Spontaneous spinal epidural hematoma following IV heparin and catheter-directed thrombolysis for deep vein thrombosis.

Spontaneous spinal epidural hematoma (SSEH) is a rare condition, and it usually presents with acute onset neck or back pain, progressive weakness, and other symptoms of spinal cord compression. Catheter-directed thrombolysis is one option for limbs threatened by iliofemoral venous thrombosis; other options, such as venous thrombectomy (either open or percutaneous), are also available. There are few reported cases of SSEH owing to catheter-directed thrombolysis for deep venous thrombosis (DVT). We present a case of a 65-year-old man who presented with left lower limb extensive iliofemoral DVT and received catheter-directed thrombolysis. The patient initially had rapid improvement in his symptoms with restoration of limb perfusion. However, within 6 hours of starting catheter-directed thrombolysis, the patient developed extensive SSEH and underwent emergent spinal decompression surgery with laminectomy of T11 to T12 with complete resolution of the neurological deficit. Clinicians should consider SSEH in differential diagnosis if the patient develops acute onset neck or back pain after catheter-guided thrombolysis for DVT.

Imaging of Deep Venous Pathology.

Imaging plays an important role in the identification and assessment of clinically suspected venous pathology. The purpose of this article is to review the spectrum of image-based diagnostic tools used in the investigation of suspected deep vein disease, both obstructive (deep vein thrombosis and post-thrombotic vein changes) as well as insufficiency (e.g., compression syndromes and pelvic venous insufficiency). Additionally, specific imaging modalities are used for the treatment and during clinical follow-up. The use of duplex ultrasound, magnetic resonance venography, computed tomography venography and intravascular ultrasound as well as conventional venography will be discussed in this pictorial review.

Pulmonary Embolism in a Young African American Male: A Diagnostic Challenge.

This case report highlights the diagnostic challenges posed by pulmonary embolism (PE) in a young, otherwise healthy 33-year-old African American male with no apparent risk factors. The patient presented with penile pain, swelling, hematuria, flank pain, and rash, and was admitted for balanoposthitis and acute urinary retention. Despite prophylactic heparin, he suffered two cardiac arrests secondary to PE on the fifth day of hospitalization. Prompt thrombolytic therapy and heparin infusion were initiated, but his course was complicated by anuric acute kidney injury requiring hemodialysis, shock liver, and gastrointestinal bleeding. Imaging revealed a substantial thrombus burden in the pulmonary arteries. Notably, a hypercoagulable workup was negative. The absence of typical risk factors, negative hypercoagulable workup, and occurrence of PE despite prophylaxis underscore the importance of vigilance in recognizing atypical presentations. This case emphasizes the need for a high index of suspicion and comprehensive evaluation to diagnose PE in young patients without clear predisposing factors.

Acute and Chronic Ilio-Femoral Venous Reconstruction.

Ilio-femoral venous reconstruction has progressed from being only performed by a limited number of pioneers (often using equipment repurposed from other areas of interventional radiology) to a discrete subspecialty of endovascular practice with a dedicated range of tools and increasingly evolved techniques to secure optimal results. This review is intended to reflect the modern practice of ilio-femoral stenting in the acute and chronic settings, from initial patient assessment to completion of procedure and follow-up care.

A Rare Case of Right Atrial Thrombus in a Patient With Recurrent Classical Hodgkin Lymphoma.

Patients with cancer are at risk for thrombotic complications due to a hypercoagulable state. However, the benefit of prophylactic anticoagulation is unclear in many subsets of these patients. For the first episode of acute thromboembolic disease (VTE) in patients with active cancer, anticoagulant therapy is administered for at least three to six months. Herein, we present a 31-year-old female with active, recurrent stage IIIa classical Hodgkin lymphoma (CHL) (nodular sclerosis), previously treated for proximal upper extremity deep vein thrombosis (DVT), presenting for evaluation of shortness of breath and eventually diagnosed with bilateral pulmonary embolism (PE) secondary to a right atrial thrombus. The patient was successfully treated with surgical resection of the thrombus. With this case report, we hope to encourage physicians to use prophylactic indefinite anticoagulation in patients with active cancer and previous DVT, including patients with upper extremity DVT.

