Incidence of venous thromboembolism in patients with peripheral arterial disease after endovascular intervention.

OBJECTIVE: Venous thromboembolism (VTE) is a well-known postoperative complication; however, the incidence of VTE after peripheral vascular intervention (PVI) has not been well described. Despite the minimally invasive nature of these procedures, the patients undergoing PVI have significant risk factors for the development of VTE. In the present study, our objective was to describe the short-term incidence of VTE after PVI, identify differences between sexes, and examine the periprocedural antiplatelet and anticoagulation regimens. METHODS: We identified adults (age >66 years) who had undergone PVI from January 1, 2008 to September 30, 2015 from the inpatient Medicare claims data. The patients were followed for 365 days after the procedure. VTE events during follow-up were identified using the International Classification of Diseases, 9th revision, diagnosis codes. The covariate-standardized 30- and 90-day cumulative incidence of VTE events, overall and stratified by sex, were estimated using Aalen-Johansen estimators, accounting for death as a competing risk. Differences in sex between females and males were identified using Gray's test. Any antiplatelet or anticoagulant prescription fill was defined as any fill from 14 days before the endovascular intervention through the date of the VTE event. Persistence with antiplatelet and anticoagulant therapy was assessed by creating daily logs of antiplatelet and anticoagulant coverage using the dispensing dates and days of supply. Over-the-counter medications (ie, aspirin) were not evaluated. RESULTS: We identified 31,593 qualifying patients with a mean age of 76.8 ± 7.4 years. Of the 31,593 patients, 46% were male, and 12% had a history of VTE. After the procedure, deep vein thrombosis (DVT) was a commonly diagnosed complication (3.8% and 4.8% at 30 and 90 days, respectively). The cumulative incidence of pulmonary embolism was 0.9% and 1.2% at 30 and 90 days after the procedure, respectively. Throughout the 90-day postoperative period, females had had a slightly increased risk of DVT compared with males (30-day risk difference, 0.007; P < .01; 90-day risk difference, 0.008; P = .02). We found no sex-based differences in the risk of pulmonary embolism. Of the patients who had developed VTE at 90 days, 970 (55%) had had no prescription fill for an antiplatelet or anticoagulant. Assuming all the patients had been taking aspirin, only 15% of the patients who had developed VTE had been taking prescribed dual antiplatelet medication persistently after PVI. In addition, among the patients who had developed VTE at 90 days, females were less likely to have had a prescription fill for an anticoagulant. CONCLUSIONS: The findings from our study have demonstrated that the incidence of VTE after PVI is high, with an increased risk of deep vein thrombosis for females. We also found that females were less likely to have been prescribed an anticoagulant after PVI. Future studies are needed to characterize the variables associated with an increased risk of VTE after PVI and to identify strategies to increase dual antiplatelet therapy or anticoagulant prescription adherence to reduce the risk of VTE.

Increased long-term bleeding complications in females undergoing endovascular revascularization for peripheral arterial disease.

OBJECTIVE: Females with peripheral arterial disease (PAD) treated with endovascular interventions have increased limb-based procedural complications compared with males. Little is known regarding long-term bleeding risk in these patients who often require long-term antiplatelet or anticoagulation therapy. We hypothesize that females have a higher incidence of bleeding events compared with males in the year after endovascular intervention for PAD. METHODS: Adults (aged ≥65 years) who underwent endovascular revascularization for PAD between 2008 and 2015 in Medicare claims data were identified. Patients were allocated by prescribed postprocedural antithrombotic therapy, including (1) antiplatelet therapy, (2) anticoagulation therapy, (3) dual antiplatelet and anticoagulation therapy, and (4) no prescription antithrombotic therapy. Bleeding events were classified as gastrointestinal, intracranial, hematoma, airway, or other. Crude and covariate-standardized 30-, 90-, and 365-day cumulative incidence of bleeding events, overall and by sex, were estimated using Aalen-Johansen estimators accounting for death as a competing risk. Sex differences were identified using Gray's test. RESULTS: Of 31,593 eligible patients, 54% were females. Females were older (77.9 years vs 75.5 years) and tended to use antiplatelet therapy more often at 30, 90, and 365 days after the intervention. Clopidogrel was the most prescribed antiplatelet, and 32% of patients continued its use at 365 days. Anticoagulants were prescribed to 26.0% of patients at the time of the procedure, and only 8.8% continued anticoagulation at 365 days. Thirty-one percent of patients were diagnosed with a bleeding event within 1 year after the intervention. The cumulative incidence of any bleeding event during the postintervention period was higher in females compared with males with a risk difference of 3% between the sex cohorts (P < .01). Specifically, females had a higher incidence of gastrointestinal bleeding and hematoma (P < .01), but a lower incidence of airway-related bleeding at each time point as compared with males (P < .01). CONCLUSIONS: Sex disparities in bleeding complications after endovascular intervention for PAD persist in the long term. Females are more likely to be readmitted with a bleeding complication up to 1 year after the procedure. Antithrombotic therapy disproportionately increases the risk of bleeding in females. Further research is necessary to understand the mechanisms responsible for abnormal coagulopathy in females after endovascular therapy.

