Allogeneic Hematopoietic Transplantation in Patients with CLL: Results of a Large Disease-Specific Risk Factor Analysis

Abstract Objectives: For medically-fit young patients with high-risk chronic lymphocytic leukemia (CLL) BTK-/PI3K-inhibitors or allogeneic stem cell transplantation (alloHCT) are considered. We hypothesized that given the choice between these drugs and transplantation in future only patients with a low risk of treatment failure will be selected for alloHCT. Therefore, we searched for risk factors for 2-year non-relapse mortality (NRM) and 5-year event-free survival (EFS) after alloHCT, the latter as a surrogate for long-term disease-control. Methods: Data from patients with CLL who had received a first alloHCT from a HLA-identical sibling (SIB) or unrelated donor between 2000 and 2011 were updated in an EBMT data quality initiative. Multivariable Cox regression models were fitted to assess the impact of baseline risk factors for NRM and EFS. Results: Data on 694 patients were included into the analysis. The median age of the cohort of patients was 55 years (19 years to 74 years). Seventy-nine percent of patients had a Karnofsky performance status of 90% or higher. A disease history of less than two years was reported in 20% of patients and 44% of patients had a disease history of more than 5 years. The median number of pretreatments was 3 (range, 0-15). Eleven percent of patients had received a previous autologous HCT. Only 9% of patients had never received purine-analogs (PA) during their treatment history. Sixty-three percent of patients had either PA-refractory disease or relapse within 24 months from the last PA-containing chemotherapy at the time of HCT. A deletion 17p had been diagnosed in 28% of patients in this cohort. Information on PA-sensitivity, early relapse after autologous transplantation or PA-combination therapy and del(17p)/TP53 is used to select patients for allogeneic HCT according to the EBMT 2007 consensus. EBMT consensus criteria were met in 76% of evaluable patients. Overall, the majority of patients analyzed in this subset of all registered patients had high-risk CLL. For the whole cohort 2-year NRM was 28% (95%-CI, 24% to 32%). The baseline risk factors age, Karnofsky performance status, donor type, and donor-recipient sex mismatch had a significant impact on 2-year-NRM. With the help of these risk factors the outcome of good risk and poor risk reference patients was predicted whose linear predictors were close to the 10th and the 90th percentile of all patients in the dataset. The good risk male reference patient has an age of 45 years, a Karnofsky performance index of 100%, is in partial remission at HCT and has a matched related male donor. The poor risk male reference patient has 55 years of age a Karnofsky performance index of 80%, SD/PD at HCT, and a matched unrelated female donor. The female reference patients had the same characteristics, apart from the donor sex. Two-year-NRM was predicted to be 11% (12%) for male (female) patients with a favorable risk compared to 40% (32%) with a poor risk profile (see Figure). The same approach was used to analyze risk factors for long-term disease control. Five-year-EFS was 37% (95%-CI, 33% to 41%) for all patients. Age, Karnofsky performance status, history of an autologous HCT, remission status, and donor-recipient sex mismatch had a significant impact. The model-based prediction of 5-year EFS was 54% (64%) for a male (female) patient with a favorable risk profile compared to 15% (30%) with a poor risk profile. Current knowledge suggests that allogeneic HCT can overcome the negative prognostic impact of high risk cytogenetic abnormalities, especially of a deletion(17p) or TP53 -mutation. Even in this large cohort we observed only a trend for a lower incidence of relapse/progression in patients without deletion(17p) CLL within the first two years after HCT with translated into a trend for better EFS at that time. The impact on long-term disease-control and mortality was even smaller. Conclusion: Information on predicted 2-year-NRM and 5-year-EFS for good and poor risk reference patients derived from a large CLL dataset may be instrumental to select patients for future alloHCT. Model-based prediction of non-relapse mortality and relapse/progression. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

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Initial and Confirmation Analyses of a Detailed Comorbidity and Organ Function Assessment In 593 Multiple Myeloma (MM) Patients (pts) Identify the Freiburger Comorbidity Index (FCI) as a Non-Weighted, Simple, Concise and Cost Effective Comorbidity Score Consisting of 3 Factors Only: Proposal of a Valuable New Tool In MM-Risk Assessment

Blood ◽

10.1182/blood.v116.21.1901.1901 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1901-1901

Author(s):

Meike Terhorst ◽

Martina Kleber ◽

David De Pasquale ◽

Gabriele Ihorst ◽

Monika Engelhardt

Keyword(s):

