisms that contribute to the transition from acute tissue insult to chronic pain and to pain conditions for which the underlying pathology is not apparent. An intact central nervous system (CNS) is required for the conscious perception of pain, and changes in the CNS are clearly evident in chronic pain states. However, the blockage of nociceptive input into the CNS can effectively relieve or markedly attenuate discomfort and pain, revealing the importance of ongoing peripheral input to the maintenance of chronic pain. Accordingly, we focus here on nociceptors: their excitability, their heterogeneity and their role in initiating and maintaining pain.
Full text
Available for:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Ulcerative colitis (UC) is linked with inflammation of the large intestine due to an overactive response of the colon-immune system. UC is associated with weight loss, rectal bleeding, diarrhea, and ...abdominal pain. Given that γ-amino butyric acid (GABA) suppresses immune cell activity and the excitability of colonic afferents, and that there is a decrease in colonic GABA during UC, we hypothesized that UC pain is due to a decrease in the inhibition of colonic afferents. Thus, restoring GABA in the colon will attenuate inflammatory hypersensitivity. We tested this hypothesis in a mouse model of colitis. Colon inflammation was induced with seven days of dextran sodium sulfate (DSS, 3%) in the drinking water. GABA (40 mg/kg) was administered orally for the same period as DSS, and body weight, colon length, colon permeability, clinical progression of colitis (disease activity index or DAI), and colon histological score (HS) were assessed to determine the effects of GABA on colitis. A day after the end of GABA treatment, visceral sensitivity was assessed with balloon distention (of the colon)-evoked visceromotor response and colon samples were collected for the measurement of GABA and cytokines. Treatment with GABA reduced the DSS-induced increase in the colon permeability, DAI, HS, and decrease in body weight and colon length. Furthermore, GABA inhibited the DSS-induced increase in the proinflammatory cytokines tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-12 (IL-12), and increased the expression of the anti-inflammatory cytokine IL-10 in the colon tissue. Importantly, GABA reduced DSS-induced visceral hypersensitivity. These data suggest that increasing gastrointestinal levels of GABA may be useful for the treatment of colitis.
GABA treatment reduces the severity of colitis and inflammation and produces inhibition of visceral hypersensitivity in colon-inflamed mice. These results raise the promising possibility that GABA treatment may be an effective therapeutic strategy for the management of symptoms associated with colitis. However, clinical studies are required to corroborate whether this mouse-model data translates to human colon.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
9.
JCD editorial, September 2024 Gold, Michael H.
Journal of cosmetic dermatology,
September 2024, 2024-09-00, 20240901, Volume:
23, Issue:
9
Journal Article
Peer reviewed
Open access
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
BACKGROUND:The Subcutaneous ICD (S-ICD) is safe and effective for sudden cardiac death prevention. However, patients in previous S-ICD studies had fewer comorbidities, less left ventricular ...dysfunction and received more inappropriate shocks (IAS) than in typical transvenous (TV)-ICD trials. The UNTOUCHED trial was designed to evaluate the IAS rate in a more typical, contemporary ICD patient population implanted with the S-ICD using standardized programming and enhanced discrimination algorithms.
METHODS:Primary prevention patients with left ventricular ejection fraction (LVEF) ≤ 35% and no pacing indications were included. Generation 2 or 3 S-ICD devices were implanted and programmed with rate-based therapy delivery for rates ≥ 250 beats per minute (bpm) and morphology discrimination for rates ≥200 and < 250 bpm. Patients were followed for 18 months. The primary endpoint was the IAS free rate compared to a 91.6% performance goal, derived from the results for the ICD-only patients in the MADIT-RIT study. Kaplan-Meier analyses were performed to evaluate event-free rates for IAS, all cause shock, and complications. Multivariable proportional hazard analysis was performed to determine predictors of endpoints.
RESULTS:S-ICD implant was attempted in 1116 patients and 1111 patients were included in post- implant follow-up analysis. The cohort had a mean age of 55.8±12.4 years, 25.6% women, 23.4% black race, 53.5% with ischemic heart disease, 87.7% with symptomatic heart failure and a mean LVEF of 26.4±5.8%. Eighteen-month freedom from IAS was 95.9% (Lower confidence limit LCL 94.8%). Predictors of reduced incidence of IAS were implanting the most recent generation of device, using the three-incision technique, no history of atrial fibrillation, and ischemic etiology. The 18-month all cause shock free rate was 90.6% (LCL 89.0%), meeting the prespecified performance goal of 85.8%. Conversion success rate for appropriate, discrete episodes was 98.4%. Complication free rate at 18 months was 92.7%.
CONCLUSIONS:This study demonstrates high efficacy and safety with contemporary S-ICD devices and programming despite the relatively high incidence of co-morbidities in comparison to earlier S-ICD trials. The inappropriate shock rate (3.1% at one year) is the lowest reported for the S-ICD and lower than many TV ICD studies using contemporary programming to reduce IAS.
CLINICAL TRIAL REGISTRATION:URL https://clinicaltrials.gov Unique Identifier NCT02433379
PDF
