Early CMV Reactivation Still Remains a Cause of Increased Transplant Related Mortality in the Current Era: A CIBMTR Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 47-47 ◽  
Author(s):  
Muthalagu Ramanathan ◽  
Pierre Teira ◽  
Minoo Battiwalla ◽  
A. John Barrett ◽  
Caroline A Lindemans ◽  
...  
Keyword(s):  
Research Funding ◽  
Negative Impact ◽  
Multivariable Analysis ◽  
Time Dependent ◽  
Positive Serology ◽  
Increased Risk ◽  
The Impact ◽  
Cmv Reactivation ◽  
Risk Of Relapse ◽  
Related Mortality

Abstract Introduction: Since the early days of allogeneic hematopoietic cell transplantation (HCT), positive serology for cytomegalovirus (CMV) in either the recipient or the donor, and CMV reactivation have been associated with poorer outcomes. In the 90’s, development of effective monitoring and potent antiviral drugs minimized and occasionally abrogated this negative impact. Recently, some studies have reported an unexpected association between early CMV reactivation and decreased incidence of relapse in AML. The Center for International Blood and Marrow Research (CIBMTR) sought to conduct a retrospective large scale study to reassess the impact of CMV serology and CMV reactivation in the current era. Methods: The analysis includes comprehensive data of 11,153 patients undergoing first allogeneic HCT between 2003 and 2010 reported to the CIBMTR. Separate analyses were conducted for each of the 6 patient categories: AML transplanted with bone marrow (BM) or peripheral blood stem cell (PBSC) (n=5310), AML transplanted with cord blood (CB) (n= 925), ALL with BM/PBSC (n=1883), ALL with CB (n= 759), CML with BM/PBSC (n=1079) and MDS with BM/PBSC (n=1197). CMV serology from the donor (D) or recipient (R), and reactivation of CMV (as a time-dependent co-variate) within the first year after HCT were analyzed as risk factors for outcomes. The median duration of follow up was 56 months (1 – 127 months). Results: The median time to CMV reactivation was 40 days (1 – 362 days) after HCT and 98% of reactivations occurred before day 100 (D+/R+ 32%, D+/R- 11%, D-/R+ 34%, D-/R- 4%). In multivariable analysis, throughout the 6 groups, a positive serology (D+/R+, D+/R-, D-/R+) vs a negative serology (D-/R-),had no effect on the risk of GVHD (acute or chronic) or the risk of relapse, except for an increased risk of chronic GVHD for BM/PBSC recipients with ALL. CMV positive serology was associated with a higher transplant related mortality (TRM) and a poorer overall survival (OS). For a R+ patient, a D- compared to a D+, had no negative impact except for ALL with BM/PBSC where a D- was associated with a poorer OS. After PBSC/BM transplantation, CMV reactivation was associated with a higher TRM for MDS (RR=1.61, p=0.0002), CML (RR=1.86, p=0.0004), AML (RR=1.68; p<0.0001) and ALL (RR=1.95; p<0.0001), translating into lower OS (range of RR from 1.27 to 1.49; p value from 0.003 to <0.0001). Only among AML patients following CB transplantation, CMV reactivation did not worsen OS. Moreover, CMV reactivation had no effect on the incidence of relapse irrespective of the diagnosis or the source of stem cells. Finally, we conducted a subset analysis focusing on the group of AML, transplanted with PBSC after a myeloablative conditioning regimen and with a GVH prophylaxis relying on Ciclosporine and Methotrexate only. In multivariable analysis, there was no difference in the risk of relapse based on CMV reactivation as a time-dependent co-variate [RR 0.96 (0.65 – 1.4), p=0.8385]. Conclusion: Positive D/R CMV serology still results in increased TRM and decreased OS after HSCT in the current era. Early CMV reactivation did not prevent relapse in patients with AML, MDS, CML or ALL after HCT. Disclosures Boeckh: Chimerix: Consultancy, Research Funding; Viropharma: Research Funding; Genentech/Roche: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Clinigen: Consultancy.

scholarly journals CMV-Seropositive Recipients Are at Higher Risk of CMV Reactivation and NRM after Haploidentical-SCT with PT-Cy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4484-4484
Author(s):  
Jacopo Mariotti ◽  
Stefania Bramanti ◽  
Raynier Devillier ◽  
Barbara Sarina ◽  
Sabine Furst ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Research Funding ◽  
Acute Gvhd ◽  
Multivariable Analysis ◽  
The Other ◽  
Time Dependent ◽  
Research Support ◽  
Free Survival ◽  
Increased Risk ◽  
Cmv Reactivation

