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11.

Background

The purpose of the study was to evaluate the association between fetal echocardiographic measurements and the need for intervention (primary coarctation repair, staged coarctation repair, or catheter intervention) in prenatally diagnosed coarctation of the aorta.

Methods

A single-centre retrospective cohort study (2005-2015) of 107 fetuses diagnosed with suspected coarctation of the aorta in the setting of an apex-forming left ventricle and antegrade flow across the mitral and aortic valves.

Results

Median gestational age at diagnosis was 32 weeks (interquartile range, 23-35 weeks). Fifty-six (52%) did not require any neonatal intervention, 51 patients (48%) underwent a biventricular repair. In univariable analysis, an increase in ascending aorta (AAo) peak Doppler flow velocity (odds ratio [OR], 1.40 [95% confidence interval [CI], 1.05-1.91] per 20 cm/s; P = 0.03) was associated with intervention. No intervention was associated with larger isthmus size (OR, 0.23; P < 0.001), transverse arch diameter (OR, 0.23; P < 0.001), and aortic (OR, 0.72; P = 0.02), mitral (OR, 0.58; P = 0.001), and AAo (OR, 0.53; P < 0.001) z-scores. In multivariable analysis, higher peak AAo Doppler (OR, 2.51 [95% CI, 1.54-4.58] per 20 cm/s; P = 0.001) and younger gestational age at diagnosis (OR, 0.81 [95% CI, 0.70-0.93] per week; P = 0.005) were associated with intervention, whereas a higher AAo z-score (OR, 0.65 [95% CI, 0.43-0.94] per z; P = 0.029) and transverse arch dimension (OR, 0.44 [95% CI, 0.18-0.97]; P = 0.05) decreased the risk of intervention.

Conclusions

In prenatally suspected coarctation, the variables associated with intervention comprised smaller AAo and transverse arch size, earlier gestational age at diagnosis, and the additional finding of a higher peak AAo Doppler.  相似文献   
12.
Abstract

Objectives: This study examined word use as an indicator of interpersonal positive reframing in daily conversations of couples coping with breast cancer and as a predictor of stress.

Design: The Electronically Activated Recorder (EAR) and Linguistic Inquiry and Word Count (LIWC) were used to examine naturally occurring word use conceptually linked to positive reframing (positive emotion, negative emotion, and cognitive processing words).

Sample: Fifty-two couples coping with breast cancer.

Methods: Couples wore the EAR, a device participants wear, that audio-recorded over one weekend (>16,000 sound files), and completed self-reports of positive reframing (COPE) and stress (Perceived Stress Scale). LIWC, a software program, measured word use.

Findings: Both partners’ word use (i.e., positive emotion and cognitive processing words) was associated with their own reported positive reframing, and spouses’ word use was also indicative of patients’ positive reframing. Results also revealed that, in general, words indicating positive reframing predicted lower levels of stress.

Conclusions: Findings supported the hypothesis that partners—and particularly spouses of breast cancer patients—may assist each other’s coping by positively reframing the cancer experience and other negative experiences in conversation.  相似文献   
13.

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Objectives

To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.

Methods

Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.

Results

Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.

Conclusions

These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.  相似文献   
14.
Purpose: To study, with computational models, the utility of power modulation to reduce tissue temperature heterogeneity for variable nanoparticle distributions in magnetic nanoparticle hyperthermia.

Methods: Tumour and surrounding tissue were modeled by elliptical two- and three-dimensional computational phantoms having six different nanoparticle distributions. Nanoparticles were modeled as point heat sources having amplitude-dependent loss power. The total number of nanoparticles was fixed, and their spatial distribution and heat output were varied. Heat transfer was computed by solving the Pennes’ bioheat equation using finite element methods (FEM) with temperature-dependent blood perfusion. Local temperature was regulated using a proportional-integral-derivative (PID) controller. Tissue temperature, thermal dose and tissue damage were calculated. The required minimum thermal dose delivered to the tumor was kept constant, and heating power was adjusted for comparison of both the heating methods.

Results: Modulated power heating produced lower and more homogeneous temperature distributions than did constant power heating for all studied nanoparticle distributions. For a concentrated nanoparticle distribution, located off-center within the tumor, the maximum temperatures inside the tumor were 16% lower for modulated power heating when compared to constant power heating. This resulted in less damage to surrounding normal tissue. Modulated power heating reached target thermal doses up to nine-fold more rapidly when compared to constant power heating.

