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Rationale: Anecdotally, short lung transplant candidates suffer from long waiting times and higher rates of death on the waiting list compared with taller candidates.Objectives: To examine the relationship between lung transplant candidate height and waiting list outcomes.Methods: We conducted a retrospective cohort study of 13,346 adults placed on the lung transplant waiting list in the United States between 2005 and 2011. Multivariable-adjusted competing risk survival models were used to examine associations between candidate height and outcomes of interest. The primary outcome was the time until lung transplantation censored at 1 year.Measurements and Main Results: The unadjusted rate of lung transplantation was 94.5 per 100 person-years among candidates of short stature (<162 cm) and 202.0 per 100 person-years among candidates of average stature (170-176.5 cm). After controlling for potential confounders, short stature was associated with a 34% (95% confidence interval [CI], 29-39%) lower rate of transplantation compared with average stature. Short stature was also associated with a 62% (95% CI, 24-96%) higher rate of death or removal because of clinical deterioration and a 42% (95% CI, 10-85%) higher rate of respiratory failure while awaiting lung transplantation.Conclusions: Short stature is associated with a lower rate of lung transplantation and higher rates of death and respiratory failure while awaiting transplantation. Efforts to ameliorate this disparity could include earlier referral and listing of shorter candidates, surgical downsizing of substantially oversized allografts for shorter candidates, and/or changes to allocation policy that account for candidate height. [ABSTRACT FROM AUTHOR]

Burn injuries in the United States account for over one million hospital admissions per year, with treatment estimated at four billion dollars. Of severe burn patients, 30–90% will develop hypertrophic scars (HSc). In this study, we evaluate the impact of an elastomeric, randomly-oriented biostable polyurethane (PU) scaffold on HSc-related outcomes. In vitro , fibroblast-seeded PU scaffolds contracted significantly less and demonstrated fewer αSMA + myofibroblasts compared to fibroblast-seeded collagen lattices. In a murine HSc model, collagen coated PU (ccPU) scaffolds significantly reduced HSc contraction as compared to untreated control wounds and wounds treated with the clinical standard of care. Our data suggest that electrospun ccPU scaffolds meet the requirements to reduce HSc contraction including reduction of in vitro HSc related outcomes, diminished scar stiffness, and reduced scar contraction. While clinical dogma suggests treating severe burn patients with rapidly biodegrading skin equivalents, our data suggest that a more long-term scaffold may possess merit in reducing HSc. Statement of Significance In severe burns treated with skin grafting, between 30% and 90% of patients develop hypertrophic scars (HSc). There are no therapies to prevent HSc, and treatments are marginally effective. This work is the first example we are aware of which studies the impact of a permanent electrospun elastomer on HSc contraction in a murine model that mimics the human condition. Collagen coated polyurethane scaffolds decrease αSMA+ myofibroblast formation in vitro , prevent stiffening of scar tissue, and mitigate HSc contraction. Unlike current standards of care, electrospun, polyurethane scaffolds do not lose architecture over time. We propose that the future bioengineering strategy of mitigating HSc contraction should consider a long-term elastomeric matrix which persists within the wound bed throughout the remodeling phase of repair. [ABSTRACT FROM AUTHOR]

Rationale: Frailty is associated with morbidity and mortality in abdominal organ transplantation but has not been examined in lung transplantation.Objectives: To examine the construct and predictive validity of frailty phenotypes in lung transplant candidates.Methods: In a multicenter prospective cohort, we measured frailty with the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB). We evaluated construct validity through comparisons with conceptually related factors. In a nested case-control study of frail and nonfrail subjects, we measured serum IL-6, tumor necrosis factor receptor 1, insulin-like growth factor I, and leptin. We estimated the association between frailty and disability using the Lung Transplant Valued Life Activities disability scale. We estimated the association between frailty and risk of delisting or death before transplant using multivariate logistic and Cox models, respectively.Measurements and Main Results: Of 395 subjects, 354 completed FFP assessments and 262 completed SPPB assessments; 28% were frail by FFP (95% confidence interval [CI], 24-33%) and 10% based on the SPPB (95% CI, 7-14%). By either measure, frailty correlated more strongly with exercise capacity and grip strength than with lung function. Frail subjects tended to have higher plasma IL-6 and tumor necrosis factor receptor 1 and lower insulin-like growth factor I and leptin. Frailty by either measure was associated with greater disability. After adjusting for age, sex, diagnosis, and transplant center, both FFP and SPPB were associated with increased risk of delisting or death before lung transplant. For every 1-point worsening in score, hazard ratios were 1.30 (95% CI, 1.01-1.67) for FFP and 1.53 (95% CI, 1.19-1.59) for SPPB.Conclusions: Frailty is prevalent among lung transplant candidates and is independently associated with greater disability and an increased risk of delisting or death. [ABSTRACT FROM AUTHOR]

