ABSTRACT

Acute myeloid leukemia (AML) accounts for 25% of all leukemia diagnosis and is characterized by distinct cytogenetic and molecular profile. Advances in the understanding of the causative driver mutations, risk-based therapy and better supportive care have led to an overall improvement in survival with frontline therapy. Despite these improvements, a significant number fail either because of primary refractory disease to the conventional 7+3 combination of anthracyclines and cytosine arabinoside (Cytarabine; Ara-C) or experience relapse post remission. Salvage therapy is complicated by the cardiotoxicity driven limitations on the reuse of anthracyclines and development of resistance to cytarabine. In this chapter authors will review the recent studies with targeted agents for refractory AML including targets for immunotherapeutic strategies.

PMID:37450248 | DOI:10.1007/s12098-023-04741-3

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PubMed articles on: Cardio-Oncology

Sacubitril/valsartan for cardioprotection in breast cancer (MAINSTREAM): design and rationale of the randomized trial

ESC Heart Fail. 2023 Jul 14. doi: 10.1002/ehf2.14466. Online ahead of print.

ABSTRACT

AIMS: In recent years, survival in patients with breast cancer has increased. Despite the improvement in outcomes of those patients, the risk of treatment-related cardiotoxicity remains high, and its presence has been associated with a higher risk of treatment termination and thus lower therapeutic efficacy. Prior trials demonstrated that a preventive initiation of heart failure drugs, including the renin-angiotensin-aldosterone inhibitors, might reduce the risk of treatment-related cardiotoxicity. However, to date, no study investigated the efficacy of sacubitril/valsartan, a novel antineurohormonal drug shown to be superior to the previous therapies, in the prevention of cardiotoxicity in patients with early-stage breast cancer, which is the aim of the trial.

METHODS AND RESULTS: MAINSTREAM is a randomized, placebo-controlled, double-blind, multicentre, clinical trial. After the run-in period, a total of 480 patients with early breast cancer undergoing treatment with anthracyclines and/or anti-human epidermal growth factor receptor 2 drugs will be randomized to the highest tolerated dose of sacubitril/valsartan, being preferably 97/103 mg twice daily or placebo in 1:1 ratio. The patients will be monitored, including routine transthoracic echocardiography (TTE) and laboratory biomarker monitoring, for 24 months. The primary endpoint of the trial will be the occurrence of a decrease in left ventricular ejection fraction by ≥5% in TTE within 24 months. The key secondary endpoints will be the composite endpoint of death from any cause or hospitalization for heart failure, as well as other imaging, laboratory, and clinical outcomes, including the occurrence of the cancer therapy-related cardiac dysfunction resulting in the necessity to initiate treatment. The first patients are expected to be recruited in the coming months, and the estimated completion of the study and publication of the results are expected in December 2027, pending recruitment.

CONCLUSIONS: The MAINSTREAM trial will determine the efficacy and safety of treatment with sacubitril/valsartan as a prevention of cardiotoxicity in patients with early breast cancer (ClinicalTrials.gov number: NCT05465031).

PMID:37449716 | DOI:10.1002/ehf2.14466

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PubMed articles on: Cardio-Oncology

Mediators and mechanisms of immune checkpoint inhibitor-associated myocarditis: Insights from mouse and human

Immunol Rev. 2023 Jul 14. doi: 10.1111/imr.13240. Online ahead of print.

ABSTRACT

The broad application of immune checkpoint inhibitors (ICIs) has led to significant gains in cancer outcomes. By abrogating inhibitory signals, ICIs promote T cell targeting of cancer cells but can frequently trigger autoimmune manifestations, termed immune-related adverse events (irAEs), affecting essentially any organ system. Among cardiovascular irAEs, immune-related myocarditis (irMyocarditis) is the most described and carries the highest morbidity. The currently recommended treatment for irMyocarditis is potent immunosuppression with corticosteroids and other agents, but this has limited evidence basis. The cellular pathophysiology of irMyocarditis remains poorly understood, though mouse models and human data have both implicated effector CD8+ T cells, some of which are specific for the cardiomyocyte protein α-myosin. While the driving molecular signals and transcriptional programs are not well defined, the involvement of chemokine receptors such as CCR5 and CXCR3 has been proposed. Fundamental questions regarding why only approximately 1% of ICI recipients develop irMyocarditis and why irMyocarditis carries a much worse prognosis than other forms of lymphocytic myocarditis remain unanswered. Further work in both murine systems and with human samples are needed to identify better tools for diagnosis, risk-stratification, and treatment.

