Unroofed Coronary Sinus as Potential Cause of Ischemic Stroke Following Left Atrial Appendage Closure.

Unroofed coronary sinus is a rare type of atrial septal defect with a strong association with persistent left superior vena cava. We describe a case with unroofed coronary sinus and persistent left superior vena cava as a cause of recurrent embolic strokes following left atrial appendage closure for atrial fibrillation. (Level of Difficulty: Advanced.).

Racial and Ethnic Disparities in All-Cause and Cardiovascular Mortality Among Cancer Patients in the U.S.

Background: With improved cancer survival, death from noncancer etiologies, especially cardiovascular disease (CVD) mortality, has come more into focus. Little is known about the racial and ethnic disparities in all-cause and CVD mortality among U.S. cancer patients. Objectives: This study sought to investigate racial and ethnic disparities in all-cause and CVD mortality among adults with cancer in the United States. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database from years 2000 to 2018, all-cause and CVD mortality among patients ≥18 years of age at the time of initial malignancy diagnosis were compared by race and ethnicity groups. The 10 most prevalent cancers were included. Cox regression models were used to estimate adjusted HRs for all-cause and CVD mortality using Fine and Gray's method for competing risks, as applicable. Results: Among a total of 3,674,511 participants included in our study, 1,644,067 (44.7%) died, with 231,386 (6.3%) deaths as a result of CVD. After adjusting for sociodemographic and clinical characteristics, non-Hispanic (NH) Black individuals had both higher all-cause (HR: 1.13; 95% CI: 1.13-1.14) and CVD (HR: 1.25; 95% CI: 1.24-1.27) mortality, whereas Hispanic and NH Asian/Pacific Islander had lower mortality than NH White patients. Racial and ethnic disparities were more prominent among patients 18 to 54 years of age and those with localized cancer. Conclusions: Significant racial and ethnic differences exist in both all-cause and CVD mortality among U.S. cancer patients. Our findings underscore the vital roles of accessible cardiovascular interventions and strategies to identify high-risk cancer populations who may benefit most from early and long-term survivorship care.

A Comparison of In-Hospital Outcomes Between the Use of Impella and IABP in Acute Myocardial Infarction Cardiogenic Shock Undergoing Percutaneous Coronary Intervention.

BACKGROUND: The use of Impella ventricular support systems and intra-aortic balloon pump (IABP) in acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) has increased in recent years and expanded treatment options, although the comparative clinical outcomes and device safety remain unclear. METHODS: We used the Nationwide Inpatient Sample database (2012-2017) to identify adults who were admitted for AMI complicated by CS and received percutaneous coronary intervention (PCI). The study sample was divided into Impella and IABP groups. Patient characteristics, hospital characteristics, and comorbidities were balanced between groups using propensity-score matching. Regression analysis was utilized to study outcome differences between groups. RESULTS: We identified 51,150 patients, of whom 44,265 (86.54%) received IABP and 6885 (13.46%) received Impella. After propensity matching, compared with the Impella group (n = 1592), the IABP group (n = 8638) had lower rates of sepsis (6.44% vs 12.69%; P=.01), blood transfusion (8.92% vs 14.28%; P=.01), mortality (28.95% vs 49.59%; P<.01), and hospitalization costs ($49,420 vs $68,087; P<.001). The IABP group had similar rates of cardiac arrest (20.32% vs 22.22%; P=.32), in-hospital stroke (1.46% vs 1.59%; P=.37), and length-of-stay (8.56 days vs 8.64 days; P=.26) compared with the Impella group. CONCLUSION: In patients with CS complicating AMI who underwent PCI, Impella use compared with IABP was associated with higher mortality with no differences in in-hospital stroke and cardiac arrest rates, although study interpretation is limited by retrospective observational design and the potential for remaining confounders. Further prospective research is warranted to elucidate the optimal mechanical circulatory support device in these patients.

The impact of atrial fibrillation on outcomes in patients undergoing radical prostatectomy.

