Evaluation of CTPA interpreted as limited in pregnant patients suspected for pulmonary embolism.

PURPOSE: The purpose of this study is to determine the rates of CT pulmonary angiography (CTPA) interpreted as limited and severely limited in pregnant patients suspected for pulmonary embolism (PE), and to evaluate factors that influence these rates. METHODS: This is a retrospective study with CTPA for evaluation of PE in pregnancy across a large health system from 2006 to 2017. CTPA was classified as limited from the radiology report with a subset of those studies classified as severely limited. Bivariate and multivariate analysis was performed for limited and severely limited rates with maternal age and patient size as a continuous variable and race, trimester, patient location study priority status, and result of chest radiograph before CTPA as categorical variables. RESULTS: 874 patients with 33% of studies limited and 4% of studies severely limited. Multivariate logistic regression of CTPA studies revealed decreasing patient age (OR 0.967, p = 0.0129) and increasing patient size (OR 1.013, p < 0.0001). Studies performed in the second trimester (OR 1.869, p = 0.0242) and third trimester (OR 2.314, p = 0.0021) were more likely to be reported as limited (each p < 0.05). Increasing patient size (OR 1.017, p = 0.0046) was the only significant predictor of severely limited versus non-severely limited studies. CONCLUSION: CTPA interpreted as limited in pregnancy are common and may be associated with younger age, larger patient size, and second and third trimesters. However, severely limited interpretations are much less common, with patient size the only significant predictor.

Correction to: An analysis of 11.3 million screening tests examining the association between recall and cancer detection rates in the English NHS breast cancer screening programme.

The original version of this article, published on 04 February 2019, unfortunately contained a mistake.

An analysis of 11.3 million screening tests examining the association between recall and cancer detection rates in the English NHS breast cancer screening programme.

OBJECTIVE: To develop methods to model the relationship between cancer detection and recall rates to inform professional standards. METHODS: Annual screening programme information for each of the 80 English NHSBSP units (totalling 11.3 million screening tests) for the seven screening years from 1 April 2009 to 31 March 2016 and some Dutch screening programme information were used to produce linear and non-linear models. The non-linear models estimated the modelled maximum values (MMV) for cancers detected at different grades and estimated how rapidly the MMV was reached (the modelled 'slope' (MS)). Main outcomes include the detection rate for combined invasive/micro-invasive and high-grade DCIS (IHG) detection rate and the low/intermediate grade DCIS (LIG) detection rate. RESULTS: At prevalent screens for IHG cancers, 99% of the MMV was reached at a recall rate of 7.0%. The LIG detection rate had no discernible plateau, increasing linearly at a rate of 0.12 per 1000 for every 1% increase in recall rate. At incident screens, 99% of the MMV for IHG cancer detection was 4.0%. LIG DCIS increased linearly at a rate of 0.18 per 1000 per 1% increase in recall rate. CONCLUSIONS: Our models demonstrate the diminishing returns associated with increasing recall rates. The screening programme in England could use the models to set recall rate ranges, and other countries could explore similar methodology. KEY POINTS: • Question: How can we determine optimum recall rates in breast cancer screening? • Findings: In this large observational study, we show that increases in recall rates above defined levels are almost exclusively associated with false positive recalls and a very small increase in low/intermediate grade DCIS. • Meaning: High recall rates are not associated with increases in detection of life-threatening cancers. The models developed in this paper can be used to help set recall rate ranges that maximise benefit and minimise harm.

Role of performance metrics in breast screening imaging - where are we and where should we be?

The NHS Breast Screening Programme (NHSBSP) was started in 1988 and is a large, organised cancer screening programme. It is delivered by 80 services across England and screens over 2 million women each year. As a screening programme, it must balance the detection of cancers against possible harm to women who do not have cancer. The NHSBSP was therefore designed with detailed information gathering and performance metrics right from the start. In this review paper, we examine how performance metrics in screening mammography have improved the national screening programme and the further developments and challenges that are expected in the years to come.

Dilute versus concentrated vasopressin administration during laparoscopic myomectomy: a randomised controlled trial.

