5366 research outputs found
Sort by
Inflammatory and Fibrogenic Factors in Proliferative Vitreoretinopathy Development.
No full textPurpose
Proliferative vitreoretinopathy (PVR) occurs in 5%-10% of rhegmatogenous retinal detachment cases and is the principle cause for failure of retinal reattachment surgery. Although there are a number of surgical adjunctive agents available for preventing the development of PVR, all have limited efficacy. Discovering predictive molecular biomarkers to determine the probability of PVR development after retinal reattachment surgery will allow better patient stratification for more targeted drug evaluations.
Methods
Narrative literature review.
Results
We provide a summary of the inflammatory and fibrogenic factors found in ocular fluid samples during the development of retinal detachment and PVR and discuss their possible use as molecular PVR predictive biomarkers.
Conclusions
Studies monitoring the levels of the above factors have found that few if any have predictive biomarker value, suggesting that widening the phenotype of potential factors and a combinatorial approach are required to determine predictive biomarkers for PVR.
Translational Relevance
The identification of relevant biomarkers relies on an understanding of disease signaling pathways derived from basic science research. We discuss the extent to which those molecules identified as biomarkers and predictors of PVR relate to disease pathogenesis and could function as useful disease predictors. (http://www.umin.ac.jp/ctr/ number, UMIN000005604)
Nelson's Syndrome: An Update.
No full textNelson's syndrome (NS) is a condition which may develop in patients with Cushing's disease after bilateral adrenalectomy. Although there is no formal consensus on what defines NS, corticotroph tumor growth and/or gradually increasing ACTH levels are important diagnostic elements. Pathogenesis is unclear and well-established predictive factors are lacking; high ACTH during the first year after bilateral adrenalectomy is the most consistently reported predictive parameter. Management is individualized and includes surgery, with or without radiotherapy, radiotherapy alone, and observation; medical treatments have shown inconsistent results. A subset of tumors demonstrates aggressive behavior with challenging management, malignant transformation and poor prognosis
The Time-Course of Changes in Muscle Mass, Architecture and Power During 6 Weeks of Plyometric Training.
No full textPurpose
To investigate the time-course of changes in knee-extensors muscle mass, architecture and function in response to plyometric training (PLT) performed on a novel training device, the Tramp-Trainer. This machine consists in a trampoline connected to an inclined sledge which allows the performance of repeated jumps while the subject is sitting on a chair.
Methods
Eight healthy males (173.6 ± 4.7 cm, 69.7 ± 13.5 kg, 25.3 ± 4.6 years) underwent 6 weeks of bilateral PLT on the tramp-trainer machine. Training was performed three times per week (between 120 and 150 bounces per session). Knee-extensor maximum voluntary torque (MVT) and power, quadriceps femoris (QF) volume (VOL), cross-sectional area from the 20% to the 60% of femur length and CSA , together with vastus lateralis (VL) architecture (fascicle length, Lf, and pennation angle, PA) were assessed after 2, 4, and 6 weeks of PLT.
Results
All results are presented as changes versus baseline values. MVT increased by 17.8% (week 2, < 0.001) and 22.2% (week 4, < 0.01), respectively, and declined to 13.3% ( < 0.05) at week 6 of PLT. Power increased by 18.2% (week 4, < 0.05) and 19.7% (week 6, < 0.05). QF VOL increased by 4.7% (week 4, < 0.05) and 5.8% (week 6, < 0.01); VL VOL increased by 5.2%, ( < 0.05), 8.2%, ( < 0.01), and 9.6% ( < 0.05) at weeks 2, 4, and 6, respectively. An increase in Lf was detected already at wk 2 (2.2%, < 0.05), with further increase at 4 and 6 weeks of PLT (4 and 4.4%, respectively, < 0.01). PA increased by 5.8% ( < 0.05) at week 6. Significant positive correlations were found between CSA and Power ( = 0.46, < 0.001) and between QF VOL and Power ( = 0.44, < 0.024).