PURPOSE: To assess the role of atrial fibrillation (AF) on complicating inpatient outcomes of radical prostatectomy (RP). MATERIALS AND METHODS: We identified patients treated with RP during 2012-2014 within National Inpatient Sample (NIS) database. Length of stay, cost of hospitalization, and in-hospital complications were compared between patients with or without diagnosis of AF. Propensity score matching methods and multivariable regression analysis were used to adjust for potential confounders and a trend analysis was conducted. RESULTS: Patients with AF had a significantly longer hospital stay (coefficient 0.19, 95% CI 0.09-0.29, P < 0.001) and higher cost (coefficient 0.10, 95% CI 0.06-0.15, P < 0.001). Post-operative cardiac complications were significantly higher for patients with AF (OR 16.38, 95% CI 7.72-34.74, P < 0.001), while no differences were found in other complications between the two groups. Similar results were shown in propensity score matching methods. The cardiac complications after laparoscopic RP (OR: 37.71, 95% CI 1.85-768.73, P = 0.018) and open RP (OR: 16.78, 95% CI 1.41-199.51, P = 0.026) were significantly higher than robot-assisted RP (RARP) in patients with AF. The results of trend study indicated that postoperative cardiac complication rates showed a trend of decreasing year by year while the prevalence of AF was rising. CONCLUSIONS: Perioperative AF is associated with increased cardiac complications, longer hospital stay and higher cost in PCa patients undergoing RP. RARP may be a preferred choice for patients with AF. Attention should be paid to this special patient population. Reasonable pre-operative risk stratification and standardized management should be done to decrease perioperative complications.

Patients With Acute Ischemic Stroke Who Receive Brain Magnetic Resonance Imaging Demonstrate Favorable In-Hospital Outcomes.

Background Use of inpatient brain magnetic resonance imaging (MRI) in patients with acute ischemic stroke is highly institution dependent and has been associated with increased length and cost of hospital stay. We examined whether inpatient brain MRI in patients with acute ischemic stroke is associated with improved clinical outcomes to justify its resource requirements. Methods and Results The National Inpatient Sample database was queried retrospectively to find 94 003 patients who were admitted for acute ischemic stroke and then received inpatient brain MRI between 2012 and 2014. Multivariable regression analysis was performed with respect to a control group to assess for differences in the rates of inpatient mortality and complications, as well as the length and cost of hospital stay based on brain MRI use. Inpatient brain MRI was independently associated with lower rates of inpatient mortality (1.67% versus 3.09%; adjusted odds ratio [OR], 0.60; 95% CI, 0.53-0.68; P<0.001), gastrostomy (2.28% versus 2.89%; adjusted OR, 0.82; 95% CI, 0.73-0.93; P<0.001), and mechanical ventilation (1.97% versus 2.82%; adjusted OR, 0.68; 95% CI, 0.60-0.77; P<0.001). Brain MRI was independently associated with ≈0.32 days (8%) and $1131 (11%) increase in the total length (P<0.001) and cost (P<0.001) of hospital stay, respectively. Conclusions Inpatient brain MRI in patients with acute ischemic stroke is associated with substantial decrease in the rates of inpatient mortality and complications, at the expense of marginally increased length and cost of hospitalization.

Extramedullary Plasmacytoma Involving the Heart: A Case Report and Focused Literature Review.

Cardiac tumors are extremely rare. Here, we report an unusual case of cardiac plasmacytoma that occurred 11 years after complete remission of the original multiple myeloma (MM). The tumor primarily manifested as a solitary extramedullary plasmacytoma (SEP) with extensive infiltration into the heart and large vessels. There was no evidence of systemic involvement. The relapsing tumor assumed a unique immunophenotype from CD138+/CD38+/CD56- to CD138-/CD38+/CD56-. The patient responded to chemotherapy consisting of carfilzomib, cyclophosphamide, and dexamethasone. This case highlights the importance of multimodal imaging evaluation and tissue diagnosis for accurately characterizing this rare disorder.

Prevalence and Clinical Impact of Atrial Fibrillation in Patients with Pulmonary Embolism.

OBJECTIVES: Atrial fibrillation (AF) has been suggested as a cause for pulmonary embolism (PE). We aimed to explore the prevalence and clinical impact of AF in patients with PE. METHODS: Using the 2012-2014 National (Nationwide) Inpatient Sample database, we identified "adult patients with PE" as the principal discharge diagnosis. The identified admissions were stratified into two cohorts based on the presence or absence of AF. We used multivariable regression models to evaluate in-hospital mortality, length of stay, nonhome discharge, and in-hospital complications. RESULTS: The prevalence of AF among the 201,360 patients with PE was 11.62%. Patients with AF were more likely to have massive PE (odds ratio 1.59, 95% confidence interval 1.4-1.81, P < 0.001), with higher mortality (adjusted odds ratio 1.48, 95% confidence interval 1.27-1.71, P < 0.001) and a greater risk of mechanical ventilation, cardiac arrest, and nonhome discharges. The length of hospital stay in patients with PE and comorbid AF was significantly longer than those without (6.24 ± 0.10 vs 4.79 ± 0.03 days). CONCLUSIONS: AF is associated with a higher rate of massive PE, higher in-hospital mortality, a longer length of hospital stay, and a higher incidence of in-hospital complications and nonhome discharge.

