Evaluating Goldberger's triad as a marker of congestive heart failure: A systematic review and retrospective study.

BACKGROUND: In 1982, Drs. Barold and Goldberger described an ECG triad associated with left ventricular dysfunction (LVD) consisting of high precordial QRS voltage, low limb lead voltage, and poor precordial R wave progression. Studies have since attempted to replicate the originally reported sensitivity (70%), specificity (>99%), and positive predictive value (PPV, 100%) of Goldberger's triad (GT) with variable results. PURPOSE: To assess sensitivity, specificity and PPV of GT as a screening tool for LVD in the current era. METHODS: We performed: (1) A systematic review of the published studies; (2) Searched our hospital ECG database (GE MUSE) for diagnoses of "low limb-voltage" and "left ventricular hypertrophy" from 2017 to 2022; identified ECGs were analyzed for GT criteria and their medical records were screened for LVD. (3) ECG analysis of patients with known idiopathic LVD for the GT. RESULTS: A total of 11,115 patients from 8 studies were included in the systematic review of published studies and showed widely varying sensitivity, specificity and PPV. A total of 4576 ECGs (in GE MUSE) from 372 patients met initial screening criteria of low limb lead voltage and LVH; only 12 patients had ECGs that satisfied GT. Of these 12, only 1 patient had evidence of LVD, yielding a PPV of 8%. Finally, of the 40 patients with known LVD, only 1 met the ECG criteria for GT, resulting in a sensitivity of 2.5%. CONCLUSION: Our literature review does not support the original results of GT. ECGs from our database that met GT (searched by low limb-voltage and left ventricular hypertrophy) over a span of 5 years were rare. When present, the PPV of GT was 8%. In patients with established LVD, the sensitivity was 2.5%. These data do not validate GT as tool to identify LVD in the current era.

Infectious Scleritis: Pathophysiology, Diagnosis, and Management.

ABSTRACT: Infectious scleritis (IS) is a rare and severe ocular disorder responsible for approximately 5%-15% of all scleritis cases. It is often associated with a poor prognosis due to its similar clinical presentation to autoimmune scleritis, resulting in a delayed diagnosis and treatment. Therefore, differentiating between infectious and noninfectious entities is critical. Several details extracted from the patient's history and clinical examination can raise suspicion for infection. The most common predisposing factor is previous ocular surgery, especially pterygium, cataract, and vitreoretinal surgeries. Ocular trauma, poor contact lens hygiene, "eye-whitening" procedures, and subtenon triamcinolone injections have also been implicated. Clinical features of infection include the presence of scleral necrosis, hypopyon, unifocal or multifocal scleral abscesses, and mucopurulent discharge. Thorough diagnostic testing is essential before excluding infection as a possibility. Empiric broad-spectrum topical and systemic antibiotic therapy should be initiated while awaiting laboratory results and adjusted accordingly. Most IS cases require both aggressive medical and surgical treatment, and various studies have reported favorable outcomes with this combination. At this time, there is no consensus on the management of this severe ocular condition, and future studies are needed to establish clear treatment guidelines.

Novel mouse models of oculopharyngeal muscular dystrophy (OPMD) reveal early onset mitochondrial defects and suggest loss of PABPN1 may contribute to pathology.

Oculopharyngeal muscular dystrophy (OPMD) is a late onset disease caused by polyalanine expansion in the poly(A) binding protein nuclear 1 (PABPN1). Several mouse models have been generated to study OPMD; however, most of these models have employed transgenic overexpression of alanine-expanded PABPN1. These models do not recapitulate the OPMD patient genotype and PABPN1 overexpression could confound molecular phenotypes. We have developed a knock-in mouse model of OPMD (Pabpn1+/A17) that contains one alanine-expanded Pabpn1 allele under the control of the native promoter and one wild-type Pabpn1 allele. This mouse is the closest available genocopy of OPMD patients. We show that Pabpn1+/A17 mice have a mild myopathic phenotype in adult and aged animals. We examined early molecular and biochemical phenotypes associated with expressing native levels of A17-PABPN1 and detected shorter poly(A) tails, modest changes in poly(A) signal (PAS) usage, and evidence of mitochondrial damage in these mice. Recent studies have suggested that a loss of PABPN1 function could contribute to muscle pathology in OPMD. To investigate a loss of function model of pathology, we generated a heterozygous Pabpn1 knock-out mouse model (Pabpn1+/Δ). Like the Pabpn1+/A17 mice, Pabpn1+/Δ mice have mild histologic defects, shorter poly(A) tails, and evidence of mitochondrial damage. However, the phenotypes detected in Pabpn1+/Δ mice only partially overlap with those detected in Pabpn1+/A17 mice. These results suggest that loss of PABPN1 function could contribute to but may not completely explain the pathology detected in Pabpn1+/A17 mice.

