Onset Of Pulmonary Embolism Research Articles

Risk factors for acute kidney injury and impact of earlier anticoagulation on renal function in patients with normotensive pulmonary embolism: a retrospective cohort study

ObjectiveWe aimed to investigate the risk factors for acute kidney injury (AKI) after normotensive pulmonary embolism (PE) and the impact of anticoagulation on renal recovery.DesignMulticentred, retrospective cohort study.SettingData from four...

Machine-learning-based models assist the prediction of pulmonary embolism in autoimmune diseases: A retrospective, multicenter study.

Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD. In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort. In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone. ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE. Chictr.org.cn : ChiCTR2200059599.

Dust particulate matter increases pulmonary embolism onset: A nationwide time-stratified case-crossover study in China

BackgroundParticulate matter (PM) has been found to elevate the risk of pulmonary embolism (PE) onset. Among the contributors to PM, dust PM stands as the second natural source, and its emissions are escalating due to climate change. Despite this, information on the effect of dust PM on PE onset is scarce. Hence, this study aims to investigate the impacts of dust PM10, dust PM2.5–10, and dust PM2.5 on PE onset. MethodsA nationwide time-stratified case-crossover study was conducted between 2015 and 2020, using data from 18,616 PE onset cases across 1,921 hospitals in China. The analysis employed a conditional logistic regression model to quantify the associations between dust PM10, dust PM2.5–10, and dust PM2.5 and PE onset. Furthermore, the study explored the time-distributed lag pattern of the effect of dust PM on PE development. Stratified analyses were performed based on sex, age, region, and season. ResultsDust PM10, dust PM2.5–10, and dust PM2.5 exhibited significant health effects on PE onset, particularly concerning exposure on the same day. The peak estimates were observed at lag 01 day, with the odds ratio being 1.011 [95 % confidence interval (CI): 1.003, 1.019], 1.014 (95 % CI: 1.003, 1.026), and 1.039 (95 % CI: 1.011, 1.068), for a 10 μg/m3 increase in the concentration of dust PM10, dust PM2.5–10, and dust PM2.5, respectively. In addition, the study identified a higher risk of PE onset associated with dust PM exposure during the warm season than that in cool season, particularly for dust PM2.5. ConclusionsThe findings from this study suggest that short-term exposure to dust PM, particularly dust PM2.5, may trigger PE onset, posing a significant health threat. Implementing measures to mitigate dust PM emissions and protect patients with PE from dust PM exposure is imperative.

Prevention of symptomatic pulmonary embolism for gynecologic malignancies with preoperative asymptomatic venous thromboembolism: GOTIC-VTE trial.

In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Between February 2018 and September 2020, 99 patients were enrolled; of these, 82 patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE. JRCT Identifier: jRCTs031180124.

Prevalence of long-term right ventricular dysfunction after acute pulmonary embolism: a systematic review and meta-analysis

Right ventricular dysfunction (RVD) is associated with adverse outcomes of acute pulmonary embolism (PE). However, there are no studies describing the long-term, full-spectrum right ventricular parameters on morphology, pressure and function at certain follow-up time points after PE onset. More exploration of right ventricular function would provide useful clues for long-term management of patients with PE. For this systematic review and meta-analysis, we completed a literature search in Pubmed, EMBASE and WebofScience (from Jan 1st, 1998 to April 20th, 2023). Studies of patients with acute PE followed-up longer than 3 months with right ventricle assessment and written in English-language were included. Right ventricular function was assessed by either echocardiography or computed tomographic pulmonary angiography (CTPA). The primary outcome was structural and functional parameters of the right ventricle, and the secondary outcomes were functional assessments [New York Heart Association (NYHA) functional classification and 6-min walk test distance (6MWD)], at each follow-up time points. Random effect meta-analyses were performed using R software (PROSPERO: CRD42023433332). A total of 33 studies (3920 patients) were included in the final analysis. The 3-month, 6-month and 1-year prevalence of right ventricular dysfunction (RVD) was 0.34 [95% confidence interval (CI) 0.21-0.48, I2=96%], 0.26 (95% CI 0.17-0.36, I2=93%) and 0.34 (95% CI 0.19-0.48, I2=94%), respectively. Pooled tricuspid annulus plane systolic excursion (TAPSE), right ventricular to left ventricular diameter (RV/LV) ratio and pulmonary artery systolic pressure (PASP) at 1-year was 21.80mm (95% CI 20.08-23.52, I2=93%), 0.64 (95% CI 0.48-0.81, I2=92%) and 27.33mmHg (95% CI 18.88-35.78) (I2=96%), respectively. The proportion of NYHA III-IV was 0.06 (95% CI 0.0-0.12) and the pooled 6MWD was 462.98m (95% CI 447.55-478.41) over 1 year. Patients treated with thrombolysis had lower prevalence of RVD (1-year 0.17 and 0.07 in systemic thrombolysis and catheter-directed thrombolysis, respectively) than those treated with anticoagulation therapy alone (1-year 0.24) but the pooled risk ratio (RR) was not statistically significant. Although the conclusion of this study may be limited by its high heterogeneity from varied study designs, inclusion criteria and definition of RVD of each study, our findings suggested that persistent RVD and functional impairment were of considerable high prevalence during long-term follow-up after acute PE. Treatment strategy may influence the prevalence of long-term RVD. This study is supported by CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-061). The National Key Research and Development Program of China (2016YFC0905600). National High Level Hospital Clinical Research Funding (2022-NHLHCRF-LX-01-02-03). CAMS Institute of Respiratory Medicine Grant for Young Scholars (2023-ZF-8).

