Outcomes of IVC Filter Use in Heparin-Induced Thrombocytopenia: A Retrospective Study

Abstract Introduction Heparin-induced thrombocytopenia (HIT) is a prothrombotic state characterized by prior exposure to heparin products and decreased platelets. Inferior vena cava filters (IVCFs) are often placed in patients with deep venous thrombus (DVT) or pulmonary emboli (PE) that are not candidates for anticoagulation. Patients with HIT are in a hypercoagulable state and presumably may have high rates of thrombotic events after IVCF placement. Recommendations against insertion of an IVCF in patients with acute HIT or acute isolated HIT have been supported by a single, small case series (n=10) and a few case reports of IVC-related thrombotic events in patients with IVCF placement either before or during time of HIT diagnosis.1 However, there have not been any larger studies looking specifically at patients with HIT and IVCF placement and subsequent outcomes. Methods We retrospectively reviewed patient charts from the Kaiser Permanente Northern California electronic medical record database (over 4 million patients) from 2006-2015 and cross-referenced patients with both an ICD-9 code for IVCF placement and for HIT. Chart review was done on the patients who met both criteria. The patients were divided into two subgroups- those with HIT diagnosis confirmed (SRA positive or HIT ab >1) and those with HIT diagnosis likely (HIT ab <1), as well as sub-groups based on the timing of IVCF placement relative to HIT diagnosis (within 14 days or not). Sub-groups were analyzed for thrombotic events after placement of IVCF, including new or extension of DVT, new or extension of PE, IVC thrombosis, lower extremity phlegmasia cerulea dolens, critical limb ischemia, and mortality. Results During this ten-year period, 3,934 patients had IVCFs placed and 814 patients were identified with HIT diagnostic codes, with 30 patients meeting criteria for both an ICD-9 code for HIT and IVCF placement. Of these 30 patients, 4 were excluded as they had IVCF placement well after diagnosis of HIT (>14 days). Of these patients (n=26), a total of 4 patients (15.4%) had thrombotic progression/complications, either a single complication or multiple complications. Overall, 11.5% (n=3) had progression of DVT noted either on ultrasound or clinically, 3.9% (n=1) had IVC thrombosis, and 3.9% (n=1) had lower extremity phlegmasia. Of these 26 patients, we further examined those who had an IVCF placed up to 14 days before or after HIT diagnosis (n=17). Of these patients, 11.8% (n=2) had progression of DVT, 5.9% (n=1) had IVC thrombosis, and no patients had lower extremity phlegmasia. There were 2 deaths (7.7%) related to thrombotic events. Six-month all-cause mortality was 23% (n=7) with similar mortality rates in patients who had HIT confirmed vs. HIT likely. Patients who had an IVCF placed within 30 days of HIT diagnosis (27% mortality) and after 30 days of HIT diagnosis (25% mortality) did not have significant difference in six-month all-cause mortality. Our data tracked mortality up to 12 months (27%). Conclusion Our study found a thrombotic rate of 15.4% in HIT patients with IVCF placement, while a rate of thrombosis after IVCF placement in patients without HIT has been reported between 2-30%.2 The rate of new thrombotic events in HIT alone is reported to be 23-35%.3 Our six-month all-cause mortality rate was 26.9%, with mortality directly related to thrombotic events at 7.7%. Six-month mortality associated with HIT without IVCF placement has been reported at 20-30%.4 One patient developed lower extremity phlegmasia, which is reported to be rare in the literature. Our results do not show an increased risk of mortality, DVT, PE, IVC thrombosis, or lower extremity phlegmasia in the setting of IVCF placement in patients diagnosed with HIT, as compared to rates of complications in patients with only HIT or in patients with only IVCF placement. While HIT is associated with an increased risk of thrombosis, and a published small case series (n=10) recommended against placing IVCFs in these patients, our larger, retrospective study does not demonstrate increased thrombotic events in this patient population beyond patients with only HIT or only IVCFs. Full references available upon request 1. Jung, 2011 2. Milovanovic, 2015 3. Bruce, 2003 4. Benjamin, 2016 Disclosures No relevant conflicts of interest to declare.

