Search

Background: In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment is associated with increased risk of preterm birth. However, early identification of women at increased risk of persistence/progression is important to ensure timely treatment. Evidence is limited on biomarkers that may be used to identify women at increased risk of persistence/progression., Objective: This study aimed to describe human papillomavirus HPV type-specific persistence/progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2., Study Design: We conducted a historical cohort study of women aged 23 to 40 years diagnosed with cervical intraepithelial neoplasia grade 2 at Aarhus University Hospital from 2000 to 2010. Women were identified through the Danish Pathology Data Bank (DPDB) and were considered as undergoing active surveillance if they had a first record of a cervical biopsy within 2 years after index diagnosis and no loop electrosurgical excision procedure before this. Human papillomavirus genotyping was performed on archived tissue samples using the HPV SPF 10 -DEIA-LiPA 25 system (DNA ELISA [enzyme-linked immunosorbent assay] HPV SPF10 kit and RHA HPV SPF10-LiPA25 kit). Persistence/progression was defined as having a record of cervical intraepithelial neoplasia grade ≥2 in the DPDB determined on the last and worst diagnosis on a biopsy or loop electrosurgical excision procedure specimen during follow-up. We estimated the relative risk (95% confidence interval) of persistence/progression using a modified Poisson model., Results: A total of 455 women were included. Two-thirds were aged ≤30 years (73.8%) at index diagnosis, and nearly half had a high-grade index cytology (48.8%). Overall, 52.2% of all women had cervical intraepithelial neoplasia grade ≥2 during follow-up; 70.5% were human papillomavirus-16-positive and 29.5% were positive for other human papillomavirus types. Human papillomavirus-16 was associated with a significantly higher risk of persistence/progression (relative risk, 1.64; 95% confidence interval, 1.37-1.95) compared with non-human papillomavirus-16. The risk of persistence/progression was highest in human papillomavirus-16-positive women with a high-grade index cytology compared with human papillomavirus-16-positive women with a low-grade cytology (relative risk, 1.29; 95% confidence interval, 1.03-1.61), whereas no differences were observed across age groups., Conclusion: The highest risk of persistence/progression was observed among human papillomavirus-16-positive women, particularly those with associated high-grade cytology. These findings suggest that early excisional treatment should be considered in this group of women., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: It has been suggested that the Lethal Triad be modified to include hypocalcemia, coined as the Lethal Diamond. Hypocalcemia in trauma has been attributed to multiple mechanisms, but new evidence suggests that traumatic injury may result in the development of hypoCa independent of blood transfusion. We hypothesize that hypocalcemia is associated with increased blood product requirements and mortality., Methods: A retrospective study of 1,981 severely injured adult trauma patients from 2016 to 2019. Ionized calcium (iCa) levels were obtained on arrival and subjects were categorized by a threshold iCa level of 1.00 mmol/L and compared. Univariable and multivariable logistic regression analysis was performed., Results: The hypocalcemia (iCa <1.00 mmol/L) group had increased rate of overall (p = 0.001), 4-hr (p = 0.007), and 24-hr (p = 0.003) mortality. There was no difference in prehospital transfusion volume between groups (p = 0.25). Hypocalcemia was associated with increased blood product requirements at 4 h (p <0.001), 24 h (p <0.001), and overall hospital length of stay (p <0.001). Logistic regression analysis showed increased odds of 4-hour mortality (OR 0.077 [95 % CI 0.011, 0.523], p = 0.009) and 24-hour mortality (OR 0.121 [95 % CI 0.019, 0.758], p = 0.024) for every mmol/L increase in iCa., Conclusions: This study shows the association of hypoCa and traumatic injury. Severe hypoCa was associated with increased odds of early and overall mortality and increased blood product requirements. These results support the need for future prospective trials assessing the role of hypocalcemia in trauma., Competing Interests: Declaration of competing interest The views represented in this presentation do not represent the views of the Department of Defense, United States Government, or any branches of the United States Military, No relevant financial relationships to disclose. The authors have no relevant conflicts of interest. Data access from institutional database and electronic medical records. Data can be accessed upon request., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aims: The aim of this study is to assess and document engagement in type 2 diabetes mellitus (T2DM) self-care behaviors and self-reported diabetes knowledge among Marshallese adults living in the Republic of the Marshall Islands (RMI)., Methods: The study uses data from a T2DM health screening study completed in the RMI; survey and biometric data were captured as part of the health screenings. Study objectives were examined using descriptive statistics to describe the characteristics of the participants, their diabetes self-care behaviors, and their levels of self-reported diabetes knowledge., Results: Results indicate many Marshallese diagnosed with T2DM did not engage in adequate self-care behaviors, including blood sugar checks and foot examinations. Participants reported having forgone needed medical care and medication due to issues with cost and/or access, and participants reported low levels of diabetes knowledge., Conclusions: The results demonstrate the need for further work in improving engagement in diabetes self-care by Marshallese living in the RMI. Increased engagement in self-care and diabetes education programs may help Marshallese with T2DM to improve control of their glucose and avoid long-term health complications, as well as reduce costs to the healthcare system., Competing Interests: Declaration of Competing Interest The authors declared no competing interests., (Copyright © 2023 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Experience in donation after circulatory-determined death (DCD) heart