Spermatozoa Obtained From Alpaca vas deferens. Effects of Seminal Plasma Added at Post-thawing

The viscous seminal plasma (SP) is currently a major impediment to the handling of ejaculate and the development of some biotechnologies in South American camelids. The vas deferens-collected spermatozoa of alpacas is a useful technique to avoid this problem. On the other hand, SP contains a large protein component that has been implicated in the function of spermatozoa within the female reproductive tract. In this sense, the low fertility achieved using transcervical insemination with frozen-thawed spermatozoa in alpacas could be improved by adding SP. This study aimed to evaluate the effect of the whole SP on some in vitro parameters of alpaca spermatozoa after the freezing-thawing-process and the fertility after artificial insemination. It would contribute to a better understanding of the interaction between thawed sperm cells and SP. Spermatozoa were obtained by surgically diverted vas deferens. The samples were diluted with a Tris-based extender, packaged in straws, and frozen. At thawing, each straw was divided into two post-thawing conditions: with the addition of 10% of PBS (control) or with 10% SP (treatment). The sperm cells were evaluated using dynamic parameters, sperm cell morphology, and morphometry. Fertility was assessed by an artificial insemination trial. All in vitro parameters were analyzed by ANOVA. A heterogeneity test was scheduled for the fertility trial. After the freezing-thawing process, motility and plasma membrane functionality was improved when SP was added. No differences were found for post-thaw viability between the control and treatment samples. The percentage of normal cells was higher with SP at post-thawing, and a decrease of the presence of bent tailed spermatozoa with a droplet in the SP group was observed. The length of the head spermatozoa was 3.4% higher in the samples with PBS compared to those in which SP was added. Females pregnant at day 25 post-insemination were 0/12 (with SP inside the straw) and 1/10 (without SP inside the straw). In conclusion, the presence of 10% SP at post-thawing improves sperm cells' motility, functionality, and morphology, indicating that it would be beneficial to improve the frozen-thawed alpaca's physiology spermatozoa. More fertility trials must be developed to increase this knowledge

Randomized elimination and prolongation of ACE inhibitors and ARBs in coronavirus 2019 (REPLACE COVID) Trial Protocol

Severe acute respiratory syndrome coronavirus 2 (SARS- CoV- 2), the virus responsible for coronavirus disease 2019 (COVID- 19), is associated with high incidence of multiorgan dysfunction and death. Angiotensin- converting enzyme 2 (ACE2), which facilitates SARS- CoV- 2 host cell entry, may be impacted by angiotensin- converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), two commonly used antihypertensive classes. In a multicenter, international randomized controlled trial that began enrollment on March 31, 2020, participants are randomized to continuation vs withdrawal of their long- term outpatient ACEI or ARB upon hospitalization with COVID- 19. The primary outcome is a hierarchical global rank score incorporating time to death, duration of mechanical ventilation, duration of renal replacement or vasopressor therapy, and multiorgan dysfunction severity. Approval for the study has been obtained from the Institutional Review Board of each participating institution, and all participants will provide informed consent. A data safety monitoring board has been assembled to provide independent oversight of the project.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163400/2/jch14011_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163400/1/jch14011.pd

Comparing algorithms for automated vessel segmentation in computed tomography scans of the lung: the VESSEL12 study

The VESSEL12 (VESsel SEgmentation in the Lung) challenge objectively compares the performance of different algorithms to identify vessels in thoracic computed tomography (CT) scans. Vessel segmentation is fundamental in computer aided processing of data generated by 3D imaging modalities. As manual vessel segmentation is prohibitively time consuming, any real world application requires some form of automation. Several approaches exist for automated vessel segmentation, but judging their relative merits is difficult due to a lack of standardized evaluation. We present an annotated reference dataset containing 20 CT scans and propose nine categories to perform a comprehensive evaluation of vessel segmentation algorithms from both academia and industry. Twenty algorithms participated in the VESSEL12 challenge, held at International Symposium on Biomedical Imaging (ISBI) 2012. All results have been published at the VESSEL12 website http://vessel12.grand-challenge.org. The challenge remains ongoing and open to new participants. Our three contributions are: (1) an annotated reference dataset available online for evaluation of new algorithms; (2) a quantitative scoring system for objective comparison of algorithms; and (3) performance analysis of the strengths and weaknesses of the various vessel segmentation methods in the presence of various lung diseases.Rudyanto, RD.; Kerkstra, S.; Van Rikxoort, EM.; Fetita, C.; Brillet, P.; Lefevre, C.; Xue, W.... (2014). Comparing algorithms for automated vessel segmentation in computed tomography scans of the lung: the VESSEL12 study. Medical Image Analysis. 18(7):1217-1232. doi:10.1016/j.media.2014.07.003S1217123218

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Randomized elimination and prolongation of ACE inhibitors and ARBs in coronavirus 2019 (REPLACE COVID) Trial Protocol

Severe acute respiratory syndrome coronavirus 2 (SARS- CoV- 2), the virus responsible for coronavirus disease 2019 (COVID- 19), is associated with high incidence of multiorgan dysfunction and death. Angiotensin- converting enzyme 2 (ACE2), which facilitates SARS- CoV- 2 host cell entry, may be impacted by angiotensin- converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), two commonly used antihypertensive classes. In a multicenter, international randomized controlled trial that began enrollment on March 31, 2020, participants are randomized to continuation vs withdrawal of their long- term outpatient ACEI or ARB upon hospitalization with COVID- 19. The primary outcome is a hierarchical global rank score incorporating time to death, duration of mechanical ventilation, duration of renal replacement or vasopressor therapy, and multiorgan dysfunction severity. Approval for the study has been obtained from the Institutional Review Board of each participating institution, and all participants will provide informed consent. A data safety monitoring board has been assembled to provide independent oversight of the project.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163400/2/jch14011_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163400/1/jch14011.pd

