Nuclear corepressors NCOR1/NCOR2 regulate B cell development, maintain genomic integrity and prevent transformation.

The nuclear corepressors NCOR1 and NCOR2 interact with transcription factors involved in B cell development and potentially link these factors to alterations in chromatin structure and gene expression. Herein, we demonstrate that Ncor1/2 deletion limits B cell differentiation via impaired recombination, attenuates pre-BCR signaling and enhances STAT5-dependent transcription. Furthermore, NCOR1/2-deficient B cells exhibited derepression of EZH2-repressed gene modules, including the p53 pathway. These alterations resulted in aberrant Rag1 and Rag2 expression and accessibility. Whole-genome sequencing of Ncor1/2 DKO B cells identified increased number of structural variants with cryptic recombination signal sequences. Finally, deletion of Ncor1 alleles in mice facilitated leukemic transformation, whereas human leukemias with less NCOR1 correlated with worse survival. NCOR1/2 mutations in human leukemia correlated with increased RAG expression and number of structural variants. These studies illuminate how the corepressors NCOR1/2 regulate B cell differentiation and provide insights into how NCOR1/2 mutations may promote B cell transformation.

Validation and comparison of fall screening tools for predicting future falls among older adults.

BACKGROUND: Falls are the leading cause of injuries among older adults in the United States (US). Falls are preventable and clinicians are advised to screen for fall risk yearly. There are many falls screening tools and not all have been validated for their ability to predict future falls. METHODS: We enrolled 1905 community-dwelling older adults into a 13-month study using a probability-based representative panel of the US population recruited from NORC at the University of Chicago's National Frame. Respondents completed a baseline survey, 11 monthly fall calendars, and a final survey. The baseline survey included six falls screening tools (the Stay Independent, Three Key Questions (3KQ), a modified American Geriatric/British Geriatric tool, the short Falls Efficacy-1[FES-I]) and two single screening questions ("I have fallen in the past year" and "How many times did you fall in the past 12 months?"). The baseline and final survey collected demographic and health information, including falls. Sensitivity, specificity, positive and negative likelihood ratios, and corresponding 95% confidence intervals were calculated in SAS using weighted proportions. RESULTS: There were 1563 respondents who completed the final survey (completion rate 82%). Sensitivity estimates ranged from 22.5% for the short FES-I to 68.7% for the 3KQ. Specificity estimates ranged from 57.9% for the 3KQ to 89.4% for the short FES-I. CONCLUSIONS: Falls screening tools have varying sensitivity and specificity for predicting the occurrence of a fall in the following 12 months.

Immune Function After Splenic Artery Embolization for Blunt Trauma: Long-Term Assessment of CD27+ IgM B-Cell Levels.

Splenic artery embolization (SAE) plays a critical role in the treatment of high-grade splenic injury not requiring emergent laparotomy. SAE preserves splenic tissue, and growing evidence demonstrates preserved short-term splenic immune function after SAE. However, long-term function is less studied. Patients who underwent SAE for blunt abdominal trauma over a 10-year period were contacted for long-term follow-up. Sixteen participants (sex: women, 10, and men, 6; age: median, 34 years, and range, 18-67 years) were followed up at a median of 7.7 years (range, 4.7-12.8 years) after embolization. Splenic lacerations were of American Association for the Surgery of Trauma grades III to V, and 14 procedures involved proximal embolization. All individuals had measurable levels of IgM memory B cells (median, 14.30 as %B cells), splenic tissue present on ultrasound (median, 122 mL), and no history of severe infection since SAE. In conclusion, this study quantitatively demonstrated that long-term immune function remains after SAE for blunt abdominal trauma based on the IgM memory B cell levels.

Single-cell analysis identifies dynamic gene expression networks that govern B cell development and transformation.

