Similar outcome for cryopreserved embryo transfer following GnRH-antagonist/GnRH-agonist, GnRH-antagonist/HCG or long protocol ovarian stimulation

The pregnancy rates after triggering of final oocyte maturation with gonadotrophin-releasing hormone (GnRH) agonist in GnRH-antagonist ovarian stimulation protocols are lower than those following triggering with human chorionic gonadotrophin (HCG). Furthermore, lower pregnancy rates following GnRH-antagonist protocols compared with long GnRH-agonist protocols have been reported. The differences might be due to an impact on oocyte number and quality or on the endometrium. If any stimulation protocol had a negative impact on oocyte quality, then further evidence of this effect would be observed following frozen-thawed embryo transfer originating from that stimulation cycle. The outcome of frozen-thawed embryo transfer was retrospectively analysed using the long protocol with triptorelin depot 3.75 mg (n = 215) or 0.1 mg/day (n = 83), or GnRH-antagonist protocol with either HCG (n = 69) or GnRH-agonist (n = 25) for final oocyte maturation. The outcomes measured were implantation rate, clinical pregnancy rate, ongoing pregnancy rate and embryo survival rate. All outcomes were similar in the four groups. It is concluded that the potential for frozen-thawed embryos to implant and develop following transfer is independent of the GnRH-analogue and the final oocyte maturation protocol used in the collection cycle. Lower IVF embryo transfer success using GnRH-antagonist/GnRH-agonist protocol does not appear to be related to an adverse effect on oocyte quality.     

Unmasking Myocardial Dysfunction in Patients Hospitalized for Community-Acquired Pneumonia Using a 4-Chamber 3-Dimensional Volume/Strain Analysis

Lower respiratory infection was reported as the most common fatal infectious disease. Community-acquired pneumonia (CAP) and myocardial injury are associated; yet, true prevalence of myocardial injury is probably underestimated. We assessed the rate and severity of myocardial dysfunction in patients with CAP. Admitted patients diagnosed with CAP were prospectively recruited. All the patients had C-reactive protein (CRP), brain natriuretic peptide (BNP), and high-sensitivity cardiac troponin (hs-cTnl) tests added to their routine workup. 2D/3D Doppler echocardiography was done on a Siemens Acuson SC2000 machine ≤ 24 h of diagnosis. 3D datasets were blindly analyzed for 4-chamber volumes/strains using EchobuildR 3D-Volume Analysis prototype software, v3.0 2019, Siemens-Medical Solutions. Volume/strain parameters were correlated with admission clinical and laboratory findings. The cohort included 34 patients, median age 60 years (95% CI 55–72). The cohort included 18 (53%) patients had hypertension, 9 (25%) had diabetes mellitus, 7 (21%) were smokers, 7 (21%) had previous myocardial infarction, 4 (12%) had chronic renal failure, and 1 (3%) was on hemodialysis treatment. 2D/Doppler echocardiography findings showed normal ventricular size/function (LVEF 63 ± 9%), mild LV hypertrophy (104 ± 36 g/m²), and LA enlargement (41 ± 6 mm). 3D volumes/strains suggested bi-atrial and right ventricular dysfunction (global longitudinal strain RVGLS =  − 8 ± 4%). Left ventricular strain was normal (LVGLS =  − 18 ± 5%) and correlated with BNP (r = 0.40, p = 0.024). The patients with LVGLS >  − 17% had higher admission blood pressure and lower SaO₂ (144 ± 33 vs. 121 ± 20, systolic, mmHg, p = 0.02, and 89 ± 4 vs. 94 ± 4%, p = 0.006, respectively). hs-cTnl and CRP were not different. Using novel 3D volume/strain software in CAP patients, we demonstrated diffuse global myocardial dysfunction involving several chambers. The patients with worse LV GLS had lower SaO₂ and higher blood pressure at presentation. LV GLS correlated with maximal BNP level and did not correlate with inflammation or myocardial damage markers.     

Automated Computational Detection of Interstitial Fibrosis,Tubular Atrophy,and Glomerulosclerosis

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Surgical management of parapharyngeal space tumors: a 10-year review.

