Risk assessment tools for bleeding in patients with unprovoked venous thromboembolism: an analysis of the PLATO-VTE study.

BACKGROUND: Guidelines suggest indefinite anticoagulation after unprovoked venous thromboembolism (VTE) unless the bleeding risk is high, yet there is no consistent guidance on assessing bleeding risk. OBJECTIVES: This study aimed to evaluate the performance of 5 bleeding risk tools (RIETE, VTE-BLEED, CHAP, VTE-PREDICT, and ABC-Bleeding). METHODS: PLATO-VTE, a prospective cohort study, included patients aged ≥40 years with a first unprovoked VTE. Risk estimates were calculated at VTE diagnosis and after 3 months of treatment. Primary outcome was clinically relevant bleeding, as per International Society on Thrombosis and Haemostasis criteria, during 24-month follow-up. Discrimination was assessed by the area under the receiver operating characteristic curve (AUROC). Patients were classified as having a "high risk" and "non-high risk" of bleeding according to predefined thresholds; bleeding risk in both groups was compared by hazard ratios (HRs). RESULTS: Of 514 patients, 38 (7.4%) had an on-treatment bleeding. AUROCs were 0.58 (95% CI, 0.48-0.68) for ABC-Bleeding, 0.56 (95% CI, 0.46-0.66) for RIETE, 0.53 (95% CI, 0.43-0.64) for CHAP, 0.50 (95% CI, 0.41-0.59) for VTE-BLEED, and 0.50 (95% CI, 0.40-0.60) for VTE-PREDICT. The proportion of high-risk patients ranged from 1.4% with RIETE to 36.9% with VTE-BLEED. The bleeding incidence in the high-risk groups ranged from 0% with RIETE to 13.0% with ABC-Bleeding, and in the non-high-risk groups, it varied from 7.7% with ABC-Bleeding to 9.6% with RIETE. HRs ranged from 0.93 (95% CI, 0.46-1.9) for VTE-BLEED to 1.67 (95% CI, 0.86-3.2) for ABC-Bleeding. Recalibration at 3-month follow-up did not alter the results. CONCLUSION: In this cohort, discrimination of currently available bleeding risk tools was poor. These data do not support their use in patients with unprovoked VTE.

Treatment Patterns of Cancer-associated Thrombosis in the Netherlands: The Four Cities Study.

Background Current guidelines recommend either low-molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs) as first-line treatment in cancer-associated venous thromboembolism (VTE). Aim This study aimed to investigate treatment regimens for cancer-associated VTE over the past 5 years, explore predictors for initial treatment (LMWH vs. DOAC), and to assess the risks of recurrent VTE and bleeding. Methods This was a Dutch, multicenter, retrospective cohort study including consecutive patients with cancer-associated VTE between 2017 and 2021. Treatment predictors were assessed with multivariable logistic regression models. Six-month cumulative incidences for recurrent VTE and major bleeding (MB) were estimated with death as competing risk. Results In total, 1,215 patients were included. The majority (1,134/1,192; 95%) started VTE treatment with anticoagulation: 561 LMWH (47%), 510 DOACs (43%), 27 vitamin K antagonist (2.3%), and 36 other/unknown type (3.0%). The proportion of patients primarily treated with DOACs increased from 18% (95% confidence interval [CI] 12-25) in 2017 to 70% (95% CI 62-78) in 2021. Poor performance status (adjusted odds ratio [aOR] 0.72, 95% CI 0.53-0.99) and distant metastases (aOR 0.61, 95% CI 0.45-0.82) were associated with primary treatment with LMWH. Total 6-month cumulative incidences were 6.0% (95% CI 4.8-7.5) for recurrent VTE and 7.0% (95% CI 5.7-8.6) for MB. During follow-up, 182 patients (15%) switched from LMWH to a DOAC, and 54 patients (4.4%) vice versa, for various reasons, including patient preference, recurrent thrombosis, and/or bleeding. Conclusion DOAC use in cancer-associated VTE has increased rapidly over the past years. Changes in anticoagulation regimen were frequent over time, and were often related to recurrent thrombotic and bleeding complications, illustrating the complexity and challenges of managing cancer-associated VTE.

RNA-sequencing to discover genes and signaling pathways associated with venous thromboembolism in glioblastoma patients: A case-control study.

