Critical Care Management of Severe Asthma Exacerbations.

Severe asthma exacerbations, including near-fatal asthma (NFA), have high morbidity and mortality. Mechanical ventilation of patients with severe asthma is difficult due to the complex pathophysiology resulting from severe bronchospasm and dynamic hyperinflation. Life-threatening complications of traditional ventilation strategies in asthma exacerbations include the development of systemic hypotension from hyperinflation, air trapping, and pneumothoraces. Optimizing pharmacologic techniques and ventilation strategies is crucial to treat the underlying bronchospasm. Despite optimal pharmacologic management and mechanical ventilation, the mortality rate of patients with severe asthma in intensive care units is 8%, suggesting a need for advanced non-pharmacologic therapies, including extracorporeal life support (ECLS). This review focuses on the pathophysiology of acute asthma exacerbations, ventilation management including non-invasive ventilation (NIV) and invasive mechanical ventilation (IMV), the pharmacologic management of acute asthma, and ECLS. This review also explores additional advanced non-pharmacologic techniques and monitoring tools for the safe and effective management of critically ill adult asthmatic patients.

Asthma morbidity measures across Black ethnic subgroups.

BACKGROUND: Black adults are disproportionately affected by asthma and are often considered a homogeneous group in research studies despite cultural and ancestral differences. OBJECTIVE: We sought to determine if asthma morbidity differs across adults in Black ethnic subgroups. METHODS: Adults with moderate-severe asthma were recruited across the continental United States and Puerto Rico for the PREPARE (PeRson EmPowered Asthma RElief) trial. Using self-identifications, we categorized multiethnic Black (ME/B) participants (n = 226) as Black Latinx participants (n = 146) or Caribbean, continental African, or other Black participants (n = 80). African American (AA/B) participants (n = 518) were categorized as Black participants who identified their ethnicity as being American. Baseline characteristics and retrospective asthma morbidity measures (self-reported exacerbations requiring systemic corticosteroids [SCs], emergency department/urgent care [ED/UC] visits, hospitalizations) were compared across subgroups using multivariable regression. RESULTS: Compared with AA/B participants, ME/B participants were more likely to be younger, residing in the US Northeast, and Spanish speaking and to have lower body mass index, health literacy, and <1 comorbidity, but higher blood eosinophil counts. In a multivariable analysis, ME/B participants were significantly more likely to have ED/UC visits (incidence rate ratio [IRR] = 1.34, 95% CI = 1.04-1.72) and SC use (IRR = 1.27, 95% CI = 1.00-1.62) for asthma than AA/B participants. Of the ME/B subgroups, Puerto Rican Black Latinx participants (n = 120) were significantly more likely to have ED/UC visits (IRR = 1.64, 95% CI = 1.22-2.21) and SC use for asthma (IRR = 1.43, 95% CI = 1.06-1.92) than AA/B participants. There were no significant differences in hospitalizations for asthma among subgroups. CONCLUSIONS: ME/B adults, specifically Puerto Rican Black Latinx adults, have higher risk of ED/UC visits and SC use for asthma than other Black subgroups.

Preference for and impact of telehealth vs in-person asthma visits among Black and Latinx adults.

BACKGROUND: Black and Latinx adults experience disproportionate asthma-related morbidity and limited specialty care access. The severe acute respiratory syndrome coronavirus 2 pandemic expanded telehealth use. OBJECTIVE: To evaluate visit type (telehealth [TH] vs in-person [IP]) preferences and the impact of visit type on asthma outcomes among Black and Latinx adults with moderate-to-severe asthma. METHODS: For this PREPARE trial ancillary study, visit type preference was surveyed by e-mail or telephone post-trial. Emergency medical record data on visit types and asthma outcomes were available for a subset (March 2020 to April 2021). Characteristics associated with visit type preferences, and relationships between visit type and asthma outcomes (control [Asthma Control Test] and asthma-related quality of life [Asthma Symptom Utility Index]), were tested using multivariable regression. RESULTS: A total of 866 participants consented to be surveyed, with 847 respondents. Among the participants with asthma care experience with both visit types, 42.0% preferred TH for regular checkups, which associated with employment (odds ratio [OR] = 1.61; 95% confidence interval [CI], 1.09-2.39; P = .02), lower asthma medication adherence (OR = 1.06; 95% CI, 1.01-1.11; P = .03), and having more historical emergency department and urgent care asthma visits (OR = 1.10 for each additional visit; 95% CI, 1.02-1.18; P = .02), after adjustment. Emergency medical record data were available for 98 participants (62 TH, 36 IP). Those with TH visits were more likely Latinx, from the Southwest, employed, using inhaled corticosteroid-only controller therapy, with lower body mass index, and lower self-reported asthma medication adherence vs those with IP visits only. Both groups had comparable Asthma Control Test (18.4 vs 18.9, P = .52) and Asthma Symptom Utility Index (0.79 vs 0.84, P = .16) scores after adjustment. CONCLUSION: TH may be similarly efficacious as and often preferred over IP among Black and Latinx adults with moderate-to-severe asthma, especially for regular checkups. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02995733.