Conclusions: Controlling the temperature at the tumor-healthy tissue boundary by modulating the heating power of magnetic nanoparticles demonstrably compensates for a variable nanoparticle distribution to deliver effective treatment.  相似文献   

15.

Aims

To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer.

Materials and methods

The analyses were based on all patients who underwent surgical treatment for endometrial, ovarian or cervical cancer who were registered in the Danish Gynecological Cancer Database in the years 2007–2014 (3059 patients with ovarian cancer, 5100 patients with endometrial cancer and 1150 with cervical cancer). Logistic regression model and Cox regression model, adjusted for relevant confounders, were used to estimate the effect of pre-existing psychiatric disorder on the course of cancer treatment. Our outcomes were (i) presurgical oncological treatment, (ii) macroradical surgery for patients with ovarian cancer, (iii) radiation/chemotherapy within 30 days and 100 days after surgery and (iv) time from surgery to first oncological treatment.

Results

In the group of patients with ovarian cancer, more patients with a psychiatric disorder received macroradical surgery versus patients without a psychiatric disorder, corresponding to an adjusted odds ratio of 1.24 (95% confidence interval 0.62–2.41) and the chance for having oncological treatment within 100 days was odds ratio = 1.26 (95% confidence interval 0.77–2.10). As for patients with endometrial cancer, all outcome estimates were close to unity. The adjusted odds ratio for oncological treatment within 30 days after surgery in patients with cervical cancer with a history of psychiatric disorder was 0.20 (95% confidence interval 0.03–1.54).

Conclusions

We did not find any significant differences in the treatment of ovarian and endometrial cancer in patients with pre-existing psychiatric diagnoses. When it comes to oncological treatment, we suggest that increased attention should be paid to patients with cervical cancer having a pre-existing psychiatric diagnosis.  相似文献   
16.

Objective

To determine whether differences in combination DTaP vaccine types at 2, 4 and 6?months of age were associated with mortality (all-cause or non-specific), within 30?days of vaccination.

Design

Observational nationwide cohort study.

Setting

Linked population data from the Australian Childhood Immunisation Register and National Death Index.

Participants

Australian infants administered a combination trivalent, quadrivalent or hexavalent DTaP vaccine (DTaP types) between January 1999 and December 2010 at 2, 4 and 6?months as part of the primary vaccination series. The study population included 2.9, 2.6, & 2.3?million children in the 2, 4 and 6?month vaccine cohorts, respectively.

Main outcome measures

Infants were evaluated for the primary outcome of all-cause mortality within 30?days. A secondary outcome was non-specific mortality (unknown cause of death) within 30?days of vaccination. Non-specific mortality was defined as underlying or other cause of death codes, R95 ‘Sudden infant death syndrome’, R96 ‘Other sudden death, cause unknown’, R98 ‘Unattended death’, R99 ‘Other ill-defined and unspecified cause of mortality’ or where no cause of death was recorded.

Results

The rate of 30?day all-cause mortality was low and declined from 127.4 to 59.3 deaths per 100,000 person-years between 2 and 6?month cohorts. When compared with trivalent DTaP vaccines, no elevated risk in all-cause or non-specific mortality was seen with any quadrivalent or hexavalent DTaP vaccines, for any cohort.

Conclusion

Use of routine DTaP combination vaccines with differing disease antigens administered during the first six months of life is not associated with infant mortality.  相似文献   
17.

Background

The optimal noninvasive test (NIT) for patients with diabetes and stable symptoms of coronary artery disease (CAD) is unknown.

Objectives

The purpose of this study was to assess whether a diagnostic strategy based on coronary computed tomographic angiography (CTA) is superior to functional stress testing in reducing adverse cardiovascular (CV) outcomes (CV death or myocardial infarction [MI]) among symptomatic patients with diabetes.

Methods

PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) was a randomized trial evaluating an initial strategy of CTA versus functional testing in stable outpatients with symptoms suggestive of CAD. The study compared CV outcomes in patients with diabetes (n = 1,908 [21%]) and without diabetes (n = 7,058 [79%]) based on their randomization to CTA or functional testing.

Results

Patients with diabetes (vs. without) were similar in age (median 61 years vs. 60 years) and sex (female 54% vs. 52%) but had a greater burden of CV comorbidities. Patients with diabetes who underwent CTA had a lower risk of CV death/MI compared with functional stress testing (CTA: 1.1% [10 of 936] vs. stress testing: 2.6% [25 of 972]; adjusted hazard ratio: 0.38; 95% confidence interval: 0.18 to 0.79; p = 0.01). There was no significant difference in nondiabetic patients (CTA: 1.4% [50 of 3,564] vs. stress testing: 1.3% [45 of 3,494]; adjusted hazard ratio: 1.03; 95% confidence interval: 0.69 to 1.54; p = 0.887; interaction term for diabetes p value = 0.02).