BACKGROUND: Glioblastoma patients are at high risk of developing venous thromboembolism (VTE). Tumor-intrinsic features are considered to play a role, but the underlying pathophysiological mechanisms remain incompletely understood. OBJECTIVES: To identify tumor-expressed genes and signaling pathways that associate with glioblastoma-related VTE by using next generation RNA-sequencing (RNA-Seq). METHODS: The tumor gene expression profile of 23 glioblastoma patients with VTE and 23 glioblastoma patients without VTE was compared using an unpaired analysis. Ingenuity Pathway Analysis (IPA) core analysis was performed on the top 50 differentially expressed genes to explore associated functions and pathways. Based on full RNA-Seq data, molecular glioblastoma subtypes were determined by performing cluster analysis. RESULTS: Of the 19,327 genes, 1246 (6.4 %) were differentially expressed between glioblastoma patients with and without VTE (unadjusted P < 0.05). The most highly overexpressed gene was GLI1, a classical target gene in the Sonic Hedgehog (Shh) signaling pathway (log2 fold change: 3.7; unadjusted P < 0.0001, adjusted P = 0.219). In line, Shh signaling was among the top canonical pathways and processes associated with VTE. The proportion of patients with the proneural/neural glioblastoma subtype was higher among those with VTE than controls. CONCLUSION: Shh signaling may be involved in the development of glioblastoma-related VTE.

Polygenic risk scores for prediction of cancer-associated venous thromboembolism in the UK Biobank cohort study.

BACKGROUND: Guidelines recommend thromboprophylaxis for patients with cancer at high risk of venous thromboembolism (VTE). Polygenic risk scores may improve VTE prediction but have not yet been evaluated in patients with cancer. OBJECTIVES: We assessed the performance of the 5-, 37-, 297-, extended 297- (additionally including factor V Leiden and prothrombin G20210A), and 100-single-nucleotide polymorphism (SNP) scores in predicting cancer-associated VTE in the UK Biobank, a population-based, prospective cohort study. METHODS: The primary outcome was VTE during 12 months after cancer diagnosis. Cancer and VTE diagnosis were based on ICD-10 codes. Discrimination was evaluated by c-indices and subdistribution hazard ratios in the upper vs 3 lower quartiles of the scores in a competing risk model. As a comparison, the c-index was calculated for the Khorana cancer type risk classification. RESULTS: Of 36 150 patients with cancer (median age, 66 years; 48.7% females), 1018 (2.8%) developed VTE. C-indices at 12 months ranged from 0.56 (95% CI, 0.54-0.58) for the 5-SNP to 0.60 (95% CI, 0.58-0.62) for the extended 297-SNP scores. The subdistribution hazard ratios ranged from 1.36 (95% CI, 1.19-1.56) for the 5-SNP to 1.90 (95% CI, 1.68-2.16) for the extended 297-SNP scores and were consistent after adjusting for cancer type. For the Khorana cancer type classification, the c-index was 0.60 (95% CI, 0.58-0.61), which increased to 0.65 (95% CI, 0.63-0.67, +0.05; 95% CI, 0.04-0.07) when combined with the extended 297-SNP score. CONCLUSION: These findings demonstrate that polygenic VTE risk scores can identify patients with cancer with a 1.9-fold higher VTE risk independent of cancer type. Combined clinical-genetic scores to improve cancer-associated VTE prediction should be evaluated further.

Treatment and prevention of cancer-associated thrombosis in the Netherlands: A national survey.

Background: In the recent years, numerous studies on the optimal treatment and prevention of cancer-associated venous thromboembolism (VTE) have been published, leading to updated (inter)national guidelines. These include direct oral anticoagulants (DOACs) as the first-line treatment agent in general and the recommendation of primary thromboprophylaxis in selected ambulatory patients. Objectives: The objective of this study was to evaluate the clinical practice regarding treatment and prevention of VTE in patients with cancer in the Netherlands and practice variation among different specialties. Methods: An online survey was conducted between December 2021, and June 2022, among Dutch physicians (oncologists, hematologists, vascular medicine specialists, acute internal medicine specialists, and pulmonologists) treating patients with cancer, in which we explored the treatment of choice for cancer-associated VTE, the use of VTE risk stratification tools, and primary thromboprophylaxis. Results: A total of 222 physicians participated, of whom the majority (81%) used DOACs as a first-line agent for treating cancer-associated VTE. The treatment varied between the following specialties: hematologists and acute internal medicine specialists more often prescribed low-molecular-weight heparin than physicians of the other specialties (OR, 0.32; 95% CI, 0.13-0.80). The minimum duration of anticoagulant treatment was usually 3 to 6 months (87%), and treatment was extended when the malignancy was still active (98%). Regarding the prevention of cancer-associated VTE, no risk stratification tool was used. Three quarters of respondents never prescribed thromboprophylaxis to ambulatory patients, mostly because the thrombosis risk was not perceived high enough to justify prophylaxis. Conclusion: Dutch physicians largely adhere to the updated guidelines regarding the treatment of cancer-associated VTE but less to the recommendations for its prevention.

