A randomized trial of vonapanitase (PATENCY-1) to promote radiocephalic fistula patency and use for hemodialysis

Objective

Arteriovenous fistulas created in patients with chronic kidney disease often lose patency and fail to become usable. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in promoting radiocephalic fistula patency and use for hemodialysis.

Epstein-Barr Virus–Related Post-Transplant Lymphoproliferative Disorders in Cystic Fibrosis Lung Transplant Recipients: A Case Series

Background

Solid organ transplantation is associated with a higher risk of Epstein-Barr virus (EBV)–related lymphoproliferative disease due to immunosuppressive regimen. Little evidence is currently available on post-transplant lymphoproliferative disorders (PTLDs) in the lung transplant (LuTx) setting, particularly in cystic fibrosis (CF) recipients.

Did a Goals-of-Care Discussion Happen? Differences in the Occurrence of Goals-of-Care Discussions as Reported by Patients,Clinicians, and in the Electronic Health Record

Context

Goals-of-care discussions are associated with improved end-of-life care for patients and therefore may be used as a process measure in quality improvement, research, and reimbursement programs.

Influence of Prior Psychiatric Disorders on the Treatment Course of Gynaecological Cancer – A Nationwide Cohort Study

Aims

To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer.

Superior efficacy of co-targeting GFI1/KDM1A and BRD4 against AML and post-MPN secondary AML cells

There is an unmet need to overcome nongenetic therapy-resistance to improve outcomes in AML, especially post-myeloproliferative neoplasm (MPN) secondary (s) AML. Studies presented describe effects of genetic knockout, degradation or small molecule targeted-inhibition of GFI1/LSD1 on active enhancers, altering gene-expressions and inducing differentiation and lethality in AML and (MPN) sAML cells. A protein domain-focused CRISPR screen in LSD1 (KDM1A) inhibitor (i) treated AML cells, identified BRD4, MOZ, HDAC3 and DOT1L among the codependencies. Our findings demonstrate that co-targeting LSD1 and one of these co-dependencies exerted synergistic in vitro lethality in AML and post-MPN sAML cells. Co-treatment with LSD1i and the JAKi ruxolitinib was also synergistically lethal against post-MPN sAML cells. LSD1i pre-treatment induced GFI1, PU.1 and CEBPα but depleted c-Myc, overcoming nongenetic resistance to ruxolitinib, or to BETi in post-MPN sAML cells. Co-treatment with LSD1i and BETi or ruxolitinib exerted superior in vivo efficacy against post-MPN sAML cells. These findings highlight LSD1i-based combinations that merit testing for clinical efficacy, especially to overcome nongenetic therapy-resistance in AML and post-MPN sAML.Subject terms: Acute myeloid leukaemia, Targeted therapies     

Effects of cancer screening restart strategies after COVID-19 disruption

Background Many breast, cervical, and colorectal cancer screening programmes were disrupted due to the COVID-19 pandemic. This study aimed to estimate the effects of five restart strategies after the disruption on required screening capacity and cancer burden.Methods Microsimulation models simulated five restart strategies for breast, cervical, and colorectal cancer screening. The models estimated required screening capacity, cancer incidence, and cancer-specific mortality after a disruption of 6 months. The restart strategies varied in whether screens were caught up or not and, if so, immediately or delayed, and whether the upper age limit was increased.Results The disruption in screening programmes without catch-up of missed screens led to an increase of 2.0, 0.3, and 2.5 cancer deaths per 100 000 individuals in 10 years in breast, cervical, and colorectal cancer, respectively. Immediately catching-up missed screens minimised the impact of the disruption but required a surge in screening capacity. Delaying screening, but still offering all screening rounds gave the best balance between required capacity, incidence, and mortality.Conclusions Strategies with the smallest loss in health effects were also the most burdensome for the screening organisations. Which strategy is preferred depends on the organisation and available capacity in a country.Subject terms: Health policy, Population screening, Cancer screening, Cancer screening     

Long-term Implications of Tracheostomy in Cardiac Surgery Patients: Decannulation and Mortality