Risk Factors ◽

High Risk ◽

Karnofsky Performance Status ◽

Performance Status ◽

Cost Effective ◽

Low Risk ◽

Organ Function ◽

Comorbidity Scores ◽

Comorbidity Index ◽

Severe Lung

Abstract Abstract 1901 Introduction: Comorbidities and a deteriorated functional status have been demonstrated to affect progression free survival (PFS) and overall survival (OS) in various cancer pts, but have as yet not been formally evaluated in MM. Structured comorbidity analyses seem to be exceedingly needed in MM, as these pts are typical elderly and some are frail. The study aim was to develop and validate an easily assessable and cost effective MM-risk score and compare this to previously established comorbidity indices (CIs). Methods: In initially 127 MM pts consecutively treated at our institution between 1997 and 2003, we determined age, Karnofsky-Performance Status, hypertension, diabetes, secondary malignancies, pain, liver-, heart-, lung-diseases and renal impairment (eGFR). Via uni- and multivariate Cox regression analyses, we developed a simple risk score, termed Freiburger comorbidity index (FCI), that consists of 3 risk factors only. We also compared previously established CIs, namely Kaplan Feinstein (KF), Charlson-Comorbidity (CCI), Satariano (SI) and Hematopoietic cell transplantation-specific comorbidity index (HCT-CI), assessing PFS and OS in ‘low- risk’ (scoring ≤median CI points) vs. ‘high-risk group’ pts (>median CI points). In another set of 466 consecutive MM pts treated in our department thereafter (2003-2009), we re-evaluated comorbidity, organ function and MM risk factors via uni- and multivariate analyses and determined the prognostic value of the FCI, KF and HCT-CI on PFS and OS. Results: The multivariate analysis on the initial 127 MM pts identified the Karnofsky-Performance Status <70%, moderate or severe lung impairment and eGFR <30ml/min/1.73m2 as most relevant prognostic factors, with hazard ratios (HR) for decreased OS of 2.2, 2.8 and 2.9, respectively. When incorporating these risk factors into the FCI, we identified a largely different median OS: with 0, 1 and 2–3 risk factors this was 118, 53 and 25 months, respectively (p<0.005). The initial comparison of all 4 CIs (KF, CCI, SI and HCT-CI) identified the KF and HCT-CI as most relevant: ’low-risk’ vs. ‘high-risk’-pts had a strikingly different median OS of 98 vs. 44 months (p=0.007), and 81 vs. 41 months (p=0.002), respectively. The confirmation analysis in 466 MM pts verified the prognostic relevance of the FCI, KF and HCT-CI, showing median OS differences between ‘low-risk’ vs. ‘high-risk’ pts of 113 vs. 39, 143 vs. 36 and 117 vs. 49 months, respectively (log rank-test p< 0.0001 each). The multivariate analysis of prognostic factors revealed that high-risk cytogenetics, elevated LDH, increased bone marrow infiltration, ß2-microglobulin (ß2-MG) and impaired albumin were most relevant. In our current test and validation analysis, we are re-evaluating all MM pts treated between 1997 and 2009, to confirm the value of specific organ function, prognostic risks and comorbidity scores in order to develop a weighted FCI for future analyses. Clinical characteristics of this combined pt set showed a median age of 62 years (27-90); 86% had stage II/III disease by Durie&Salmon and 18% stage B disease. The descriptive comorbidity evaluation revealed a Karnofsky-Performance Status <70% in 64% (median 70%; range: 20–100%), moderate or severe lung disease in 18% and eGFR <30 in 16%. Current results also indicate that weighted comorbidity scores- as realized with the in MM valuable KF and HCT-CI - allow to distinguish significantly different MM risk groups. The by our group developed FCI is currently a non-weighted, but simple, concise and cost effective comorbidity tool consisting of 3 factors only, namely Karnofsky-Performance Status, lung- and renal function, which is of importance to develop further to a weighted score as well as in combination with other indispensable risk factors. Conclusions: The new FCI, KF and HCT-CI proved as useful tools for risk evaluation in MM. The development of a weighted FCI within a test- and validation-set is currently being pursued as well as the inclusion of other prognostic parameters therein (such as ISS). Our results highlight the strong debate on comorbidity scores and comprehensive risk assessment in MM which have not as yet moved into routine clinical practise, but appear appealing and useful to implement into future analyses and clinical trials. Disclosures: No relevant conflicts of interest to declare.