Platelet RNA sequencing for cancer screening in patients with unprovoked venous thromboembolism: a prospective cohort study.

BACKGROUND: Platelet RNA sequencing has been shown to accurately detect cancer in previous studies. OBJECTIVES: To compare the diagnostic accuracy of platelet RNA sequencing with standard-of-care limited cancer screening in patients with unprovoked venous thromboembolism (VTE). METHODS: Patients aged ≥40 years with unprovoked VTE were recruited at 13 centers and followed for 12 months for cancer. Participants underwent standard-of-care limited cancer screening, and platelet RNA sequencing analysis was performed centrally at study end for cases and selected controls. Sensitivity and specificity were calculated, using the predefined primary positivity threshold of 0.54 for platelet RNA sequencing aiming at 86% test sensitivity, and an additional predefined threshold of 0.89 aiming at 99% test specificity. RESULTS: A total of 476 participants were enrolled, of whom 25 (5.3%) were diagnosed with cancer during 12-month follow-up. For each cancer patient, 3 cancer-free patients were randomly selected for the analysis. The sensitivity of limited screening was 72% (95% CI, 52-86) at a specificity of 91% (95% CI, 82-95). The area under the receiver operator characteristic for platelet RNA sequencing was 0.54 (95% CI, 0.41-0.66). At the primary positivity threshold, all patients had a positive test, for a sensitivity estimated at 100% (95% CI, 87-99) and a specificity of 8% (95% CI, 3.7-16.4). At the secondary threshold, sensitivity was 68% (95% CI, 48-83; p value compared with limited screening 0.71) at a specificity of 36% (95% CI, 26-47). CONCLUSION: Platelet RNA sequencing had poor diagnostic accuracy for detecting occult cancer in patients with unprovoked VTE with the current algorithm.

Risk of venous thromboembolism and bleeding after major surgery for ovarian cancer: standard in-hospital versus extended duration of thromboprophylaxis.

BACKGROUND: Venous thromboembolism (VTE) is a frequent complication in patients with ovarian cancer after major surgery. Based on limited data, international guidelines recommend extended thromboprophylaxis for up to 28 days. OBJECTIVES: To assess the incidence of VTE and bleeding within 30 days following major surgery in patients with ovarian cancer and to evaluate the association between VTE and thromboprophylaxis duration. METHODS: This was a single-center, retrospective, "before-after" cohort study in patients with ovarian cancer undergoing major surgery. Before July 2019, the local protocol mandated a standard course of thromboprophylaxis during hospital stay only. From July 2019 onward, patients received extended thromboprophylaxis for 28 days. The cumulative incidences of VTE and major bleeding within 30 days after surgery were estimated using the Kaplan-Meier method, with 95% confidence intervals (CIs). Cox regression analysis was performed to evaluate the association between thromboprophylaxis duration and VTE incidence. RESULTS: Between January 2018 and December 2020, 250 women were included, of which 118 (47.2%) received extended and 132 (52.8%) standard thromboprophylaxis. During follow-up, 12 patients developed VTE (cumulative incidence, 4.8%; 95% CI, 2.1-7.4) and 2 major bleeding (cumulative incidence 0.8%; 95% CI, 0.0-1.9). Compared with standard thromboprophylaxis, VTE incidence was numerically lower with extended duration of thromboprophylaxis (5/118 [4.2%] vs 7/132 [5.3%]) but not significantly different (hazard ratio, 0.80; 95% CI, 0.25-2.52). The risk of major bleeding was similar in both groups (1/118 [0.8%] vs 1/132 [0.8%]; hazard ratio, 1.12; 95% CI, 0.07-17.89). CONCLUSIONS: The cumulative VTE incidence in patients with ovarian cancer following major surgery was considerable. Extended thromboprophylaxis was safe and associated with a numerically lower risk of VTE but not significantly different.