transplantation (HTx) is expanding. There is limited information on the functional outcomes of DCD HTx recipients. We sought to evaluate functional outcomes in our cohort of DCD recipients. We performed a single-center, retrospective, observational cohort study comparing outcomes in consecutive DCD and donation after brain death (DBD) HTx recipients between 2015 and 2019. Primary outcome was allograft function by echocardiography at 12 and 24 months. Secondary outcomes included incidence of cardiac allograft vasculopathy, treated rejection, renal function, and survival. Seventy-seven DCD and 153 DBD recipients were included. There was no difference in left ventricular ejection fraction at 12 months (59% vs 59%, P = .57) and 24 months (58% vs 58%, P = .87). There was no significant difference in right ventricular function at 12 and 24 months. Unadjusted survival between DCD and DBD recipients at 5 years (85.7% DCD and 81% DBD recipients; P = .45) was similar. There were no significant differences in incidence of cardiac allograft vasculopathy (odds ratio 1.59, P = .21, 95% confidence interval 0.77-3.3) or treated rejection (odds ratio 0.60, P = .12, 95% confidence interval 0.32-1.15) between DBD and DCD recipients. Post-transplant renal function was similar at 1 and 2 years. In conclusion, cardiac allografts from DCD donors perform similarly to a contemporary population of DBD allografts in the medium term., Competing Interests: Disclosure The authors of this manuscript have conflicts of interest to disclose, as described by the American Journal of Transplantation. S. Messer and S.R. Large have applied for a patent for organ perfusion system and methods. S.R. Large has a patent awarded for apparatus for testing, assessment and maintenance of procured hearts for transplantation. Remaining authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: We describe baseline characteristics, disease progression and mortality in chronic thromboembolic pulmonary disease patients as a function of mean pulmonary artery pressure (mPAP) according to new and previous definitions of pulmonary hypertension., Methods: All patients diagnosed with chronic thromboembolic pulmonary disease between January, 2015 and December, 2019 were dichotomized according to initial mPAP: ≤ 20 mmHg ('normal') vs 21-24 mmHg ('mildly-elevated'). Baseline features were compared between the groups, and pairwise analysis performed to determine changes in clinical endpoints at 1-year, excluding those who underwent pulmonary endarterectomy or did not attend follow-up. Mortality was assessed for the whole cohort over the entire study period., Results: One hundred thirteen patients were included; 57 had mPAP ≤ 20 mmHg and 56 had mPAP 21-24 mmHg. Normal mPAP patients had lower pulmonary vascular resistance (1.6 vs 2.5WU, p < 0.01) and right ventricular end-diastolic pressure (5.9 vs 7.8 mmHg, p < 0.01) at presentation. At 3 years, no major deterioration was seen in either group. No patients were treated with pulmonary artery vasodilators. Eight had undergone pulmonary endarterectomy. Over 37 months median follow-up, mortality was 7.0% in the normal mPAP group and 8.9% in the mildly-elevated mPAP group. Cause of death was malignancy in 62.5% of cases., Conclusions: Chronic thromboembolic pulmonary disease patients with mild pulmonary hypertension have statistically higher right ventricular end-diastolic pressure and pulmonary vascular resistance than those with mPAP ≤ 20 mmHg. Baseline characteristics were otherwise similar. Neither group displayed disease progression on non-invasive tests up to 3 years. Mortality over 37 months follow-up is 8%, and mainly attributable to malignancy. Further prospective study is required to validate these findings., (Copyright © 2023 International Society for the Heart and Lung Transplantation. All rights reserved.)

Background: The United Kingdom (UK) was one of the first countries to pioneer heart transplantation from donation after circulatory death (DCD) donors. To facilitate equity of access to DCD hearts by all UK heart transplant centers and expand the retrieval zone nationwide, a Joint Innovation Fund (JIF) pilot was provided by NHS Blood and Transplant (NHSBT) and NHS England (NHSE). The activity and outcomes of this national DCD heart pilot program are reported., Methods: This is a national multi-center, retrospective cohort study examining early outcomes of DCD heart transplants performed across 7 heart transplant centers, adult and pediatric, throughout the UK. Hearts were retrieved using the direct procurement and perfusion (DPP) technique by 3 specialist retrieval teams trained in ex-situ normothermic machine perfusion. Outcomes were compared against DCD heart transplants before the national pilot era and against contemporaneous donation after brain death (DBD) heart transplants, and analyzed using Kaplan-Meier analysis, chi-square test, and Wilcoxon's rank-sum., Results: From September 7, 2020 to February 28, 2022, 215 potential DCD hearts were offered of which 98 (46%) were accepted and attended. There were 77 potential donors (36%) which proceeded to death within 2 hours, with 57 (27%) donor hearts successfully retrieved and perfused ex situ and 50 (23%) DCD hearts going on to be transplanted. During this same period, 179 DBD hearts were transplanted. Overall, there was no difference in the 30-day survival rate between DCD and DBD (94% vs 93%) or 90 day survival (90% vs 90%) respectively. There was a higher rate of ECMO use post-DCD heart transplants compared to DBD (40% vs 16%, p = 0.0006), and DCD hearts in the pre pilot era, (17%, p = 0.002). There was no difference in length of ICU stay (9 DCD vs 8 days DBD, p = 0.13) nor hospital stay (28 DCD vs 27 DBD days, p = 0.46)., Conclusion: During this pilot study, 3 specialist retrieval teams were able to retrieve DCD hearts nationally for all 7 UK heart transplant centers. DCD donors increased overall heart transplantation in the UK by 28% with equivalent early posttransplant survival compared with DBD donors., Competing Interests: Disclosure The authors have no conflicts of interest to declare. This research was funded by the National Health Service Blood and Transplant and National Health Service England., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Objectives: We aim to use real-world data in evidence synthesis to optimize