Modeling and Correction of Protein Conformational Disease in iPSC-derived Neurons through Personalized Base Editing.

Altered protein conformation can cause incurable neurodegenerative disorders. Mutations in SERPINI1 , the gene encoding neuroserpin, alter protein conformation resulting in cytotoxic aggregation in neuronal endoplasmic reticulum. Aggregates cause oxidative stress impairing function, leading to neuronal death. Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a rare autosomal dominant progressive myoclonic epilepsy. Patients present with seizures and cognitive impairments that progress to dementia and premature death. We developed HEK293T and induced pluripotent stem cell (iPSC) models of FENIB, harboring the patient's pathogenic SERPINI1 variant or stably overexpressing mutant neuroserpin fused to GFP (MUT NS-GFP). FENIB cells form neuroserpin inclusions which increase in size and number. Here, we utilized a personalized adenine base editor (ABE)-mediated approach to efficiently correct the pathogenic variant and to restore neuronal dendritic morphology. ABE-treated MUT NS-GFP cells demonstrated reduced inclusion size and number. Using an inducible MUT NS-GFP neuron system, we identified early prevention of toxic protein expression allowed aggregate clearance, while late prevention halted neuronal impairments. To address several challenges for clinical applications of gene correction, we developed a neuron-specific engineered virus-like particle to optimize neuronal ABE delivery. Preventing mutant protein with altered conformation production improved toxic protein clearance. Our findings provide a targeted strategy and may treat FENIB and potentially other neurodegenerative diseases due to altered protein conformation such as Alzheimer's and Huntington's diseases.

Incidence of New-Onset Hypertension Post-COVID-19: Comparison With Influenza.

BACKGROUND: SARS-CoV-2 may trigger new-onset persistent hypertension. This study investigated the incidence and risk factors associated with new-onset persistent hypertension during COVID-19 hospitalization and at ≈6-month follow-up compared with influenza. METHODS: This retrospective observational study was conducted in a major academic health system in New York City. Participants included 45 398 patients with COVID-19 (March 2020 to August 2022) and 13 864 influenza patients (January 2018 to August 2022) without a history of hypertension. RESULTS: At 6-month follow-up, new-onset persistent hypertension was seen in 20.6% of hospitalized patients with COVID-19 and 10.85% of nonhospitalized patients with COVID-19. Persistent hypertension incidence among hospitalized patients did not vary across the pandemic, whereas that of hospitalized patients decreased from 20% in March 2020 to ≈10% in October 2020 (R2=0.79, P=0.003) and then plateaued thereafter. Hospitalized patients with COVID-19 were 2.23 ([95% CI, 1.48-3.54]; P<0.001) times and nonhospitalized patients with COVID-19 were 1.52 ([95% CI, 1.22-1.90]; P<0.01) times more likely to develop persistent hypertension than influenza counterparts. Persistent hypertension was more common among older adults, males, Black, patients with preexisting comorbidities (chronic obstructive pulmonary disease, coronary artery disease, chronic kidney disease), and those who were treated with pressor and corticosteroid medications. Mathematical models predicted persistent hypertension with 79% to 86% accuracy. In addition, 21.0% of hospitalized patients with COVID-19 with no prior hypertension developed hypertension during COVID-19 hospitalization. CONCLUSIONS: Incidence of new-onset persistent hypertension in patients with COVID-19 is higher than those with influenza, likely constituting a major health burden given the sheer number of patients with COVID-19. Screening at-risk patients for hypertension following COVID-19 illness may be warranted.

Feasibility of Global Assessment of Bone Metastases in Prostate Cancer with 18F-Sodium Fluoride-PET/Computed Tomography.