Safety of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients with Thrombocytopenia.

BACKGROUND: Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) is an effective treatment of acute ischemic stroke (AIS). The safety of intravenous rtPA in patients with thrombocytopenia is unclear. This study sought to evaluate the impact of thrombocytopenia on in-hospital outcomes in patients with AIS who received intravenous thrombolysis. METHODS: This was a retrospective study using the 2012-2014 National Inpatient Sample (20% stratified sample of US hospitals). The study identified adult patients admitted with AIS who received intravenous rtPA during hospitalization. The identified admissions were stratified into 2 cohorts based on the presence or absence of thrombocytopenia. Multilevel, multivariate regression analysis and propensity matching were performed to evaluate in-hospital mortality, length of stay, and in-hospital complications. RESULTS: Of 101,527 patients admitted for AIS and received intravenous rtPA from 2012 to 2014, 3,520 (3.47%) had thrombocytopenia. In-hospital mortality was 10.8 vs. 6.9% in patients with and without thrombocytopenia in original data, p < 0.001. In-hospital length of stay was significantly higher in the thrombocytopenia group (5.9 vs. 8.2 days, p < 0.001). The differences were significant in both the multivariate regression model and the propensity score matching model. Patients with thrombocytopenia also had a statistically higher incidence of intracranial hemorrhage, postprocedural bleeding, blood transfusion, tracheotomy, and mechanical ventilation. CONCLUSION: Thrombocytopenia is associated with higher in-hospital mortality, longer length of stay, a higher incidence of intracranial hemorrhage, postprocedural bleeding, and mechanical ventilation in stroke patients who received intravenous rtPA.

BK Virus-associated Nephropathy in a Patient with T Cell Leukemia/Lymphoma Syndrome.

BK virus-associated nephropathy develops in renal transplant patients with the main manifestation of tubulointerstitial nephritis or ureteral stenosis. Nephrotic syndrome is a rare manifestation of BK virus-associated nephropathy. Here we report a case of a 69-year-old female presenting with nephrotic and nephritic syndrome related to BK virus infection. Kidney biopsy revealed severe acute tubular injury, collapsing glomerulopathy, and focal microangiopathic changes. Four weeks of leflunomide and intravenous immunoglobulin (IVIG) resulted in the recovery of kidney function and improvement of proteinuria.

Impact of Atrial Fibrillation on In-Hospital Outcomes in Patients With Diabetic Ketoacidosis.

BACKGROUND: Diabetic ketoacidosis entails a huge health burden among patients with diabetes. Atrial fibrillation (AF) is the most common type of heart arrhythmia. This study aimed to evaluate the impact of AF on clinical outcomes in patients with diabetic ketoacidosis. METHODS: Using the 2012-2014 National Inpatient Sample database, we identified adult patients hospitalized with diabetic ketoacidosis as the principal discharge diagnosis. The identified admissions were stratified into 2 cohorts based on the AF presence. We used multivariable regression models and propensity score matching models to evaluate in-hospital mortality, length of stay, comorbidities, and in-hospital complications. RESULTS: The study included 478,890 adult patients who were admitted for diabetic ketoacidosis in the year 2012-2014. A total of 467,780 (97.68%) had no AF and 11,125 (2.32%) had AF. In both multivariable regression models and propensity score matching models, compared with nonatrial fibrillation group, the AF group had higher in-hospital mortality rates (2.36 [1.69-3.32], P < 0.001) and longer length of stay (5.5 versus 3.3 days, P < 0.001). AF was also associated with a significantly higher incidence of complications including septic shock, pulmonary failure, mechanical ventilation, neurological failure, cerebral edema, acute kidney injury, acute hematologic failure, and cardiac arrest. CONCLUSIONS: Among patients who were hospitalized for diabetic ketoacidosis, comorbid AF led to increasing in-hospital mortality rates and longer length of stay. A potential explanation was that AF increased the risk of in-hospital complications including respiratory failure with a more frequent requirement for mechanical ventilation, cardiac arrest, and metabolic encephalopathy.

