Abstract Background Transcaval access may enable fully percutaneous transcatheter aortic valve replacement (TAVR) without the hazards and discomfort of transthoracic (transapical or transaortic) ...access. Objectives We performed a prospective, independently-adjudicated, multi-center, single-arm Investigational Device Exemption trial of transcaval access for TAVR in patients ineligible for femoral artery access and high or prohibitive risk of complications from transthoracic access. Methods 100 subjects underwent attempted percutaneous transcaval access to the abdominal aorta by electrifying a caval guidewire and advancing into a prepositioned aortic snare. After exchanging for a rigid guidewire, conventional TAVR was performed through transcaval introducer sheaths. Transcaval access ports were closed with nitinol cardiac occluders. A core lab analyzed pre-discharge and 30-day abdominal CT. The STS predicted risk of mortality was 9.6 ± 6.3%. Results Transcaval access was successful in 99/100 subjects. Device success (access and closure with a nitinol cardiac occluder without death or emergency surgical rescue) was 98/99, except for one closed only with a covered stent. Inpatient survival was 96% and 30-day survival was 92%. VARC2 life-threatening bleeding and modified VARC2 major vascular complications possibly related to transcaval access were 7% and 13%, respectively. Median length of stay was 4 (2-6) days. There were no vascular complications after discharge. Conclusion Transcaval access enabled TAVR in patients who were not good candidates for transthoracic access. Bleeding and vascular complications, using permeable nitinol cardiac occluders to close the access ports, were common but acceptable in this high risk cohort. Transcaval access should be investigated in patients who are eligible for transthoracic access. Purpose-built closure devices are in development that may simplify the procedure and reduce bleeding.
The composition and distribution of deep-sea sediments is the result of a multitude of climatic, biotic and oceanic conditions relating to biogeochemical cycles and environmental change. Here we ...utilize the extensive sediment archives of the International Ocean Discovery Program (IODP) and its predecessors to construct maps of deep-sea sediment type across two critical but contrasting boundaries in the Paleogene, one characterised by an interval of extreme warmth (Paleocene/Eocene) and the other by global cooling (Eocene/Oligocene). Ocean sediment distribution shows significant divergence both between the latest Paleocene and Paleocene Eocene Thermal Maximum (PETM), across the Eocene-Oligocene Transition (EOT), and in comparison to modern sediment distributions. Carbonate sedimentation in the latest Paleocene extends to high southern latitudes. Disappearance of carbonate sediments at the PETM is well documented and can be attributed to dissolution caused by significant ocean acidification as a result of carbon-cycle perturbation. Biosiliceous sediments are rare and it is posited that the reduced biogenic silica deposition at the equator is commensurate with an overall lack of equatorial upwelling in the early Paleogene ocean. In the Southern Ocean, we attribute the low in biosiliceous burial, to the warm deep water temperatures which would have impacted biogenic silica preservation. In the late Eocene, our sediment depositional maps record a tongue of radiolarian ooze in the eastern equatorial Pacific. Enhanced biosiliceous deposits in the late Eocene equatorial Pacific and South Atlantic are due to increased productivity and the spin-up of the oceans. Our compilation documents the enhanced global carbonate sedimentation in the early Oligocene, confirming that the drop in the carbonate compensation depth was global.
Background
Fifteen regional studies published over the last six decades surveying prevalence, mortality and hospital admissions have suggested that Scotland is amongst the highest risk nations for ...multiple sclerosis (MS) in the world. However, substantial intranational variation in rates (between regions) has been described in numerous countries, including in the only previous Scottish national survey, which used hospital admission data, to address this issue. Against this backdrop, the Scottish Multiple Sclerosis Register (SMSR) was established in 2010 to prospectively collect nationally comprehensive incidence data and to allow for regional comparisons.
Methods
Here, we present the SMSR and analyse the variation in crude and age–sex standardized incidence rates, lifetime risk (cumulative incidence), and the sex distribution of cases and rates, between the 14 administrative Health Boards or regions of Scotland: 01 January 2010 to 31 December 2017.