18F-sodium fluoride (NaF) PET/computed tomography (CT) allows detection of bone metastases in patients with prostate cancer (PCa). The aim of this study was to test the feasibility of assessing global metastatic bone disease in patients with PCa by using a threshold-based PET segmentation technique. This retrospective analysis was performed in 32 patients with PCa with known bone metastases who underwent NaF-PET/CT imaging. An adaptive contrast-oriented thresholding technique was used to segment NaF avid lesions. The mean metabolic volumetric product (MVPmean), partial volume-corrected MVPmean (cMVPmean), and metabolically active volume (MAV) were calculated. Lesional values were summed within each patient to obtain the global PET disease burden. Pearson correlation analysis was used to assess the associations between global NaF-PET/CT metrics and clinical biomarkers of metastatic disease activity. Global MVPmean, cMVPmean, and MAV were significantly correlated with alkaline phosphatase (ALP) levels (p < 0.05). No correlation was observed between global NaF-PET/CT measures and prostate-specific antigen (PSA) levels. Global assessment is a feasible method to quantify metastatic bone disease activity in patients with PCa. Convergent validity was supported by demonstrating a significant correlation between NaF-PET/CT parameters and blood ALP levels.

Assessing Coronary Artery and Aortic Calcification in Patients with Prostate Cancer Using 18F-Sodium Fluoride PET/Computed Tomography.

The aim of this study was to assess coronary artery and aortic calcification in healthy controls, angina pectoris patients, and prostate cancer patients using 18F-sodium fluoride PET/computed tomography (NaF-PET/CT). A retrospective analysis compared 33 prostate cancer patients with 33 healthy subjects and 33 patients with angina pectoris. Increased target-to-background ratio (TBR) of the coronary arteries, ascending aorta, aortic arch, and descending aorta was observed in cancer patients compared to healthy controls but not compared to angina pectoris patients. These results demonstrate the feasibility of assessing vascular microcalcification with NaF-PET/CT, with significant differences in uptake according to comorbidities.

Challenges and Opportunities in Aligning Conservation with Development in China's National Parks: A Narrative Literature Review.

As part of its effort to balance economic development with environmental objectives, China has established a new national park system, with the first five locations formally established in 2021. However, as the new parks all host or are proximate to human populations, aligning the socioeconomic needs and aspirations of local communities with conservation aims is critical for the long-term success of the parks. In this narrative review, the authors identify the ecological priorities and socioeconomic stakeholders of each of the five national parks; explore the tensions and synergies between these priorities and stakeholders; and synthesize the policy recommendations most frequently cited in the literature. A total of 119 studies were reviewed. Aligning traditional livelihoods with conservation, limiting road construction, promoting education and environmental awareness, and supporting the development of a sustainable tourism industry are identified as important steps to balance conservation with economic development in the new national parks.

Effects of chronic mild hyperoxia on retinal and choroidal blood flow and retinal function in the DBA/2J mouse model of glaucoma.

PURPOSE: To test the hypothesis that mild chronic hyperoxia treatment would improve retinal function despite a progressive decline in ocular blood flow in the DBA/2J mouse model of glaucoma. MATERIALS AND METHODS: DBA/2J mice were treated with chronic mild hyperoxia (30% O2) beginning at 4.5 months of age or were untreated by giving normal room air. Retinal and choroidal blood flow (RBF and ChBF, respectively) were measured at 4, 6, and 9 months of age by MRI. Blood flow was additionally measured under hypercapnia challenge (5% CO2 inhalation) to assess vascular reactivity. Intraocular pressure (IOP) was measured using a rebound tonometer at the same time points. Scotopic flash electroretinograms (ERGs) were recorded at 9 months of age. RESULTS: Both ChBF and RBF were reduced and significantly affected by age (p < 0.01), but neither were significantly affected by O2-treatment (p > 0.05). ChBF significantly increased in response to hypercapnia (p < 0.01), which was also unaffected by O2-treatment. Significant effects of age (p < 0.001) and of the interaction of age with treatment (p = 0.028) were found on IOP. IOP significantly decreased in O2-treated mice at 6 months compared to 4 months of age (p < 0.001), while IOP trended to increase with age in untreated mice. The amplitude of the b-wave from ERG was significantly increased in O2-treated DBA/2J compared to the untreated mice (p = 0.012), while the a-wave and oscillatory potentials were not significantly affected (p > 0.05). CONCLUSION: This study investigated the effects of chronic mild hyperoxia on retinal function and on retinal and choroidal blood flow in a mouse model of glaucoma. Retinal function was improved in the O2-treated mice at late stage, despite a progressive decline of RBF and ChBF with age that was comparable to untreated mice.