Conclusions
PLT induced rapid increases in muscle volume, fascicle length, pennation angle, torque and power in healthy younger adults. Notably, changes in VL VOL and Lf were detectable already after 2 weeks, followed by increases in knee extensors VOL and power from week 4 of PLT. Since the increase in CSA and QF VOL cannot fully explain the increment in muscle power, it is likely that other factors (such as adaptations in neural drive or tendon mechanical properties) may have contributed to such fucntional changes
Changes in Blood Pressure and Arterial Hemodynamics following Living Kidney Donation.
No full textBACKGROUND AND OBJECTIVES
The Effect of a Reduction in GFR after Nephrectomy on Arterial Stiffness and Central Hemodynamics (EARNEST) study was a multicenter, prospective, controlled study designed to investigate the associations of an isolated reduction in kidney function on BP and arterial hemodynamics.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Prospective living kidney donors and healthy controls who fulfilled criteria for donation were recruited from centers with expertise in vascular research. Participants underwent office and ambulatory BP measurement, assessment of arterial stiffness, and biochemical tests at baseline and 12 months.
RESULTS
A total of 469 participants were recruited, and 306 (168 donors and 138 controls) were followed up at 12 months. In the donor group, mean eGFR was 27 ml/min per 1.73 m lower than baseline at 12 months. Compared with baseline, at 12 months the mean within-group difference in ambulatory day systolic BP in donors was 0.1 mm Hg (95% confidence interval, -1.7 to 1.9) and 0.6 mm Hg (95% confidence interval, -0.7 to 2.0) in controls. The between-group difference was -0.5 mm Hg (95% confidence interval, -2.8 to 1.7; =0.62). The mean within-group difference in pulse wave velocity in donors was 0.3 m/s (95% confidence interval, 0.1 to 0.4) and 0.2 m/s (95% confidence interval, -0.0 to 0.4) in controls. The between-group difference was 0.1 m/s (95% confidence interval, -0.2 to 0.3; =0.49).
CONCLUSIONS
Changes in ambulatory peripheral BP and pulse wave velocity in kidney donors at 12 months after nephrectomy were small and not different from controls.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER
NCT01769924 (https://clinicaltrials.gov/ct2/show/NCT01769924)
Urine steroid metabolomics for the differential diagnosis of adrenal incidentalomas in the EURINE-ACT study: a prospective test validation study.
No full textBACKGROUND
Cross-sectional imaging regularly results in incidental discovery of adrenal tumours, requiring exclusion of adrenocortical carcinoma (ACC). However, differentiation is hampered by poor specificity of imaging characteristics. We aimed to validate a urine steroid metabolomics approach, using steroid profiling as the diagnostic basis for ACC.
METHODS
We did a prospective multicentre study in adult participants (age ≥18 years) with newly diagnosed adrenal masses. We assessed the accuracy of diagnostic imaging strategies based on maximum tumour diameter (≥4 cm vs <4 cm), imaging characteristics (positive vs negative), and urine steroid metabolomics (low, medium, or high risk of ACC), separately and in combination, using a reference standard of histopathology and follow-up investigations. With respect to imaging characteristics, we also assessed the diagnostic utility of increasing the unenhanced CT tumour attenuation threshold from the recommended 10 Hounsfield units (HU) to 20 HU.