Results
The overall incidence rate for Scotland was 8.76/100,000 person-years (standardized: 8.54). Regional incidence rates varied significantly—up to threefold—between Health Boards (
p
< 1 × 10
–13
). The national female-to-male sex ratio was 2.3:1, but this too varied regionally (outlier regions result in a range from 1.0 to 4.2:1). Lifetime risk ranged from 19.9/1000 for females in Orkney (58.98°N) to 1.6/1000 for males in the Borders (55.60°N). Comparison with a previous national survey suggests that these differences are longstanding. In 6 of 14 regions the lifetime risk for women exceeds 1%.
Conclusions
This study introduces a national incidence register: a valuable research tool and the result of substantial public investment. The wide variation in incidence rates and sex ratios between regions, in a relatively homogenous population, raises questions for future study.
To determine whether reformatted computed tomography (CT) scans would increase surgeons' confidence in placing a trans sacral (TS) screw in the first sacral segment.
Level 1 trauma center.
A ...retrospective cohort study.
There were 50 patients with uninjured pelvises who were reviewed by 9 orthopaedic trauma fellowship-trained surgeons and 5 orthopaedic residents.
The overall percentage of surgeons who believe it was safe to place a TS screw in the first sacral segment with standard (axial cuts perpendicular to the scanner gantry) versus reformatted (parallel to the S1 end plate) CT scans.
Overall, 58% of patients were believed to have a safe corridor in traditional cut axial CT scans, whereas 68% were believed to have a safe corridor on reformatted CT scans ( P < 0.001). When grouped by dysplasia, those without sacral dysplasia (n = 28) had a safe corridor 93% of the time on traditional scans and 93% of the time with reformatted CT scans ( P = 0.87). However, of those who had dysplasia (n = 22), only 12% were believed to have a safe corridor on original scans compared with 35% on reformatted scans ( P < 0.001).
CT scan reformatting parallel to the S1 superior end plate increases the likelihood of identifying a safe corridor for a TS screw, especially in patients with evidence of sacral dysplasia. The authors would recommend the routine use of reformatting CT scans in this manner to provide a better understanding of the upper sacral segment osseous fixation pathways.
Summary We report concurrent metastatic prostatic adenocarcinoma (PC) and functioning androgen-secreting adrenocortical carcinoma (ACC) in a 77-year-old man. The failure to achieve adequate ...biochemical castration via androgen deprivation therapy (ADT) as treatment for PC metastases, together with elevated DHEA-S, androstenedione, and discordant adrenal tracer uptake on FDG-PET and PSMA-PET, suggested the presence of a concurrent functional primary adrenal malignancy. On histopathological analysis, scant foci of PC were present throughout the ACC specimen. Castration was achieved post adrenalectomy with concurrent drop in prostate-specific antigen. We outline the literature regarding failure of testosterone suppression on ADT and salient points regarding diagnostic workup of functioning adrenal malignancies. Learning points Failure to achieve castration with androgen deprivation therapy is rare and should prompt careful review to identify the underlying cause. All adrenal lesions should be evaluated for hormone production, as well as assessed for risk of malignancy (either primary or secondary). Adrenocortical carcinomas are commonly functional, and can secrete steroid hormones or their precursors (androgens, progestogens, glucocorticoids and mineralocorticoids). In this case, a co-incident, androgen-producing adrenocortical carcinoma was the cause of failure of testosterone suppression from androgen deprivation therapy as treatment for metastatic prostate cancer. Pathological adrenal androgen production contributed to the progression of prostate cancer.