Integration of external signals and B-lymphoid transcription factor activities organise B cell lineage commitment through alternating cycles of proliferation and differentiation, producing a diverse repertoire of mature B cells. We use single-cell transcriptomics/proteomics to identify differentially expressed gene networks across B cell development and correlate these networks with subtypes of B cell leukemia. Here we show unique transcriptional signatures that refine the pre-B cell expansion stages into pre-BCR-dependent and pre-BCR-independent proliferative phases. These changes correlate with reciprocal changes in expression of the transcription factor EBF1 and the RNA binding protein YBX3, that are defining features of the pre-BCR-dependent stage. Using pseudotime analysis, we further characterize the expression kinetics of different biological modalities across B cell development, including transcription factors, cytokines, chemokines, and their associated receptors. Our findings demonstrate the underlying heterogeneity of developing B cells and characterise developmental nodes linked to B cell transformation.

Incidence and Outcomes of Hypertensive Phase Following Aurolab Aqueous Drainage Implant Surgery in Adults with Refractory Glaucoma.

PURPOSE: To report the incidence and outcomes of hypertensive phase (HP) following Aurolab Aqueous Drainage Implant (AADI) (Aurolab) surgery in adults with refractory glaucoma. DESIGN: Retrospective, noncomparative, interventional case series. METHODS: All eyes that received the AADI and had a minimum of 2-year follow-up were identified, and data of patients who had intraocular pressure (IOP) ≤21 mm Hg at 6 weeks (ie, the time at which the tube-ligature suture dissolves) were used for statistical analysis. HP was defined as IOP >21 mm Hg during the first 3 months after the release of the tube ligating suture (with or without medications) in the absence of tube obstruction. RESULTS: A total of 200 eyes were included in the study, and HP was seen in 64 eyes (32%) with a peak IOP (mean ± SD) of 29.6 ± 7.8 mm Hg and peak incidence at 2-3 months after surgery. HP resolved within 3 months of its onset in 60 of the 64 eyes (94%) with additional IOP-lowering medications. The cumulative success rates were 71.8% (95% CI = 59.3%-81.2%) in HP eyes and 76.4% (95% CI = 68.7%-82.7%) in non-HP eyes (P = .23). Unadjusted Cox proportional hazards analysis showed that eyes experiencing HP had a marginally higher risk of failure (HR = 1.16, 95% CI = 0.6-2.1), but this relationship was not statistically significant (P = .61). CONCLUSIONS: A third of eyes that underwent AADI placement experienced HP. HP was successfully managed with additional IOP-lowering medications in a majority of cases and did not have a significant influence on long-term success rate.

Surgical Outcomes of Superotemporal Versus Inferonasal Placement of Aurolab Aqueous Drainage Implant in Refractory Pediatric Glaucoma.

PURPOSE: We sought to describe the outcomes of the Aurolab aqueous drainage implant (AADI) placed in the superotemporal (ST) versus the inferonasal (IN) quadrant in pediatric eyes with refractory glaucoma. DESIGN: Retrospective comparative interventional case series. METHODS: This was a retrospective study of patients ≤18 years of age who underwent AADI implantation and completed a minimum of 2-year follow-up. The choice of the quadrant depended upon the amount of scarring and conjunctival mobility. Cumulative success at 2 years was defined as intraocular pressure (IOP) ≤21 mm Hg or reduced by ≥20% below baseline on 2 consecutive follow-up visits after 3 months, IOP ≤5 mm Hg on 2 consecutive follow-up visits after 3 months, reoperation for glaucoma or a complication, or loss of light perception vision. RESULTS: A total of 144 patients (144 eyes) underwent AADI placement, including 48 eyes (33%) in the IN and 96 eyes (67%) in the ST quadrants. The IOP was significantly higher in the IN group (17.5 ± 7.4 mm Hg vs 13.7 ± 6.2 mm Hg, P = .005) with a greater number of medications (1.5 ± 1.0 vs 0.8 ± 0.9, P = .001) after 2 years of follow-up. Cumulative success rates at 2 years were 50.7% (95% confidence interval 35.4%-63.9%) in the IN group and 65.6% (95% confidence interval 56.5%-75.7%) in the ST group (P = .15). Complications occurred more frequently in the IN group, with significantly more tube exposure (12% vs 0%, P = .05). CONCLUSIONS: Placement of the AADI in the ST quadrant has better IOP-related outcomes and is a safer surgical option in pediatric eyes compared with the IN quadrant. It may be prudent to avoid AADI in the IN quadrant in children unless the ST location is not a viable option.