Potential and Most Relevant Applications of Total Body PET/CT Imaging.

ABSTRACT: The introduction of total body (TB) PET/CT instruments over the past 2 years has initiated a new and exciting era in medical imaging. These instruments have substantially higher sensitivity (up to 68 times) than conventional modalities and therefore allow imaging the entire body over a short period. However, we need to further refine the imaging protocols of this instrument for different indications. Total body PET will allow accurate assessment of the extent of disease, particularly, including the entire axial and appendicular skeleton. Furthermore, delayed imaging with this instrument may enhance the sensitivity of PET for some types of cancer. Also, this modality may improve the detection of venous thrombosis, a common complication of cancer and chemotherapy, in the extremities and help prevent pulmonary embolism. Total body PET allows assessment of atherosclerotic plaques throughout the body as a systematic disease. Similarly, patients with widespread musculoskeletal disorders including both oncologic and nononcologic entities, such as degenerative joint disease, rheumatoid arthritis, and osteoporosis, may benefit from the use of TB-PET. Finally, quantitative global disease assessment provided by this approach will be superior to conventional measurements, which do not reflect overall disease activity. In conclusion, TB-PET imaging may have a revolutionary impact on day-to-day practice of medicine and may become the leading imaging modality in the future.

The home language environment and early language ability in rural Southwestern China.

Using premier Language Environment Analysis technology to measure and analyze the home language environment, this observational study aims to describe the home language environment and child language ability, drawing on empirical data from 77 households with children aged 18-24 months from rural China. The results show large variation in measures of the home language environment and early language ability, similar to other rural Chinese samples. Results also demonstrate significant correlations between child age and the home language environment, maternal employment and the home language environment, father's educational attainment and the home language environment, adult-child conversations and early language ability, and child vocalizations and early language ability.

Emerging role of 18F-FDG PET/CT in Castleman disease: a review.

Castleman disease (CD) describes a group of rare hematologic conditions involving lymphadenopathy with characteristic histopathology and a spectrum of clinical abnormalities. CD is divided into localized or unicentric CD (UCD) and multicentric CD (MCD) by imaging. MCD is further divided based on etiological driver into human herpesvirus-8-associated MCD, POEMS-associated MCD, and idiopathic MCD. There is notable heterogeneity across MCD, but increased level of pro-inflammatory cytokines, particularly interleukin-6, is an established disease driver in a portion of patients. FDG-PET/CT can help determine UCD versus MCD, evaluate for neoplastic conditions that can mimic MCD clinico-pathologically, and monitor therapy responses. CD requires more robust characterization, earlier diagnosis, and an accurate tool for both monitoring and treatment response evaluation; FDG-PET/CT is particularly suited for this. Moving forward, future prospective studies should further characterize the use of FDG-PET/CT in CD and specifically explore the utility of global disease assessment and dual time point imaging.Trial registration ClinicalTrials.gov, NCT02817997, Registered 29 June 2016, https://clinicaltrials.gov/ct2/show/NCT02817997.

18F-FDG-PET/CT in the assessment of atherosclerosis in lung cancer.