Diagnosing Glucose Transporter 1 Deficiency at Initial Presentation Facilitates Early Treatment.

OBJECTIVE: To profile the initial clinical events of glucose transporter 1 deficiency syndrome (Glut1 DS) in order to facilitate the earliest possible diagnosis. STUDY DESIGN: We retrospectively reviewed 133 patients with Glut1 DS from a single institution. Family interviews and medical record reviews identified the first clinical event(s) reported by the caregivers. RESULTS: Average age of the first event was 8.15 ± 11.9 months (range: 0.01-81). Ninety-one patients experienced the first symptom before age 6 months (68%). Thirty-three additional patients (25%) presented before age 2 years. Only 9 patients (7%), reported the first event after age 2 years. Seizures were the most common first event (n = 81, 61%), followed by eye movement abnormalities (n = 51, 38%) and changes in muscle strength and tone (n = 30, 22%). Eye movement abnormalities, lower cerebrospinal fluid glucose values, and lower Columbia Neurological Scores correlated with earlier onset of the first event (r: -0.17, 0.22, and 0.25 respectively, P < .05). There was no correlation with age of first event and red blood cell glucose uptake or mutation type. CONCLUSIONS: Glut1 DS is a treatable cause of infantile onset encephalopathy. Health care providers should recognize the wide spectrum of paroxysmal events that herald the clinical onset of Glut1 DS in early infancy to facilitate prompt diagnosis, immediate treatment, and improved long-term outcome.

Epibulbar simple cartilaginous choristoma associated with unique pigmented multicystic component.

PURPOSE: To report an atypical presentation of an epibulbar simple cartilaginous choristoma with a unique pigmented multicystic component. CASE DESCRIPTION: A 69-year-old African American female presented for evaluation of a right nasal epibulbar lesion that had progressed over the prior year. Slit-lamp evaluation revealed an immobile, mildly pigmented multicystic lesion measuring 6.0 × 4.5 mm that involved the nasal bulbar conjunctiva and the plica semilunaris. The lesion appeared benign, without feeder vessels or features of epithelial dysplasia. Given its recent growth and the patient's cosmetic concerns, the lesion was excised with ocular surface reconstruction. Histopathological evaluation disclosed a well-circumscribed nodule of well-differentiated cartilage in the substantia propria, consistent with a simple cartilaginous choristoma. The overlying conjunctival stroma contained multiple cysts lined by focally pigment epithelium. The patient recovered well from surgery, with satisfactory cosmetic results. CONCLUSIONS: Our case of epibulbar simple cartilaginous choristoma includes a prominent superficial component of pigmented epithelial cysts, which has not been previously reported in the literature. This augments our knowledge on the spectrum of presentations of cartilaginous choristomas and underscores the importance of histopathological evaluation for definitive diagnosis.

Dynamics of Corneal Swelling With Hypoosmolar Riboflavin After Induction During Corneal Collagen Crosslinking in Patients With Progressive Keratoconus.

PURPOSE: To evaluate the rate of corneal swelling induced by hypoosmolar riboflavin in patients with progressive keratoconus (KCN) with corneal thickness <400 µm after the induction phase using riboflavin with 20% dextran during epithelium-off corneal crosslinking (CXL). METHODS: Prospective, nonrandomized, single-center consecutive case series. Preoperative assessments included tomography, specular microscopy, and hysteresis. After epithelial debridement, riboflavin with 20% dextran (Photrexa Viscous; Glaukos, Burlington, MA) was applied at 2-min intervals during a 30-min induction phase. Eyes that dehydrated to a minimum corneal thickness (MCT) of <400 µm after induction (postinduction pachymetry) were recruited. Hypoosmolar riboflavin 0.146% (Photrexa; Glaukos) was used every 10 s to induce stromal swelling, with pachymetry performed every 30 s until the MCT was ≥400 µm (postswelling pachymetry). Corneal swelling rate was compared with variables using regression analysis. RESULTS: In 31 eyes of 31 patients, mean postinduction pachymetry was 338.4 ± 28.7 µm. Hypoosmolar riboflavin induced a postswelling pachymetry of 413.4 ± 15.0 µm over a mean of 5.2 ± 3.2 min, and the average stromal swelling rate was 10.3 ± 8.7 µm/30 s. All eyes reached a postswelling pachymetry MCT ≥400 µm and no cases were aborted. Eyes with highly severe KCN (Kmax >70 and Belin/Ambrosio enhanced ectasia display final D score >17) experienced quicker swelling (14.4 ± 12.8 µm/30 s and 14.9 ± 12.4 µm/30 s, respectively; P < 0.05 for both). A thicker postinduction pachymetry was moderately associated with a faster rate of swelling (rs = 0.389; P = 0.030). CONCLUSIONS: Hypoosmolar riboflavin 0.146% can be safely employed in thinner corneas, allowing for swelling to ≥400 µm for epithelium-off CXL. Associations between swelling rate, KCN severity, and postinduction pachymetry were determined, allowing for a more accurate prediction of procedure time during CXL.