FINDINGS
Of 2169 participants recruited between Jan 17, 2011, and July 15, 2016, we included 2017 from 14 specialist centres in 11 countries in the final analysis. 98 (4·9%) had histopathologically or clinically and biochemically confirmed ACC. Tumours with diameters of 4 cm or larger were identified in 488 participants (24·2%), including 96 of the 98 with ACC (positive predictive value [PPV] 19·7%, 95% CI 16·2-23·5). For imaging characteristics, increasing the unenhanced CT tumour attenuation threshold to 20 HU from the recommended 10 HU increased specificity for ACC (80·0% [95% CI 77·9-82·0] vs 64·0% [61·4-66.4]) while maintaining sensitivity (99·0% [94·4-100·0] vs 100·0% [96·3-100·0]; PPV 19·7%, 16·3-23·5). A urine steroid metabolomics result indicating high risk of ACC had a PPV of 34·6% (95% CI 28·6-41·0). When the three tests were combined, in the order of tumour diameter, positive imaging characteristics, and urine steroid metabolomics, 106 (5·3%) participants had the result maximum tumour diameter of 4 cm or larger, positive imaging characteristics (with the 20 HU cutoff), and urine steroid metabolomics indicating high risk of ACC, for which the PPV was 76·4% (95% CI 67·2-84·1). 70 (3·5%) were classified as being at moderate risk of ACC and 1841 (91·3%) at low risk (negative predictive value 99·7%, 99·4-100·0).
INTERPRETATION
An unenhanced CT tumour attenuation cutoff of 20 HU should replace that of 10 HU for exclusion of ACC. A triple test strategy of tumour diameter, imaging characteristics, and urine steroid metabolomics improves detection of ACC, which could shorten time to surgery for patients with ACC and help to avoid unnecessary surgery in patients with benign tumours.
FUNDING
European Commission, UK Medical Research Council, Wellcome Trust, and UK National Institute for Health Research, US National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research
WavelinQ created arteriovenous fistulas versus surgical radiocephalic arteriovenous fistulas? A single-centre observational study.
No full textPURPOSE
Devices to permit percutaneous endovascular arteriovenous fistula formation have recently been introduced into clinical practice with promising initial evidence. As guidelines support a distal fistula first policy, the question of whether an endovascular arteriovenous fistula should be performed as an initial option is introduced. The aims of this study were to compare a matched cohort of endovascular arteriovenous fistula with surgical radiocephalic arteriovenous fistulas.
MATERIALS AND METHODS
Using data from a prospectively collected database over a 3-year period, a matched comparative analysis was performed.
RESULTS
WavelinQ arteriovenous fistulas (group W, = 30) were compared with radiocephalic arteriovenous fistulas (group RC; = 40). Procedural success was high with 96.7% for group W and 92.6% for group RC. Primary patency at 6 and 12 months was greater in group W (65.5% 6mo and 56.5% 12mo) compared to group RC (53.4% 6mo and 44% 12mo) ( = 0.69 and 0.63). Mean primary patency was significantly lower for RC (235 ± 210 days) vs W (362 ± 240 days) ( < 0.05). Secondary patency for group W was 75.8% and 69.5% at 6 and 12 months, respectively. Secondary patency for RC was lower at 66.7% and 57.6% at 6 and 12 months, respectively.
CONCLUSION
Outcomes of WavelinQ arteriovenous fistulas in this series are similar to published results. When compared to a contemporaneously created group of surgical fistulas, WavelinQ demonstrated superior outcomes. These data would support that WavelinQ endovascular arteriovenous fistulas may be considered as a first option in the access pathway particularly if vessels at the wrist are absent or less than ideal
Ex Situ Arterial Reconstruction During Normothermic Perfusion of the Liver.
No full textBackground
Aberrant hepatic arterial anatomy may be seen in up to 30% of liver grafts, and reconstruction prolongs the cold ischemic time or the arterialization times. If normothermic machine preservation (NMP) is used to preserve liver grafts, the presence of aberrant arterial anatomy poses a challenge. Dual arterial cannulation is a temporary solution to enable effective perfusion, until optimal circumstances are met for arterial reconstruction, without compromising ischemia time. To date the technical and logistical feasibility of arterial reconstruction ex situ and NMP has not been reported.
Methods
Series of 5 cases from the Consortium for Organ Preservation in Europe randomized controlled trial in which grafts with arterial anatomic variations were reconstructed while organs were perfused on NMP.