an evidence base for the effectiveness of biologic therapies in rheumatoid arthritis to allow for evidence on first-line therapies to inform second-line effectiveness estimates., Study Design and Setting: We use data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis to supplement randomized controlled trials evidence obtained from the literature, by emulating target trials of treatment sequences to estimate treatment effects in each line of therapy. Treatment effects estimates from the target trials inform a bivariate network meta-analysis (NMA) of first-line and second-line treatments., Results: Summary data were obtained from 21 trials of biologic therapies including two for second-line treatment and results from six emulated target trials of both treatment lines. Bivariate NMA resulted in a decrease in uncertainty around the effectiveness estimates of the second-line therapies, when compared to the results of univariate NMA, and allowed for predictions of treatment effects not evaluated in second-line randomized controlled trials., Conclusion: Bivariate NMA provides effectiveness estimates for all treatments in first and second line, including predicted effects in second line where these estimates did not exist in the data. This novel methodology may have further applications; for example, for bridging networks of trials in children and adults., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Intramuscular medroxyprogesterone acetate (MPA) products are commonly used to treat endometriosis and are the most widely used injectable contraceptives worldwide. Therefore, dependable quality screening of MPA injectables is a crucial measure necessary for ensuring that consumers are provided with safe and effective medications. Here, a thin-layer chromatography (TLC) method for MPA identification is combined with image analysis using a smartphone, 3D-printed light box, and open-source ImageJ software. The method's validation included two brands of MPA injectables, both at 150 mg mL -1 dosage. The TLC procedure used was based on the identity test found in The International Pharmacopoeia's Medroxyprogesterone injection monograph. Spots produced on the TLC plates were then photographed using a smartphone camera and quantified using ImageJ's image analysis software. The pixel data collected from each plate's standard spots were compared to the data generated from its sample spots. Data sets collected across multiple TLC plates and numerous days of method performance were evaluated to assess linearity, accuracy, precision, specificity, and robustness. Across the range of 75-125% of the target concentration, the method was found to have linearity of standard spots (with R 2 generally greater than 0.99), overall accuracy of 101.0% (4.1% RSD), repeatability pooled standard deviation of 2.44%, intermediate precision pooled standard deviation of 3.68%, and observed demonstration of specificity and robustness. In low and middle-income countries (LMICs), quality screening of pharmaceutical products like MPA injectables can be challenging when testing resources are expensive, difficult to procure, or complex to utilize. The results of the TLC/ImageJ method validation suggest that this simple procedure that requires minimal resources may serve as a viable option for reliable quality screening of MPA levels in injectable suspensions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Increasing usage of both nanomaterials and pharmaceuticals and their unabated release to the marine ecosystem pose a serious concern nowadays. The toxicity of the mixture of TiO 2 NPs and tetracycline (TC) in the marine species are not very well covered in prior literature. The current study explores the joint toxic effects of TiO 2 NPs and TC in a simulated marine food chain: Chlorella sp. and Artemia salina. Chlorella sp. was interacted with pristine TiO 2 NPs (0.05, 05, and 5 mg/L), TC (0.5 mg/L), and their combinations for 48 h. The toxicity induced in Chlorella sp. by pristine TiO 2 NPs through oxidative stress and chloroplast damage was not significantly changed in the presence of TC. Principal component analysis for the toxicity parameters revealed a strong association between growth inhibition and adsorption/internalization. In the second trophic level (A. salina), the waterborne exposure of TC additively increased the toxicity of TiO 2 NPs. Both adsorption and degradation played a major role in the removal of TC from the suspension, resulting in additive toxic effects in both Chlorella sp. and A. salina. Compared to the waterborne exposure, the foodborne exposure of TiO 2 NPs and TC induced lesser toxic effects owing to reduced uptake and accumulation in A. salina. Biomagnification results indicate that the dietary transfer of TiO 2 NPs and TC does not pose a serious environmental threat in this two-level marine food chain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Quality assurance of finished pharmaceuticals is a necessity in ensuring the safety of consumers. There is a need for low-cost and portable rapid screening methods of pharmaceuticals in resource limited areas. Recent advances in technology have made handheld and low-cost diffuse reflectance spectrometers available to the public. While these handheld spectrometers offer advantages over benchtop spectrometers, the accuracy and repeatability must be assessed before these instruments can be used for quality assurance screening. Here, five handheld spectrometers of the same model were purchased, where an in-house installation qualification and operational qualification (IQOQ) was subsequently established for the instruments. Wavelength and photometric accuracy (and repeatability), spectroscopic noise, stray light, and bandpass were assessed between instruments. Results were found to be consistent between the spectrometers, passing IQOQ procedures, and were determined to be ready for field use. Once the handheld spectrometer's performance was verified, a practical and low-cost daily performance verification was established using common high density polyethylene vial caps on location in South Africa, Thailand, and the United States. A Mahalanobis distance-based classifier found the five spectrometers to be in agreement., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