A new opportunity for patient selection and optimization: Systematic review of cognitive frailty in patients undergoing left ventricular assist device implantation.

The prognostic implication of cognitive frailty assessment in patients undergoing left ventricular assist device (LVAD) implantation remains unclear. We conducted a systematic review to evaluate assessment strategies and their significance for patients undergoing LVAD implantation. A comprehensive search of PubMed, Embase, and the Cumulative Index to Nursing and Allied Health Literature from inception until September 2022 and a review of meeting proceedings were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies that investigated the prognostic value of cognitive frailty or any related cognition-based assessment in patients undergoing LVAD implantation were included. Study characteristics, patient demographics, and type of cognitive assessment were extracted. Primary outcomes included length of stay, readmissions, and all-cause mortality. Of 664 records retrieved, 12 (4 prospective, 8 retrospective) involving 16 737 subjects (mean age, 56.9 years; 78.3% men) met inclusion criteria; 67% of studies used the Montreal Cognitive Assessment to assess cognitive frailty. Outcomes reported were highly variable, with 42% reporting readmission, 33% reporting LOS, and 83% reporting mortality data; only two studies provided data on all three. Cognitive frailty was associated with prolonged length of stay in 75% of studies reporting this outcome. Only 40% and 60% of studies that reported readmissions and mortality outcomes, respectively, suggested a predictive association. Pre-LVAD cognitive frailty is likely associated with worse outcomes postimplant. However, the heterogenous reporting of outcomes data and lack of consistent definitions in the literature limit its prognostic value. Additional research on markers for cognitive frailty and improved standards of reporting may allow for future analyses and enhance preoperative risk assessment and patient care. Geriatr Gerontol Int 2024; 24: 204-210.

Graft Outcomes After Temporary Keratoprosthesis in Combined Penetrating Keratoplasty and Vitreoretinal Surgery.

PURPOSE: Corneal pathology can obstruct the visualization required for surgical management of coexisting posterior segment diseases, and use of a temporary keratoprosthesis (TKP) permits combined penetrating keratoplasty (PK) and vitreoretinal surgery. We evaluated graft outcomes after TKP for combined PK and vitreoretinal surgery and analyzed risk factors for graft failure. METHODS: We reviewed the electronic medical records for patients who underwent TKP for PK combined with vitreoretinal surgery at Wills Eye Hospital between May 2007 and April 2021. Overall, 28 variables were analyzed. The main outcome measure was corneal graft failure, defined as irreversible graft edema or opacification. RESULTS: A total of 46 eyes of 46 patients underwent combined surgery and were included in the study. The mean age at surgery was 55.7 ± 18.6 years (range 19-86 years), and the mean follow-up was 31.8 ± 30.5 months (range 1.6-114.0 months). Multivariable analysis revealed 2 factors significantly associated with graft failure: history of trauma (hazard ratio = 5.38; 95% confidence interval, 1.53-18.91; P = 0.009) and intraocular silicone oil after transplant (hazard ratio = 5.67; confidence interval 1.66-19.44; P = 0.006). Corneal graft failure occurred in 60.9% of all cases over the course of follow-up, but the absence of both variables yielded a 33.3% failure rate. CONCLUSIONS: Although outcomes vary, previous ocular trauma and the presence of intraocular silicone oil are risk factors for failure that may facilitate patient selection and improve counseling about long-term graft potential after TKP for combined PK and vitreoretinal surgery.