Posthospitalization outcomes after extracorporeal membrane oxygenation (ECMO) for COVID-19.

BACKGROUND: Critical illness from COVID-19 is associated with prolonged hospitalization and high mortality rates. Extracorporeal membrane oxygenation is used for refractory severe acute respiratory distress syndrome in COVID-19 with outcomes comparable to other indications for extracorporeal membrane oxygenation. However, long-term functional outcomes have yet to be fully elucidated. METHODS: We performed a retrospective chart review of 24 consecutive patients who required extracorporeal membrane oxygenation due to COVID-19 associated severe acute respiratory distress syndrome and survived to hospital discharge. After hospitalization, we contacted patients and administered the Patient-Reported Outcomes Measurement Information System (PROMIS) Global-10 tool to assess longer-term outcomes. We abstracted demographics, clinical course, outcomes, and disposition variables from the electronic medical record. Descriptive statistical analysis was used on the retrospective data collection. RESULTS: Inpatient data were analyzed for 24 patients, and 21 of 24 (88%) patients completed the Patient-Reported Outcomes Measurement Information System tool at an average of 8.8 months posthospitalization. At hospital discharge, 62.5% of patients had ongoing oxygen requirements (nasal cannula, trach collar, or mechanical ventilation); 70.8% were discharged to a location other than home. However, at the time of follow-up, only 9.5% of patients required supplemental oxygen, all tracheostomies had been removed, and all patients resided at home. Patients reported relatively high levels of global physical function, and though there was a high reported incidence of fatigue, overall pain scores were low. CONCLUSION: Long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome from coronavirus disease 2019 are promising. Extracorporeal membrane oxygenation therapy may confer morbidity benefits in patients with coronavirus disease and remains a valuable modality with excellent functional outcomes and preserved quality of life for survivors.

Trends and Outcomes in Minimally Invasive Surgery for Locally Advanced Non-Small-Cell Lung Cancer With N2 Disease.

Few studies examine outcomes by surgical approach in non-small-cell lung cancer (NSCLC) with N2 disease. We examined time trends in surgical approach and outcomes among patients undergoing minimally invasive (MIS, robotic and video-assisted thoracoscopic surgery [VATS]) vs open lobectomy in this patient population. We performed a retrospective analysis of patients from the National Cancer Database diagnosed with clinical Stage IIIA-N2 NSCLC from 2010 to 2016. We examined the yearly proportion of MIS vs open resections. Multivariable regression was used to assess the association of surgical approach with length of stay, unplanned readmissions, 30-day and 90-day mortality. Multivariable Cox proportional hazards modeling was used to assess the association of surgical approach with 5-year overall mortality. We identified 5741 patients who underwent lobectomy for Stage IIIA-N2 NSCLC (459 robotic, 1403 VATS, 3879 open). From 2010 to 2016, the proportion of minimally invasive procedures increased from 20% to 45%. MIS patients, on average, stayed 1 day less in the hospital (95% confidence interval [CI] 0.7, 1.5) and had lower odds of 90-day (odds ratio [OR] 0.74; 95% CI 0.54, 0.99) and 5-year mortality (OR 0.82; 95% CI 0.75, 0.91), compared to open resections. There was no difference in odds of readmission by surgical approach (OR 0.97; 95% CI 0.71, 1.33). Among MIS procedures, robotic resections had lower odds of 90-day mortality (OR 0.42; 95% CI 0.18, 0.97) than VATS. Among patients undergoing lobectomy for locally advanced N2 NSCLC robotic and VATS techniques appear safe and effective compared to open surgery and may offer short- and long-term advantages.

Does routine uniportal thoracoscopy during rib fixation identify more injuries and impact outcomes?

BACKGROUND: Flail chest and severely displaced rib fractures due to blunt trauma can be associated with intrathoracic injuries. At our institution, two thoracic surgeons perform all surgical stabilization of rib fractures (SSRF): one performs routine uniportal thoracoscopy (R-VATS) at the time of SSRF and the other for only select cases (S-VATS). In this pilot study, we hypothesized that R-VATS at the time of SSRF identifies and addresses intrathoracic injuries not seen on imaging and may impact patient outcomes. METHODS: A retrospective review of all patients who underwent SSRF from 2013-2019 at our institution was performed for severely displaced rib fractures or flail chest. Data collected included demographics, imaging results, treatment strategy, and operative findings. RESULTS: Ninety-nine patients underwent SSRF. Uniportal thoracoscopy was performed on 69% of these patients. When thoracoscopy was performed, 31 additional injuries were identified. R-VATS identified 23 additional intrathoracic findings at time of thoracoscopy not seen on CT scan compared to 8 findings in the S-VATS group (P=0.367). At 3 months follow-up, one empyema and one diaphragmatic hernia required reoperation-neither of which underwent thoracoscopy at time of SSRF. There were no differences in LOS, operative times, and overall mortality between the SSRF/thoracoscopy and SSRF only groups. CONCLUSIONS: R-VATS at the time of SSRF did not identify a statistically significant greater number of occult intrathoracic injuries compared to S-VATS. R-VATS was not associated with increased operative time, LOS, and mortality. Further study is needed to determine if there is benefit to R-VATS in patients meeting requirements for rib fracture repair.

