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Takudzwa Mkorombindo, Mark T DransfieldLung Health Center, Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USAAbstract: Despite maximal medical therapy, a subset of patients with chronic obstructive pulmonary disease continue to suffer acute exacerbations. It is also clear that a subset of this population has elevated blood eosinophils. In addition to clearly responding better to inhaled corticosteroids, it is also possible that this subgroup may benefit from biologic treatments targeting eosinophilic inflammation. Mepolizumab, a humanized monoclonal antibody against interleukin-5 (IL-5), may have a therapeutic effect in a subgroup of patients with COPD and eosinophilic airway inflammation. In this review, we discuss the biologic rationale for mepolizumab targeting IL-5 in eosinophilic COPD as well as the results of recently published clinical trials.Keywords: COPD, acute exacerbations of COPD, eosinophils, mepolizumab

Study Design: This study was a retrospective propensity-matched study of patients receiving opioid sparing anesthesia (OSA) and those who did not receive an opioid sparing anesthesia regimen., Objectives: To determine whether patients undergoing spine fusion for deformity fared better with an OSA regimen than those not having an OSA regimen., Summary of Background Data: There has been a tremendous focus on opioid overuse. Accordingly, OSA regimens are being introduced to reduce narcotic use. However, OSA has not been studied in the adult spine deformity population., Methods: 43 patients undergoing fusion of at least five levels in the thoracolumbar spine received OSA. They were matched to 43 patients who did receive an OSA regimen. We analyzed a number of metrics including blood loss, anesthesia time, post anesthesia care unit (PACU) pain scores, postoperative pain scores, complications, length of stay, and readmissions., Results: The OSA group had significantly lower pain scores both before transfer to (4.6 vs. 7.6, P=0.000) and after transfer from (4.2 vs. 6.2 P=0.002) the PACU. Opioid use was significantly lower in the OSA group (454 vs. 241 MMEs by POD4, P=0.022). Fewer patients required blood transfusion in the OSA (1 vs. 28, P=0.000) group. Fewer patients in the OSA group had constipation and urinary retention (1 vs. 9, P=0.015). There was no difference in discharge home or to a facility. The lengths of hospital (4.33 vs. 6.19, P=0.009) and ICU (0.12 vs. 0.70 days, P=0.009) stay were significantly shorter in the OSA group., Conclusion: OSA regimens have numerous benefits in patients undergoing spinal deformity surgery including less opioid use, fewer postoperative complications, and a reduced length of stay., Competing Interests: Authors have no conflicts of interest to declare related to the subject of the manuscript., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale: Pulmonary hypertension (PH) in COPD confers increased risk of exacerbations (ECOPD). Electrocardiogram (ECG) indicators of PH are prognostic both in PH and COPD. In the Beta-Blockers for the Prevention of Acute Exacerbations of COPD (BLOCK-COPD) trial, metoprolol increased risk of severe ECOPD through unclear mechanisms., Objective: We evaluated whether an ECG indicator of PH, P-pulmonale, would be associated with ECOPD and whether participants with P-pulmonale randomized to metoprolol were at higher risk of ECOPD and worsened respiratory symptoms given the potential detrimental effects of beta-blockers in PH., Methods: ECGs of 501 participants were analyzed for P-pulmonale (P wave enlargement in lead II). Cox proportional hazards models evaluated for associations between P-pulmonale and time to ECOPD (all and severe) for all participants and by treatment assignment (metoprolol vs. placebo). Linear mixed-effects models evaluated the association between treatment assignment and P-pulmonale on change in symptom scores (measured by CAT and SOBQ)., Results: We identified no association between P-pulmonale and risk of any ECOPD or severe ECOPD. However, in individuals with P-pulmonale, metoprolol was associated with increased risk for ECOPD (aHR 2.92, 95% CI: 1.45-5.85). There was no association between metoprolol and ECOPD in individuals without P-pulmonale (aHR 1.01, 95% CI: 0.77-1.31). Individuals with P-pulmonale assigned to metoprolol experienced worsening symptoms (mean increase of 3.95, 95% CI: 1.32-6.58) whereas those assigned to placebo experienced a mean improvement in CAT score of -2.45 (95% CI: -0.30- -4.61)., Conclusions: In individuals with P-pulmonale, metoprolol was associated with increased exacerbation risk and worsened symptoms. These findings may explain the findings observed in BLOCK-COPD., (© 2023. The Author(s).)