Aurolab Aqueous Drainage Implant With and Without Scleral Patch Graft in Refractory Adult and Pediatric Glaucomas: A Comparative Study.

PURPOSE: To compare the 2-year outcomes of eyes that received the Aurolab aqueous drainage implant (AADI) with and without a scleral patch graft. DESIGN: Retrospective comparative interventional case series. METHODS: Eyes with AADI and a minimum of a 2-year follow-up were included. Eyes that underwent implantation before January 2016 had surgery with a scleral patch graft covering the distal end of the tube, whereas those that were implanted after this period underwent surgery using a needle-generated scleral tunnel without the patch graft. The cumulative failure of the AADI was defined as intraocular pressure (IOP) >18 mm Hg or not reduced by 30% below baseline on 2 consecutive follow-up visits after 3 months. RESULTS: We included 215 adult eyes (n = 147 with patch graft, n = 68 without patch graft) and 111 pediatric eyes (n = 73 with patch graft, n = 38 without a patch graft). The mean IOP in eyes without the patch graft was higher at 1 month in adult eyes (before, 27.5 ± 14.1 vs after, 22.3 ± 11.1; P = .01) but not in pediatric eyes (14.3 ± before, 5.8 vs after, 17.8 ± 11.0; P = .39); there were no differences in IOP, vision, number of antiglaucoma medications, and complications between groups at all other time points. None of the eyes without the patch graft experienced tube exposure. Cumulative success rates at 2 years in adults (66.2% vs 63.9%, respectively; P = .85) were similar to those in children (77.2% vs 71.9%, respectively; P = .83) with both techniques. CONCLUSIONS: AADI placed without a scleral patch graft is as safe and effective as AADI placed with a patch graft in pediatric and adult refractory glaucomas.

Discovery and Characterization of the Antimetabolite Action of Thioacetamide-Linked 1,2,3-Triazoles as Disruptors of Cysteine Biosynthesis in Gram-Negative Bacteria.

Increasing rates of drug-resistant Gram-negative (GN) infections, combined with a lack of new GN-effective antibiotic classes, are driving the need for the discovery of new agents. Bacterial metabolism represents an underutilized mechanism of action in current antimicrobial therapies. Therefore, we sought to identify novel antimetabolites that disrupt key metabolic pathways and explore the specific impacts of these agents on bacterial metabolism. This study describes the successful application of this approach to discover a new series of chemical probes, N-(phenyl)thioacetamide-linked 1,2,3-triazoles (TAT), that target cysteine synthase A (CysK), an enzyme unique to bacteria that is positioned at a key juncture between several fundamental pathways. The TAT class was identified using a high-throughput screen against Escherichia coli designed to identify modulators of pathways related to folate biosynthesis. TAT analog synthesis demonstrated a clear structure-activity relationship, and activity was confirmed against GN antifolate-resistant clinical isolates. Spontaneous TAT resistance mutations were tracked to CysK, and mode of action studies led to the identification of a false product formation mechanism between the CysK substrate O-acetyl-l-serine and the TATs. Global transcriptional responses to TAT treatment revealed that these antimetabolites impose substantial disruption of key metabolic networks beyond cysteine biosynthesis. This study highlights the potential of antimetabolite drug discovery as a promising approach to the discovery of novel GN antibiotics and the pharmacological promise of TAT CysK probes.

Dopamine D2 receptor modulates Wnt expression and control of cell proliferation.