OBJECTIVE: To determine if higher-volume, fixed-dose administration of vasopressin further reduces blood loss at the time of minimally invasive myomectomy. DESIGN: Randomised multicentre clinical trial. SETTING: Tertiary-care academic centres in the USA. POPULATION: Women undergoing conventional laparoscopic or robot-assisted laparoscopic myomectomy. METHODS: All participants received the same 10-unit (U) dose of vasopressin, but were randomly assigned to one of two groups: (i) received 200 ml of diluted vasopressin solution (20 U in 400 ml normal saline), and (ii) received 30 ml of concentrated vasopressin solution (20 U in 60 ml normal saline). MAIN OUTCOME MEASURES: The primary study outcome was estimated blood loss; the study was powered to detect a 100-ml difference. RESULTS: A total of 152 women were randomised; 76 patients in each group. Baseline demographics were similar between groups. The primary outcome of intraoperative blood loss was not significantly different, as measured by three parameters: surgeon estimate (mean estimated blood loss 178 ± 265 ml and 198 ± 232 ml, dilute and concentrated groups respectively, P = 0.65), suction canister-calculated blood loss, or change in haematocrit levels. There were no vasopressin-related adverse events. CONCLUSION: Both dilute and concentrated vasopressin solutions that use the same drug dosing demonstrate comparable safety and tolerability when administered for minimally invasive myomectomy; however, higher volume administration of vasopressin does not reduce blood loss. TWEETABLE ABSTRACT: This randomised trial failed to show benefit of high-volume dilute vasopression.

Acute renal failure after cardiothoracic surgery: a review of three years experience.

2,683 cardiothoracic operations were carried out over a 3-year period. Patients requiring haemofiltration after surgery had a much greater mortality than those not haemofiltered. Of the 1,177 cardiothoracic intensive care unit (ICU) patients, 91 required haemofiltration for acute renal failure (ARF; 7.7%). Of the 1,506 cardiothoracic high-dependency unit patients 13 were transferred to the renal unit for dialysis (0.86%). Mortality for cardiothoracic patients overall was 14.4% and for those who required haemofiltration 58.7%. 74 of these haemofiltered patients had normal renal function preoperatively; mortality 61%. 15 patients had pre-existing renal impairment; mortality 53.3%. 15 patients were on dialysis prior to surgery; mortality 60%. Age was not a predictor of requirement for renal replacement therapy or of mortality. Operation type was a risk factor for ARF: of patients having a coronary artery bypass graft (CABG) 2.4% were filtered (mortality 37.8%), of patients having valve replacements 14.2% were haemofiltered (mortality 60.9%), and of the patients having redo-CABGs or redo-valve replacements 12.3% required haemofiltration (mortality 100%).

EMG biofeedback: the effects of CRF, FR, VR, FI, and VI schedules of reinforcement on the acquisition and extinction of increases in forearm muscle tension.

Biofeedback was used to increase forearm-muscle tension. Feedback was delivered under continuous reinforcement (CRF), variable interval (VI), fixed interval (FI), variable ratio (VR), and fixed ratio (FR) schedules of reinforcement when college students increased their muscle tension (electromyograph, EMG) above a high threshold. There were three daily sessions of feedback, and Session 3 was immediately followed by a session without feedback (extinction). The CRF schedule resulted in the highest EMG, closely followed by the FR and VR schedules, and the lowest EMG scores were produced by the FI and VI schedules. Similarly, the CRF schedule resulted in the greatest amount of time-above-threshold and the VI and FI schedules produced the lowest time-above-threshold. The highest response rates were generated by the FR schedule, followed by the VR schedule. The CRF schedule produced relatively low response rates, comparable to the rates under the VI and FI schedules. Some of the data are consistent with the partial-reinforcement-extinction effect. The present data suggest that different schedules of feedback should be considered in muscle-strengthening-contexts such as during the rehabilitation of muscles following brain damage or peripheral nervous-system injury.

Treadmill and cycle ergometry testing in 5- to 6-year-old children.

The primary purpose of this study was to determine the maximal cardiorespiratory responses of 48, 5- to 6-year-old children (24 girls and 24 boys), who were tested on a treadmill (TM) and an electronically braked cycle ergometer (CE). We also examined the percentage of boys and girls who were able to achieve the criteria for reaching maximal oxygen consumption (VO2max) on each testing mode. After an orientation period, each child was tested twice (once on the TM and once on the CE), with an interval of 1 week between tests. VO2max was measured during progressive, all out, continuous TM and CE tests using standardized procedures. A 2 x 2 analysis of variance test (genderxexercise mode) with Bonferroni adjustment revealed the following: (1) there were no gender differences in any of the measured dependent variables, (2) the children produced a significantly higher relative VO2max (ml x kg(-1) x min(-1) and a higher absolute VO2max (l x min(-1)) on the TM than on the CE (P < 0.001), (3) the children produced a higher heart rate on the TM than on the CE (P < 0.001), (4) the CE generated significantly higher values for respiratory exchange ratio (P < 0.001), (5) the criteria necessary to establish a maximal exercise effort were achieved on both the TM and the CE, and (6) all of the children reached two of the criteria associated with a maximal effort, while only 46% of the children reached three criterion measures. There were no significant differences in the attainment of criterion measures between the TM and the CE. The results of this study indicate a lack of gender differences in maximal exercise testing in 5- to 6-year-old children, and that both the CE and the TM are effective modes of maximal cardiorespiratory testing in this age group.