Association between tunneled catheter placement and catheter-associated deep venous thrombosis in adults with inflammatory bowel disease receiving home parenteral nutrition: A retrospective cohort study.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of thrombosis. They often need parenteral nutrition (PN) requiring intravenous access for prolonged periods. We assessed the risk of deep vein thrombosis (DVT) associated with peripherally inserted central catheters (PICCs) and tunneled catheters for patients with IBD receiving home PN (HPN). METHODS: Using the Cleveland Clinic HPN Registry, we retrospectively studied a cohort of adults with IBD who received HPN between June 30, 2019 and January 1, 2023. We collected demographics, catheter type, and catheter-associated DVT (CADVT) data. We performed descriptive statistics and Poisson tests to compare CADVT rates among parameters of interest. We generated Kaplan-Meier graphs to illustrate longevity of CADVT-free survival and a Cox proportional hazard model to calculate the hazard ratio associated with CADVT. RESULTS: We collected data on 407 patients, of which, 276 (68%) received tunneled catheters and 131 (32%) received PICCs as their initial catheter. There were 17 CADVTs with an overall rate of 0.08 per 1000 catheter days, whereas individual rates of DVT for PICCs and tunneled catheters were 0.16 and 0.05 per 1000 catheter days, respectively (P = 0.03). After adjusting for age, sex, and comorbidity, CADVT risk was significantly higher for PICCs compared with tunneled catheters, with an adjusted hazard ratio of 2.962 (95% CI=1.140-7.698; P = 0.025) and adjusted incidence rate ratio of 3.66 (95% CI=2.637-4.696; P = 0.013). CONCLUSION: Our study shows that CADVT risk is nearly three times higher with PICCs compared with tunneled catheters. We recommend tunneled catheter placement for patients with IBD who require HPN infusion greater than 30 days.

Heparin-Induced Hemorrhagic Bullous Dermatosis: A Rare Complication of Unfractionated Heparin.

We present a case of an 82-year-old female with a significant medical history of hypertension and Alzheimer's disease who developed heparin-induced hemorrhagic bullous dermatosis during treatment for a subsegmental pulmonary embolism. The patient was admitted with lower extremity edema and cyanosis, diagnosed with a subsegmental pulmonary embolism, and started on therapeutic doses of unfractionated heparin. On the sixth day of heparin therapy, she developed abdominal bloating and a diffuse exanthematous rash, which progressed to hemorrhagic bullae on the plantar and dorsal aspects of her feet, alongside extensive purpura on her legs. Laboratory findings revealed thrombocytopenia. Multidisciplinary consultations confirmed the diagnosis of heparin-induced hemorrhagic bullous dermatosis. Management included continuing unfractionated heparin with close monitoring, supportive topical treatments, and a subsequent transition to rivaroxaban. The patient's condition improved significantly, and she was discharged in stable condition. This case highlights the importance of recognizing rare adverse reactions to heparin and raises the question of preventive measures or risk factors related to this manifestation.

The effectiveness and safety of Rivaroxaban and Edoxaban in the treatment of lower extremity deep vein thrombosis.

INTRODUCTION: Deep vein thrombosis (DVT) is a medical condition characterized by forming a blood clot, or thrombus, in one of the deep veins, typically in the legs. It is a type of venous thromboembolism (VTE), which refers to the formation of blood clots in the veins. It is caused by Virchow's triad (stasis, hypercoagulation, and endothelial injury). OBJECTIVE: Our main objective is to explore the effectiveness and safety of Rivaroxaban and Edoxaban in treating lower extremity deep vein thrombosis. METHODS: We conducted a retrospective study involving 406 patients subjected to DVT treatment using DOACs (Edoxaban and Rivaroxaban) at our hospital. We recruited adult patients (18 years and above) diagnosed with lower extremity deep vein thrombosis and received treatment with either Rivaroxaban or Edoxaban as the primary anticoagulant therapy for DVT. We excluded patients who received treatment with other anticoagulant medications (warfarin heparin) as the primary therapy for DVT. RESULTS: The groups showed statistically significant differences in red blood cell count and haemoglobin levels, with the Edoxaban group having high values. However, the two groups observed no statistically significant differences in creatinine clearance, white blood cell count, platelet count, C-reactive protein, and D-dimer levels. The difference in the incidence of PE between the two groups was statistically significant (P value < 0.001). The Edoxaban group had fewer PE patients than the rivaroxaban group. The reduction in recurrent thrombosis was significantly higher in the rivaroxaban group compared to the Edoxaban group. There were no significant differences in the major bleeding at various sites across the two treatment groups (p > 0.05). CONCLUSION: Rivaroxaban's pharmacokinetic profile includes rapid absorption and a relatively short half-life. It means that once administered, Rivaroxaban quickly reaches its peak concentration in the blood and is subsequently eliminated from the body within a relatively short period. Edoxaban's pharmacokinetic profile may include slower absorption and a longer half-life than Rivaroxaban. It can result in a slower rate of achieving peak concentration and a more prolonged presence in the bloodstream. These results emphasize the need for careful consideration of anticoagulant therapy in patients with underlying cancer and underscore the importance of managing risks while providing adequate anticoagulation to prevent thrombotic events.

