Publications by authors named "Stéphanie Nguyen"

124 Publications

Comparing Public Sentiment towards COVID-19 Vaccines across Canadian Cities: Analysis of Comments on Reddit.

J Med Internet Res 2021 Sep 8. Epub 2021 Sep 8.

Department of Mathematics & Statistics, York University, Ross 533N4700 Keele Street, Toronto, CA.

Background: Social media enables the rapid consumption of news related to COVID-19 and serves as a platform for discussions. Its richness in text-based data in the form of posts and comments allows researchers to identify popular topics and assess public sentiment. Yet, the vast majority of topic extraction and sentiment analysis based on social media is done on the platform or country level and does not account for local culture and policies.

Objective: The aim of this study is to use location-based subreddits on Reddit to study city-level variations in sentiments toward vaccine-related topics.

Methods: Comments made on posts providing regular updates on COVID-19 statistics in the Vancouver (r/vancouver, 49,291), Toronto (r/toronto, 20,764), and Calgary (r/calgary, 21,277) subreddits between July 13th, 2020 and June 14th, 2021 were extracted. Latent Dirichlet allocation was used to identify frequently discussed topics. Sentiment (joy, sadness, fear, and anger) scores were assigned to comments using random forest regression.

Results: The number of comments made on the 250 posts from the Vancouver subreddit positively correlated with the number of new daily COVID-19 cases in British Columbia (R = 0.51, 95% CI for slope = [0.18,0.29], P < 0.001). From the comments, thirteen topics were identified. Two were related to vaccines, one regarding vaccine uptake and the other about vaccine supply. The levels of discussion for both topics were linked to the total number of vaccinations given (Granger test for causality: P < 0.001). Comments pertaining to either topic displayed higher scores for joy compared to comments about other topics (P < 0.001). Calgary and Toronto also discussed vaccine uptake. Sentiment scores for this topic differed across the three cities (P < 0.001).

Conclusions: Our work demonstrates that data from city-specific subreddits can be used to better understand concerns and sentiments around COVID-19 vaccines at the local level. This can potentially lead to more targeted and publicly-acceptable policies based on content on social media.

Clinicaltrial:
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http://dx.doi.org/10.2196/32685DOI Listing
September 2021

Improved outcome in children compared to adolescents and young adults after allogeneic hematopoietic stem cell transplant for acute myeloid leukemia: a retrospective study from the Francophone Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC).

J Cancer Res Clin Oncol 2021 Sep 4. Epub 2021 Sep 4.

Department of Haematology, Hôpital de Haute-Pierre, 67200, Strasbourg, France.

Background: There are currently few data on the outcome of acute myeloid leukemia (AML) in adolescents after allogeneic HSCT. The aim of this study is to describe the outcome and its specific risk factors for children, adolescents and young adults after a first allogeneic HSCT for AML.

Methods: In this retrospective study, we compared the outcome of AML patients receiving a first allogeneic HSCT between 2005 and 2017 according to their age at transplantation's time: children (< 15 years, n = 564), adolescent and post-adolescent (APA) patients (15-25 years, n = 647) and young adults (26-40 years; n = 1434).

Results: With a median follow-up of 4.37 years (min-max 0.18-14.73 years), the probability of 2-year overall survival (OS) was 71.4% in children, 61.1% in APA patients and 62.9% in young adults (p = 0.0009 for intergroup difference). Both relapse and non-relapse mortality (NRM) Cumulative Incidence (CI) estimated at 2 years were different between the age groups (30.8% for children, 35.2% for APA patients and 29.4% for young adults-p = 0.0254, and 7.0% for children, 10.6% for APA patients and 14.2% for young adults, p < 0.0001; respectively). Whilst there was no difference between the three groups for grade I to IV acute GVHD CI at 3 months, the chronic GVHD CI at 2 years was higher in APA patients and young adults (31.4% and 36.4%, respectively) in comparison to the children (17.5%) (p < 0.0001). In multivariable analysis, factors associated with death were AML cytogenetics (HR1.73 [1.29-2.32] for intermediate risk 1, HR 1.50 [1.13-2.01] for intermediate risk 2, HR 2.22 [1.70-2.89] for high cytogenetics risk compared to low risk), use of TBI ≥ 8 Grays (HR 1.33 [1.09-1.61]), disease status at transplant (HR 1.40 [1.10-1.78] for second Complete Remission (CR), HR 2.26 [1.02-4.98] for third CR and HR 3.07 [2.44-3.85] for active disease, compared to first CR), graft source (HR 1.26 [1.05-1.50] for Peripheral Blood Stem Cells compared to Bone Marrow) and donor age (HR 1.01 (1-1.02] by increase of 1 year).

Conclusion: Age is an independent risk factor for NRM and extensive chronic GVHD. This study suggests that APA patients with AML could be beneficially treated with a chemotherapy-based MAC regimen and bone marrow as a stem cells source.
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http://dx.doi.org/10.1007/s00432-021-03761-wDOI Listing
September 2021

Commentary: The second cut is the deepest.