ISHLT members have recognized the importance of a consensus statement on the evaluation and management of patients with chronic thromboembolic pulmonary hypertension. The creation of this document required multiple steps, including the engagement of the ISHLT councils, approval by the Standards and Guidelines Committee, identification and selection of experts in the field, and the development of 6 working groups. Each working group provided a separate section based on an extensive literature search. These sections were then coalesced into a single document that was circulated to all members of the working groups. Key points were summarized at the end of each section. Due to the limited number of comparative trials in this field, the document was written as a literature review with expert opinion rather than based on level of evidence., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Medroxyprogesterone acetate (MPA) injectable suspensions are used by millions of women for family planning and hormonal therapy. Falsified or substandard medications may result in a health risk for consumers. Near-infrared spectroscopy (NIR) has previously been applied as a means of non-destructive and rapid screening of product quality compliance. These methods offer advantages but can be logistically and cost prohibitive for field use in resource limited areas. Here, a handheld spectrometer (900-1700 nm) with open-sourced software is used to evaluate vials of MPA from three suppliers (N = 227 vials) and verified by a benchtop UV-VIS-NIR (350-2500 nm) with licensed software. Multivariate data analysis assesses the spectral signatures of samples and builds a discriminant classification method based on Mahalanobis distances calculated from a principal component analysis scores. The handheld device paired with open-source software resulted in a product discrimination accuracy of 100% (verified by benchtop UV-VIS-NIR and chemical testing data) as well indicating that the low-cost field portable device is suitable for rapidly assessing samples in resource limited areas for consistency of manufacturing and sourcing., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Balloon pulmonary angioplasty (BPA) is delivered as a series of treatments for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) however, there is little published data on the procedural determinants of outcome., Methods: Pre- and post-BPA clinical and hemodynamic data, as well as serial hemodynamic and procedural data at each BPA session were evaluated to determine patient and procedure-related factors that influence hemodynamic response., Results: Per procedure data from 210 procedures in 84 patients and per patient data from 182 procedures in 63 patients with completed treatment and 3-month follow-up were analyzed. A median of 3 (range 1-6) BPA procedures treating a median of 2 segments per procedure (range 1-3) were performed per patient with a median interval between procedures of 42 (range 5-491) days. Clinical outcome correlated with hemodynamic change (pulmonary vascular resistance [ΔPVR] vs Cambridge Pulmonary Hypertension Outcome Review [CAMPHOR] symptom score: p < 0.001, Pearson's r = 0.48, n = 49). Responders to BPA had more severe disease at baseline and 37.5 % of non-responders were post-PEA. There was a dose-response relationship between per procedure and total number of segments treated and hemodynamic improvement (ΔPVR: 1 segment: -0.9%, 2: -14.5%, 3 or more: -16.1%, p < 0.001). Treating totally occluded vessels had a greater hemodynamic effect (mean pulmonary artery pressure [ΔmPAP]: sessions with occlusion: -8.0%, without occlusion treated: -3.2%, p < 0.05) without an increased complication rate., Conclusions: The magnitude of clinical benefit is related to the hemodynamic effect of BPA which in turn is related to the number of segments treated and lesion severity. Patients who were post-PEA were less likely to respond to BPA., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: While orthopedic residency training varies among programs, an inevitable phenomenon is a transition for interns from consistent oversight to independent call with indirect supervision. It is therefore crucial to reliably assess trainees' ability to perform basic procedures. The objective of the study was to evaluate the utility of a novel Orthopaedic Intern Skills Assessment (OISA) to assess skill level., Design: In a cohort study, participants were evaluated on their ability to complete eleven skills in a simulated environment. Using a standardized patient and/or cadaveric specimen, we assessed skeletal traction, joint aspiration, joint injection, laceration repair, ankle brachial index measurement, compartment pressure monitoring, upper and lower extremity splinting, informed consent, spine trauma exam, and cervical spine clearance abilities., Setting: The assessment took place in a medical simulation lab at the Oregon Health & Science University in Portland, Oregon., Participants: Third- or fourth-year medical students interested in orthopedics, incoming interns (preinterns), and residents within 1 month of completing their intern year (postinterns) were invited to participate in the study. All interested individuals were included. Of the 20 individuals contacted, 14 (70%) consented: 4 medical students (40%), 5 preinterns (100%), and 5 postinterns (100%). All consenting individuals finished their participation in the research., Results: Postintern skill completion rate was significantly higher than preinterns (p = 0.006) and medical students (p < 0.001). Completion rates for preinterns were also significantly higher rate than medical students (p = 0.035)., Conclusions: Our OISA found that postinterns had reached a basic orthopedic skill level expected of a junior resident without in-house supervision. Our OISA also highlighted areas of training that needed further attention, which will help orthopedic training programs verify an appropriate level of skill as trainees' progress from a supervised intern year to taking indirectly supervised junior resident call, and help identify areas where increased training is needed., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Potable water in developing countries often contains levels of toxic metals that exceed the recommended international limits, with impacts on human health. The aim of the present study was to develop a low cost aerogel synthesised from graphene