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Correlation of ELISA Optic Density with Clinical Diagnosis of Heparin-Induced Thrombocytopenia: A Retrospective Study of 104 Patients with Positive Anti-PF4/Heparin Antibodies.

Blood ◽

10.1182/blood.v120.21.2242.2242 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2242-2242

Author(s):

Marc-Andre Pearson ◽

Normand Blais

Keyword(s):

Retrospective Study ◽

Likelihood Ratio ◽

Clinical Diagnosis ◽

Conflicts Of Interest ◽

Density Level ◽

Laboratory Findings ◽

Heparin Induced Thrombocytopenia ◽

Retrospective Diagnosis ◽

Optic Density ◽

Significant Difference

Abstract Abstract 2242 Introduction Heparin-induced thrombocytopenia (HIT), which is characterized by thrombotic events, is a serious complication of heparin use. Its diagnosis is primarily clinical but can be supported by several laboratory tests. ELISA for anti-PF4/heparin antibodies, which is the most widely-available technique, is expressed in terms of optical density (OD) results. This test was shown to have good sensitivity but poor positive predictive value. The goal of this study is to correlate OD levels with the probability of HIT diagnosis. Contrarily to previous studies where the diagnosis of HIT was mainly based on laboratory findings, we have defined HIT based on the strength of the original diagnosis, the retrospective adjudication performed by one or two clinicians familiar with HIT diagnosis, the absence of thrombosis and the absence of a clearly identified alternative diagnosis for the thrombocytopenia. Method We conducted a retrospective study involving 104 patients with a positive ELISA for anti-PF4/heparin antibodies (Stago Asserachrom HPIA essay) between 2008 and May 2012. For all patients who were hospitalized at the CHUM, an extensive chart review was performed from the day of admission and for a period of 3 months following the positive ELISA assay. For each patient that was included in the study, the Greinacher clinical score was calculated. According to the clinical evolution and the laboratory results, a final, clinical, retrospective diagnosis was made for each patient (which was either HIT-positive or HIT-negative). The OD result was collected only after diagnosis was made. Results In our study, 28.8% of the patients were HIT-positive and 71.2% HIT-negative. There was a statistically significant difference in ELISA results between these two groups (Figure 1). Mean OD was 0.83 (SD ± 0.62) for HIT-negative patients, versus 2.15 (SD ± 0.76) for HIT-positive ones (P< 0.001). Figure 2 shows a distribution of patients according to Greinacher score and final diagnosis. In patients with low clinical probability, HIT-positive patients had statistically higher mean OD than HIT-negative patients (3.0 ± 0.14 versus 0.66 ± 0.36, P<0.01). This was also true for patients with intermediate probability score (1.88 ± 0.78 versus 0.67 ± 0.29, P<0.01). In high probability patients, there was only one patient with negative diagnosis. Patients were divided into 3 groups according to their OD result. There were 59 patients who had an OD of less than 1.0. Of these, only 2 (3.4%) had a positive diagnosis for HIT. In comparison, the percentage of HIT-positive patients was 45.5% (10 patients out of 22) for the group with OD 1.0–2.0, and 78.2% (18 out of 23) when OD was more than 2.0. A Roc curve (figure 3) showed that specificity of the test increased from 28% to 78% when the cut-off for OD was moved from baseline threshold to 1.0 unit. In this situation, the sensitivity of the test was only decreased to 93%. Conclusion This study is a clinical confirmation that ELISA OD results are directly correlated with the probability of a clinical diagnosis of HIT. An OD of less than 1.0 was shown to be rarely associated with clinical HIT. To the opposite, OD values above 2.0 are highly correlated with the diagnosis, and should be considered as strong evidence for clinical HIT. Furthermore, this study showed that OD results are useful when used in addition to the clinical scores. In fact, OD could discriminate between positive and negative diagnosis in patients with low and moderate clinical suspicion. Finally, the use of baseline threshold (which corresponds to OD of 0.4) was associated with a very low specificity and likelihood ratio for HIT diagnosis. By increasing the threshold to 1.0, the specificity was increased to 78.4% with a sensitivity of 93.3%. ELISA specificity and likelihood ratio were directly proportional to optic density level. Disclosures: No relevant conflicts of interest to declare.

