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Purpose: To demonstrate and evaluate uterine peristalsis on cine magnetic resonance imaging (MRI) using ultrafast imaging. Materials and Methods:Serial MR uterine images (300) were obtained from 15 normal volunteers over four menstrual phases using true fast imaging with steady-state precession (true FISP) technique over 117 seconds and videotaped. Three radiologists independently evaluated videotapes of 59 studies. Uterine peristalsis was defined as wavy movements of subendometrial myometrium or endometrium. Interobserver reliability was evaluated using a Kappa coefficient. Fifty-four studies obtained in appropriate phases were analyzed.Results: Cine MRI displayed uterine peristalsis in 30 of 59 studies; consensus reading showed direction in 23 studies. Reliability between the final consensus of the recognition of uterine peristalsis and those of the three readers was extremely concordant, with a Kappa coefficient of 0.908. Wave direction was cervico-fundal in follicular and periovulatory phases, with frequency of contraction waves being 1.2-2.3 per minute in positive studies. Conclusion:Uterine peristalsis was demonstrated on cine MR using ultrafast MRI. Direction and frequency of peristaltic waves are closely related to menstrual cycle phases. Supplementary material for this article can be found on the JMRI website at www.interscience.wiley.com/jpages/ 1053-1807/suppmat/index.html.

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Patients with less severe obstructive sleep apnoea (OSA) are usually prescribed oral appliances and/or smaller optimal nasal continuous positive airway pressure (PnCPAP) in nCPAP therapy. We hypothesised that OSA patients with greater PnCPAP would not respond favourably to oral appliances.Oral appliances were inserted in nCPAP users after washing-out the nCPAP effect. Follow-up polysomnography was undertaken with the adjusted oral appliance in place. The predictability of PnCPAP was evaluated with receiver-operating characteristic (ROC) curves.The median baseline apnoea/hypopnoea index (AHI) was reduced with the oral appliance from 36 to 12 events?h -1 in 35 patients. When responders were defined as patients showing a follow-up AHI of ,5 events?h -1 with .50% reduction in baseline AHI, the area under the ROC curve for PnCPAP was 0.76. The best cut-off value of PnCPAP turned out to be 10.5 cmH 2 O with a high negative predictive value (0.93) and a low negative likelihood ratio (0.18). OSA patients with a PnCPAP of .10.5 cmH 2 O are unlikely to respond to oral appliance therapy. This prediction is clinically helpful to both OSA patients and medical personnel in discussing oral appliances as a temporary substitute and/or alternative for nCPAP.

Aims: The pleiotropic effects of statins on recurrent stroke remain unclear. We investigated the effects of pravastatin on high-sensitivity C-reactive proteins (Hs-CRP) in ischemic stroke, and explored the impact of Hs-CRP on recurrent stroke and vascular events.Methods: This randomized open-label trial was ancillary to the J-STARS trial. One thousand and ninety-five patients with non-cardiogenic ischemic stroke were assigned to the pravastatin (n = 545) or control groups (n = 550). The primary and secondary endpoints were serum Hs-CRP reduction and stroke recurrence, including both ischemic and hemorrhagic ones, respectively. Onset of vascular events and each stroke subtype in relation to Hs-CRP levels were also determined.Results: In the pravastatin treatment group, Hs-CRP levels (median 711 µg/L, IQR 344–1500) significantly decreased 2 months later (median 592 µg/L, IQR 301–1390), and they remained significantly lower until the end of the study. However, in the control group, baseline Hs-CRP levels were similar to those 2 months later. The reduction of Hs-CRP levels from the baseline to 2 months in the pravastatin group was statistically significant compared with the control (p = 0.007). One SD increase in log-transformed Hs-CRP increased the risk of stroke recurrence (HR 1.17, 95% CI 0.97–1.40) and vascular events (HR 1.30, 95% CI 1.12–1.51). With an Hs-CRP cut-off of 1000 µg/L, higher Hs-CRP significantly increased the risk of recurrent stroke (HR 1.50, 95% CI 1.03–2.17) and vascular events (HR 1.68, 95% CI 1.23–2.29).Conclusion: In non-cardiogenic ischemic stroke, pravastatin treatment may reduce vascular inflammation as assessed by Hs-CRP, and higher Hs-CRP levels appeared to increase the risk of recurrent stroke and vascular events.

