Pre-transplant Anemia as a Marker of Short-term Outcomes in Lung Transplant Recipients.

BACKGROUND: Anemia is a risk factor for increased morbidity and mortality in multiple medical conditions, yet the impact of pretransplant anemia in patients with advanced lung disease on post-transplant outcomes remains under-explored. We sought to determine whether pretransplant anemia serves as a marker of altered inflammation in the host and associates with short-term outcomes following lung transplantation. STUDY DESIGN AND METHODS: We performed a single-center, retrospective analysis of 238 lung transplant recipients. We assessed for risk factors of pretransplant anemia and identified associations with short-term post-transplant outcomes. RESULTS: Pretransplant anemia was associated with increased intraoperative transfusion of packed red blood cells and a trend towards increased index hospital length of stay and 1-year mortality. Conversely, pretransplant anemia was associated with a decreased incidence of acute cellular rejection. CONCLUSION: These preliminary data suggest that anemia may be a biomarker of altered inflammation in the host recipient and influences post-transplant outcomes.

The Effect of Anesthesia on Passive Ankle Dorsiflexion.

BACKGROUND: Equinus contractures can commonly be due to contractures of gastrocnemius muscle or combined contractures of the gastrocnemius-soleus Achilles tendon complex. The decision to release part or all of the gastrocnemius-soleus Achilles tendon complex is often assessed intraoperatively while the patient is under anesthesia. It remains unknown whether the administration of general anesthesia affects the measurement of passive ankle dorsiflexion. METHODS: The unaffected, nonoperative limb on 46 foot and ankle patients underwent a Silfverskiold test measuring passive ankle dorsiflexion preoperatively and intraoperatively after administration of general anesthesia using an instrumented force-angular displacement goniometer. To determine clinical significance, we surveyed experienced surgeons to estimate the perceived minimally detectable clinical accuracy for measuring passive ankle dorsiflexion. RESULTS: Forty-six subjects were included with mean age of 42 ± 14.8 years, mean body mass index of 26.2 ± 4.9, and 52% female. The mean change in dorsiflexion values from before anesthesia to after the administration of general anesthesia was 1.9 degrees with 10 lb of pressure with knee extended (E10), 2.3 degrees with 20 lb of pressure with knee extended (E20), 2.8 degrees with 10 lb of pressure with knee flexed (F10), and 2.3 degrees with 20 lb of pressure with knee flexed (F20) (all P < .001). Thirty-three of 45 (73%) surgeons responded to the survey; all thought their minimally detectable clinical accuracy was 5 degrees or greater. CONCLUSION: After the administration of general anesthesia, a small but likely not clinically detectable increase in passive ankle dorsiflexion occurs. The common clinical practice of making intraoperative treatment decisions regarding the presence of a gastrocnemius-soleus driven equinus contractures after general anesthesia without use of paralytic agents appears reasonable given the magnitude of the changes identified in this study.

Evaluation of Costs Associated With Acute Achilles Tendon Repair.

Background: Increasing attention is being paid to the costs associated with various orthopaedic surgeries. Here, we studied the factors that influence costs associated with surgically treated acute Achilles tendon tears. Methods: We retrospectively identified patients with surgically repaired acute Achilles tendon tears, excluding insertional ruptures or chronic tendon issues. Using the Value Driven Outcome (VDO) tool from our institution, we assessed total direct costs as well as facility costs. Briefly, the VDO tool includes an item-level database that can capture detailed cost data-costs are then reported as relative mean data. Cost variables were adjusted to 2022 US dollars, and total direct cost was compared with patient characteristics using gamma regressions to report cost ratios with 95% CIs. Results: Our cohort consisted of 224 patients with Achilles tendon tears surgically repaired by one of 4 fellowship-trained orthopaedic foot and ankle surgeons. There were no differences in demographics, total direct costs, or facility costs based on surgical positioning (prone n = 156, supine n = 68). Open repairs (n = 215), compared with percutaneous techniques (n = 9) that used commercially available instrumentation, had 37% less total direct costs (P < .001, 95% CI 0.55-0.72). Compared with surgery at a main academic hospital (n = 15), procedures at an ambulatory care center (n = 207) had 19% lower total direct costs (P = .040, 95% CI 0.66-0.99) and 41% lower facility costs (P < .001, 95% CI 0.5-0.7). Conclusion: Improving cost-effective orthopaedic care remains an increasingly important goal. Patient positioning for Achilles tendon repair does not appear to have meaningful impacts on cost. When clinically appropriate, considering surgery location at an ambulatory center appears to reduce surgical costs. Level of Evidence: Level III, retrospective comparative study.