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The effect of additional antimicrobial therapy on the outcomes of patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Respiratory Research ◽

10.1186/s12931-021-01839-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Ching-Yi Chen ◽

Chao-Hsien Chen ◽

Cheng-Yi Wang ◽

Chih-Cheng Lai ◽

Chien-Ming Chao ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Usual Care ◽

Antimicrobial Therapy ◽

Antimicrobial Agents ◽

Meta Analysis ◽

Lung Function Decline ◽

Increased Risk ◽

Significant Difference ◽

All Cause Mortality

Abstract Background The effect of additional antimicrobial agents on the clinical outcomes of patients with idiopathic pulmonary fibrosis (IPF) is unclear. Methods We performed comprehensive searches of randomized control trials (RCTs) that compared the clinical efficacy of additional antimicrobial agents to those of placebo or usual care in the treatment of IPF patients. The primary outcome was all-cause mortality, and the secondary outcomes were changes in forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and the risk of adverse events (AEs). Results Four RCTs including a total of 1055 patients (528 receiving additional antibiotics and 527 receiving placebo or usual care) were included in this meta-analysis. Among the study group, 402 and 126 patients received co-trimoxazole and doxycycline, respectively. The all-cause mortality rates were 15.0% (79/528) and 14.0% (74/527) in the patients who did and did not receive additional antibiotics, respectively (odds ratio [OR] 1.07; 95% confidence interval [CI] 0.76 to 1.51; p = 0.71). No significant difference was observed in the changes in FVC (mean difference [MD], 0.01; 95% CI − 0.03 to 0.05; p = 0.56) and DLCO (MD, 0.05; 95% CI − 0.17 to 0.28; p = 0.65). Additional use of antimicrobial agents was also associated with an increased risk of AEs (OR 1.65; 95% CI 1.19 to 2.27; p = 0.002), especially gastrointestinal disorders (OR 1.54; 95% CI 1.10 to 2.15; p = 0.001). Conclusions In patients with IPF, adding antimicrobial therapy to usual care did not improve mortality or lung function decline but increased gastrointestinal toxicity.

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Abstract WP112: Thrombolysis for AIS in the Unwitnessed or Extended Therapeutic Time Window: A Systematic Review and Meta-Analysis

Stroke ◽

10.1161/str.51.suppl_1.wp112 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Aristeidis H Katsanos ◽

Konark Malhotra ◽

Amrou Sarraj ◽

Andrew Barreto ◽

Martin Köhrmann ◽

...

Keyword(s):

Symptom Onset ◽

Time Window ◽

Meta Analysis ◽

Onset Time ◽

Intravenous Thrombolysis ◽

Functional Independence ◽

Functional Improvement ◽

Increased Risk ◽

Significant Difference ◽

All Cause Mortality

Introduction: We sought to assess the utility of intravenous thrombolysis (IVT) treatment in acute ischemic stroke (AIS) patients with unclear symptom onset time or outside the 4.5 hour time window, selected by advanced neuroimaging. Methods: We performed random-effects meta-analyses on the unadjusted and adjusted for potential confounders associations of IVT (alteplase 0.9 mg/kg) with the following outcomes: 3-month favorable functional outcome [FFO, modified Rankin Scale (mRS) scores: 0-1], 3-month functional independence (FI, mRS-scores: 0-2), 3-month mortality, 3-month functional improvement (assessed with ordinal analysis on the mRS-scores), symptomatic intracranial hemorrhage (sICH) and complete recanalization (CR). Results: We identified 4 eligible RCTs (859 total patients). In unadjusted analyses IVT was associated with higher likelihood of 3-month FFO (OR=1.48, 95%CI:1.12-1.96), FI (OR=1.42, 95%CI:1.07-1.90), sICH (OR=5.28, 95%CI:1.35-20.68) and CR (OR=3.29, 95%CI:1.90-5.69), with no significant difference in the odds of all-cause mortality risk at three months (OR=1.75, 95%CI: 0.93-3.29). In the adjusted analyses IVT was also associated with higher odds of 3-month FFO (OR adj =1.62, 95%CI:1.20-2.20), functional improvement (OR adj =1.42, 95%CI: 1.11-1.81) and sICH (OR adj =6.22, 95%CI: 1.37-28.26). There was no association between IVT and FI (OR adj =1.61, 95%CI: 0.94-2.75) or all-cause mortality at three months (OR adj =1.75, 95%CI: 0.93-3.29). No evidence of heterogeneity was evident in any of the analyses (I 2 =0). Conclusion: IVT in AIS patients with unknown symptom onset time or elapsed time from symptom onset more than 4.5 hours, selected with advanced neuroimaging, results in a higher likelihood of complete recanalization and functional improvement at three months despite the increased risk of sICH.