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JAK2V617F Variant Allele Frequency Identifies Patients with Polycythemia Vera (PV) at High Risk for Venous Thrombosis

Blood ◽

10.1182/blood-2018-99-112287 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1776-1776

Author(s):

Paola Guglielmelli ◽

Giacomo Coltro ◽

Giuseppe Gaetano Loscocco ◽

Benedetta Sordi ◽

Francesco Mannelli ◽

...

Keyword(s):

Risk Factors ◽

High Risk ◽

Venous Thrombosis ◽

Allele Frequency ◽

Variant Allele ◽

Continuous Variables ◽

Variant Allele Frequency ◽

Thrombotic Risk ◽

History Of ◽

The Impact

Abstract Background. Cardiovascular (CV) events are leading cause of morbidity and mortality in PV. Current risk stratification is based on variables predicting thrombotic risk, ie age >60y and history of thrombosis. Recent studies focused on additional thrombotic risk factors in PV, including generic CV factors and leukocytosis. PV patients (pts) are JAK2V617F mutated, and present wide heterogeneity in variant allele frequency (VAF); it was shown that a VAF >75% was associated with higher number of thrombotic events after diagnosis (Vannucchi AM, Leukemia 2007), but the prognostic role of JAK2 VAF is still debated. Aim. The aim of the study was to evaluate the impact of JAK2V617F VAF on rate of thrombosis in WHO-2016 defined PV pts. Patients and Method. In the CRIMM (Florence) database, a total of 577 pts with a JAK2VF VAF determined within 3 years from diagnosis, who met the 2016 WHO criteria for PV, were identified. All pts had information regarding thromboembolic events, including history of thrombosis, occurrence, type and date of thrombosis in the follow-up (FU) and presence of CV risk factors (smoking, hypertension, and diabetes mellitus). Thrombosis‐free survival (TFS) was determined from the time of diagnosis to the time the first thrombotic event occurred. Pts in whom thrombosis did not occur were censored at the time of last FU. Pre-receiver operating characteristic (ROC) plots were used to determine cutoff levels for continuous variables of interest. Differences in the distribution of continuous variables between categories were analyzed by Mann-Whitney or Kruskal-Wallis test. Pts' groups with nominal variables were compared by χ2 test. TFS was estimated by Kaplan Meier analysis; log rank test was used to compare TFS difference between groups. Cox proportional hazards regression was used for multivariable analysis. A two tailed P ≤ 0.05 was considered statistically significant. Results. The median age of pts at diagnosis was 61y, 308 (53.4%) were above 60y; 57.2% were males. All pts were mutated for JAK2V617F with a median VAF 43% (range 1-100%), 62% had at least one CV risk factor; 83 (14.4%) pts suffered from an episode of thrombosis within 3 yr from, or coincident with, diagnosis. The median FU was 7.3y (0.6-35.9y) during which 87 pts (15.1%) developed thrombosis. (50 arterial and 45 venous thrombosis). During the FU, 110 pts (19.1%) died. A JAK2VAF of ≥60% cutoff level, as determined by ROC analysis, correlated with measurements of stimulated erythropoiesis (higher hematocrit, lower mean cell volume and serum ferritin; all P<.01), leukocytosis (P<.0001), lower platelets count (P=.02) and elevated serum lactate dehydrogenase (LDH) (P<.03). Pts with ≥60% JAK2V617F VAF were at higher relative risk (RR) of having splenomegaly (RR 3.1; P<0.001), suffering from pruritus (RR 2.5; P<0.001) or constitutional symptoms (RR 1.9; P=0.01), harboring a BM fibrosis grade-1 (RR 3.1; P<0.001). Additionally, pts with a VAF>60% had greater risk to progress to PPV-MF (RR 8.5, P<.0001) and acute leukemia (RR 4.4, P=0.04) or to die (RR 3.8, P<0.0001). The JAK2VF VAF (continuous or ≥60%) did not correlate with occurrence of thrombosis at diagnosis, while the rate of thrombosis during FU was significantly increased in pts with VAF ≥60% (23.4% vs 11.0%, RR 2.4, 95%CI = 1.4-4.0; P<0.0001), more marked for venous (RR 3.7, 95%CI = 2.0-6.8; P<0.0001) than arterial (RR 1.8, 95%CI = 0.9-3.3; P=0.05) thrombosis. The impact of VAF on thrombosis during FU was then estimated according to the conventional risk category. In low risk pts (LR) (n=236), factors significantly associated with occurrence of FU thrombosis were CV risk factors (dyslipidemia (RR 3.3, P = 0.02) and hypertension (RR 1.8, P=0.048)), a G1 BM fibrosis (RR 5.3, P=0.006), presence of splenomegaly (RR, 3.2, P=0.001) or constitutional symptoms (RR 3.3, P=0.003) and a VAF ≥60% (RR 2.2, P = 0.024). In high risk pts (HR) (n=341), factors significant for FU thrombosis were splenomegaly (RR 2.0, P=0.03), elevated LDH (RR 4.0, P=0.009) and a VAF ≥60% (RR 2.3, P = 0.012). A VAF ≥60% was correlated with shortened venous TFS after diagnosis in HR (P = 0.01, HR = 3.2, 95%CI = 1.2−8.3; fig.) but not in LR pts (P = 0.20, HR = 1.1, 95%CI = 0.5−2.9). Conclusions. This study indicates that conventionally-defined high-risk PV pts with a JAK2V617F VAF ≥60% suffer from increased rate of venous events and might be worthwhile of more intensive antithrombotic prophylaxis. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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Characteristics of osteoporosis in patients with rheumatic diseases