PMID:37449556 | DOI:10.1111/imr.13240

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PubMed articles on: Cardio-Oncology

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PubMed articles on: Cardio-Oncology

Pre-discharge and early post-discharge management of patients hospitalized for acute heart failure: A scientific statement by the Heart Failure Association of the ESC

Eur J Heart Fail. 2023 May 18. doi: 10.1002/ejhf.2888. Online ahead of print.

ABSTRACT

Acute heart failure is a major cause of urgent hospitalizations. These are followed by marked increases in death and rehospitalization rates, which then decline exponentially though they remain higher than in patients without a recent hospitalization. Therefore, optimal management of patients with acute heart failure before discharge and in the early post-discharge phase is critical. First, it may prevent rehospitalizations through the early detection and effective treatment of residual or recurrent congestion, the main manifestation of decompensation. Second, initiation at pre-discharge and titration to target doses in the early post-discharge period, of guideline-directed medical therapy may improve both short- and long-term outcomes. Third, in chronic heart failure, medical treatment is often left unchanged, so the acute heart failure hospitalization presents an opportunity for implementation of therapy. The aim of this scientific statement by the Heart Failure Association of the European Society of Cardiology is to summarize recent findings that have implications for clinical management both in the pre-discharge and the early post-discharge phase after a hospitalization for acute heart failure.

PMID:37448210 | DOI:10.1002/ejhf.2888

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PubMed articles on: Cardio-Oncology

Therapeutic Effects of Plant Extracts of Anoectochilus roxburghii on Side Effects of Chemotherapy in BALB/c Breast Cancer Mice

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PubMed articles on: Cancer & VTE/PE

Evaluation of the Khorana Predictive Thrombotic Risk and Thromboprophylaxis Score in Cancer Patients in a Third Level Hospital

Open Respir Arch. 2022 Mar 2;4(2):100170. doi: 10.1016/j.opresp.2022.100170. eCollection 2022 Apr-Jun.

ABSTRACT

INTRODUCTION: Current clinical guidelines do not recommend the routine use of thromboprophylaxis in cancer primary unselected patients. Identifying cancer patients who could be beneficiaries of thrombotic prophylaxis is a real challenge. We aimed to analyse the application of Khorana score in cancer patients. We also tried to evaluate the prescription of primary thromboprophylaxis in cancer patients at risk of venous thromboembolic disease (VTED).

METHODS: A retrospective observational study of survival of hospitalised patients diagnosed with pulmonary embolism (PE) at the Hospital Central de la Defensa from January 2009 to March 2018. They were stratified into tumour PE (TPE) and non-tumour PE (nTPE). A case-control study was also carried out by TPE patients and non PE cancer patients (nPEC).

RESULTS: 108 patients were diagnosed with TPE, 260 nTPE and 324 nPEC. Gynaecological tumours were the most frequent (23.1%), followed by lung, digestive and urological cancer (20.4% each) in the TPE group. Death risk was 1.9 times higher in cancer patients (95% CI: 1.23-2.8) (p < 0.001). Khorana score was ≥3 points in 9.7% of TPE and 3.1% of nPEC compared to 26.2% of TPE and 9.9% of nPEC with Khorana score ≥2 points (p < 0.001). 7.4% of TPE patients received thromboprophylaxis. Khorana score in TPE patients without thromboprophylaxis was ≥3 points in the 9% and ≥2 points in the 24%.

CONCLUSIONS: There is an underutilisation of thromboprophylaxis in our cancer patients and mainly in those with high risk of VTED, as well as poor adherence to the Khorana score. More studies are needed to validate these findings and to optimise predictive strategies in the management of these patients.