腹臥位から仰臥位へ体位交換時に肺血栓塞栓症を発症した重症COVID–19肺炎の2例(Two cases of pulmonary embolism after position change from prone position during mechanical ventilation due to severe COVID–19 pneumonia)

COVID–19肺炎では腹臥位呼吸療法の有効性が注目されている。今回，腹臥位から仰臥位への体位交換時に発症した肺血栓塞栓症を2例経験したので報告する。1例目は59歳の男性，発症11日目に人工呼吸を開始し，15日目から腹臥位呼吸療法を開始した。17日目に仰臥位へ体位交換した30分後より，SpO2が94%から85%へと低下し，心拍数も90bpmから120bpmへ上昇した。D–ダイマーが9.2μg/mLから22.5μg/mLへ上昇していたため，肺血栓塞栓症を疑い，造影CTで左肺動脈血栓が判明した。2例目は46歳の男性，発症13日目で人工呼吸を開始し，同日腹臥位呼吸療法を開始した。14日目に仰臥位へ体位交換した10分後より血圧低下，12分後からSpO2が97%から84%へと低下した。D–ダイマーが5.6μg/mLから48.1μg/mLへ上昇していたことと，心臓超音波検査で右心負荷所見がみられたことから肺血栓塞栓症を疑い，造影CTで左内頸静脈血栓と右肺動脈血栓が判明した。今回の2症例は，いずれも腹臥位から仰臥位に体位交換した際に肺血栓塞栓症を発症しており，いずれも中心静脈カテーテル挿入側の内頸静脈に血栓を認めた。長時間の腹臥位から仰臥位への体位交換は，内頸静脈血栓から肺血栓塞栓症を発症させる可能性が示唆され，バイタルサインに留意して行うことが望ましい。 The prone position during mechanical ventilation has been reported to be effective in respiratory failure caused by COVID–19 pneumonia. We report two cases of pulmonary thromboembolism that may have occurred during return to the supine position. A 59–year–old man, with COVID–19 pneumonia, was put on mechanical ventilation in supine position from day 11 to day 15, and prone position from day 15 to day 17. Thirty minutes after returning to the supine position on day 17, he developed hypoxemia and tachycardia. Pulmonary thromboembolism was suspected based upon elevated D–dimer levels. Echo venogram of the right internal jugular vein showed thrombi, and contrast–enhanced computed tomography (CECT) showed thrombi in the left pulmonary artery. A 46–year–old man, with COVID–19 pneumonia, was put on mechanical ventilation in prone position from day 13 to day 14. On day 14, when he was returned to the supine position, he developed hypotension after 10 minutes, and hypoxemia after 12 minutes. CECT showed thrombi in the left internal jugular vein and right pulmonary artery. During mechanical ventilation, a change to the supine position after prolonged prone position may cause pulmonary thromboembolism from thrombi in the internal jugular vein, and should be performed with attention to vital signs. 腹臥位呼吸療法は，acute respiratory distress syndrome（ARDS）の死亡率を低下させる可能性があり 1，COVID–19肺炎にもしばしば実施される。当院でも，集中治療管理を要するCOVID–19肺炎患者に対し，16時から翌日10時の18時間を腹臥位，残りの6時間を仰臥位とする腹臥位呼吸療法を施行した。腹臥位呼吸療法での合併症として，気管チューブ閉塞，事故抜管，静脈路の事故抜去，褥瘡，視力障害，腕神経叢損傷などが報告されている 2。今回，腹臥位から仰臥位への体位交換を契機に発症した肺血栓塞栓症（pulmonary embolism: PE）を2例経験したので報告する。 なお，本症例の報告は倫理委員会の承諾は不要であり，個人情報保護法に基づいて匿名化がなされ，患者・家族の同意を得ている。 患 者：59歳の男性 既往歴：痛風，脂質異常症 現病歴：発熱・頭痛で発症し，同日SARS–CoV–2 PCR陽性と判明した。発症5日目に酸素化不良のため，当院に入院となった。11日目に呼吸状態悪化のため気管挿管し，人工呼吸管理となった。 入院後経過：気管挿管後より，深部静脈血栓症（deep vein venous thrombosis: DVT）予防を目的として，ヘパリンカルシウム5,000単位の皮下注射を1日2回開始した。発症13日目に撮像した体幹部造影CTでは，PE，DVTともに指摘されなかったが，14日目にD–ダイマーが9.8µg/mLと上昇した。超音波検査で，中心静脈カテーテル挿入側である右内頸静脈に血栓を認め（Fig. 1a），リバーロキサバン15mg内服を開始した。また，13日目に撮像したCTでは背側の無気肺が著明であり，人工呼吸器関連肺炎も併発したため，背面開放と体位ドレナージを目的とし，15日目より腹臥位呼吸療法を開始した。17日目に，腹臥位から仰臥位に体位交換した30分後より，SpO2が94%から85%へと低下し，心拍数も90bpmから120bpmへ上昇した（Fig. 2）。 Case 1: Jugular vein echo (a). major and minor axis image showing right internal jugular vein (white arrow). Chest computed tomography (b). Axial view showing left main pulmonary artery thrombus (white triangle). Case 1: Course at onset of pulmonary embolism. ベッドサイドで可能な検査や理学所見では，気胸や痰による閉塞性無気肺を認めなかった。超音波検査では右心拡大を認めなかったが，依然として右内頸静脈に血栓が存在していた。両側大腿静脈，膝窩静脈には，血栓はみられなかった。右内頸静脈血栓があること，D–ダイマーが22.5µg/mLと上昇（前日9.2µg/mL）していること，また長時間の腹臥位から体位交換をした際に起きた酸素化低下と頻脈であることから，PEを強く疑った。既にリバーロキサバン内服が行われていたが，治療量でなかったため30mgに増量し，翌日待機的に造影CTを施行した。造影CTでは，左主肺動脈に血栓塞栓症がみられた（Fig. 1b）。以上の所見より，腹臥位から仰臥位への体位交換を契機に発症したPEと診断した。 その後，COVID–19肺炎後器質化肺炎に対して，プレドニゾロン60mg/day（1mg/kg）を開始した。