The Functional Outcomes of Delayed Surgical Reconstruction in Nonsport-Induced Multiligament Knee Injuries: A Retrospective Cohort Study.

Multiligament knee injuries (MLKIs) are among the most detrimental injuries, which can cause significant compromise of joint stability and function. Our aim was to investigate the functional outcomes of nonsport-induced MLKIs who presented late after injury and underwent delayed arthroscopic reconstruction. In a retrospective cohort of 18 MLKI patients (19 knees, January 2012-2018) who had undergone arthroscopic reconstruction, we assessed the knee range of motion, return to work/sport, International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Arthritis Index, Lysholm, and Tegner scores. The preoperative scores were retrieved from the patients' registry database. We reviewed their surgical notes and extracted the operation data, including the damaged ligaments, stages of the surgery, and associated meniscal injury. There were 14 males and 4 females with a mean age of 30.57 ± 10.31 years. The mean time from injury to surgery was 17.31 ± 11.98 months. The most common injury was anterior cruciate ligament/posterior cruciate ligament (31.6%). The mechanisms of injury were motor vehicle accidents (72.2%), falls (22.2%), and sports (5.6%). The reconstruction was either single (61.2%) or multiple stage (38.8%). The pre- and postoperative scores were 45.31 ± 7.30 versus 79.16 ± 11.86 IKDC, 3.84 ± 1.26 versus 8.37 ± 1.16 Tegner, and 60.42 ± 7.68 versus 89.42 ± 8.81 Lysholm, respectively. All the scores showed significant improvement at mean follow-up of 24.05 ± 9.55 months (p < 0.001). In conclusion, delayed arthroscopic reconstruction of MLKIs significantly improved the functional outcomes and return to work in patients presenting late to the orthopaedic clinic. There was no relationship between the demographic variables, mechanism of injury, number of injured ligaments, and the stages of surgery and the functional outcomes in this group of patients.

Evaluation of the Khorana, PROTECHT, and 5-SNP scores for prediction of venous thromboembolism in patients with cancer.

BACKGROUND: The Khorana score is a validated tool to identify cancer patients at higher risk of venous thromboembolism (VTE). OBJECTIVE: We compared its predictive performance to that of the clinical PROTECHT and the polygenic 5-SNP scores in patients who participated in the Dutch CPCT-02 study. PATIENTS/METHODS: Data on VTE and its risk factors were retrospectively collected for 2729 patients with advanced stage solid tumors planned for systemic cancer treatment. Patients were followed for 6 months. Overall discriminatory performance of the scores was evaluated by time-dependent c-indices. The scores were additionally evaluated dichotomously in competing risk models. RESULTS: A total of 160 (5.9%) patients developed VTE during follow-up. Time-dependent c-indices at 6 months for the Khorana, PROTECHT, and 5-SNP scores were 0.57 (95% confidence interval [CI]: 0.55-0.60), 0.60 (95% CI: 0.57-0.62), and 0.54 (95% CI: 0.51-0.57), respectively. The dichotomous scores classified 9.6%, 16.8%, and 9.5% as high-risk, respectively. VTE risk was about 2-fold higher among high-risk patients than low-risk patients for the Khorana (subdistribution hazard ratio [SHR] 1.9, 95% CI: 1.3-3.0), PROTECHT (SHR 2.1, 95% CI: 1.5-3.0), and 5-SNP scores (SHR 1.7, 95% CI: 1.03-2.8). The sensitivity at 6 months was 16.6% (95% CI: 10.5-22.7), 28.9% (95% CI: 21.5-36.3), and 14.9% (95% CI: 8.5-21.2), respectively. CONCLUSIONS: Performance of the PROTECHT or 5-SNP score was not superior to that of the Khorana score. The majority of cancer patients who developed VTE during 6-month follow-up were not identified by these scores. Future directions for studies on cancer-associated VTE prediction may include combined clinical-genetic scores.

Risk Assessment Models for Thrombosis and Anticoagulant-Related Bleeding in Ambulatory Cancer Patients.