The primary lung allocation unit was expanded from the donation service area to a 250-mile radius in 2017. Prior to the change, geographic disparities in donor lung availability impacted waitlist outcomes. We sought to determine if the new allocation system improved these disparities. We conducted a retrospective cohort study comparing the 2-year period before and after the change. Donor lung availability was defined as the ratio of donor lungs to waitlist candidates in the primary allocation unit. Transplant centers were divided into quartiles by donor lung availability. Multivariable competing risk models were used to determine the association between lung availability and waitlist outcomes. Multivariable Cox proportional hazards models compared post-transplant survival. Prior to the allocation change, the unadjusted transplant rate at centers in the lowest and highest quartiles was 132 and 607 transplants per 100 waitlist years. Candidates in the lowest quartile of donor lung availability had a 61% adjusted lower transplantation rate compared to candidates in highest quartile (sub-hazard ratio [sHR]: 0.39, 95% confidence interval [CI]: 0.34-0.44). After the allocation change, the disparity decreased resulting in an unadjusted transplant rate of 141 and 309 among centers in the lowest and highest quartiles. Candidates in the lowest quartile had a 38% adjusted lower transplantation rate compared to those in the highest (sHR: 0.62, 95% CI: 0.57-0.68). There was no significant difference in 1-year post-transplant survival. Although the expansion of the primary allocation unit improved disparities in waitlist outcomes without any change in post-transplant survival, there still remain significant differences due to geography. [ABSTRACT FROM AUTHOR]

Avian metapneumovirus (aMPV), classified within the Pneumoviridae family, wreaks havoc on poultry health. It typically causes upper respiratory tract and reproductive tract infections, mainly in turkeys, chickens, and ducks. Four subtypes of AMPV (A, B, C, D) and two unclassified subtypes have been identified, of which subtypes A and B are widely distributed across the world. In January 2024, an outbreak of severe respiratory disease occurred on turkey and chicken farms across different states in the US. Metagenomics sequencing of selected tissue and swab samples confirmed the presence of aMPV subtype B. Subsequently, all samples were screened using an aMPV subtype A and B multiplex real-time RT-PCR kit. Of the 221 farms, 124 (56%) were found to be positive for aMPV-B. All samples were negative for subtype A. Six whole genomes were assembled, five from turkeys and one from chickens; all six assembled genomes showed 99.29 to 99.98% nucleotide identity, indicating a clonal expansion event for aMPV-B within the country. In addition, all six sequences showed 97.74 to 98.58% nucleotide identity with previously reported subtype B sequences, e.g., VCO3/60616, Hungary/657/4, and BR/1890/E1/19. In comparison to these two reference strains, the study sequences showed unique 49-62 amino acid changes across the genome, with maximum changes in glycoprotein (G). One unique AA change from T (Threonine) to I (Isoleucine) at position 153 in G protein was reported only in the chicken aMPV sequence, which differentiated it from turkey sequences. The twelve unique AA changes along with change in polarity of the G protein may indicate that these unique changes played a role in the adaptation of this virus in the US poultry. This is the first documented report of aMPV subtype B in US poultry, highlighting the need for further investigations into its genotypic characterization, pathogenesis, and evolutionary dynamics.