Low-density lipoprotein cholesterol-to-lymphocyte count ratio (LLR) is a promising novel predictor of postoperative new-onset deep vein thrombosis following open wedge high tibial osteotomy: a propensity score-matched analysis.

BACKGROUND: The association of low-density lipoprotein cholesterol (LDL-C) and lymphocyte counts with the development of deep vein thrombosis (DVT) has been demonstrated in many fields but remains lacking in open wedge high tibial osteotomy (OWHTO). This study aimed to assess the predictive value of LDL-C to lymphocyte count ratio (LLR) in screening for postoperative new-onset DVT. METHODS: Clinical data were retrospectively collected from patients who underwent OWHTO between June 2018 and May 2023. The limited restricted cubic spline (RCS) was conducted to evaluate the nonlinear relationship between LLR and the risk of postoperative new-onset DVT. The receiver operating characteristic (ROC) curves were plotted and the predictive value of biomarkers was assessed. After adjusting for intergroup confounders by propensity score matching, the univariate logistic regression was applied to assess the association between LLR and DVT. RESULTS: 1293 eligible patients were included. RCS analysis showed a linear positive correlation between LLR and the risk of DVT (P for overall = 0.008). We identified LLR had an area under the curve of 0.607, accuracy of 74.3%, sensitivity of 38.5%, and specificity of 80.7%, and LLR > 1.75 was independently associated with a 1.45-fold risk of DVT (95% CI: 1.01-2.08, P = 0.045). Furthermore, significant heterogeneities were observed in the subgroups of age, BMI, diabetes mellitus, hypertension, Kellgren-Lawrence grade, the American Society of Anesthesiologists (ASA) score, and intraoperative osteotomy correction size. CONCLUSION: LLR is a valuable biomarker for predicting postoperative new-onset DVT in patients with OWHTO, and routine screening is expected to yield positive benefits.

Persistent Peril: Recurrent Deep Vein Thrombosis and Pulmonary Embolism in a Patient With Protein S Deficiency Despite Optimal Anticoagulation Therapies.

The clotting system has evolved as an adaptive mechanism to prevent blood loss during vascular damage. However, the intricate nature of the clotting cascade and the complexities of human life can sometimes lead to the unnatural activation of this delicate cascade. This can result in blood clot formation within the cardiovascular system, contributing to a wide range of pathological conditions. Abnormal intravascular coagulation most commonly occurs in the deep veins of the lower extremities, and can emboli to other organs, hence, it is termed "venous thromboembolism" (VTE). In this report, we introduce a challenging case of VTE that poses a dilemma for current medical management. The patient with possible protein S deficiency underwent various guideline-directed medical treatments, yet experienced recurrent VTE episodes, including deep vein thrombosis (DVT) and pulmonary embolism (PE), leading to hospital readmissions. This case report sheds light on our challenges in effectively treating VTE.

The Harms of Unnecessary CT Pulmonary Angiography: A Case Report and Literature Review.

Pulmonary embolism (PE) poses a significant health risk in the United States, with high mortality rates. Clinicians maintain a low threshold for suspecting PE, potentially leading to deviation from guideline-recommended algorithms and unnecessary computed tomography pulmonary angiography (CTPA). This case discusses a 46-year-old woman who presented with symptoms suggestive of PE following a prolonged road trip. Despite a low Wells score and negative D-dimer results, she underwent CTPA, resulting in an unnecessary and harmful interventional radiology-guided thrombectomy. This highlights the importance of adhering to guidelines in PE diagnosis to mitigate potential harms associated with the overuse of available medical tools.

