Long-acting Erwinia chrysanthemi, Pegcrisantaspase, induces alternate amino acid biosynthetic pathways in a preclinical model of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease without meaningful therapeutic options beyond the first salvage therapy. Targeting PDAC metabolism through amino acid restriction has emerged as a promising new strategy, with asparaginases, enzymes that deplete plasma glutamine and asparagine, reaching clinical trials. In this study, we investigated the anti-PDAC activity of the asparaginase formulation Pegcrisantaspase (PegC) alone and in combination with standard-of-care chemotherapeutics. METHODS: Using mouse and human PDAC cell lines, we assessed the impact of PegC on cell proliferation, cell death, and cell cycle progression. We further characterized the in vitro effect of PegC on protein synthesis as well as the generation of reactive oxygen species and levels of glutathione, a major cellular antioxidant. Additional cell line studies examined the effect of the combination of PegC with standard-of-care chemotherapeutics. In vivo, the tolerability and efficacy of PegC, as well as the impact on plasma amino acid levels, was assessed using the C57BL/6-derived KPC syngeneic mouse model. RESULTS: Here we report that PegC demonstrated potent anti-proliferative activity in a panel of human and murine PDAC cell lines. This decrease in proliferation was accompanied by inhibited protein synthesis and decreased levels of glutathione. In vivo, PegC was tolerable and effectively reduced plasma levels of glutamine and asparagine, leading to a statistically significant inhibition of tumor growth in a syngeneic mouse model of PDAC. There was no observable in vitro or in vivo benefit to combining PegC with standard-of-care chemotherapeutics, including oxaliplatin, irinotecan, 5-fluorouracil, paclitaxel, and gemcitabine. Notably, PegC treatment increased tumor expression of asparagine and serine biosynthetic enzymes. CONCLUSIONS: Taken together, our results demonstrate the potential therapeutic use of PegC in PDAC and highlight the importance of identifying candidates for combination regimens that could improve cytotoxicity and/or reduce the induction of resistance pathways.

Network-based drug repositioning of linagliptin as a potential agent for uterine fibroids targeting transforming growth factor-beta mediated fibrosis.

Uterine fibroid is the most common non-cancerous tumor with no satisfactory options for long-term pharmacological treatment. Fibroblast activation protein-α (FAP) is one of the critical enzymes that enhances the fibrosis in uterine fibroids. Through STITCH database mining, we found that dipeptidyl peptidase-4 inhibitors (DPP4i) have the potential to inhibit the activity of FAP. Both DPP4 and FAP belong to the dipeptidyl peptidase family and share a similar catalytic domain. Hence, ligands which have a binding affinity with DPP4 could also bind with FAP. Among the DPP4i, linagliptin exhibited the highest binding affinity (Dock score = -8.562 kcal/mol) with FAP. Our study uncovered that the differences in the S2 extensive-subsite residues between DPP4 and FAP could serve as a basis for designing selective inhibitors specifically targeting FAP. Furthermore, in a dynamic environment, linagliptin was able to destabilize the dimerization interface of FAP, resulting in potential inhibition of its biological activity. True to the in-silico results, linagliptin reduced the fibrotic process in estrogen and progesterone-induced fibrosis in rat uterus. Furthermore, linagliptin reduced the gene expression of transforming growth factor-ß (TGF-ß), a critical factor in collagen secretion and fibrotic process. Masson trichrome staining confirmed that the anti-fibrotic effects of linagliptin were due to its ability to reduce collagen deposition in rat uterus. Altogether, our research proposes that linagliptin has the potential to be repurposed for the treatment of uterine fibroids.

Severe hypocalcaemia mimicking acute coronary syndrome.