発症25日目に38度台の発熱があり，膿性痰が出現したため，人工呼吸器関連肺炎としてピペラシリン・タゾバクタム13.5ｇ/日を投与開始した。その後のCTで，左肺に多発空洞影を認め，肺化膿症と診断した。抗菌薬治療を60日間継続した後，発症93日目に，リハビリテーション目的に転院となった。 患 者：49歳の男性 既往歴：慢性中耳炎 現病歴：咽頭痛・発熱で発症し，翌日SARS–CoV–2 PCR陽性と判明した。呼吸困難感が出現したため，発症11日目に前医入院となった。呼吸状態悪化のため翌日当院に転院となり，13日目に気管挿管を施行し，人工呼吸管理を開始した。 入院後経過：気管挿管後より，DVT予防を目的として，ヘパリンカルシウム5,000単位の皮下注射を1日2回開始した。気管挿管後も酸素化が改善しなかったため，同日夕方より腹臥位呼吸療法を開始した。翌日，腹臥位から仰臥位に体位交換した10分後から，徐々に血圧が低下し，SpO2も低下した（Fig. 3）。 Case 2: Course at onset of pulmonary embolism. ベッドサイドで可能な検査や理学所見では，気胸や痰による閉塞性無気肺を認めなかった。超音波検査では，両側大腿静脈，膝窩静脈には血栓を認めなかったが，左内頸静脈の中心静脈カテーテル周囲に血栓を認め，右心拡大も認めた。左内頸静脈血栓があること，D–ダイマーが48.1µg/mLと上昇（前日5.6µg/mL）していること，右心負荷所見があり，長時間の腹臥位から体位交換をした際に起きた血圧低下，酸素化低下であることから，PEを強く疑った。APTTの目標を50secとしてヘパリンナトリウム14,000U/dayの持続静脈注射を開始し，同日に造影CTを施行した。造影CTでは左内頸静脈（下顎角から胸鎖関節付近の鎖骨下静脈合流部），および右肺動脈に血栓を認めた（Fig. 4a, b）。 Case 2: Chest computed tomography. Axial view showing right pulmonary artery thrombus in the middle lobe (a. white triangle). Axial view showing left internal jugular vein thrombus (b. white arrow). 以上の所見より，腹臥位から仰臥位へ体位交換した際に発症したPEと診断した。発症第15日目に人工呼吸器関連肺炎を発症したため，セフェピム3g/日を投与開始した。16日目に，P/F ratioが191から289へ改善し，18日目に気管チューブを抜去した。また，19日目にヘパリンからリバーロキサバン30mg/dayへ変更し，22日目に前医に再転院となった。 PEの塞栓源は，約90%が下肢あるいは骨盤内の静脈とされている。しかし，2例とも内頸静脈に血栓があり，超音波検査と造影CTで，両下肢静脈内に明らかな血栓はみられなかった。このことから，内頸静脈血栓からの塞栓子が原因で，PEを発症したと考えられる。集中治療を行う場合，内頸静脈への中心静脈カテーテル留置を行う機会が多いが，中心静脈カテーテルの挿入は内頸静脈血栓形成のリスクとして知られている 3。また，2例ともヘパリンの予防投与を行っていたが，中心静脈カテーテル挿入側の内頸静脈に血栓を認めた。COVID–19では，血管内皮細胞にもSARS–CoV–2感染が成立する。ウイルス感染により障害された血管内皮細胞からの凝固第VIII因子とvon Willebrand factorの放出や，サイトカインストームが血栓傾向の誘引となり，深部静脈血栓症の発症率が上昇するとされている 4。 なお，今回の2症例目では，中心静脈カテーテルを挿入した同日16時ごろから翌日10時ごろまで腹臥位呼吸療法を行い，仰臥位に体位交換をした際にPEを生じている。中心静脈カテーテル挿入時の超音波検査では血栓を認めておらず，腹臥位呼吸療法を行っている18時間の間に，血栓が形成された可能性が高い。鎖骨による鎖骨下静脈合流部への圧迫で内頸静脈の血流うっ滞が生じ，内頸静脈血栓の形成に腹臥位が寄与していた可能性が考えられる。1例目においても，長時間の腹臥位が，既存の内頸静脈血栓の伸展を助長した可能性がある。このような血栓形成のリスクが重なり，ヘパリン予防投与を行っていたにもかかわらず血栓が形成されたと考えられる。 DVTは，通常発生部位から中枢へ成長する過程で，血栓中枢端や伸展血栓が遊離，もしくは血栓の静脈壁接着面が剥離して塞栓子となる。関節周囲や下腿筋ポンプ内のような特殊な状況では，起立，歩行などの際に下肢の筋肉が収縮し，伸展血栓が容易に塞栓化しやすいとされている 5。腹臥位呼吸療法において，腹臥位から仰臥位へ体位交換したことを契機としてPEを発症したという報告は，我々の渉猟する限りみられなかったが，脊椎手術では数例報告されている 6, 7。腹臥位中は，鎖骨による圧迫や胸腔内圧上昇に伴い，内頸静脈や下大静脈のうっ滞が起こることが示唆されている。腹臥位から仰臥位への体位交換で，これらが解除されることにより，血行動態が一時的に変化しうる。それにより，体位交換という受動的な運動であっても，長時間の腹臥位の間に伸展，形成された内頸静脈血栓が遊離した可能性が考えられる。 腹臥位から仰臥位に体位交換した際の酸素化低下はしばしば経験され，原病が重篤，あるいは背側無気肺が著明である場合は，対症療法を行うのみで見過ごされてしまう可能性もある。しかし，今回1例目は頻脈，2例目では血圧低下と，SpO2の低下以外にもバイタルサインの変化を認めていた。COVID–19の血栓症発症リスクが高いことも踏まえ 8, 9，PEを鑑別にあげて対応し，治療介入することができた。さらに2例目は，1例目の経験から，仰臥位への体位交換が内頸静脈血栓を塞栓子としたPE発症の契機となる可能性があることを認識していた。そのため，ベッドサイドでの超音波検査で，両側大腿静脈に加え内頸静脈も観察を行い，内頸静脈血栓を認知することができ，PEを鑑別疾患の上位に挙げることができた。なお，両症例ともPE発症日の採血でD–ダイマーの上昇がみられていた。腹臥位呼吸療法施行中のD–ダイマー上昇は，血栓形成もしくは伸展を示唆している可能性があり，仰臥位に復帰した際にバイタルサイン変動がみられた場合には，PEの発症を疑う必要があると考える。なお，ARDS患者の腹臥位では健常人と異なり，換気血流比不均等の改善による右心負荷の軽減や，左心前負荷増大により，心拍出量が増加する 10。仰臥位への体位交換時には，これらの血行動態の変化は速やかに元に戻り，心拍出量は低下する。これは，PEを発症した際の重症度を高める可能性がある。 当院では，腹臥位からの体位交換時はSpO2，心電図，end–tidal CO2などの観血的動脈圧以外の一部モニターを外していた。同様にモニターを外しており初期症状であるバイタルサインの変化を察知できずに 11，心停止まで至った脊椎手術症例の報告もある 6。今回2例とも，モニターは仰臥位復帰後早急に再装着され，バイタルサインの変化に早期に気づくことができた。モニター未装着となる時間を短縮することが，早期にPEの兆候を察知するために重要である。なお，PE発症時にSpO2低下はよくみられるが，より劇的な症例では急激にend–tidal CO2が低下することが知られており，脊椎手術中end–tidal CO2低下がPE発症覚知の一助となった報告もある 12。当院では腹臥位から仰臥位への体位交換時，end–tidal CO2モニターを外していることがほとんどであった。end–tidal CO2モニターは，頭側で回路混線せずに装着したまま安全に体位交換できるため，今後の腹臥位療法では，装着を継続して体位交換することも，検討の余地がある。 腹臥位呼吸療法時は，内頸静脈還流のうっ滞などにより形成・伸展した内頸静脈血栓が，仰臥位への体位交換で遊離しPEを発症する恐れがあるため，注意して体位交換を行う必要がある。また，腹臥位からの体位復帰時に生じる循環虚脱や肺酸素化能の低下にはPEが関与している可能性があり，これらのバイタルサインの変化を早期に察知するために，装着可能なモニターはできる限り装着を継続し，困難な場合にもモニター未装着時間を可能な限り短縮して迅速な体位交換を行うことが望ましい。 著者全員に本論文に関する利益相反はない。