Dual Cardiac Arrests Leading to Hypercoagulability and Extensive Upper Extremity Deep Vein Thrombosis: A Hematological Case Report.

Upper extremity (UE) deep vein thrombosis (DVT) is a rare yet significant complication that can occur following cardiac arrest (CA). CA initiates a prothrombotic state via various processes, including stasis, endothelial damage, and an impaired balance between thrombogenesis and fibrinolysis, which may contribute to UE DVT formation. Inadequate cardiopulmonary resuscitation (CPR) in the field may further exacerbate blood stasis and clot formation. This case report describes an 80-year-old male with a history of bladder cancer who experienced two cardiac arrest events and subsequently developed an extensive left UE DVT. Despite treatment with a heparin drip and other supportive measures, the patient's condition deteriorated, and he passed away on the tenth day of hospitalization. This case is the first to describe UE DVT post-CA. It underscores the importance of recognizing and proactively managing hypercoagulable states post-CA, which can lead to significant DVTs in atypical locations that may evolve into life-threatening conditions.

Efficacy and safety of rivaroxaban versus warfarin in the management of unusual site deep vein thrombosis: a retrospective cohort study.

Background: Unusual site deep vein thrombosis (DVT) was defined as venous thromboembolism (VTE) occurring outside the conventional deep veins of the lower extremity or pulmonary arteries. However, the optimal anticoagulation therapy for unusual site DVT remained unclear. This study aims to evaluate the efficacy and safety of rivaroxaban in unusual site DVT. Methods: This retrospective cohort study enrolled consecutive patients at Nanjing Drum Tower Hospital between January 2011 and December 2021 who were diagnosed with unusual site DVT. Patients were divided into two groups based on their ultimate medication choice: the warfarin group and the rivaroxaban group. The demographic characteristics were recorded for all enrolled patients. Clinical outcomes included recurrent VTE, bleeding complications and major bleeding. Results: A total of 1,088 patients were divided into warfarin (n = 514) and rivaroxaban (n = 574) groups. After the stabilized inverse probability of treatment weighting, Hazard Ratios for warfarin vs. rivaroxaban of recurrent VTE, bleeding complications and major bleeding were 0.52(95% CI: 0.25-1.08), 0.30(95% CI: 0.14-0.60), and 0.33 (95% CI, 0.13-0.74), respectively. Risk of clinical outcomes in specified subgroups for age, gender, renal function, thrombosis sites and diagnosis were assessed. The interaction of gender and treatment on major bleeding was significant (P for interaction = 0.062). Otherwise, there was no significant interaction between the other subgroups and the treatment group in terms of clinical outcomes. Conclusion: Compared with warfarin, rivaroxaban exhibited comparable efficacy for the anticoagulant treatment of unusual site DVT, associated with a lower risk of bleeding complications and major bleeding.

Magnetic Resonance Imaging Features of Plantar Vein Thrombosis.

Plantar vein thrombosis (PVT) is an underdiagnosed condition affecting the deep plantar veins, with challenging clinical diagnosis, often presenting with non-specific symptoms that mimic other foot pathologies. This study assessed the magnetic resonance imaging (MRI) features of patients diagnosed with PVT to contribute to the understanding of this condition. We performed the comprehensive analysis of a substantial dataset, including 112 patients, with a total of 130 positive MRI scans (86 of the forefoot and 44 of the ankle) presenting with PVT. Upon evaluating all the veins of the feet, we observed a higher frequency of involvement of the lateral plantar veins (53.1%) when compared to the medial veins (3.8%). The most affected vascular segments in the forefeet were the plantar metatarsal veins (45.4%), the plantar venous arch (38.5%), and the plantar communicating veins (25.4%). The characteristic findings on MRI were perivascular edema (100%), muscular edema (86.2%), venous ectasia (100%), perivascular enhancement (100%), and intravenous filling defects (97.7%). Our study provides valuable insights into the imaging evaluation of PVT and shows that MRI is a reliable resource for such diagnosis.

Incidence of venous thromboembolic disease and risk of bleeding in critically ill patients with hematologic malignancies: A retrospective study.

