A
bstract
We present a search for the charged lepton-flavor-violating decays ϒ(1
S
)
→
ℓ
±
ℓ
′
∓
and radiative charged lepton-flavour-violating decays ϒ(1
S
)
→ γ
ℓ
±
ℓ
′
∓
ℓ
,
ℓ
′ =
e, μ, τ
using ...the 158 million ϒ(2
S
) sample collected by the Belle detector at the KEKB collider. This search uses ϒ(1
S
) mesons produced in ϒ(2
S
)
→ π
+
π
−
ϒ(1
S
) transitions. We do not find any significant signal, so we provide upper limits on the branching fractions at the 90% confidence level.
To evaluate clinical outcomes in a large group of advanced-stage carcinoid patients (stage IV) following multimodal surgical therapy.
Patients with advanced-stage carcinoid have traditionally ...experienced poor 5-year survival (18%-30%). Few recent series have evaluated a large number of patients treated with aggressive surgical rescue therapy.
This single-center retrospective review analyzes the records of 82 consecutive carcinoid patients treated by the same 2 surgeons, from August 1998 through August 2004 with a 3- to 72-month follow-up.
Surprisingly, one third of 26 (32%) patients were found to have intestinal obstructions; 10 being moribund at presentation. Mesenteric encasement with intestinal ischemia was successfully relieved in 10 of 12 cases. Five of eighty-two "terminal" patients were rendered free of macroscopic disease. Karnofsky performance scores improved from 65 to 85 (P < 0.0001). Two- and four-year survival for patients with no or unilateral liver metastases (n = 23) was 89%, while 2- and 4-year survival for patients with bilateral liver disease (n = 59) was 68% and 52% (P = 0.072), respectively.
We think that all patients with advanced-stage carcinoid should be evaluated for possible multimodal surgical therapy. Primary tumors should be resected, even in the presence of distant metastases to prevent future intestinal obstruction. The "wait and see" method of management of this slow-growing cancer no longer has merit. We offer an algorithm for the surgical evaluation and management of these patients.
Abstract
Funding Acknowledgements
Type of funding sources: Other. Main funding source(s): The DEVICE registries were financed by “Stiftung Institut für Herzinfarktforschung (IHF)”, with additional ...support by grants from Biotronik, Medtronic, and St. Jude Medical.
Background
Experimental data and early clinical trials suggested that amiodarone may alter the defibrillation threshold of ICD systems. However, because of its potent antiarrhythmic effect and lack of alternatives, amiodarone is frequently used for antiarrhythmic therapy in ICD or CRT-D patients, leading to the question of whether ICD testing with ventricular fibrillation induction should be repeated in these patients after starting amiodarone.
Objective
This study was designed to assess the impact of amiodarone therapy on the success of ventricular fibrillation induction tests in this "real life" cohort of ICD recipients of the German DEVICE registry.
Methods
3,680 patients who underwent ICD implantation, revision, or upgrade in 49 centers participating in the German DEVICE Registry were enrolled 03/2007-02/2014.
Results
Intraoperative defibrillation testing was conducted in 2,705 patients receiving only beta-blockes as antiarrhythmic therapy and in 422 patients under betablocker plus amiodarone therapy. With regard to ineffective defibrillation tests, no difference could be described between the two groups (0.6% vs. 0.5%; p=0.77). In a similar fashion 488 patients receiving beta-blockers only and 65 patients under beta-blocker plus amiodarone therapy who were scheduled for postoperative defibrillation testing showed comparable rates of ineffective testing (14.5% vs. 15.4%; p=0.86).
Conclusions
Based on 3,127 intraoperative and 553 postoperative defibrillator testings, our study failed to show a significant association of amiodarone therapy and ineffective defibrillator testings in this "real life" cohort of ICD recipients of the German DEVICE registry. Our results thus underline that, apart from special situations such as right-sided implantation, HCM, extravenous ICD systems, etc., it might not be necessary to perform a DFT test after the start of an amiodarone therapy in ICD patients.