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Prognosis of adult idiopathic inflammatory myopathy-associated interstitial lung disease: a retrospective study of 679 adult cases

Rheumatology ◽

10.1093/rheumatology/keaa372 ◽

2020 ◽

Author(s):

Shan Li ◽

Yuxin Sun ◽

Chi Shao ◽

Hui Huang ◽

Qian Wang ◽

...

Keyword(s):

Prognostic Factors ◽

Retrospective Study ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Inflammatory Myopathy ◽

Idiopathic Inflammatory Myopathy ◽

Mortality Rates ◽

Trna Synthetase ◽

Significant Difference ◽

All Cause Mortality

Abstract Objectives Few studies have investigated the prognostic factors for idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) across different clinical/serological phenotypes. Methods We conducted a retrospective analysis of patients diagnosed with IIM between January 2012 and December 2017. Results Of the 760 IIM cases registered, 679 adult cases were included in this study. ILD was present in 508 cases, and the presence of ILD in the clinically amyopathic DM, DM and PM groups was 92.7, 73.6 and 55.1%, respectively (P < 0.01). The prevalence of ILD in the anti-synthetase antibody (ASA)+-IIM group was higher than that in ASA–-IIM group (95.2 vs 72.4%, P < 0.01); no such difference was found between the anti-histidyl-tRNA synthetase (Jo-1)+-IIM and Jo-1–ASA+-IIM groups (93.0 vs 98.5%, P > 0.05). The prevalence of ILD in the melanoma differentiation-associated protein-5 (MDA-5)+-IIM group was higher than that in MDA-5–-IIM group (97.8 vs 72.1%, P < 0.01). Among adults with IIM, men with concurrent ILD, who were older than 50 years, were most likely to die. No significant difference was found in the all-cause mortality rates between DM-ILD and clinically amyopathic DM-ILD groups (33.3 vs 23%, P > 0.05), although both were higher than that in PM group (13.2%, P = 0.01 and P < 0.05, respectively). No difference was found in the all-cause mortality rates between MDA5–ASA–-IM-ILD and MDA5–ASA+-IM-ILD groups (17.2 vs 12.8%, P > 0.05), and both were lower than that in MDA5+ASA–-IM-ILD group (33.7%, P < 0.05). Conclusion The prevalence of ILD in IIM and the prognosis of IIM-ILD patients may vary depending on the statuses of the ASA and MDA-5 antibodies.

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The safety of morphine use in acute coronary syndrome: a meta-analysis

Heart Asia ◽

10.1136/heartasia-2018-011142 ◽

2019 ◽

Vol 11 (1) ◽

pp. e011142 ◽

Cited By ~ 1

Author(s):

Rugheed Ghadban ◽

Tariq Enezate ◽

Joshua Payne ◽

Haytham Allaham ◽

Ahmad Halawa ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Major Bleeding ◽