PMID:37497323 | PMC:PMC10369566 | DOI:10.1016/j.opresp.2022.100170

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PubMed articles on: Cancer & VTE/PE

Predictors of Survival in Patients With Ischemic Stroke and Active Cancer: A Prospective, Multicenter, Observational Study

J Am Heart Assoc. 2023 Jul 25:e029618. doi: 10.1161/JAHA.123.029618. Online ahead of print.

ABSTRACT

Background Limited data exist on the prognostic factors for patients with ischemic stroke and active cancer. Methods and Results We conducted a prospective, multicenter, observational study in Japan, including patients with acute ischemic stroke and active cancer, to investigate the prognostic factors. We followed up the patients for 1 year after stroke onset. The patients were divided into 2 groups according to cryptogenic stroke and known causes (small-vessel occlusion, large-artery atherosclerosis, cardioembolism, and other determined cause), and survival was compared. The hazard ratios (HRs) and 95% CIs for mortality were calculated using Cox regression models. We identified 135 eligible patients (39% women; median age, 75 years). Of these patients, 51% had distant metastasis. A total of 65 (48%) and 70 (52%) patients had cryptogenic stroke and known causes, respectively. Patients with cryptogenic stroke had significantly shorter survival than those with known causes (HR [95% CI], 3.11 [1.82-5.32]). The multivariable Cox regression analysis revealed that distant metastasis, plasma D-dimer levels, venous thromboembolism (either deep venous thrombosis or pulmonary embolism) complications at stroke onset were independent predictors of mortality after adjusting for potential confounders. Cryptogenic stroke was associated with prognosis in univariable analysis but was not significant in multivariable analysis. The plasma D-dimer levels stratified the prognosis of patients with ischemic stroke and active cancer. Conclusions The prognosis of patients with acute ischemic stroke and active cancer varied considerably depending on stroke mechanism, distant metastasis, and coagulation abnormalities. The present study confirmed that coagulation abnormalities were crucial in determining the prognosis of such patients.

PMID:37489755 | DOI:10.1161/JAHA.123.029618

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PubMed articles on: Cancer & VTE/PE

Preoperative D-dimer Value and Lower Limb Venous Ultrasound for Deep Venous Thrombosis Prevents Postoperative Symptomatic Venous Thromboembolism in Patients Undergoing Colorectal Surgery: A Retrospective Study

J Anus Rectum Colon. 2023 Jul 25;7(3):159-167. doi: 10.23922/jarc.2022-071. eCollection 2023.

ABSTRACT

OBJECTIVES: Preoperative deep venous thrombosis (DVT) can cause potentially life-threatening postoperative venous thromboembolism (VTE). Lower limb venous ultrasound (LLVU) is a modality that can detect DVT. However, the threshold for performing preoperative LLVU in the population undergoing colorectal resection is controversial. In this context, we evaluated whether a preoperative D-dimer value can identify patients who benefit from LLVU from the perspective of preventing postoperative symptomatic VTE.

METHODS: Patients undergoing colorectal resection in our institute from 2013 to 2020 were retrospectively enrolled (n=2071). We divided the patients into two groups: the clinical indication group (CG: including patients from 2013 to 2016, n=875) and the D-dimer-orientated group (DG: including patients from 2017 to 2020, n=1196). In the CG, LLVU was performed when DVT was clinically suspected; in the DG, preoperative LLVU was performed in patients with a preoperative D-dimer>1.0 μg/ml.

RESULTS: In the surveyed period, 277 LLVUs were performed, among which DVT was detected in 34 cases (12.3%). In the CG, DVT was detected in 0.7% of patients, whereas in the DG, it was detected in 2.3% of patients. Postoperative symptomatic VTE was significantly reduced in the DG at both 3 and 6 months after surgery (p=0.041 and 0.020, respectively). Moreover, Multivariate analysis showed that a past medical history of PE and treatment following the CG protocol were independent risk factors for postoperative symptomatic VTE within 6 months of surgery (p<0.0001

CONCLUSIONS: LLVU in patients with a preoperative D-dimer>1.0 μg/ml is a useful method to prevent postoperative symptomatic VTE.