OBJECTIVE: Our objectives were to describe the use of thromboprophylaxis and the incidence of VTE/bleeding in critically ill patients with hematologic malignancies (HM). DESIGN: Retrospective cohort study (2014-2022). SETTING: Medic-Surgical Intensive Care Unit (ICU) in a tertiary care academic center. PATIENTS: Adult patients admitted to ICU with a concomitant diagnosis of a hematological malignancy. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: We analyzed demographic data, use of thromboprophylaxis and secondary outcomes that included incidence of VTE (venous thromboembolism), bleeding, mortality, severity scores and organ support. We applied a multivariable logistic regression model to examine the risk of thrombosis in the ICU. RESULTS: We included 862 ICU admissions (813 unique patients). Thromboprophylaxis was given during 65% of admissions (LMWH 14%, UFH 8%, and SCDs 43%); in 21% it was contraindicated due to thrombocytopenia; 14% of cases lacked documentation on prophylaxis. There were 38 unique incident cases of VTE (27 DVT, 11 PE), constituting 4.4% of ICU episodes. Most of VTE cases happened in patients with various degrees of thrombocytopenia. In the multivariable analysis, SOFA score on the first ICU day was independently associated (OR 0.85, 95% CI 0.76-0.96) with the risk of VTE. Bleeding occurred in 7.2% (minor) and 14.4% (major) of episodes; most frequent sites being CNS, abdomen/GI and pulmonary. CONCLUSIONS: In this cohort of critically ill patients with HM, there was considerable variability in the utilization of DVT prophylaxis, with predominant use of SCDs. The incidence of VTE was 4.4% and major bleeding 14%. CLINICAL TRIAL REGISTRATION: NCT05396157. Venous Thromboembolism in Hematologic Malignancy and Hematopoietic Cell Transplant Patients: a Retrospective Study (https://clinicaltrials.gov/).

Venous Thromboembolism in Foot and Ankle Trauma.

Every surgeon may have experienced a tragic event associated with death or debilitation secondary to deep vein thrombosis (DVT) or pulmonary embolism (PE) after foot and ankle trauma and surgery. Nevertheless, the prevention of such a tragic event needs to be carefully evaluated rationally with currently available epidemiologic data. With great postoperative protocols and access to care, most PE events can be prevented. There are modifiable risk factors, such as length/type of immobilization and operative trauma/time that can lower the incidence of DVT/PE. In addition, chemical prophylaxis may be warranted in certain people within the foot and ankle trauma population.

Bilateral lower limb examinations for deep vein thrombosis: A single-centre pilot study comparing request and report parameters for bilateral and unilateral referrals.

INTRODUCTION: Deep vein thrombosis (DVT) is a common pathology with significant morbidity and mortality, often occurring in the lower limb. Ultrasound is the modality of choice for diagnosis of DVT, but all guidance in the United Kingdom assumes a single leg referral. Few studies have addressed the question of bilateral referrals and bilateral DVTs, and it is not known how these should be included in ultrasound protocols. This study aims to compare the request and report parameters of bilateral examinations with those for single leg examinations over a six-month period. METHODS: A single-centre feasibility study collected data on all single and bilateral leg examinations performed by sonographers, over a six-month period at a small general hospital. Data collected for each examination included the referral and report findings. These were compared using basic statistical methods to compare DVT yield by laterality, referrer, DVT site, and patient factors. RESULTS: Six hundred and thirty examinations were included, eighteen of which were bilateral examinations. Although the bilateral leg cohort was small, there were significant differences in DVT yield between the groups, with single leg referrals more than eight times more likely to demonstrate a DVT at ultrasound. CONCLUSION: In a context of limited ultrasound resource, the low DVT yield of bilateral examinations has implications for service design. Further data collection will be needed to validate initial results, and to establish suitable criteria for acceptance of bilateral DVT referrals. IMPLICATIONS FOR PRACTICE: Low yield of DVTs in bilateral examinations can be validated via further research. Bilateral examinations can be explicitly included in DVT service design.

Lower Limb Deep Venous Thrombosis After Posterior Spinal Fusion as an Initial Manifestation of Factor V Leiden Mutation in a Pediatric Patient: A Case Report.