Hypocalcaemia is a common electrolyte deficiency that can be found in up to 28% of hospitalised patients. It may affect cardiac and smooth muscle tone, leading to ECG abnormalities and, in rare cases, coronary spasms and heart failure. This is a case of a pregnant woman in preterm labour who developed vasospastic angina and corrected QT interval (QTc) prolongation on ECG from severe hypocalcaemia, which likely occurred due to iatrogenic hypermagnesaemia. She had a negative diagnostic workup for acute coronary syndrome, and her chest pain and QTc prolongation ultimately resolved with intravenous electrolyte repletion. This case highlights the importance of considering hypocalcaemia on the differential of chest pain that is possibly cardiac in origin.

Outcomes in non-ST-segment elevation myocardial infarction complicated by in-hospital cardiac arrest based on management strategy.

BACKGROUND: There are limited data on in-hospital cardiac arrest (IHCA) complicating non-ST-segment-elevation myocardial infarction (NSTEMI) based on management strategy. METHODS: We used National Inpatient Sample (2000-2017) to identify adults with NSTEMI (not undergoing coronary artery bypass grafting) and concomitant IHCA. The cohort was stratified based on use of early (hospital day 0) or delayed (≥hospital day 1) coronary angiography (CAG), percutaneous coronary intervention (PCI), and medical management. Outcomes included incidence of IHCA, in-hospital mortality, adverse events, length of stay, and hospitalization costs. RESULTS: Of 6,583,662 NSTEMI admissions, 375,873 (5.7 %) underwent early CAG, 1,133,143 (17.2 %) received delayed CAG, 2,326,391 (35.3 %) underwent PCI, and 2,748,255 (41.7 %) admissions were managed medically. The medical management cohort was older, predominantly female, and with higher comorbidities. Overall, 63,085 (1.0 %) admissions had IHCA, and incidence of IHCA was highest in the medical management group (1.4 % vs 1.1 % vs 0.7 % vs 0.6 %, p < 0.001) compared to early CAG, delayed CAG and PCI groups, respectively. In adjusted analysis, early CAG (adjusted OR [aOR] 0.67 [95 % confidence interval {CI} 0.65-0.69]; p < 0.001), delayed CAG (aOR 0.49 [95 % CI 0.48-0.50]; p < 0.001), and PCI (aOR 0.42 [95 % CI 0.41-0.43]; p < 0.001) were associated with lower incidence of IHCA compared to medical management. Compared to medical management, early CAG (adjusted OR 0.53, CI: 0.49-0.58), delayed CAG (adjusted OR 0.34, CI: 0.32-0.36) and PCI (adjusted OR 0.19, CI: 0.18-0.20) were associated with lower in-hospital mortality (all p < 0.001). CONCLUSION: Early CAG and PCI in NSTEMI was associated with lower incidence of IHCA and lower mortality among NSTEMI-IHCA admissions.

In-Hospital cardiac arrest complicating ST-elevation myocardial Infarction: Temporal trends and outcomes based on management strategy.

BACKGROUND: There are limited data on the relationship of ST-segment-elevation myocardial infarction (STEMI) management strategy and in-hospital cardiac arrest (IHCA). AIMS: To investigate the trends and outcomes of IHCA in STEMI by management strategy. METHODS: Adult with STEMI complicated by IHCA from the National Inpatient Sample (2000-2017) were stratified into early percutaneous coronary intervention (PCI) (day 0 of hospitalization), delayed PCI (PCI ≥ day 1), or medical management (no PCI). Coronary artery bypass surgery was excluded. Outcomes of interest included in-hospital mortality, adverse events, length of stay, and hospitalization costs. RESULTS: Of 3,967,711 STEMI admissions, IHCA was noted in 102,424 (2.6%) with an increase in incidence during this study period. Medically managed STEMI had higher rates of IHCA (3.6% vs 2.0% vs 1.3%, p < 0.001) compared to early and delayed PCI, respectively. Revascularization was associated with lower rates of IHCA (early PCI: adjusted odds ratio [aOR] 0.44 [95% confidence interval (CI) 0.43-0.44], p < 0.001; delayed PCI aOR 0.33 [95% CI 0.32-0.33], p < 0.001) compared to medical management. Non-revascularized patients had higher rates of non-shockable rhythms (62% vs 35% and 42.6%), but lower rates of multiorgan damage (44% vs 52.7% and 55.6%), cardiogenic shock (28% vs 65% and 57.4%) compared to early and delayed PCI, respectively (all p < 0.001). In-hospital mortality was lower with early PCI (49%, aOR 0.18, 95% CI 0.17-0.18), and delayed PCI (50.9%, aOR 0.18, 95% CI 0.17-0.19) (p < 0.001) compared to medical management (82.5%). CONCLUSION: Early PCI in STEMI impacts the natural history of IHCA including timing and type of IHCA.