The Stroke Treatment Academic Industry Roundtable (STAIR) convened a session and workshop regarding enrollment in acute stroke trials during the STAIR XII meeting on March 22, 2023. This forum brought together stroke physicians and researchers, members of the National Institute of Neurological Disorders and Stroke, industry representatives, and members of the US Food and Drug Administration to discuss the current status and opportunities for improving enrollment in acute stroke trials. The workshop identified the most relevant issues impacting enrollment in acute stroke trials and addressed potential action items for each. Focus areas included emergency consent in the United States and other countries; careful consideration of eligibility criteria to maximize enrollment and representativeness; investigator, study coordinator, and pharmacist availability outside of business hours; trial enthusiasm/equipoise; site start-up including contractual issues; site champions; incorporation of study procedures into standard workflow as much as possible; centralized enrollment at remote sites by study teams using telemedicine; global trials; and coenrollment in trials when feasible. In conclusion, enrollment of participants is the lifeblood of acute stroke trials and is the rate-limiting step for testing an exciting array of new approaches to improve patient outcomes. In particular, efforts should be undertaken to broaden the medical community's understanding and implementation of emergency consent procedures and to adopt designs and processes that are easily incorporated into standard workflow and that improve trials' efficiencies and execution. Research and actions to improve enrollment in ongoing and future trials will improve stroke outcomes more broadly than any single therapy under consideration., Competing Interests: Disclosures Dr Broderick receives monies from National Institute of Neurological Disorders and Stroke (NINDS) for research grants, receives study medication and monies for temperature monitoring and after-business hour enrollments from Novo Nordisk for NINDS-funded FASTEST Trial (rFVIIa for Acute Hemorrhagic Stroke Administered at Earliest Time Trial). The Department of Neurology receives monies to an educational/research fund from Genentech for his role on Executive Committee of Timeless Trial; from Roche Pharmaceuticals for consulting, from BrainsGate Ltd for consulting; from Basking Biosciences, from Kroger Prescription Plans Inc’s Pharmacy &Therapeutics Committee as voting member of committee. Dr Silva reports funding from the Brazilian Ministry of Health for the Resilient and OPTIMAL trials; consulting and speaker fees from AstraZeneca, Biogen, Boehringer Ingelheim, and Pfizer; consulting fees from IschemaView and Bayer, and speaker fees from Abbott. Dr Selim receives grant funding from the NINDS and NIA (related to and outside of the current work), and royalties from Up to Date and Cambridge University Press and is on the Advisory Board of MedRhythms Inc. Dr Kasner has received grant funding (to institution) from Genentech, Diamedica, Bristol-Myers Squibb, Bayer, Stryker, and Medtronic; consulting fees from Shionogi, Abbvie, Artivion, AstraZeneca, and NeuExcell; and royalties from UpToDate and Elsevier. Dr Adeoye receives funding from NINDS and has equity in and is the Chief Medical Officer for Sense Diagnostics, Inc and receives compensation from NICO Corporation for data and safety monitoring services. Dr Hill reports grants from MicroVention Inc; employment by University of Calgary; grants from Medtronic; grants from Boehringer Ingelheim; grants from Medtronic; grants from Medtronic; grants from Canadian Institutes of Health Research; grants from Biogen Inc; compensation from Brainsgate Ltd for consultant services; and grants from NoNO Inc. Dr Mistry receives funding from National Institutes of Health/NINDS and Patient-Centered Outcomes Research Institute (PCORI) and receives monies for consulting for RAPID AI, Abbvie, and the American Heart Association. Dr Smith is an employee of AbbVie Inc, and holds AbbVie stock and stock options. All inputs to this article are based on personal experiences and opinions, and do not necessarily reflect AbbVie’s views. J. Sutherland is the Clinical Operations Manager for Revalesio. Dr Lyden receives royalty Income for “Thrombolytic Therapy for Acute Stroke” Third Edition Springer Press, is the PI for NINDS grants U24 NS13006000 and UG3 NS119199, and monies for consulting for Apex Innovations. Dr Jauch receives monies for consulting for RapidAI, and reports compensation from Schultz & Pogue, LLP, and McLeod Law Group for expert witness services. Dr Hernandez-Jimenez works for aptaTargets Dr Mocco receives grant funding from Stryker Neurovascular, Penumbra, and Microvention, as well as a research award from PCORI. Dr Mocco reports stock holdings in Endostream; stock holdings in Viz.ai; stock options in Neuroradial Technologies; stock options in Echovate; compensation from CVAid for consultant services; compensation from Penumbra Inc for other services; stock options in Whisper; compensation from RIST Neurovascular, Inc, for consultant services; stock options in Neurotechnology Investors, LLC, Managers; stock holdings in Q’Apel; grants from PCORI; compensation from Stryker for other services; compensation from MicroVention Inc for other services; stock holdings in Vastrax; stock holdings in Imperative Care Inc; compensation from Synchron for consultant services; stock holdings in Blinktbi; stock holdings in Cerebrotech; stock options in Sim&Cure; stock holdings in Spinaker; stock options in Spinaker; compensation from CVAid for consultant services; stock options in Songbird; stock options in E8; compensation from Perflow for consultant services; employment by Mount Sinai Health System; stock options in Tulavi; stock options in Borvo; stock holdings in Viseon Inc; stock options in Radical; and stock options in Neurolutions. E. Deljkich is Vice President, Clinical Affairs, Imperative Care. Dr Kamel is the PI for the ARCADIA trial (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke; NIH/NINDS U01NS095869), which received in-kind study drug from the BMS-Pfizer Alliance for Eliquis and ancillary study support from Roche Diagnostics; other funding from NIH (R01HL144541, R01NS123576, and U01NS106513); Deputy Editor for JAMA Neurology; clinical trial steering/executive committees for Medtronic, Janssen, and Javelin Medical; end point adjudication committees for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim; and household ownership interests in TETMedical, Spectrum Plastics Group, and Burke Porter Group.