Lung Transplantation for COVID-19 Pulmonary Sequelae.

BACKGROUND: The role of lung transplantation for coronavirus disease 2019 (COVID-19)-related lung failure is evolving as the pandemic persists. METHODS: From January 2021 to April 2022, 20 patients (median age 62 y; range 31-77) underwent lung transplantation for COVID-related lung failure at our institution. We reviewed their clinical and intraoperative characteristics and early outcomes including postoperative complications. RESULTS: Eleven patients (55%) had chronic lung disease when they contracted COVID-19. All 20 patients required hospitalization for antivirus treatment. Median lung allocation score was 74.7 (33.1-94.0). Thirteen patients (65%) underwent single-lung transplants, and 7 patients (35%) underwent double-lung transplants. Concomitant coronary artery bypass graft surgery was performed in 2 (10%) patients because of severe coronary artery disease. Postoperatively, venovenous extracorporeal membrane oxygenation was needed in 3 patients (15%) because of severe primary graft dysfunction; all were eventually weaned. Ten patients (50%) experienced deep venous thrombosis, and 1 eventually developed a major pulmonary embolus. The median intensive care unit stay and hospital stays were 6.5 d (3-44) and 18 d (7-77), respectively. During a median follow-up of 201 d (47-418), we experienced 1 late mortality due to COVID-19-related myocarditis. Among the 13 patients with single-lung transplant, 5 demonstrated improvement in their native lungs. CONCLUSIONS: Lung transplantation yielded favorable early outcomes in a heterogeneous patient cohort that included older patients, obese patients, and patients with coronary artery disease or preexisting chronic lung disease. Our data also shed light on the transforming role of lung transplantation for the pulmonary sequelae of a complex multisystem COVID-19 disorder.

Single-institution experience of extracorporeal membrane oxygenation for near-fatal asthma.

Near-fatal asthma (NFA) is the most severe presentation of asthma. It is characterized by hypoxemic and hypercapnic respiratory failure requiring ventilatory assistance, including non-invasive ventilation and mechanical ventilation. However, NFA has a high mortality rate despite conventional therapy. Extracorporeal membrane oxygenation (ECMO) is a treatment modality that is increasingly being utilized as rescue therapy in patients with NFA that is refractory to mechanical ventilation. Prior analyses of the international Extracorporeal Life Support Organization (ELSO) registry data showed a survival rate of over 83% in patients placed on venovenous (VV) ECMO for NFA, but with notable rate of hemorrhagic complications. We report seven cases of adults with NFA requiring ECMO support at our large quaternary care institution between the years 2019 and 2022. All seven patients presented with respiratory failure in the setting of asthma exacerbation that progressed despite standard pharmacotherapy and mechanical ventilation. All patients survived to hospital discharge after ECMO support without hemorrhagic complications, highlighting the effectiveness and safety of ECMO when appropriately used in this population.

Caribbean Latinx with moderate-severe asthma bear greater asthma morbidity than other Latinx.