The complete sequence of the 1,267,782 bp genome of Wolbachia pipientis wMel, an obligate intracellular bacteria of Drosophila melanogaster, has been determined. Wolbachia, which are found in a ...variety of invertebrate species, are of great interest due to their diverse interactions with different hosts, which range from many forms of reproductive parasitism to mutualistic symbioses. Analysis of the wMel genome, in particular phylogenomic comparisons with other intracellular bacteria, has revealed many insights into the biology and evolution of wMel and Wolbachia in general. For example, the wMel genome is unique among sequenced obligate intracellular species in both being highly streamlined and containing very high levels of repetitive DNA and mobile DNA elements. This observation, coupled with multiple evolutionary reconstructions, suggests that natural selection is somewhat inefficient in wMel, most likely owing to the occurrence of repeated population bottlenecks. Genome analysis predicts many metabolic differences with the closely related Rickettsia species, including the presence of intact glycolysis and purine synthesis, which may compensate for an inability to obtain ATP directly from its host, as Rickettsia can. Other discoveries include the apparent inability of wMel to synthesize lipopolysaccharide and the presence of the most genes encoding proteins with ankyrin repeat domains of any prokaryotic genome yet sequenced. Despite the ability of wMel to infect the germline of its host, we find no evidence for either recent lateral gene transfer between wMel and D. melanogaster or older transfers between Wolbachia and any host. Evolutionary analysis further supports the hypothesis that mitochondria share a common ancestor with the alpha-Proteobacteria, but shows little support for the grouping of mitochondria with species in the order Rickettsiales. With the availability of the complete genomes of both species and excellent genetic tools for the host, the wMel-D. melanogaster symbiosis is now an ideal system for studying the biology and evolution of Wolbachia infections.
The use of a microfilaricidal drug for the control of onchocerciasis and lymphatic filariasis necessitates prolonged yearly dosing. Prospects for elimination or eradication of these diseases would be ...enhanced by availability of a macrofilaricidal drug. Flubendazole (FLBZ), a benzimidazole anthelmintic, is an appealing candidate macrofilaricide. FLBZ has demonstrated profound and potent macrofilaricidal effects in a number of experimental filarial rodent models and one human trial. Unfortunately, FLBZ was deemed unsatisfactory for use in mass drug administration (MDA) campaigns due to its markedly limited oral bioavailability. However, a new formulation that provided sufficient bioavailability following oral administration could render FLBZ an effective treatment for onchocerciasis and LF. This study characterized the effects of FLBZ and its reduced metabolite (FLBZ-R) on filarial nematodes in vitro to determine the exposure profile which results in demonstrable damage. Adult female Brugia malayi were exposed to varying concentrations of FLBZ or FLBZ-R (100 nM–10 μM) for up to five days, after which worms were fixed for histology. Morphological damage following exposure to FLBZ was observed prominently in the hypodermis and developing embryos at concentrations as low as 100 nM following 24 h exposure. The results indicate that damage to tissues required for reproduction and survival can be achieved at pharmacologically relevant concentrations.
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•Detrimental effects observed in tissues required for development and survival.•Damage occurs at concentrations ≥100 nM.•Hypodermal and embryonic tissues exhibited the most severe damage.•Oocytes and early morula are the most affected embryonic tissues.
Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by gradual renal enlargement and cyst growth prior to loss of renal function. Standard radiographic imaging has not provided the ...resolution and accuracy necessary to detect small changes in renal volume or to reliably measure renal cyst volumes. The Consortium for Radiologic Imaging Studies in Polycystic Kidney Disease (CRISP) is longitudinally observing ADPKD individuals using high-resolution magnetic resonance (MR) imaging to determine if change in renal and cyst volumes can be detected over a short period of time, and if they correlate with decline in renal function early in disease.
Standardization studies were conducted in phantoms and four subjects at each participating clinical center. After, in the full-scale protocol, healthy ADPKD individuals 15 to 45 years old with creatinine clearance>70 mL/min underwent standardized MR renal imaging, renal iothalamate clearance, comprehensive clinical evaluation, and determination of 24-hour urinary albumin and electrolyte excretion. Stereology was used from T1-weighted images to quantify renal volume, and region-growing thresholding was used from T2-weighted images to determine cyst volume. Renal structures were evaluated in relation to demographic, clinical, and biochemical variables using means/medians, standard deviations, and Pearson correlations.