Background: Recent publications on minimally invasive surgery (MIS) for hematoma evacuation have suggested survival benefits in select patients. Since 2015, our center has been performing an MIS technique using continuous irrigation with aspiration through an endoscope (stereotactic intracerebral underwater blood aspiration [SCUBA]). It is unknown how these patient outcomes compare with intracerebral hemorrhage (ICH) score predictions. Our aim is to determine if SCUBA patients had better 30-day mortality than predicted by their presenting ICH score., Methods: Retrospective review of consecutively admitted patients who underwent SCUBA between December 2015 and March 2019. Operative criteria for MIS evacuation included supratentorial hematoma volume ≥15 mL, age >18, National Institutes of Health Stroke Scale score ≥6, and modified Rankin Scale (mRS) score ≤3. Demographic, radiographic, and clinical data were collected prospectively. The prespecified primary outcome was observed 30-day mortality of SCUBA patients compared with predicted mortality by ICH score on presentation., Results: One-hundred and fifteen patients underwent SCUBA for hematoma evacuation. Initial mean ICH volume was 51.4 mL (standard deviation 33.9 mL), with a median National Institutes of Health Stroke Scale score of 17 and ICH score of 2. At 1 month, 12 of the 115 SCUBA patients had passed away (30-day mortality rate 10.4%). This was significantly lower than the predicted mortality of 35.1% when calculated using the presenting ICH score (χ 2 (1, N = 115) = 9.5, P < 0.0001), equating to an absolute risk reduction of 24.7%., Conclusions: This study suggests that minimally invasive hematoma evacuation with the SCUBA technique for ICH may reduce predicted 30-day mortality, with a number needed to treat of 4 to prevent 1 mortality., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Skin cancer is the most common malignancy affecting solid organ transplant recipients (SOTR), and SOTR experience increased skin cancer-associated morbidity and mortality. There are no formal multidisciplinary guidelines for skin cancer screening after transplant, and current practices are widely variable. We conducted three rounds of Delphi method surveys with a panel of 84 U.S. dermatologists and transplant physicians to establish skin cancer screening recommendations for SOTR. The transplant team should risk stratify SOTR for screening, and dermatologists should perform skin cancer screening by full-body skin examination. SOTR with a history of skin cancer should continue regular follow-up with dermatology for skin cancer surveillance. High-risk transplant patients include thoracic organ recipients, SOTR age 50 and above, and male SOTR. High-risk Caucasian patients should be screened within 2 years after transplant, all Caucasian, Asian, Hispanic, and high-risk African American patients should be screened within 5 years after transplant. No consensus was reached regarding screening for low-risk African American SOTR. We propose a standardized approach to skin cancer screening in SOTR based on multidisciplinary expert consensus. These guidelines prioritize and emphasize the need for screening for SOTR at greatest risk for skin cancer., (© 2019 Steunstichting ESOT.)

Importance: Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations., Objective: To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) ε4 alleles, the most potent genetic risk factor for ICH., Design, Setting, and Participants: This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study., Main Outcomes and Measures: Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies., Results: In total, 13 124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE ε2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P < .001) and APOE ε4 (OR, 1.51; 95% CI, 1.23-1.85; P < .001) were associated with lobar ICH risk; however, within self-identified Hispanic and black participants, no associations were found. After propensity score matching for hypertension burden, APOE ε4 was associated with lobar ICH risk among Hispanic (OR, 1.14; 95% CI, 1.03-1.28; P = .01) but not in black (OR, 1.02; 95% CI, 0.98-1.07; P = .25) participants. APOE ε2 and ε4 did not show an association with nonlobar ICH risk in any race/ethnicity., Conclusions and Relevance: APOE ε4 and ε2 alleles appear to affect lobar ICH risk variably by race/ethnicity, associations that are confirmed in white individuals but can be shown in Hispanic individuals only when the excess burden of hypertension is propensity score-matched; further studies are needed to explore the interactions between APOE alleles and environmental exposures that vary by race/ethnicity in representative populations at risk for ICH.

Objectives: To examine whether tobacco initiation via e-cigarettes increases the likelihood of subsequent tobacco use among a large representative sample of US adolescents., Methods: This study is a retrospective longitudinal analysis from a representative sample of US middle and high school students (n = 39,718) who completed the 2014 and 2015 National Youth Tobacco Survey. The adjusted odds ratios of lifetime and current use of tobacco use were estimated by logistic regression analysis while controlling for important socio-ecological factors associated with tobacco use., Results: E-cigarette initiators were more likely to report current use of cigarettes (AOR 2.7; 1.9-4.0, p < 0.001), cigars (AOR 1.7; 1.2-2.4, p < 0.01), or smokeless tobacco (AOR 3.1; 2.2-5.4, p < 0.001), and lifetime use of the same products as well. Also, lifetime and current use of e-cigarettes significantly increased the likelihood of cigarettes, cigars, and smokeless tobacco use., Conclusions: Initiation of tobacco via e-cigarette, lifetime, and current use of e-cigarettes are associated with higher odds of lifetime and current use of cigarettes, cigars, and smokeless tobacco. Collectively this suggests e-cigarettes may lead to an increased use of tobacco among adolescents.