Prognostic factors of systemic lupus erythematosus patients with pulmonary embolism: An 11-year cohort study.

Systemic lupus erythematosus (SLE) patients have a higher risk of pulmonary embolism (PE) which is life-threatening, but there has been no research focusing on the prognosis of SLE patients with PE. This study was conducted to explore the prognostic factors of mortality in SLE patients with PE. In this observational cohort study, SLE inpatients with PE treated at Peking Union Medical College Hospital between January 2010 and December 2020 were included and age, gender, smoking history, the onset of SLE and PE, organ involvement, SLE disease activity index-2000 (SLEDAI-2K), severity of PE, and treatment regimen were collected. Kaplan-Meier survival curve and univariate and multivariate COX regression analysis were used to explore the prognostic factors of SLE patients with PE. A total of 86 SLE patients with PE were enrolled, with the age of 37.72±15.79 years old and the average lupus duration of 46.5 months. 17 patients (19.77%) died. 1- and 3-year survival rates were 83.40% and 79.40%. Thrombocytopenia (log-rank p = 0.004) and lymphocytopenia (log-rank p = 0.030) were predictors of mortality, and effective anticoagulation (log-rank p = 0.032), hydroxychloroquine (HCQ) (log-rank p = 0.021) were protective factors of mortality in SLE patients with PE. Effective anticoagulation was an independent protective factor of mortality in SLE patients with PE (HR = 0.14, p = 0.006). Patients with thrombocytopenia and lymphocytopenia are more likely to develop a poor prognosis. Effective anticoagulation and HCQ could improve the prognosis.

P12.05 Pulmonary embolism in neuroncological patients: Monoistitutional experience