A Rare Case of Irinotecan-induced Interstitial Pulmonary Disease and Diffuse Alveolar Hemorrhage in a Patient with Pancreatic Cancer.

Irinotecan is a cytotoxic medication used to treat various cancers. Diffuse alveolar hemorrhage (DAH) and interstitial pulmonary disease (IPD) are both serious and life-threatening complications, which are rarely reported to be associated with irinotecan. In our case, however, a pancreatic cancer patient developed both DAH and IPD after administration of irinotecan with fluorouracil (5FU).

Association of sirolimus with pericardial effusion in renal transplant patient and discussion of potential mechanism.

Sirolimus is an important immunosuppressive drug in renal transplantation but contains numerous side effects. In this study, we describe a case of renal transplant recipient treated with sirolimus who developed pericardial effusion associated with interstitial pneumonia. An extensive search for alternative causes were all negative, and all symptoms disappeared after sirolimus interruption. Therefore, this case demonstrates that sirolimus can cause pericardial effusion possibly through a proinflammatory mechanism.

Associations of EDNRA and EDNRB Polymorphisms with Intracerebral Hemorrhage.

OBJECTIVE: The most potent vasoconstrictor, endothelin-1 and its receptors, endothelin receptor A (EDNRA) and endothelin receptor B (EDNRB) are involved in hypertension. Hypertension is a major risk factor of intracerebral hemorrhage (ICH). Recent studies have demonstrated increased plasma endothelin-1 level in ICH patients and relationships between EDNRA and EDNRB genetic variants and ischemic stroke. The aim of the current study was to investigate whether EDNRA and EDNRB polymorphisms are associated with ICH by interacting with blood pressure levels. METHODS: Five EDNRA and EDNRB polymorphisms were genotyped in this case-control study. RESULTS: We identified that EDNRA rs5333 T allele might be a protective factor of ICH (adjusted odds ratio [OR] = 0.638, 95% CI: 0.417-0.977, P = 0.038), while EDNRB rs5351 A allele could be a risk factor of ICH (adjusted OR = 1.476, 95% CI: 1.042-2.089, P = 0.028). Moreover, we only found that the GG genotype of EDNRA rs5335 had higher diastolic blood pressure than the GC + CC genotypes in ICH patients (91.69 ± 18.77 vs. 84.71 ± 21.48, P = 0.004). CONCLUSIONS: These findings support the important role of EDNRA and EDNRB polymorphisms in ICH, and suggest that they do not interact with blood pressure levels on altering ICH risk.

Targeting the BDNF/TrkB pathway for the treatment of tumors.

Neurotrophins are a family of growth factors that regulate neural survival, development, function and plasticity in the central and the peripheral nervous system. There are four neurotrophins: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and NT-4. Among them, BDNF is the most studied due to its high expression in the brain. Over the past two decades, BDNF and its receptor tropomyosin receptor kinase B (TrkB) have been reported to be upregulated in a wide range of tumors. This activated signal stimulates a series of downstream pathways, including phosphoinositide 3-kinase/protein kinase B, Ras-Raf-mitogen activated protein kinase kinase-extracellular signal-regulated kinases, the phospholipase-C-γ pathway and the transactivation of epidermal growth factor receptor. Activation of these signaling pathways induces oncogenic effects by increasing cancer cell growth, proliferation, survival, migration and epithelial to mesenchymal transition, and decreasing anoikis, relapse and chemotherapeutic sensitivity. The present review summarizes recent findings to discuss the role of BDNF in tumors, the underlying molecular mechanism, targeting Trk receptors for treatment of cancers and its potential risk.

Reversible Acute Kidney Injury Associated with Sildenafil Overdose.

Sildenafil is a phosphodiesterase type 5 inhibitor that is approved to treat erectile dysfunction and pulmonary hypertension. Generally, sildenafil is safe, with mild side effects. Here, we report a case of acute kidney injury caused by a sildenafil overdose. A 67-year-old man took 400 mg of sildenafil for erectile dysfunction. The patient was found to have acute kidney injury from acute tubular necrosis during hospitalization with a peak serum creatinine of 5.07 mg/dL though his renal function recovered with supportive care.