Impact of anticoagulation intensity on blood transfusion for venoarterial extracorporeal membrane oxygenation during lung transplantation.

Venoarterial extracorporeal membrane oxygenation is increasingly used for mechanical circulatory support during lung transplant. Optimal intensity of intraoperative anticoagulation would be expected to mitigate thromboembolism without increasing bleeding and blood product transfusions. Yet, the optimal intensity of intraoperative anticoagulation is unknown. We performed a retrospective cohort study of 163 patients who received a bilateral lung transplant at a single center. We categorized the intensity of anticoagulation into 4 groups (very low to high) based on the bolus dose of unfractionated heparin given during lung transplant and compared the rates of intraoperative blood transfusions and the occurrence of thromboembolism between groups. When compared to the very low-intensity group, each higher intensity group was associated with higher red blood cell, fresh frozen plasma, and platelet transfusions. The occurrence of thromboembolism was similar across groups. These preliminary data suggest that lower intensity anticoagulation may reduce the rate of intraoperative blood transfusions, although further study is needed.

Association of circulating fibroblast growth factor 21 levels with all-cause and cardiovascular mortality: The multi-ethnic study of atherosclerosis.

BACKGROUND: Fibroblast growth factor 21 (FGF21) levels are often elevated in cardiovascular disease (CVD). However, no study has assessed its association with cardiovascular and all-cause mortality in a population free of clinically evident CVD. METHODS: A total of 5543 Multi-Ethnic Study of Atherosclerosis (MESA) participants (mean age 62.7 years, 47.5 % male), free of clinically evident CVD at baseline, were studied. From baseline (2000-2002), 1606 deaths (including 387 CVD deaths) were observed over a median follow-up of 17.7 years. Multivariable Cox regression analysis was performed to assess the association of plasma FGF21 levels with mortality. RESULTS: FGF21 levels at baseline were associated with all-cause mortality, even after adjustment for traditional risk factors, including demographic, socioeconomic and cardiovascular risk factors (adjusted hazard ratio 1.08 [95% confidence interval 1.01, 1.16] per 1 SD increase in ln-transformed levels; 1.27 for the highest vs, lowest quartile). Baseline FGF21 levels were significantly associated with both CVD and non-CVD mortality in unadjusted models. However, the association with non-CVD mortality, but not CVD mortality, remained statistically significant after adjusting for covariates. Similar results were obtained in FGF21 quartile analyses and also when using competing risk regression or matched case-control cohort in sensitivity analyses. CONCLUSIONS: In subjects without clinically-evident CVD at baseline, over 17.7 years follow-up there is a modest association of baseline FGF21 levels with all-cause mortality. The finding that this is driven primarily by a significant association with non-CVD mortality over almost two decades merits further investigation.

Ambulatory 7-day mechanical circulatory support in sheep model of pulmonary hypertension and right heart failure.

BACKGROUND: Right heart failure is the major cause of death in pulmonary hypertension. Lung transplantation is the only long-term treatment option for patients who fail medical therapy. Due to the scarcity of donor lungs, there is a critical need to develop durable mechanical support for the failing right heart. A major design goal for durable support is to reduce the size and complexity of devices to facilitate ambulation. Toward this end, we sought to deploy wearable mechanical support technology in a sheep disease model of chronic right heart failure. METHODS: In 6 sheep with chronic right heart failure, a mechanical support system consisting of an extracorporeal blood pump coupled with a gas exchange unit was attached in a right atrium-to-left atrium configuration for up to 7 days. Circuit performance, hematologic parameters, and animal hemodynamics were analyzed. RESULTS: Six subjects underwent the chronic disease model for 56 to 71 days. Three of the subjects survived to the 7-day end-point for circulatory support. The circuit provided 2.8 (0.5) liter/min of flow compared to the native pulmonary blood flow of 3.5 (1.1) liter/min. The animals maintained physiologically balanced blood gas profile with a sweep flow of 1.2 (1.0) liter/min. Two animals freely ambulated while wearing the circuit. CONCLUSIONS: Our novel mechanical support system provided physiologic support for a large animal model of pulmonary hypertension with right heart failure. The small footprint of the circuit and the low sweep requirement demonstrate the feasibility of this technology to enable mobile ambulatory applications.

Using machine learning to predict cardiovascular risk using self-reported questionnaires: Findings from the 45 and Up Study.