Study Design: Longitudinal observational comparative cohorts., Objective: The objective of this study is to compare 3 and 12-month radiographic sagittal parameters and patient-reported outcomes (PROs) in patients who underwent 3-level ACDF or a hybrid procedure., Summary of Background Data: Anterior Cervical Discectomy and Fusion (ACDF), Anterior Cervical Corpectomy and Fusion (ACCF), and hybrids (combination ACCF-ACDF) are common procedures used to treat symptomatic cervical spondylosis. Although there is a relative abundance of literature comparing 1-level ACCF versus 2-level ACDF and 2-level ACCF versus 3-level ACDF, detailed comparisons of 3-level ACDF versus hybrid procedures have not been extensively addressed., Methods: Patients who underwent a 3-Level ACDF (3L-ACDF, N=47) or 1-Level Corpectomy/1-Level ACDF (Hybrid, N=52) with at least a 12-month post-op data available were identified. Standard demographic, surgical and PROs were collected in addition to preoperative and postoperative radiographic data, including C2 plumb line (C2PL), C2-C7 lordosis (CL), segmental lordosis (SL), and T1 slope (T1S)., Results: The 2 cohorts were similar in terms of demographics. At 3 months post-op, CL (9.04° vs. -2.12°, P =0.00) and SL (6.06° vs. -2.26°, P =0.003) were significantly greater in the 3L-ACDF group versus the HYBRID group. This significant difference was maintained at 12 months postoperative for CL [(6.62° vs. -0.60°, P =0.015) but not for SL (2.36° vs. -1.09°, P =0.199)]. There were no differences in PROs between the 2 groups before surgery, at 3 months postoperative or 12 months postoperative. Seven patients required revision surgery in the 1-year study period (1 in the 3L-ACDF, and 6 in the Hybrid P <0.001)., Conclusions: Three level ACDF resulted in greater C2-C7 lordosis and segmental lordosis postoperatively, which was maintained at 1 year for cervical lordosis. While PROs were similar between the groups, patients with hybrid instrumentation required significantly more revision surgeries than those treated with 3-level ACDF., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale: The BLOCK COPD (β-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease) study found that metoprolol was associated with a higher risk of severe exacerbation. Objectives: To determine the mechanism underlying these results, we compared changes in lung function over the course of the study between treatment groups and evaluated whether baseline bronchodilator response or early reduction in forced expiratory volume in 1 second (FEV 1 ) or forced vital capacity (FVC) was associated with exacerbation risk. Methods: We compared changes in lung function (FEV 1 and FVC) over the treatment period between treatment groups using linear mixed-effect models. Cox proportional hazards models were used to evaluate the association between baseline bronchodilator responsiveness (FEV 1 , FVC, and combined FEV 1 and FVC), early post-randomization (14 d) change in lung function, and the interaction between treatment assignment and these measures with risk of any or severe or very severe exacerbations. Negative binomial models were used to evaluate the relationship between bronchodilator responsiveness, the interaction between bronchodilator responsiveness and treatment assignment, and exacerbation rate. Results: Over the 336-day treatment period, individuals in the metoprolol group had a significantly greater decrease in logarithmic FEV 1 from baseline to visit on Day 28 than individuals in the placebo group. Individuals in the metoprolol group had a significantly greater decrease in FVC from baseline to visits on Days 14 and 28, and also a significantly greater decrease in logarithmic FVC from baseline to visits on Days 42 and 112 than individuals in the placebo group. There were no associations between early lung function reduction or interactions between lung function reduction and treatment assignment and time to any or severe or very severe exacerbations. There were no interactions between treatment arm and baseline bronchodilator responsiveness measures on risk or rate of exacerbations. However, those with baseline FVC bronchodilator responsiveness had a higher rate of severe or very severe exacerbations (adjusted rate ratio, 1.62; 95% confidence interval, 1.04-2.48). Conclusions: Metoprolol was associated with reduced lung function during the early part of the treatment period, but these effects were modest and did not persist. Early lung function reduction and baseline bronchodilator responsiveness did not interact with the treatment arm to predict exacerbations; however, baseline FVC bronchodilator responsiveness was associated with a 60% higher rate of severe or very severe exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT02587351).