OBJECTIVE: The purpose of this article is to describe the diagnostic evaluation and surgical approaches to parapharyngeal space tumors in a tertiary referral center. STUDY DESIGN AND SETTING: The study is a retrospective review of 47 patients diagnosed with tumors of the parapharyngeal space (12 with malignant diseases and 35 with benign lesions) and surgically treated during a 10-year period. The transcervical (40%) and the transcervical-transparotid approaches (46%) were the most commonly performed surgical procedures followed by the orbitozygomatic-middle fossa approach (12%) and the transmandibular approach (2%). RESULTS: The surgical procedures were uneventful and there were no postoperative mortalities. Complications were rare; the most common was transient facial nerve paralysis (5 patients). After an average follow-up of 35 months, only 1 of 35 patients with benign diseases had a recurrence 5 years following transcervical resection of a pleomorphic adenoma. Of 12 patients with malignant tumors, 5 (42%) are alive with no evidence of disease. The sensitivity of preoperative fine needle aspiration biopsy (n = 23 patients) was 87% for detection of malignant disease and specificity was 100%. CONCLUSIONS: Most benign parapharyngeal space tumors can be removed surgically with a low rate of complications and recurrence. Malignant neoplasms, however, carry an ominous prognosis and a low rate of disease-free survival. Fine needle aspiration may be helpful in preoperative diagnostic evaluation of patients with parapharyngeal space tumors.     

Phase I and scintigraphy studies to evaluate safety,tolerability, pharmacokinetics,and lung deposition of inhaled GDC‐0214 in healthy volunteers

Several inflammatory cytokines that promote inflammation and pathogenesis in asthma signal through the Janus kinase 1 (JAK1) pathway. This phase I, randomized, placebo‐controlled trial assessed the pharmacokinetics and safety of single and multiple ascending doses up to 15 mg twice daily for 14 days of a JAK1 inhibitor, GDC‐0214, in healthy volunteers (HVs; n = 66). Doses were administered with a dry powder, capsule‐based inhaler. An accompanying open‐label gamma scintigraphy study in HVs examined the lung deposition of a single dose of inhaled Technetium‐99m (^99mTc)‐radiolabeled GDC‐0214. GDC‐0214 plasma concentrations were linear and approximately dose‐proportional after both single and multiple doses. Peak plasma concentrations occurred at 15–30 min after dosing. The mean apparent elimination half‐life ranged from 32 to 56 h across all single and multiple dose cohorts. After single and multiple doses, all adverse events were mild or moderate, and none led to treatment withdrawal. There was no clear evidence of systemic toxicity due to JAK1 inhibition, and systemic exposure was low, with plasma concentrations at least 15‐fold less than the plasma protein binding‐corrected IC50 of JAK1 at the highest dose. Scintigraphy showed that approximately 50% of the emitted dose of radiolabeled GDC‐0214 was deposited in the lungs and was distributed well to the peripheral airways. ^99mTc‐radiolabeled GDC‐0214 (1 mg) exhibited a mean plasma C_max similar to that observed in phase I at the same dose level. Overall, inhaled GDC‐0214 exhibited pharmacokinetic properties favorable for inhaled administration.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Many factors drive asthma pathogenesis, including several cytokines that signal through the Janus kinase 1 (JAK1) pathway. Inhibition of JAK1 is a possible target for asthma treatments, but previous studies show oral JAK1 inhibitors lead to increased risk of severe infections, malignancy and cardiovascular events.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This study investigated the safety, pharmacokinetics, and lung deposition of GDC‐0214, an inhaled JAK1 inhibitor designed to target the lungs.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Inhaled delivery of a JAK inhibitor for 14 days exhibited low systemic exposure, leading to few adverse events and limited systemic toxicity, while demonstrating high deposition in the lungs.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Local pulmonary application of JAK inhibitors may be an effective treatment for asthma with limited systemic risks.     

School engagement,risky peers,and student–teacher relationships as mediators of school violence in Taiwanese vocational versus academically oriented high schools

Educational tracking based on academic ability accounts for different school dynamics between vocational versus academically‐oriented high schools in Taiwan. Many educational practitioners predict that the settings of vocational schools and academic schools mediate school violence in different ways. Alternatively, some researchers argue the actual mediating mechanism may not vary significantly between the different school types in different cultures. The purpose of this study was to examine how within‐school variables (school engagement, risky peers, and student–teacher interaction) mediate external‐school variables (personal traits, parental monitoring, and victimization) and school violence in Taiwanese vocational and academically‐oriented schools. Structural equation modeling analysis, based on a national representative sample (N=7,841), suggested school violence was mediated through school variables. Similar mediational findings were found between academic and vocational schools as well as between males and females. Findings suggest that school violence is mediated by within‐school variables in similar ways across different school types, genders, and cultures. © 2010 Wiley Periodicals, Inc.