JTCVS Tech 2021 Aug 14;8:73-74. Epub 2021 May 14.

Division of Cardiac, Thoracic and Vascular Surgery, Department of Surgery, Columbia University Medical Center/New York-Presbyterian, New York, NY.

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http://dx.doi.org/10.1016/j.xjtc.2021.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350883PMC
August 2021

Allogeneic hematopoietic stem cell transplantation from unmanipulated haploidentical donor and unrelated cord blood for T-cell lymphoma: a retrospective study from the Société Francophone de Greffe de Moelle et de Therapie Cellulaire.

Bone Marrow Transplant 2021 Aug 6. Epub 2021 Aug 6.

CHU de Clermont-Ferrand, Clermont-Ferrand, France.

After chemotherapy, fewer than 30% of patients with T-cell lymphoma (T-NHL) are long-term disease-free survivors. Thus, there is a growing interest in allogeneic stem cell transplantation (alloSCT) and its potential graft-versus-lymphoma effect (GVL) for patient with high-risk or recurrent T-NHL with the aim at providing durable disease control in T-NHL. We conducted this registry study to evaluate the outcome of recipients of alternative donor alloSCT for T-NHL. Patients transplanted with Haploidentical donor (Haplo, n = 41) or Umbilical Cord Blood (UCB, n = 54) were analyzed for overall survival (OS), non-relapse mortality (NRM), relapse, and acute/chronic graft-versus-host disease (aGVHD/cGVHD) incidence. At 2 years, OS and PFS were, respectively, of 59% and 53%, without significant difference between Haplo and UCB. In multivariate analysis, disease status at transplant was an independent risk factor for OS and PFS, and aGVHD III-IV was the main factor for OS and NRM. While no major impact of donor source on survival and mortality was noted, this study suggests that alternative donor transplantation appears feasible and offers benefits to patients with T-cell lymphoma.
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http://dx.doi.org/10.1038/s41409-021-01426-3DOI Listing
August 2021

FLAMSA-Busulfan-Melphalan as a Sequential Conditioning Regimen in HLA-Matched or Haploidentical Hematopoietic Stem Cell Transplantation for High-Risk Myeloid Diseases.

Transplant Cell Ther 2021 Jul 28. Epub 2021 Jul 28.

Service d'Hématologie Clinique, Hôpital Pitié-Salpêtrière, APHP, Sorbonne Université, Paris, France.

Given the poor prognosis of relapsed/refractory myeloid malignancies, the concept of sequential conditioning before allogeneic hematopoietic stem cell transplantation (allo-HSCT) has proven to be an effective approach. We sought to evaluate a sequential scheme combining fludarabine, amsacrine, and cytarabine (FLAMSA) for cytoreduction, followed by reduced-intensity conditioning with busulfan and melphalan (FLAMSA-BuMel), which was designed to be suitable for both HLA-matched and haploidentical HSCT. This single-center retrospective study included 36 adult patients with high-risk myeloid malignancies who underwent allo-HSCT from HLA-matched (n = 19) or haploidentical (n = 17) donors. Along with the standard prophylaxis for graft-versus-host disease (GVHD), patients with a haploidentical donor received post-transplantation high-dose cyclophosphamide. A post-transplantation consolidation treatment with low-dose 5-azacytidine and prophylactic donor lymphocyte infusions was provided whenever possible. Thirty patients (83%) achieved complete remission on day +30. With a median follow-up of 30.0 months, the 2-year overall survival was 89% in the HLA-matched group versus 34% in the haploidentical group (P = .0018). The 2-year disease-free survival in these 2 groups was 68% and 34%, respectively (P = .013). At 2 years, the probability of relapse was 32% and 20%, respectively, and nonrelapse mortality was 0% and 58%, respectively (P = .0003). The leading cause of death was relapse in the HLA-matched group (3 of 19) and hemorrhagic events (5 of 17) in the haploidentical group, favored by significantly delayed platelet reconstitution and a severe GVHD context. These data confirm the feasibility of FLAMSA-BuMel as a sequential conditioning in allo-HSCT for high-risk myeloid malignancies. The use of bone marrow as the preferred graft source might reduce the incidence of acute GVHD and nonrelapse mortality in the haploidentical transplantation setting.
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http://dx.doi.org/10.1016/j.jtct.2021.07.018DOI Listing
July 2021

Commentary: Less-invasive approaches to big complex problems in patients with end-stage heart disease.

JTCVS Tech 2020 Dec 16;4:200-201. Epub 2020 Sep 16.

Department of Cardiothoracic and Vascular Surgery, University of Texas Health Science Center Houston, McGovern Medical School, Memorial Hermann Hospital-Heart and Vascular Institute, Houston, Tex.