Study Objectives: Sleep is an important dimension in the care of chronic obstructive pulmonary disease (COPD), but its relevance to exacerbations is unclear. We wanted to assess whether sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI) is associated with an increased risk of COPD exacerbations and does this differ by socio-environmental exposures., Methods: We included 1647 current and former smokers with spirometrically confirmed COPD from the SPIROMICS cohort. We assessed incidence rate ratios for exacerbation using zero-inflated negative binomial regression adjusting for demographics, medical comorbidities, and multiple metrics of disease severity, including respiratory medications, airflow obstruction, and symptom burden. Our final model adjusted for socio-environmental exposures using the Area Deprivation Index, a composite measure of contemporary neighborhood quality, and Adversity-Opportunity Index, a composite measure of individual-level historic and current socioeconomic indicators. We used a pre-determined threshold of 20% missingness to undertake multiple imputation by chained equations. As sensitivity analyses, we repeated models in those with complete data and after controlling for prior exacerbations. As an exploratory analysis, we considered an interaction between socio-environmental condition and sleep quality., Results: After adjustment for all co-variates, increasing PSQI scores (range 0-21) were associated with a 5% increased risk for exacerbation per point (p = .001) in the imputed dataset. Sensitivity analyses using complete cases and after controlling for prior exacerbation history were similar. Exploratory analysis suggested less effect among those who lived in poor-quality neighborhoods (p-for-interaction = .035)., Conclusions: Poor sleep quality may contribute to future exacerbations among patients with COPD. This represents one target for improving disease control., Clinical Trial Registration: Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). ClinicalTrials.gov Identifier# NCT01969344. Registry URL: https://clinicaltrials.gov/ct2/show/., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background Context: Computed tomography (CT) measurement of Hounsfield Units (HU) has been described as a tool for assessing BMD. For surgeons considering a revision lumbar fusion, knowledge of the BMD of the UIV is of value for surgical planning. However, the presence of metal artifact from instrumentation presents a potential confounder, and prior studies have not validated measurements of HU in this setting., Purpose: To determine if HU can be measured reliably at the supra-adjacent and upper instrumented levels of a lumbar fusion., Study Design: Retrospective observational cohort PATIENT SAMPLE: Consecutive series of patients who had lumbar CT scans after an instrumented posterior lumbar fusion., Outcome Measures: Hounsfield Units at the upper instrumented vertebra and levels proximal., Methods: We analysed pre- and postoperative CT scans of 50 patients who underwent L2 and distal instrumented lumbar fusion whose scans were no greater than 1 year apart, obtaining HU measurements of analogous axial cuts at the upper instrumented level (immediately caudal to the halo of the pedicle screw), as well as additional control levels above the construct., Results: The HU at the pre-and postoperative UIV exhibited a strong correlation (r=0.917, p<.001), as did one (r=0.887, p<.001) and two (r=0.853, p<.001) levels above the UIV. There were significant but predictable reductions in the postoperative HU compared to preoperative at one (-9.0±26.2) and two (-12.2±30.2) levels above the UIV, as well as T12 (-13.9±42.2). There was no significant difference in HU at the UIV (4.6±34.1)., Conclusions: Postoperative HU at the UIV was strongly correlated with and not significantly different from the preoperative HU. Although the HU in the vertebrae proximal to the UIV were slightly lower postoperatively, this change was predictable using a correction factor., Competing Interests: Declarations of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background Context: In patients with lumbar spinal stenosis, it is crucial for clinicians to identify all symptomatic levels. Prior studies have demonstrated that CT myelography has a greater sensitivity in revealing stenosis (94.4%) compared to MRI (75.9%). However, this is an invasive test that should be used judiciously. No study has identified subgroups of patients that do or do not benefit from this additional invasive testing., Purpose: The objective of this study was to identify subgroups of patients with lumbar stenosis for whom CT myelogram could be expected to provide additional information following an MRI scan., Study Design: Retrospective chart review., Patient Sample: Consecutive series of patients with lumbar