BACKGROUND: Hispanic/Latinx (HL) ethnicity encompasses racially and culturally diverse subgroups. Studies suggest that Puerto Ricans (PR) may bear greater asthma-related morbidity than Mexicans, but these were conducted in children or had limited clinical characterization. OBJECTIVES: This study sought to determine whether disparities in asthma morbidity exist among HL adult subgroups. METHODS: Adults with moderate-severe asthma were recruited from US clinics, including from Puerto Rico, for the Person Empowered Asthma Relief (PREPARE) trial. Considering the shared heritage between PR and other Caribbean HL (Cubans and Dominicans [C&D]), the investigators compared baseline self-reported clinical characteristics between Caribbean HL (CHL) (PR and C&D: n = 457) and other HLs (OHL) (Mexicans, Spaniards, Central/South Americans; n = 141), and between CHL subgroups (C&D [n = 56] and PR [n = 401]). This study compared asthma morbidity measures (self-reported exacerbations requiring systemic corticosteroids, emergency department/urgent care (ED/UC) visits, hospitalizations, health care utilization) through negative binomial regression. RESULTS: CHL compared to OHL were similar in age, body mass index, poverty status, blood eosinophils, and fractional exhaled nitric oxide but were prescribed more asthma controller therapies. Relative to OHL, CHL had significantly increased odds of asthma exacerbations (odds ratio [OR]: 1.84; 95% CI: 1.4-2.4), ED/UC visits (OR: 1.88; 95% CI: 1.4-2.5), hospitalization (OR: 1.98; 95% CI: 1.06-3.7), and health care utilization (OR: 1.91; 95% CI: 1.44-2.53). Of the CHL subgroups, PR had significantly increased odds of asthma exacerbations, ED/UC visits, hospitalizations, and health care utilization compared to OHL, whereas C&D only had increased odds of exacerbations compared to OHL. PR compared to C&D had greater odds of ED/UC and health care utilization. CONCLUSIONS: CHL adults, compared with OHL, adults reported nearly twice the asthma morbidity; these differences are primarily driven by PR. Novel interventions are needed to reduce morbidity in this highly impacted population.

Single Lung Transplant Remains a Viable Option for Patients With Severe Secondary Pulmonary Hypertension.

BACKGROUND: Although double lung transplant is recommended in patients with severe secondary pulmonary hypertension (SPH), our institutional experiences suggest a role for single lung transplant in these patients. Here, we review our experience prioritizing single lung transplant in patients with SPH to minimize their surgical burden. METHODS: We conducted a retrospective review of our lung transplant database to identify patients with SPH who underwent single lung transplant. Patients were stratified as either mild SPH (mean pulmonary artery pressure 25-40 mm Hg) or severe SPH (mean pulmonary artery pressure >40 mm Hg). Singe lung recipients without PH transplanted over the same time were also examined. RESULTS: Between January 2017 and December 2019, 318 patients underwent single lung transplantation; 217 had mild SPH (68%), and 59 had severe SPH (18.5%). Forty-two patients without PH underwent single lung transplant. When the groups were compared, significantly higher pulmonary vascular resistance was noted in the severe SPH group, and obesity was noted in both the mild and severe SPH groups. Although the severe SPH group required more intraoperative cardiopulmonary support (37.3% versus 10.3% versus 4.7%, P < 0.05), there were no significant differences in most major postoperative parameters, including the duration of postoperative mechanical ventilation or the incidence of severe primary graft dysfunction. Survival 1 y posttransplant was not significantly different among the groups (93.2% versus 89.4% versus 92.9%, P = 0.58). CONCLUSIONS: Our experience supports the option of single lung transplantation with appropriate intraoperative mechanical circulatory support in patients with SPH. This strategy is worth pursuing, especially with ongoing donor lung shortages.

Reliever-Triggered Inhaled Glucocorticoid in Black and Latinx Adults with Asthma.