Continuation versus discontinuation of renin–angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial

Background: Biological considerations suggest that renin–angiotensin system inhibitors might influence the severity of COVID-19. We aimed to evaluate whether continuing versus discontinuing renin–angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19. Methods: The REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide. Eligible participants were aged 18 years and older who were admitted to hospital with COVID-19 and were receiving a renin–angiotensin system inhibitor before admission. Individuals with contraindications to continuation or discontinuation of renin–angiotensin system inhibitor therapy were excluded. Participants were randomly assigned (1:1) to continuation or discontinuation of their renin–angiotensin system inhibitor using permuted block randomisation, with allocation concealed using a secure web-based randomisation system. The primary outcome was a global rank score in which participants were ranked across four hierarchical tiers incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalisation. Primary analyses were done in the intention-to-treat population. The REPLACE COVID trial is registered with ClinicalTrials.gov, NCT04338009. Findings: Between March 31 and Aug 20, 2020, 152 participants were enrolled and randomly assigned to either continue or discontinue renin–angiotensin system inhibitor therapy (continuation group n=75; discontinuation group n=77). Mean age of participants was 62 years (SD 12), 68 (45%) were female, mean body-mass index was 33 kg/m2 (SD 8), and 79 (52%) had diabetes. Compared with discontinuation of renin–angiotensin system inhibitors, continuation had no effect on the global rank score (median rank 73 [IQR 40–110] for continuation vs 81 [38–117] for discontinuation; β-coefficient 8 [95% CI −13 to 29]). There were 16 (21%) of 75 participants in the continuation arm versus 14 (18%) of 77 in the discontinuation arm who required intensive care unit admission or invasive mechanical ventilation, and 11 (15%) of 75 participants in the continuation group versus ten (13%) of 77 in the discontinuation group died. 29 (39%) participants in the continuation group and 28 (36%) participants in the discontinuation group had at least one adverse event (χ2 test of adverse events between treatment groups p=0·77). There was no difference in blood pressure, serum potassium, or creatinine during follow-up across the two groups. Interpretation: Consistent with international society recommendations, renin–angiotensin system inhibitors can be safely continued in patients admitted to hospital with COVID-19. Funding: REPLACE COVID Investigators, REPLACE COVID Trial Social Fundraising Campaign, and FastGrants.Fil: Cohen, Jordana B.. State University of Pennsylvania; Estados UnidosFil: Hanff, Thomas C.. State University of Pennsylvania; Estados UnidosFil: William, Preethi. University of Arizona; Estados UnidosFil: Sweitzer, Nancy. University of Arizona; Estados UnidosFil: Rosado Santander, Nelson R.. Hospital Nacional Carlos Alberto Seguin Escobedo; PerúFil: Medina, Carola. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: Rodriguez-Mori, Juan E. Hospital Nacional Alberto Sabogal Sologuren; PerúFil: Renna, Nicolas Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo; ArgentinaFil: Chang, Tara I.. University of Stanford; Estados UnidosFil: Corrales Medina, Vicente. Ottawa Hospital Research Institute; CanadáFil: Andrade Villanueva, Jaime F.. Hospital Civil de Guadalajara; MéxicoFil: Barbagelata, Alejandro. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. University of Duke; Estados UnidosFil: Cristodulo Cortez, Roberto. No especifíca;Fil: Díaz-Cucho, Omar A. Hospital Alberto Leopoldo Barton Thompson; PerúFil: Spaak, Jonas. Danderyd University Hospital; SueciaFil: Alfonso, Carlos E.. University of Miami; Estados UnidosFil: Valdivia Vega, Renzo. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: Villavicencio Carranza, Mirko. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: Ayala García, Ricardo J.. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: Castro Callirgos, Carlos A.. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: González Hernández, Luz A.. Hospital Civil de Guadalajara; MéxicoFil: Bernales Salas, Eduardo F.. Hospital Nacional Carlos Alberto Seguin Escobedo; PerúFil: Coacalla Guerra, Johanna C.. Hospital Nacional Carlos Alberto Seguin Escobedo; PerúFil: Salinas Herrera, Cynthia D.. Hospital Nacional Carlos Alberto Seguin Escobedo; PerúFil: Nicolosi, Liliana. Hospital Espanol; ArgentinaFil: Basconcel, Mauro. Hospital Espanol; ArgentinaFil: Byrd, James B.. University of Michigan; Estados UnidosFil: Sharkoski, Tiffany. University of Pennsylvania; Estados UnidosFil: Bendezú Huasasquiche, Luis E.. Hospital Alberto Leopoldo Barton Thompson; PerúFil: Chittams, Jesse. University of Pennsylvania; Estados UnidosFil: Edmonston, Daniel L.. University of Duke; Estados UnidosFil: Vasquez, Charles R.. University of Pennsylvania; Estados UnidosFil: Chirinos, Julio A.. University of Pennsylvania; Estados Unido

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)