Health care of Tajikistan ◽

10.52888/0514-2515-2021-350-48-54 ◽

2021 ◽

pp. 48-54

Author(s):

O. Kh. Mirzovaliev ◽

S. M. Shukurova

Keyword(s):

Risk Factors ◽

High Risk ◽

Rheumatic Diseases ◽

Absolute Risk ◽

Osteoporotic Fractures ◽

Case Histories ◽

Mineral Density ◽

Major Osteoporotic Fractures ◽

History Of

Aim. To present a comprehensive assessment of rheumatic diseases in association with osteoporosis.Material and methods. A retrospective analysis was made of 180 case histories with various RDs, who were under inpatient observation at the Sughd Regional Clinical Hospital for the period 2018-2019 for the frequency of osteoporosis (OP). Densitometry was used to determine the projection mineral density (in g / cm2) in various parts of the skeleton.Results. When asked about a history of fractures, every third respondent (33.3%) answered positively. According to the results of densitometry, osteoporosis in patients with inflammatory RD was diagnosed in 32.2% of patients. At the same time, the indicators differed significantly by nosology, and the frequency of OP correlated with the intake of corticosteroids. Osteoporosis was detected in every third patient with OA according to densitometry data and in 25% of cases in patients with gout. The results of the analysis to assess the absolute risk of major osteoporotic fractures according to FRAX showed high risk in 2 groups.Conclusion. Thus, the nature and frequency of risk factors for osteoporosis in patients with RA and OA have their characteristics. A history of fractures in patients with RA is often associated with long-term use of GCS, and the presence of menopause in women and the presence of cardiometabolic concomitant diseases play an important role in the progression of AP in patients with OA.

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Safety and Long-Term Efficacy of Maintenance Therapy with Alternating Azacytidine (AZA) and Lenalidomide (Len) Cycles in Elderly (≥ 60) Fit Patients (Pts) with Poor Prognosis AML in First Complete Remission (CR) After LIA Induction. A Phase II Multicentric GOELAMS Trial

Blood ◽

10.1182/blood.v126.23.3787.3787 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3787-3787

Author(s):

Mathilde Hunault ◽

Nathalie Maillard ◽

Aline Tanguy-Schmidt ◽

Chantal Himberlin ◽

Bachra Choufi ◽

...

Keyword(s):