BACKGROUND: Machine learning has been shown to outperform traditional statistical methods for risk prediction model development. We aimed to develop machine learning-based risk prediction models for cardiovascular mortality and hospitalisation for ischemic heart disease (IHD) using self-reported questionnaire data. METHODS: The 45 and Up Study was a retrospective population-based study in New South Wales, Australia (2005-2009). Self-reported healthcare survey data on 187,268 participants without a history of cardiovascular disease was linked to hospitalisation and mortality data. We compared different machine learning algorithms, including traditional classification methods (support vector machine (SVM), neural network, random forest and logistic regression) and survival methods (fast survival SVM, Cox regression and random survival forest). RESULTS: A total of 3687 participants experienced cardiovascular mortality and 12,841 participants had IHD-related hospitalisation over a median follow-up of 10.4 years and 11.6 years respectively. The best model for cardiovascular mortality was a Cox survival regression with L1 penalty at a re-sampled case/non-case ratio of 0.3 achieved by under-sampling of the non-cases. This model had the Uno's and Harrel's concordance indexes of 0.898 and 0.900 respectively. The best model for IHD hospitalisation was a Cox survival regression with L1 penalty at a re-sampled case/non-case ratio of 1.0 with Uno's and Harrel's concordance indexes of 0.711 and 0.718 respectively. CONCLUSION: Machine learning-based risk prediction models developed using self-reported questionnaire data had good prediction performance. These models may have the potential to be used in initial screening tests to identify high-risk individuals before undergoing costly investigation.

The association of circulating fibroblast growth factor 21 levels with incident heart failure: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Fibroblast growth factor 21 (FGF21) levels are often elevated in heart failure (HF), although this has not been assessed using a longitudinal study design. Therefore, we investigated the association between baseline plasma FGF21 levels and incident HF in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: A total of 5408 participants, free of clinically apparent cardiovascular disease, were included in the analysis, of which 342 developed HF over a median follow-up period of 16.7 years. Multivariable Cox regression analysis was performed and the additive value of FGF21 in the performance of risk prediction over other well-established cardiovascular biomarkers was assessed. RESULTS: The mean age of the participants was 62.6 years with 47.6 % male. Regression spline analysis demonstrated a significant association of FGF21 levels with incident HF among participants with FGF21 levels ≥239.0 pg/mL (hazard ratio = 1.84 [95 % confidence interval 1.21, 2.80] per SD increase in ln-transformed levels) after adjustment for traditional cardiovascular risk factors and biomarkers, but not in participants with FGF21 levels <239.0 pg/mL (p for heterogeneity = 0.004). Among participants with FGF21 levels ≥239.0 pg/mL, FGF21 levels were associated with HF with preserved ejection fraction (HR [95 % CI] = 2.57 [1.51, 4.37]), but not HF with reduced ejection fraction. CONCLUSIONS: The present study suggests baseline FGF21 levels could predict the development of incident HF with preserved ejection fraction, among participants with elevated FGF21 levels at baseline. This study may suggest a pathophysiological role of FGF21 resistance in HF with preserved ejection fraction.

Consensus-based recommendations for optical coherence tomography angiography reporting in uveitis.

BACKGROUND/AIMS: To establish a consensus in the nomenclature for reporting optical coherence tomography angiography (OCTA findings in uveitis. METHODS: The modified Delphi process consisted of two rounds of electronic questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-one items were included for discussion. The three main areas of discussion were: wide field OCTA (WF-OCTA), nomenclature of OCTA findings and OCTA signal attenuation assessment and measurement. Seventeen specialists in uveitis and retinal imaging were selected by the executive committee to constitute the OCTA nomenclature in Uveitis Delphi Study Group. The study endpoint was defined by the degree of consensus for each question: 'strong consensus' was defined as >90% agreement, 'consensus' as 85%-90% and 'near consensus' as >80% but <85%. RESULTS: There was a strong consensus to apply the term 'wide field' to OCTA images measuring over 70° of field of view, to use the terms 'flow deficit' and 'non-detectable flow signal' to describe abnormal OCTA flow signal secondary to slow flow and to vessels displacement respectively, to use the terms 'loose' and 'dense' to describe the appearance of inflammatory choroidal neovascularisation, and to use the percentage of flow signal decrease to measure OCTA ischaemia with a threshold greater than or equal to 30% as a 'large area'. CONCLUSIONS: This study sets up consensus recommendations for reporting OCTA findings in uveitis by an expert panel, which may prove suitable for use in routine clinical care and clinical trials.

Fibroblast growth factor 21 in heart failure.