The aim of this study was to assess the risk of atherosclerosis in patients with lung cancer compared to patients with extrapulmonary malignancies using 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT). We hypothesized that patients with lung cancer would demonstrate increased FDG uptake in the thoracic aorta compared to patients with extrapulmonary cancers. Thirty-four lung cancer patients (21 male, 13 female, 64.1 ± 12.9 yo) were retrospectively compared to seventy-eight patients with extrapulmonary malignancies (46 male, 32 female, 59.6 ± 12.8 yo). Average maximum standardized uptake value (avgSUVmax) and maximum target-to-blood pool ratio (TBRmax) were measured by mapping regions of interest of the ascending aorta, aortic arch, and descending aorta. Two-tailed Student's t-test was used to assess the differences in avgSUVmax and TBRmax between the two groups and between smokers and non-smokers. Age and gender distribution between the groups were not statistically different. AvgSUVmax and TBRmax were statistically significant increase in lung cancer patients compared to extrapulmonary cancer patients in the ascending aorta, aortic arch, and descending aorta, suggesting a lung cancer-associated increased risk of atherosclerosis development. AvgSUVmax was not significantly different between smokers and non-smokers in all sections of the thoracic aorta. Moving forward, large, prospective studies that directly compare PET data between different malignancies of different stages will help determine the role of FDG-PET/CT in assessing paraneoplastic vascular disease.

An understanding of the atherosclerotic molecular calcific heterogeneity between coronary, upper limb, abdominal, and lower extremity arteries as assessed by NaF PET/CT.

We aimed to quantify the heterogeneity of atherosclerosis in upper and lower limb vessels using 18F-NaF-PET/CT and compare calcification in coronary arteries to peripheral arteries. 68 healthy controls (42±13.5 years, 35 females, 33 males) and 40 patients at-risk for cardiovascular disease (55±11.9 years, 22 females, 18 males) underwent PET/CT imaging 90 minutes after the injection of 18F-NaF (2.2 Mbq/Kg). The following arteries were examined: coronary artery (CA), ascending aorta (AS), arch of aorta (AR), descending aorta (DA), abdominal aorta (AA), common iliac artery (CIA), external iliac artery (EIA), femoral artery (FA), popliteal artery (PA). Average SUVmean (aSUVmean) was calculated for each arterial segment. A paired t-test compared the aSUVmean between CA vs. AS, AR, DA, AA, CIA, EIA, FA, and PA. CA aSUVmean in the at-risk group was higher than the healthy control group (0.74±0.04 vs. 0.67±0.04, P=0.03). Furthermore, the 18F-NaF uptake in the CA was lower than in AS, AR, DA, AA, CIA, EIA, FA, and PA in both healthy (all P≤0.0001) and at-risk (all P≤0.0001). Higher 18F-NaF uptake in non-cardiac arteries in both healthy controls and patients at-risk suggests CA calcification is a late manifestation of atherosclerosis. This differential expression of atherosclerosis is likely due to interaction of hemodynamic parameters specific to the vascular bed and systemic factors related to the development of atherosclerosis.

Global brain glucose uptake on 18F-FDG-PET/CT is influenced by chronic cardiovascular risk.

PURPOSE: The goal of this study was to assess global cerebral glucose uptake in subjects with known cardiovascular risk factors by employing a quantitative 18F-fluorodeoxyglucose-PET/computed tomography (FDG-PET/CT) technique. We hypothesized that at-risk subjects would demonstrate decreased global brain glucose uptake compared to healthy controls. METHODS: We compared 35 healthy male controls and 14 male subjects at increased risk for cardiovascular disease (CVD) as assessed by the systematic coronary risk evaluation (SCORE) tool. All subjects were grouped into two age-matched cohorts: younger (<50 years) and older (≥50 years). The global standardized uptake value mean (Avg SUVmean) was measured by mapping regions of interest of the entire brain across the supratentorial structures and cerebellum. Wilcoxon's rank-sum test was used to assess the differences in Avg SUVmean between controls and at-risk subjects. RESULTS: Younger subjects demonstrated higher brain Avg SUVmean than older subjects. In addition, in both age strata, the 10-year risk for fatal CVD according to the SCORE tool was significantly greater in the at-risk groups than in healthy controls (younger: P = 0.0304; older: P = 0.0436). In the younger cohort, at-risk subjects demonstrated significantly lower brain Avg SUVmean than healthy controls (P = 0.0355). In the older cohort, at-risk subjects similarly had lower Avg SUVmean than controls (P = 0.0343). CONCLUSIONS: Global brain glucose uptake appears to be influenced by chronic cardiovascular risk factors. Therefore, FDG-PET/CT may play a role in determining the importance of CVD on brain function and has potential for monitoring the efficacy of various therapeutic interventions.