Deep venous thrombosis (DVT) is a serious condition in which a blood clot forms in a deep vein, usually of the lower extremity. In pediatric orthopedic surgery, the incidence of thrombotic events is rare. This is a case presentation of a 12-year-old female patient without previous events or a family history of thrombotic events who underwent a posterior spinal fusion due to severe adolescent idiopathic scoliosis. The patient developed a DVT due to an underlying Factor V Leiden mutation. The purpose of this case report is to create awareness, facilitate the diagnosis and management, and aid in future interventions and clinical outcomes.

Incidental finding of an undifferentiated sarcoma during lower limb Doppler ultrasound: A case report.

Introduction: Undifferentiated sarcoma is considered a rare and aggressive type of soft tissue sarcoma with the lower extremity reported as the common site for soft tissue sarcomas. Case presentation: We present a rare incidental finding of undifferentiated sarcoma during lower limb Doppler ultrasound with a presenting symptom of right thrombotic-like calf pain in a 49-year-old female. Discussion: On ultrasound, the presented undifferentiated sarcoma appeared as a large heterogeneous, oval-shaped, soft tissue mass deeply seated in the right calf with involvement of the soleus muscle. The features on ultrasound mimicked those of a hematoma; however, the possibility of the lesion being a haematoma was promptly ruled out with the demonstration of internal vascularity on colour Doppler application. The case was then referred to a sarcoma triage multidisciplinary team for a review. Magnetic resonance imaging, computed tomography and biopsy were parts of the diagnostic workup for this case, histology confirmed the soft tissue lesion to be an undifferentiated sarcoma. Emergency above knee amputation of the right leg was performed as part of the patient's treatment. Conclusion: This case report presents a rare incidental finding of undifferentiated sarcoma encountered during lower limb Doppler ultrasound causing thrombotic-like calf pain. Sonographers are encouraged to pay necessary attention and carefully examine any adjacent and incidental soft tissue lesion during lower limb Doppler ultrasound using compression, two-dimensional imaging and colour imaging, especially those that appear with characteristic features of malignancy; urgent referral should be made of such cases to a tertiary soft tissue sarcoma centre for further evaluation and management.

Effect of the administration route on the hemostatic efficacy of tranexamic acid in patients undergoing short-segment posterior lumbar interbody fusion: a systematic review and meta-analysis.

OBJECTIVE: Tranexamic acid (TXA) is an FDA-approved antifibrinolytic that is seeing increased popularity in spine surgery owing to its ability to reduce intraoperative blood loss (IOBL) and allogeneic transfusion requirements. The present study aimed to summarize the current literature on these formulations in the context of short-segment instrumented lumbar fusion including ≥ 1-level posterior lumbar interbody fusion (PLIF). METHODS: The PubMed, Cochrane, and Web of Science databases were queried for all full-text English studies evaluating the use of topical TXA (tTXA), systemic TXA (sTXA), or combined tTXA+sTXA in patients undergoing PLIF. The primary endpoints of interest were operative time, IOBL, and total blood loss (TBL); secondary endpoints included venous thromboembolic complication occurrence, and allogeneic and autologous transfusion requirements. Outcomes were compared using random effects. Comparisons were made between the following treatment groups: sTXA, tTXA, and sTXA+tTXA. Given that sTXA is arguably the standard of care in the literature (i.e., the most common route of administration that to this point has been studied the most), the authors compared sTXA versus tTXA and sTXA versus sTXA+tTXA. Study heterogeneity was assessed with the I2 test, and grouped analysis using the Hedge's g test was performed for measurement of effect size. RESULTS: Forty-five articles were identified, of which 17 met the criteria for inclusion with an aggregate of 1008 patients. TXA regimens included sTXA only, tTXA only, and various combinations of sTXA and tTXA. There were no significant differences in operative time, TBL, or postoperative drainage between the sTXA and tTXA groups or between the sTXA and sTXA+tTXA groups. CONCLUSIONS: The present meta-analysis suggested clinical equipoise between isolated sTXA, isolated tTXA, and combinatorial tTXA+sTXA formulations as hemostatic adjuvants/neoadjuvants in short-segment fusion including ≥ 1-level PLIF. Given the theoretically lower venous thromboembolism risk associated with tTXA, additional investigations using large cohorts comparing these two formulations within the posterior fusion population are merited. Although TXA has been shown to be effective, there are insufficient data to support topical or systemic administration as superior within the open PLIF population.