degenerative disease seen at a single multisurgeon tertiary spine center., Outcome Measures: Degree of stenosis on MRI or CT myelo., Methods: Medical records were reviewed to collect standard demographic and surgical data and patient diagnoses. MRI and CT myelo obtained within 6 months of each other in patients >45 years old with a diagnosis of central stenosis, spondylolisthesis or degenerative scoliosis were reviewed. Each lumbar level was recorded as mild, moderate, or severe based on the radiologist's report. Fisher exact test was performed with change in recorded severity of stenosis from MRI to CT myelo as the primary outcome of interest., Results: Of 269 patients, 207 (80%) had at least one level of moderate or severe central stenosis on MRI and 62 had mild or no stenosis on MRI. Of the 207, 139 (67%) had multilevel stenosis and 68 (33%) had single level stenosis. CT myelo identified a greater proportion of additional stenotic levels in patients with multilevel stenosis (80/139, 58%) compared to patients with single-level stenosis (27/68, 40%, p=.018). In 62 patients with a clinical diagnosis of lumbar stenosis but no moderate to severe stenosis on MRI, CT myelogram identified three additional stenotic levels (3/65, 5%, p=.836)., Conclusions: CT myelography is not as useful in providing additional information in patients with no stenosis or single level stenosis as compared to patients with multilevel stenosis., Competing Interests: Declarations of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Autonomic dysfunction is common in chronic obstructive pulmonary disease (COPD), and worse autonomic function may be a marker of risk for acute exacerbations of COPD (AECOPD). Heart rate variability (HRV) is a measure of autonomic function. Our objective was to test whether lower (worse) HRV is a risk factor for AECOPD., Methods: We measured standard deviation of normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD) on 10-second electrocardiograms (ECGs) performed at screening and day 42 in participants in the Beta Blockers for the Prevention of Acute Exacerbations of COPD trial ( BLOCK-COPD), a placebo-controlled trial of metoprolol for prevention of AECOPD. We used Cox-proportional hazards models to test if these HRV measures were associated with risk of any AECOPD, and separately, hospitalized AECOPD. We tested associations using baseline HRV measures and incorporating HRV measures from day 42 as a time-varying covariate. We also tested for interactions with metoprolol assignment., Results: Of 532 trial participants, 529 (forced expiratory volume in 1 second [FEV 1 ]41 ± 16.3 % predicted) were included in this analysis. We did not find a significant association between HRV measures and risk of AECOPD when all participants were analyzed together. There was a significant interaction between RMSSD and assignment to metoprolol on time to first hospitalized AECOPD; in the placebo group greater RMSSD was associated with a lower risk of hospitalized AECOPD (adjusted hazard ratio0.71, 95% confidence interval: 0.52 to 0.96, per 10 ms increase) but there was no association in the metoprolol group., Conclusions: Autonomic dysfunction as measured by HRV may be a risk factor for AECOPD. Future studies should analyze longer HRV recordings and their performance in broader samples of people with COPD, including those on beta-blockers., (JCOPDF © 2022.)

Background: Lower heart rate (HR) increases during exercise and slower HR recovery (HRR) after exercise are markers of worse autonomic function that may be associated with risk of acute respiratory events (ARE)., Methods: Data from 6-min walk testing (6MWT) in COPDGene were used to calculate the chronotropic index (CI) [(HR immediately post 6MWT - resting HR)/((220 - age) - resting HR)] and HRR at 1 min after 6MWT completion. We used zero-inflated negative binomial regression to test associations of CI and HRR with rates of any ARE (requiring steroids and/or antibiotics) and severe ARE (requiring emergency department visit or hospitalization), among all participants and in spirometry subgroups (normal, chronic obstructive pulmonary disease [COPD], and preserved ratio with impaired spirometry)., Results: Among 4,484 participants, mean follow-up time was 4.1 years, and 1,966 had COPD. Among all participants, CI-6MWT was not associated with rate of any ARE [adjusted incidence rate ratio (aIRR) 0.98 (0.95-1.01)], but higher CI-6MWT was associated with lower rate of severe ARE [0.95 (0.92-0.99)]. Higher HRR was associated with a lower rate of both any ARE [0.97 (0.95-0.99)] and severe ARE [0.95 (0.92-0.98)]. Results were similar in the COPD spirometry subgroup., Conclusion: Heart rate measures derived from 6MWT tests may have utility in predicting risk of acute respiratory events and COPD exacerbations., (Published by Elsevier Ltd.)