Vocal fold scar and sulcus are intractable diseases with no effective established treatments. Hepatocyte growth factor (HGF) has preclinically proven to have potent antifibrotic and regenerative effects on vocal fold scar. The current Phase I/II clinical trial aims to examine the safety and effectiveness of intracordal injection of a recombinant human HGF drug for patients with vocal fold scar or sulcus. This is an open-label, dose-escalating, first-in-human clinical trial. Eighteen patients with bilateral vocal fold scar or sulcus were enrolled and divided into three groups: Step I received 1 μg of HGF per vocal fold; Step II received 3 μg of HGF; and Step III received 10 μg of HGF. Injections were administered once weekly for 4 weeks. The protocol treatment was performed starting with Step I and escalating to Step III. Patients were followed for 6 months post-treatment. Local and systemic safety aspects were examined as primary endpoints, and therapeutic effects were assessed as secondary endpoints using voice handicap index-10; maximum phonation time; vocal fold vibratory amplitude; grade, rough, breathy, asthenic, strained scale; and jitter. The results indicated no serious drug-related adverse events in either the systemic or local examinations. In whole-subject analysis, voice handicap index-10, vocal fold vibratory amplitude, and grade, rough, breathy, asthenic, strained scale were significantly improved at 6 months, whereas maximum phonation time and jitter varied. There were no significant differences in phonatory data between the step groups. In conclusion, intracordal injection of a recombinant human HGF drug was safe, feasible, and potentially effective for human patients with vocal fold scar or sulcus.

IMPORTANCE The Gynecologic Cancer InterGroup (GCIG) recommended that progression-free survival (PFS) can serve as a primary end point instead of overall survival (OS) in advanced ovarian cancer. Evidence is lacking for the validity of PFS as a surrogate marker of OS in the modern era of different treatment types. OBJECTIVE To evaluate whether PFS is a surrogate end point for OS in patients with advanced ovarian cancer. DATA SOURCES In September 2016, a comprehensive search of publications in MEDLINE was conducted for randomized clinical trials of systematic treatment in patients with newly diagnosed ovarian, fallopian tube, or primary peritoneal cancer. The GCIG groups were also queried for potentially completed but unpublished trials. STUDY SELECTION Studies with a minimum sample size of 60 patients published since 2001 with PFS and OS rates available were eligible. Investigational treatments considered included initial, maintenance, and intensification therapy consisting of agents delivered at a higher dose and/or frequency compared with that in the control arm. DATA EXTRACTION AND SYNTHESIS Using the meta-analytic approach on randomized clinical trials published from January 1, 2001, through September 25, 2016, correlations between PFS and OS at the individual level were estimated using the Kendall τ model; between-treatment effects on PFS and OS at the trial level were estimated using the Plackett copula bivariate (R 2) model. Criteria for PFS surrogacy required R 2 Ն 0.80 at the trial level. Analysis was performed from January 7 through March 20, 2019. MAIN OUTCOMES AND MEASURES Overall survival and PFS based on measurement of cancer antigen 125 levels confirmed by radiological examination results or by combined GCIG criteria. RESULTS In this meta-analysis of 17 unique randomized trials of standard (n = 7), intensification (n = 5), and maintenance (n = 5) chemotherapies or targeted treatments with data from 11 029 unique patients (median age, 58 years [range, 18-88 years]), a high correlation was found between PFS and OS at the individual level (τ = 0.724; 95% CI, 0.717-0.732), but a low correlation was found at the trial level (R 2 = 0.24; 95% CI, 0-0.59). Subgroup analyses led to similar results. In the external (continued) Key Points Question Is progression-free survival a validated surrogate end point for overall survival in first-line systemic treatment of ovarian cancer? Findings In this systematic review and meta-analysis of 17 unique trials with individual data from 11 029 unique patients, a high correlation between progression-free and overall survival was found at the individual level, but a low correlation was found at the trial level. Meaning These findings suggest that overall survival is the preferred end point in trials of first-line treatment or maintenance treatment, and progressive-free survival must be supported by additional end points if used as the primary end point.

Objectives In the present study, using a large automated health records database, we investigated the incidence of cardio-cerebrovascular events, diabetes new-onset events, and dialysis initiation events in hypertensive patients, and examined the effects of antihypertensive medications on these incidences. Materials and methods We conducted a search of an automated health records database that contained anonymous information from the health insurance claims and the results of laboratory tests at 15 medical facilities across Japan. The study cohort was defined as patients who were diagnosed with hypertension and who visited a medical institution in the registration period. Events were defined by diagnosis, medication history, and laboratory test results. Results We obtained a cohort of 20,686 patients diagnosed with hypertension. The mean (standard deviation, SD) age in the cohort was 67.9 (13.2) years, and the follow-up period was 2.56 (1.42) years. The total incidence rates per 1,000 person-years in the present study population showed good agreement with rates in reported cohort studies: 8.10 (5.6-11.1) for cerebrovascular events, 1.27 (0.5-7.4) for cerebral hemorrhage, 6.57 (4.6-8.9) for cerebral infarction, 0.46 (0.1-1.0) for subarachnoid hemorrhage, and 1.75 (1.6-4.4) for myocardial infarction. The standardized incidence rates of cardio-cerebrovascular events, diabetes new-onset events, and dialysis initiation events were 9.73, 20.94, and 5.99 events/1,000 personyears, respectively. Conclusions In terms of the incidence of the investigated events in hypertensive patients, the study results suggested that the automated health records database data were as valid and reliable as data from other epidemiological studies.