Importance of Fibrosis in the Pathogenesis of Uterine Leiomyoma and the Promising Anti-fibrotic Effects of Dipeptidyl Peptidase-4 and Fibroblast Activation Protein Inhibitors in the Treatment of Uterine Leiomyoma.

Uterine fibroid or leiomyoma is the most common benign uterus tumor. The tumor is primarily composed of smooth muscle (fibroid) cells, myofibroblast, and a significant amount of extracellular matrix components. It mainly affects women of reproductive age. They are uncommon before menarche and usually disappear after menopause. The fibroids have excessive extracellular matrix components secreted by activated fibroblast cells (myofibroblast). Myofibroblast has the characteristics of fibroblast and smooth muscle cells. These cells possess contractile capability due to the expression of contractile proteins which are normally found only in muscle tissues. The rigid nature of the tumor is responsible for many side effects associated with uterine fibroids. The current drug treatment strategies are primarily hormone-driven and not anti-fibrotic. This paper emphasizes the fibrotic background of uterine fibroids and the mechanisms behind the deposition of excessive extracellular matrix components. The transforming growth factor-ß, hippo, and focal adhesion kinase-mediated signaling pathways activate the fibroblast cells and deposit excessive extracellular matrix materials. We also exemplify how dipeptidyl peptidase-4 and fibroblast activation protein inhibitors could be beneficial in reducing the fibrotic process in leiomyoma. Dipeptidyl peptidase-4 and fibroblast activation protein inhibitors prevent the fibrotic process in organs such as the kidneys, lungs, liver, and heart. These inhibitors are proven to inhibit the signaling pathways mentioned above at various stages of their activation. Based on literature evidence, we constructed a narrative review on the mechanisms that support the beneficial effects of dipeptidyl peptidase-4 and fibroblast activation protein inhibitors for treating uterine fibroids.

Combined atrial fibrillation ablation and left atrial appendage occlusion procedure in the United States: a propensity score matched analysis from 2016-2019 national readmission database.

AIMS: The safety and feasibility of combining percutaneous catheter ablation (CA) for atrial fibrillation with left atrial appendage occlusion (LAAO) as a single procedure in the USA have not been investigated. We analyzed the US National Readmission Database (NRD) to investigate the incidence of combined LAAO + CA and compare major adverse cardiovascular events (MACEs) with matched LAAO-only and CA-only patients. METHODS AND RESULTS: In this retrospective study from NRD data, we identified patients undergoing combined LAAO and CA procedures on the same day in the USA from 2016 to 2019. A 1:1 propensity score match was performed to identify patients undergoing LAAO-only and CA-only procedures. The number of LAAO + CA procedures increased from 28 (2016) to 119 (2019). LAAO + CA patients (n = 375, mean age 74 ± 9.2 years, 53.4% were males) had non-significant higher MACE (8.1%) when compared with LAAO-only (n = 407, 5.3%) or CA-only patients (n = 406, 7.4%), which was primarily driven by higher rate of pericardial effusion (4.3%). All-cause 30-day readmission rates among LAAO + CA patients (10.7%) were similar when compared with LAAO-only (12.7%) or CA-only (17.5%) patients. The most frequent primary reason for readmissions among LAAO + CA and LAAO-only cohorts was heart failure (24.6 and 31.5%, respectively), while among the CA-only cohort, it was paroxysmal atrial fibrillation (25.7%). CONCLUSION: We report an 63% annual growth (from 28 procedures) in combined LAAO and CA procedures in the USA. There were no significant difference in MACE and all-cause 30-day readmission rates among LAAO + CA patients compared with matched LAAO-only or CA-only patients.