Background: Cytomegalovirus (CMV) reactivation still represents a common complication after allogeneic stem cell transplantation and is associated with increased non-relapse mortality (NRM) and reduced overall survival (OS). Patients receiving T cell-replete haploidentical stem cell transplantation (haplo-SCT) with high dose post-transplant cyclophosphamide (PT-Cy) are considered at higher risk of developing CMV reactivation due to their particular immuno-suppressed status. Letermovir was recently shown to significantly reduce the frequency of CMV reactivation in a phase 3 clinical trial. We decided to perform a retrospective analysis among patients treated with haplo-SCT with PT-Cy in order to identify whether every patients should receive CMV prophylaxis with letermovir or it is possible to identify a particular subgroup that may benefit more of prophylactic treatment. Methods: We retrospectively analyzed 513 consecutive patients receiving Haplo-SCT with PT-Cy at our institutions between April 2009 and December 2018. Median age was 56 years old (range 15-77), main diagnosis was represented by acute myeloid leukemia (31%), Hodgkin lymphoma (22%), non-Hodgkin lymphoma (21%) and myelodisplastic syndrome (12%). Donor/recipient CMV serostatus was as follows: neg/neg (G1) 16%, pos/pos (G2) 50%, pos/neg (G3) 12% and neg/pos (G4) 22%. Conditioning regimen was non-myeloablative/reduced intensity in 90% of the cases, graft source was represented by bone marrow for 25% of the patients. Results: With a median follow-up of 35 months, 3-year OS was 57%, 3-year NRM 24% and 3-year graft-versus-host-disease (GVHD)/relapse free survival (GRFS) 43%. 180-days cumulative incidence of grade 2-4 acute GVHD was 23% and 2-year moderate-severe chronic GVHD was 9%. Median day of CMV reactivation was 41 days (range 10-275), 100-days and 1-year cumulative incidence of CMV reactivation was 43% and 48%, respectively. Cumulative incidence of CMV reactivation was more common among seropositive recipients: G1 1% vs G2 60% vs G3 32% vs G4 67% (Table I, p<0.001). Recipient CMV positive serostatus and increasing patient age (hazard ratio (HR): 1.01, p=0.033) were the only variables associated with increased risk of CMV reactivation. 3-year OS, 3-year progression-free survival (PFS) and 3-year GRFS were worse among seropositive recipients, and consistently 3-year NRM was higher for G2 and G4 (Table I). By a time-dependent analysis we investigated the impact of CMV reactivation on main outcomes. Only 180-day cumulative incidence of grade 2-4 acute GVHD, and none of the other analyzed outcomes, was more frequent after CMV reactivation (HR 2.064, p=0.001). By time-dependent multivariable analysis, positive recipient CMV serostatus, was an independent predictor of increased NRM (G2: HR 2.47 and G4 HR: 2.61, p=0.007) and worse GRFS (G2: HR 1.71, p=0.003 and G4 HR 1.32, p=0.183). Pre-transplant active disease and hematopoietic cell transplant comorbidity index (HCT-CI) ≥3 were the other independent variables affecting OS, NRM, PFS and GRFS by multivariable analysis. Based on landmark analysis at day 100, patients experiencing CMV reactivation had a higher NRM rate compared with those without reactivation (18% vs 10%, p=0.034) and a tendency for lower OS (72% vs 78%, p=0.065) and GRFS (50% vs 55%, p=0.061). Moreover, by multivariable analysis, CMV reactivation and increasing donor age were the main independent predictors of grade 2-4 acute GVHD: HR 2.21, (p=0.01) and 1.01 (p=0.016), respectively. Conclusion: Recipient positive CMV serostatus is associated with increased risk of CMV reactivation, increased rate of NRM and worse GRFS. CMV reactivation is associated with increased risk of developing grade 2-4 acute GVHD and higher NRM. We conclude that also in the platform of haplo-SCT with PT-Cy, letermovir prophylaxis should be given not to all patients, but mainly to CMV seropositive recipients, that probably may benefit the most in terms of CMV reactivation, acute GVHD incidence and NRM. Disclosures Chabannon: Gilead: Other: speaker's fees, hospitalities; Sanofi SA: Other: research support, speaker's fees, hospitalities; Novartis: Other: speaker's fees; Celgene: Other: speaker's fees; Terumo BCT: Other: speaker's fees; Miltenyi Biotech: Other: research support; Fresenius Kabi: Other: research support; EBMT: Other: Working Party Chair, Board member. Carlo-Stella:Boehringer Ingelheim: Consultancy; Rhizen Pharmaceuticals: Research Funding; Celgene: Research Funding; Genenta Science srl: Consultancy; F. Hoffmann-La Roche Ltd: Honoraria, Other: Travel, accommodations, Research Funding; ADC Therapeutics: Consultancy, Other: Travel, accommodations, Research Funding; Servier: Consultancy, Honoraria, Other: Travel, accommodations; Novartis: Consultancy, Research Funding; MSD: Honoraria; Sanofi: Consultancy, Research Funding; Amgen: Honoraria; AstraZeneca: Honoraria; Janssen Oncology: Honoraria; BMS: Honoraria; Janssen: Other: Travel, accommodations; Takeda: Other: Travel, accommodations. Santoro:Bayer: Consultancy, Speakers Bureau; MSD: Speakers Bureau; Sandoz: Speakers Bureau; Eisai: Consultancy, Speakers Bureau; BMS: Consultancy; Novartis: Speakers Bureau; Lilly: Speakers Bureau; Arqule: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Servier: Consultancy, Speakers Bureau; Celgene: Speakers Bureau; Amgen: Speakers Bureau; Abb-Vie: Speakers Bureau; Roche: Speakers Bureau; Takeda: Speakers Bureau; BMS: Speakers Bureau. Blaise:Pierre Fabre medicaments: Honoraria; Molmed: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria; Sanofi: Honoraria.