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http://dx.doi.org/10.1016/j.xjtc.2020.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306215PMC
December 2020

[Immunomonitoring of patients treated with CAR-T cells for hematological malignancy: Guidelines from the CARTi group and the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

Bull Cancer 2021 Jul 9. Epub 2021 Jul 9.

Université de Paris, Hôpital Saint-Louis, AP-HP Nord, Laboratoire d'Immunologie, France.

CAR-T cells represent a new anti-tumor immunotherapy which has shown its clinical efficacy in B-cell malignancies. The results of clinical trials carried out in this context have shown that certain immunological characteristics of patients before (at the time of apheresis) and after the administration of the treatment, or of the CAR-T cells themselves, are correlated with the response to the treatment or to its toxicity. However, to date, there are no recommendations on the immunological monitoring of patients treated in real life. The objectives of this workshop were to determine, based on data from the literature and the experience of the centers, the immunological analyses to be carried out in patients treated with CAR-T cells. The recommendations relate to the characterization of the patient's immune cells at the time of apheresis, the characterization of the injected CAR-T cells, as well as the monitoring of the CAR-T cells and other parameters of immune reconstitution in the patient after administration of the treatment. Harmonization of practices will allow clinical-biological correlation studies to be carried out in patients treated in real life with the aim of identifying factors predictive of response and toxicity. Such data could have a major medico-economic impact by making it possible to identify the patients who will optimally benefit from these expensive treatments.
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http://dx.doi.org/10.1016/j.bulcan.2021.04.008DOI Listing
July 2021

Increasing Use of Ambulatory Video Visits for Pediatric Patients by Using Quality Improvement Methods.

Pediatr Qual Saf 2021 Jul-Aug;6(4):e424. Epub 2021 Jun 23.

Department of Pediatrics, University of California at Davis, Sacramento, Calif.

Introduction: Live video visits for ambulatory encounters offer potential benefits, including access to remote subspecialty services, care coordination between providers, and improved convenience for patients. We aimed to increase the utilization of video visits for pediatric patients at our medical center using an iterative quality improvement process.

Methods: A multispecialty improvement team identified opportunities to increase video visit utilization and prioritized interventions using benefit-effort analyses. Interventions focused on 6 key drivers. The outcome measure was the percentage of ambulatory encounters conducted by video. The process measure was the percentage of ambulatory pediatricians conducting video visits. The balancing measure was the percentage of no-shows among scheduled video visits. All measures were analyzed using statistical process control.

Results: Interventions were associated with increases in our outcome and process measures from 0.1% to 1.2% and 0.6% to 6.3%, respectively, during the first 8 months. Subsequently, the novel coronavirus (COVID-19) pandemic was associated with further increases in these measures to 41.8% and 73.5%, respectively, over 3 months. The balancing measure increased from 0% at baseline to 14.7% with no special cause variation during the intervention period. The most impactful interventions included clinician training outreach, providing equipment, and streamlining MyChart patient enrollment.

Conclusions: This improvement project effectively increased pediatric ambulatory video visit utilization, although the most significant driver of utilization was the COVID-19 pandemic. Project interventions implemented before COVID-19 facilitated rapid video visit adoption during the pandemic. A similar improvement process may be beneficial for other medical centers aiming to improve video visit utilization.
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http://dx.doi.org/10.1097/pq9.0000000000000424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225361PMC
June 2021

Valve Sparing Root Replacement versus Bio-Bentall: Inverse Propensity Weighting of 796 Patients.

Ann Thorac Surg 2021 Jun 8. Epub 2021 Jun 8.

Columbia University Vagelos College of Physicians and Surgeons, New York, NY; Division of Cardiothoracic and Vascular Surgery, New York Presbyterian Hospital, Columbia University Medical Center, New York, NY. Electronic address:

Background: This large cohort, single center study aims to compare the 10-year survival and freedom from aortic valve reintervention between valve sparing root replacement (VSRR) and bioprosthetic Bentall (bio-Bentall).

Methods: All patients undergoing elective VSRR or bio-Bentall for aortic root aneurysm between March 2005 through October 2019 were retrospectively reviewed (n=796 [VSRR = 360]). Inverse probability of treatment weighting (IPTW) balanced clinical variables between groups. Mean follow-up was 58.0 +/- 45.4 (range 0-167) months.

Results: After IPTW adjustment, 10-year survival did not differ between groups (VSRR: 87.0% vs bio-Bentall: 92.7%, p=0.780). Cumulative incidence of aortic valve reintervention was 5.9% for VSRR (95% CI, 2.9%-10.4%) and 10.6% for bio-Bentall (95% CI, 6.2%-16.4%, p=0.798). Fine and Gray computing risk regression model identified age at surgery (sHR 0.97, 95% CI, 0.95-0.99, p=0.015), body surface area (sHR 6.21, 95% CI, 1.97-19.59, p=0.002) and bicuspid aortic valve (sHR 2.15, 95% CI, 1.04-4.44, p =0.038) as independently associated with aortic valve reintervention. For patients ≤50-year-old, cumulative incidence of aortic valve reintervention was 16.2% for VSRR (95% CI, 7.0%-28.8%) and 17.8% for bio-Bentall (95% CI, 6.9%-32.8%)(p=0.363).