Hospitalization Duration for Acute Myocardial Infarction: A Temporal Analysis of 18-Year United States Data.

Background and objectives: Primary percutaneous coronary intervention (PCI)-related outcomes in acute myocardial infarction (AMI) have improved over time, but there are limited data on the length of stay (LOS) in relation to in-hospital mortality. Materials and Methods: A retrospective cohort of adult AMI admissions was identified from the National Inpatient Sample (2000−2017) and stratified into short (≤3 days) and long (>3 days) LOS. Outcomes of interest included temporal trends in LOS and associated in-hospital mortality, further sub-stratified based on demographics and comorbidities. Results: A total 11,622,528 admissions with AMI were identified, with a median LOS of 3 (interquartile range [IQR] 2−6) days with 49.9% short and 47.3% long LOS, respectively. In 2017, compared to 2000, temporal trends in LOS declined in all AMI, with marginal increases in LOS >3 days and decreases for ≤3 days (median 2 [IQR 1−3]) vs. long LOS (median 6 [IQR 5−9]). Patients with long LOS had lower rates of coronary angiography and PCI, but higher rates of non-cardiac organ support (respiratory and renal) and use of coronary artery bypass grafting. Unadjusted in-hospital mortality declined over time. Short LOS had comparable mortality to long LOS (51.3% vs. 48.6%) (p = 0.13); however, adjusted in-hospital mortality was higher in LOS >3 days when compared to LOS ≤ 3 days (adjusted OR 3.00, 95% CI 2.98−3.02, p < 0.001), with higher hospitalization (p < 0.001) when compared to long LOS. Conclusions: Median LOS in AMI, particularly in STEMI, has declined over the last two decades with a consistent trend in subgroup analysis. Longer LOS is associated with higher in-hospital mortality, higher hospitalization costs, and less frequent discharges to home compared to those with shorter LOS.

Impact of Active and Historical Cancers on the Management and Outcomes of Acute Myocardial Infarction Complicating Cardiogenic Shock.

BACKGROUND: There are limited data on the outcomes of acute myocardial infarction-cardiogenic shock (AMI-CS) in patients with concomitant cancer. METHODS: A retrospective cohort of adult AMI-CS admissions was identified from the National Inpatient Sample (2000-2017) and stratified by active cancer, historical cancer, and no cancer. Outcomes of interest included in-hospital mortality, use of coronary angiography, use of percutaneous coronary intervention, do-not-resuscitate status, palliative care use, hospitalization costs, and hospital length of stay. RESULTS: Of the 557,974 AMI-CS admissions during this 18-year period, active and historical cancers were noted in 14,826 (2.6%) and 27,073 (4.8%), respectively. From 2000 to 2017, there was a decline in active cancers (adjusted odds ratio, 0.70 [95% CI, 0.63-0.79]; P < .001) and an increase in historical cancer (adjusted odds ratio, 2.06 [95% CI, 1.89-2.25]; P < .001). Compared with patients with no cancer, patients with active and historical cancer received less-frequent coronary angiography (57%, 67%, and 70%, respectively) and percutaneous coronary intervention (40%, 47%, and 49%%, respectively) and had higher do-not-resuscitate status (13%, 15%, 7%%, respectively) and palliative care use (12%, 10%, 6%%, respectively) (P < .001). Compared with those without cancer, higher in-hospital mortality was found in admissions with active cancer (45.9% vs 37.0%; adjusted odds ratio, 1.29 [95% CI, 1.24-1.34]; P < .001) but not historical cancer (40.1% vs 37.0%; adjusted odds ratio, 1.01 [95% CI, 0.98-1.04]; P = .39). AMI-CS admissions with cancer had a shorter hospitalization duration and lower costs (all P < .001). CONCLUSION: Concomitant cancer was associated with less use of guideline-directed procedures. Active, but not historical, cancer was associated with higher mortality in patients with AMI-CS.