Acquisition of Cytogenetic Abnormalities (CA) Is a Very Poor Prognostic Feature in Patients (pts) with Low and Intermediate-1 (int-1) Risk Myelodysplastic Syndromes (MDS),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3802-3802
Author(s):  
Elias Jabbour ◽  
Hagop M. Kantarjian ◽  
Xuemei Wang ◽  
Lynne V. Abruzzo ◽  
A Megan Cornelison ◽  
...  
Keyword(s):  
Lower Risk ◽  
Research Funding ◽  
Regression Models ◽  
Cox Model ◽  
Time Dependent ◽  
P Value ◽  
Increased Risk ◽  
History Of ◽  
Previously Treated ◽  
The Impact

Abstract Abstract 3802 Background and Aim: The impact of the CA on prognosis and transformation into acute myeloid leukemia among pts with low and int-1 risk MDS is not known. The aims of the study were to assess the impact of CA on the natural history of pts with lower risk MDS and to identify factors associated with its development. Methods: We reviewed 721 pts clinical records of low and intermediate risk MDS pts from 2000–2010 and conducted a retrospective analysis of all pts with at least two consecutive cytogenetic analysis (365 patients, 51%). The acquisition of CA was defined by structural change or gain in at least 2 metaphases and loss in 3 metaphases, or otherwise confirmed by FISH. Cox proportional hazards regression models were fit to assess the association between transformation-free survival (TFS) or overall survival (OS) and pt characteristics. The acquisition of CA was fitted in the Cox model as a time-dependent covariate. The association between the acquisition of CA and pt characteristics was assessed through univariate and multiple logistic regression models. Results: CA was detected in 107 pts (29%) after a median follow-up of 34 months (mos). CA was observed in a median number of 4 metaphases (range, 2–30). At diagnosis, 21% and 79% of pts who acquired CA were low-and int-1risk MDS; 50% were diploid, 22% harbored chromosome 5 /7 abnormalities. At the time of acquisition of CA, the median percentage of bone marrow blasts was 4% (range, 0% to 89%), the median WBC, hemoglobin and platelets were 3.1 × 109/L, 9.5 g/dL, and 65 × 109/L, respectively; pts were low, int-1, int-2, and high-risk MDS in 3%, 42%, 26%, 29%, respectively. The median TFS and OS were 31 (95% CI: 27– 37) and 34 (95% CI: 30 – 44) mos respectively. Assessing CA as time-dependent covariate, patients with CA had a worse TFS and OS, with a median TFS and OS of 16 and 18 mos compared to 56 and 60 mos, respectively in pts without CA. Based on the multivariable Cox model and after adjusting for effects of all other covariates, pts who had acquired CA had an increased risk of transformation (HR=1.46; p-value = 0.01) or death (HR=1.50; p-value = 0.01). By multivariate analysis, female pts with prior chemotherapy had an increased risk of developing CA (OR= 5.26; p-value <0.0001). 96 pts had history of previous malignancy treated with chemotherapy +/− radiation therapy. Of those, 34 (35%) patients acquired CA. Median time from previous chemotherapy to the acquisition of CA was 61 mos (range, 11 to 180). Pts previously treated who did not acquire CA had similar outcomes to those who had never been treated and did not develop CA, while those who did develop CA whether they were previously treated or not had worse TFS and OS. Conclusion: CA occurs at a rate of 29% of pts with lower risk MDS, more common among pts with previously treated malignancy, and has a significant impact on TFS and OS, possibly reflecting genomic instability in the natural history of MDS. Disclosures: Cortes: BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding.

scholarly journals Cytomegalovirus Gastroenteritis in Patients with Acute Graft-Versus-Host Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3918-3918
Author(s):  
Yu Akahoshi ◽  
Shun-ichi Kimura ◽  
Yuma Tada ◽  
Toshihiro Matsukawa ◽  
Masaharu Tamaki ◽  
...  
Keyword(s):  
Research Funding ◽  
Acute Gvhd ◽  
Multivariate Analyses ◽  
Time Dependent ◽  
Chugai Pharmaceutical ◽  
Graft Versus Host ◽  
Otsuka Pharmaceutical ◽  
Cmv Disease ◽  
The Impact ◽  
Cmv Reactivation