The Wnt/ß-catenin pathway is one of the most conserved signaling pathways across species with essential roles in development, cell proliferation, and disease. Wnt signaling occurs at the protein level and via ß-catenin-mediated transcription of target genes. However, little is known about the underlying mechanisms regulating the expression of the key Wnt ligand Wnt3a or the modulation of its activity. Here, we provide evidence that there is significant cross-talk between the dopamine D2 receptor (D2R) and Wnt/ß-catenin signaling pathways. Our data suggest that D2R-dependent cross-talk modulates Wnt3a expression via an evolutionarily-conserved TCF/LEF site within the WNT3A promoter. Moreover, D2R signaling also modulates cell proliferation and modifies the pathology in a renal ischemia/reperfusion-injury disease model, via its effects on Wnt/ß-catenin signaling. Together, our results suggest that D2R is a transcriptional modulator of Wnt/ß-catenin signal transduction with broad implications for health and development of new therapeutics.

Evaluation of Pharmacist Intervention on Discharge Medication Reconciliation.

BACKGROUND: Discharge medication reconciliation (Discharge MedRec) was implemented on one unit at a large urban teaching hospital, and was to be expanded across the rest of the hospital and the health authority's various sites by the end of 2018. Clinical pharmacists on the Acute Care for the Elderly unit carried out discharge planning and led Discharge MedRec during a pilot period, to inform the future implementation. OBJECTIVES: The primary objective was to examine the number and type of medication discrepancies before and after implementation of Discharge MedRec. The secondary objectives were to compare documented medication changes, pharmacist recommendations, discharge counselling, communication with community pharmacists, polypharmacy, and 30-day readmission rates. METHODS: Patients seen in December 2015 constituted the control (pre-implementation) group, who received usual care. Patients seen from January to April 2016 constituted the intervention group, for whom pharmacists performed Discharge MedRec and other discharge activities as per the hospital-to-home checklist of the Institute for Safe Medication Practices Canada. RESULTS: There were 66 patients in the control group and 306 in the intervention group. Median discrepancies per patient decreased from 6.5 to 3 (p = 0.007), median number of documented changes without rationale increased from 2 to 3 (p = 0.01), and median number of documented changes with rationale increased from 1 to 2 (p < 0.001). Pharmacists made a per-patient median of 1 progress note recommendation in the control group and 2 progress note recommendations in the intervention group (p = 0.007), and a per-patient median of 2 orders in both the control and intervention groups (p = 0.62). Median recommendation acceptance was 100% for both groups, but twice as many recommendations were made per patient for the intervention group. Discharge counselling increased from 22.7% to 65%. Communication with community pharmacists increased from 10.6% to 60.8%. CONCLUSIONS: Clinical pharmacist involvement improved Discharge MedRec planning and documentation. Decreases in medication discrepancies, combined with an increase in discharge counselling, should improve continuity of care across the health care team and increase patient adherence with medication therapy. This study further demonstrates the leadership role that pharmacists play in the assessment and clear documentation of medication changes at all transitions of care.