BACKGROUND: Black and Latinx patients bear a disproportionate burden of asthma. Efforts to reduce the disproportionate morbidity have been mostly unsuccessful, and guideline recommendations have not been based on studies in these populations. METHODS: In this pragmatic, open-label trial, we randomly assigned Black and Latinx adults with moderate-to-severe asthma to use a patient-activated, reliever-triggered inhaled glucocorticoid strategy (beclomethasone dipropionate, 80 µg) plus usual care (intervention) or to continue usual care. Participants had one instructional visit followed by 15 monthly questionnaires. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included monthly asthma control as measured with the Asthma Control Test (ACT; range, 5 [poor] to 25 [complete control]), quality of life as measured with the Asthma Symptom Utility Index (ASUI; range, 0 to 1, with lower scores indicating greater impairment), and participant-reported missed days of work, school, or usual activities. Safety was also assessed. RESULTS: Of 1201 adults (603 Black and 598 Latinx), 600 were assigned to the intervention group and 601 to the usual-care group. The annualized rate of severe asthma exacerbations was 0.69 (95% confidence interval [CI], 0.61 to 0.78) in the intervention group and 0.82 (95% CI, 0.73 to 0.92) in the usual-care group (hazard ratio, 0.85; 95% CI, 0.72 to 0.999; P = 0.048). ACT scores increased by 3.4 points (95% CI, 3.1 to 3.6) in the intervention group and by 2.5 points (95% CI, 2.3 to 2.8) in the usual-care group (difference, 0.9; 95% CI, 0.5 to 1.2); ASUI scores increased by 0.12 points (95% CI, 0.11 to 0.13) and 0.08 points (95% CI, 0.07 to 0.09), respectively (difference, 0.04; 95% CI, 0.02 to 0.05). The annualized rate of missed days was 13.4 in the intervention group and 16.8 in the usual-care group (rate ratio, 0.80; 95% CI, 0.67 to 0.95). Serious adverse events occurred in 12.2% of the participants, with an even distribution between the groups. CONCLUSIONS: Among Black and Latinx adults with moderate-to-severe asthma, provision of an inhaled glucocorticoid and one-time instruction on its use, added to usual care, led to a lower rate of severe asthma exacerbations. (Funded by the Patient-Centered Outcomes Research Institute and others; PREPARE ClinicalTrials.gov number, NCT02995733.).

The Incidence of Adjacent Segment Pathology After Cervical Disc Arthroplasty Compared with Anterior Cervical Discectomy and Fusion: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

OBJECTIVE: The aim of this study was to assess rates of adjacent segment degeneration (ASDeg), adjacent segment disease (ASDis), and reoperation rates as a result of adjacent segment pathology in patients who have undergone anterior cervical discectomy and fusion (ACDF) versus cervical disc arthroplasty (CDA). METHODS: A comprehensive search of randomized controlled trials was performed in PubMed from 2012 to 2019. Relevant studies included were assessed for quality using the Cochrane Beck Review Group guidelines. Rates of ASDeg, ASDis, and reoperation because of adjacent segment pathology were extracted and included in the final analysis. A random-effects and fixed-effects model was run among studies that showed high and low heterogeneity, respectively. RESULTS: A total of 19 studies were included in the final analysis, comprising 4655 patients. Overall, ACDFs reported significantly higher rates of ASDeg (19.7% vs. 14.4%; P < 0.001), ASDis (6.1% vs. 3.8%; P < 0.001), and reoperation rates (6.1% vs. 3.1%; P < 0.001) compared with CDAs, which was further corroborated in fixed-effects analysis. When stratified by length of follow-up, a significant difference was seen in ASDeg, ASDis, and reoperation rates of studies with follow-up of 12-48 months versus >48 months, with the exception of ASDeg rates in the CDA cohort. CONCLUSIONS: Our study shows CDA results in significantly lower ASDeg, ASDis, and reoperation rates. Although CDA may be a viable alternative to ACDF, further long-term studies are warranted to ensure consistency and establish longevity of our findings.

Spine Patient Satisfaction With Telemedicine During the COVID-19 Pandemic: A Cross-Sectional Study.

STUDY DESIGN: Original research, cross-sectional study. OBJECTIVES: Evaluate patient satisfaction with spine care delivered via telemedicine. Identify patient- and visit-based factors associated with increased satisfaction and visit preference. METHODS: Telemedicine visits with a spine surgeon at 2 practices in the United States between March and May 2020 were eligible for inclusion in the study. Patients were sent an electronic survey recording overall satisfaction, technical or clinical issues encountered, and preference for a telemedicine versus an in-person visit. Factors associated with poor satisfaction and preference of telemedicine over an in-person visit were identified using multivariate logistic regression. RESULTS: A total of 772 responses were collected. Overall, 87.7% of patients were satisfied with their telemedicine visit and 45% indicated a preference for a telemedicine visit over an in-person visit if given the option. Patients with technical or clinical issues were significantly less likely to achieve 5 out of 5 satisfaction scores and were significantly more likely to prefer an in-person visit. Patients who live less than 5 miles from their surgeon's office and patients older than 60 years were also significantly more likely to prefer in-person visits. CONCLUSIONS: Spine telemedicine visits during the COVID-19 pandemic were associated with high patient satisfaction. Additionally, 45% of respondents indicated a preference for telemedicine versus an in-patient visit in the future. In light of these findings, telemedicine for spine care may be a preferable option for a subset of patients into the future.