Abstract [Background] A pre-emptive strategy has successfully decreased the incidence of cytomegalovirus (CMV) disease after allogeneic hematopoietic cell transplantation (HCT). However, it is difficult to completely prevent breakthrough CMV gastroenteritis, especially after acute graft-versus-host disease (GVHD) because a routine monitoring test with antigenemia or PCR assay often shows negative results before the development of CMV gastroenteritis that is considered as a localized infection initially. Actually, gastroenteritis is the predominant CMV disease in a pre-emptive strategy era. In addition, letermovir has recently been available for prophylactic strategies against CMV in clinical practice. However, little is known about the incidence, prognostic factors, and impact of subsequent CMV gastroenteritis after acute GVHD under recent advances in HCT including the introduction of letermovir. [Methods] This nationwide retrospective study evaluated adult patients who received their first allogeneic transplantation between 2008 and 2019 and developed grade II-IV acute GVHD (G24GVHD). Patients with a CMV-seronegative donor and recipient were excluded. Weekly monitoring using pp65 antigenemia assay was performed from the time of engraftment. A diagnosis of CMV gastroenteritis was made by gastrointestinal symptoms with histological proof of CMV on biopsy samples. The day when patients developed G24GVHD was considered as day 0 in all analyses. Nonrelapse mortality (NRM) by day 365 was set as the primary end-point. Cox proportional hazards regression models were used in all multivariate analyses. The impact of CMV reactivation and gastroenteritis as a time-dependent covariate were graphically plotted using a Simon-Makuch method. This study was approved by the data management committee of the Japan Society for Transplantation and Cellular Therapy (JSTCT) and by the Institutional Review Board of Jichi Medical University Saitama Medical Center. [Results] In total, 3759 patients with G24GVHD fulfilled eligibility and were included in this analysis. The median age at HCT was 50 years (range, 16 to 74). Of the 3759 patients with G24GVHD, 1120 (29.8%) developed grade III-IV acute GVHD. Letermovir prophylaxis was administered in 275 patients (7.3%), and the median start timing was 1 day after HCT (range, -8 to 36). The median duration of letermovir administration was 91 days (range, 2 to 332). The median observation period of survivors with letermovir prophylaxis was 320 days from the development of G24GVHD. By day 365, 207 patients developed CMV gastroenteritis and the cumulative incidence was 5.7% (95% CI, 5.0-6.5%). The median duration between the development of G24GVHD and CMV gastroenteritis was 22 days (range, 1 to 235). Before the onset of CMV gastroenteritis, 37 (17.9%) did not develop CMV reactivation. In multivariate analyses, advanced age (hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.16-2.22; P = 0.004), GVHD prophylaxis using mycophenolate mofetil with calcineurin inhibitor (HR, 1.73; 95% CI, 1.08-2.77; P = 0.024), lower-gut acute GVHD at the development of G24GVHD (HR, 2.17; 95% CI, 1.58-2.98; P &lt; 0.001), and use of systemic steroids (HR, 1.78; 95% CI, 1.16-2.74; P = 0.008) were independent risk factors for cytomegalovirus gastroenteritis. Moreover, CMV prophylaxis with letermovir was significantly associated with a decreased risk of CMV reactivation (HR, 0.25; 95% CI, 0.20-0.32; P &lt; 0.001) and cytomegalovirus gastroenteritis (HR, 0.50; 95% CI, 0.25-0.99; P = 0.047). Then, we evaluated the impact of cytomegalovirus gastroenteritis on NRM by day 365. We found that patients who developed cytomegalovirus gastroenteritis (time-dependent covariate) had a higher risk of NRM (HR, 1.89; 95% CI, 1.50-2.39; P &lt; 0.001) (Figure A). Meanwhile, letermovir prophylaxis reduced the risk of NRM (HR, 0.72; 95% CI, 0.52-0.99; P = 0.043). We illustrated the adjusted cumulative incidence of NRM in patients with and without letermovir prophylaxis in Figure B. [Conclusion] To our knowledge, this is the largest study summarizing the characteristics and outcomes of cytomegalovirus gastroenteritis after acute GVHD. Our findings underscore the importance of more stringent surveillance with endoscopy and prevention with letermovir based on a comprehensive risk assessment. Figure 1 Figure 1. Disclosures Kimura: SymBio Pharmaceutical: Honoraria; Takeda Pharmaceutical: Honoraria; Nippon Kayaku: Honoraria; Eisai: Honoraria; Ono Pharmaceutical: Honoraria; Bristol-Myers Squibb: Honoraria; Chugai Pharmaceutical: Honoraria; Kyowa Kirin: Honoraria; Pfizer: Honoraria; Astellas: Honoraria; Sumitomo Dainippon Pharma: Honoraria; MSD: Honoraria. Uchida: Chugai Pharmaceutical Co., Ltd.: Honoraria; Astellas Pharma Inc.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; Novartis Pharma Inc.: Honoraria. Nakamae: Astellas Pharma Inc.: Honoraria; Otsuka Pharmaceutical Co., Ltd: Honoraria; ONO PHARMACEUTICAL CO., LTD.: Honoraria; Simon-Kucher & Partners: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria; Takeda Pharmaceutical Company Limited.: Honoraria; Novartis: Honoraria, Research Funding; Pfizer Japan Inc.: Honoraria; Bristol-Myers Squibb　Company: Honoraria, Research Funding; Alexion: Research Funding; PPD-SNBL K.K: Research Funding; CMIC HOLDINGS Co., Ltd: Research Funding. Kanda: Sanofi: Research Funding; MSD: Honoraria; Otsuka Pharmaceutical: Honoraria, Research Funding. Atsuta: Mochida Pharmaceutical Co., Ltd.: Speakers Bureau; Astellas Pharma Inc.: Speakers Bureau; AbbVie GK: Speakers Bureau; Kyowa Kirin Co., Ltd: Honoraria; Meiji Seika Pharma Co, Ltd.: Honoraria. Murata: GlaxoSmithKline: Honoraria; Asahi Kasei: Honoraria; Miyarisan Pharmaceutical: Honoraria; Astellas: Honoraria; JCR Pharmaceutical: Honoraria; Novartis: Honoraria; Toyama Chemical: Honoraria; FUJIFILM: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Kyowa Kirin: Honoraria; MSD: Honoraria; Celgene: Honoraria; Otsuka Pharmaceutical: Honoraria. Nakasone: Eisai: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Otsuka Pharmaceutical: Honoraria; Takeda Pharmaceutical: Honoraria; Chugai Pharmaceutical: Honoraria; Nippon Shinyaku: Honoraria.