E-cigarette advertising has been shown to be associated with use of e-cigarettes, but its association with tobacco use has not been studied. Therefore, we examined the association between e-cigarettes advertisement and tobacco use. Data from nationally representative 22,007 middle and high school students (grades 6-12) were used to conduct the analysis. Logistic regression models estimated the adjusted odds ratios (AOR) of ever and current use of cigarette, hookah, cigar, and polytobacco use. Odds ratios were weighted and adjusted for study design, non-response rates, school level, gender, race/ethnicity, e-cigarette use, and smoking at home. E-cigarette marketing exposure was significantly associated with ever use of cigarettes (AOR: 1.3, 95% CI: 1.1-1.5), hookah (AOR: 1.4, 95% CI: 1.2-1.7), cigars (AOR: 1.5, 95% CI: 1.4-1.6), and polytobacco (AOR: 1.7, 95% CI: 1.5-1.8). Likewise, E-cigarette marketing exposure was significantly associated with current use of cigarettes (AOR: 1.3, 95% CI: 1.1-1.6), hookah (AOR: 1.3, 95% CI: 1.03-1.7), cigars (AOR: 1.3, 95% CI: 1.1-1.6), and polytobacco use (AOR: 1.8, 95% CI: 1.5-2.1). The results suggest that e-cigarette advertisement is associated with use of cigarettes, hookah, cigars, and polytobacco products. These results add to the evidence about the risks of e-cigarette marketing and highlight the need for stricter regulation of e-cigarette advertisements., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Rationale: The frail phenotype has gained popularity as a clinically relevant measure in adults with advanced lung disease and in critical illness survivors. Because respiratory disease and chronic illness can greatly limit physical activity, the measurement of participation in traditional leisure time activities as a frailty component may lead to substantial misclassification of frailty in pulmonary and critical care patients., Objectives: To test and validate substituting the Duke Activity Status Index (DASI), a simple 12-item questionnaire, for the Minnesota Leisure Time Physical Activity (MLTA) questionnaire, a detailed questionnaire covering 18 leisure time activities, as the measure of low activity in the Fried frailty phenotype (FFP) instrument., Methods: In separate multicenter prospective cohort studies of adults with advanced lung disease who were candidates for lung transplant and older survivors of acute respiratory failure, we assessed the FFP using either the MLTA or the DASI. For both the DASI and MLTA, we evaluated content validity by testing floor effects and construct validity through comparisons with conceptually related factors. We tested the predictive validity of substituting the DASI for the MLTA in the FFP assessment using Cox models to estimate associations between the FFP and delisting/death before transplant in those with advanced lung disease and 6-month mortality in older intensive care unit (ICU) survivors., Results: Among 618 adults with advanced lung disease and 130 older ICU survivors, the MLTA had a substantially greater floor effect than the DASI (42% vs. 1%, and 49% vs. 12%, respectively). The DASI correlated more strongly with strength and function measures than did the MLTA in both cohorts. In models adjusting for age, sex, comorbidities, and illness severity, substitution of the DASI for the MLTA led to stronger associations of the FFP with delisting/death in lung transplant candidates (FFP-MLTA hazard ratio [HR], 1.42; 95% confidence interval [CI], 0.55-3.65; FFP-DASI HR, 2.99; 95% CI, 1.03-8.65) and with mortality in older ICU survivors (FFP-MLTA HR, 2.68; 95% CI, 0.62-11.6; FFP-DASI HR, 5.71; 95% CI, 1.34-24.3)., Conclusions: The DASI improves the construct and predictive validity of frailty assessment in adults with advanced lung disease or recent critical illness. This simple questionnaire should replace the more complex MLTA in assessing the frailty phenotype in these populations.

Rationale: Obesity and underweight are contraindications to lung transplantation based on their associations with mortality in studies performed before implementation of the lung allocation score (LAS)-based organ allocation system in the United States Objectives: To determine the associations of body mass index (BMI) and plasma leptin levels with survival after lung transplantation., Methods: We used multivariable-adjusted regression models to examine associations between BMI and 1-year mortality in 9,073 adults who underwent lung transplantation in the United States between May 2005 and June 2011, and plasma leptin and mortality in 599 Lung Transplant Outcomes Group study participants. We measured body fat and skeletal muscle mass using whole-body dual X-ray absorptiometry in 142 adult lung transplant candidates., Measurements and Main Results: Adjusted mortality rates were similar among normal weight (BMI 18.5-24.9 kg/m(2)), overweight (BMI 25.0-29.9), and class I obese (BMI 30-34.9) transplant recipients. Underweight (BMI < 18.5) was associated with a 35% increased rate of death (95% confidence interval, 10-66%). Class II-III obesity (BMI ≥ 35 kg/m(2)) was associated with a nearly twofold increase in mortality (hazard ratio, 1.9; 95% confidence interval, 1.3-2.8). Higher leptin levels were associated with increased mortality after transplant surgery performed without cardiopulmonary bypass (P for interaction = 0.03). A BMI greater than or equal to 30 kg/m(2) was 26% sensitive and 97% specific for total body fat-defined obesity., Conclusions: A BMI of 30.0-34.9 kg/m(2) is not associated with 1-year mortality after lung transplantation in the LAS era, perhaps because of its low sensitivity for obesity. The association between leptin and mortality suggests the need to validate alternative methods to measure obesity in candidates for lung transplantation. A BMI greater than or equal to 30 kg/m(2) may no longer contraindicate lung transplantation.

Background: Limited data exist on the economic implications of stroke among patients with atrial fibrillation (AF). This study assesses the impact of AF on healthcare costs associated with ischemic stroke (IS), hemorrhagic stroke (HS), or transient ischemic attack (TIA)., Methods and Results: A retrospective analysis of MarketScan claims data (2005-2011) for AF patients ≥18 years old with ≥1 inpatient claim for stroke, or ≥1 ED or inpatient claim for TIA as identified by ICD-9-CM codes who had ≥12 months continuous enrollment prior to initial stroke. Initial event- and stroke-related costs 12 months post-index were compared among patients with AF and without AF. Adjusted costs were estimated, controlling for demographics, comorbidities, anticoagulant use, and baseline resource use. Data from 23,807 AF patients and 136,649 patients without AF were analyzed. Unadjusted mean cost of the index event was $20,933 for IS, $59,054 for HS, $8616 for TIA hospitalization, and $3395 for TIA ED visit. After controlling for potential confounders, adjusted mean incremental costs (index plus 12-month post-index) for AF patients were higher than those for non-AF patients by: $4726, $7824, and $1890 for index IS, HS, TIA (identified by hospitalization), respectively, and $1700 for TIA (identified by ED) (all P<0.01). In multivariate regression analysis, AF was associated with a 20% (IS), 13% (HS), and 18% (TIA) increase in total stroke-related costs., Conclusion: Stroke-related care for IS, HS, and TIA is costly, especially among individuals with AF. Reducing the risk of AF-related stroke is important from both clinical and economic standpoints.