Postoperative Glycemic Variability as a Predictor of Adverse Outcomes Following Lumbar Fusion.

STUDY DESIGN: A retrospective cross-sectional study. OBJECTIVE: This study aims to evaluate the effect size of postoperative glycemic variability on surgical outcomes among patients who have undergone one- to three-level lumbar fusion. SUMMARY OF BACKGROUND DATA: While numerous patient characteristics have been associated with surgical outcomes after lumbar fusion, recent studies have described the measuring of postoperative glycemic variability as another promising marker. METHODS: A total of 850 patients were stratified into tertiles (low, moderate, high) based on degree of postoperative glycemic variability defined by coefficient of variation (CV). Surgical site infections were determined via chart review based on the Centers for Disease Control and Prevention definition. Demographic factors, surgical characteristics, inpatient complications, readmissions, and reoperations were determined by chart review and telephone encounters. RESULTS: Overall, a statistically significant difference in 90-day adverse outcomes was observed when stratified by postoperative glycemic variability. In particular, patients with high CV had a higher odds ratio (OR) of readmission (OR = 2.19 [1.17, 4.09]; P = 0.01), experiencing a surgical site infection (OR = 3.22 [1.39, 7.45]; P = 0.01), and undergoing reoperations (OR = 2.65 [1.34, 5.23]; P = 0.01) compared with patients with low CV. No significant association was seen between low and moderate CV groups. Higher CV patients were more likely to experience longer hospital stays (ß: 1.03; P = 0.01). Among the three groups, high CV group experienced the highest proportion of complications. CONCLUSION: Our study establishes a significant relationship between postoperative glycemic variability and inpatient complications, length of stay, and 90-day adverse outcomes. While HbA1c has classically been used as the principal marker to assess blood glucose control, our results show CV to be a strong predictor of postoperative adverse outcomes. Future high-quality, prospective studies are necessary to explore the true effect of CV, as well as its practicality in clinical practice. Nevertheless, fluctuations in blood glucose levels during the inpatient stay should be limited to improve patient results.Level of Evidence: 4.

Bone Graft Options in Spinal Fusion: A Review of Current Options and the Use of Mesenchymal Cellular Bone Matrices.

BACKGROUND: Spinal fusion is the mainstay treatment for various spinal conditions ranging from lumbar and cervical stenosis to degenerative spondylolisthesis as well as extensive deformity corrections. A new emerging category of allograft is cellular bone matrices (CBMs), which take allogeneic mesenchymal stem cells and incorporate them into an osteoconductive and osteoinductive matrix. This study reviewed the current spinal fusion options and new emerging treatment options. METHODS: Articles were searched using PubMed. The search included English publications since January 1, 2014, using the search terms "cellular bone matrix," "mesenchymal stem cells spinal fusion," "spinal arthrodesis AND mesenchymal stem cells," and "spine fusion AND cellular bone matrix." RESULTS: Spinal fusion is accomplished through the use of allografts, autografts, and bone graft substitutes in combination or alone. An emerging category of allograft is CBMs, in which an osteoconductive and osteoinductive matrix is filled with mesenchymal stem cells. Studies demonstrate that CBMs have achieved equivalent or better fusion rates compared with traditional options for anterior cervical discectomy and fusions and posterolateral lumbar fusions; however, the studies have been retrospective and lacking control groups and therefore not ideal. CONCLUSIONS: Many treatment options have been successfully used in spinal fusion. Newer allografts such as CBMs have shown promising results in both animal and clinical studies. Further research is needed to determine the therapeutic dose of mesenchymal stem cells delivered within CBMs.

Venous thromboembolism in lung transplant recipients real world experience from a high volume center.