oxide (GO) cross-linked with alginate to remove Pb 2+ from potable water. Aerogels were made by a sol-gel of the composite materials followed by a freeze drying method. The shape of the aerogels were 50 mm diameter disks, 5 mm deep and characterised by an open porous network of 50 to 150 micrometres which are mechanically robust upon hydration. Firstly, the study was conducted using a batch adsorption method from a starting concentration 0.48 mM (100 mg/l) of Pb 2+ in ultrapure water over 240 min, n = 4 with controls. A second series of experiments compared the adsorption of different competing ions at different valencies (Na + , Ca 2+ , Cu 2+ , La 3+ ) in an equivalent media. A third series of experiments explored Pb 2+ desorption from the aerogel at low pH and in highly acidic conditions. This simple filter system, based on a batch adsorption methodology expresses a high affinity for Pb 2+ resulting in an ultra-high mean maximum adsorption capacity of 504 mg/g of Pb 2+ within 240 mins at pH 5. The aerogel can also adsorb other toxic metal salts such as La 3+ and Cu 2+ with a capacity of 146 and 193 mg/g respectively. Furthermore, the aerogel structure can be acid washed removing 98% of the Pb 2+ from the structure within three minutes. Overall, the data shows that GO alginate aerogels are highly effective at removing Pb 2+ from water and the primary mechanism involved is ion exchange, although other phenomenon such as proton tunnelling may be a contributing factor to the ultra-high efficiency of the aerogel for Pb 2+ remediation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: In an effort to address the increasing demand for heart transplantation within the United Kingdom (UK), we established a clinical program of heart transplantation from donation after circulatory-determined death (DCD) donors in 2015. After 5 years, we report the clinical early outcomes and impact of the program., Methods: This is a single-center, retrospective, matched, observational cohort study comparing outcomes of hearts transplanted from DCD donors from March 1, 2015 to February 29, 2020 with those from matched donation after brain death (DBD) donors at Royal Papworth Hospital (RPH) (Cambridge, UK). DCD hearts were either retrieved using thoracoabdominal normothermic regional perfusion or the direct procurement and perfusion technique. All DBD hearts were procured using standard cold static storage. The primary outcomes were recipient 30-day and 1-year survival., Results: During the 5-year study, DCD heart donation increased overall heart transplant activity by 48% (79 for DCD and 164 for DBD). There was no difference in survival at 30 days (97% for DCD vs 99% for DBD, p = 1.00) or 1 year (91% for DCD vs 89% for DBD, p = 0.72). There was no difference in the length of stay in the intensive care unit (7 for DCD vs 6 for DBD days, p = 0.24) or in the hospital (24 for DCD vs 25 for DBD days, p = 0.84)., Conclusions: DCD heart donation increased overall heart transplant activity at RPH by 48%, with no difference in 30-day or 1-year survival in comparison with conventional DBD heart transplantations. DCD heart donation is set to make a dramatic difference in the number of patients who can benefit from heart transplantation., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Alcohol's impairment of both hepatic lipid metabolism and insulin resistance (IR) are key drivers of alcoholic steatosis, the initial stage of alcoholic liver disease (ALD). Pharmacologic reduction of lipotoxic ceramide prevents alcoholic steatosis and glucose intolerance in mice, but potential off-target effects limit its strategic utility. Here, we employed a hepatic-specific acid ceramidase (ASAH) overexpression model to reduce hepatic ceramides in a Lieber-DeCarli model of experimental alcoholic steatosis. We examined effects of alcohol on hepatic lipid metabolism, body composition, energy homeostasis, and insulin sensitivity as measured by hyperinsulinemic-euglycemic clamp. Our results demonstrate that hepatic ceramide reduction ameliorates the effects of alcohol on hepatic lipid droplet (LD) accumulation by promoting VLDL secretion and lipophagy, the latter of which involves ceramide cross-talk between the lysosomal and LD compartments. We additionally demonstrate that hepatic ceramide reduction prevents alcohol's inhibition of hepatic insulin signaling. These effects on the liver are associated with a reduction in oxidative stress markers and are relevant to humans, as we observe peri- LD ASAH expression in human ALD. Together, our results suggest a potential role for hepatic ceramide inhibition in preventing ALD., (Copyright © 2020 Correnti et al. Published by The American Society for Biochemistry and Molecular Biology, Inc.)

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon complication of acute pulmonary emboli necessitating lifelong anticoagulation. Despite this, few data exist on the safety and efficacy of vitamin K antagonists (VKAs) in CTEPH and none for direct oral anticoagulants (DOACs)., Objectives: To evaluate outcomes and complication rates in CTEPH following pulmonary endarterectomy (PEA) for individuals receiving VKAs or DOACs., Methods: Consecutive CTEPH patients undergoing PEA between 2007 and 2018 were included in a retrospective analysis. Postoperative outcomes, recurrent venous thromboembolism (VTE), and bleeding events were obtained from patient medical records., Results: Seven hundred ninety-four individuals were treated with VKAs and 206 with DOACs following PEA. Mean observation period was 612 (standard deviation: 702) days. Significant improvements in hemodynamics and functional status were observed in both groups following PEA (P < .001). Major bleeding events were equivalent (P = 1) in those treated with VKAs (0.67%/person-year) and DOACs (0.68%/person-year). The VTE recurrence was proportionately higher (P = .008) with DOACs (4.62%/person-year) than VKAs (0.76%/person-year), although survival did not differ., Conclusions: Post-PEA functional and hemodynamic outcomes appear unaffected by anticoagulant choice. Bleeding events were similar, but recurrent VTE rates significantly higher in those receiving DOACs. Our study provides a strong rationale for prospective registry data and/or studies to evaluate the safety of DOACs in CTEPH., (© 2019 International Society on Thrombosis and Haemostasis.)