Pain Control ◽

Controlled Trial ◽

Cochrane Central Register ◽

Minor Bleeding ◽

Coronary Syndrome ◽

Increased Risk ◽

Significant Difference ◽

All Cause Mortality

BackgroundMorphine is widely used for pain control in patients with acute coronary syndrome (ACS). Several studies have questioned the safety of morphine in this setting with a concern of interaction with and reduced efficacy of antiplatelet agents.ObjectiveThis study aims to systematically review the safety of morphine use in ACS.MethodsMEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were queried from inception through April 2018. Studies comparing morphine to nonmorphine use in ACS were included. Study endpoints included: in-hospital myocardial infarction (MI), all-cause mortality, stroke, major bleeding, minor bleeding and dyspnoea.ResultsA total of 64 323 patients with ACS were included from eight studies, seven of which were observational studies and one was a randomised controlled trial. The use of morphine was associated with increased risk of in-hospital recurrent MI (OR 1.30, 95% CI 1.18 to 1.43, p < 0.00001). There was, however, no significant difference in terms of all-cause mortality (OR 0.87, 95% CI 0.62 to 1.22, p = 0.44), stroke (OR 0.81, 95% CI 0.39 to 1.66, p = 0.57), major bleeding (OR 0.49, 95% CI 0.24 to 1.00, p = 0.05), minor bleeding (OR 0.98, 95% CI 0.41 to 2.34, p = 0.97), or dyspnoea (OR 0.55, 95% CI 0.16 to 1.83, p = 0.33).ConclusionThe use of morphine for pain control in ACS was associated with an increased risk of in-hospital recurrent MI. Randomised clinical trials are needed to further investigate the safety of morphine in ACS.

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P4792Dabigatran versus vitamin K antagonists in patients with atrial fibrillation and valvular heart disease

European Heart Journal ◽

10.1093/eurheartj/ehz745.1168 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

J E Strange ◽

C Sindet-Pedersen ◽

L Staerk ◽

E L Grove ◽

T A Gerds ◽

...

Keyword(s):

Atrial Fibrillation ◽

Heart Disease ◽

Vitamin K ◽

Valvular Heart Disease ◽

Cox Regression ◽

Absolute Risk ◽

Risk Difference ◽

Increased Risk ◽

Significant Difference ◽

All Cause Mortality

Abstract Background Atrial fibrillation (AF) and valvular heart disease (VHD) are both associated with an increased risk of stroke. Outside post-hoc analyses of randomized controlled trials, knowledge on the effectiveness and safety of dabigatran in patients with AF and VHD is scarce. Objectives To compare the risk of all-cause mortality, stroke, and bleeding in patients with AF and VHD treated with dabigatran or a vitamin K antagonist (VKA). Methods All Danish residents are provided a unique personal identification number enabling cross-linking of data from Danish nationwide registries. We identified all patients with AF and VHD initiating treatment with dabigatran or VKA between the 22nd of August 2011 and the 31st of December 2014. We defined VHD as aortic stenosis/regurgitation, mitral regurgitation, bioprosthetic heart valves, mitral-, and aortic valve repair. Outcomes were all-cause mortality, stroke, and bleeding. 2-year standardized absolute risks were calculated from cause-specific Cox regression models with death as competing risk. Results In total, 599 (27.3%) and 1,596 (72.7%) patients initiated treatment with dabigatran and VKA. The 2-year standardized absolute risk of all-cause mortality (95% CI) for VKA was 27.6% (25.1% to 30.1%) and 25.4% (21.8% to 29.0%) for dabigatran with a corresponding absolute risk difference of −2.2% (−6.3% to 1.9%) (Figure 1). The 2-year standardized absolute risk of stroke for VKA was 3.4% (2.3% to 4.5%) and 3.9% (2.2% to 5.5%) for dabigatran with a corresponding absolute risk difference of 0.5% (−1.6% to 2.5%). Lastly, the 2-year standardized absolute risk of bleeding for VKA was 8.2% (6.6% to 9.7%) and 7.6% (5.1% to 10.1%) for dabigatran with a corresponding absolute risk difference of −0.5% (−3.4% to 2.4%). Figure 1 Conclusions In this nationwide cohort study, we found no significant difference in the risk of all-cause mortality, stroke, or bleeding in patients with AF and VHD when comparing VKA to dabigatran.