Prognostic Value of Frailty for Heart Failure Patients Undergoing Left Ventricular Assist Device Implantation: A Systematic Review.

Frailty is associated with poor clinical outcomes in heart failure patients. The impact of frailty on outcomes following left ventricular assist device (LVAD) implantation, however, is less clearly defined. We therefore sought to conduct a systematic review to evaluate current frailty assessment strategies and their significance for patients undergoing LVAD implantation. We conducted a comprehensive electronic search of PubMed, Embase, and CINAHL databases from inception until April 2021 for studies examining frailty in patients undergoing LVAD implantation. Study characteristics, patient demographics, type of frailty measurement, and outcomes were extracted. Outcomes were organized into 5 basic categories: implant length of stay (iLOS), 1-year mortality, rehospitalization, adverse events, and quality of life (QOL). Of the 260 records retrieved, 23 studies involving 4935 patients satisfied the inclusion criteria. Approaches to measuring frailty varied, with the 2 most common being sarcopenia determined by computed tomography and Fried's frailty phenotype assessment. Outcomes of interest were also widely variable, with iLOS stay and mortality being the most frequently reported, albeit with differing definitions of both between studies. The heterogeneity among included studies precluded quantitative synthesis. Narrative synthesis showed that frailty by any measure is more likely to be associated with higher mortality, longer iLOS, more adverse events and worse QOL post-LVAD implant. Frailty can be a valuable prognostic indicator in patients undergoing LVAD implantation. Further studies are needed to determine the most sensitive frailty assessment, as well as the ways in which frailty may serve as a modifiable target to improve outcomes following LVAD implantation.

Contemporary Mechanical Circulatory Support With Continuous-Flow Biventricular Assist Devices: A Systematic Review.

As the incidence of heart failure increases, so too has that of biventricular failure. While transplantation remains the gold standard therapy for end-stage heart failure, the limited organ supply has increased the need for durable mechanical circulatory support. We therefore sought to conduct a systematic review of continuous-flow ventricular assist devices in a biventricular configuration (CF-BiVAD). An electronic search of PubMed and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases was performed using the keyword "BIVAD." Studies were reviewed to identify discrete variables, including implant indication, INTERMACs profile, timing of implant, mean age and BMI, and the anticoagulation/antiplatelet regimens employed post implant. Outcomes of interest included mortality and the incidence of thrombus, bleeding, infection, stroke, and renal failure. A total of 25 studies met inclusion criteria. No single variable was consistently reported, with only 4 studies reporting all 5 adverse effects. INTERMACs profile at implant and anticoagulation/antiplatelet regimen were reported in less than 50% of studies. Of those reporting mortality, there was a wide range of follow-up, from less than 6 months to >10 years, and the survival rate was similarly widely variable. Additionally, more than 50% of studies failed to isolate CF-BiVAD from alternative means of biventricular support, such as temporary support platforms, TAH, and pulsatile VADs. Therefore, high-quality quantitative analysis is not possible. In summary, the CF-BiVAD literature has a very heterogenous reporting of data. Standard reporting criteria may allow for future analyses to determine which patient characteristics portend a favorable outcome with CF-BiVAD implantation.

Smartphone-Detected Ambient Speech and Self-Reported Measures of Anxiety and Depression: Exploratory Observational Study.

BACKGROUND: The ability to objectively measure the severity of depression and anxiety disorders in a passive manner could have a profound impact on the way in which these disorders are diagnosed, assessed, and treated. Existing studies have demonstrated links between both depression and anxiety and the linguistic properties of words that people use to communicate. Smartphones offer the ability to passively and continuously detect spoken words to monitor and analyze the linguistic properties of speech produced by the speaker and other sources of ambient speech in their environment. The linguistic properties of automatically detected and recognized speech may be used to build objective severity measures of depression and anxiety. OBJECTIVE: The aim of this study was to determine if the linguistic properties of words passively detected from environmental audio recorded using a participant's smartphone can be used to find correlates of symptom severity of social anxiety disorder, generalized anxiety disorder, depression, and general impairment. METHODS: An Android app was designed to collect periodic audiorecordings of participants' environments and to detect English words using automatic speech recognition. Participants were recruited into a 2-week observational study. The app was installed on the participants' personal smartphones to record and analyze audio. The participants also completed self-report severity measures of social anxiety disorder, generalized anxiety disorder, depression, and functional impairment. Words detected from audiorecordings were categorized, and correlations were measured between words counts in each category and the 4 self-report measures to determine if any categories could serve as correlates of social anxiety disorder, generalized anxiety disorder, depression, or general impairment. RESULTS: The participants were 112 adults who resided in Canada from a nonclinical population; 86 participants yielded sufficient data for analysis. Correlations between word counts in 67 word categories and each of the 4 self-report measures revealed a strong relationship between the usage rates of death-related words and depressive symptoms (r=0.41, P<.001). There were also interesting correlations between rates of word usage in the categories of reward-related words with depression (r=-0.22, P=.04) and generalized anxiety (r=-0.29, P=.007), and vision-related words with social anxiety (r=0.31, P=.003). CONCLUSIONS: In this study, words automatically recognized from environmental audio were shown to contain a number of potential associations with severity of depression and anxiety. This work suggests that sparsely sampled audio could provide relevant insight into individuals' mental health.