A Comprehensive Appraisal of Risk Prediction Models for Cardiogenic Shock.

ABSTRACT: Despite advances in early revascularization, percutaneous hemodynamic support platforms, and systems of care, cardiogenic shock (CS) remains associated with a mortality rate higher than 50%. Several risk stratification models have been derived since the 1990 s to identify patients at high risk of adverse outcomes. Still, limited information is available on the differences between scoring systems and their relative applicability to both acute myocardial infarction and advanced decompensated heart failure CS. Thus, we reviewed the similarities, differences, and limitations of published CS risk prediction models and herein discuss their suitability to the contemporary management of CS care.

Concomitant Sepsis Diagnoses in Acute Myocardial Infarction-Cardiogenic Shock: 15-Year National Temporal Trends, Management, and Outcomes.

OBJECTIVES: Mixed cardiogenic-septic shock is common and associated with high mortality. There are limited contemporary data on concomitant sepsis in acute myocardial infarction complicated by cardiogenic shock (AMI-CS). DESIGN: Observational study. SETTING: Twenty percent stratified sample of all community hospitals (2000-2014) in the United States. PARTICIPANTS: Adults (> 18 yr) with AMI-CS with and without concomitant sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcomes of interest included inhospital mortality, development of noncardiac organ failure, complications, utilization of guideline-directed procedures, length of stay, and hospitalization costs. Over 15 years, 444,253 AMI-CS admissions were identified, of which 27,057 (6%) included sepsis. The sepsis cohort had more comorbidities and had higher rates of noncardiac multiple organ failure (92% vs 69%) (all p < 0.001). In 2014, compared with 2000, the prevalence of sepsis increased from 0.5% versus 11.5% with an adjusted odds ratio (aOR) 11.71 (95% CI, 9.7-14.0) in ST-segment elevation myocardial infarction and 24.6 (CI, 16.4-36.7) (all p < 0.001) in non-ST segment elevation myocardial infarction. The sepsis cohort received fewer cardiac interventions (coronary angiography [65% vs 68%], percutaneous coronary intervention [43% vs 48%]) and had greater use of mechanical circulatory support (48% vs 45%) and noncardiac support (invasive mechanical ventilation [65% vs 41%] and acute hemodialysis [12% vs 3%]) (p < 0.001). The sepsis cohort had higher inhospital mortality (44.3% vs 38.1%; aOR, 1.21; 95% CI, 1.18-1.25; p < 0.001), longer length of stay (14.0 d [7-24 d] vs 7.0 d [3-12 d]), greater hospitalization costs (×1,000 U.S. dollars) ($176.0 [$85-$331] vs $77.0 [$36-$147]), fewer discharges to home (22% vs 44%) and more discharges to skilled nursing facilities (51% vs 28%) (all p < 0.001). CONCLUSIONS: In AMI-CS, concomitant sepsis is associated with higher mortality and morbidity highlighting the need for early recognition and integrated management of mixed shock.

Outcomes and predictors of readmission after implantation of a percutaneous left atrial appendage occlusion device in the United States: A propensity score-matched analysis from The National Readmission Database.