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The Prohibitin 3′ Untranslated Region Polymorphisms Are Associated with AML Susceptibility.

Blood ◽

10.1182/blood.v114.22.5038.5038 ◽

2009 ◽

Vol 114 (22) ◽

pp. 5038-5038

Author(s):

Hye-Ran Kim ◽

Myung-Geun Shin ◽

Sun-Seog Kweon ◽

Hee-Nam Kim ◽

Hyeoung-Joon Kim ◽

...

Keyword(s):

Untranslated Region ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Inhibitory Effects ◽

Increased Risk ◽

Significant Difference ◽

Hardy Weinberg Equilibrium ◽

Control Study ◽

Increased Susceptibility ◽

Subsequent Risk

Abstract Abstract 5038 The prohibitin gene, which is located on human chromosome 17q21 encodes a certain regulatory RNA molecule responsible for inhibitory effects and the respective tumor suppressor function. Common C/T and A/G polymorphisms occur at nucleotide 10701 and 10730 respectively in the 3' untranslated region (UTR) of the prohibitin gene. Recent findings indicate that presence of at least one mutant allele within the 3' UTR prohibitin gene polymorphism causes inactivation of bioactive RNA, resulting in loss of its pro-apoptotic function and subsequent risk for malignant growth. These observations led to the hypothesis that individual carrying the prohibitin T allele has increased susceptibility to acute myeloid leukemia (AML). To assess this, we carried out a case-control study of the prohibitin genotype in 381 patients with AML and 372 healthy controls. The distribution of genotypes for the prohibitin 3' UTR polymorphism in patients with AML (P=0.79) and controls (P = 0.10) were in Hardy–Weinberg equilibrium. The prohibitin 3'UTR 10701TT genotype was associated with an increased risk for AML (odds ratios (OR)=2.6; 95 percent confidence interval (CI)=1.90 to 6.19, P = 0.031). However, the prohibitin 3'UTR 10730 polymorphism was not related to AML susceptibility. Haplotype (10701T-10730A) increased risk (OR=2.11; CI=1.28-2.94) for AML. There was a significant difference in the frequency of T-allele carriers between the patients and controls (OR=1.34; CI=1.01-1.77; P=0.046). Interestingly, AML patients having 10730GG genotype had shorter overall survival rate than those with AA and AG genotypes. In conclusion, the prohibitin 3'UTR region genotyping is valuable in assessing risk of AML and estimating prognosis. Disclosures No relevant conflicts of interest to declare.

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Cytogenetic Evolution (CE) In Patients (pts) with Low and Intermediate Risk Myelodysplastic Syndromes (MDS) Is Associated with Poor Prognosis

Blood ◽

10.1182/blood.v116.21.2941.2941 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2941-2941

Author(s):

Liunan Li ◽

Elias Jabbour ◽

Gautam Borthakur ◽

Stefan Faderl ◽

Tapan Kadia ◽

...

Keyword(s):