Dual-mode optical projection tomography microscope using gold nanorods and hematoxylin-stained cancer cells.

An optical projection tomography microscope (OPTM) can improve axial resolution by viewing a sample from different perspectives. Here, we report a dual-mode OPTM that can generate 3D images of single cancer cells in both absorption mode and polarization mode. Cancer cells were labeled with hematoxylin for absorption imaging and nanorods for polarization imaging. Absorption images can provide morphologic information, and polarization images can provide molecular information. The combination of molecular detection and 3D cytological cell analysis may help with early cancer diagnosis.

The Relationship Between Smartphone-Recorded Environmental Audio and Symptomatology of Anxiety and Depression: Exploratory Study.

BACKGROUND: Objective and continuous severity measures of anxiety and depression are highly valuable and would have many applications in psychiatry and psychology. A collective source of data for objective measures are the sensors in a person's smartphone, and a particularly rich source is the microphone that can be used to sample the audio environment. This may give broad insight into activity, sleep, and social interaction, which may be associated with quality of life and severity of anxiety and depression. OBJECTIVE: This study aimed to explore the properties of passively recorded environmental audio from a subject's smartphone to find potential correlates of symptom severity of social anxiety disorder, generalized anxiety disorder, depression, and general impairment. METHODS: An Android app was designed, together with a centralized server system, to collect periodic measurements of the volume of sounds in the environment and to detect the presence or absence of English-speaking voices. Subjects were recruited into a 2-week observational study during which the app was run on their personal smartphone to collect audio data. Subjects also completed self-report severity measures of social anxiety disorder, generalized anxiety disorder, depression, and functional impairment. Participants were 112 Canadian adults from a nonclinical population. High-level features were extracted from the environmental audio of 84 participants with sufficient data, and correlations were measured between the 4 audio features and the 4 self-report measures. RESULTS: The regularity in daily patterns of activity and inactivity inferred from the environmental audio volume was correlated with the severity of depression (r=-0.37; P<.001). A measure of sleep disturbance inferred from the environmental audio volume was also correlated with the severity of depression (r=0.23; P=.03). A proxy measure of social interaction based on the detection of speaking voices in the environmental audio was correlated with depression (r=-0.37; P<.001) and functional impairment (r=-0.29; P=.01). None of the 4 environmental audio-based features tested showed significant correlations with the measures of generalized anxiety or social anxiety. CONCLUSIONS: In this study group, the environmental audio was shown to contain signals that were associated with the severity of depression and functional impairment. Associations with the severity of social anxiety disorder and generalized anxiety disorder were much weaker in comparison and not statistically significant at the 5% significance level. This work also confirmed previous work showing that the presence of voices is associated with depression. Furthermore, this study suggests that sparsely sampled audio volume could provide potentially relevant insight into subjects' mental health.

Neuronal competition: microcircuit mechanisms define the sparsity of the engram.

Extensive work in computational modeling has highlighted the advantages for employing sparse yet distributed data representation and storage Kanerva (1998), properties that extend to neuronal networks encoding mnemonic information (memory traces or engrams). While neurons that participate in an engram are distributed across multiple brain regions, within each region, the cellular sparsity of the mnemonic representation appears to be quite fixed. Although technological advances have enabled significant progress in identifying and manipulating engrams, relatively little is known about the region-dependent microcircuit rules governing the cellular sparsity of an engram. Here we review recent studies examining the mechanisms that help shape engram architecture and examine how these processes may regulate memory function. We speculate that countervailing forces in local microcircuits contribute to the generation and maintenance of engrams and discuss emerging questions regarding how engrams are formed, stored and used.