Comparison of atherosclerotic burden in non-lower extremity arteries in patients with and without peripheral artery disease using 18F-NaF-PET/CT imaging.

Atherosclerosis is the most common cause of peripheral artery disease (PAD). We compared the atherosclerotic burden in non-lower extremity arteries in patients with and without PAD using 18F-sodium fluoride (NaF)-PET/CT. We identified five individuals (61.8±6.6 years, one male, four females) with PAD and matched to five individuals without PAD based on age and gender from the unfavorable cardiovascular risk profile group of the CAMONA trial (60±7.2 years, one male, four females). Individuals underwent PET/CT imaging 90 minutes after the injection of NaF (2.2 Mbq/Kg). CT imaging was conducted to account for attenuation correction and anatomic referencing. The NaF uptake was measured by manually defining regions of interest on each axial slice on the following arteries: coronary artery (CA), carotid artery (CR), ascending aorta (AS), arch of aorta (AR), descending aorta (DA), and abdominal aorta (AA). Average SUVmean (aSUVmean) was calculated for each segment. Wilcoxon's signed rank test was used for statistical analysis. The total aSUVmean was higher in the PAD group compared to the non-PAD group (6.54±0.9 vs. 5.03±0.45, P=0.043). Comparison revealed higher NaF uptake in CR, AS, AR, and DA in the PAD group compared to the non-PAD group (0.93±0.25 vs. 0.54±0.14, P=0.01; 1.28±0.20 vs. 0.86±1.19, P<0.01; 1.18±0.17 vs. 0.90±0.19, P=0.03; 1.32±0.24 vs. 0.91±0.15, P=0.01). The NaF uptake in CA and AA was similar between the two groups (0.77±0.04 vs. 0.71±0.05, P=0.11; 1.07±0.28 vs. 1.12±0.30, P=0.82). We found individuals with PAD had higher atherosclerotic burden in the carotid arteries and thoracic aorta compared to non-PAD subjects.

Utilization of NaF-PET/CT in assessing global cardiovascular calcification using CHADS2 and CHADS2-VASc scoring systems in high risk individuals for cardiovascular disease.

CHADS2 and CHA2DS2-VASc scores are used to estimate the risk of strokes in patients with atrial fibrillation. We sought to determine the global quantification of cardiovascular molecular calcification in high risk individuals by NaF-PET/CT and compare it with CHADS2 and CHA2DS2-VASc scores. We identified 40 high risk individuals for cardiovascular disease from the Cardiovascular Molecular Calcification Assessed by 18F-NaF PET CT (CAMONA) trial and calculated CHADS2 and CHADS2-VASc scores for each. Ninety minutes after NaF injection (2.2 Mbq/kg), PET/CT imaging was performed. CT imaging was done for attenuation correction and anatomic correlation. The global cardiac uptake was calculated from regions of interest manually drawn on axial PET/CT images made in OsirixMD. Global cardiac average SUVmean (aSUVmean) values were calculated, and linear regression analysis was employed for statistical purposes. Subjects had mean age of 55 ± 11.9 SD years, (Range: 23-73 years), female 55%. The sample consisted of subjects with a mean aSUVmax of 2.9 ± 1.4, aSUVmean was 0.8 ± 0.2, CHADS2 0.9 ± 0.6 (Range: 0-3), CHA2DS2-VASc 1.8 ± 1.3 (Range: 0-5). Based on the linear regression models, we found a direct correlation between global cardiac aSUVmean and CHADS2 score (r=0.58, P≤0.0001) and also between global cardiac aSUVmean and CHA2DS2-VASc (r=0.37, P=0.01). Based on the results of our study we conclude that patients with a higher CHADS2 and CHA2DS2-VASc scores had a higher atherosclerotic burden and could be at greater risk of cardiovascular events. These scoring systems can help with risk stratification for predicting future adverse atherosclerotic events.