Conclusions: VSRR and bio-Bentall show similar excellent survival and freedom from aortic reintervention rates up to 10 years; however, a durable valve solution for young patients with bicuspid aortic valve remains a challenge.
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http://dx.doi.org/10.1016/j.athoracsur.2021.05.044DOI Listing
June 2021

Mass Cytometry: a robust platform for the comprehensive immunomonitoring of CAR-T-cell therapies.

Br J Haematol 2021 Aug 26;194(4):788-792. Epub 2021 May 26.

Assistance Publique-Hôpitaux de Paris (AP-HP), Service d'Hématologie, Hôpital Pitié Salpêtrière, Paris, F-75013, France.

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http://dx.doi.org/10.1111/bjh.17551DOI Listing
August 2021

Gut microbiota diversity after autologous fecal microbiota transfer in acute myeloid leukemia patients.

Nat Commun 2021 05 25;12(1):3084. Epub 2021 May 25.

Service d'hématologie clinique et de thérapie cellulaire, Hôpital Saint Antoine, APHP, Sorbonne Université, INSERM UMRs 938, Paris, France.

Acute myeloid leukemia (AML) intensive chemotherapy combined with broad-spectrum antibiotics, leads to gut microbiota dysbiosis promoting pathological conditions and an increased incidence of complications. Here we report findings from a phase II single-arm, multicenter study evaluating autologous fecal microbiota transfer (AFMT) in 25 AML patients treated with intensive chemotherapy and antibiotics (ClinicalTrials.gov number: NCT02928523). The co-primary outcomes of the study are to evaluate the efficacy of AFMT in dysbiosis correction and multidrug-resistant bacteria eradication. The main secondary outcomes are to define a dysbiosis biosignature, to evaluate the effect of dysbiosis correction on patient clinical status, to assess the short and mid-term safety of AFMT in this immunocompromised population, and to evaluate the feasibility of the AFMT procedure and acceptability by the patient. Intensive induction chemotherapy induces a dramatic decrease of α-diversity indices, and a microbial dysbiosis with a significant shift of the microbial communities and domination of pro-inflammatory families. After AFMT treatment, α-diversity indices return to their initial mean levels and the similarity index shows the restoration of microbial communities. The trial meets pre-specified endpoints. AFMT appears to be safe and may be effective for gut microbiota restoration in AML patients receiving intensive chemotherapy and antibiotics, with an excellent gut microbiota reconstruction based on both richness and diversity indices at the species level.
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http://dx.doi.org/10.1038/s41467-021-23376-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149453PMC
May 2021

Association Between Perioperative Atrial Fibrillation and Long-term Risks of Stroke and Death in Noncardiac Surgery: Systematic Review and Meta-analysis.

CJC Open 2021 May 12;3(5):666-674. Epub 2021 Jan 12.

Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Background: Atrial fibrillation (AF) is frequently reported as a complication of noncardiac surgery. It is unknown whether new-onset perioperative AF is associated with an increased risk of stroke and death beyond the perioperative period. We performed a systematic review and meta-analysis to assess the long-term risks of stroke and mortality associated with new-onset perioperative AF after noncardiac surgery.

Methods: MEDLINE and EMBASE were searched from inception to March 2020 for studies reporting on the association between perioperative AF and the risk of stroke and death occurring beyond 30 days after noncardiac surgery. Reference screening, study selection, data extraction, and quality assessment were performed in duplicate. Data were pooled using inverse variance-weighted random-effects models and presented as risk ratios (RRs).

Results: From 7344 citations, we included 31 studies (3,529,493 patients). The weighted mean incidence of perioperative AF was 0.7%. During a mean follow-up of 28.1 ± 9.4 months, perioperative AF was associated with an increased risk of stroke (1.5 vs 0.9 strokes per 100 patient-years; RR: 2.9, 95% confidence interval [CI]: 2.1-3.9, I = 78%). Perioperative AF was also associated with a significantly higher risk of all-cause mortality (21.0 vs 7.6 deaths per 100 patient-years; RR: 1.8, 95% CI: 1.5-2.2, I = 94%). The pooled adjusted hazard ratios for stroke and all-cause mortality were 1.9 (95% CI: 1.6-2.2, I = 31%) and 1.5 (95% CI: 1.3-1.7, I = 20%), respectively.

Conclusions: Patients who had perioperative AF after noncardiac surgery had a higher long-term risk of stroke and mortality compared with patients who did not. Whether this risk is modifiable with oral anticoagulation therapy should be investigated.
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http://dx.doi.org/10.1016/j.cjco.2020.12.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134907PMC
May 2021

Aortic Valve Neocuspidization In a Pulmonary Autograft.