Disease Progression ◽

Cytogenetic Analysis ◽

Conflicts Of Interest ◽

Myelogenous Leukemia ◽

Intermediate Risk ◽

Hematopoietic Stem ◽

Increased Risk ◽

Significant Difference ◽

The Impact ◽

Cytogenetic Evolution

Abstract Abstract 2941 Introduction: MDS is a spectrum of abnormalities in the proliferation and differentiation of hematopoietic stem cells that result in peripheral cytopenias, bone marrow dysplasia and increased risk of transformation to acute myelogenous leukemia (AML). Cytogenetic abnormalities occur in more than 50% of patients (pts) and have an impact on survival and risk of transformation to AML. CE, or acquisition of additional clonal chromosomal abnormalities, has been reported to occur in 30 to 50% of primary MDS pts. Their impact on prognosis and transformation into AML among pts with low and intermediate risk MDS is not known. In this study, we analyzed the impact of CE on prognosis in lower risk MDS. Methods: we reviewed 722 pts clinic records of low and intermediate risk MDS pts at MD Anderson Cancer Center (MDACC) from 2000–2010 and conducted a retrospective analysis of all MDS pts with at least two consecutive cytogenetic analysis (365 patients, 50.6%) and compared the cytogenetic evolution group (CE group) with the group without cytogenetic changes (no CE group). Cytogenetic analysis was performed in the Cytogenetics Laboratory at MDACC. Results: CE was detected in 200 pts (55%). Characteristics of patients with CE are: median age 65 years (23-91), IPSS int-1 79%, diploid CG 42%, excess blasts 25%. Pts with CE were more frequently female (p=0.005), and had more frequently abnormalities of chromosome 5 and 7 (p<0.001) at baseline. There were no statistically significant difference between these two groups (p>0.05) regarding age, WBC, platelet, hgb, ANC, BM blasts percent, diagnosis (RA or RAEB), and IPSS score. There were more chr.-5/-7, insufficient metaphases, and other abnormalities, but less diploid cases in CE group compared with no CE group (p<0.001). History of malignancy (p=0.001) and prior chemotherapy exposure were also associated with CE (p=0.001), but this was not as strong for radiation exposure (p=0.066). Also, more CE patients required therapy for MDS compared to no CE patients (p=0.039). Progression free survival was significantly extended in no CE patients (p=0.02). Overall survival was a longer in no CE (34.1months), compared with CE group (26.2 months), although this was not statistically significant. Conclusion: CE is more commonly observed among pts with high-risk features, and is usually associated with disease progression and resistance. Also, prior malignancy and chemotherapy exposure were associated with CE in this study. This data indicates that genomic instability has a role in disease progression in MDS. Further analysis of CE in MDS is needed. Disclosures: No relevant conflicts of interest to declare.

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Genetic Factors Related with Early Onset of Osteonecrosis of the Jaw in Patients with Multiple Myeloma Under Zoledronic Acid Therapy

Blood ◽

10.1182/blood.v124.21.2115.2115 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2115-2115

Author(s):

Pelagia Melea ◽

Tina Bagratuni ◽

Evangelos Terpos ◽

Evangelos Eleutherakis-Papaiakovou ◽

Maria Gavriatopoulou ◽

...

Keyword(s):