Risk Factors ◽

Maintenance Therapy ◽

Poor Prognosis ◽

Conflicts Of Interest ◽

Time Interval ◽

Conventional Chemotherapy ◽

Poor Risk ◽

The Impact

Abstract In elderly pts, the prognosis of AML associated with poor risk cytogenetics or secondary to either MDS or previous cancer is so bad that only supportive care or investigational studies are usually recommended. Fit patients may achieve CR after conventional induction, but early relapse appears to be nearly inescapable whatever classical consolidation or maintenance therapy is used. Therefore, the GOELAMS investigated the impact of a maintenance using two agents mainly used in MDS, ie AZA and Len. Between March 2011 and February 2013, 117 pts from 27 centers (median age 69 yrs; 60-80) with previously untreated poor prognosis AML were included. Poor Risk factors were either preceding MDS (n=52), previous cancer (n=37) or centrally reviewed (IL) poor risk cytogenetics (n=83) defined as complex karyotype (≥3 abnormalities, n=65), monosomal karyotypes (n=54), del or - 5 (n=61) or 7 (n=44), 3q abnormality (n=9) or MLL rearrangement except for t(9;11) (n=5). Median WBC was 2.9 G/L (0.5-160), 7 pts had WBC ≥ 30 G/L. Induction chemotherapy included Lomustine 200 mg/m² po d1, Idarubicine 8 mg/m²/d (d1-5), Cytarabine 100mg/m²/d CI (d1-7). Patients in CR received 12 maintenance cycles alternating every 28 days AZA (sc 75 mg/m²/d1-7) and Len (10mg/d1-21), which started if PMN and platelets were >1 G/L and 100 G/L respectively. After d42, subsequent cycles were reduced to 50 mg/m²/d and 5 mg/d. GCSF was allowed in case of PMN < 0.5 G/L after 7 days or febrile neutropenia. At the end of induction, CR was achieved in 56% (65 pts) without any predictive factor, 9% died from infection (n=6), cerebral hemorrhage (n=1) or MOF (n=4) and 35% (41pts including 5 CRp) failed to achieve CR. The 12 planned maintenance courses could be given to 21 pts (32%) (median: 6). Few toxicities were observed. AZA courses were slightly more toxic than Len courses (table 1). Table 1.AZA courses %Len courses %Gr 3/4 neutropenia46.8/ 27.339.7 /17.6Antibiotics for fever at home6.97Hospitalization for febrile neutropenia0.52.7RBC transfusions55.4Gr 3 Thrombopenia2016Platelets transfusion8.67.9Interval between courses > 35 days26.118.4Median time interval between courses31 d28 dCourses with doses reductions9.621.6 Maintenance courses were interrupted because of relapse (n= 34, 77%), alloSCT (n=4 %), count error (n=1 %) or toxicities (n =5, 11%) occurring after Len (depression, vascular purpura and pseudomembranous diarrhea, sudden death, all during cycle 1) or after Aza (atrial fibrillation and cardiac dysfunction). Twenty Gr3/4 AE were reported among 441 cycles (0.56%/courses). Median follow-up for survivors was 38 mo (26-47). Median OS was 10 mo, with 21% 2y OS. Median CR duration was 7 mo (1-30). Impact of prognostic factors on DFS is shown table 2. Within poor risk factors, Cytogenetic abnormalities appeared as even poorer than previous MDS or cancer. Table 2.CR %CR NDFS median moP VALUE1y DFS %2y DFS %All patients56657.941.512.3Age ≥ 7058.3288.6 vs 7.746.417.9WBC ≥ 3.3 G/L48.1267.0 vs12.423.111.5Previous MDS51.92713.8 vs 6.4.0551.922.2MDS only68.41316.8 vs 6.4.00869.230.8Previous cancer54207.5 vs 7.9355Cancer only80812.4 vs 7.755012.5Poor cytogenetic53445.1 vs 15.3.0429.56.8Complex caryotype49.2324.8 vs 12.9.012259.4Monosomal caryotype50274.6 vs 12.9.00218.57.4Chromosome 5 abnormality52.5325 vs 13.8.00218.86.3Chromosome 7 abnormality54.5243.6 vs 12.00120.84.23q55.6510.4 vs 7.740017p deletion48.5165.0 vs 10.52512.5MLL8043.4 vs 8.4250poor cytogenetic + MDS42.997.7 vs 7.944.422poor cytogenetic + cancer46.774.8 vs 7.928.90poor cytogenetic + cancer + MDS71.453.4 vs 8.4200cancer + MDS00---Poor cytogenetic only rev aza57.5236.3 vs 12.9.05521.74.3Poor cytogenetic only SA255436.430.220.9 In the previous GOELAMS SA2 trial, 78 pts with poor risk cytogenetics without secondary leukemia received the same LIA induction followed in CR by maintenance therapy with 6 mini-reinductions (Ida 10mg/m² d1, cytarabine 50 mg/m²x2/d d1-5) and 6MP-MTX for 2years. In the present study, the DFS of the group of pts with poor risk cytogenetics without previous cancer or MDS is very similar. This alternating azacitidine/lenalidomide maintenance improved DFS and OS of pts without poor risk cytogenetics (median 15.7 and 24 mo). In this setting, it could be randomly compared to conventional chemotherapy maintenance. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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The Impact of Emergency Interventions and Patient Characteristics on the Risk of Heart Failure in Patients with Nontraumatic OHCA

Emergency Medicine International ◽

10.1155/2019/6218389 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10

Author(s):

Cheng Hsu Chen ◽

Chih-Yu Chang ◽

Mei-Chueh Yang ◽

Jr-Hau Wu ◽

Ching-Hui Liao ◽

...