Background: Women are more susceptible than men to several forms of pulmonary hypertension, but have better survival. Sparse data are available on chronic thromboembolic pulmonary hypertension (CTEPH)., Methods: We investigated sex-specific differences in the clinical presentation of CTEPH, performance of pulmonary endarterectomy (PEA), and survival., Results: Women constituted one-half of the study population of the European CTEPH registry (N = 679) and were characterized by a lower prevalence of some cardiovascular risk factors, including prior acute coronary syndrome, smoking habit, and chronic obstructive pulmonary disease, but more prevalent obesity, cancer, and thyroid diseases. The median age was 62 (interquartile ratio, 50-73) years in women and 63 (interquartile ratio, 53-70) in men. Women underwent PEA less often than men (54% vs 65%), especially at low-volume centers (48% vs 61%), and were exposed to fewer additional cardiac procedures, notably coronary artery bypass graft surgery (0.5% vs 9.5%). The prevalence of specific reasons for not being operated, including patient's refusal and the proportion of proximal vs distal lesions, did not differ between sexes. A total of 57 (17.0%) deaths in women and 70 (20.7%) in men were recorded over long-term follow-up. Female sex was positively associated with long-term survival (adjusted hazard ratio, 0.66; 95% confidence interval, 0.46-0.94). Short-term mortality was identical in the two groups., Conclusions: Women with CTEPH underwent PEA less frequently than men, especially at low-volume centers. Furthermore, they had a lower prevalence of cardiovascular risk factors and were less often exposed to additional cardiac surgery procedures. Women had better long-term survival., (© 2019 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.)

Background: Antimicrobial resistance (AMR) is one of the greatest threats in 21st century medicine. AMR has been characterized as a social dilemma. A familiar version describes the situation in which a collective resource (in this case, antibiotic efficacy) is exhausted due to over-exploitation. The dilemma arises because individuals are motivated to maximize individual payoffs, although the collective outcome is worse if all act in this way., Objectives: We aim to outline the implications for antimicrobial stewardship of characterizing antibiotic overuse as a social dilemma., Sources: We conducted a narrative review of the literature on interventions to promote the conservation of resources in social dilemmas., Content: The social dilemma of antibiotic over-use is complicated by the lack of visibility and imminence of AMR, a loose coupling between individual actions and the outcome of AMR, and the agency relationships inherent in the prescriber role. We identify seven strategies for shifting prescriber behaviour and promoting a focus on the collectively desirable outcome of conservation of antibiotic efficacy: (1) establish clearly defined boundaries and access rights; (2) raise the visibility and imminence of the problem; (3) enable collective choice arrangements; (4) conduct behaviour-based monitoring; (5) use social and reputational incentives and sanctions; (6) address misalignment of goals and incentives; and (7) provide conflict resolution mechanisms., Implications: We conclude that this theoretic analysis of antibiotic stewardship could make the problem of optimizing antibiotic prescribing more tractable, providing a theory base for intervention development., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Tongue worms utilise herbivorous mammals as intermediate hosts and reside in the nasopharynx of carnivores as their definitive hosts. A recent study in south eastern Australia showed an unexpectedly high infection (67%) of wild dogs with these parasites. The present study aimed at determining the pathogenicity of the parasite in both definitive (dog) and intermediate (cattle) hosts by histopathology. The definitive host showed multifocal haemorrhage of the interstitium of the nasal mucosa, multifocal mucosal erosion, congestion and haemorrhage, with haemosiderin laden macrophages present in those foci and distortion and destruction of the nasal mucosa. Histopathologic examination of lymph nodes from an infected cow showed diffuse eosinophilic granulomatous necrotising lymphadenitis and perinodal panniculitis with intralesional parasitic remnants and comparatively large numbers of eosinophils. A large, ~300-500 μm diameter, area of necrosis was also observed in one lymph node. This is the first time a study has been undertaken in Australia to determine the pathogenicity of tongue worms in both their definitive and intermediate hosts. This is a preliminary study and to properly estimate the health impact of infection with this pathogenic parasites on Australian production and companion animals more studies are necessary., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Data on several infections of sheep and goats, including parasite infections, are routinely collected during inspection of harvested rangeland goats after slaughter. This is an important role of the Australian National Sheep Health Monitoring Program (NSHMP). Our study investigated the presence of metacestodes of Taenia hydatigena, T. ovis and Echinococcus granulosus in slaughtered goats from Queensland, New South Wales and Western Australia. During the period of the study (2007-2013) 374,580 goats were slaughtered and inspected by trained abattoir meat inspectors as part of the NSHMP. Taenia hydatigena was found most commonly, followed by T. ovis. Despite one probable false positive, the surveyed population of goats was demonstrated to be free of infection by E. granulosus at a design prevalence of 0.1%. In areas where goats, foxes and wild dogs (dingoes [Canis lupus dingo] and dingo/domestic dog [Canis lupus] hybrids) co-exist they could be perpetuating