Cancer patients have a high risk of developing venous thromboembolism and arterial thrombosis, along with an increased risk of anticoagulant-related bleeding with primary and secondary prophylaxis of cancer-associated thrombosis. Decisions on initiation, dosing, and duration of anticoagulant therapy for prevention and treatment of cancer-associated thrombosis are challenging, as clinicians have to balance patients' individual risk of (recurrent) thrombosis against the risk of bleeding complications. For this purpose, several dedicated risk assessment models for venous thromboembolism in cancer patients have been suggested. However, most of these scores perform poorly and have received limited to no validation. For bleeding and arterial thrombosis, no risk scores have been developed specifically for cancer patients, and treatment decisions remain based on clinical gestalt and rough and unstructured estimation of the risks. The aims of this review are to summarize the characteristics and performance of risk assessment scores for (recurrent) venous thromboembolism and discuss available data on risk assessment for bleeding and arterial thrombosis in the cancer population. This summary can help clinicians in daily practice to make a balanced decision when considering the use of risk assessment models for cancer-associated venous thromboembolism. Future research attempts should aim at improving risk assessment for arterial thrombosis and anticoagulant-related bleeding in cancer patients.

Patterns of substance use among adolescents: A systematic review.

PURPOSE: This review characterizes empirically derived patterns of multiple (multi-) substance use among adolescents. A secondary objective was to examine the extent to which mental health symptomatology was included in the empirical analyses examining substance use patterns. METHODS: Eligible studies included those that used cluster-based approaches, included the assessment of at least two different substances, and were based on study samples with mean ages between 11 and 18 years. 4665 records were screened including 461 studies for full-text screening. RESULTS: 70 studies were included with common clusters being: low use, single or dual substance use, moderate general multi-use, and high multi-use. The most common patterns of single or multi-substance use were: alcohol only, alcohol with cannabis and/or tobacco, and use of alcohol, tobacco, and cannabis with and without other drugs. Lower socioeconomic status, older age, and male gender were consistent predictors of multi-use clusters. Only 37 % of studies compared differences in levels of mental health across clusters with symptoms consistently associated with a greater likelihood of multi-use. Only 29 % of studies included mental health indicators in cluster-based analyses, with over half identifying distinct mental health and substance use clusters. Fit indices in cluster analyses and measurement properties of substance use were heterogeneous and inconsistently reported across studies. CONCLUSIONS: Distinct patterns of substance use were derived but methodological differences prevented direct comparison and reduced capacity to generalize across studies. There is a need to establish standardized methodological approaches to identify robust patterns of substance use to enhance etiological, prognostic, and intervention research.

Automated identification of cephalometric landmarks: Part 2-Might it be better than human?

OBJECTIVES: To compare detection patterns of 80 cephalometric landmarks identified by an automated identification system (AI) based on a recently proposed deep-learning method, the You-Only-Look-Once version 3 (YOLOv3), with those identified by human examiners. MATERIALS AND METHODS: The YOLOv3 algorithm was implemented with custom modifications and trained on 1028 cephalograms. A total of 80 landmarks comprising two vertical reference points and 46 hard tissue and 32 soft tissue landmarks were identified. On the 283 test images, the same 80 landmarks were identified by AI and human examiners twice. Statistical analyses were conducted to detect whether any significant differences between AI and human examiners existed. Influence of image factors on those differences was also investigated. RESULTS: Upon repeated trials, AI always detected identical positions on each landmark, while the human intraexaminer variability of repeated manual detections demonstrated a detection error of 0.97 ± 1.03 mm. The mean detection error between AI and human was 1.46 ± 2.97 mm. The mean difference between human examiners was 1.50 ± 1.48 mm. In general, comparisons in the detection errors between AI and human examiners were less than 0.9 mm, which did not seem to be clinically significant. CONCLUSIONS: AI showed as accurate an identification of cephalometric landmarks as did human examiners. AI might be a viable option for repeatedly identifying multiple cephalometric landmarks.

Automated identification of cephalometric landmarks: Part 1-Comparisons between the latest deep-learning methods YOLOV3 and SSD.