Ann Thorac Surg 2021 May 4. Epub 2021 May 4.

Management of aortic valve (AV) disease in the pediatric population is challenged by a lack of attractive valve replacement options. The Ross procedure has been prominent for these patients, however long-term reports have revealed concerns, namely neo-aortic root dilation and regurgitation. More recently, AV neocuspidization (AVNeo) has emerged as an alternative to the Ross operation or other valve replacement procedures in pediatric patients with congenital AV disease. We report the first successful case of AVNeo of a previously implanted pulmonary autograft.
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http://dx.doi.org/10.1016/j.athoracsur.2021.04.053DOI Listing
May 2021

Simplified heavy-atom derivatization of protein structures via co-crystallization with the MAD tetragon tetrabromoterephthalic acid.

Acta Crystallogr F Struct Biol Commun 2021 May 28;77(Pt 5):156-162. Epub 2021 Apr 28.

School of Biological Sciences, The University of Adelaide, Adelaide, South Australia 5005, Australia.

The phase problem is a persistent bottleneck that impedes the structure-determination pipeline and must be solved to obtain atomic resolution crystal structures of macromolecules. Although molecular replacement has become the predominant method of solving the phase problem, many scenarios still exist in which experimental phasing is needed. Here, a proof-of-concept study is presented that shows the efficacy of using tetrabromoterephthalic acid (B4C) as an experimental phasing compound. Incorporating B4C into the crystal lattice using co-crystallization, the crystal structure of hen egg-white lysozyme was solved using MAD phasing. The strong anomalous signal generated by its four Br atoms coupled with its compatibility with commonly used crystallization reagents render B4C an effective experimental phasing compound that can be used to overcome the phase problem.
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http://dx.doi.org/10.1107/S2053230X21004052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098126PMC
May 2021

Quantifying Bone Quality Using Computed Tomography Hounsfield Units in the Mid-sagittal View of the Lumbar Spine.

World Neurosurg 2021 07 20;151:e418-e425. Epub 2021 Apr 20.

Department of Neurological Surgery, University of Miami MILLER School of Medicine, Miami, Florida, USA.

Background: Computed tomography Hounsfield unit (HU) is an alternative tool to the dual energy x-ray absorptiometry scan T-score to quantify the bone quality. DEXA scan can overestimate the bone mineral density. We studied the correlation of the vertebral mid-axial and mid-sagittal HU to the T-score.

Methods: We retrospectively reviewed the electronic medical records of patients who underwent dual energy x-ray absorptiometry and computed tomography scans within 1 year. Age, sex, mid-axial and mid-sagittal HU, and T-score were collected and statistically analyzed.

Results: We identified 100 patients with computed tomography of the L1-L4. There were 80 female and 20 male patients. The average age was 60.25 years (±12.54 years). Nineteen patients were diagnosed with degenerative spine disease. There were 56 patients with a normal T-score, 33 with osteopenia, and 11 with osteoporosis. The average HU for the mid-sagittal view was 163 (±59) for L1, 159 (±62) for L2, 151 (±59) for L3, and 150 (±62) for L4. The mid-axial and mid-sagittal HU were positively correlated to the DEXA T-score (P < 0.001). The HU was 177 (95% CI: 160-194) for normal T-scores, 132 (120-143) for T-scores indicating osteopenia, and 106 (88-124) for T-scores indicating osteoporosis (P < 0.001). Post hoc analysis showed no difference between osteopenia and osteoporosis (P = 0.46).

Conclusions: Mid-sagittal HU is positively correlated to the T-score, similar to the mid-axial HU. Therefore, it can be used to acquire a general overview of the bone quality before spinal instrumentation.
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http://dx.doi.org/10.1016/j.wneu.2021.04.051DOI Listing
July 2021

Bicuspid-Associated Aortic Root Aneurysm: Mid to Long-Term Outcomes of David V Versus the Bio-Bentall Procedure.

Semin Thorac Cardiovasc Surg 2021 Feb 17. Epub 2021 Feb 17.