Keyword(s):

Risk Factors ◽

Myocardial Infarction ◽

Heart Failure ◽

Comparison Group ◽

Patient Characteristics ◽

Emergency Interventions ◽

History Of ◽

The Impact ◽

New Onset

Background. Since out-of-hospital cardiac arrest- (OHCA-) related dysfunction (ischemic/reperfusion injury and inflammatory response) might result in long-term impairment, we suspect that new-onset heart failure might be common in long-term survivors. However, these relationships had not been well addressed, and we aimed to analyze the impact of emergency interventions and patient characteristics on the risk of new-onset heart failure in patients with nontraumatic OHCA. Methods. The Taiwanese government healthcare database contains data for 49,101 nontraumatic OHCA adult patients from 2011-2012, which were analyzed in this study. Nontraumatic OHCA patients who survived to the intensive care unit (ICU) were included as the study group (n = 7,321). Matched patients (n = 21,963) were recruited as a comparison group. Patients with any history of heart failure or cardiac arrest were not included in either group. All patients were followed-up for 6 months for the identification of new-onset heart failure. Adjustments were made for demographics, age, emergency interventions, and comorbidities as potential risk factors. Results. In all, 3.84% (n = 281) of OHCA patients suffered new-onset heart failure, while only 1.24% (n = 272) of matched patients in the comparison group suffered new-onset heart failure. Strong risk factors for heart failure were age (60–75 years, HR: 11.4; 95% CI: 9–14.4), medical history (myocardial infarction, HR: 2.47; 95% CI: 2.05–2.98 and cardiomyopathy, HR: 2.94; 95% CI: 1.45–5.94), and comorbidities during hospitalization (ischemic heart disease, HR: 4.5; 95% CI: 3.46–5.86). Only extracorporeal membrane oxygenation (ECMO) decreased the risk of heart failure. Most (53.6%) heart failure events occurred within 60 days after OHCA. Conclusion. An age from 61 to 75 years, a history of myocardial infarction or cardiomyopathy, and ischemic heart disease or infection as comorbidities occurring during hospitalization were strong risk factors for new-onset heart failure in OHCA patients. However, ECMO could decrease this risk. More importantly, most heart failure events occurred within 60 days after OHCA.

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Risk factors for early severe preeclampsia in obstetric antiphospholipid syndrome with conventional treatment. The impact of hydroxychloroquine

Lupus ◽

10.1177/0961203320952850 ◽

2020 ◽

Vol 29 (13) ◽

pp. 1736-1742

Author(s):

José Omar Latino ◽

Sebastián Udry ◽

Federico Aranda ◽

Silvia Perés Wingeyer ◽

Diego Santiago Fernández Romero ◽

...

Keyword(s):

Risk Factors ◽

High Risk ◽

Antiphospholipid Syndrome ◽

Conventional Treatment ◽

Severe Preeclampsia ◽

Factors Associated ◽

High Risk Factors ◽

History Of ◽

Obstetric Antiphospholipid Syndrome ◽

The Impact

Objective The first aim was to retrospectively identify risk factors for the development of early severe preeclampsia (sPE) in patients with obstetric antiphospholipid syndrome (OAPS) who received conventional treatment (CT). The second aim was to evaluate the impact of hydroxychloroquine (HCQ) in preventing early sPE among a subgroup of patients considered at high risk. Methods A total of 102 women diagnosed with OAPS and treated with CT since the diagnosis of pregnancy were selected. At the end of pregnancy, we identified risk factors associated with early sPE. According to these risk factors, we collected a new cohort of 42 patients who presented high-risk factors for developing early sPE and split them into two groups according to the treatment received: group A, CT (30 patients); and group B, CT+HCQ (12 patients). We evaluated and compared pregnancy outcomes in both groups. Results According to the multivariate analysis, risk factors associated with early sPE and CT were triple positivity for antiphospholipid antibodies (aPL) (OR = 24.70, [4.27–142.92], p < 0.001) and a history of early sPE (OR = 7.11, [1.13–44.64], p = 0.036). A low-risk aPL profile was associated with a good response to CT in preventing early sPE (OR = 0.073, [0.014–0.382], p = 0.002). High-risk patients treated with CT+HCQ had a significantly lower early sPE rate than those treated with CT only (8.3% vs 40.0%; p = 0.03). Conclusion Triple positivity for aPL and a history of early sPE are potential strong risk factors for the development of early sPE. HCQ might be an interesting therapeutic option for patients with high-risk factors for early sPE.