scholarly journals Analysis of Free-Text Responses in an International Myeloproliferative Neoplasms Patient Survey to Assess Impact of the COVID-19 Pandemic on Clinical Care

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 11-12
Author(s):  
Blake T. Langlais ◽  
Carolyn Mead-Harvey ◽  
Heidi E. Kosiorek ◽  
Gina L. Mazza ◽  
Ruben Mesa ◽  
...  
Keyword(s):  
Research Funding ◽  
Negative Impact ◽  
Myeloproliferative Neoplasms ◽  
Clinical Care ◽  
Healthcare Delivery ◽  
Lead Author ◽  
Free Text ◽  
Increased Risk ◽  
The Impact ◽  
Positive Impacts

Background The COVID-19 pandemic continues to challenge effective treatment delivery to hematologically-compromised patients, including those with myeloproliferative neoplasms (MPNs). MPNs are characterized by clonal proliferation of hematopoietic cell lines in bone marrow. As such, increasing reports of COVID-19 related thrombotic events highlight how MPN patients are at an increased risk in navigating potential complications during this pandemic. Mitigation strategies to lesson MPN patient exposure to COVID-19 are vital. Though, such efforts come at an inherent cost to effective healthcare delivery. Restriction of regular in-clinic treatments and reported shortages of MPN pharmacotherapies present these patients with diminishing continued care. To understand how MPN patient care has been impacted by COVID-19, an internet-based questionnaire was deployed surveying a variety of disease and pandemic related items (reported elsewhere; Palmer J et al, ASH 2020 submitted). A single free-text response item instructed respondents to: "Please tell us anything else (bad or good) about how the COVID-19 outbreak has impacted your MPN care." This qualitative analysis evaluated first-hand comments directly from patients in order to form a richer understanding of how those with MPNs have been managing disease-related care amidst this pandemic. Methods This COVID-19 survey was hosted via Mayo Clinic's secured REDCap system for online surveys and posted on MPN organizational partner websites. Surveys were completely anonymous. The free-text responses describing impacts to MPN care were each independently reviewed by 2 individuals for overall sentiment (positive, negative, both, or neutral [no impact]) and categorized for themes. The 2 reviewers were assessed for agreement. Conflicting reviews were evaluated then adjudicated by an algorithm for cases meeting selected conditions or by lead author review for all remaining cases. Descriptive statistics are reported. Results Of the 1217 consenting adult patients participating in the overall COVID-19 study, 824 provided free-text responses. Of these, respondent MPN diagnoses included, essential thrombocythemia (n=324, 39%), polycythemia vera (n=251, 30%), myelofibrosis (n=153, 19%), and other/undisclosed (96, 12%); 69% (n=567) were female; median age was 63 (range 21-93); 38% (n=313) were from the US, 38% (n=313) UK, and 24% (n=198) other/unknown. There was 89% (n=734) sentiment agreement between reviewers. Free-text responses about the impact of COVID-19 on MPN care were 49% (n=400) negative, 21% (n=177) positive, 8% (n=65) both positive and negative, and 22% (n=182) neutral/no impact. Table 1 shows a selection of MPN patient free-text responses reflecting common negative and positive sentiment themes. Negative impact (n=400): The most common negative impact involved delays or cancellations of visits or perceived inaccessibility to regular providers (n=261, 65%). Primarily this sentiment was driven by lack of clinic availability and restrictions at treatment centers or by providers. However, some respondents reported delaying or canceling visits themselves due to fear of COVID-19 exposure. Perceived health consequences from this delay were also expressed. There were 129 (32%) respondents with concern regarding changes or access to medications, including explicit drug supply shortages. Some patients resorted to self-adjusting medications and reusing single-use supplies. General anxiety, stress, and isolation were also reported (n=98, 25%). Positive impact (n=177): Availability of telemedicine comprised the majority of positive impacts of the pandemic (n=95, 54%), with many noting the reduced travel time to visits. Routine local testing coupled with follow-up telemedicine was favorable. Despite general positivity towards telemedicine, some reported preferences for in-person visits; commenting that telemedicine was impersonal, difficult to schedule or receive virtual communication, and expressed concern for lack of spleen examinations during virtual visits. Conclusion Positive and negative aspects were reported including MPN-specific issues. Healthcare systems should use such data to emerge from the COVID-19 pandemic and retain the positive impacts such as telemedicine, while developing education materials and other resources to address the reported negative impacts where possible. Disclosures Mesa: CTI BioPharma: Research Funding; Promedior: Research Funding; Novartis: Consultancy; Sierra Oncology: Consultancy; Samus Therapeutics: Research Funding; Genentech: Research Funding; AbbVie: Research Funding; Incyte: Research Funding; LaJolla Pharmaceutical Company: Consultancy; Bristol Myers Squibb: Research Funding.