Division of Cardiac, Thoracic, and Vascular Surgery, Department of Surgery, New York Presbyterian-Columbia University Medical Center, New York, New York. Electronic address:

David V valve-sparing root replacement (VSRR) and bio-Bentall (BB) are increasingly performed for aortic root aneurysms associated with a bicuspid aortic valve (BAV). However, durability remains a concern in both procedures. We compared the 10-year outcomes of VSRR vs BB for BAV-associated root aneurysms. A retrospective review identified 134 patients with a BAV-associated root aneurysm who underwent VSRR (n = 65) or BB (n = 69) from 2005 to 2019. Patients with aortic stenosis, endocarditis, previous aortic valve replacement, and emergent cases were excluded. Propensity-score matching was performed, resulting in 2 risk-adjusted groups (n = 40 per group). Median follow-up was 6.21 (1.43-8.28) years. The VSRR cohort was younger (46.0 years vs 56.0 years, P < 0.001) and had a lower incidence of at least moderate aortic insufficiency (AI) (78.5% vs 92.8%, P = 0.02). The incidence of Marfan syndrome, aortic root diameter, and ascending aortic diameter were similar. In-hospital mortality was 1.5% (n = 1) and 1.4% (n = 1) for VSRR and BB, respectively. There was no difference between VSRR and BB in 10-year survival (98.3% [95% confidence interval (CI): 88.6-99.8%] vs 96.2% [95% CI: 85.5-99.0%], P = 0.567) and aortic valve reintervention at 10 years (16.1% [95% CI: 6.3-29.8%] vs 12.9% [95% CI: 3.7-28.0%], P = 0.309). The most common reason for valve reintervention in both groups was AI. Survival and valve reintervention at 10 years were similar in the matched cohort. David V VSRR yields similar mid to long-term outcomes to BB for select patients with a BAV-associated aortic root aneurysm in regards to survival and reintervention rates. Further studies comparing longer term outcomes between root replacement techniques and native valve durability are needed.
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http://dx.doi.org/10.1053/j.semtcvs.2021.02.004DOI Listing
February 2021

Commentary: Atrial Fibrillation, Statin, and Septal Myectomy.

Semin Thorac Cardiovasc Surg 2021 Autumn;33(3):720-721. Epub 2021 Feb 15.

Division of Cardiac, Thoracic and Vascular Surgery, Department of Surgery, Hypertrophic Cardiomyopathy Center, Columbia University Medical Center/NewYork-Presbyterian, New York, New York.

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http://dx.doi.org/10.1053/j.semtcvs.2020.12.021DOI Listing
February 2021

Commentary: Latent messages in a study for latent gradient in hypertrophic cardiomyopathy.

J Thorac Cardiovasc Surg 2021 Jan 19. Epub 2021 Jan 19.

Division of Cardiac, Thoracic, and Vascular Surgery, Department of Surgery, Columbia University Medical Center/NewYork-Presbyterian, New York, NY. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2021.01.039DOI Listing
January 2021

Hybrid repair of ascending aortic pseudoaneurysm.

J Card Surg 2021 Mar 1;36(3):1154-1156. Epub 2021 Feb 1.

Department of Surgery, Columbia University, New York, New York, USA.

For ascending aortic pseudoaneurysms with a large aortic entry site and thrombus burden, temporary stent-graft placement at induction of circulatory arrest can prevent thrombotic complication.
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http://dx.doi.org/10.1111/jocs.15388DOI Listing
March 2021

Derivatization of Protein Crystals with I3C using Random Microseed Matrix Screening.

J Vis Exp 2021 01 16(167). Epub 2021 Jan 16.

School of Biological Sciences, The University of Adelaide;

Protein structure elucidation using X-ray crystallography requires both high quality diffracting crystals and computational solution of the diffraction phase problem. Novel structures that lack a suitable homology model are often derivatized with heavy atoms to provide experimental phase information. The presented protocol efficiently generates derivatized protein crystals by combining random microseeding matrix screening with derivatization with a heavy atom molecule I3C (5-amino-2,4,6-triiodoisophthalic acid). By incorporating I3C into the crystal lattice, the diffraction phase problem can be efficiently solved using single wavelength anomalous dispersion (SAD) phasing. The equilateral triangle arrangement of iodine atoms in I3C allows for rapid validation of a correct anomalous substructure. This protocol will be useful to structural biologists who solve macromolecular structures using crystallography-based techniques with interest in experimental phasing.
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http://dx.doi.org/10.3791/61894DOI Listing
January 2021

Targeting Unconventional Pathways in Pursuit of Novel Antifungals.

Front Mol Biosci 2020 12;7:621366. Epub 2021 Jan 12.

Institute of Photonics and Advanced Sensing (IPAS), School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia.

The impact of invasive fungal infections on human health is a serious, but largely overlooked, public health issue. Commonly affecting the immunocompromised community, fungal infections are predominantly caused by species of , and . Treatments are reliant on the aggressive use of pre-existing antifungal drug classes that target the fungal cell wall and membrane. Despite their frequent use, these drugs are subject to unfavorable drug-drug interactions, can cause undesirable side-effects and have compromised efficacy due to the emergence of antifungal resistance. Hence, there is a clear need to develop novel classes of antifungal drugs. A promising approach involves exploiting the metabolic needs of fungi by targeted interruption of essential metabolic pathways. This review highlights potential antifungal targets including enolase, a component of the enolase-plasminogen complex, and enzymes from the mannitol biosynthesis and purine nucleotide biosynthesis pathways. There has been increased interest in the enzymes that comprise these particular pathways and further investigation into their merits as antifungal targets and roles in fungal survival and virulence are warranted. Disruption of these vital processes by targeting unconventional pathways with small molecules or antibodies may serve as a promising approach to discovering novel classes of antifungals.
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http://dx.doi.org/10.3389/fmolb.2020.621366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835888PMC
January 2021

Vanishing white matter: Eukaryotic initiation factor 2B model and the impact of missense mutations.