the transmission of T. hydatigena and T. ovis as a wildlife reservoir. Rangeland goats do not appear to be an intermediate host for E. granulosus. Despite having similar lifecycles, T. hydatigena and T. ovis appeared to occur with different geographical patterns. This is the first time rangeland goats have been investigated for infection with taeniid metacestodes in such large numbers and over a wide geographical area., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Oxidative stress derived from perinatal asphyxia appears to be closely linked to neonatal brain damage and lipid peroxidation biomarkers have shown to provide predictive power of oxidative stress related pathologies in situations of hypoxia and reoxygenation in the newborn. The objective of this work was to develop and validate of a comprehensive liquid chromatography tandem mass spectrometry approach for the quantitative profiling of 28 isoprostanoids in newborn plasma samples covering a broad range of lipid peroxidation product classes. The method was developed taking into account the specific requirements for its use in neonatology (i.e. limited sample volumes, straightforward sample processing and high analytical throughput). The method was validated following stringent FDA guidelines and was then applied to the analysis of 150 plasma samples collected from newborns. Information obtained from the quantitative analysis of isoprostanoids was critically compared to that provided by a previously developed approach aiming at the semi-quantitative detection of total parameters of fatty acid derived lipid peroxidation biomarkers., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The requirement for heart transplantation is increasing, vastly outgrowing the supply of hearts available from donation after brain death (DBD) donors. Transplanting hearts after donation after circulatory-determined death (DCD) may be a viable additive alternative to DBD donors. This study compared outcomes from the largest single-center experience of DCD heart transplantation against matched DBD heart transplants., Methods: DCD hearts were retrieved using normothermic regional perfusion (NRP) or direct procurement and perfusion (DPP). During NRP, perfusion was restored to the arrested heart within the donor with the exclusion of the cerebral circulation, whereas DPP hearts were removed directly. All hearts were maintained on machine perfusion during transportation. A retrospective cohort of DBD heart transplants, matched for donor and recipient characteristics, was used as a comparison group. The primary outcome measure of this study (set by the United Kingdom regulatory body) was 90-day survival., Results: There were 28 DCD heart transplants performed during the 25-month study period. Survival at 90 days was not significantly different between DCD and matched DBD transplant recipients (DCD, 92%; DBD, 96%; p = 1.0). Hospital length of stay, treated rejection episodes, allograft function, and 1-year survival (DCD, 86%; DBD, 88%; p = 0.98) were comparable between groups. The method of retrieval (NRP or DPP) was not associated with a difference in outcome., Conclusions: These results suggest that heart transplantation from DCD heart donation provides comparable short-term outcomes to traditional DBD heart transplants and can serve to increase heart transplant activity in well-selected patients., (Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Approximately half of moderate to severely hypoxic-ischemic (HI) newborns do not respond to hypothermia, the only proven neuroprotective treatment. N-acetylcysteine (NAC), an antioxidant and glutathione precursor, shows promise for neuroprotection in combination with hypothermia, mitigating post-HI neuroinflammation due to oxidative stress. As mechanisms of HI injury and cell death differ in males and females, sex differences must be considered in translational research of neuroprotection. We assessed the potential toxicity and efficacy of NAC in combination with hypothermia, in male and female neonatal rats after severe HI injury. NAC 50mg/kg/d administered 1h after initiation of hypothermia significantly decreased iNOS expression and caspase 3 activation in the injured hemisphere versus hypothermia alone. However, only females treated with hypothermia +NAC 50mg/kg showed improvement in short-term infarct volumes compared with saline treated animals. Hypothermia alone had no effect in this severe model. When NAC was continued for 6 weeks, significant improvement in long-term neuromotor outcomes over hypothermia treatment alone was observed, controlling for sex. Antioxidants may provide insufficient neuroprotection after HI for neonatal males in the short term, while long-term therapy may benefit both sexes., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Objective: To describe medroxyprogesterone acetate (MPA) levels among Kenyan depot medroxyprogesterone acetate (DMPA) users in the FEM-PrEP HIV prevention trial, and to compare MPA levels between ARV for HIV prevention (treatment) and placebo groups., Study Design: We measured MPA in previously collected plasma samples from 63 Kenyan trial participants who used DMPA for one or two complete intervals. We separately assessed MPA levels among the nine DMPA users who became pregnant at this site., Results: Mean MPA levels at the end of each 12week injection interval were 0.37ng/ml (95% CI: 0.25, 1.99) and 0.28ng/ml (95% CI: 0.19, 1.22) among participants assigned TDF/FTC and 0.49 (95% CI: 0.40, 1.27) and 0.39 (95% CI: 0.31, 1.17) among those assigned placebo. The difference between groups was not statistically significant overall, or in an analysis which adjusted for the observed low adherence to TDF/FTC. Unanticipated findings of this analysis were low 12-week MPA levels among DMPA users in both study arms. Of 61 women who contributed data for the first DMPA injection interval, 