IMPORTANCE: A short cervix as assessed by transvaginal ultrasound is an established risk factor for preterm birth. Study findings for a cervical pessary to prevent preterm delivery in singleton ...pregnancies with transvaginal ultrasound evidence of a short cervix have been conflicting. OBJECTIVE: To determine if cervical pessary placement decreases the risk of preterm birth or fetal death prior to 37 weeks among individuals with a short cervix. DESIGN, SETTING, AND PARTICIPANTS: We performed a multicenter, randomized, unmasked trial comparing a cervical pessary vs usual care from February 2017 through November 5, 2021, at 12 centers in the US. Study participants were nonlaboring individuals with a singleton pregnancy and a transvaginal ultrasound cervical length of 20 mm or less at gestations of 16 weeks 0 days through 23 weeks 6 days. Individuals with a prior spontaneous preterm birth were excluded. INTERVENTIONS: Participants were randomized 1:1 to receive either a cervical pessary placed by a trained clinician (n = 280) or usual care (n = 264). Use of vaginal progesterone was at the discretion of treating clinicians. MAIN OUTCOME AND MEASURES: The primary outcome was delivery or fetal death prior to 37 weeks. RESULTS: A total of 544 participants (64%) of a planned sample size of 850 were enrolled in the study (mean age, 29.5 years SD, 6 years). Following the third interim analysis, study recruitment was stopped due to concern for fetal or neonatal/infant death as well as for futility. Baseline characteristics were balanced between participants randomized to pessary and those randomized to usual care; 98.9% received vaginal progesterone. In an as-randomized analysis, the primary outcome occurred in 127 participants (45.5%) randomized to pessary and 127 (45.6%) randomized to usual care (relative risk, 1.00; 95% CI, 0.83-1.20). Fetal or neonatal/infant death occurred in 13.3% of those randomized to receive a pessary and in 6.8% of those randomized to receive usual care (relative risk, 1.94; 95% CI, 1.13-3.32). CONCLUSIONS AND RELEVANCE: Cervical pessary in nonlaboring individuals with a singleton gestation and with a cervical length of 20 mm or less did not decrease the risk of preterm birth and was associated with a higher rate of fetal or neonatal/infant mortality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02901626
We present a search for periodic gravitational waves from the neutron star in the supernova remnant Cassiopeia A. The search coherently analyzes data in a 12 day interval taken from the fifth science ...run of the Laser Interferometer Gravitational-Wave Observatory. It searches gravitational-wave frequencies from 100 to 300 Hz and covers a wide range of first and second frequency derivatives appropriate for the age of the remnant and for different spin-down mechanisms. No gravitational-wave signal was detected. Within the range of search frequencies, we set 95% confidence upper limits of (0.7-1.2) X 10--24 on the intrinsic gravitational-wave strain, (0.4-4) X 10--4 on the equatorial ellipticity of the neutron star, and 0.005-0.14 on the amplitude of r-mode oscillations of the neutron star. These direct upper limits beat indirect limits derived from energy conservation and enter the range of theoretical predictions involving crystalline exotic matter or runaway r-modes. This paper is also the first gravitational-wave search to present upper limits on the r-mode amplitude.
Herein we describe the discovery of A-1331852, a first-in-class orally active BCL-XL inhibitor that selectively and potently induces apoptosis in BCL-XL-dependent tumor cells. This molecule was ...generated by re-engineering our previously reported BCL-XL inhibitor A-1155463 using structure-based drug design. Key design elements included rigidification of the A-1155463 pharmacophore and introduction of sp3-rich moieties capable of generating highly productive interactions within the key P4 pocket of BCL-XL. A-1331852 has since been used as a critical tool molecule for further exploring BCL-2 family protein biology, while also representing an attractive entry into a drug discovery program.
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