BACKGROUND: Venous thromboembolism (VTE) post lung transplantation is common and has been associated with worse post transplant survival. We report a comprehensive single center review of VTE incidence in the first post transplant year, investigate modifiable risk factors and assess impact on short term outcomes. METHODS: Retrospective review of all lung transplant recipients between August 2016 to 2018 at Temple University Hospital. Patients were followed for 1 year post transplant. All patients were screened for deep venous thrombosis (DVT) within the first 2 weeks with a venous duplex study. Pre transplant, intra operative, post operative variables, and peri-operative practice patterns were compared between VTE positive and VTE negative groups. Logistic regression modeling was used to identify risk factors for early VTE (VTE within 30 days after transplant). RESULTS: A total of 235 patients were included in the study, 58 patients (24.7%) developed a VTE in the first post transplant year. Median time to diagnosis was 17 days. Of the patients with VTE, 76% had an isolated DVT, 13.5 % had an isolated pulmonary embolism (PE), and 10.3% had concomitant DVT and PE. In a multivariate logistic regression model, cardiopulmonary bypass (CPB) (OR 1.93 p = 0.015) and interruption of VTE prophylaxis (OR 4.42 p < 0.0001) were predictive of early VTE. CONCLUSION: VTE post lung transplant is common despite the use of prophylactic anticoagulation. CPB use and interruption of DVT prophylaxis are risk factors for early post transplant VTE. Measures to ensure consistent and uninterrupted prophylaxis may help decrease VTE incidence after lung transplantation.

An Investigation of a Novel Dural Repair Device for Intraoperative Incidental Durotomy Repair.

Incidental durotomies, or dural tears, can be very difficult and time consuming to repair properly when they are encountered in confined spaces. A novel dural repair device was developed to address these situations. In this paper, the novel device was assessed against the use of traditional tools and techniques for dural repairs in two independent studies using an intricate clinical simulation model. The aim was to examine the results of the two assessments and link the outcomes to the clinical use of the novel device in the operating room. The novel device outperformed conventional techniques as measured by dural repair time, CSF leak pressure and nerve root avoidance in the simulation. The results were generally replicable clinically, however, numerous additional clinical scenarios were also encountered that the simulation model was unable to capture due to various inherent limitations. The simulation model design, potential contributors to watertightness, clinical experiences, and limitation are discussed.

Tezepelumab as an Emerging Therapeutic Option for the Treatment of Severe Asthma: Evidence to Date.

Asthma is a complex heterogeneous disease defined by chronic inflammation of the airways. Patients present with wheezing, chest tightness, cough and shortness of breath. Bronchial hyperresponsiveness and variable expiratory airflow limitation are hallmark features. About 3.6-6.1% of patients, despite receiving high-dose inhaled corticosteroids (ICS) and a second controller medication, report persistent symptoms referred to as severe asthma. Uncontrolled severe asthma is associated with increased mortality, morbidity, diminished quality of life and increased health expenditures. The development of modern biological therapy has revolutionized severe asthma treatment. By targeting specific chemokines, asthma control has drastically improved, resulting in better quality of life, less emergency department visits and inpatient admissions, and decreased chronic systemic corticosteroid utilization. Despite these advances, there remains a subset of asthma patients who remain symptomatic with poor quality of life and heavy utilization of the healthcare system. Recently attention has been given to pharmaceutical therapy directed at receptors and cytokines on the epithelial layer of the lung referred to as "alarmins". Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like receptor family found on the epithelial layer of the lung that releases a cytokine cascade inducing eosinophilic inflammation, mucus production and airflow obstruction in asthmatics. Tezepelumab is the first investigational monoclonal antibody that inhibits TSLP. Proof of concept study and phase IIb studies demonstrated reduced asthma exacerbations, improvement in quality of life, less decline in FEV1 and decrease in biochemical inflammatory markers in comparison to placebo. It is presently undergoing three phase III studies and an additional phase II study.

Guiding therapeutic plasma exchange for antibody-mediated rejection treatment in lung transplant recipients - a retrospective study.

Antibody-Mediated Rejection (AMR) due to donor-specific antibodies (DSA) is associated with poor outcomes after lung transplantation. Currently, there are no guidelines regarding the selection of treatment protocols. We studied how DSA characteristics including titers, C1q, and mean fluorescence intensity (MFI) values in undiluted and diluted sera may predict a response to therapeutic plasma exchange (TPE) and inform patient prognosis after treatment. Among 357 patients consecutively transplanted without detectable pre-existing DSAs between 01/01/16 and 12/31/18, 10 patients were treated with a standardized protocol of five TPE sessions with IVIG. Based on DSA characteristics after treatment, all patients were divided into three groups as responders, partial responders, and nonresponders. Kaplan-Meier Survival analyses showed a statistically significant difference in patient survival between those groups (P = 0.0104). Statistical analyses showed that MFI in pre-TPE 1:16 diluted sera was predictive of a response to standardized protocol (R2  = 0.9182) and patient survival (P = 0.0098). Patients predicted to be nonresponders who underwent treatment with a more aggressive protocol of eight TPE sessions with IVIG and bortezomib showed improvements in treatment response (P = 0.0074) and patient survival (P = 0.0253). Dilutions may guide clinicians as to which patients would be expected to respond to a standards protocol or require more aggressive treatment.