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Tractography of the Cerebellar Peduncles in Second- and Third-Trimester Fetuses

BACKGROUND AND PURPOSE:Little is known about microstructural development of cerebellar white matter in vivo. This study aimed to investigate developmental changes of the cerebellar peduncles in second- and third-trimester healthy fetuses using motion-corrected DTI and tractography.MATERIALS AND METHODS:3T data of 81 healthy fetuses were reviewed. Structural imaging consisted of multiplanar T2-single-shot sequences; DTI consisted of a series of 12-direction diffusion. A robust motion-tracked section-to-volume registration algorithm reconstructed images. ROI-based deterministic tractography was performed using anatomic landmarks described in postnatal tractography. Asymmetry was evaluated qualitatively with a perceived difference of >25% between sides. Linear regression evaluated gestational age as a predictor of tract volume, ADC, and fractional anisotropy.RESULTS:Twenty-four cases were excluded due to low-quality reconstructions. Fifty-eight fetuses with a median gestational age of 30.6 weeks (interquartile range, 7 weeks) were analyzed. The superior cerebellar peduncle was identified in 39 subjects (69%), and it was symmetric in 15 (38%). The middle cerebellar peduncle was identified in all subjects and appeared symmetric; in 13 subjects (22%), two distinct subcomponents were identified. The inferior cerebellar peduncle was not found in any subject. There was a significant increase in volume for the superior cerebellar peduncle and middle cerebellar peduncle (both, P < .05), an increase in fractional anisotropy (both, P < .001), and a decrease in ADC (both, P < .001) with gestational age. The middle cerebellar peduncle had higher volume (P < .001) and fractional anisotropy (P = .002) and lower ADC (P < .001) than the superior cerebellar peduncle after controlling for gestational age.CONCLUSIONS:A robust motion-tracked section-to-volume registration algorithm enabled deterministic tractography of the superior cerebellar peduncle and middle cerebellar peduncle in vivo and allowed characterization of developmental changes.

In the second half of pregnancy, the cerebellum is growing rapidly and is extremely vulnerable.¹ Despite the increasingly recognized association of antenatal and perinatal cerebellar injury with adverse motor and neurologic outcomes later in life,^2-5 little is known about normal cerebellar developmental in the later part of gestation, in particular with regard to changes in microstructure. In fact, most existing fetal MR imaging data addresses primarily changes in cerebellar volume with gestational age (GA) or changes in volume and their association with specific diseases such as congenital heart disease.^6-8In vivo evaluation of cerebellar microstructure using fetal MR imaging has been limited by the technical challenges related to imaging the gravid abdomen, particularly patient motion. However, data from ex vivo MR imaging studies are promising. For instance, Takahashi et al^9,10 performed high-resolution ex vivo DTI of fetal specimens and demonstrated the feasibility of using tractography to outline the cerebellar peduncles prenatally. Even though tractography of the cerebellar peduncles has been sporadically reported in vivo in technical articles or general review articles on fetal DTI,¹¹ the GA-related microstructural changes that occur in the cerebellar peduncles in the second half of pregnancy remain largely unexplored.Recent advances in hardware and software have improved fetal MR imaging substantially. The use of 3T magnets, which have been shown to be safe, results in improvement of the SNR and spatial resolution, which is advantageous to image the small structures of the fetal brain.^12,13 In addition, postprocessing algorithms that enable reconstruction of motion-corrected fetal DTI data are increasingly available and have been used by several groups to characterize the development of the supratentorial white matter tracts in vivo.^14-16 We hypothesize that fetal DTI performed at 3T and processed with a robust section-to-volume motion-correction and registration¹⁴ algorithm will enable tractography of the cerebellar peduncles in fetuses in the second and third trimesters of pregnancy. We aimed to characterize fetal cerebellar tract microstructure and to investigate tract-specific developmental changes.     