CONTEXTE: Le processus de bilan comparatif des médicaments au moment du congé a été mis en place dans une unité d'un important hôpital universitaire en milieu urbain et devait être mis en place dans le reste de l'hôpital et dans les différents sites de la régie de santé avant la fin de 2018. Des pharmaciens cliniciens de l'Unité de soins gériatriques de courte durée ont réalisé la planification des congés et ont dirigé le processus de bilan comparatif des médicaments au moment du congé, au cours d'une période d'essai, afin de contribuer à une future mise en place d'un tel processus. OBJECTIFS: L'objectif principal consistait en l'étude du nombre et du type de divergences relatives aux médicaments avant et après la mise en place du processus de bilan comparatif des médicaments au moment du congé. Les objectifs secondaires portaient sur la comparaison des éléments suivants : les changements apportés à la pharmacothérapie, les recommandations des pharmaciens, l'offre de conseils au moment du congé, les échanges avec les pharmaciens communautaires, la polypharmacie et les taux de réadmissions dans les 30 jours suivant le congé. MÉTHODES: Les patients rencontrés en décembre 2015 constituaient le groupe témoin (avant la mise en place du processus) ayant reçu les soins habituels. Les patients rencontrés entre janvier et avril 2016 formaient le groupe expérimental pour lequel les pharmaciens avaient réalisé un processus de bilan comparatif des médicaments au moment du congé et d'autres activités en lien avec le congé, en fonction de la liste de vérification du transfert de l'hôpital à la maison de l'Institut pour la sécurité des médicaments aux patients du Canada. RÉSULTATS: Il y avait 66 patients dans le groupe témoin et 306 dans le groupe expérimental. Le nombre médian de divergences par patient a diminué et est passé de 6,5 à 3 (p = 0,007), le nombre médian de changements consignés, apportés sans raison apparente a augmenté et est passé de 2 à 3 (p = 0,01) et le nombre médian de changements consignés, dont la raison apparaissait aux dossiers a augmenté et est passé de 1 à 2 (p < 0,001). Le nombre médian de recommandations par patient dans les notes d'évolution réalisées par les pharmaciens était de un dans le groupe témoin et de deux dans le groupe expérimental (p = 0,007) et le nombre médian d'ordonnances par patient réalisées par des pharmaciens était de deux, tant dans le groupe témoin que dans le groupe expérimental (p = 0,62). Les taux médians d'acceptation des recommandations étaient de 100 % dans les deux groupes, mais il y a eu deux fois plus de recommandations par patient réalisées dans le groupe expérimental. L'offre de conseils au moment du congé a augmenté et est passée de 22,7 % à 65 %. Les échanges avec les pharmaciens communautaires ont augmenté et sont passés de 10,6 % à 60,8 %. CONCLUSIONS: La participation des pharmaciens cliniciens a amélioré la planification et l'enregistrement du bilan comparatif des médicaments au moment du congé. Une réduction des divergences concernant les médicaments, associée à une augmentation de l'offre de conseils au moment du congé, devrait améliorer la continuité des soins au sein de l'équipe de soins de santé et accroître l'observance thérapeutique du patient. La présente étude est un nouvel exemple du rôle de leader que les pharmaciens jouent dans l'évaluation et la description claire des changements apportés à la pharmacothérapie à chaque transfert des soins.

Curation and bioinformatic analysis of strabismus genes supports functional heterogeneity and proposes candidate genes with connections to RASopathies.

Strabismus refers to the misalignment of the eyes and occurs in 2-4% of individuals. The low-resolution label "strabismus" covers a range of heterogeneous defects, which makes it challenging to unravel this condition. Consequently a coherent understanding of the causes is lacking. Here, we attempt to gain a better understanding of the underlying genetics by combining gene curation, diverse bioinformatic analyses (including gene ontology, pathway mapping, expression and network-based methods) and literature review. Through a phenotype-based curation process, we identify high-confidence and permissive sets of 54 and 233 genes potentially involved in strabismus. These genes can be grouped into 10 modules that together span a heterogeneous set of biological and molecular functions, and can be linked to clinical sub-phenotypes. Multiple lines of evidence associate retina and cerebellum biology with the strabismus genes. We further highlight a potential role of the Ras-MAPK pathway. Independently, sets of 11 genes and 15 loci tied to strabismus with definitive genetic basis have been compiled from the literature. We identify strabismus candidate genes for 5 of the 15 reported loci (CHD7; SLC9A6; COL18A1, COL6A2; FRY, BRCA2, SPG20; PARK2). Finally, we synthesize a Strabismus Candidate Gene Collection, which together with our curated gene sets will serve as a resource for future research. The results of this informatics study support the heterogeneity and complexity of strabismus and point to specific biological pathways and brain regions for future focus.

A network-centric approach to drugging TNF-induced NF-κB signaling.

Target-centric drug development strategies prioritize single-target potency in vitro and do not account for connectivity and multi-target effects within a signal transduction network. Here, we present a systems biology approach that combines transcriptomic and structural analyses with live-cell imaging to predict small molecule inhibitors of TNF-induced NF-κB signaling and elucidate the network response. We identify two first-in-class small molecules that inhibit the NF-κB signaling pathway by preventing the maturation of a rate-limiting multiprotein complex necessary for IKK activation. Our findings suggest that a network-centric drug discovery approach is a promising strategy to evaluate the impact of pharmacologic intervention in signaling.

