Prospective cohort of cryobiopsy in interstitial lung diseases: a single center experience.

RATIONALE: Transbronchial cryobiopsy has been increasingly used to diagnose interstitial lung diseases. However, there is uncertainty regarding its accuracy and risks, mainly due to a paucity of prospective or randomized trials comparing cryobiopsy to surgical biopsy. OBJECTIVES: To evaluate the diagnostic yield and complications of cryobiopsy in patients selected by multidisciplinary discussion. METHODS: This was a prospective cohort from 2017 to 2019. We included consecutive patients with suspected interstitial lung diseases being considered for lung biopsy presented at our multidisciplinary meeting. MEASUREMENTS AND MAIN RESULTS: Of 112 patients, we recommended no biopsy in 31, transbronchial forceps biopsy in 16, cryobiopsy in 54 and surgical biopsy in 11. By the end of the study, 34 patients had had cryobiopsy and 24 patients, surgical biopsy. Overall pathologic and multidisciplinary diagnostic yield of cryobiopsy was 47.1% and 61.8%, respectively. The yield increased over time for both pathologic (year 1: 28.6%, year 2: 54.5%, year 3: 66.7%, p = 0.161) and multidisciplinary (year 1: 50%, year 2: 63.6%, year 3: 77.8%, p = 0.412) diagnosis. Overall rate of grade 4 bleeding after cryobiopsy was 11.8%. Cryobiopsy required less chest tube placement (11.8% vs 100%, p < 0.001) and less hospitalizations compared to surgical biopsy (26.5% vs 95.7%, p < 0.001), but hospitalized patients had a longer median hospital stay (2 days vs 1 day, p = 0.004). CONCLUSIONS: Diagnostic yield of cryobiopsy increased over time but the overall grade 4 bleeding rate was 11.8%.

Performance of diagnostic criteria in patients clinically judged to have cardiac sarcoidosis: Is it time to regroup?

BACKGROUND: The diagnosis of cardiac sarcoidosis (CS) is challenging. Because of the current limitations of endomyocardial biopsy as a reference standard, physicians rely on advanced cardiac imaging, multidisciplinary evaluation, and diagnostic criteria to diagnose CS. AIMS: To compare the 3 main available diagnostic criteria in patients clinically judged to have CS. METHODS: We prospectively included patients clinically judged to have CS by a multidisciplinary sarcoidosis team from November 2016 to October 2017. We included only incident cases (diagnosis of CS within 1 year of inclusion). We applied retrospectively the following diagnostic criteria: the World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG), the Heart Rhythm Society (HRS), and the Japanese Circulation Society (JCS) 2016 criteria. RESULTS: We identified 69 patients. Diagnostic criteria classified patients as follows: WASOG as highly probable (1.4%), probable (52.2%), possible (0%), some criteria (40.6%), and no criteria (5.8%); HRS as histological diagnosis (1.4%), probable (52.2%), some criteria (40.6%), and no criteria (5.8%); JCS as histological diagnosis (1.4%), clinical diagnosis (58%), some criteria (39.1%), and no criteria (1.4%). Concordance was high between WASOG and HRS (κ = 1) but low between JCS and the others (κ = 0.326). CONCLUSIONS: A high proportion of patients clinically judged to have CS are unable to be classified according to the 3 main diagnostic criteria. There is low concordance between JCS criteria and the other 2 criteria (WASOG and HRS).

Use of leflunomide in patients with chronic hypersensitivity pneumonitis.