PMID:37496573 | PMC:PMC10368439 | DOI:10.23922/jarc.2022-071

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Role of Intravascular Ultrasound in Pulmonary Embolism Patients Undergoing Mechanical Thrombectomy: A Systematic Review

Tomography. 2023 Jul 14;9(4):1393-1407. doi: 10.3390/tomography9040111.

ABSTRACT

BACKGROUND: Traditionally, mechanical thrombectomy performed for pulmonary embolism (PE) necessitates the utilization of iodinated contrast. Intravascular ultrasound (IVUS) has been used as a diagnostic and therapeutic modality in the management of acute high and intermediate-risk PE. Recently, with the shortage of contrast supplies and the considerable incidence of contrast-induced acute kidney injury (CI-AKI), other safer and more feasible IVUS methods have become desirable. The purpose of this systematic review was to evaluate the importance of IVUS in patients with PE undergoing thrombectomy.

METHODS: Medline/PubMed, Embase, Scopus, and Google Scholar were searched for review studies, case reports, and case series. Clinical characteristics, outcomes and the usage of IVUS-guided mechanical thrombectomy during the treatment of acute high and intermediate-risk PE were examined in a descriptive analysis.

RESULTS: In this systematic review, we included one prospective study, two case series, and two case reports from July 2019 to May 2023. A total of 39 patients were evaluated; most were female (53.8%). The main presenting symptoms were dyspnea and chest pain (79.5%); three patients (7.9%) presented with syncope, one with shock and one with cardiac arrest. Biomarkers (troponin and BNP) were elevated in 94.6% of patients. Most patients (87.2%) had intermediate-risk PE, and 12.8% had high-risk PE. All patients presented with right-heart strain (RV/LV ratio ≥ 0.9, n= 39). Most patients (56.4%) had bilateral PE. Mechanical thrombectomy was performed using IVUS without contrast utilization in 39.4% of the patients. After the initial learning curve, contrast usage decreased gradually over time. There was a significant decrease in the composite mean arterial pressure immediately following IVUS-guided thrombectomy from 35.1 ± 7.2 to 25.2 ± 8.3 mmHg (p < 0.001). Post-procedure, there was no reported (0%) CI-AKI, no all-cause mortality, no major bleeding, or other adverse events. There was a significant improvement in symptoms and RV function at the mean follow-up.

CONCLUSIONS: New evidence suggests that IVUS-guided mechanical thrombectomy is safe, with visualization of the thrombus for optimal intervention, and reduces contrast exposure.

PMID:37489479 | PMC:PMC10366920 | DOI:10.3390/tomography9040111

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PubMed articles on: Cancer & VTE/PE

Incidence and Risk Factors of Venous Thromboembolism in Patients with Lung Adenocarcinoma Receiving Anti-tumor Therapy

Zhongguo Fei Ai Za Zhi. 2023 Jun 20;26(6):439-448. doi: 10.3779/j.issn.1009-3419.2023.102.22.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) as the most common cancer-associated complication has become the second death-causing reason among cancer patients. The management of VTE in patients with lung adenocarcinoma should focus on early and timely detection of risk factors. The aim of the study is to investigate the current situation of VTE in patients with lung adenocarcinoma treated with anti-tumor therapy and then explore the risk factors associated with the occurrence of VTE during anti-tumor therapy for early detection and screening of VTE.

METHODS: The present study included patients diagnosed as lung adenocarcinoma undergoing anti-tumor therapy in First Affiliated Hospital of Nanjing Medical University between December 2019 and May 2021. The risk factors were identified via univariate and multivariate Cox analysis. The incidence of independent risk factors were investigated through Kaplan-Meier curves combined with Log-rank test.

RESULTS: The results of univariate and multivariate Cox regression showed that history of VTE, targeted therapy and radiotherapy were risk factors for VTE in patients with lung adenocarcinoma treated with anti-tumor therapy (P<0.05).

