A systematic review of the impact of contemporary treatment modalities for cervical cancer on women's self-reported health-related quality of life.

PURPOSE: Given the high survival rate of cervical cancer patients, understanding women's health-related quality of life (HRQL) during and after treatment is of major clinical importance. We conducted a systematic review to synthesize all available evidence about the effects of each contemporary treatment modality for cervical cancer on all dimensions of women's HRQL, including symptoms, functioning, and global HRQL. METHODS: We searched four electronic databases from January 2000 to September 2019, cross-referenced and searched by author name for studies of patients treated for cervical cancer that reported patient-reported outcomes (PROs) before treatment and with at least one post-treatment measurement. Two independent reviewers applied inclusion and quality criteria and extracted findings. Studies were categorized by treatment to determine specific treatment effects on PROs. Results were narratively summarized. RESULTS: We found twenty-nine papers reporting 23 studies. After treatments with curative intent for early or locally advanced disease, lymphedema, diarrhea, menopausal symptoms, tight and shorter vagina, pain during intercourse, and sexual worries remained long-term problems; however, sexual activity improved over time. HRQL and psychological distress were impacted during treatment with also worsening of global HRQL but improved 3-6 months after treatment. In patients with metastatic or recurrent disease, pain improved during palliative treatment or remained stable, with no differences in global HRQL found over time. CONCLUSION: Whereas most symptoms worsen during treatment and improve in the first 3 months after completing treatment, symptoms like lymphedema, menopausal symptoms, and sexual worries develop gradually and persist after curative treatment. These findings can be used to inform clinical practice and facilitate communication and shared decision-making. More research is needed in very early cervical cancer and the impact of fertility sparing therapy on PROs.

Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung.

Phagocytes not only coordinate acute inflammation and host defense at mucosal sites, but also contribute to tissue damage. Respiratory infection causes a globally significant disease burden and frequently progresses to acute respiratory distress syndrome, a devastating inflammatory condition characterized by neutrophil recruitment and accumulation of protein-rich edema fluid causing impaired lung function. We hypothesized that targeting the intracellular protein myeloid cell leukemia 1 (Mcl-1) by a cyclin-dependent kinase inhibitor (AT7519) or a flavone (wogonin) would accelerate neutrophil apoptosis and resolution of established inflammation, but without detriment to bacterial clearance. Mcl-1 loss induced human neutrophil apoptosis, but did not induce macrophage apoptosis nor impair phagocytosis of apoptotic neutrophils. Neutrophil-dominant inflammation was modelled in mice by either endotoxin or bacteria (Escherichia coli). Downregulating inflammatory cell Mcl-1 had anti-inflammatory, pro-resolution effects, shortening the resolution interval (Ri) from 19 to 7 h and improved organ dysfunction with enhanced alveolar-capillary barrier integrity. Conversely, attenuating drug-induced Mcl-1 downregulation inhibited neutrophil apoptosis and delayed resolution of endotoxin-mediated lung inflammation. Importantly, manipulating lung inflammatory cell Mcl-1 also accelerated resolution of bacterial infection (Ri; 50 to 16 h) concurrent with enhanced bacterial clearance. Therefore, manipulating inflammatory cell Mcl-1 accelerates inflammation resolution without detriment to host defense against bacteria, and represents a target for treating infection-associated inflammation.

The origin of pelletal lapilli in explosive kimberlite eruptions.

Kimberlites are volatile-rich magmas from mantle depths of ≥ 150 km and are the primary source of diamonds. Kimberlite volcanism involves the formation of diverging pipes or diatremes, which are the locus of high-intensity explosive eruptions. A conspicuous and previously enigmatic feature of diatreme fills are 'pelletal lapilli'--well-rounded clasts consisting of an inner 'seed' particle with a complex rim, thought to represent quenched juvenile melt. Here we show that these coincide with a transition from magmatic to pyroclastic behaviour, thus offering fundamental insights into eruption dynamics and constraints on vent conditions. We propose that pelletal lapilli are formed when fluid melts intrude into earlier volcaniclastic infill close to the diatreme root zone. Intensive degassing produces a gas jet in which locally scavenged particles are simultaneously fluidised and coated by a spray of low-viscosity melt. A similar origin may apply to pelletal lapilli in other alkaline volcanic rocks, including carbonatites, kamafugites and melilitites.

Nonsurgical closure of patent ductus arteriosus: clinical application of the Rashkind PDA Occluder System.

The first successful application of a transcatheter closure technique for patent ductus arteriosus (PDA) suitable for use in infants and children was performed by us in 1977. Since that time, there has been continued improvement and simplification of the equipment as well as in the implantation technique. Following a Food and Drug Administration protocol, a multicenter study was conducted to test the safety and effectiveness of this interventional method. The clinical results from three major regional test centers (Philadelphia, Houston, and New Haven) are presented. One hundred forty-six patients from a test population of 156 were treated for PDA with use of the Rashkind PDA Occluder Systems. Successful closure was accomplished in 94 (66%) of the total cases. Ten patients (7%) retained residual ductal murmurs despite correct placement of the occlusion devices; five additional patients (3%) were considered failures due to the presence of abnormal Doppler flow patterns after the procedure. Postrelease embolizations occurred in 19 (15%) instances. One patient required emergency surgical intervention after attempted retrieval of an embolized occluder. With the improvements in the manufacturing of the double-disk occluder systems as well as the perfection of the transvenous delivery technique, the incidences of closure failure and postrelease complications have decreased. Since January 1984, 78% of all transcatheter closure attempts were successful, with 10% embolization.

Historical aspects of interventional cardiology: past, present and future.

The purpose of this presentation is to report the progress of two interventional catheter techniques that have occupied my attention for the last 10 years; namely, transcatheter patent ductus arteriosus occlusion and patch atrial septal defect closure. A brief survey of the aspects of interventional cardiology, including its past, present and future, will also be included.