BACKGROUND: Left atrial appendage occlusion (LAAO) devices have become a favorable alternative option among nonvalvular atrial fibrillation (AF) patients with long-term contraindication to anticoagulation. Real-world experience with postprocedural readmission rates and predictors of readmission in LAAO patients is limited. OBJECTIVE: To assess all-cause 30-day readmission rate and predictors of readmission after LAAO procedure in the United States. METHOD: This retrospective observational study included all AF patients undergoing percutaneous LAAO procedures in the United States from January 1, 2016, and December 31, 2017, in the National Readmission Database. The primary outcome measure was all-cause 30-day readmission. A propensity score-matched analysis compared outcomes with a non-LAAO AF cohort. RESULT: Among 14 024 LAAO procedures (age: 76 ± 8 years; 60.5% males), 9.4% were readmitted within 30-days and, 0.2% died during their index hospitalization. The most frequent primary diagnosis during readmission among LAAO was gastrointestinal bleeding (12%). The incidence of LAAO procedures increased by 102%. In the multivariate model, gender and CHA2 DS2 -VASc failed to predict readmission. Age 55-64 years had lower odds (adjusted odds ratios [aOR]: 0.41; 95% confidence interval [CI]: 0.18-0.94), while drug abuse (aOR: 4.1; 95% CI: 1.34-12.54), and deficiency anemia (aOR: 1.88; 95% CI: 1.12-3.18) had higher odds of readmission. In propensity-matched cohort, compared to non-LAAO AF, LAAO patients had lower 30-day readmission (9.4% vs. 10.98%, p = .002) and all-cause in-hospital mortality (0.19% vs. 0.57%, p < .001). CONCLUSION: The readmission rate following the LAAO procedure is substantial (approximately 10%), and largely attributable to gastrointestinal bleeding. Factors such as drug abuse and anemia must be explored further to minimize readmission risk.

A scoring system derived from electronic health records to identify patients at high risk for noninvasive ventilation failure.

OBJECTIVE: To develop and validate a clinical risk prediction score for noninvasive ventilation (NIV) failure defined as intubation after a trial of NIV in non-surgical patients. DESIGN: Retrospective cohort study of a multihospital electronic health record database. PATIENTS: Non-surgical adult patients receiving NIV as the first method of ventilation within two days of hospitalization. MEASUREMENT: Primary outcome was intubation after a trial of NIV. We used a non-random split of the cohort based on year of admission for model development and validation. We included subjects admitted in years 2010-2014 to develop a risk prediction model and built a parsimonious risk scoring model using multivariable logistic regression. We validated the model in the cohort of subjects hospitalized in 2015 and 2016. MAIN RESULTS: Of all the 47,749 patients started on NIV, 11.7% were intubated. Compared with NIV success, those who were intubated had worse mortality (25.2% vs. 8.9%). Strongest independent predictors for intubation were organ failure, principal diagnosis group (substance abuse/psychosis, neurological conditions, pneumonia, and sepsis), use of invasive ventilation in the prior year, low body mass index, and tachypnea. The c-statistic was 0.81, 0.80 and 0.81 respectively, in the derivation, validation and full cohorts. We constructed three risk categories of the scoring system built on the full cohort; the median and interquartile range of risk of intubation was: 2.3% [1.9%-2.8%] for low risk group; 9.3% [6.3%-13.5%] for intermediate risk category; and 35.7% [31.0%-45.8%] for high risk category. CONCLUSIONS: In patients started on NIV, we found that in addition to factors known to be associated with intubation, neurological, substance abuse, or psychiatric diagnoses were highly predictive for intubation. The prognostic score that we have developed may provide quantitative guidance for decision-making in patients who are started on NIV.

Evaluation of the American Association of Cardiovascular and Pulmonary Rehabilitation Exercise Risk Stratification Classification Tool Without Exercise Testing.