Effective communication in the era of precision medicine: A pilot intervention with low health literacy patients to improve genetic counseling communication.

Effective communication, where all parties share a common understanding, is necessary to realize the promise of Genomic Medicine. It is especially salient given the imperative to increase the participation of diverse populations in genomics research and to expand the reach of clinical genomics. We have previously shown that cancer genetic counseling is suboptimal for patients with limited health literacy. To address this finding, we implemented a pilot study to improve verbal communication between genetic counselors and their patients of limited health literacy that consisted of: i) curriculum development and delivery of a Genetic Counselors (GC) communication workshop; ii) two-month post-workshop interviews with GC participants (n = 9); iii) observations/audio recordings of counseling sessions involving 24 patients and two GC workshop participants; iv) post-counseling interviews with patients (n = 9). The 4.5-h workshop presented evidenced-based principles and strategies for effective communication with limited health literacy patients (e.g. use of plain language and teach-back), and offered specific techniques and exercises to practice adoption of such practices in the genetic counseling context. GCs expressed appreciation for the opportunity to refine their skills; however, they reported that some strategies were challenging given their professional training and communication habits. For example, GCs were concerned that use of plain language could undermine efforts to obtain informed consent and provide scientifically accurate information. Observations and patient interviews after the workshop revealed that GCs were able to employ the communication strategies with positive effects, with patients indicating sufficient understanding of the genetic test and its implications as well as satisfaction with the counselors' communication. While derived from research on communication with those of limited health literacy, the communication approaches taught in the GC workshop could benefit most patients, given the high rates of low health literacy in many countries, and the many factors beyond health literacy that can contribute to reduced comprehension in health care environments.

The Potential to Reduce Falls and Avert Costs by Clinically Managing Fall Risk.

INTRODUCTION: Falls often cause severe injuries and are one of the most costly health conditions among older adults. Yet, many falls are preventable. The number of preventable medically treated falls and associated costs averted were estimated by applying evidence-based fall interventions in clinical settings. METHODS: A review of peer-reviewed literature was conducted in 2017 using literature published between 1994 and 2017, the authors estimated the prevalence of seven fall risk factors and the effectiveness of seven evidence-based fall interventions. Then authors estimated the number of older adults (aged ≥65 years) who would be eligible to receive one of seven fall interventions (e.g., Tai Chi, Otago, medication management, vitamin D supplementation, expedited first eye cataract surgery, single-vision distance lenses for outdoor activities, and home modifications led by an occupational therapist). Using the reported effectiveness of each intervention, the number of medically treated falls that could be prevented and the associated direct medical costs averted were calculated. RESULTS: Depending on the size of the eligible population, implementing a single intervention could prevent between 9,563 and 45,164 medically treated falls and avert $94-$442 million in direct medical costs annually. The interventions with the potential to help the greatest number of older adults were those that provided home modification delivered by an occupational therapist (38.2 million), and recommended daily vitamin D supplements (16.7 million). CONCLUSIONS: This report is the first to estimate the number of medically treated falls that could be prevented and the direct medical costs that could be adverted. Preventing falls can benefit older adults substantially by improving their health, independence, and quality of life.

Shift from stochastic to spatially-ordered expression of serine-glycine synthesis enzymes in 3D microtumors.

Cell-to-cell differences in protein expression in normal tissues and tumors are a common phenomenon, but the underlying principles that govern this heterogeneity are largely unknown. Here, we show that in monolayer cancer cell-line cultures, the expression of the five metabolic enzymes of serine-glycine synthesis (SGS), including its rate-limiting enzyme, phosphoglycerate dehydrogenase (PHGDH), displays stochastic cell-to-cell variation. By contrast, in cancer cell line-derived three-dimensional (3D) microtumors PHGDH expression is restricted to the outermost part of the microtumors' outer proliferative cell layer, while the four other SGS enzymes display near uniform expression throughout the microtumor. A mathematical model suggests that metabolic stress in the microtumor core activates factors that restrict PHGDH expression. Thus, intracellular enzyme expression in growing cell ecosystems can shift to spatially ordered patterns in 3D structured environments due to emergent cell-cell communication, with potential implications for the design of effective anti-metabolic cancer therapies.