Mol Genet Genomic Med 2021 03 12;9(3):e1593. Epub 2021 Jan 12.

Department of Child Neurology, Emma Children's Hospital, Amsterdam University Medical Centers, Vrije Universiteit and Amsterdam Neuroscience, Amsterdam, the Netherlands.

Background: Vanishing white matter (VWM) is a leukodystrophy, caused by recessive mutations in eukaryotic initiation factor 2B (eIF2B)-subunit genes (EIF2B1-EIF2B5); 80% are missense mutations. Clinical severity is highly variable, with a strong, unexplained genotype-phenotype correlation.

Materials And Methods: With information from a recent natural history study, we severity-graded 97 missense mutations. Using in silico modeling, we created a new human eIF2B model structure, onto which we mapped the missense mutations. Mutated residues were assessed for location in subunits, eIF2B complex, and functional domains, and for information on biochemical activity.

Results: Over 50% of mutations have (ultra-)severe phenotypic effects. About 60% affect the ε-subunit, containing the catalytic domain, mostly with (ultra-)severe effects. About 55% affect subunit cores, with variable clinical severity. About 36% affect subunit interfaces, mostly with severe effects. Very few mutations occur on the external eIf2B surface, perhaps because they have minor functional effects and are tolerated. One external surface mutation affects eIF2B-substrate interaction and is associated with ultra-severe phenotype.

Conclusion: Mutations that lead to (ultra-)severe disease mostly affect amino acids with pivotal roles in complex formation and function of eIF2B. Therapies for VWM are emerging and reliable mutation-based phenotype prediction is required for propensity score matching for trials and in the future for individualized therapy decisions.
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http://dx.doi.org/10.1002/mgg3.1593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104162PMC
March 2021

Neonatal Cone Valvuloplasty for Pulmonary Atresia/Intact Ventricular Septum and Ebsteinoid Valve.

Ann Thorac Surg 2021 Jan 6. Epub 2021 Jan 6.

Section of Congenital and Pediatric Cardiothoracic Surgery, Division of Cardiac, Thoracic and Vascular Surgery, Department of Surgery, Morgan Stanley Children's Hospital, New York-Presbyterian Hospital/Columbia University Medical Center, New York, NY, USA.

Pulmonary atresia with intact ventricular septum (PA/IVS) is a rare lesion with wide anatomic variability. A rare variant exists, marked by right-sided dilatation, an Ebsteinoid tricuspid valve (TV), and severe tricuspid regurgitation. Neonatal cone valvuloplasty allows for a biventricular circulation and avoids complications of prosthetic valves; however, this technique inevitably requires reintervention to exchange the RV-PA conduit as the patient grows. We present a successful complete repair cone tricuspid valvuloplasty in a 9-day-old (2.8 kg) neonate with trisomy 21, PA/IVS, and an Ebsteinoid TV.
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http://dx.doi.org/10.1016/j.athoracsur.2020.09.086DOI Listing
January 2021

Scoring system for clinically significant CMV infection in seropositive recipients following allogenic hematopoietic cell transplant: an SFGM-TC study.

Bone Marrow Transplant 2021 06 18;56(6):1305-1315. Epub 2020 Dec 18.

Department of Hematology, Univ. Lille, CHU Lille, F-59000, Lille, France.

In order to identify cytomegalovirus (CMV)-seropositive patients who are at risk of developing CMV infection following first allogeneic hematopoietic cell transplantation (allo-HCT), we built up a scoring system based on patient/donor characteristics and transplantation modalities. To this end, 3690 consecutive patients were chronologically divided into a derivation cohort (2010-2012, n = 2180) and a validation cohort (2013-2014, n = 1490). Haploidentical donors were excluded. The incidence of first clinically significant CMV infection (CMV disease or CMV viremia leading to preemptive treatment) at 1, 3, and 6 months in the derivation cohort was 13.8%, 38.5%, and 39.6%, respectively. CMV-seropositive donor, unrelated donor (HLA matched 10/10 or HLA mismatched 9/10), myeloablative conditioning, total body irradiation, antithymocyte globulin, and mycophenolate mofetil significantly and independently affected the incidence of 3-month infection. These six factors were selected to build up the prognostic model. Four risk groups were defined: low, intermediate-low, intermediate-high, and high-risk categories, with a 3-month predicted incidence of first clinically significant CMV infection in the derivation cohort of 22.2%, 31.1%, 45.4%, and 56.9%, respectively. This score represents a framework for the evaluation of patients who are at risk of developing clinically significant CMV infection following allo-HCT. Prospective studies using this score may be of benefit in assessing the value of anti-CMV prophylaxis in well-defined patient cohorts.
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http://dx.doi.org/10.1038/s41409-020-01178-6DOI Listing
June 2021

Orthotopic heart transplantation and concomitant aortic arch replacement in an adult Fontan patient with hypoplastic left heart syndrome.