PURPOSE: The American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) recommends that patients starting cardiac rehabilitation (CR) undergo stratification to identify risk for exercise-related adverse events (AE), but this tool has not been recently evaluated. METHODS: Among patients who enrolled in CR in 2016, we used the AACVPR risk stratification tool to evaluate the risk for AE and clinical events (CE). We defined AE as signs or symptoms that precluded or interrupted exercise during CR, and CE as events requiring an urgent evaluation outside of CR exercise sessions. RESULTS: During the study period, 657 patients with cardiovascular diagnoses were included and classified as high (58%), medium (31%), or low risk (11%). Over the course of CR (76 d, 17 sessions), there were 63 AE and 33 CE. Adverse events were mostly minor (no cardiac arrests or deaths) and managed by CR staff members. When compared with the low- or medium-risk groups, the high-risk group was more likely to have AE (HR 3.0 [95% CI, 1.7-5.9], P = .002) and CE (HR 3.7 [95% CI, 1.5-10.8], P = .002) with fair model discrimination (area under the curve: 0.637, P < .001). CONCLUSION: The AACVPR risk stratification tool was predictive of both AE and CE with fair discrimination, although event rates were low and mostly minor. Thus, the AACVPR model may require reevaluation to better identify truly at-risk patients for major AE.

Cardiac rehabilitation in Takotsubo cardiomyopathy: Predictors of utilization and effects of exercise training.

BACKGROUND: Takotsubo cardiomyopathy (TCM) patients may benefit from cardiac rehabilitation (CR). OBJECTIVES: The purpose to this study is to examine utilization of CR in TCM. METHODS: We conducted a review of hospitalized TCM patients at Baystate Medical Center between 2010 and 2017. We evaluated rates of referral, enrollment, adherence, and changes in exercise capacity. Predictors of CR utilization were analyzed using t-test, chi-square/odds ratio and multivariable hierarchical modeling when appropriate. RESULTS: Over 8 years, 35% of 590 patients with TCM were evaluated by phase I (inpatient) and 13.6% enrolled in phase II (outpatient) CR. Inpatient CR evaluation (OR 21, 95% CI 7-64) and cardiac catheterization (OR 5.7, 95% CI 1.9-17) were strong predictors of outpatient CR participation. Patients enrolling in CR attended 15±14 sessions and increased their exercise capacity by 1.2 METs (95% CI 0.9-1.5). CONCLUSION: CR is inconsistently used in TCM, despite the potential physiologic benefits of exercise in TCM.

Hemopericardium in a Sirolimus-Treated Renal Transplant Patient.

Sirolimus is an immunosuppressant frequently prescribed to prevent graft-vs-host disease in renal transplant patients. Pericardial effusion is recognized as a rare and potentially lethal side effect of this medication. Hemopericardium, specifically, is an even rarer complication that has yet to be reported in the literature. We report the first case of sirolimus-induced hemopericardium in a renal transplant patient.

Effects of spirulina on weight loss and blood lipids: a review.

Spirulina, a cyanobacteria commonly referred to as a blue-green algae, is one of the oldest lifeforms on Earth. Spirulina grows in both fresh and saltwater sources and is known for its high protein and micronutrient content. This review paper will cover the effects of spirulina on weight loss and blood lipids. The currently literature supports the benefits of spirulina for reducing body fat, waist circumference, body mass index and appetite and shows that spirulina has significant benefits for improving blood lipids.

Impact of Change in 2010 American Heart Association Cardiopulmonary Resuscitation Guidelines on Survival After Out-of-Hospital Cardiac Arrest in the United States: An Analysis From 2006 to 2015.