Poor glycemic control is associated with significant increase in major limb amputation and adverse events in the 30-day postoperative period after infrainguinal bypass.

OBJECTIVE: Understanding modifiable risk factors to improve surgical outcomes is increasingly important in value-based health care. There is an established association between peripheral artery disease (PAD), diabetes, and limb loss, but less is known about expected outcomes after revascularization relative to the degree of glycemic control. The purpose of this study was to determine the association between hemoglobin A1c (HbA1c) management in diabetics and surgical outcomes after open infrainguinal bypass. METHODS: The Vascular Quality Initiative infrainguinal bypass module was used to identify adult patients (≥18 years) with a history of diabetes who underwent bypass for PAD between 2011 and 2018. Exclusion criteria included missing or illogical HbA1c values and if the indication for the limb treated was not PAD. Patients were categorized by preoperative HbA1c levels as low severity/controlled (<7.0%), high severity (7.0%-10.0%), and very high severity (>10.0%). Primary outcomes were 30-day incidence of major adverse cardiac events (MACEs), major adverse limb events (MALEs), ipsilateral amputation, and 1-year all-cause mortality. Thirty-day outcomes were calculated using multivariable regression to compute odds ratios; hazard ratios were calculated for all-cause mortality. All analyses were adjusted for demographics, comorbidities, and clinical characteristics. RESULTS: The final sample included 30,813 operations (27,988 unique patients): 17,517 (57%) nondiabetic patients, 5194 patients with low-severity/controlled diabetes, and 8102 (26%) patients with poorly controlled diabetes, including 5531 (70%) treated with insulin. There were 6439 (21%) patients with high-severity HbA1c values and 1663 (5%) patients with very-high-severity HbA1c values. Those with a very high HbA1c level were more likely to be nonwhite, insulin dependent, and active smokers. Compared with nondiabetics, patients with very-high-severity HbA1c had an 81% increase in MACEs and 31% increase in MALEs, whereas patients with high-severity HbA1c only had a 49% increase in MACEs and a 12% increase in MALEs. Each one-step increase in severity category (eg, low to high to very high) was associated with an average 29% increase in the odds of MACEs and an 8% increase in the odds of MALEs. CONCLUSIONS: Uncontrolled diabetes with an HbA1c value >10.0% was associated with significantly worse 30-day surgical outcomes. Patients with incrementally better glycemic control (HbA1c level of 7.0%-10.0%) did not suffer the same rate of complications, suggesting that preoperative attempts at improving diabetes management even slightly could lead to improved surgical outcomes in open infrainguinal bypass patients.

Engineering Parvalbumin for the Heart: Optimizing the Mg Binding Properties of Rat ß-Parvalbumin.

Parvalbumin (PV), an EF-hand protein family member, is a delayed calcium buffer that exchanges magnesium for calcium to facilitate fast skeletal muscle relaxation. Genetic approaches that express parvalbumin in the heart also enhance relaxation and show promise of being therapeutic against various cardiac diseases where relaxation is compromised. Unfortunately, skeletal muscle PVs have very slow rates of Ca(2+) dissociation and are prone to becoming saturated with Ca(2+), eventually losing their buffering capability within the constantly beating heart. In order for PV to have a more therapeutic potential in the heart, a PV with faster rates of calcium dissociation and high Mg(2+) affinity is needed. We demonstrate that at 35°C, rat ß-PV has an ~30-fold faster rate of Ca(2+) dissociation compared to rat skeletal muscle α-PV, and still possesses a physiologically relevant Ca(2+) affinity (~100 nM). However, rat ß-PV will not be a delayed Ca(2+) buffer since its Mg(2+) affinity is too low (~1 mM). We have engineered two mutations into rat ß-PV, S55D and E62D, when observed alone increase Mg(2+) affinity up to fivefold, but when combined increase Mg(2+) affinity ~13-fold, well within a physiologically relevant affinity. Furthermore, the Mg(2+) dissociation rate (172/s) from the engineered S55D, E62D PV is slow enough for delayed Ca(2+) buffering. Additionally, the engineered PV retains a high Ca(2+) affinity (132 nM) and fast rate of Ca(2+) dissociation (64/s). These PV design strategies hold promise for the development of new therapies to remediate relaxation abnormalities in different heart diseases and heart failure.