BACKGROUND: Prednisone has been shown to reverse lung function declines in hypersensitivity pneumonitis patients without established fibrosis. Second line immunosuppressants like azathioprine and mycophenolate mofetil have a steroid sparing effect and improve DLCO. There is no published literature on the use of leflunomide in such patients. METHODS: We reviewed our experience with leflunomide for treatment of chronic hypersensitivity pneumonitis in 40 patients. We stratified patients according to the presence or absence of significant (> 20%) fibrosis. We studied the effect of leflunomide on FVC and DLCO trajectory and reported the changes at 12 months. RESULTS: Treatment with leflunomide tended to improve the estimated FVC slope from 0.18 ± 1.90% (SEM) of predicted per year to 4.62 ± 1.65% of predicted (NS, p = 0.118). It significantly improved the FVC at 12 months of treatment by 4.4% of predicted (p = 0.02). DLCO continued to increase at 1.45 ± 1.44% (SEM) of predicted per year. Non-fibrotic cHP patients had the largest gain in pulmonary function. Their FVC increased by 8.3% (p = 0.001) and DLCO by 4.8% (p = 0.011). Patients with fibrotic cHP did not improve. Leflunomide treatment was associated with significant gastrointestinal and other adverse effects leading 40% of patients to discontinue therapy. It had a significant steroid sparing effect with half the patients weaned off prednisone entirely. CONCLUSIONS: Leflunomide appears to be a fairly well tolerated steroid sparing immunosuppressant that improves pulmonary function in cHP patients. It is most effective in patients without significant fibrosis.

Results From a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Repository Corticotropin Injection for the Treatment of Pulmonary Sarcoidosis.

INTRODUCTION: Long-term treatment of pulmonary sarcoidosis with glucocorticoids has been associated with toxicity and other adverse events, highlighting the need for alternative therapies. The goal of this study was to evaluate the efficacy and safety of repository corticotropin injection (RCI, Acthar® Gel) in patients with pulmonary sarcoidosis and to validate endpoints for use in future clinical trials. METHODS: In this multicenter, randomized, placebo-controlled trial, subjects received subcutaneous RCI (80 U) twice weekly or matching placebo through 24 weeks in a double-blind treatment phase, followed by an optional 24-week open-label extension. Efficacy was measured by glucocorticoid tapering, pulmonary function tests, chest imaging, patient-reported outcomes, and a novel sarcoidosis treatment score (STS). Safety was assessed by adverse events, physical examinations, vital signs, clinical laboratory abnormalities, and imaging. The study was terminated early due to low enrollment caused by the COVID-19 pandemic, thereby precluding statistical analysis. RESULTS: Fifty-five subjects were randomized to receive either RCI (n = 27) or placebo (n = 28). Mean STS at week 24 showed greater improvement with RCI (1.4) compared with placebo (0.7). At week 48, those who remained on RCI had an STS of 1.8 compared with 0.9 in those who switched from placebo to RCI. More subjects in the RCI group discontinued glucocorticoids at week 24 compared to the placebo group. Glucocorticoid discontinuation was comparable at week 48 for those who switched from placebo to RCI and those who continued RCI. Similar trends in favor of RCI over placebo were observed with the other efficacy endpoints. No new or unexpected safety signals were identified. CONCLUSIONS: RCI was safe and well tolerated, with trends in efficacy data suggesting greater improvement with RCI compared to placebo in patients receiving standard-of-care therapy for pulmonary sarcoidosis. The study also provided validation of efficacy endpoints that may be used in larger trials for pulmonary sarcoidosis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03320070.

Pulmonary sarcoidosis is a disease characterized by inflammation of the lungs. Standard treatments include glucocorticoids, which may have harmful side effects. This clinical trial investigated whether repository corticotropin injection (RCI, Acthar^® Gel) was safe and effective in patients who were already taking glucocorticoids to treat pulmonary sarcoidosis. Patients were randomly assigned to be in one of two treatment groups: RCI or placebo. In the first 24 weeks of the study, 27 patients were injected with RCI twice weekly, while 28 patients were injected with an inactive substance (placebo). Forty-seven patients continued into an optional phase of the study for an additional 24 weeks in which all patients received RCI twice weekly. A sarcoidosis treatment score and assessments of lung health, general health, and fatigue were used to determine whether RCI was effective. These assessments showed greater improvements with RCI compared to placebo. Patients who switched from placebo to RCI showed similar improvements to those who remained on RCI throughout the entire study. Patients receiving RCI were able to discontinue their use of glucocorticoids more quickly than those taking placebo, thus helping them to avoid the harmful side effects of the glucocorticoids. Side effects for RCI were mostly mild or moderate, and no new or unexpected safety concerns for RCI were seen throughout the study.