Competition between engrams influences fear memory formation and recall.

Collections of cells called engrams are thought to represent memories. Although there has been progress in identifying and manipulating single engrams, little is known about how multiple engrams interact to influence memory. In lateral amygdala (LA), neurons with increased excitability during training outcompete their neighbors for allocation to an engram. We examined whether competition based on neuronal excitability also governs the interaction between engrams. Mice received two distinct fear conditioning events separated by different intervals. LA neuron excitability was optogenetically manipulated and revealed a transient competitive process that integrates memories for events occurring closely in time (coallocating overlapping populations of neurons to both engrams) and separates memories for events occurring at distal times (disallocating nonoverlapping populations to each engram).

Topography of brain glucose hypometabolism and epileptic network in glucose transporter 1 deficiency.

RATIONALE: (18)F fluorodeoxyglucose positron emission tomography ((18)F FDG-PET) facilitates examination of glucose metabolism. Previously, we described regional cerebral glucose hypometabolism using (18)F FDG-PET in patients with Glucose transporter 1 Deficiency Syndrome (Glut1 DS). We now expand this observation in Glut1 DS using quantitative image analysis to identify the epileptic network based on the regional distribution of glucose hypometabolism. METHODS: (18)F FDG-PET scans of 16 Glut1 DS patients and 7 healthy participants were examined using Statistical parametric Mapping (SPM). Summed images were preprocessed for statistical analysis using MATLAB 7.1 and SPM 2 software. Region of interest (ROI) analysis was performed to validate SPM results. RESULTS: Visual analysis of the (18)F FDG-PET images demonstrated prominent regional glucose hypometabolism in the thalamus, neocortical regions and cerebellum bilaterally. Group comparison using SPM analysis confirmed that the regional distribution of glucose hypo-metabolism was present in thalamus, cerebellum, temporal cortex and central lobule. Two mildly affected patients without epilepsy had hypometabolism in cerebellum, inferior frontal cortex, and temporal lobe, but not thalamus. Glucose hypometabolism did not correlate with age at the time of PET imaging, head circumference, CSF glucose concentration at the time of diagnosis, RBC glucose uptake, or CNS score. CONCLUSION: Quantitative analysis of (18)F FDG-PET imaging in Glut1 DS patients confirmed that hypometabolism was present symmetrically in thalamus, cerebellum, frontal and temporal cortex. The hypometabolism in thalamus correlated with the clinical history of epilepsy.

The synergistic effect of functional status and comorbidity burden on mortality: a 16-year survival analysis.

OBJECTIVES: The relationship between disability and comorbidity on mortality is widely perceived as additive in clinical models of frailty. DESIGN: National data were retrospectively extracted from medical records of community hospital. DATA SOURCES: There were of 12,804 acutely-disabled patients admitted for inpatient rehabilitation in Singapore rehabilitation community hospitals from 1996 through 2005 were followed up for death till 31 December 2011. OUTCOME MEASURE: Cox proportional-hazards regression to assess the interaction of comorbidity and disability at discharge on all-cause mortality. RESULTS: During a median follow-up of 10.9 years, there were 8,565 deaths (66.9%). The mean age was 73.0 (standard deviation: 11.5) years. Independent risk factors of mortality were higher comorbidity (p<0.001), severity of disability at discharge (p<0.001), being widowed (adjusted hazard ratio [aHR]: 1.38, 95% confidence interval [CI]:1.25-1.53), low socioeconomic status (aHR:1.40, 95%CI:1.29-1.53), discharge to nursing home (aHR:1.14, 95%CI:1.05-1.22) and re-admission into acute care (aHR:1.54, 95%CI:1.45-1.65). In the main effects model, those with high comorbidity had an aHR = 2.41 (95%CI:2.13-2.72) whereas those with total disability had an aHR = 2.28 (95%CI:2.12-2.46). In the interaction model, synergistic interaction existed between comorbidity and disability (p<0.001) where those with high comorbidity and total disability had much higher aHR = 6.57 (95%CI:5.15-8.37). CONCLUSIONS: Patients with greater comorbidity and disability at discharge, discharge to nursing home or re-admission into acute care, lower socioeconomic status and being widowed had higher mortality risk. Our results identified predictive variables of mortality that map well onto the frailty cascade model. Increasing comorbidity and disability interacted synergistically to increase mortality risk.