Background: Orthopaedic surgery is the least diverse surgical subspecialty in medicine. However, to date, there is no literature that shows which medical schools have successfully contributed to improving orthopaedic surgeon diversity., Objective: The purpose of this study is to identify the top U.S. medical schools that have successfully matched black applicants into orthopaedic surgery residencies and juxtapose this ranking to the current top medical schools as ranked by the U.S. News and World Report (USNWR)., Methods: The J. Robert Gladden Orthopaedic Society (JRGOS) database was queried for all orthopaedic surgeons, fellows, and residents who identified as black or multi-racial with black being one of the included races, yielding 938 physicians, of which 672 met our inclusion criteria. From this list, a ranking of the top 20 medical schools was generated., Results: The top five medical schools ranked in the JRGOS database are Howard University College of Medicine (HUCOM), Meharry Medical College, Harvard Medical School (HMS), the University of Pennsylvania, and Morehouse School of Medicine (MSM). In addition, 10 (50%) of the medical schools ranked in the top 20 by the JRGOS database were also ranked by the USNWR. When ranking medical schools for black female applicants, HUCOM, MSM, HMS are the top three programs. Lastly, a ranking by region identified that the northeast contained the highest number of ranked medical schools., Conclusion: There are both historically black and non-historically black medical schools which have a proven track record of producing a significant number of future black orthopaedic surgery residents., (Copyright © 2022 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Background Context: Surgical decision making for cervical spondylotic myelopathy (CSM) relies on evaluation of symptoms and physical examination. The Romberg test is a clinical exam used to identify balance issues with CSM. However, the Romberg test has a subjective interpretation and has a binary (positive or negative) result., Purpose: This study aims to compare force plate pressure readings during a standard Romberg test in patients with CSM to age-matched normal healthy volunteers., Study Design/setting: Prospective cross sectional observational comparative cohort from a single multi-surgeon spine center., Patient Sample: Patients who were clinically diagnosed with CSM were compared to age-matched healthy volunteers without a clinical history of spine pathology., Outcome Measures: Quantitative Romberg Force Plate Measurements METHODS: Patients with CSM requiring surgery and healthy normal volunteers were asked to perform the Romberg test while on a force plate measuring the center of pressure (COP): standing up straight with arms extended for 30 seconds with eyes open, followed by 30 seconds with eyes closed. The change for total sway area, sway frequency and sway speed with eyes closed and eyes open were calculated and compared between patients with CSM and healthy volunteers., Results: Thirty-four CSM patients were age-matched to 34 healthy volunteers. There was a larger change in quantitative Romberg measurements with eyes open versus eyes closed in CSM patients compared to normal volunteers for maximum lateral movement (10.79 cm vs. 0.94 cm, p=.003), maximum anterior-posterior movement (15.06 cm vs. 10.00 cm p=.201), total lateral CoP movement (89.82cm vs. 18.71cm, p=.007), total AP CoP movement (154.68 cm vs. 87.47 cm, p=.601), total CoP trace movement (199.79 cm vs. 88.44 cm, p=.014), sway area (284.74 cm 2 vs. 57.76 cm 2 , p=.006), and average speed (7.00 cm/s vs. 2.91 cm/s, p=.006)., Discussion: Poor standing balance can be quantified in patients with CSM. Quantifying standing balance in patients with CSM shows significantly worse objective measures than age-matched healthy volunteers. The Romberg test on a force plate may help diagnose and evaluate patients with CSM, guide patient management and potentially grade the severity of spinal pathology. Further studies are needed to determine its utility in monitoring disease progression and measure treatment effectiveness., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose of Review: Current guidelines does not include current or former smokers who do not have spirometric airflow limitation in their diagnostic or therapeutic algorithms for chronic obstructive pulmonary disease (COPD). The purpose of this review is to outline the burden of respiratory morbidity in this population and to discuss the potential utility of their classification as pre-COPD., Recent Findings: It is increasingly clear that patients with a history of exposure to cigarette smoke or other