Early Doffing among Frontline Healthcare Workers Working in the COVID Areas in Resource-Limited Settings: Lessons Learned and Interventions Taken.

Background: In the fight against the pandemic, personal protective equipment (PPE) has played a vital role. However, working with PPE has its own difficulties and problems. The aim of this study was to find out the reasons of early doffing, that is, in doffing in emergency situations before the shift among healthcare workers (HCWs) working in PPE in the COVID areas in resource-limited settings. Methods: This cross-sectional, survey-based study was carried out on healthcare workers involved in direct care of patients with COVID-19 in tertiary care COVID center, India. The questionnaire was sent as a Google form through email and social media platforms like WhatsApp and Facebook. The data was reported as the mean ± SD for continuous variables and as the percentage for categorical variables. Findings: Among 252 healthcare workers who participated in the survey, 145 (57.5%) participants doffed early on 300 occasions. Out of these 145, 50% doffed early only once and rest doffed early multiple times. The most common reason of early doffing was found to be breach in PPE (15.33%) followed by fogging (14%) and headache (12%), and most commonly, breach was in mask or coverall/gown (32.6% each). Conclusion: Although PPE decreases the risk of infection, it is challenging for HCWs to work in PPE leading to instances of early doffing. The most common reason for early doffing in our study was the breach in PPE and the most common component of breach was found to be mask and coverall/gown. Therefore, we suggest that the proper sizes of the PPE should be made available and proper training in donning should be imparted to HCWs working in PPE.

Association between Hypocalcemia and Outcome in COVID-19 Patients: A Retrospective Study.

Background Calcium has been shown to play a vital role in the pathophysiology of severe acute respiratory syndrome-coronavirus-2 and middle east respiratory syndrome coronavirus diseases, but less is known about hypocalcemia in coronavirus disease 2019 (COVID-19) patients and its association with the disease severity and the final outcome. Therefore, this study was conducted with an aim to assess clinical features in COVID-19 patients having hypocalcemia and to observe its impact on COVID-19 disease severity and the final outcome. Methods In this retrospective study, consecutive COVID-19 patients of all age groups were enrolled. Demographical, clinical, and laboratory details were collected and analyzed. On the basis of albumin-corrected calcium levels, patients were classified into normocalcemic ( n = 51) and hypocalcemic ( n = 110) groups. Death was the primary outcome. Results The mean age of patients in the hypocalcemic group was significantly lower ( p < 0.05). A significantly higher number of hypocalcemic patients had severe COVID-19 infection (92.73%; p < 0.01), had comorbidities (82.73%, p < 0.05), and required ventilator support (39.09%; p < 0.01) compared with normocalcemic patients. The mortality rate was significantly higher in the hypocalcemic patients (33.63%; p < 0.05). Hemoglobin ( p < 0.01), hematocrit ( p < 0.01), and red cell count ( p < 0.01) were significantly lower with higher levels of absolute neutrophil count (ANC; p < 0.05) and neutrophil-to-lymphocyte ratio (NLR; p < 0.01) in the hypocalcemic patients. Albumin-corrected calcium levels had a significant positive correlation with hemoglobin levels, hematocrit, red cell count, total protein, albumin, and albumin-to-globulin ratio and a significant negative correlation with ANC and NLR. Conclusion The disease severity, ventilator requirement, and mortality were considerably higher in hypocalcemic COVID-19 patients.

Double-blind randomized proof-of-concept trial of canakinumab in patients with COVID-19 associated cardiac injury and heightened inflammation.