scholarly journals Does deeper hypothermia reduce the risk of acute kidney injury after circulatory arrest for aortic arch surgery?

2021 ◽  
Author(s):  
Andrew M Vekstein ◽  
Babtunde A Yerokun ◽  
Oliver K Jawitz ◽  
Julie W Doberne ◽  
Jatin Anand ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Circulatory Arrest ◽  
Aortic Surgery ◽  
Multivariable Analysis ◽  
Kidney Injury ◽  
Deep Hypothermia ◽  
Moderate Hypothermia ◽  
Bladder Temperature ◽  
Increased Risk ◽  
The Impact

Abstract OBJECTIVES The impact of hypothermic circulatory arrest (HCA) temperature on postoperative acute kidney injury (AKI) has not been evaluated. This study examined the association between circulatory arrest temperatures and AKI in patients undergoing proximal aortic surgery with HCA. METHODS A total of 759 consecutive patients who underwent proximal aortic surgery (ascending ± valve ± root) including arch replacement requiring HCA between July 2005 and December 2016 were identified from a prospectively maintained institutional aortic surgery database. The primary outcome was AKI as defined by Risk, Injury, Failure, Loss, End Stage Renal Disease (ESRD) criteria. The association between minimum nasopharyngeal (NP) and bladder temperatures during HCA and postoperative AKI was assessed, adjusting for patient-level factors using multivariable logistic regression. RESULTS A total of 85% (n = 645) of patients underwent deep hypothermia (14.1–20.0°C), 11% (n = 83) low-moderate hypothermia (20.1–24.0°C) and 4% (n = 31) high-moderate hypothermia (24.1–28.0°C) as classified by NP temperature. When analysed by bladder temperature, 59% (n = 447) underwent deep hypothermia, 22% (n = 170) low-moderate, 16% (n = 118) high-moderate and 3% mild (n = 24) (28.1–34.0°C) hypothermia. The median systemic circulatory arrest time was 17 min. The incidence of AKI did not differ between hypothermia groups, whether analysed using minimum NP or bladder temperature. In the multivariable analysis, the association between degree of hypothermia and AKI remained non-significant whether analysed as a categorical variable (hypothermia group) or as a continuous variable (minimum NP or bladder temperature) (all P &gt; 0.05). CONCLUSIONS In patients undergoing proximal aortic surgery including arch replacement requiring HCA, degree of systemic hypothermia was not associated with the risk of AKI. These data suggest that moderate hypothermia does not confer increased risk of AKI for patients requiring circulatory arrest, although additional prospective data are needed.

The Obesity Paradox in Emergency General Surgery Patients

2021 ◽  
pp. 000313482096852
Author(s):  
Sean R. Maloney ◽  
Caroline E. Reinke ◽  
Abdelrahman A. Nimeri ◽  
Sullivan A. Ayuso ◽  
A. Britton Christmas ◽  
...  
Keyword(s):  
General Surgery ◽  
Multivariable Analysis ◽  
Operative Management ◽  
Chronic Obstructive ◽  
High Morbidity ◽  
Emergency General Surgery ◽  
Common Procedure ◽  
Increased Risk ◽  
Social Security Death Index ◽  
The Impact