Background: Acute rejection remains a major source of morbidity after lung transplantation. Given the importance of this diagnosis, an international grading system was developed to standardize the diagnosis of acute lung-allograft rejection. The reliability of this grading system has not been adequately assessed by previous studies., Methods: We examined the level of agreement in grading transbronchial biopsy specimens obtained from a large multicenter study (AIRSAC [Comparison of a Tacrolimus/Sirolimus/Prednisone Regimen vs Tacrolimus/Azathioprine/Prednisone Immunosuppressive Regimen in Lung Transplantation] trial). Biopsy specimens were initially graded for acute rejection and lymphocytic bronchiolitis by the site pathologist and subsequently graded by a central pathologist. Reliability of interobserver grading was evaluated using Cohen κ coefficients., Results: A total of 481 transbronchial biopsy specimens were graded by both the site and central pathologists. The overall concordance rates were 74% and 89% for grade A and grade B biopsy specimens, respectively. When samples from biopsies performed at different time points after transplantation were assessed, there was a higher level of agreement early (≤ 6 weeks) after transplant compared with later time points for acute rejection. However, there was still only moderate agreement for both grade A (κ score 0.479; 95% CI, 0.29-0.67) and grade B (κ score 0.465; 95% CI, 0.08-0.85) rejection., Conclusions: These results expand upon previous reports of interobserver variability in grading transbronchial biopsy specimens after lung transplantation. Given the variability in grading these specimens, we advocate further education of the histopathologic findings in lung transplant biopsy specimens, as well as revisiting the current criteria for grading transbronchial biopsy specimens to improve concordance among lung transplant pathologists., Trial Registry: ClinicalTrials.gov; No. NCT00321906; URL: www.clinicaltrials.gov.

We reviewed our multicenter experience with gamma-delta (γδ) T-cell lymphomas first presenting in the skin. Fifty-three subjects with a median age of 61 years (range, 25 to 91 y) were diagnosed with this disorder. The median duration of the skin lesions at presentation was 1.25 years (range, 1 mo to 20 y). The most common presentation was deep plaques (38 cases) often resembling a panniculitis, followed by patches resembling psoriasis or mycosis fungoides (10 cases). These lesions tended to ulcerate overtime (27 cases). Single lesions or localized areas of involvement resembling cellulitis or pyoderma were reported in 8 cases. The most common anatomic site of involvement was the legs (40 cases), followed by the torso (30 cases) and arms (28 cases). Constitutional symptoms were reported in 54% (25/46) of the patients, including some with limited skin involvement. Significant comorbidities included autoimmunity (12 cases), other lymphoproliferative disorders (5 cases), internal carcinomas (4 cases), and viral hepatitis (2 cases). Lymphadenopathy (3/42 cases) and bone marrow involvement (5/28 cases) were uncommon, but serum lactose dehydrogenase (LDH) was elevated in 55% (22/39) of the patients. Abnormal positron emission tomography and/or computed tomography scans in 20/37 subjects mostly highlighted soft tissue or lymph nodes. Disease progression was associated with extensive ulcerated lesions resulting in 27 deaths including complications of hemophagocytic syndrome (4) and cerebral nervous system involvement (3). Median survival time from diagnosis was 31 months. Skin biopsies varied from a pagetoid pattern to purely dermal or panniculitic infiltrates composed of intermediate-sized lymphocytes with tissue evidence of cytotoxicity. The most common immunophenotype was CD3+/CD4⁻/CD5⁻/CD8⁻/BF1⁻/γ-M1+/TIA-1+/granzyme-B+/CD45RA-/CD7-, and 4 cases were Epstein-Barr virus positive. This is the largest study to date of cutaneous γδ T-cell lymphomas and demonstrates a variety of clinical and pathologic presentations with a predictable poor outcome.

Rationale: Obesity has been linked to acute lung injury and is a risk factor for early mortality after lung transplantation., Objectives: To examine the associations of obesity and plasma adipokines with the risk of primary graft dysfunction after lung transplantation., Methods: We performed a prospective cohort study of 512 adult lung transplant recipients with chronic obstructive pulmonary disease or interstitial lung disease enrolled in the Lung Transplant Outcomes Group Study. In a nested case-control study, we measured plasma leptin, adiponectin, and resistin before lung transplantation and 6 and 24 hours after lung transplantation in 40 cases of primary graft dysfunction and 80 control subjects. Generalized linear mixed models and logistic regression were used to estimate risk ratios and odds ratios., Measurements and Main Results: Grade 3 primary graft dysfunction developed within 72 hours of transplantation in 29% participants. Obesity was associated with a twofold increased risk of primary graft dysfunction (adjusted risk ratio 2.1; 95% confidence interval, 1.7-2.6). The risk of primary graft dysfunction increased by 40% (confidence interval, 30–50%) for each 5 kg/m(2) increase in body mass index after accounting for center, diagnosis, cardiopulmonary bypass, and transplant procedure. Higher plasma leptin levels were associated with a greater risk of primary graft dysfunction (sex-adjusted P = 0.02). The associations of both obesity and leptin with primary graft dysfunction tended to be stronger among those who did not undergo cardiopulmonary bypass., Conclusions: Obesity is an independent risk factor for primary graft dysfunction after lung transplantation.