Aims: In coronavirus disease 2019 (COVID-19), myocardial injury is associated with systemic inflammation and higher mortality. Our aim was to perform a proof of concept trial with canakinumab, a monoclonal antibody to interleukin-1ß, in patients with COVID-19, myocardial injury, and heightened inflammation. Methods and results: This trial required hospitalization due to COVID-19, elevated troponin, and a C-reactive protein concentration more than 50 mg/L. The primary endpoint was time to clinical improvement at Day 14, defined as either an improvement of two points on a seven-category ordinal scale or discharge from the hospital. The secondary endpoint was mortality at Day 28. Forty-five patients were randomly assigned to canakinumab 600 mg (n = 15), canakinumab 300 mg (n = 14), or placebo (n = 16). There was no difference in time to clinical improvement compared to placebo [recovery rate ratio (RRR) for canakinumab 600 mg 1.15, 95% confidence interval (CI) 0.46-2.91; RRR for canakinumab 300 mg 0.61, 95% CI 0.23-1.64]. At Day 28, 3 (18.8%) of 15 patients had died in the placebo group, compared with 3 (21.4%) of 14 patients with 300 mg canakinumab, and 1 (6.7%) of 15 patients with 600 mg canakinumab. There were no treatment-related deaths, and adverse events were similar between groups. Conclusion: There was no difference in time to clinical improvement at Day 14 in patients treated with canakinumab, and no safety concerns were identified. Future studies could focus on high dose canakinumab in the treatment arm and assess efficacy outcomes at Day 28.

Thoracic imaging in COVID-19.

The typical findings of COVID-19 on chest radiography and computed tomography (CT) include bilateral, multifocal parenchymal opacities (ground-glass opacities with or without consolidation, and "crazy paving"). In most cases, the opacities are predominantly in the peripheral and lower lung zones, and several have rounded morphology. However, these imaging findings are not pathognomonic for COVID-19 pneumonia and can be seen in other viral and bacterial infections, as well as with noninfectious causes such as drug toxicity and connective tissue disease. Most radiology professional organizations and societies recommend against routine screening CT to diagnose or exclude COVID-19.

Canakinumab to reduce deterioration of cardiac and respiratory function in SARS-CoV-2 associated myocardial injury with heightened inflammation (canakinumab in Covid-19 cardiac injury: The three C study).

BACKGROUND: In patients with Covid-19, myocardial injury and increased inflammation are associated with morbidity and mortality. We designed a proof-of-concept randomized controlled trial to evaluate whether treatment with canakinumab prevents progressive respiratory failure and worsening cardiac dysfunction in patients with SARS-CoV2 infection, myocardial injury, and high levels of inflammation. HYPOTHESIS: The primary hypothesis is that canakiumab will shorten time to recovery. METHODS: The three C study (canakinumab in Covid-19 Cardiac Injury, NCT04365153) is a double-blind, randomized controlled trial comparing canakinumab 300 mg IV, 600 mg IV, or placebo in a 1:1:1 ratio in hospitalized Covid-19 patients with elevations in troponin and C-reactive protein (CRP). The primary endpoint is defined as the time in days from randomization to either an improvement of two points on a seven category ordinal scale or discharge from the hospital, whichever occurs first up to 14 days postrandomization. The secondary endpoint is mortality at day 28. A total of 45 patients will be enrolled with an anticipated 5 month follow up period. RESULTS: Baseline characteristics for the first 20 randomized patients reveal a predominantly male (75%), elderly population (median 67 years) with a high prevalence of hypertension (80%) and hyperlipidemia (75%). CRPs have been markedly elevated (median 16.2 mg/dL) with modest elevations in high-sensitivity troponin T (median 21 ng/L), in keeping with the concept of enrolling patients with early myocardial injury. CONCLUSIONS: The three C study will provide insights regarding whether IL-1ß inhibition may improve outcomes in patients with SARS-CoV2 associated myocardial injury and increased inflammation.

Toxicity risk from glucocorticoids in sarcoidosis patients.