CONCLUSIONS: History of VTE, radiotherapy and targeted therapy are found as independent risk factors for the occurrence of VTE, which should be identified and monitored for reduction of VTE incidence. .

PMID:37488081 | PMC:PMC10365962 | DOI:10.3779/j.issn.1009-3419.2023.102.22

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PubMed articles on: Cancer & VTE/PE

Recommendations for thromboembolic disease in oncological processes. A view from primary care

Semergen. 2023 Jul 22;49(7):102030. doi: 10.1016/j.semerg.2023.102030. Online ahead of print.

ABSTRACT

Venous thromboembolic disease (VTE) is a frequent complication in patients diagnosed with cancer and a cause of morbidity and mortality. Approximately 20% of thromboembolic episodes develop in association with active cancer. On the other hand, it is estimated that about 2-12% of cases, the thromboembolic episode is the first manifestation of an occult cancer, diagnosed at that time or subsequently, which offers an opportunity for early diagnosis and treatment. There are multiple factors that contribute to increase the risk of VTE in oncological patients in relation to specific characteristics of the patient, the tumor and the treatments. Knowledge of these risk factors will contribute to early diagnosis when signs of VTE appear, as well as the assessment of thromboprophylaxis if indicated. The diagnosis of VTE in patients with cancer does not differ of those who do not suffer from it. Regarding the treatment of VTE in these patients, low molecular weight heparin (LMWH), direct acting anticoagulants (DACs) and antivitamin K (VKA) are the most commonly used, although the dosing regimen and length are not clear yet. The management of these patients should be interdisciplinary and early, so the primary care physician plays a key role in this process as he/she is liaise with his/her patients. It is also necessary to update knowledge in order to improve the care of these patients. For these reasons, this document has been prepared by the Working Group on Vasculopathies of the Spanish Society of Primary Care Physicians (SEMERGEN) whose objective is to present the available information regarding the management of VTE that may appear in oncological patients, as well as the assessment of thromboprophylaxis and treatment, if appropriate, from an approach focused on a primary care field.

PMID:37487423 | DOI:10.1016/j.semerg.2023.102030

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PubMed articles on: Cancer & VTE/PE

Comparative Effectiveness of Anticoagulants in Patients With Cancer-Associated Thrombosis

JAMA Netw Open. 2023 Jul 3;6(7):e2325283. doi: 10.1001/jamanetworkopen.2023.25283.

ABSTRACT

IMPORTANCE: Patterns of clinical utilization and comparative effectiveness of anticoagulants for cancer-associated thrombosis (CAT) remain largely unexplored.

OBJECTIVES: To assess patterns of and factors associated with anticoagulant use and to evaluate the comparative effectiveness of contemporary anticoagulants in patients with active cancer in a clinical setting.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study obtained deidentified OptumLabs electronic health record claims data from January 1, 2012, to September 30, 2019. Adult patients (≥18 years of age) with a primary cancer diagnosis (except skin cancer) during at least 1 inpatient or 2 outpatient visits within 6 months before the venous thromboembolism (VTE) date were included. Data were analyzed from April 2020 to September 2021.

EXPOSURES: The patients were grouped according to the anticoagulant prescribed: (1) direct oral anticoagulants (DOACs), (2) low-molecular-weight heparin (LMWH), and (3) warfarin.

MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) were used to present the association between factors of interest and utilization of anticoagulants. Main efficacy outcomes included risk of VTE recurrence and all-cause mortality. Main safety outcomes included the risk of hospitalization due to major bleeding. Relative treatment effect estimates were expressed as hazard ratios (HRs) with 95% CIs.