NF-κB-Chromatin Interactions Drive Diverse Phenotypes by Modulating Transcriptional Noise.

Noisy gene expression generates diverse phenotypes, but little is known about mechanisms that modulate noise. Combining experiments and modeling, we studied how tumor necrosis factor (TNF) initiates noisy expression of latent HIV via the transcription factor nuclear factor κB (NF-κB) and how the HIV genomic integration site modulates noise to generate divergent (low-versus-high) phenotypes of viral activation. We show that TNF-induced transcriptional noise varies more than mean transcript number and that amplification of this noise explains low-versus-high viral activation. For a given integration site, live-cell imaging shows that NF-κB activation correlates with viral activation, but across integration sites, NF-κB activation cannot account for differences in transcriptional noise and phenotypes. Instead, differences in transcriptional noise are associated with differences in chromatin state and RNA polymerase II regulation. We conclude that, whereas NF-κB regulates transcript abundance in each cell, the chromatin environment modulates noise in the population to support diverse HIV activation in response to TNF.

Clinical outcomes after burns in elderly patients over 70 years: A 17-year retrospective analysis.

INTRODUCTION: In the United Stated population >70years is likely to double by the year 2050. Elderly population (>70years) are most vulnerable to burns and outcomes following such injuries in this special group is poorly studied. This study aimed to look at outcomes following burns in patients >70years over a period of 17 years. MATERIALS AND METHODS: Data on 6512 patients admitted to a Level I Burn Center between 1995 and 2011 was analyzed. Age, gender, ethnicity, TBSA, burn etiology, hospital and burn intensive care unit (ICU) length of stay (LOS) and status at discharge were abstracted. Three broad categories were created based on presence or absence of smoke inhalation, No smoke inhalation (Group A), smoke inhalation only (Group B) and smoke inhalation with burn injury (Group C). Differences were analyzed using the student's t-test for continuous variables and Chi-Square test for categorical variables. RESULTS: The study group was comprised of 564 patients, 72.3% in group A, 4.8% in group B and 22.9% in group C formed the study population. The mean age of the patients studied was 80.4±6.7, with female patients being more common (58%). The number of Caucasians (72.9%) was highest in group C compared to other racial groups (p=0.047). Majority of patients in the group B (59.3%) were admitted directly compared to other two groups (group A=24.0%, group B=34.9%, p<0.001). Overall percent total body surface area (% TBSA) and % TBSA third degree burns were higher in group C, whereas % TBSA second degree burns were common in group B (p<0.05). The number ICU admissions, the mean length of ICU stay, mean duration of ventilator support and mean length of hospitalization were all highest in group C patients (p<0.001). The number of discharges to home without home health aide were higher in group A, whereas the number of discharges to nursing home/rehabilitation/extended care facility were higher in group B (p<0.001). The in-hospital mortality (58.1%, p<0.001) and overall burn related mortality (62.8%, p<0.001) were highest in group C. There was no significant difference between the groups for the number of patients converted to hospice care (p=0.21). On multivariate analysis ICU admission (Odds Ratio [OR]=3.7, 95% Confidence Interval [95% CI]=2.1-6.5), ventilator support (OR=7.1, 95% CI=4.1-12.0), and %TBSA >10% (OR=3.1, 95% CI=1.9-5.0) significantly increased mortality. In terms of complications, group C had a significantly higher incidence of pneumonia (18.6%, p<0.001), respiratory failure (17.1%, p=0.001), and sepsis (7.8%, p=0.003). CONCLUSIONS: Patients >70 years constitute small (8.6%) but significant number among burn patients. The overall ICU admissions, number of days on ventilator, ICU stay, in-hospital mortality and overall mortality is higher in this group of population even for low % TBSA burns. Presence of smoke inhalation increases mortality.