BACKGROUND: Glucocorticoids (GC) are considered first-line therapy for treating sarcoidosis, but there are few data about the adverse consequences of GC. Although there are several steroid-sparing medications available for treatment, a large proportion of patients are treated with prolonged courses of GC. The toxicities of GC in sarcoidosis populations have not been carefully evaluated. METHODS: We performed a retrospective cohort study of all newly diagnosed sarcoidosis patients who had the entirety of their medical care in a single health system. We analyzed the time to development of a composite toxicity end-point, including diabetes, hypertension, weight gain, hyperlipidemia, low bone density and ocular complications of GC using Cox proportional hazards analysis. RESULTS: One hundred and five patients were ever treated with GC, whereas 49 were not treated during a median follow-up of 101 months. GC-treated patients developed 1.3 ± 1.1 toxicities during therapy, versus 0.6 ± 1.0 in the non-treated group. After adjustment for age, gender, race and preexisting conditions, the hazard ratio for ever-treated patients was 2.37 (1.34-4.17) for the composite end-point. Age and the presence of preexisting conditions also were associated with reaching the end-point. Similar effects were seen when analyzed for cumulative GC dose and for duration of GC use. For individual end-points, weight gain (HR 2.04) and new hypertension (HR 3.36) were associated with any use of GC. CONCLUSIONS: Our data suggest that GC are associated with clinically important toxicities in sarcoidosis patients, associated with both the cumulative dose and duration of treatment.

Brain injury tolerance limit based on computation of axonal strain.

Traumatic brain injury (TBI) is the leading cause of death and permanent impairment over the last decades. In both the severe and mild TBIs, diffuse axonal injury (DAI) is the most common pathology and leads to axonal degeneration. Computation of axonal strain by using finite element head model in numerical simulation can enlighten the DAI mechanism and help to establish advanced head injury criteria. The main objective of this study is to develop a brain injury criterion based on computation of axonal strain. To achieve the objective a state-of-the-art finite element head model with enhanced brain and skull material laws, was used for numerical computation of real world head trauma. The implementation of new medical imaging data such as, fractional anisotropy and axonal fiber orientation from Diffusion Tensor Imaging (DTI) of 12 healthy patients into the finite element brain model was performed to improve the brain constitutive material law with more efficient heterogeneous anisotropic visco hyper-elastic material law. The brain behavior has been validated in terms of brain deformation against Hardy et al. (2001), Hardy et al. (2007), and in terms of brain pressure against Nahum et al. (1977) and Trosseille et al. (1992) experiments. Verification of model stability has been conducted as well. Further, 109 well-documented TBI cases were simulated and axonal strain computed to derive brain injury tolerance curve. Based on an in-depth statistical analysis of different intra-cerebral parameters (brain axonal strain rate, axonal strain, first principal strain, Von Mises strain, first principal stress, Von Mises stress, CSDM (0.10), CSDM (0.15) and CSDM (0.25)), it was shown that axonal strain was the most appropriate candidate parameter to predict DAI. The proposed brain injury tolerance limit for a 50% risk of DAI has been established at 14.65% of axonal strain. This study provides a key step for a realistic novel injury metric for DAI.

Development of skull fracture criterion based on real-world head trauma simulations using finite element head model.

The objective of this study was to enhance an existing finite element (FE) head model with composite modeling and a new constitutive law for the skull. The response of the state-of-the-art FE head model was validated in the time domain using data from 15 temporo-parietal impact experiments, conducted with postmortem human surrogates. The new model predicted skull fractures observed in these tests. Further, 70 well-documented head trauma cases were reconstructed. The 15 experiments and 70 real-world head trauma cases were combined to derive skull fracture injury risk curves. The skull internal energy was found to be the best candidate to predict skull failure based on an in depth statistical analysis of different mechanical parameters (force, skull internal energy), head kinematic-based parameter, the head injury criterion (HIC), and skull fracture correlate (SFC). The proposed tolerance limit for 50% risk of skull fracture was associated with 453mJ of internal energy. Statistical analyses were extended for individual impact locations (frontal, occipital and temporo-parietal) and separate injury risk curves were obtained. The 50% risk of skull fracture for each location: frontal: 481mJ, occipital: 457mJ, temporo-parietal: 456mJ of skull internal energy.

Head injury assessment of non-lethal projectile impacts: A combined experimental/computational method.