Postprocedural Antiplatelet Treatment after Emergent Carotid Stenting in Tandem Lesions Stroke: Impact on Stent Patency beyond Day 1

BACKGROUND AND PURPOSE:Postprocedural dual-antiplatelet therapy is frequently withheld after emergent carotid stent placement during stroke thrombectomy. We aimed to assess whether antiplatelet regimen variations increase the risk of stent thrombosis beyond postprocedural day 1.MATERIALS AND METHODS:Retrospective review was undertaken of all consecutive thrombectomies for acute stroke with tandem lesions in the anterior circulation performed in a single comprehensive stroke center between January 9, 2011 and March 30, 2020. Patients were included if carotid stent patency was confirmed at day 1 postprocedure. The group of patients with continuous dual-antiplatelet therapy from day 1 was compared with the group of patients with absent/discontinued dual-antiplatelet therapy.RESULTS:Of a total of 109 tandem lesion thrombectomies, 96 patients had patent carotid stents at the end of the procedure. The early postprocedural stent thrombosis rate during the first 24 hours was 14/96 (14.5%). Of 82 patients with patent stents at day 1, in 28 (34.1%), dual-antiplatelet therapy was either not initiated at day 1 or was discontinued thereafter. After exclusion of cases without further controls of stent patency, there was no significant difference in the rate of subacute/late stent thrombosis between the 2 groups: 1/50 (2%) in patients with continuous dual-antiplatelet therapy versus 0/22 (0%) in patients with absent/discontinued dual-antiplatelet therapy (P = 1.000). In total, we observed 88 patient days without any antiplatelet treatment and 471 patient days with single antiplatelet treatment.CONCLUSIONS:Discontinuation of dual-antiplatelet therapy was not associated with an increased risk of stent thrombosis beyond postprocedural day 1. Further studies are warranted to better assess the additional benefit and optimal duration of dual-antiplatelet therapy after tandem lesion stroke thrombectomy.

In around 15% of endovascular procedures for anterior circulation stroke,¹ there is a tight stenosis or occlusion of the cervical carotid artery in addition to the intracranial artery occlusion. The optimal endovascular management of tandem lesions has yet to be defined; however, there is mounting evidence^2,3 that emergent stent placement in the carotid artery associated with at least 1 antiplatelet agent could lead to better recanalization rates and improved clinical outcomes. A more definitive answer should be provided by the Thrombectomy In TANdem lesions (TITAN) randomized multicenter trial,⁴ designed to assess the safety and efficacy of emergent internal carotid artery stent placement in tandem lesion thrombectomy. This study recently enrolled the first patient in early 2020.In patients undergoing emergent carotid stent placement, there is no consensus regarding the optimal periprocedural antiplatelet therapy. Many groups^5,6 chose to avoid dual-antiplatelet therapy (DAPT) during the first 24 hours in an attempt to reduce the risk of hemorrhagic transformation. Conversely, less aggressive antiplatelet regimens might increase the risk of carotid stent thrombosis.Stent thrombosis was recently identified as a predictor of unfavorable clinical outcome.^7,8 To date, available data regarding stent patency rates remain scarce. Most case series of endovascular management for tandem lesions^5,9-11 do not report postprocedural stent patency, while some publications^12-15 offer partial data for a subgroup of patients for whom carotid imaging controls were available. Reported rates of stent thrombosis ranged between 1.2% and 22.0%.^{6-8,12-14,16,17}To date, no study has attempted to differentiate between early (first 24 hours) and subacute/late postprocedural stent thrombosis. During the first 24 hours, protection against stent thrombosis is conferred by antiplatelet agents administered during the procedure (periprocedural antiplatelets). Beyond 24 hours, the recommended antiplatelet regimen is DAPT for 4–12 weeks,^9,17 but in reality, antiplatelets are often tailored in view of neurological and extra-neurological hemorrhagic events. It is currently unknown whether discontinuation of DAPT is associated with an increased risk of late stent thrombosis.Thus, we aimed to describe the variations in the postprocedural antiplatelet regimen in a large consecutive cohort of tandem lesion thrombectomies with emergent carotid artery stent placement and to assess whether discontinuation of DAPT was associated with an increased risk of carotid stent thrombosis.