Results
One donor after cardiac death and 4 donor after brain death livers with arterial anatomical variations reconstructed while on NMP were included. All patients survived transplantation, spending 1-7 d in intensive care unit and discharged home after 5-15 d. None of the cases developed early allograft dysfunction or any early technical complications. At follow-up, there were no late hepatic artery thrombosis, stenosis, or any other vascular-related complication. Four of 5 patients underwent magnetic resonance cholangiopancreatography at 6 mo with no evidence of ischemic cholangiopathy.
Conclusions
The case series described above suggests that ex vivo arterial reconstruction surgery on liver grafts while on board the NMP device is feasible, safe, and effective
Pharmacokinetics of intramuscular tranexamic acid in bleeding trauma patients: a clinical trial.
No full textBACKGROUND
Intravenous tranexamic acid (TXA) reduces bleeding deaths after injury and childbirth. It is most effective when given early. In many countries, pre-hospital care is provided by people who cannot give i.v. injections. We examined the pharmacokinetics of intramuscular TXA in bleeding trauma patients.
METHODS
We conducted an open-label pharmacokinetic study in two UK hospitals. Thirty bleeding trauma patients received a loading dose of TXA 1 g i.v., as per guidelines. The second TXA dose was given as two 5 ml (0·5 g each) i.m. injections. We collected blood at intervals and monitored injection sites. We measured TXA concentrations using liquid chromatography coupled to mass spectrometry. We assessed the concentration time course using non-linear mixed-effect models with age, sex, ethnicity, body weight, type of injury, signs of shock, and glomerular filtration rate as possible covariates.
RESULTS
Intramuscular TXA was well tolerated with only mild injection site reactions. A two-compartment open model with first-order absorption and elimination best described the data. For a 70-kg patient, aged 44 yr without signs of shock, the population estimates were 1.94 h for i.m. absorption constant, 0.77 for i.m. bioavailability, 7.1 L h for elimination clearance, 11.7 L h for inter-compartmental clearance, 16.1 L volume of central compartment, and 9.4 L volume of the peripheral compartment. The time to reach therapeutic concentrations (5 or 10 mg L) after a single intramuscular TXA 1 g injection are 4 or 11 min, with the time above these concentrations being 10 or 5.6 h, respectively.
CONCLUSIONS
In bleeding trauma patients, intramuscular TXA is well tolerated and rapidly absorbed.
CLINICAL TRIAL REGISTRATION
2019-000898-23 (EudraCT); NCT03875937 (ClinicalTrials.gov)
Importance and Assessment of Quality of Life in Symptomatic Permanent Atrial Fibrillation: Patient Focus Groups from the RATE-AF Trial.
No full textAIMS
To establish the extent and impact of symptoms in patients with atrial fibrillation (AF), the importance of different aspects of quality of life (QoL), and how we should assess wellbeing.
METHODS
Focus groups of patients with symptomatic permanent AF in a trial of heart rate control; the RATE-AF trial randomised 160 patients aged ≥60 years with permanent AF and at least NYHA class II dyspnoea to either digoxin or beta-blockers. Patient and public representatives led the focus groups and performed all data acquisition and analysis, using thematic approaches to interpret patient views about QoL and its measurement.
RESULTS
Substantial impairment of health-related QoL was noted in 160 trial patients, with impact on all domains apart from mental health. Eight women and 11 men aged 61-87 years participated in the focus groups. Common themes were a lack of information from healthcare professionals about AF, a lack of focus on QoL in consultations, and a sense of frustration, isolation, and reduced confidence. There was marked variability in symptoms in individual patients, with some describing severe impact on activities of daily living, and profound interaction with comorbidities such as arthritis. Day-to-day variation in QoL and difficulty in attributing symptom burden to AF or other comorbidities led to challenges in questionnaire completion. Consensus was reached that collecting both general and AF-specific QoL would be useful in routine practice, along with participation in peer support, which was empowering for the patients.
CONCLUSIONS
The impact of comorbidities is poorly appreciated in the context of AF, with considerable variability in QoL that requires both generic and AF-specific assessment. Improvement in QoL should direct the appraisal, and reappraisal, of treatment decisions for patients with permanent AF