The main objective of this study is to develop a methodology to assess this risk based on experimental tests versus numerical predictive head injury simulations. A total of 16 non-lethal projectiles (NLP) impacts were conducted with rigid force plate at three different ranges of impact velocity (120, 72 and 55m/s) and the force/deformation-time data were used for the validation of finite element (FE) NLP. A good accordance between experimental and simulation data were obtained during validation of FE NLP with high correlation value (>0.98) and peak force discrepancy of less than 3%. A state-of-the art finite element head model with enhanced brain and skull material laws and specific head injury criteria was used for numerical computation of NLP impacts. Frontal and lateral FE NLP impacts to the head model at different velocities were performed under LS-DYNA. It is the very first time that the lethality of NLP is assessed by axonal strain computation to predict diffuse axonal injury (DAI) in NLP impacts to head. In case of temporo-parietal impact the min-max risk of DAI is 0-86%. With a velocity above 99.2m/s there is greater than 50% risk of DAI for temporo-parietal impacts. All the medium- and high-velocity impacts are susceptible to skull fracture, with a percentage risk higher than 90%. This study provides tool for a realistic injury (DAI and skull fracture) assessment during NLP impacts to the human head.

Influence of head mass on temporo-parietal skull impact using finite element modeling.

The effect of head mass on its biomechanical response during lateral impact to the head is investigated in this computational study. The mass of the head of a state-of-the-art validated finite element head model is altered by ± 10 % from the base value of 4.7 kg. Numerical simulations of lateral head impacts for 30 cases (representing 15 human cadaver experiments × 2 mass configurations) are performed using the LS-DYNA solver at different velocities ranging from 2.4 to 6.5 m/s and three impacting conditions representing different stiffness and shapes of the contact/impact surfaces. Results are compared with the original model using the baseline head mass, thus resulting in a total of 45 simulations. Present findings show that the head mass has greater influence for peak interaction forces and the force has a greater dependency on stiffness of contact surface than the shape. Mass variations have also influence on skull strain energy. Regardless of increase/decrease in skull strain energy influenced by head mass variations used in the computational study, the 50 % fracture tolerance limit was unaltered, which was 544 mJ. The present study gives a better understanding of the mechanism of temporo-parietal skull impact.

Outcome of cardiac sarcoidosis after radiofrequency ablation and placement of AICD- A propensity matched analysis.

BACKGROUND: Cardiac Sarcoidosis (CS) can lead to life-threatening ventricular dysrhythmias and sudden death. Immunosuppressive medications, radiofrequency ablation (RFA), and implantable cardioverter defibrillators (ICD) have been utilized to manage ventricular dysrhythmias but their benefits remain poorly defined. OBJECTIVE: The aim of this study is to assess the durability of RFA in CS population and to determine outcome predictors after RFA. METHODS: We compared the CS patients who had RFA±ICD against those with only ICD placement and contemporaneous patients with arrhythmogenic right ventricular dysplasia (ARVD) who had RFA. We analyzed time to a composite first event of appropriate ICD therapy, subsequent RFA, cardiac transplantation or death. We also evaluated variables predicting recurrence of ventricular dysrhythmias, including LVEF, cardiac involvement on PET scan, percent of ventricular ectopic beats, number of inducible VT foci and success of the RFA procedure. We used propensity matching and multivariable regression to adjust for baseline differences between the groups to identify outcome predictors. RESULTS: Thirty ablations for VT were performed in 20 CS patients (13 had concomitant ICD placement); 12 ablations were done in eight ARVD patients and 33 CS patients with only ICD placements were included in this cohort. The median follow-up period was 48 (9-173) months. Fourteen (70%) patients reached composite end points after RFA compared to 13 (63%) following ICD placement and five (87%) in the ARVD cohort. There was a significant time difference to reach composite end points (p=0.02) in favor of ICD only cohort. The median number of ICD therapies were higher in the CS-RFA group (p=0.01). The requirement for ICD therapy increased over time following RFA, especially after 12 months. Variables predicting earlier time-to-event were EF <40% (OR=13.2) and unsuccessful RFA procedure (OR=7.9). The presence of more than one inducible VT morphology was associated with higher likelihood of unsuccessful RFA (p=0.03). CONCLUSION: RFA can be an effective modality for the short-term treatment of ventricular dysrhythmias in cardiac sarcoidosis; however, after more than 12 months, the number of appropriate therapies escalates. Accordingly, ICD placement is recommended for all patients who undergo RFA for VT associated with CS, whether it is successful or not. Low LVEF and unsuccessful ablation were strong predictors of future events.