Conclusions

In diabetic patients presenting with stable chest pain, a CTA strategy resulted in fewer adverse CV outcomes than a functional testing strategy. CTA may be considered as the initial diagnostic strategy in this subgroup. (PROspective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550)  相似文献   
18.
BACKGROUND AND PURPOSE:In the chronic phase after traumatic brain injury, DTI findings reflect WM integrity. DTI interpretation in the subacute phase is less straightforward. Microbleed evaluation with SWI is straightforward in both phases. We evaluated whether the microbleed concentration in the subacute phase is associated with the integrity of normal-appearing WM in the chronic phase.MATERIALS AND METHODS:Sixty of 211 consecutive patients 18 years of age or older admitted to our emergency department ≤24 hours after moderate to severe traumatic brain injury matched the selection criteria. Standardized 3T SWI, DTI, and T1WI were obtained 3 and 26 weeks after traumatic brain injury in 31 patients and 24 healthy volunteers. At baseline, microbleed concentrations were calculated. At follow-up, mean diffusivity (MD) was calculated in the normal-appearing WM in reference to the healthy volunteers (MDz). Through linear regression, we evaluated the relation between microbleed concentration and MDz in predefined structures.RESULTS:In the cerebral hemispheres, MDz at follow-up was independently associated with the microbleed concentration at baseline (left: B = 38.4 [95% CI 7.5–69.3], P = .017; right: B = 26.3 [95% CI 5.7–47.0], P = .014). No such relation was demonstrated in the central brain. MDz in the corpus callosum was independently associated with the microbleed concentration in the structures connected by WM tracts running through the corpus callosum (B = 20.0 [95% CI 24.8–75.2], P < .000). MDz in the central brain was independently associated with the microbleed concentration in the cerebral hemispheres (B = 25.7 [95% CI 3.9–47.5], P = .023).CONCLUSIONS:SWI-assessed microbleeds in the subacute phase are associated with DTI-based WM integrity in the chronic phase. These associations are found both within regions and between functionally connected regions.

The yearly incidence of traumatic brain injury (TBI) is around 300 per 100,000 persons.1,2 Almost three-quarters of patients with moderate to severe TBI have traumatic axonal injury (TAI).3 TAI is a major predictor of functional outcome,4,5 but it is mostly invisible on CT and conventional MR imaging.6,7DTI provides direct information on WM integrity and axonal injury.5,8 However, DTI abnormalities are neither specific for TAI nor stable over time. Possibly because of the release of mass effect and edema and resorption of blood products, the effects of concomitant (non-TAI) injury on DTI are larger in the subacute than in the chronic phase (>3 months).4,9,10 Therefore, DTI findings are expected to reflect TAI more specifically in the chronic than in the subacute phase (1 week–3 months).4 Even in regions without concomitant injury, the effects of TAI on DTI are dynamic, possibly caused by degeneration and neuroplastic changes.6,11,12 These ongoing pathophysiological processes possibly contribute to the emerging evidence that DTI findings in the chronic phase are most closely associated with the eventual functional outcome.12,13Although DTI provides valuable information, its acquisition, postprocessing, and interpretation in individual patients are demanding. SWI, with which microbleeds can be assessed with high sensitivity, is easier to interpret and implement in clinical practice. In contrast to DTI, SWI-detected traumatic microbleeds are more stable1 except in the hyperacute14,15 and the late chronic phases.16 Traumatic cerebral microbleeds are commonly interpreted as signs of TAI. However, the relation is not straightforward. On the one hand, nontraumatic microbleeds may be pre-existing. On the other hand, even if traumatic in origin, microbleeds represent traumatic vascular rather than axonal injury.17 Indeed, TAI is not invariably hemorrhagic.18 Additionally, microbleeds may secondarily develop after trauma through mechanisms unrelated to axonal injury, such as secondary ischemia.18DTI is not only affected by pathophysiological changes but also by susceptibility.19 The important susceptibility-effect generated by microbleeds renders the interpretation of DTI findings at the location of microbleeds complex. In the chronic phase, mean diffusivity (MD) is the most robust marker of WM integrity.4,6 For these reasons, we evaluated MD in the normal-appearing WM.Much TAI research focuses on the corpus callosum because it is commonly involved in TAI5,18,20 and it can reliably be evaluated with DTI,5,21 and TAI in the corpus callosum is related to clinical prognosis.6,20 The corpus callosum consists of densely packed WM tracts that structurally and functionally connect left- and right-sided brain structures.22 The integrity of the corpus callosum is associated with the integrity of the brain structures it connects.23 Therefore, microbleeds in brain structures that are connected through the corpus callosum may affect callosal DTI findings. Analogous to this, microbleeds in the cerebral hemispheres, which exert their function through WM tracts traveling through the deep brain structures and brain stem,24,25 may affect DTI findings in the WM of the latter.Our purpose was to evaluate whether the microbleed concentration in the subacute phase is associated with the integrity of normal-appearing WM in the chronic phase. We investigated this relation within the cerebral hemispheres and the central brain and between regions that are functionally connected by WM tracts.  相似文献   
19.