environmental pollutants may have substantial lung pathology and respiratory impairment even in the absence of airflow limitation, as detected by spirometry. Not all of these patients will develop airflow limitation, but many will have considerable respiratory morbidity and a comparable prognosis to those with classical, spirometrically defined COPD. The use of the term pre-COPD may allow for the identification of these individuals in order to target preventive and earlier therapeutic strategies., Summary: Spirometry is not adequately sensitive to identify many current and former smokers and other exposed populations with significant lung pathology and respiratory symptoms. Though the pathologic processes present in these patients differ, the earlier identification of this pre-COPD population may foster the development of more effective and disease-modifying treatments., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: No medical treatment has proven efficacy for acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF), and this syndrome has a very high mortality. Based on data indicating humoral autoimmune processes are involved in IPF pathogenesis, we treated AE-IPF patients with an autoantibody reduction regimen of therapeutic plasma exchange, rituximab, and intravenous immunoglobulin. This study aimed to identify clinical and autoantibody determinants associated with survival after autoantibody reduction in AE-IPF., Methods: Twenty-four(24) AE-IPF patients received the autoantibody reduction regimen. Plasma anti-epithelial autoantibody titers were determined by HEp-2 indirect immunofluorescence assays in 22 patients., Results: Mean age of the patients was 70 + 7 years old, and 70% were male. Beneficial clinical responses that occurred early during therapy were a favorable prognostic indicator: supplemental O2 flows needed to maintain resting SaO2>92% significantly decreased and/or walk distances increased among all 10 patients who survived for at least one year. Plasma anti-HEp-2 autoantibody titers were ~-three-fold greater in survivors compared to non-survivors (p<0.02). Anti-HEp-2 titers >1:160 were present in 75% of the evaluable one-year survivors, compared to 29% of non-survivors, and 10 of 12 patients (83%) with anti-HEP-2 titers <1:160 died during the observation period (Hazard Ratio = 3.3, 95% Confidence Interval = 1.02-10.6, p = 0.047)., Conclusions: Autoantibody reduction therapy is associated with rapid reduction of supplemental oxygen requirements and/or improved ability to ambulate in many AE-IPF patients. Facile anti-epithelial autoantibody assays may help identify those most likely to benefit from these treatments., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: SRD reports personal fees from Novartis and aTyr Pharma, outside the submitted work. TK reports personal fees from Boehringer Ingelheim and Aluda, outside the submitted work. TL reports personal fees from Boehringer Ingelheim, outside the submitted work. HPP reports personal fees from Alexion and Elsevier, outside the submitted work. VGV, FF, TKT-N, LDQ, SCS, TM and KGD have no relevant disclosures. This does not alter our adherence to PLOS ONE policies on sharing data and materials

A role for hereditary influences in the susceptibility for chronic obstructive pulmonary disease (COPD) is widely recognized. Cytotoxic lymphocytes are implicated in COPD pathogenesis, and functions of these leukocytes are modulated by interactions between their killer cell Ig-like receptors (KIR) and human leukocyte antigen-Class I (HLA-Class I) molecules on target cells. We hypothesized HLA-Class I and KIR inheritance affect risks for COPD. HLA-Class I alleles and KIR genotypes were defined by candidate gene analyses in multiple cohorts of patients with COPD (total n = 392) and control smokers with normal spirometry (total n = 342). Compared with controls, patients with COPD had overrepresentations of HLA-C*07 and activating KIR2DS1, with underrepresentations of HLA-C*12. Particular HLA-KIR permutations were synergistic; e.g., the presence of HLA-C*07 + KIR2DS1 + HLA-C12null versus HLAC*07null + KIR2DS1null + HLA-C12 was associated with COPD, especially among HLA-C1 allotype homozygotes. Cytotoxicity of COPD lymphocytes was more enhanced by KIR stimulation than those of controls and was correlated with lung function. These data show HLA-C and KIR polymorphisms strongly influence COPD susceptibility and highlight the importance of lymphocyte-mediated cytotoxicity in COPD pathogenesis. Findings here also indicate that HLA-KIR typing could stratify at-risk patients and raise possibilities that HLA-KIR axis modulation may have therapeutic potential.