BACKGROUND: In October 2010, the American Heart Association/Emergency Cardiovascular Care updated cardiopulmonary resuscitation guidelines. Its impact on the survival rate among out-of-hospital cardiac arrest patients (OHCA) is not well studied. We sought to assess the survival trends in OHCA patients before and after the introduction of the 2010 American Heart Association cardiopulmonary resuscitation guidelines in the United States. METHODS: A retrospective observational study from the National Emergency Department (ED) Sample was designed to identify patients presenting to the ED primarily after an OHCA in the United States between January 1, 2006, and December 31, 2015. The main outcome studied was the change in trends of ED survival and survival-to-discharge rates before and after guideline modification. RESULTS: Among 1 282 520 patients presenting to the ED after OHCA (mean [SD] age, 65.8 [17.2] years; 62% men), ED survival rate (23%) and survival-to-discharge rate (16%) trends showed significant improvement after implementation of the 2010 American Heart Association cardiopulmonary resuscitation guidelines, 1.25% ([95% CI, 0.72%-1.78%] P=0.001) and 0.89% ([95% CI, 0.35%-1.43%] P=0.006), respectively. Notably, among patients with nonshockable rhythm (change in ED survival rate trend, 1.3% [95% CI, 0.89%-1.74%]; P<0.001 and survival-to-discharge trend, 0.94% [95% CI, 0.42%-1.47%]; P=0.004). Among patients admitted to the presenting hospital (n=145 592), 46% were discharged alive, of which 49% were discharged home. Significant decrease in discharge to home was noted (-1.7% [95% CI, -3.18% to -0.22%]; P=0.03), while a significant increase in neurological complication (0.17% [95% CI, 0.06%-0.28%]; P=0.007) was noted with the guideline modification. CONCLUSIONS: The change in 2010 American Heart Association cardiopulmonary resuscitation guidelines was associated with only slight improvement in ED survival and survival-to-discharge trends among US OHCA patients and only 1 in 6 OHCA patients survival to discharge.

Utility of ICD Codes for Stress Cardiomyopathy in Hospital Administrative Databases: What Do They Signify?

Prior studies of stress cardiomyopathy (SCM) have used International Classification of Diseases (ICD) codes to identify patients in administrative databases without evaluating the validity of these codes. Between 2010 and 2016, we identified 592 patients discharged with a first known principal or secondary ICD code for SCM in our medical system. On chart review, 580 charts had a diagnosis of SCM (positive predictive value 98%; 95% CI: 96.4-98.8), although 38 (6.4%) did not have active clinical manifestations of SCM during the hospitalization. Moreover, only 66.8% underwent cardiac catheterization and 91.5% underwent echocardiography. These findings suggest that, although all but a few hospitalized patients with an ICD code for SCM had a diagnosis of SCM, some of these were chronic cases, and numerous patients with a new diagnosis of SCM did not undergo a complete diagnostic workup. Researchers should be mindful of these limitations in future studies involving administrative databases.

Influence of comorbidity on survival after out-of-hospital cardiac arrest in the United States.

AIM: Association between survival rate and Elixhauser Comorbidity Index (ECI) among individuals suffering an out-of-hospital cardiac arrest (OHCA) in the United States (US). METHODS: We utilized the US National Emergency Department Sample (NEDS) dataset to retrospectively identify individuals experiencing OHCA between January 1, 2006 to December 31, 2015; using the International Classification of Diseases, Ninth Revision-Clinical Modification (ICD-9-CM) and Tenth Revision-Clinical Modification (ICD-10-CM) codes. Logistic regression analysis with twenty-nine ECIs as predictor variables were performed to compute for odds ratio (OR), after controlling for age and gender. Linear regression analysis performed to assess survival trend after clustering based on ECI. We also assessed the association of ECI with survival rate after stratifying patients based on cardiac rhythm (shockable versus non-shockable). RESULTS: We identified 1,282,520 (16.4%, survived-to-discharge) weighted observations presenting primarily after OHCA in the US during the study period. Annual percentage change (APC) in survival rate among OHCA patients with no ECI and those with >3 ECI was -1.53% (95% CI: -1.98% to -1.09%, Ptrend < 0.001) and 1.2% (95% CI: 0.69%-1.7%, Ptrend = 0.001), respectively. Adjusted OR for ECI was 1.31 (95% CI: 1.3-1.31, P < 0.001). Percentage change in the survival rate among shockable and non-shockable rhythm was 5.6% (95% CI: -3.9% to 15.13%, Ptrend = 0.127) and 1.04% (95% CI: 0.01%-2.07%, Ptrend = 0.05), respectively, with a unit increase in ECI. CONCLUSION: In the US, OHCA patients with higher ECI have greater survival-to-discharge rate, demonstrating "comorbidity paradox".