Background

In a pooled analysis of the phase 3 Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment I (COMFORT-I) and COMFORT-II clinical trials, adult patients with intermediate-2 or high-risk myelofibrosis who received oral ruxolitinib at randomization or after crossover from placebo or best available therapy (BAT) had improved overall survival (OS).

Methods

This post hoc analysis of pooled COMFORT data examined relevant disease outcomes based on the disease duration (≤12 or >12 months from diagnosis) before ruxolitinib initiation.

Results

The analysis included 525 patients (ruxolitinib: ≤12 months, n = 84; >12 months, n = 216; placebo/BAT: ≤12 months, n = 66; >12 months, n = 159); the median age was 65.0–70.0 years. Fewer thrombocytopenia and anemia events were observed among patients who initiated ruxolitinib treatment earlier. At Weeks 24 and 48, the spleen volume response (SVR) was higher for patients who initiated ruxolitinib earlier (47.6% vs. 32.9% at Week 24, p = .0610; 44.0% vs. 26.9% at Week 48, p = .0149). In a multivariable analysis of factors associated with spleen volume reduction, a logistic regression model that controlled for confounding factors found that a significantly greater binary reduction was observed among patients with shorter versus longer disease duration (p = .022). At Week 240, OS was significantly improved among patients who initiated ruxolitinib earlier (63% [95% CI, 51%‒73%] vs. 57% [95% CI, 49%‒64%]; hazard ratio, 1.53; 95% CI, 1.01‒2.31; p = .0430). Regardless of disease duration, a longer OS was observed for patients who received ruxolitinib versus those who received placebo/BAT.

Conclusions

These findings suggest that earlier ruxolitinib initiation for adult patients with intermediate-2 and high-risk myelofibrosis may improve clinical outcomes, including fewer cytopenia events, durable SVR, and prolonged OS.

Plain Language Summary

  • Patients with myelofibrosis, a bone marrow cancer, often do not live as long as the general population. These patients may also have an enlarged spleen and difficult symptoms such as fatigue.
  • Two large clinical trials showed that patients treated with the drug ruxolitinib lived longer and had improved symptoms compared to those treated with placebo or other standard treatments.
  • Here it was examined whether starting treatment with ruxolitinib earlier (i.e., within a year of diagnosis) provided benefits versus delaying treatment.
  • Patients who received ruxolitinib within a year of diagnosis lived longer and experienced fewer disease symptoms than those whose treatment was delayed.
  相似文献   
20.
Objective: To assess the quality of images and video clips of fetal central nervous (CNS) structures obtained by ultrasound and transmitted via tele-ultrasound from Brazil to Australia.

Methods: In this cross-sectional study, 15 normal singleton pregnant women between 20 and 26 weeks were selected. Fetal CNS structures were obtained by images and video clips. The exams were transmitted in real-time using a broadband internet and an inexpensive video streaming device. Four blinded examiners evaluated the quality of the exams using the Likert scale. We calculated the mean, standard deviation, mean difference, and p values were obtained from paired t tests.

Results: The quality of the original video clips was slightly better than that observed by the transmitted video clips; mean difference considering all observers = 0.23 points. In 47/60 comparisons (78.3%; 95% CI?=?66.4–86.9%) the quality of the video clips were judged to be the same. In 182/240 still images (75.8%; 95% CI?=?70.0–80.8%) the scores of transmitted image were considered the same as the original.

Conclusion: We demonstrated that long distance tele-ultrasound transmission of fetal CNS structures using an inexpensive video streaming device provided images of subjective good quality.  相似文献   
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