Abstract BACKGROUND Venous thromboembolism (VTE) is a frequent and potentially fatal event in cancer patients. Patients with brain tumors in particular have one of the highest risk of developing VTE among cancer patients (25–39%), contributing significantly to mortality and morbidity. VTE is particularly high in the postoperative period, with almost half of the events occurring at that time, but it also persists in the first 12 months, with a risk ranging between 7–28%. Despite the high incidence of VTE in patients with brain tumors, to date there are no sufficient data to predict teh real risk or to lead to a standardized approach in the management of these patients. We conducted a retrospective analysis to assess the prevalence of pulmonary embolism complication in patients with brain tumors treated by our Institution in the last 3 years. MATERIAL AND METHODS Clinical data, treatment modalities, and patients outcome were analyzed and described. In particular, In particular, the dosages of D-dimer performed in the clinical suspicion of thromboembolic complication were reviewed, and the data of patients with pulmonary embolism confirmed by chest CT scan were recorded. RESULTS Overall 372 patients were treated at our Institute in the last 3 years for brain tumors. 14 patients (3.7%) 9 males and 5 females, with a median age of 62 years and a median KPS of 80, affected by glioblastoma (69%), cerebral lymphoma (23%) and low-grade gliomas (8%) had pulmonary embolism during the course of treatment. None of the 14 patients was on prophylactic anticoagulant treatment. One patient developed the embolic event during radio and chemotherapy concomitant treatment, 5 patients during chemotherapy only (2 with PCV scheme and 3 with fotemustine scheme), 2 patients with primary nervous system lymphoma during methotrexate infusion. Six patients were not receiving any chemotehrapy treatment at the onset of pulmonary embolism. At the time of pulmonary embolism diagnosis, more than half of the patients had clinical signs suggestive of deep venous thrombosis, confirmed by echocolor Doppler, 10/14 patients were treated with high-dose enoxaparin, the others with fondaparinux and calcium nadroparin. CONCLUSION Despite the high incidence of VTE in patients with brain tumors, there is currently no gold standard in the prevention and treatment of this complication. In fact, many questions are still open, for example the efficacy of low molecular weight heparins vs oral anticoagulants as a prophylactic treatment, the timing of onset and the real risk of bleeding. Future prospective studies should be designed to identify parameters for optimize stratification of thrombotic / haemorrhagic risk in this group of patients. This could allow patients at high risk to undergo more aggressive prophylactic therapy or closer clinical-instrumental surveillance, without incurring the opposite risk of bleeding.

ENDOGENOUS THROMBIN GENERATION POTENTIAL IN PATIENTS WITH PULMONARY EMBOLISM AND ITS RELEVANCE TO THROMBOTIC AND INFLAMMATORY BIOMARKERS

SESSION TITLE: Pulmonary Vascular Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Pulmonary embolism (PE) is a catastrophic outcome in patients with venous thrombosis. In the United States around 900,000 people (1 to 2 per 1,000) patients are affected each year with the mortality rate ranging from 10 – 30 %. Inflammation, hemostatic dysregulation and vascular complications contribute to the pathogenesis of PE. Endogenous thrombin generation contributes to the overall pathology of PE. The purpose of this study is to investigate endogenous thrombin potential (ETP) and the circulating biomarkers of inflammation, hemostatic activation and endothelial dysfunction in plasma samples obtained from the patients at the onset of PE. METHODS: Citrated blood samples from 78 patients with confirmed PE were collected at Loyola University Medical Center and Gottlieb Memorial Hospital under an IRB approved protocol. Normal human plasma (NHP) comprised of 25 male and 25 female samples were obtained from a commercial source (George King Biomedical, Overland park, KS.) Thrombin generation studies were carried out using a commercially available a kinetic system (Diagnostica Stago, Paris, France). Thrombin generation parameters such as peak thrombin, lag time and area under the curve (AUC) were compiled. Frozen samples were retrospectively analyzed for biomarkers, including D-Dimer, PAI-1, TNFa, IL6, IL1b, VEGF and TFPI using commercially available sandwich ELISA methods. Results were compiled as mean ± SD and analyzed for significance and correlation. Applicable statistical analysis was carried out by using GraphPad Prism software. RESULTS: On a cumulative basis, PE patients showed a wide variation in thrombin generation parameters. Peak thrombin levels (91.1 nM vs 160.0 nM) and AUC (554.7 nM*min vs 700.9 nM*min) were decreased in PE patients while lag time was increased (6.41 min vs 2.7 min). Biomarkers analysis showed elevated levels of D-Dimer (7521.3 ng/ml) in comparison to NHP (192.8 ng/ml), PAI (67.3 ng/ml) in comparison to NHP (10.5 ng/ml), TNF-a (3.2 pg/ml) in comparison to NHP (1.9 pg/ml), IL6 (99.9 pg/ml) in comparison to NHP (1.24 pg/ml), IL1b (1.6 pg/ml) in comparison to NHP (0.79 pg/ml) and TFPI (139.1ng/ml) in comparison to NHP (62.3 ng/ml) while and VEGF (31.24 pg/ml) levels were decreased in comparison to NHP (45.5 pg/ml. The biomarker levels did not show any correlation with peak thrombin levels with the exception of VEGF and TFPI. Samples with higher thrombin generation (>150 nM) showed marked elevation of all of the biomarkers studied. CONCLUSIONS: PE patients exhibit a wide variation in endogenous thrombin generation parameters. However, biomarkers of hemostatic activation, vascular dysfunction and inflammation were increased. CLINICAL IMPLICATIONS: Measurement of thrombin generation parameters along with the biomarkers of inflammation and endothelial dysfunctions may be useful in the overall management of PE patients. DISCLOSURES: No relevant relationships by Emily Bontekoe, source=Web Response No relevant relationships by Yevgeniy Brailovsky, source=Web Response No relevant relationships by Amir Darki, source=Web Response No relevant relationships by Jawed Fareed, source=Web Response No relevant relationships by ambar Farooqui, source=Web Response No relevant relationships by Debra Hoppensteadt, source=Web Response No relevant relationships by Omer Iqbal, source=Web Response No relevant relationships by Fakiha Siddiqui, source=Web Response

Inhaled nitric oxide has pulmonary vasodilator efficacy both in the immediate and prolonged phase of acute pulmonary embolism.