Purpose: The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of acute spontaneous intracerebral hemorrhage., Methods: A formal literature search of MEDLINE was performed. Data were synthesized with the use of evidence tables. Writing committee members met by teleconference to discuss data-derived recommendations. The American Heart Association Stroke Council's Levels of Evidence grading algorithm was used to grade each recommendation. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council Scientific Statements Oversight Committee and Stroke Council Leadership Committee. It is intended that this guideline be fully updated in 3 years' time., Results: Evidence-based guidelines are presented for the care of patients presenting with intracerebral hemorrhage. The focus was subdivided into diagnosis, hemostasis, blood pressure management, inpatient and nursing management, preventing medical comorbidities, surgical treatment, outcome prediction, rehabilitation, prevention of recurrence, and future considerations., Conclusions: Intracerebral hemorrhage is a serious medical condition for which outcome can be impacted by early, aggressive care. The guidelines offer a framework for goal-directed treatment of the patient with intracerebral hemorrhage.

Rationale: Obesity is considered a relative contraindication to lung transplantation, based on studies that have not accounted for key confounders. Little is known about the risk of death for underweight candidates after transplantation., Objectives: To examine the associations of pretransplant obesity and underweight with the risk of death after lung transplantation., Methods: We examined 5,978 adults with cystic fibrosis, chronic obstructive pulmonary disease, and diffuse parenchymal lung disease who underwent lung transplantation in the United States between 1995 and 2003. We used Cox models and generalized additive models to examine the association between pretransplant body mass index and the risk of death after lung transplantation with adjustment for donor and recipient factors., Measurements and Main Results: The median follow-up time was 4.2 years. Compared with normal weight recipients, the multivariable-adjusted rates of death were 15% higher for underweight recipients (95% confidence interval, 3 to 28%), 15% higher for overweight recipients (95% confidence interval, 6 to 26%), and 22% higher for obese recipients (95% confidence interval, 8 to 39%). These relationships persisted when stratified by diagnosis. The multivariable-adjusted population attributable fraction was 12% at 1 year and 8% at 5 years., Conclusions: Both obesity and underweight are independent risk factors for death after lung transplantation, contributing to up to 12% of deaths in the first year after transplantation. Primary care providers and pulmonologists should promote a healthy weight for patients with lung disease long before transplantation is considered.

Rationale: Blacks with chronic illness have poorer outcomes than whites in the United States. The health outcomes of minorities with chronic obstructive pulmonary disease (COPD) on the lung transplant waiting list have not been studied., Objectives: To compare outcomes of black and white patients with COPD after listing for lung transplantation in the United States., Methods: Retrospective cohort study of all 280 non-Hispanic black and 5,272 non-Hispanic white adults 40 years and older with COPD listed for lung transplantation in the United States between 1995 and 2004., Measurements and Main Results: Blacks with COPD were more likely to have pulmonary hypertension, obesity, and diabetes; to lack private health insurance; and to live in poorer neighborhoods than whites. Blacks were less likely to undergo transplantation after listing compared with whites, despite adjustment for age, lung function, pulmonary hypertension, cardiovascular risk factors, insurance coverage, and poverty level (adjusted hazard ratio, 0.83; 95% confidence interval, 0.70-0.98; P = 0.03). This was accompanied by a greater risk of dying or being removed from the list among blacks (unadjusted hazard ratio, 1.31; 95% confidence interval, 1.05-1.63; P = 0.02)., Conclusions: After listing for lung transplantation, black patients with COPD were less likely to undergo transplantation and more likely to die or be removed from the list compared with white patients. Unequal access to care may have contributed to these differences.

Rationale: Characteristics of and survival estimates for recipients of lung retransplantation in the modern era are unknown., Objectives: To compare lung retransplant patients in the modern era with historical retransplant patients, to compare retransplant patients with initial transplant patients in the modern era, and to determine the predictors of the risk of death after lung retransplantation., Methods: We performed a retrospective cohort study of patients who underwent lung retransplantation between January 2001 and May 2006 in the United States (modern retransplant cohort). The characteristics and survival of this cohort were compared with those of patients who underwent first lung retransplantation between January 1990 and December 2000 (historical retransplant cohort) and patients who underwent initial lung transplantation between January 2001 and May 2006 (modern initial transplant cohort)., Measurements and Main Results: Modern retransplant recipients (n = 205) had a lower risk of death compared with that of the historical retransplant cohort (n = 184) (hazard ratio, 0.7; 95% confidence interval, 0.5-0.9; P = 0.006). However, modern retransplant recipients had a higher risk of death than that of patients who underwent initial lung transplantation (n = 5,657) (hazard ratio, 1.3; 95% confidence interval, 1.2-1.5; P = 0.001), which appeared to be explained by a higher prevalence of certain comorbidities. Retransplantation at less than 30 days after the initial transplant procedure was associated with worse survival., Conclusions: Outcomes after lung retransplantation have improved; however, retransplantation continues to pose an increased risk of death compared with the initial transplant procedure. Retransplantation early after the initial transplant poses a particularly high mortality risk.