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Death In Complete Remission Among Patients with Acute Myeloid Leukemia: A Preventable Problem?

Blood ◽

10.1182/blood.v116.21.2710.2710 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2710-2710

Author(s):

Gloria Mattiuzzi ◽

Hagop Kantarjian ◽

Farhad Ravandi ◽

Guillermo Garcia-Manero ◽

Gautam Borthakur ◽

...

Keyword(s):

Risk Factors ◽

Stem Cell ◽

High Risk ◽

Causes Of Death ◽

Performance Status ◽

Poor Performance ◽

Poor Performance Status ◽

Newly Diagnosed ◽

History Of ◽

Prior Malignancy

Abstract Abstract 2710 Background: Significant advances in the treatment of patients with acute myelogenous leukemia (AML) and high risk myelodysplastic syndrome (HR-MDS) have improved their outcome. Mortality among patients with newly diagnosed AML and HR-MDS is mainly attributed to persistent disease (i.e., failure to achieve or loss of complete remission [CR]), infectious and other complications during induction chemotherapy. However, a small but significant proportion of patients die in CR. The aim of this study was to investigate the cause of death in AML and HR-MDS patients in CR and to analyze the associated risk factors. Methods: Retrospective review of medical records of patients with newly diagnosed AML, APL and HR-MDS who received induction chemotherapy at the Department of Leukemia at MD Anderson from January 2000 to December 2009. Results: During the study period, 2156 patients were treated. One thousand one hundred fifty patients achieved CR for an overall CR rate of 53%. Among them, 114 patients (10%) died in CR. The median time from achievement of CR to death was 5.3 months (range, 0.2 – 79). There was a decline in the rate of death in CR over the 10 years of analysis reported (p=0.010). [Table 1] Information about the causes of death in 35 patients (31%) was not available. The most frequent causes of death in the remaining 79 patients were infections (27%); SCT-related complications (19%); relapse of prior malignancy (8%); hemorrhage (4%); multi-organ failure (4%); and others (9%). Among patients who died in CR, 105 (92%) had AML and 9 high-risk MDS, 60% were female, and the median age was 64 years (range 21–86). Forty-two patients (37%) had history of a prior malignancy, 22% had received previous chemotherapy (for other malignancies), and 20% prior radiotherapy. Sixty-eight percent received high-dose cytarabine-containing regimen for induction therapy, 92% achieved CR after one cycle of chemotherapy, with a median of 33 days (range 21–152) to achievement of CR. Nineteen percent underwent stem cell transplantation while in CR. In comparison to patients who did not die in CR, patients who died in remission were significantly older at the time of diagnosis [64 vs. 57 years, p <.001]; were more likely to have history of prior malignancy, chemotherapy or radiotherapy [37% vs.21%, p<0.001; 22% vs.11%, p<0.001; 20% vs. 9%, p<0.001, respectively]; had worse performance status at the time of diagnosis [26% vs. 14%, p = 0.004]; and were more likely to have undergone stem cell transplantation (SCT) while in CR [19% vs. 8%, p<0.001]. Sixty-three percent of the patients who died in CR were 60 years or older. Among patients age 60 years or older, the probability of death in CR was 14% compared to 7% for patients younger than 60 (p<0.001). Multivariate logistic regression analysis confirmed that older age (p<0.000), prior malignancy (p<0.001), poor performance status (p<0.001) and SCT while in CR (p<0.000) were independently associated with the probability of dying in CR. Risk factors for dying from infections included only older age (p<0.003) and poor performance status (p, 0.05). Conclusion: Death in CR affects a significant number of patients with AML, with older patients with poor performance status having the highest probability of dying in CR, particularly from infections. Special attention should be put to these patients to minimize their risk of death in CR to improve their long term outcome. Disclosures: No relevant conflicts of interest to declare.

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Protocol for a randomized controlled trial to test the acceptability and adherence to 6-months of walnut supplementation in Chinese adults at high risk of cardiovascular disease

Nutrition Journal ◽

10.1186/s12937-020-00660-7 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Yishu Liu ◽

Nan Li ◽

Ni Yan ◽

Xiong-fei Pan ◽

Qiang Li ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Randomized Controlled Trial ◽