Mass spectrometry as a tool for protein crystallography.

Atomic resolution structure determinations of proteins by X-ray crystallography are formidable multidisciplinary undertakings, requiring protein construct design, expression and purification, crystallization trials, phase determination, and model building. Modern mass spectrometric methods can greatly facilitate these obligate tasks. Thus, mass spectrometry can be used to verify that the desired protein construct has been correctly expressed, to define compact domains in the target protein, to assess the components contained within the protein crystals, and to screen for successful incorporation of seleno-methionine and other heavy metal reagents used for phasing. In addition, mass spectrometry can be used to address issues of modeling, topology, and side-chain proximity. Here, we demonstrate how rational use of mass spectrometry assists and expedites high resolution X-ray structure determination through each stage of the process of protein crystallography.

Mass spectrometric analysis of mercury incorporation into proteins for X-ray diffraction phase determination.

Heavy-atom incorporation is an essential and often rate-limiting step in the determination of phases for X-ray diffraction studies of protein structures. Until the present, there has been no practical method (short of the X-ray diffraction experiment itself) to judge the success and extent of incorporation. Here we show that mass spectrometry is an effective tool for determining the extent of heavy-atom incorporation in proteins. In particular, we demonstrate the utility of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and electrospray ionization mass spectrometry (ESI-MS) for assaying mercury derivatization of cysteinyl thiol groups in proteins. Each of these mass spectrometric methods has advantages and drawbacks. ESI-MS provides a more accurate quantitative measurement of the extent of mercury incorporation, while MALDI-MS provides a useful lower limit to the level of mercury incorporation. Conversely, MALDI-MS does not require removal of excess derivatization reagents, salts and buffers, thus permitting facile analysis of single protein crystals as well as rapid, semiquantitative evaluation of the extent of protein mercuration. The approaches described in the present paper have contributed to the successful X-ray analyses of several noteworthy protein structures.

Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain.

The HERG voltage-dependent K+ channel plays a role in cardiac electrical excitability, and when defective, it underlies one form of the long QT syndrome. We have determined the crystal structure of the HERG K+ channel N-terminal domain and studied its role as a modifier of gating using electrophysiological methods. The domain is similar in structure to a bacterial light sensor photoactive yellow protein and provides the first three-dimensional model of a eukaryotic PAS domain. Scanning mutagenesis of the domain surface has allowed the identification of a hydrophobic "hot spot" forming a putative interface with the body of the K+ channel to which it tightly binds. The presence of the domain attached to the channel slows the rate of deactivation. Given the roles of PAS domains in biology, we propose that the HERG N-terminal domain has a regulatory function.

Structural conservation in prokaryotic and eukaryotic potassium channels.

Toxins from scorpion venom interact with potassium channels. Resin-attached, mutant K+ channels from Streptomyces lividans were used to screen venom from Leiurus quinquestriatus hebraeus, and the toxins that interacted with the channel were rapidly identified by mass spectrometry. One of the toxins, agitoxin2, was further studied by mutagenesis and radioligand binding. The results show that a prokaryotic K+ channel has the same pore structure as eukaryotic K+ channels. This structural conservation, through application of techniques presented here, offers a new approach for K+ channel pharmacology.

The structure of the potassium channel: molecular basis of K+ conduction and selectivity.

The potassium channel from Streptomyces lividans is an integral membrane protein with sequence similarity to all known K+ channels, particularly in the pore region. X-ray analysis with data to 3.2 angstroms reveals that four identical subunits create an inverted teepee, or cone, cradling the selectivity filter of the pore in its outer end. The narrow selectivity filter is only 12 angstroms long, whereas the remainder of the pore is wider and lined with hydrophobic amino acids. A large water-filled cavity and helix dipoles are positioned so as to overcome electrostatic destabilization of an ion in the pore at the center of the bilayer. Main chain carbonyl oxygen atoms from the K+ channel signature sequence line the selectivity filter, which is held open by structural constraints to coordinate K+ ions but not smaller Na+ ions. The selectivity filter contains two K+ ions about 7.5 angstroms apart. This configuration promotes ion conduction by exploiting electrostatic repulsive forces to overcome attractive forces between K+ ions and the selectivity filter. The architecture of the pore establishes the physical principles underlying selective K+ conduction.