Interact Cardiovasc Thorac Surg 2021 01;32(2):325-327

Department of Surgery, Columbia University Irving Medical Center, New York, NY, USA.

Heart failure and neoaortic dilation are common long-term complications in patients with hypoplastic left heart syndrome after single-ventricle palliation. Orthotopic heart transplantation and concomitant transverse aortic arch replacement can be performed safely and effectively. The addition of preoperative three-dimensional modelling can supplement operative planning, facilitate intraoperative execution, and optimize clinical outcomes.
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http://dx.doi.org/10.1093/icvts/ivaa243DOI Listing
January 2021

Commentary: Just do it?

J Thorac Cardiovasc Surg 2020 Oct 31. Epub 2020 Oct 31.

Hypertrophic Cardiomyopathy Center; Division of Cardiac, Thoracic and Vascular Surgery, Department of Surgery, Columbia University Irvine Medical Center/New York-Presbyterian, New York, NY. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2020.10.082DOI Listing
October 2020

Combined valve surgery with sutureless and rapid-deployment aortic valve replacement: when and why.

Ann Cardiothorac Surg 2020 Sep;9(5):408-410

Department of Cardiothoracic and Vascular Surgery, University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, USA.

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http://dx.doi.org/10.21037/acs-2019-surd-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548217PMC
September 2020

Nucleoside selectivity of Aspergillus fumigatus nucleoside-diphosphate kinase.

FEBS J 2021 04 6;288(7):2398-2417. Epub 2020 Nov 6.

Institute of Photonics and Advanced Sensing (IPAS), School of Biological Sciences, The University of Adelaide, Australia.

Aspergillus fumigatus infections are rising at a disconcerting rate in tandem with antifungal resistance rates. Efforts to develop novel antifungals have been hindered by the limited knowledge of fundamental biological and structural mechanisms of A. fumigatus propagation. Biosynthesis of NTPs, the building blocks of DNA and RNA, is catalysed by NDK. An essential enzyme in A. fumigatus, NDK poses as an attractive target for novel antifungals. NDK exhibits broad substrate specificity across species, using both purines and pyrimidines, but the selectivity of such nucleosides in A. fumigatus NDK is unknown, impeding structure-guided inhibitor design. Structures of NDK in unbound- and NDP-bound states were solved, and NDK activity was assessed in the presence of various NTP substrates. We present the first instance of a unique substrate binding mode adopted by CDP and TDP specific to A. fumigatus NDK that illuminates the structural determinants of selectivity. Analysis of the oligomeric state reveals that A. fumigatus NDK adopts a hexameric assembly in both unbound- and NDP-bound states, contrary to previous reports suggesting it is tetrameric. Kinetic analysis revealed that ATP exhibited the greatest turnover rate (321 ± 33.0 s ), specificity constant (626 ± 110.0 mm ·s ) and binding free energy change (-37.0 ± 3.5 kcal·mol ). Comparatively, cytidine nucleosides displayed the slowest turnover rate (53.1 ± 3.7 s ) and lowest specificity constant (40.2 ± 4.4 mm ·s ). We conclude that NDK exhibits nucleoside selectivity whereby adenine nucleosides are used preferentially compared to cytidine nucleosides, and these insights can be exploited to guide drug design. ENZYMES: Nucleoside-diphosphate kinase (EC 2.7.4.6). DATABASE: Structural data are available in the PDB database under the accession numbers: Unbound-NDK (6XP4), ADP-NDK (6XP7), GDP-NDK (6XPS), IDP-NDK (6XPU), UDP-NDK (6XPT), CDP-NDK (6XPW), TDP-NDK (6XPV).
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http://dx.doi.org/10.1111/febs.15607DOI Listing
April 2021

Salvage extracorporeal membrane oxygenation for acute type A aortic dissection with coronary malperfusion.

J Card Surg 2020 Dec 28;35(12):3614-3616. Epub 2020 Sep 28.

Division of Cardiac, Thoracic, and Vascular Surgery, Department of Surgery, New York Presbyterian, Columbia University Irving Medical Center, New York, New York, USA.

Perioperative use of extracorporeal membrane oxygenation (ECMO) in type A aortic dissection is a topic of contention with limited available data. We report the case of a patient presenting in severe cardiogenic shock due to coronary malperfusion and severe aortic insufficiency who was resucitated with ECMO as a bridge to recovery.
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http://dx.doi.org/10.1111/jocs.15058DOI Listing
December 2020
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