Inhaled nitric oxide (iNO) effectively reduces right ventricular afterload when administered in the immediate phase of acute pulmonary embolism (PE) in preclinical animal models. In a porcine model of intermediate-risk PE, we aimed to investigate whether iNO has pulmonary vasodilator efficacy both in the immediate and prolonged phase of acute PE. Anesthetized pigs (n = 18) were randomized into three subgroups. An acute PE iNO-group (n = 6) received iNO at 40 ppm at one, three, six, nine and 12 hours after onset of PE. Vehicle animals (n = 6) received PE, but no active treatment. A third group of sham animals (n = 6) received neither PE nor treatment. Animals were evaluated using intravascular pressures, respiratory parameters, biochemistry and intracardiac pressure-volume measurements. The administration of PE increased mean pulmonary artery pressure (mPAP) (vehicle vs sham; 33.3 vs 17.7 mmHg, p < 0.0001), pulmonary vascular resistance (vehicle vs sham; 847.5 vs 82.0 dynes, p < 0.0001) and right ventricular arterial elastance (vehicle vs sham; 1.2 vs 0.2 mmHg/ml, p < 0.0001). Significant mPAP reduction by iNO was preserved at 12 hours after the onset of acute PE (vehicle vs iNO; 0.5 vs -3.5 mmHg, p < 0.0001). However, this response was attenuated over time (p = 0.0313). iNO did not affect the systemic circulation. iNO is a safe and effective pulmonary vasodilator both in the immediate and prolonged phase of acute PE in an in-vivo porcine model of intermediate-risk PE.

Influence of weather and air pollution on the occurrence of idiopathic pulmonary embolism in the region of Sousse (Tunisia).

Pulmonary embolism (PE) is the most serious manifestation of thromboembolic conditions. Its incidence varies considerably between countries, suggesting its interaction with the external environment. To analyze the influence of climate and air pollution on the occurrence of idiopathic PE in the region of Sousse (Tunisia). A total of 142 patients with idiopathic PE at two academic hospitals in Sousse (Tunisia) were enrolled in the study over a 7-year period. An analysis of two time series (environmental data and PE cases) was performed. Climatic data were collected from the National Institute of Meteorology. Air pollution data were obtained from the modeling platform of the National Agency for Protection of the Environment. The year 2015 was marked by the occurrence of the highest number of cases (24.6%). A statistically significant decrease in PE risk of 41.9% was observed during the summer with an OR of 0.59 (95% CI [0.36-0.94] and p = 0.026), compared with other seasons. Poisson GLM regression showed a significant increased risk of PE of 3.3% for each 1°C temperature drop. After multiple binary logistic regression, the elevation of PM10 concentration was independently associated with an increased risk of PE (p < 10-3, OR 79.55, 95% CI [42.28-149.6]). Some environmental parameters may predispose to the onset of idiopathic PE. Understanding their accurate influence may have preventive and curative implications.

Venous Thromboembolism in Lower Extremity Amputees: A Systematic Review of the Literature

Patients undergoing lower extremity amputation (LEA) are at risk of developing deep venous thrombosis (DVT) and pulmonary embolism (PE), but no generally accepted prevention guidelines exist. This systematic review aimed at understanding the incidence of VTE with or without thromboprophylaxis in adult patients with major lower extremity amputation (LEA). Primary outcomes were onset of DVT, PE, or mortality. Secondary outcomes were any major adverse events due to treatment. We searched English language full-text papers in multiple databases using keywords, including amputation/adverse effects, amputation/complications, venous thromboembolism, deep vein thrombosis, and pulmonary embolism. Twenty-eight studies providing observations for 4,841 patients were selected. The fatal PE risk was 2.6% without prophylaxis and significantly decreased to a non-zero residual risk of 0.9% with VTE prophylaxis. Above-knee amputees were at greatest risk of VTE and subsequent complications. The risk was not confined to the amputated stump and can involve the contralateral limb. The role of compression ultrasonography screening in asymptomatic patients remains controversial in various populations at risk for VTE. All patients undergoing major LEA should be considered at high risk for the development of VTE, even after discharge from hospital. We recommend prophylactic anticoagulation (if not contraindicated) and clinical surveillance in all patients undergoing LEA and further studies to determine the optimal prophylactic strategy. Disclosures No relevant conflicts of interest to declare.

Clozapine-Associated Pulmonary Embolism: A High-Mortality, Dose-Independent and Early-Onset Adverse Effect.

Recent epidemiological studies have identified an excess of pulmonary embolism (PE) cases in patients treated with antipsychotic drugs. The findings are particularly relevant for patients treated with clozapine, which has many potentially life-threatening adverse drug effects. Among these adverse drug effects are myocarditis and agranulocytosis that have early onset and are dose independent, but also seizures and myocardial repolarization delay, which are dose dependent and may occur at any time. Together with death rates, these variables have important implications for clinical practice. Study Question: What are the time of onset, dose relationship, and mortality of clozapine-associated PE? The published case reports of clozapine-associated PE were identified in a MEDLINE search. Cases occurring within 6 months of starting clozapine were considered to have early onset. Dosages of clozapine at the time of PE were defined as low (200 mg/d or less) or high (300 mg/d or greater). Patient outcome was divided into survival of the PE event and death. The search identified 23 cases of clozapine-associated PE. The PE had early onset (6.4 ± 7.0 weeks) in 20 patients (87%, 95% confidence interval 67.9%-95.5%). PE occurred in 9 patients treated with low doses (152.8 ± 50.7 mg/d) and in 11 patients on high doses (372.7 ± 127.2 mg/d) of clozapine. Six patients (26.1%, 95% confidence interval 12.6%-46.5%) died. A systematic review of the published case reports of clozapine-associated PE indicates that this adverse effect is highly lethal, has early onset and is dose independent. The findings should prompt careful monitoring and consideration of prophylactic treatment for venous thromboembolism for 6 months after starting treatment with clozapine.