Operative management of emergency general surgery (EGS) diagnoses involves a range of procedures which can carry high morbidity and mortality. Little is known about the impact of obesity on patient outcomes. The aim of this study was to examine the association between body mass index (BMI) >30 kg/m2 and mortality for EGS patients. We hypothesized that obese patients would have increased mortality rates. A regional integrated health system EGS registry derived from The American Association for the Surgery of Trauma EGS ICD-9 codes was analyzed from January 2013 to October 2015. Patients were stratified into BMI categories based on WHO classifications. The primary outcome was 30-day mortality. Longer-term mortality with linkage to the Social Security Death Index was also examined. Univariate and multivariable analyses were performed. A total of 60 604 encounters were identified and 7183 (11.9%) underwent operative intervention. Patient characteristics include 53% women, mean age 58.2 ± 18.7 years, 64.2% >BMI 30 kg/m2, 30.2% with chronic obstructive pulmonary disease, 19% with congestive heart failure, and 31.1% with diabetes. The most common procedure was laparoscopic cholecystectomy (36.4%). Overall, 90-day mortality was 10.9%. In multivariable analysis, all classes of obesity were protective against mortality compared to normal BMI. Underweight patients had increased risk of inpatient (OR = 1.9, CI = 1.7-2.3), 30-day (OR = 1.9, CI = 1.7-2.1), 90-day (OR = 1.8, CI 1.6-2.0), 1-year (OR = 1.8, CI = 1.7-2.0), and 3-year mortality (OR = 1.7, CI = 1.6-1.9). When stratified by BMI, underweight EGS patients have the highest odds of death. Paradoxically, obesity appears protective against death, even when controlling for potentially confounding factors. Increased rates of nonoperative management in the obese population may impact these findings.

scholarly journals Impact of the COVID-19 Pandemic on the Patient’s Decision about Bariatric Surgery: Results of a National Survey

Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 756
Author(s):  
Maciej Walędziak ◽  
Anna Różańska-Walędziak ◽  
Paweł Bartnik ◽  
Joanna Kacperczyk-Bartnik ◽  
Andrzej Kwiatkowski ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Online Survey ◽  
Negative Impact ◽  
Weight Loss Surgery ◽  
General Information ◽  
Open Questions ◽  
Increased Risk ◽  
Bariatric Patients ◽  
The Moment ◽  
The Impact

Background: the COVID-19 pandemic and the implemented restrictions have changed the functioning of healthcare systems worldwide. The purpose of the study was to evaluate the impact of the present epidemiological situation on patients’ decisions about undergoing weight loss surgery. Methods: data were collected from 906 bariatric patients by the means of a national online survey, the majority of whom were women (87.9%). The survey started on 9 April 2020 and was open until 28 April 2020. The questionnaire included multiple choice and open questions, divided into three chapters: general information about the patient, life during the COVID-19 pandemic, and bariatric care during the COVID-19 pandemic. Results: despite the pandemic and the associated risk of COVID-19 infection, 443 responders (48.9%) would have decided to undergo bariatric surgery. Awareness of the negative impact of obesity on the course of COVID-19 illness had only marginable impact on patients’ decision-making (76.6% vs. 75.3%; p < 0.80). Contact with COVID-19 prior to the survey had a negative impact on the willingness to undergo bariatric surgery (3.0% vs. 4.4%; p < 0.55). There was a positive correlation between the BMI and preference for bariatric surgery in the time of the pandemic (37.4 ± 9.0 vs. 34.9 ± 8.7; p < 0.001). Conclusions: the level of awareness about the advantages of operative treatment of obesity is high among bariatric patients. The majority of patients awaiting bariatric surgery at the moment of the survey were positive about undergoing bariatric surgery despite the increased risk of a serious course of COVID-19 infection. Therefore, a large proportion of patients was determined to have bariatric treatment even during the pandemic, being aware of the increased risk of worse pace of COVID-19 disease in case of obesity and related diseases.

Abstract 5857: Low Operative Mortality with implantation of a Continuous Flow LVAD and Impact of Concurrent Cardiac Procedures

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Jay D Pal ◽  
Charles T Klodell ◽  
Ranjit John ◽  
Francis Pagani ◽  
Joseph G Rogers ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Continuous Flow ◽  
Operative Mortality ◽  
Negative Impact ◽  
Venous Pressure ◽  
Heartmate Ii ◽  
Cardiac Procedures ◽  
Increased Risk ◽  
The Impact ◽  
Tricuspid Repair

Objective: Our goal was to determine the operative mortality of isolated implantation of the HeartMate II continuous flow LVAD and the impact of additional concurrent cardiac procedures on patient outcomes. Methods: In a multicenter trial, 279 patients at 33 clinical sites underwent implantation of the HeartMate II continuous flow LVAD as a bridge to transplantation from March 2005 to March 2007. HeartMate II implantation (HM II) was the only procedure required in 172 patients while 80 patients required concurrent cardiac procedures in conjunction with LVAD implantation (HM II+CCP). Results: Preoperative characteristics were similar, but central venous pressure (14.5 vs 11.6 mmHg) was greater for patients requiring concurrent cardiac procedures, suggesting worse right heart dysfunction. Mean cardiopulmonary bypass times increased from 97 to 120 minutes when a concurrent cardiac procedure was performed (p<0.001). Length of stay slightly increased from 23 to 26 days (p=0.17). Overall 30- and 180-day mortality was 5.8% and 13.3% for the HM II group, and 11.3% and 20.0% for the HM II+CCP group. Concurrent valvular procedures increased the risk to 8.5% and 19.1%. Patients who underwent an aortic valve replacement with cardioplegic arrest had a 30-day mortality of 25%, higher than for isolated concurrent mitral (0%) or tricuspid repair (3.3%). Other cardiac procedures were associated with a 30-day mortality of 27.8%. Survival at 180 days was 87% for HMII alone and 80% for HMII+CCP. Conclusion: There is a low 5.8% operative mortality for patients requiring uncomplicated HeartMate II implantation, with no apparent increased risk for concurrent PFO closure, mitral or tricuspid repair. However, concurrent aortic valve and other cardiac procedures are associated with a significantly decreased survival. The increased risk of these procedures must be balanced against the negative impact of uncorrected aortic insufficiency during VAD support.