Fibroblast growth factor 21 (FGF21) is a peptide hormone involved in energy homeostasis that protects against the development of obesity and diabetes in animal models. Its level is elevated in atherosclerotic cardiovascular diseases (CVD) in humans. However, little is known about the role of FGF21 in heart failure (HF). HF is a major global health problem with a prevalence that is predicted to rise, especially in ageing populations. Despite improved therapies, mortality due to HF remains high, and given its insidious onset, prediction of its development is challenging for physicians. The emergence of cardiac biomarkers to improve prediction, diagnosis, and prognosis of HF has received much attention over the past decade. Recent studies have suggested FGF21 is a promising biomarker candidate for HF. Preclinical research has shown that FGF21 is involved in the pathophysiology of HF through the prevention of oxidative stress, cardiac hypertrophy, and inflammation in cardiomyocytes. However, in the available clinical literature, FGF21 levels appear to be paradoxically raised in HF, potentially implying a FGF21 resistant state as occurs in obesity. Several potential confounding variables complicate the verdict on whether FGF21 is of clinical value as a biomarker. Further research is thus needed to evaluate whether FGF21 has a causal role in HF, and whether circulating FGF21 can be used as a biomarker to improve the prediction, diagnosis, and prognosis of HF. This review draws from preclinical and clinical studies to explore the role of FGF21 in HF.

Implementing integrated care in ophthalmology: a community case study.

Introduction: In 2017, in a context of financial and patient care challenges, Moorfields Eye Hospital in the borough of Croydon launched the first Ophthalmology Integrated Care Contract in the United Kingdom. Description: A realistic, systematic approach is presented for an efficient implementation of an integrated care ophthalmology contract under a lead provider. The main elements of the new contract are portrayed. Discussion: A new healthcare contract that would lead to system-wide transformation requires significant time commitment, vision, shared narrative, leadership, multi-functional working culture, shared accountability of all participating parties and education and support of all parties involved. Key levers to elevate the quality of care are collaborative relationships between health professionals, investing in information and technology and facilitating bottom-up innovation. Conclusion: System-wide changes such, as integrated care contracts are possible, although the interplay between context, design and implementation is more complex than expected.

Debridement Versus Simple Scrubbing of External Fixator Pin Sites.

Introduction: Irrigation and debridement of external fixator pin sites are methods utilized by some orthopedic surgeons to minimize the risk of surgical site infections in patients undergoing definitive internal fixation after temporization in an external fixation device. This study aimed to determine if irrigation and debridement of external fixator pin sites leads to fewer deep surgical site infections, compared to simply scrubbing the external fixator pin sites with a chlorhexidine scrub-brush. Methods: This single center retrospective cohort study was performed at a university level I trauma center. All cases in which a single surgeon removed an external fixator and followed this with definitive open reduction and internal fixation (ORIF) in the same operative setting between October 2007 and October 2018 were reviewed. A total of 313 patients were temporized in 334 external fixators prior to ORIF and were included in the study. Results: Eighteen of the 179 Irrigation and Debridement cohort (10.0%) and 8 of the 155 Simple Scrubbing cohort (5.2%) had infections that required a return to the operating room. No statistical difference (p = 0.10) or meaningful effect size (Cohen's d = 0.18) were found between irrigation and debridement and simple scrubbing of external fixator pin sites. Conclusions: Given no significant differences were found in deep infection rates between debridement of pin sites versus simply scrubbing, it is reasonable to ask whether the time and resources required for debriding external fixator pin sites is worthwhile.

Nationwide Analysis of Total Ankle Replacement and Ankle Arthrodesis in Medicare Patients: Trends, Complications, and Cost.

BACKGROUND: Surgical management of end-stage ankle arthritis consists of either ankle arthrodesis (AA) or total ankle replacement (TAR). The purpose of this study was to evaluate utilization trends in TAR and AA and compare cost and complications. METHODS: Medicare patients with the diagnosis of ankle arthritis were reviewed. Patients undergoing surgical intervention were split into AA and TAR groups, which were evaluated for trends as well as postoperative complications, revision rates, and procedure cost. RESULTS: A total of 673 789 patients were identified with ankle arthritis. A total of 19 120 patients underwent AA and 9059 underwent TAR. While rates of AA remained relatively constant, even decreasing, with 2080 performed in 2005 and 1823 performed in 2014, TAR rates nearly quadrupled. Average cost associated with TAR was $12559.12 compared with $6962.99 for AA (P < .001). Overall complication rates were 24.9% in the AA group with a 16.5% revision rate compared with 15.1% and 11.0%, respectively, in the TAR group (P < .001). Patients younger than 65 years had both higher complication and revision rates. DISCUSSION: TAR has become an increasingly popular option for the management of end-stage ankle arthritis. In our study, TAR demonstrated both lower revision and complication rates than AA. However, TAR represents a more expensive treatment option. LEVELS OF EVIDENCE: Level III: Retrospective comparative study.