Objectives: Little is known about the descriptive epidemiology of pancreatic cancer in many developing countries, such as Egypt. It is believed to be rare in developing countries, but this may reflect lack of systematic cancer registration. Mortality may serve as a surrogate for incidence, since the disease is lethal. Because of availability of reliable mortality registration in Egypt, we used the national mortality data to estimate pancreatic cancer mortality in 2765 deaths from 2000 to 2004, and to gain insights into the disease incidence., Methods: Mortality data in Egypt was obtained from the electronic national mortality records of the Ministry of Health. We calculated population-based age-specific and age-standardized pancreatic cancer mortality rates for Egypt, and compared them with the Surveillance, Epidemiology, and End Results (SEER) mortality data of the United States., Results: Comparisons of age-specific mortality demonstrated higher rates in Egypt compared to the United States for subjects under age 20 years (relative risks (RR) of 7.7 and 4.2, for the age groups 0-15 and 15-20, respectively), and significantly higher rates in the United States compared to Egypt for subjects 40 years and older (RR 1.8-80.5 for the age groups of 40-45 to 75+). For the majority of age groups in Egypt and the United States, mortality in males was higher than in females. Analysis of regional distribution of pancreatic cancer mortality in Egypt showed significant variations in rates among provinces (p<0.0001) with Northern provinces having average rate that is 2.85 times the rate of Southern provinces. The highest mortality rates were observed in the Nile Delta compared to southern Egypt and the oasis., Conclusions: The findings of this study demonstrate both international and regional variation in pancreatic cancer mortality, and highlight the importance of further investigation to explore the possible factors that may contribute to the observed epidemiological patterns.

Background: Lung transplantation is currently limited by the number of suitable donor organs. Many lung-transplant programs use lungs that do not meet the formal criteria for acceptability; however, the immediate and long-term consequences of this approach remain unclear., Methods: We performed a retrospective cohort study of all patients who underwent lung transplantation at the Columbia University Medical Center from July 2001 to July 2003. We assessed the outcomes of recipients of extended donor lungs compared with those of recipients of optimal donor lungs after adjusting for confounding variables., Results: Fifty-one patients underwent lung transplantation, of which 27 (53%) received extended donor lungs. Recipients of extended donor lungs had fewer intensive care unit-free days at 30 days (P=0.002) and a longer time to hospital discharge (P=0.007) than did recipients of optimal donor lungs. Extended donor recipients also had lower forced expiratory volume in 1 second % predicted at 1 year than did optimal donor recipients (P=0.03). There were no differences in the 30-day or longer-term survival of extended and optimal donor lung recipients., Conclusions: Recipients of extended donor lungs have a longer intensive care unit course, a prolonged hospital stay, and lower pulmonary function at 1 year than recipients of optimal lungs. Despite these differences, survival is similar between the two groups. The criteria for the optimal lung donor should be re-evaluated considering the current shortage of acceptable organs. Although some outcomes may differ with the use of extended donor lungs, the clinical impact of these differences should be assessed in future prospective multicenter studies.

The goals of this project were to evaluate and compare the efficiency and reproducibility of three methods for sampling lead-containing dust in homes. Lead-containing dust was generated in a 1-m3 chamber and uniformly deposited onto surfaces typically found in the home (painted wood, unpainted wood, varnished wood, linoleum, and carpet). Trials with three levels of lead concentrations were performed for each surface. Replicate, side-by-side, surface samples were collected using the Occupational Safety and Health Administration (OSHA) wipe method, the Department of Housing and Urban Development (HUD) wipe method, and a vacuum-filter method. Samples were digested with nitric acid and analyzed using graphite furnace atomic absorption spectroscopy per National Institute of Occupational Safety and Health Method 7105. Recovery for the HUD method was consistently the highest on most surfaces (linoleum, 89.9 to 108.9%; painted wood, 71.2 to 153.7%; unpainted wood, 25.3 to 76.0%; varnished wood, 8.7 to 165.6%). On carpet the vacuum method had a significantly higher recovery (26.2 to 47.8%). For all sampling methods the percent recovery depended on type of surface and lead concentration. The reproducibility of percent recovery for the HUD (pooled coefficient of variation [CV] = 0.22) and OSHA (pooled CV = 0.27) methods was lower than that of the vacuum method (pooled CV = 0.46), though not statistically significant. Reproducibility for all methods did not vary significantly over surface type or lead concentration. Overall, the HUD method yielded the most accurate measurements, with recoveries closest to 100%. It was also more durable than the OSHA method, where Whatman filters were observed to tear.