Study Design: Retrospective chart review., Objectives: To determine if the addition of an anterior lumbar interbody fusion (ALIF) improves the fractional curve in adult spinal deformity correction when compared to posterior surgery alone. ALIF is commonly advocated to improve lordosis and fusion in adult deformity surgery. Improved fractional curve correction may help level the pelvis and minimize proximal malalignment., Methods: Patients undergoing thoracolumbar fusion to the pelvis with S2AI screws for deformity were identified and stratified into patients who had an ALIF as part of their deformity correction procedure (ALIF + PSF), and those who had a posterior approach alone. The posterior approach (PSF) includes patients who had a posterolateral fusion with or without a transforaminal lumbar interbody fusion (TLIF). Radiographic parameters measured included pre-op and post-op fractional coronal curve Cobb angle, lumbar lordosis, pelvic tilt, pelvic incidence and sacral slope, major Cobb angle, coronal and sagittal SVA., Results: There were 31 cases in the ALIF + PSF group and 28 in the PSF group. Baseline demographic characteristics of the two groups were similar. Mean pre-op fractional coronal Cobb (18.3° vs 13.4°, p = 0.027) was larger in the ALIF + PSF group, whereas lumbar lordosis (31.0° vs 33.6°, p = 0.487) and pelvic parameters were similar between the two groups. Post-op lumbar lordosis was similar (48.2° vs 43.0°, p = 0.092). Greater fractional coronal curve correction was achieved in the ALIF + PSF group (67%) compared to the PSF group (36%) with a smaller post-op fractional coronal curve in the ALIF + PSF group (6.1°) compared to the PSF group (8.6°, p = 0.053)., Conclusion: There is a greater correction of the fractional curve in the ALIF + PSF group compared with the PSF group. While this may not be the primary indication for ALIF, it is a benefit which may facilitate overall deformity correction and leveling of the pelvis., (© 2021. Scoliosis Research Society.)

Pulmonary fat embolism is a common phenomenon in cases of traumatic long bone fractures, with only a minority developing the more catastrophic Fat Embolism Syndrome (FES). Diagnosis is clinical and requires a high index of suspicion. Treatment remains under-investigated, with common interventions having low quality level-of-evidence and no mortality benefit. In severe cases, focus should be on supporting the failing right ventricle through use of inotropes, pulmonary vasodilators, and mechanical circulatory support. This requires a thorough understanding of the unique physiology through the pulmonary circulation., Competing Interests: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (© 2021 Published by Elsevier Ltd.)

Study Design: Multicenter retrospective study., Objective: Flexion-extension radiographs are frequently used to assess motion in patients with degenerative spondylolisthesis. However, they expose patients to additional radiation and increase cost. The aim of this study is to determine if flexion-extension radiographs provide additional information not seen on upright neutral radiographs and supine magnetic resonance imaging (MRI) that may guide surgical decision making., Summary of Background Data: Supine MRI and upright neutral radiographs are routinely performed in patients with degenerative spondylolisthesis. It is unclear whether additional flexion-extension views play a significant role in surgical planning for this patient population., Methods: From the Quality Outcomes Database, patients who had surgery for grade 1 degenerative spondylolisthesis were identified. Magnitude of slip on pre-op supine MRI, upright neutral, flexion, and extension radiographs were measured. Additional motion was defined as 3 mm or more slip difference between radiographs. For the purpose of this analysis, patients with a slip of 7 mm or more on upright neutral radiographs were assumed to require a fusion., Results: A total of 191 patients were identified. Mean age was 61.6 years (114 females, 60%). Only 31 patients (16%) had additional motion on flexion-extension views not seen on upright neutral x-rays versus supine MRI. Of these 31 patients, 19 had slips less than 7 mm on upright x-ray, generating equipoise for fusion., Conclusion: Flexion-extension radiographs may play a limited role in management of degenerative spondylolisthesis. The subset of patients for which flexion-extension views were most likely to provide value were patients with smaller slips (<7 mm) with no evidence of motion on standing radiographs versus MRI. In 90% of spondylolisthesis cases, information used for surgical planning may be ascertained by comparing motion between supine MRI and upright lateral radiographs.Level of Evidence: 3., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Invasive mucinous adenocarcinoma is a multi-centric adenocarcinoma that accounts for less than 5% of all lung cancer diagnoses. The most common presenting symptoms (cough, sputum production, and chest pain) in conjunction with its radiographic findings (patchy, multi-lobar infiltrates) make invasive mucinous adenocarcinoma challenging to distinguish from both infectious and inflammatory pneumonia. However, due to its aggressive nature, invasive mucinous adenocarcinoma should be considered if a presumed case of pneumonia lacks symptoms of infection (e.g., fever, leukocytosis) and/or does not respond to antibiotics. We report the case of a 75-year-old male who was admitted in the setting of a presumed case of recurrent pneumonia, which had failed to respond to prior antibiotic therapy. Further workup, including trans-bronchial biopsy, confirmed mucinous adenocarcinoma with a lepidic pattern. This case highlights the importance of establishing a broad differential in the setting of unresolved pneumonia following appropriate antibiotic coverage., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Rentas et al.)