Abstract T P136: Potential Contributors to the Declining Impact of Stroke Risk Factors with Age: Implications for Stroke Epidemiology in the Elderly

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
George Howard ◽  
Mary Cushman ◽  
Maciej Banach ◽  
Brett M Kissela ◽  
David C Goff ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Stroke Risk ◽  
Multivariable Analysis ◽  
The Elderly ◽  
Stroke Risk Factors ◽  
Age Related ◽  
Increased Risk ◽  
The Impact ◽  
Age Related Changes

Purpose: The importance of stroke research in the elderly is increasing as America is “graying.” For most risk factors for most diseases (including stroke), the magnitude of association with incident events decreases at older ages. Potential changes in the impact of risk factors could be a “true” effect, or could be due to methodological issues such as age-related changes in residual confounding. Methods: REGARDS followed 27,748 stroke-free participants age 45 and over for an average of 5.3 years, during which 715 incident strokes occurred. The association of the “Framingham” risk factors (hypertension [HTN], diabetes, smoking, AFib, LVH and heart disease) with incident stroke risk was assessed in age strata of 45-64 (Young), 65-74 (Middle), and 75+ (Old). For those with and without an “index” risk factor (e.g., HTN), the average number of “other” risk factors was calculated. Results: With the exception of AFib, there was a monotonic decrease in the magnitude of the impact across the age strata, with HTN, diabetes, smoking and LVH even becoming non-significant in the elderly (Figure 1). However, for most factors, the increasing prevalence of other risk factors with age impacts primarily those with the index risk factor absent (Figure 2, example HTN as the “index” risk factor). Discussion: The impact of stroke risk factors substantially declined at older ages. However, this decrease is partially attributable to increases in the prevalence of other risk factors among those without the index risk factor, as there was little change in the prevalence of other risk factors in those with the index risk factor. Hence, the impact of the index risk factor is attenuated by increased risk in the comparison group. If this phenomenon is active with latent risk factors, estimates from multivariable analysis will also decrease with age. A deeper understanding of age-related changes in the impact of risk factors is needed.

The effect of acenocoumarol on the antiplatelet effect of clopidogrel

2015 ◽  
Vol 114 (10) ◽  
pp. 708-716 ◽  
Author(s):  
Thomas Bergmeijer ◽  
Johannes Kelder ◽  
Christian Hackeng ◽  
Jurriën ten Berg ◽  
Willem Dewilde ◽  
...  
Keyword(s):  
Platelet Reactivity ◽  
Multivariable Analysis ◽  
Coumarin Derivative ◽  
Concomitant Treatment ◽  
Confounding By Indication ◽  
Increased Risk ◽  
Percutaneous Coronary ◽  
Propensity Matching ◽  
Multivariable Analyses ◽  
The Impact

SummaryPatients exhibiting high on-clopidogrel platelet reactivity (HPR) are at an increased risk of atherothrombotic events following percutaneous coronary interventions (PCI). The use of concomitant medication which is metabolised by the hepatic cytochrome P450 system, such as phenprocoumon, is associated with HPR. We assessed the level of platelet reactivity on clopidogrel in patients who received concomitant treatment with acenocoumarol (another coumarin derivative). Patients scheduled for PCI were included in a prospective, single centre, observational registry. Patients who were adequately pre-treated with clopidogrel were eligible for this analysis, which included 1,582 patients, of whom 104 patients (6.6 %) received concomitant acenocoumarol treatment. Platelet reactivity, as measured with the VerifyNow P2Y12 assay and expressed in P2Y12 Reaction Units (PRU), was significantly higher in patients on concomitant acenocoumarol treatment (mean PRU 229 ± 88 vs 187 ± 95; p< 0.001). In patients with concomitant acenocoumarol use, the proportion of patients with HPR was higher, defined as PRU > 208 (57.7 % vs 41.1 %; p=0.001) and PRU236 (49.0 % vs 31.4 %; p< 0.001). In multivariable analysis, concomitant acenocoumarol use was independently associated with a higher PRU and the occurrence of HPR defined as PRU236 (OR 2.00, [1.07–3.79]), but not with HPR defined as PRU > 208 (OR 1.37, [0.74–2.54]). PRU also was significantly increased after 1:1 propensity matching (+28.2; p< 0.001). As this was an observational study, confounding by indication cannot be excluded, although multivariable analyses and propensity matching were performed. The impact of the findings from this hypothesis-generating study on clinical outcome requires further investigation.

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