Brief cardiovascular imaging with pocket-size ultrasound devices improves the accuracy of the initial assessment of suspected pulmonary embolism

Pulmonary embolism onset is frequently neglected due to the non-specific character of its symptoms. Pocket-size imaging devices (PSID) present an opportunity to implement imaging diagnostics into conventional physical examination. The aim of this study was to test the hypothesis that supplementation of the initial bedside assessment of patients with suspected pulmonary embolism (PE) with four-point compression venous ultrasonography (CUS) and right ventricular size assessment with the use of PSID equipped with dual probe could positively influence the accuracy of clinical predictions. A single-centre, prospective analysis was conducted on 100 patients (47 men, mean age 68 ± 13 years) with suspected PE. Clinical assessment on the basis of Wells and revised Geneva score and physical examination were supplemented with CUS and RV measurements by PSID. The mean time of PSID scanning was 4.9 ± 0.8 min and was universally accepted by the patients. Fifteen patients had deep venous thrombosis and RV enlargement was observed in 59 patients. PE was confirmed in 24 patients. If the both CUS was positive and RV enlarged, the specificity was 100% and sensitivity 54%, ROC AUC 0.771 [95% CI 0.68–0.85]. The Wells rule within our study population had the specificity of 86% and sensitivity of 67%, ROC AUC 0.776 (95% CI 0.681–0.853, p < 0.0001). Similar values calculated for the revised Geneva score were as follows: specificity 58% and sensitivity 63%, ROC AUC 0.664 (95% CI 0.563–0.756, p = 0.0104). Supplementing the revised Geneva score with additional criteria of CUS result and RV measurement resulted in significant improvement of diagnostic accuracy. The difference between ROC AUCs was 0.199 (95% Cl 0.0893–0.308, p = 0.0004). Similar modification of Wells score increased ROC AUC by 0.133 (95% CI 0.0443–0.223, p = 0.0034). Despite the well-acknowledged role of the PE clinical risk assessment scores the diagnostic process may benefit from the addition of basic bedside ultrasonographic techniques.

Epidemiology, Risk Factors, and In-Hospital Mortality of Venous Thromboembolism in Liver Cirrhosis: A Single-Center Retrospective Observational Study.

BackgroundRisk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), may be increased in liver cirrhosis. We conducted a single-center study to explore the epidemiology, risk factors, and in-hospital mortality of VTE in Chinese patients with liver cirrhosis.Material/MethodsAll patients with liver cirrhosis who were consecutively admitted to our hospital between January 2011 and December 2013 were retrospectively included.ResultsOf 2006 patients with liver cirrhosis included, 9 patients were diagnosed with or developed VTE during hospitalization, including 5 patients with a previous history of DVT, 1 patient with either a previous history of DVT or new onset of PE, and 3 patients with new onset of VTE (PE, n=1; DVT, n=2). Risk factors for VTE included a significantly higher proportion of hypertension and significantly higher red blood cells, hemoglobin, alanine aminotransferase, aspartate aminotransferase, prothrombin time (PT), international normalized ratio (INR), D-dimer, and Child-Pugh scores. The in-hospital mortality was significantly higher in patients with VTE than those without VTE (33.3% [3/9] versus 3.4% [67/1997], P<0.001).ConclusionsVTE was observed in 0.4% of patients with liver cirrhosis during hospitalization and it significantly increased the in-hospital mortality. Elevated PT/INR aggravated the risk of VTE.

Subacute pulmonary embolism in a hemodialysis patient, successfully treated with surgical thrombectomy.

A 53-year-old woman was admitted to our hospital with a 1-month history of gradually progressive resting dyspnea and lumbar backache. For the preceding 6years, she had received regular hemodialysis for end-stage renal disease caused by autosomal dominant polycystic kidney disease and had taken tamoxifen for 3years as post-operative chemotherapy for breast cancer. Before admission, the patient's symptoms had been attributed to volume overload, based on right thoracic fluid and leg edema. However, despite volume correction by dialysis therapy, her symptoms had not improved. The patient was transferred to our hospital, where she was diagnosed with subacute pulmonary embolism (PE). Emergent pulmonary thrombectomy was performed using cardio-pulmonary bypass. The patient was discharged from our hospital on post-operative day 23. Recent reports have shown that hemodialysis patients have a relatively higher risk of PE compared with the general population. Our case had additional risk factors for PE: female sex, decreased protein C level, tamoxifen use, and autosomal dominant polycystic kidney disease. These factors may have had a synergistic effect on the onset of PE.

Are Meteorological Parameters a Risk Factor for Pulmonary Embolism? A Retrospective Analysis of 530 Patients.

The influence of meteorological conditions on cardiovascular morbidity and mortality has been known for a long time. However, few reports have been published on the influence of meteorological parameters on the occurrence of acute pulmonary embolism (PE). In this retrospective study, we compared the meteorological parameters between PE patients with risk factors and idiopathic PE patients. Cross-sectional study. Medical documentation of 1180 patients with suspected acute pulmonary embolism diagnosed between January 2010 and December 2012 was retrospectively analyzed. A total of 530 patients with PE confirmed by computed tomography pulmonary angiography and/or ventilation/perfusion scan were included for further analysis. We divided the patients into two groups: PE with risk factors (provoked) and PE without risk factors (unprovoked). The meteorological data were collected from the relevant time period: temperature, humidity, pressure, and wind velocity. As the exact time of PE onset was unknown, the meteorological values attributed to each patient were the means of the values in the months or weeks at the time of diagnosis of PE. The highest numbers of cases were seen in autumn (29.8%), followed by summer (28.9%), spring (22.1%), and winter (19.2%). In terms of months, the greatest number of cases occurred in June (57), followed by November (56) and October (54). Case distribution according to the months and seasons were statistically significant. The wind direction also affected the incidence of PE. There was a statistically significant positive correlation between case frequency and air temperature (r=0.300; p=0.031). No correlation was found between the unprovoked PE cases' monthly distribution and pressure, humidity, or temperature. However, there was a statistically significant positive correlation between the monthly distribution of the group with provoked PE cases and air temperature (r=0.586; p=0.045). A statistically significant inverse correlation between atmospheric pressure and temperature and the number of all PE cases was observed in our study, which is in accordance with other reports. However, in unprovoked PE cases, there was no correlation between meteorological parameters and case incidence.