Association of triglyceride to high density lipoprotein ratio with global cardiac microcalcification to evaluate subclinical coronary atherosclerosis in non-diabetic individuals.

OBJECTIVE: Triglycerides (TG) to high density lipoprotein (HDL) ratio has been proposed as a marker of insulin resistance and atherosclerosis. We hypothesize that TG/HDL ratio correlates positively with global cardiac microcalcification as assessed by NaF-PET/CT as a surrogate marker for coronary atherosclerosis in healthy non-diabetic individuals. METHOD: We identified 68 healthy, non-diabetic individuals (age 41.7 ± 13.5 years; 35/33 female/male) from the CAMONA trial. All underwent PET/CT imaging 90 minutes after NaF injection (2.2 Mbq/Kg). Global cardiac average SUVmean (aSUVmean) was calculated by a trained physician for each individual. Fasting plasma lipid profile (total cholesterol (TC), low-density lipoprotein (LDL), HDL, and TG) and fasting plasma glucose were recorded. TG/HDL ratio was calculated for every individual. Univariate and multivariate linear regression models were used to assess the association between TG/HDL ratio and global cardiac aSUVmean. RESULT: On univariate analysis, there was a positive linear association of TG/HDL ratio and global cardiac aSUVmean (r=0.244, B=0.047, P=0.045). On multivariate analysis adjusted for age, gender, systolic blood pressure, diastolic blood pressure, smoking status, total cholesterol, low-density lipoprotein, and fasting plasma glucose, TG/HDL ratio was found to be independently associated with global cardiac aSUVmean (B=0.060, 95% CI: 0.007-0.114, P=0.027). CONCLUSION: There was a positive correlation between TG/HDL ratio with global cardiac microcalcification assessed by NaF-PET/CT imaging.

Diagnosis and Monitoring of Osteoporosis with Total-Body 18F-Sodium Fluoride-PET/CT.

In recent years, 18F-Sodium Fluoride (NaF)-PET/CT has seen its role in the detection and management of osteoporosis increase. This article reviews the extent of this application in the literature, its efficacy compared with other comparable imaging tools, and how total-body PET/CT combined with global disease assessment can revolutionize measurement of total osteoporotic disease activity. NaF-PET/CT eventually can be the modality of choice for metabolic bone disorders, especially with these advances in technology and computation.

NaF-PET/CT global assessment in detecting and quantifying subclinical cardiac atherosclerosis and its association with blood pressure in non-dyslipidemic individuals.

BACKGROUND: We used 18F-sodium fluoride (NaF) to assess early atherosclerosis in the global heart in asymptomatic individuals with a coronary calcium score of zero and without a formal diagnosis of hypertension. We hypothesized that these individuals might present with subclinical atherosclerosis that correlates with systolic, diastolic and mean arterial pressure (SBP, DBP, and MAP). METHODS: We identified 20 asymptomatic individuals (41.6 ± 13.8 years, 8 females) from the CAMONA trial with C-reactive protein ≥3 mg/L, no smoking history, diabetes (fasting blood glucose <126 mg/dl) and dyslipidemia per the Adult Treatment Panel III Guidelines: untreated LDL <160 mg/dL, total cholesterol <240 mg/dL, HDL >40 mg/dL. All underwent PET/CT imaging 90 minutes after NaF injection (2.2 Mbq/Kg). The global cardiac average SUVmean (aSUVmean) was calculated for each individual. Correlation coefficients and linear regression models were employed for statistical analysis. RESULTS: Significant positive correlation was revealed between global cardiac NaF uptake and all blood pressures: SBP (r=0.44, P=0.05), DBP (r=0.64, P=0.002), and MAP (r=0.59, P=0.007). After adjusting for age and gender, DBP and MAP were independent predictors of higher global cardiac NaF uptake. CONCLUSION: NaF-PET/CT for detecting and quantifying subclinical atherosclerosis in asymptomatic individuals revealed that cardiac NaF uptake correlated independently with DBP and MAP.