High Risk ◽

Controlled Trial ◽

High Dose ◽

Cvd Risk ◽

Randomized Controlled ◽

History Of

Abstract Background Consumption of nuts improves cardio-metabolic risk factors in clinical trials and relates to lower risk of cardiovascular disease (CVD) in prospective observational studies. However, there has not been an adequately powered randomized controlled trial to test if nuts supplementation actually reduces incident CVD. In order to establish the feasibility of such a trial, the current study aimed to assess the acceptability and adherence to long-term nut supplementation amongst individuals at high CVD risk in China. Methods This protocol described a 6-month trial performed in Ningxia Province in China among participants with a history of CVD or older age (female ≥65 years, male ≥60 years) with multiple CVD risk factors. Participants were randomized to control (received non-edible gift), low dose walnut (30 g/d), or high dose walnut (60 g/d) groups in a 1:1:1 ratio. Walnuts were provided at no cost to participants and could be consumed according to personal preferences. Follow-up visits were scheduled at 2 weeks, 3 months and 6 months. The primary outcome was fasting plasma alpha linolenic acid (ALA) levels used as an indicator of walnut consumption. Secondary outcomes included self-reported walnut intake from the 24 h dietary recalls. The target sample size of 210 provided 90% statistical power with two-sided alpha of 0.05 to detect a mean difference of 0.12% (as percent of total fatty acid) in plasma ALA between randomized groups. Results Two hundred and ten participants were recruited and randomized during October 2019. Mean age of participants was 65 years (SD = 7.3), 47% were females, and 94% had a history of CVD at baseline. Across the three study groups, participants had similar baseline demographic and clinical characteristics. Discussion This trial will quantify acceptability and adherence to long-term walnut supplementation in a Chinese population at high risk of CVD. The findings will support the design of a future large trial to test the effect of walnut supplementation for CVD prevention. Trial registration NCT04037943 Protocol version: v3.0 August 14 2019

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Stress, Cortisol and Suicide Risk

10.31234/osf.io/92b7z ◽

2019 ◽

Author(s):

Daryl Brian O'Connor

Keyword(s):

Risk Factors ◽

Suicidal Behavior ◽

Suicide Risk ◽

Stressful Events ◽

Additional Risk ◽

Global Health Issue ◽

History Of ◽

Hpa Axis Activity ◽

The Impact

Suicide is a global health issue accounting for at least 800,000 deaths per annum. Numerous models have been proposed that differ in their emphasis on the role of psychological, social, psychiatric and neurobiological factors in explaining suicide risk. Central to many models is a stress-diathesis component which states that suicidal behavior is the result of an interaction between acutely stressful events and a susceptibility to suicidal behavior (a diathesis). This article presents an overview of studies that demonstrate that stress and dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, are important additional risk factors for suicide. Evidence for other putative stress-related suicide risk factors including childhood trauma, impaired executive function, impulsivity and disrupted sleep are considered together with the impact of family history of suicide, perinatal and epigenetic influences on suicide risk.

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Premature Adrenarche and its Association with Cardiovascular Risk in Females

Current Pharmaceutical Design ◽

10.2174/1381612826666201012164726 ◽

2020 ◽

Vol 26 (43) ◽

pp. 5609-5616

Author(s):

Sarantis Livadas ◽

Christina Bothou ◽

Djuro Macut

Keyword(s):

Polycystic Ovary ◽

Dehydroepiandrosterone Sulfate ◽

Adrenal Androgen ◽

Premature Adrenarche ◽

Adrenal Hyperandrogenism ◽

Long Term Follow Up ◽

History Of ◽

Hormonal Milieu ◽

The Impact

Early activation of the adrenal zona reticularis, leading to adrenal androgen secretion, mainly dehydroepiandrosterone sulfate (DHEAS), is called premature adrenarche (PA). The fact that adrenal hyperandrogenism in females has been linked to a cluster of cardiovascular (CV) risk factors, even in prepubertal children, warrants investigation. Controversial results have been obtained in this field, probably due to genetic, constitutional, and environmental factors or differences in the characteristics of participants. In an attempt to understand, in depth, the impact of PA as a potential activator of CV risk, we critically present available data stratified according to pubertal status. It seems that prepubertally, CV risk is increased in these girls, but is somewhat attenuated during their second decade of life. Furthermore, different entities associated with PA, such as polycystic ovary syndrome, non-classical congenital adrenal hyperplasia, heterozygosity of CYP21A2 mutations, and the impact of DHEAS on CV risk, are reviewed. At present, firm and definitive conclusions cannot be drawn. However, it may be speculated that girls with a history of PA display a hyperandrogenic hormonal milieu that may lead to increased CV risk. Accordingly, appropriate long-term follow-up and early intervention employing a patient-oriented approach are recommended.

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