Value of syncope in patients with high-to-intermediate risk pulmonary artery embolism

Syncope may develop in 9-35% of patients with pulmonary embolism (PE). Despite its severity and importance, the prognostic value of syncope in PE is unclear. We aimed to assess the value of syncope in patients with high-to-intermediate risk PE. A total of 117 patients (62 males and 55 females, median age 51,86 ± 13,4 years) were enrolled into the study. According to the presence of syncope at the onset of PE, all patients were divided into two groups: the syncope group (SG) comprised 35 patients (48.8 ± 15.5 years, male 54.3%) who experienced at least one syncopal episode. The remaining 82 patients (53.4 ± 12.6 years, male 42.7%) without syncope comprised the control group (CG). The main predisposing risk factors of PE were the same except fewer recurrent episodes of PE (8.5 vs. 24.5% in patients from SG (p=0.048). Clinical probability of PE according to the Revised Geneva and Wells scores was high almost in every second patient in both groups (p=NS). There were twice as many patients with a high risk of fatal outcome among patients with syncope in comparison with CG patients (45.7 vs. 25.6%, respectively, p=0.032). Massive PE on computed tomography scans was found again significantly more frequently in patients with syncope (60 vs. 39%, p=0.036). The vast majority (60%) of patients with a history of syncope were treated by thrombolytic therapy (21/35) vs. only 29% of patients without syncopal events (24/82; p=0.001). In-hospital mortality was higher in patients with syncope than the control group (14.2 vs. 8.5%, p=NS). The history of syncope in patients with suspected PE should be considered as a possible criterion of high risk of fatal complications of in-hospital period due to frequent embolism of the pulmonary trunk and its main branches. The use of thrombolytic therapy showed a tendency in improving outcomes.

Deep venous thrombosis after major abdominal surgery in a Ugandan hospital: a prospective study

BackgroundDeep venous thrombosis (DVT) is a major cause of morbidity and mortality among postoperative patients. Its incidence has been reported to range between 16% and 38% among general surgery patients and may be as high as 60% among orthopaedic patients. The most important clinical outcome of DVT is pulmonary embolism, which causes about 10% of hospital deaths. In over 90% of patients, occurrence of DVT is silent and presents no symptoms until onset of pulmonary embolism and/or sudden death. The only effective way of guarding against this fatal condition is therefore prevention/prophylaxis. However, prophylaxis programs are usually based on the estimated prevalence of DVT in that particular community. There is currently no data concerning rates of postoperative DVT in Uganda.The purpose of the study was therefore to determine the prevalence of DVT among postoperative patients at Mulago Uganda’s National Referral Hospital.MethodsA cross sectional descriptive study was conducted between March and June 2011. Eligible patients were identified and screened and patient details were collected. Clinical examinations were done on postoperative days (PODs) 1, 2, and 4 and Doppler ultrasounds were done on POD 7 and POD 21 to assess for DVT. Patients found with DVT were treated appropriately according to local treatment guidelines.ResultsA total of 82 patients were recruited, 4/82 (5%) had DVT. The most common risk factor was cancer. The overall mean age was 45 years (range 20–83 years). The male to female ratio was 1.6:1. Participants with more than one risk factor for DVT were 16/82 (20%).ConclusionsPrevalence of DVT among major post-abdominal surgery patients was low (5%). Cancer was the most common associated factor apart from surgery.

Color doppler ultrasound parameters of deep vein thrombosis of lower limbs may predict the severity of lung perfusion impairment of pulmonary embolism and the level of its mortality risk

Purpose: This study evaluated if the color doppler ultrasound (CDU) parameters such as location, extention and adhesion of thrombi of Deep Vein Thrombosis (DVT) of the lower limbs are predictive of Pulmonary Embolism (PE) complication and its gravity. The latter was assessed on clinical evaluations and imaging including pathognomonic symptoms (dyspnea, thoracic pain and syncope), perfusion lung scans and mortality risk. Methods: 224 patients (pts) diagnosed of PE were subjected to lower limb deep vein CDU and perfusion lung scan within 5 days from admission. The sample was divided into 4 categories by the presence or absence of DVT and its position. The presence or absence of symptoms at the PE emergence, the average Perfusion Damage Index for each category as well as the early mortality risk (calculated on the base of right ventricular disfunction using echocardiography and/or miocardial injury marker based on European Society of Cardiology 2008 guidelines) were also considered. Moreover cancer pts (n° 101, 45%) were evaluated indipendently, as well as pts with freefloating thrombus (FFT) proximal DVT. Results: See Table 1. View this table: Table 1 Conclusions: Pts without DVT had similar clinical and imaging PE results compared to pts with DVT. Distal DVT has less risk and gravity of PE compared to the Proximal DVT, whereas in the FFT and bilateral cases the gravity is higher. We can conclude that neoplasms are the most frequent causes of secondary venous thromboembolic disease, particularly in pts with bilateral DVT as well as in pts without DVT. In our study also emerged that cancer pts are prevalently asymptomatic at onset of PE.