RESULTS: This study included 5100 patients (mean [SD] age, 66.3 [12.3] years; 2670 [52.4%] women; 799 [15.7%] Black, 389 [7.6%] Hispanic, and 3559 [69.8%] White individuals). Overall, 2512 (49.3%), 1488 (29.2%), and 1460 (28.6%) filled prescriptions for DOACs, LMWH, and warfarin, respectively. The median (IQR) treatment duration was 3.2 (1.0-6.5) months for DOACs, 3.1 (1.0-6.8) months for warfarin, and 1.8 (0.9-3.8) months for LWMH. Patients with lung (OR, 2.07; 95% CI, 1.12-3.65), urological (OR, 1.94; 95% CI,1.08-3.49), gynecological (OR, 4.25; 95% CI, 2.31-7.82), and colorectal (OR, 2.26; 95% CI, 1.20-4.32) cancer were associated with increased prescriptions for LMWH compared with DOACs. LMWH (HR, 1.47; 95% CI, 1.14-1.90) and warfarin (HR, 1.46; 95% CI, 1.13-1.87) were associated with an increased risk of VTE recurrences compared with DOACs. LMWH was associated with an increased risk of major bleeding (HR, 2.27; 95% CI, 1.62-3.20) and higher all-cause mortality (HR, 1.61; 95% CI, 1.15-2.25) compared with DOACs.

CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study of claims-based data, patients with CAT received anticoagulation for a remarkably short duration in clinical settings. DOACs was associated with a lower risk of VTE recurrence, major bleeding, and mortality. Warfarin may still be considered for patients with contraindications to DOACs and those with poor persistence on LMWH.

PMID:37486628 | PMC:PMC10366701 | DOI:10.1001/jamanetworkopen.2023.25283

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PubMed articles on: Cancer & VTE/PE

Clinical outcome of open ankle fractures in patients above 70 years of age

World J Orthop. 2023 Jul 18;14(7):554-561. doi: 10.5312/wjo.v14.i7.554. eCollection 2023 Jul 18.

ABSTRACT

BACKGROUND: Open fractures of the ankle are complex injuries requiring multidisciplinary input and are associated with significant morbidity and mortality. However, data on the clinical outcomes of open ankle fracture management in patients older than 70 is minimal.

AIM: To evaluate the clinical outcomes following open ankle fracture management in patients older than 70. Our secondary aim is to look at predictors of poor outcomes.

METHODS: Following local research and audit department registration, 22 years of prospectively collated data from an electronic database in a district general hospital were assessed. All patients older than 70 years of age with an open ankle fracture requiring surgical intervention were identified. Demographic information, the nature, and the number of surgical interventions were collated. Complications, including surgical site infection (SSI), venous thromboembolic events (VTEs) during hospital stay, and mortality rate, were reviewed.

RESULTS: A total of 37 patients were identified (median age: 84 years, range: 70-98); n= 30 females median age: 84 years, range: 70-97); n= 7 males median age: 74 years, range: 71-98)) who underwent surgical intervention after an open ankle fracture. Sixteen patients developed SSIs (43%). Superficial SSIs (n = 8) were managed without surgical intervention and treated with antibiotics and regular dressing changes. Deep SSIs (n = 8; 20%) required a median of 3 (range: 2-9) surgical interventions, with four patients requiring multiple washouts and one patient having metalwork removed. VTE incidence was 5% during the hospital stay. Eight patients died within 30 d, and mortality at one year was 19%. The 10-year mortality rate was 57%. The presence of a history of stroke, cancer, or prolonged inpatient stay was found to be predictive of lower survivorship in this population (log-rank test: cancer P= 0.008, stroke P= 0.001, length of stay > 33 d P= 0.015). The presence of a cardiac history was predictive of wound complications (logistic regression, P= 0.045). Age, number of operations, and diabetic history were found to be predictive of an increase in the length of stay (general linear model; age P< 0.001, number of operations P< 0.001, diabetes P= 0.041).

CONCLUSION: An open ankle fracture in a patient older than 70 years has at least a 20% chance of requiring repeated surgical intervention due to deep SSIs. The presence of a cardiac history appears to be the main predictor for wound complications.

PMID:37485433 | PMC:PMC10359747 | DOI:10.5312/wjo.v14.i7.554

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Using Machine Learning (ML) Models to Predict Risk of Venous Thromboembolism (VTE) Following Spine Surgery

Clin Spine Surg. 2023 Jul 24. doi: 10.1097/BSD.0000000000001498. Online ahead of print.