Global quantification of pulmonary artery atherosclerosis using 18F-sodium fluoride PET/CT in at-risk subjects.

The goal of this study was to assess pulmonary artery calcification in healthy controls and subjects with suspicion of stable angina pectoris through the usage of quantitative 18F-sodium fluoride positron emission tomography/computed tomography (NaF-PET/CT). We hypothesized that these 'at-risk subjects' would demonstrate increase pulmonary artery NaF uptake compared to healthy controls. Retrospectively, 15 healthy controls were compared to 15 at-risk subjects, all of whom underwent full-body NaF-PET/CT scans. The healthy controls and at-risk patients were all randomly sampled from larger datasets. The two sampled groups were male-dominated and similar in age. The global mean standard uptake value (SUVmean), the max standard uptake value (SUVmax), and the mean target-to-background ratio (TBRmean) were acquired through mapping of regions of interest (ROI's) around the pulmonary artery of the subjects. A two-tailed Mann-Whitney U test was used to determine the significance of difference between the two groups. For global SUVmean (0.79 compared to 0.58), global TBRmean (1.15 compared to 0.93), and global SUVmax (1.78 compared to 1.60), the NaF uptake was significantly higher in the at-risk patients compared to the controls (all P<0.05). NaF-PET/CT is a suitable imaging modality for quantification of molecular calcification in the pulmonary artery. Additionally, the connection between atherosclerosis and the risk factor of angina pectoris is further reinforced. We believe that future studies are needed to validate our proof-of-concept, and better confirm the clinical future of NaF-PET/CT as a tracer of atherosclerotic plaques.

Trends, Outcomes, and Predictors of Sepsis and Severe Sepsis in Patients with Left Ventricular Assist Devices.

Left ventricular assist device (LVAD) is used in end-stage heart failure that is refractory to medical treatment. However, there is a paucity of data looking at the rates of sepsis and severe sepsis (SSS). Therefore, this study was conceived with the purpose of analyzing the SSS burden and outcomes associated with LVAD implantation. The national inpatient sample database was queried from 2010 to 2014 using ICD-9 procedure code for LVAD use among patients 18 years or older and 2359 patients were identified. During the five-year study period, the average incidence of SSS was 11.8% and it was noted that cases with SSS were associated with an increased likelihood of mortality, greater length of hospital stay (LOS), and higher hospital-related charges (p < .001) compared to controls. Controlling for age, sex, and LOS, hierarchical multivariate logistic regression revealed that significant predictors of SSS were acute kidney injury [Adjusted odd's ratio (AOR) = 2.75, 95% CI = 1.87, 4.14)], mechanical ventilation (AOR = 2.34, 95% CI = 1.70, 3.23), venous thromboembolism (AOR = 1.76, 95% CI = 1.12, 2.75), gastrointestinal bleed (AOR = 1.77, 95% CI = 1.12, 2.76), chronic obstructive pulmonary disease (COPD) (AOR = 0.55, 95% CI = 0.40, 0.77), acute myocardial infarction (AOR = 0.54, 95% CI = 0.36, 0.80) and mild liver disease (AOR = 2.18, 95% CI = 1.55, 3.06). The rate of incidence of sepsis has remained constant and is often associated with a worse clinical outcome. This provides a basis to identify high-risk groups and helps argue for earlier detection of such patients and better patient selection so as to reduce infectious complications.