26.2% had MPA levels<0.1ng/ml and 9.8% had levels below the detection level (0.02ng/ml) at 12weeks post-injection. Levels were similar at the end of the second injection interval. Five of nine women who became pregnant had levels below 0.15ng/mL at the time of their last negative pregnancy test., Conclusions: Use of TDF/FTC did not appear to affect serum MPA levels, however we found lower than expected MPA concentrations at the end of the dosing interval among DMPA users in the FEM-PrEP trial, the cause of which are unknown., Implications: This study presents some of the few available data on MPA levels among DMPA users in Africa. The low levels among users described here, together with a number of pregnancies among DMPA users, are potentially concerning and require further investigation., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Compared to a DASH-type diet, an intensively applied dietary portfolio reduced diastolic blood pressure at 24 weeks as a secondary outcome in a previous study. Due to the importance of strategies to reduce blood pressure, we performed an exploratory analysis pooling data from intensively and routinely applied portfolio treatments from the same study to assess the effect over time on systolic, diastolic and mean arterial pressure (MAP), and the relation to sodium (Na(+)), potassium (K(+)), and portfolio components., Methods and Results: 241 participants with hyperlipidemia, from four academic centers across Canada were randomized and completed either a DASH-type diet (control n = 82) or a dietary portfolio that included, soy protein, viscous fibers and nuts (n = 159) for 24 weeks. Fasting measures and 7-day food records were obtained at weeks 0, 12 and 24, with 24-h urines at weeks 0 and 24. The dietary portfolio reduced systolic, diastolic and mean arterial blood pressure compared to the control by 2.1 mm Hg (95% CI, 4.2 to -0.1 mm Hg) (p = 0.056), 1.8 mm Hg (CI, 3.2 to 0.4 mm Hg) (p = 0.013) and 1.9 mm Hg (CI, 3.4 to 0.4 mm Hg) (p = 0.015), respectively. Blood pressure reductions were small at 12 weeks and only reached significance at 24 weeks. Nuts, soy and viscous fiber all related negatively to change in mean arterial pressure (ρ = -0.15 to -0.17, p ≤ 0.016) as did urinary potassium (ρ = -0.25, p = 0.001), while the Na(+)/K(+) ratio was positively associated (ρ = 0.20, p = 0.010)., Conclusions: Consumption of a cholesterol-lowering dietary portfolio also decreased blood pressure by comparison with a healthy DASH-type diet. CLINICAL TRIAL REG. NO.: NCT00438425, clinicaltrials.gov., (Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Type 17 helper T-cell cytokines have been implicated in the pathogenesis of inflammatory bowel disease, a chronic condition affecting the gastrointestinal tract, but information regarding their contribution to pathology in different regions of the gut is lacking. By using a murine model of bacteria-induced typhlocolitis, we investigated the role of IL-17A, IL-17F, and IL-22 in cecal versus colonic inflammation. Cecal, but not colonic, pathology in C57BL/6 mice inoculated with Helicobacter hepaticus plus anti-IL-10 receptor (IL-10R) monoclonal antibody was exacerbated by co-administration of anti-IL-17A monoclonal antibody, suggesting a disease-protective role for IL-17A in the cecum. In contrast, anti-IL-17F had no effect on H. hepaticus-induced intestinal pathology. Neutralization of IL-22 prevented the development of colonic, but not cecal, inflammation in H. hepaticus-infected anti-IL-10R-treated mice, demonstrating a pathogenic role for IL-22 in the colon. Analysis of transcript levels revealed differential expression of IL-22R, IL-22 binding protein, and IL-23R between cecum and colon, a finding that may help explain why these tissues respond differently after anti-IL-22 treatment. Analysis of microarray data from healthy human intestine further revealed significant differences in cytokine receptor transcript levels (including IL-22RA1 and IL-23R) in distinct parts of the human gut. Together, our findings demonstrate that individual type 17 helper T-cell cytokines can have proinflammatory or anti-inflammatory effects in different regions of the intestine, an observation that may have implications for interventions against human inflammatory bowel disease., (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The positive and negative health effects of dietary carbohydrates are of interest to both researchers and consumers., Methods: International experts on carbohydrate research held a scientific summit in Stresa, Italy, in June 2013 to discuss controversies surrounding the utility of the glycemic index (GI), glycemic load (GL) and glycemic response (GR)., Results: The outcome was a scientific consensus statement which recognized the importance of postprandial glycemia in overall health, and the GI as a valid and reproducible method of classifying carbohydrate foods for this purpose. There was consensus that diets low in GI and GL were relevant to the prevention and management of diabetes and coronary heart disease, and probably obesity. Moderate to weak associations were observed for selected cancers. The group affirmed that diets low in GI and GL should always be considered in the context of diets otherwise understood as healthy, complementing additional ways of characterizing carbohydrate foods, such as fiber and whole grain content. Diets of low GI and GL were considered particularly important in individuals with insulin resistance., Conclusions: Given the high prevalence of diabetes and pre-diabetes worldwide and the consistency of the scientific evidence reviewed, the expert panel confirmed an urgent need to communicate information on GI and GL to the general public and health professionals, through channels such as national dietary guidelines, food composition tables and food labels., (Copyright © 2015 Elsevier B.V. All rights reserved.)