Inhaled corticosteroids (ICSs), when used in combination with long-acting bronchodilators, reduce the risk of exacerbations and improve health-related quality of life in patients with chronic obstructive pulmonary disease (COPD) compared with bronchodilator or ICS therapy alone. Potential side effects of ICSs include adverse effects on glycemic control, bone density, cataract formation, skin changes, oral candidiasis, and pulmonary infections. Pneumonia is observed at increased rates in COPD patients, in particular those with greater airflow limitation, low body mass index, advanced age, and male gender, and ICSs may increase this risk. Risk assessment is essential in selecting appropriate patients for ICS-containing therapy., Competing Interests: Disclosure M.T. Dransfield reports grants support from the American Lung Association, NIH, Department of Defense, and Department of Veterans Affairs; consulting fees from AstraZeneca, GlaxoSmithKline, Mereo, Pulmonx, PneumRx/BTG, and Quark; and contracted clinical trial support from AstraZeneca, Boehringer Ingelheim, Boston Scientific, GALA, GlaxoSmithKline, Nuvaira, Pulmonx, and PneumRx/BTG., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality. Guideline-discordant care of COPD is not uncommon. Further, there is a push to incorporate quality improvement (QI) training into internal medicine (IM) residency curricula. This study compared quality of care of COPD patients in an IM residents' clinic and a pulmonary fellows' clinic and, subsequently, the results of a quality improvement program in the residents' clinic. Pre-intervention rates of quality measure adherence were compared between the IM teaching clinic ( n = 451) and pulmonary fellows' clinic ( n = 177). Patient encounters in the residents' teaching clinic after quality improvement intervention ( n = 119) were reviewed and compared with pre-intervention data. Prior to intervention, fellows were significantly more likely to offer smoking cessation counseling ( p = 0.024) and document spirometry showing airway obstruction ( p < 0.001). Smoking cessation counseling, pneumococcal vaccination, and diagnosis of COPD by spirometry were targets for QI. A single-cycle, resident-led QI project was initiated. After, residents numerically improved in the utilization of spirometry (66.5% vs. 74.8%) and smoking cessation counseling (81.8% vs. 86.6%), and significantly improved rates of pneumococcal vaccination ( p = 0.024). One cycle of resident-led QI significantly improved the rates of pneumococcal vaccination, with numerical improvement in other areas of COPD care.

Absorbable implants made of magnesium alloys may revolutionize surgical intervention, and fine magnesium wire will be critical to many applications. Functionally, the wires must have sufficient mechanical properties to withstand implantation and in-service loading, have excellent tissue tolerance, and exhibit an appropriate degradation rate for the application. Alloy chemistry and thermomechanical processing conditions will significantly impact the material's functional performance, but the exact translation of these parameters to implant performance is unclear. With this in mind, fine (127 µm) WE43B magnesium alloy wires in five thermomechanical process (TMP) conditions (90% cold work [CW], and 250, 375, 400, and 450°C heat treatments) were investigated for their effect on mechanical and corrosion behavior. The TMP conditions gave clear metallurgical differences: transverse grain dimensions ranged from 200 nm (CW) to 3 µm (450°C), UTS varied from 324 MPa (450°C) to 608 MPa (250°C), and surgical knotting showed some were suitable (CW, 400°C, 450°C) while others were not (250°C, 350°C). In vitro and in vivo corrosion testing yielded interesting and in some cases conflicting results. After 1 month immersion in cell culture medium, wire corrosion was extensive, and TMP conditions altered the macrocorrosion morphology but not the rate or total release of magnesium ions. After 1 month subdermal implantation in mice, all wires were well tolerated and showed very little corrosion (per µCT and histology), but differences in localized corrosion were detected between conditions. This study indicates that WE43B wires treated at 450°C may be most suitable for surgical knotting procedures. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1987-1997, 2018., (© 2017 Wiley Periodicals, Inc.)