Zoledronic Acid ◽

High Risk ◽

Conflicts Of Interest ◽

Dose Intensity ◽

Osteonecrosis Of The Jaw ◽

Acid Therapy ◽

Ppar Γ ◽

Pathologic Fractures ◽

Increased Risk ◽

Significant Difference

Abstract Bisphosphonates are extensively used in the treatment of myeloma-related bone disease as they reduce pain and skeletal related events (SREs), such as pathologic fractures, need for radiation and surgery to the bone. One of the complications of prolonged therapy with bisphosphonates, especially of amino-bisphosphonates, such as zoledronic acid (ZA) is osteonecrosis of the jaw (ONJ). Recent studies have attempted to correlate specific genetic polymorphisms (SNPs) and ONJ. Such SNPs include cytochrome P4502C8 (CYP2C8; Sarasquete et al, Blood 2008) and peroxisome proliferator-activated receptor gamma (PPAR-γ; Di Martin et al, Br J Haematol 2011) that have been linked to increased risk of ONJ in two different series. The aim of this study was to investigate a possible association between SNPs in CYP2C8 and PPAR-γ and the risk of developing ONJ in a large number of MM patients who received ZA. We screened 36 patients who developed ONJ and 104 patients who did not develop ONJ for the SNPs of interest in PPAR-γ (rs1152003) and CYP2C8 (rs193495) genes by direct sequencing of peripheral blood derived DNA. All patients were treated with similar systemic anti-myeloma therapies during the same period of time, had received only ZA as antiresorptive therapy and were followed prospectively for the development of ONJ in a single center (Department of Clinical Therapeutics, University of Athens, Greece). The median follow up of the cohort was 72 months. The median number of ZA infusions was 27 (range: 4-107). Patients who developed ONJ had a median of 31 infusions versus 25 infusions for patients who did not develop ONJ. However, 31% of patients who developed ONJ had received less than 24 infusions of ZA. Median time to development of ONJ was 47 months (range: 7-182 months). The median relative dose intensity for ZA was 2.85 mg/month; it was 3.3 mg/month for those who developed ONJ and 2.7 mg/month for those who did not. An extraction preceded the development of ONJ in 60% of patients who developed ONJ, it was unprovoked in 20%, it was associated with trauma from dentures in another 15% and in 5% ONJ was preceded by a periodontal and/or periappical inflammation (abscess formation etc). There was no significant difference in frequency of the presence of SNPs in the two studied genes between patients with and without ONJ. However, there is a subset of patients who develop ONJ rather early, after the infusion of relatively few doses of ZA while others develop ONJ after protracted exposure to ZA. Since the most important factor associated with the development of ONJ after ZA therapy in patients with myeloma is the total dose of ZA, we analyzed separately patients who had less than 24 versus those who had at least 24 infusions of ZA. In patients with <24 infusions of ZA, the presence of SNPs in both PPAR-γ and CYP2C8 was associated with a significantly higher probability and a shorter time to development of ONJ. More specifically, the presence of SNPs in the PPAR-γ was associated with a significantly higher risk of development of ONJ with less than 24 ZA infusions (55% versus 16%, p=0.011) and at a significantly shorter time to development of ONJ (19 versus 69 months, p<0.001). The presence of SNPs in the CYP2C8 was associated with a higher risk of developing ONJ with less than 24 ZA infusions (29% versus 7%, p=0.07) and at a shorter time (44% versus 13% at 3 years, p=0.037). Combining the genotype risk, those with high risk of SNPs in both genes had a 70% cumulative incidence of ONJ within 24 months from initiation of ZA versus 17% for those carrying one of the two SNPs and 0% for those without any high risk of SNPs (p<0.001). In conclusion, our data indicate that SNPs in the CYP2C8 and PPAR-γ genes are associated with a risk of early development of ONJ. However, increasing cumulative dose of ZA increases substantially the risk of ONJ in all patients, independently of genotype-defined risk. Disclosures No relevant conflicts of interest to declare.

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Intra operative assessment of the coronal balance in spinal deformity surgery : a technical note and retrospective study

Acta Orthopaedica Belgica ◽

10.52628/87.1.22 ◽

2021 ◽

Vol 87 (1) ◽

pp. 175-179

Author(s):

Thibault Dewilde ◽

Sebastiaan Schelfaut ◽

Sven Bamps ◽

Matthias Papen ◽

Pierre Moens

Keyword(s):

Retrospective Study ◽

Case Series ◽

Technical Note ◽

Coronal Alignment ◽

Level Of Evidence ◽

Coronal Balance ◽

Scoliotic Deformity ◽

Significant Difference ◽

The Mean ◽

The Right

Obtaining a spine that is well balanced after fusion for scoliotic deformity is primordial for the patients’ quality of life. A simple T-shaped instrument combined with standard intraoperative fluoroscopy can be of great help to evaluate the coronal alignment quickly. The aim of this study was to evaluate if a T-shaped device could predict the postoperative coronal balance. Before finalization of the rod fixation, the balance was checked by verifying the relationship between the T-shaped instrument and the upper instrumented vertebra (UIV), and final adjustments were made to correct the coronal balance. A retrospective study was conducted on 48 patients who underwent surgery to correct scoliotic deformity. Intraoperative and postoperative coronal alignment was measured independently by two observers. The mean intraoperative horizontal offset measured between T-shaped instrument and the center of the UIV was 1,69mm to the right with a standard deviation (SD) of 12,43 mm. On postoperative full spine radiographs, the mean offset between the centra sacral vertical line and the center of the UIV was 2,44mm to the left with a SD of 13,10mm. There is no significant difference in coronal balance between both measurements (p=0,12). With this technique we were able to predict the postoperative coronal balance in all but one patient (97,92%). We conclude that the use of a simple T-shaped instrument can provide adequate intraoperative assessment of coronal balance in correcting scoliotic deformity. Level of evidence : IV – case series

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