OBJECTIVE: To compare the accuracy and computational efficiency of two of the latest deep-learning algorithms for automatic identification of cephalometric landmarks. MATERIALS AND METHODS: A total of 1028 cephalometric radiographic images were selected as learning data that trained You-Only-Look-Once version 3 (YOLOv3) and Single Shot Multibox Detector (SSD) methods. The number of target labeling was 80 landmarks. After the deep-learning process, the algorithms were tested using a new test data set composed of 283 images. Accuracy was determined by measuring the point-to-point error and success detection rate and was visualized by drawing scattergrams. The computational time of both algorithms was also recorded. RESULTS: The YOLOv3 algorithm outperformed SSD in accuracy for 38 of 80 landmarks. The other 42 of 80 landmarks did not show a statistically significant difference between YOLOv3 and SSD. Error plots of YOLOv3 showed not only a smaller error range but also a more isotropic tendency. The mean computational time spent per image was 0.05 seconds and 2.89 seconds for YOLOv3 and SSD, respectively. YOLOv3 showed approximately 5% higher accuracy compared with the top benchmarks in the literature. CONCLUSIONS: Between the two latest deep-learning methods applied, YOLOv3 seemed to be more promising as a fully automated cephalometric landmark identification system for use in clinical practice.

Frailty and clinical benefits with lung transplantation.

BACKGROUND: The Fried frailty phenotype is associated with morbidity and mortality in lung transplant (LTx) candidates, but its clinical application and association with post-transplant outcomes are not well defined. We assessed 2 alternate frailty indices in LTx candidates and evaluated associations of frailty with early post-transplant outcomes and 1-year mortality. METHODS: Frailty was prospectively evaluated in 50 LTx candidates using the Fried and 2 alternate phenotypic indices, one using variables readily available to clinicians and one using variables from an existing data set. Agreement between indices and associations with related measures were assessed to establish validity. The data set index was then applied retrospectively to 221 LTx patients. Post-transplant outcomes were compared between frail and non-frail patients using t-tests and multivariable regression analysis. RESULTS: Frailty prevalence among the 3 indices was 26% to 30%, and the κ agreement was 0.38 to 0.41. All indices had moderate correlations with London Chest Activity of Daily Living (r = 0.48-0.62) and Short-Physical Performance Battery (r = -0.43 to -0.52). In the retrospective cohort, frail LTx candidates had a worse St. George's Respiratory Questionnaire total score (73 ± 12vs 62 ± 12, p < 0.001). Frail candidates had a larger improvement with transplant in the St. George's Respiratory Questionnaire (-52 ± 19vs -43 ± 18, p = 0.002) and 6-minute walk distance (191 ± 119vs 129 ± 94m, p = 0.001). Frailty was not associated with hospital length of stay or 1-year mortality. CONCLUSIONS: There was good construct validity and acceptable agreement among the frailty indices. Despite significant disability pre-transplant, frail LTx candidates derived significant benefit with transplantation.

Preoperative expectations for health-related quality of life after lung transplant.

How patients' health-related quality of life (HRQL) after lung transplant compares to their preoperative expectations is unclear. As part of a previously published prospective cohort study, we compared 328 subjects' expectations for their post-transplant HQRL with and without chronic lung allograft dysfunction (CLAD) to their actual HRQL scores after transplant, using the visual analog scale (VAS) and standard gamble (SG). Subjects' expectations were considered met when the absolute difference between the expected and actual scores (the "expectation error") was <0.1 units, based on the minimally important difference for VAS and SG. On average, subjects' post-transplant HRQL without CLAD met their expectations (mean expectation error: -0.09 units [VAS] and +0.02 units [SG]) and subjects' post-transplant HRQL with CLAD met or exceeded their expectations (mean expectation error: +0.08 units [VAS] and +0.19 units [SG]). When subjects developed CLAD stages 1 and 2, their HRQL was better than they expected (mean expectation error of each disease group: >+0.1 units). When subjects developed CLAD stage 3, their HRQL was as they expected (mean expectation error of each disease group except COPD and CF: within ± 0.1 units). Patients' expectations for their HRQL after transplant are at least met and may be exceeded.

Evaluation of Skeletal Muscle Function in Lung Transplant Candidates.