A randomized, open-label, pragmatic study to assess reliever-triggered inhaled corticosteroid in African American/Black and Hispanic/Latinx adults with asthma: Design and methods of the PREPARE trial.

BACKGROUND: Asthma prevalence, morbidity, and mortality disproportionately impact African American/Black (AA/B) and Hispanic/Latinx (H/L) communities. Adherence to daily inhaled corticosteroid (ICS), recommended by asthma guidelines in all but the mildest cases of asthma, is generally poor. As-needed ICS has shown promise as a patient-empowering asthma management strategy, but it has not been rigorously studied in AA/B or H/L patients or in a real-world setting. Design and Aim The PeRson EmPowered Asthma RElief (PREPARE) Study is a randomized, open-label, pragmatic study which aims to assess whether a patient-guided, reliever-triggered ICS strategy called PARTICS (Patient-Activated Reliever-Triggered Inhaled CorticoSteroid) can improve asthma outcomes in AA/B and H/L adult patient populations. In designing and implementing the study, the PREPARE research team has relied heavily on advice from AA/B and H/L Patient Partners and other stakeholders. Methods PREPARE is enrolling 1200 adult participants (600 AA/Bs, 600H/Ls) with asthma. Participants are randomized to PARTICS + Usual Care (intervention) versus Usual Care (control). Following a single in-person enrollment visit, participants complete monthly questionnaires for 15 months. The primary endpoint is annualized asthma exacerbation rate. Secondary endpoints include asthma control; preference-based quality of life; and days lost from work, school, or usual activities. Discussion The PREPARE study features a pragmatic design allowing for the real-world assessment of a patient-centered, reliever-triggered ICS strategy in AA/B and H/L patients. Outcomes of this study have the potential to offer powerful evidence supporting PARTICS as an effective asthma management strategy in patient populations that suffer disproportionately from asthma morbidity and mortality.

Clinical predictors and explant lung pathology of acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterised by constant threat of acute exacerbation of IPF (AE-IPF). It would be significant to identify risk factors of AE-IPF. We sought to determine the prognostic value of lung transplantation candidacy testing for AE-IPF and describe explant pathology of recipients with and without AE-IPF before lung transplantation. METHODS: Retrospective cohort study of 89 IPF patients listed for lung transplantation. Data included pulmonary function testing, echocardiography, right heart catheterisation, imaging, oesophageal pH/manometry and blood tests. Explanted tissue was evaluated by pulmonary pathologists and correlated to computed tomography (CT) findings. RESULTS: Out of 89 patients with IPF, 52 were transplanted during stable IPF and 37 had AE-IPF before transplantation (n=28) or death (n=9). There were no substantial differences in candidacy testing with and without AE-IPF. AE-IPF had higher rate of decline of forced vital capacity (FVC) (21±22% versus 4.8±14%, p=0.00019). FVC decline of >15% had a hazard ratio of 7.2 for developing AE-IPF compared to FVC decline of <5% (p=0.004). AE-IPF had more secondary diverse histopathology (82% versus 29%, p<0.0001) beyond diffuse alveolar damage. There was no correlation between ground-glass opacities (GGO) on chest CT at any point to development of AE-IPF (p=0.077), but GGO during AE-IPF predicted secondary pathological process beyond diffuse alveolar damage. CONCLUSIONS: Lung transplantation candidacy testing including reflux studies did not predict AE-IPF besides FVC absolute decline. CT did not predict clinical or pathological AE-IPF. Secondary diverse lung pathology beyond diffuse alveolar damage was present in most AE-IPF, but not in stable IPF.

Impact of preoperative weakness and duration of symptoms on health-related quality-of-life outcomes following anterior cervical discectomy and fusion.