Reliability coefficients for MR renal and cyst volume measurements in phantoms were 99.9% and 89.2%, respectively. In the full-scale protocol, 241 ADPKD individuals (145 women and 96 men) were enrolled. Total renal, cyst, and % cyst volume were significantly greater in each decade group. Hypertensive individuals demonstrated greater renal, cyst, and % cyst volume than normotensive subjects. Age-adjusted renal (r = -0.31, P < 0.0001), cyst (r = -0.36, P < 0.0001), and % cyst volume (r = -0.35, P < 0.0001) were inversely related to glomerular filtration rate (GFR). Age-adjusted renal volume (r = 0.42, P < 0.0001), cystic (r = 0.39, P < 0.0001, and % cyst volume (r = 0.41, P < 0.0001) were related with urinary albumin excretion.
MR measures of renal and cyst volume are reliable and accurate in patients with ADPKD. ADPKD is characterized by significant cystic involvement that increases with age. Structure (renal and cyst volume) and function (GFR) are inversely related and directly related with the presence of hypertension and urinary albumin excretion in individuals with normal renal function.
In North America, brood parasitic bees of the genus Coelioxys attack nests of solitary nest-provisioning bees of the genus Megachile. Using trap-nests in central New York State, we found Coelioxys ...modesta (Smith) in 49% of 72 nests and 27% of 313 cells provisioned by Megachile campanulae (Robertson). Because we had a nearly complete record of the species and sex of individuals developing in nest cells, we were able to use logistic regression to test several hypotheses concerning the risk of brood parasitism, the spatial distribution of infested cells, and the sex and size of C. modesta at different cell positions. The probabilities that a nest was infested or contained multiple C. modesta were higher in nests of larger diameter and in those had been active for longer durations. Cells of the host and cells infested with C. modesta tended to cluster with those of conspecifics within nests, an observation consistent with the hypothesis that individual female C. modesta remain at or frequently revisit individual host nests in which they have already oviposited. One nest contained a string of six consecutive cells attacked by C. modesta. As is typical of cavity-nesting Megachile, M. campanulae female offspring tended to predominate in inner cells of nests. Because the risk of attack by C. modesta was unrelated to cell position, however, M. campanulae offspring sex ratio did not differ between infested and uninfested nests. Brood parasites within inner nest cells were more likely to be Females. Males in inner cells tended to be above average in body size, probably as a result of inner cells containing larger pollen masses. A review of studies of Coelioxys brood parasitism of Megachile revealed that the percent of M. campanulae nests infested in our study is one of the highest published values.
Electronic prescribing is increasingly being used in primary care and in hospitals. Studies on the effects of e-prescribing systems have found evidence for both benefit and harm. The aim of this ...study was to identify features of e-prescribing software systems that support patient safety and quality of care and that are useful to the clinician and the patient, with a focus on improving the quality use of medicines.
Software features were identified by a literature review, key informants and an expert group. A modified Delphi process was used with a 12-member multidisciplinary expert group to reach consensus on the expected impact of the features in four domains: patient safety, quality of care, usefulness to the clinician and usefulness to the patient. The setting was electronic prescribing in general practice in Australia.
A list of 114 software features was developed. Most of the features relate to the recording and use of patient data, the medication selection process, prescribing decision support, monitoring drug therapy and clinical reports. The expert group rated 78 of the features (68%) as likely to have a high positive impact in at least one domain, 36 features (32%) as medium impact, and none as low or negative impact. Twenty seven features were rated as high positive impact across 3 or 4 domains including patient safety and quality of care. Ten features were considered "aspirational" because of a lack of agreed standards and/or suitable knowledge bases.
This study defines features of e-prescribing software systems that are expected to support safety and quality, especially in relation to prescribing and use of medicines in general practice. The features could be used to develop software standards, and could be adapted if necessary for use in other settings and countries.
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