BACKGROUND: Lung transplantation (LTx) is offered to older and more complex patients who may be at higher risk of skeletal muscle dysfunction, but the clinical implications of this remain uncertain. The study aims were to characterize deficits in skeletal muscle mass, strength and physical performance, and examine the associations of these deficits with clinical outcomes. METHODS: Fifty LTx candidates (58% men; age, 59 ± 9 years) were prospectively evaluated for skeletal muscle deficits: muscle mass using bioelectrical impedance, quadriceps, respiratory muscle and handgrip strength, and physical performance with the Short Physical Performance Battery. Comparisons between number of muscle deficits (low muscle mass, quadriceps strength and physical performance) and 6-minute walk distance (6MWD), London Chest Activity of Daily Living Questionnaire, and quality of life were assessed using one-way analysis of variance. Associations with pretransplant and posttransplant delisting/mortality, hospital duration, and 3-month posttransplant 6MWD were evaluated using Fisher exact test and Spearman correlation. RESULTS: Deficits in quadriceps strength (n = 27) and physical performance (n = 24) were more common than muscle mass (n = 8). LTx candidates with 2 or 3 muscle deficits (42%) compared with those without any deficits (26%) had worse 6MWD = -109 m (95% confidence interval [CI], -175 to -43), London Chest Activity of Daily Living Questionnaire = 18 (95% CI, 7-30), and St. George's Activity Domain = 12 (95% CI, 2-21). Number of muscle deficits was associated with posttransplant hospital stay (r = 0.34, P = 0.04), but not with delisting/mortality or posttransplant 6MWD. CONCLUSIONS: Deficits in quadriceps muscle strength and physical performance are common in LTx candidates and further research is needed to assess whether modifying muscle function pretransplant can lead to improved clinical outcomes.

Thoracic muscle cross-sectional area is associated with hospital length of stay post lung transplantation: a retrospective cohort study.

Low muscle mass is common in lung transplant (LTx) candidates; however, the clinical implications have not been well described. The study aims were to compare skeletal muscle mass in LTx candidates with controls using thoracic muscle cross-sectional area (CSA) from computed tomography and assess the association with pre- and post-transplant clinical outcomes. This was a retrospective, single-center cohort study of 527 LTx candidates [median age: 55 IQR (42-62) years; 54% male]. Thoracic muscle CSA was compared to an age- and sex-matched control group. Associations between muscle CSA and pre-transplant six-minute walk distance (6MWD), health-related quality of life (HRQL), delisting/mortality, and post-transplant hospital outcomes and one-year mortality were evaluated using multivariable regression analysis. Muscle CSA for LTx candidates was about 10% lower than controls (n = 38). Muscle CSA was associated with pre-transplant 6MWD, but not HRQL, delisting or pre- or post-transplant mortality. Muscle CSA (per 10 cm2 difference) was associated with shorter hospital stay [0.7 median days 95% CI (0.2-1.3)], independent of 6MWD. In conclusion, thoracic muscle CSA is a simple, readily available estimate of skeletal muscle mass predictive of hospital length of stay, but further study is needed to evaluate the relative contribution of muscle mass versus functional deficits in LTx candidates.

Effects of Recipient Age and Diagnosis on Health-related Quality-of-Life Benefit of Lung Transplantation.

RATIONALE: The average age of lung transplant recipients is increasing, and the mix of recipient indications for transplantation is changing. OBJECTIVES: To determine whether the health-related quality-of-life (HRQL) benefit of lung transplantation differs by recipient age and diagnosis. METHODS: In this prospective cohort study, we obtained serial HRQL measurements in adults with advanced lung disease who subsequently underwent lung transplantation (2004-2012). HRQL assessments included the St. George's Respiratory Questionnaire, 36-Item Short-Form Health Survey (SF-36), EQ-5D, Standard Gamble, and Visual Analog Scale for current health. We used linear mixed effects models for associations between age or diagnosis and changes in HRQL with transplantation. To address potential survivorship bias, we fitted Markov models to the distribution of discrete post-transplant health states (HRQL better than pretransplant, not better, or dead) and estimated quality-adjusted life-years post-transplant. MEASUREMENTS AND MAIN RESULTS: A total of 430 subjects were listed, 387 were transplanted, and 326 provided both pretransplant and post-transplant data. Transplantation conferred large improvements in all HRQL measures: St. George's change of -47 units (95% confidence interval, -48 to -44), 36-Item Short-Form Health Survey physical component summary score of 17.7 (16.5-18.9), EQ-5D of 0.27 (0.24-0.30), Standard Gamble of 0.48 (0.44-0.51), and Visual Analog of 44 (42-47). Age was not associated with meaningful differences in the HRQL benefits of transplantation. There was less HRQL benefit in interstitial lung disease than in cystic fibrosis. CONCLUSIONS: Lung transplantation confers large HRQL benefits, which vary by recipient diagnosis, but do not differ substantially in older recipients.