Disease Recurrence and Acute Cellular Rejection Episodes During the First Year After Lung Transplantation Among Patients With Sarcoidosis.

INTRODUCTION: Sarcoidosis is reported to recur after lung transplantation (LT). We sought to determine the frequency of recurrent disease after LT and predictors of recurrence. We also evaluated the incidence and severity of acute cellular rejection (ACR) episodes among these patients. METHODS: The database of LT patients at Cleveland Clinic was interrogated for sarcoidosis patients who underwent LT between May 1993 and 2011. Charts were reviewed for demographics, type of transplant, posttransplant biopsy findings, and outcomes. RESULTS: Data were available for 30 patients (mean age, 50 ± 9.3 years; range, 30-65 years; M-to-F ratio, 17:13; single-to-double-to-heart lung ratio, 5:24:1). Recurrence of sarcoidosis was noted among 7 patients (pathological recurrence in all and radiological findings suggesting recurrence in 1 patient) with no impact on overall outcomes. Presence of granulomas on explanted lungs was the only predictor of recurrence (85.7% vs 30.4%, odds ratio, 13.7; 1.4-136.2; P = 0.02).Overall burden of ACR episodes on all bronchoscopies was significantly lower in patients with disease recurrence (7.6 % vs 21.3% of biopsies, P = 0.038). Among patients with recurrent disease, ACR did not develop once disease recurrence had been seen on transbronchial biopsy. CONCLUSIONS: A significant proportion of sarcoidosis patients have disease recurrence after LT and presence of active granulomas on explant is associated with subsequent recurrence. There may be an association of recurrence with lower frequency of ACR episodes. There does not appear to be any impact of sarcoidosis recurrence on 1-, 3-, or 5-year survivals.

Development and validation of an advanced anisotropic visco-hyperelastic human brain FE model.

This paper proposes the implementation of fractional anisotropy and axonal fiber orientation from diffusion tensor imaging (DTI) of 12 healthy patients into an existing human FE head model to develop a more realistic brain model with advanced constitutive laws. Further, the brain behavior was validated in terms of brain strain against experimental data published by Hardy et al. (2001, 2007) and for brain pressure against Nahum et al. (1977) experimental impacts. A reasonable agreement was observed between the simulation and experimental data. Results showed the feasibility of integrating axonal direction information into FE analysis and established the context of computation of axonal elongation in case of head trauma.

Characteristics and outcomes of patients with lung transplantation requiring admission to the medical ICU.

BACKGROUND: There are few data on characteristics and outcomes among patients with lung transplantation (LT) requiring admission to the medical ICU (MICU) beyond the perioperative period. METHODS: We interrogated the registry database of all admissions to the MICU at Cleveland Clinic (a 53-bed closed unit) to identify patients with history of LT done > 30 days ago (n = 101; mean age, 55.4 ± 12.6 years; 53 men, 48 women). We collected data regarding demographics, history of bronchiolitis obliterans syndrome, preadmission FEV1, clinical and laboratory variables at admission, MICU course, length of stay, hospital survival, and 6-month survival. RESULTS: The most common indication for MICU admission was acute respiratory failure (n = 51, 50.5%). Infections were most frequently responsible for respiratory failure, whereas acute rejection (cellular or humoral) was less likely (16%). Nearly one-fourth of the patients required hemodialysis (24.1%), and more than one-half required invasive mechanical ventilation (53.5%). Despite excellent hospital survival (88 of 101), 6-month survival was modest (56.4%). APACHE (Acute Physiology and Chronic Health Evaluation) III score at admission and single LT were independent predictors of hospital survival but did not predict outcome at 6 months. Functional status at discharge was the only independent predictor of 6-month survival (adjusted OR, 5.1; 95% CI, 1.1-22.7; P = .035). CONCLUSIONS: Acute rejection is an infrequent cause of decompensation among patients with LT requiring MICU admission. For patients admitted to the MICU, 6-month survival is modest. Functional status at the time of discharge is an independent predictor of survival at 6 months.