BACKGROUND CONTEXT: The majority of patients with preoperative upper extremity weakness show improvements in motor function after anterior cervical discectomy and fusion (ACDF). Although numerous studies have examined both the extent and time course to which motor function can be expected to improve, few have shown that these improvements in motor function translate to improved health related quality of life (HRQOL) outcomes. PURPOSE: The purpose of this study was to examine the effect of preoperative weakness and duration of symptoms on HRQOL outcomes in patients who underwent ACDF. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Adult patients who underwent an ACDF procedure at an academic hospital from January 2015 to December 2016 by a fellowship-trained spine surgeon. OUTCOME MEASURES: The primary outcomes of interest were HRQOL outcomes: Short Form-12 Physical/Mental Component Scores (SF-12 PCS/MCS), Neck Disability Index (NDI), and Visual Analog Scale Arm/Neck scores (VAS Arm/Neck). METHODS: Patient demographics, surgical case characteristics, and motor strength exams were collected in patients who underwent ACDF over a 2-year period. Preoperative weakness was defined by a strength grade ≤3 (on a scale from 0 to 5) in at least one upper extremity muscle group. Multivariate linear regression analysis was performed to determine the effect of the preoperative weakness on HRQOL outcomes. RESULTS: Of the 276 patients identified, 45 (16.3%) showed evidence of preoperative weakness, 44 (97.8%) of which showed subsequent postoperative motor improvements after ACDF. All patients reported significant improvements in all HRQOL outcome measures. Patients with preoperative weakness reported significantly worse preoperative VAS Arm (6.9 vs. 5.2; p=.01) and VAS Neck (6.1 vs. 4.8; p=.02) pain scores. Compared with patients without preoperative weakness, those with preoperative weakness reported significantly more improvement in NDI (ß: -10.9; p=.001). Patients with symptoms greater than or equal to 12 months and preoperative weakness showed significantly less improvement in NDI (ß: 14.8; p=.03). CONCLUSIONS: Patients with preoperative weakness generally exhibited worse pain and HRQOL measures preoperatively, and showed greater potential for improvement after ACDF. Patients with a shorter duration of preoperative weakness had greater potential for improvement in HRQOL measures after ACDF compared with those with longer duration of symptoms. ACDF is an effective procedure to improve strength and HRQOL measures across all patient groups under appropriate indications.

Hepatitis C Virus Infection as a Predictor of Complications and Increased Costs Following Primary Lumbar Fusion Surgery.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim of this study was to identify whether hepatitis C virus (HCV) diagnosis influences in-hospital lengths of stay (LOS), postoperative complications, readmission rates, or costs following primary posterior lumbar fusions in an elective setting. SUMMARY OF BACKGROUND DATA: Although joint arthroplasty literature has shown increased complication rates and costs for patients seropositive with HCV without liver disease compared to those without HCV, this comorbidity has not been explored in the spine literature. To our knowledge, this is the first publication in the lumbar spine literature to solely focus on HCV as the disease burden. METHODS: A national database was queried for patients who underwent primary lumbar spine fusion for degenerative lumbar pathology with Medicare insurance from 2005 to 2014. The 90-day postoperative complication rates, readmission rates, and treatment costs were queried. To limit confounding, HCV patients were matched with a control cohort of non-HCV patients using patient demographics, treatment modality, and comorbid conditions, and then analyzed by multivariate logistic regression. Patients with active liver disease were excluded to better isolate HCV as the comorbidity. RESULTS: A cohort of 28,841 patients were included in the final analysis. Postoperatively, compared to those without HCV infection, those with HCV had significantly higher odds of blood transfusions (odds ratio [OR]: 3.06), pneumonia (OR: 2.49), respiratory failure (OR: 2.49), urinary tract infections (OR: 1.89), wound-/implant-related infections (OR: 1.74), cerebrovascular events (OR: 1.70), or any postoperative complication within 90 days (OR: 2.93; all P < 0.0001). Furthermore, HCV positive patients had higher day of surgery costs ($28,713.26 vs. $25,448.26, P < 0.0001) and 90-day costs ($33,447.39 vs. $29,016.77, P < 0.0001). There was not a significant difference for patients with HCV infection compared to those without in regard to hospital LOS (10 days vs. 8 days, P = 0.332) and rates of a 90-day readmission (0.37% vs. 0.22%; OR: 1.70, 95% confidence interval: 1.00-2.90, P: 0.050). CONCLUSION: In patients undergoing primary lumbar fusion, a seropositivity for HCV without liver disease is associated with higher costs and complication rates, including higher rates of blood transfusion requirements and pneumonia-related complications. This data shed new light on elective spine surgery in HCV patients and may influence the risks and benefits considerations for surgeons considering lumbar fusion in this population. LEVEL OF EVIDENCE: 3.