A Survival Case of Super-refractory Status Epilepticus due to Glutamic Acid Decarboxylase Antibodies-associated Limbic Encephalitis.

Limbic encephalitis (LE) is a neurological syndrome that mainly affects mesial temporal lobes. It may present in association with cancer or infection. Limbic encephalitis associated with glutamic acid decarboxylase antibodies (anti-GAD) is rare. Here, we report a case of anti-GAD limbic encephalitis to heighten the awareness of this rare cause of autoimmune encephalitis. Anti-GAD-associated epilepsy is often poorly responsive to seizure medications. Treatment is challenging. Early initiation of immunotherapy is important.

Association of protein Z and factor VII gene polymorphisms with risk of cerebral hemorrhage: a case-control and a family-based association study in a Chinese Han population.

Protein Z (PZ) and factor (F) VII are two important factors in the clotting pathway which have similar structure, linked function and nearby gene sites. The aims of this study were to investigate whether the common variants of PZ and FVII genes are associated with the risk of cerebral hemorrhage (CH) and to explore the combined effects of PZ and FVII polymorphisms for CH risk. We performed genotyping analysis for two single-nucleotide polymorphisms (SNPs) of FVII (rs510317 and rs6046) and three SNPs of PZ (rs2273971, rs3024718 and rs3024731) both in a population-based case-control study and in a family-based association study. Case-control analysis found no evidence of significant association. But family-based association study revealed that the G allele of PZ rs2273971, and three haplotypes carrying the 'G' allele of PZ rs2273971: haplotype GA, CG and CGA of PZ and FVII genes, all had a significant effect on CH susceptibility (Z = 1.882, P = 0.049; Z = 1.922, P = 0.044; Z = 1.826, P = 0.047; Z = 1.977, P = 0.048, respectively). While, the A allele of PZ rs2273971, and four haplotypes carrying or crossing the 'A' allele of PZ rs2273971: haplotypes CA, ACAA, ACAT and ACAAT of PZ and FVII genes, may confer protection against CH (Z= -1.882, P = 0.049; Z= -2.000, P = 0.045; Z= -2.319, P = 0.020; Z= -2.002, P = 0.045; Z= -2.015, P = 0.043, respectively). This is a first family-based association study providing genetic evidences that PZ and FVII genes, especially PZ rs2273971 are involved in the development of CH in Han-Chinese families.

Association between ECE1 gene polymorphisms and risk of intracerebral haemorrhage.

OBJECTIVE: To determine whether endothelin converting enzyme-1 (ECE1) gene polymorphisms contribute to susceptibility to intracerebral haemorrhage (ICH) by influencing blood pressure. METHODS: This case-control study enrolled patients with ICH and healthy control subjects from a Southern Han Chinese population. The ECE1 gene polymorphisms rs212528 and rs213045 were genotyped. The association between the genotypes and the risk of ICH was assessed. The effects of these two ECE1 gene polymorphisms on blood pressure were also analysed. RESULTS: A total of 389 patients with ICH and 404 healthy control subjects participated in the study. There was no significant association between the ECE1 rs212528 and rs213045 polymorphisms and ICH even after adjusting for different confounding variables. In patients with ICH, the systolic blood pressure of patients with the rs212528 AA genotype was significantly lower than that of patients with the AG/GG genotypes. CONCLUSIONS: These results indicated that the ECE1 rs212528 and rs213045 polymorphisms had no major role to play in the genetic susceptibility to ICH, although rs212528 might influence blood pressure in patients with ICH.

Combination of early constraint-induced movement therapy and fasudil enhances motor recovery after ischemic stroke in rats.

PURPOSE: Constraint-induced movement therapy (CIMT) is a promising technique for the recovery of upper extremity movement in chronic stroke patients. However, the effectiveness of its use in acute ischemia has not been confirmed. Myelin-associated inhibitors, which have upregulated functions in tissues affected by acute focal infarction, limit axonal regeneration via activation of the Rho-Rho-associated protein kinase (ROCK) pathway. The present study examined whether early CIMT combined with the ROCK inhibitor fasudil promotes motor recovery after acute ischemic stroke. MATERIALS AND METHODS: Rats were trained to perform the skilled-reach test and then subjected to middle cerebral artery occlusion (MCAO), producing a stroke affecting the preferred forelimb. Rats were assigned to one of four groups (N = 6/group): (nontreated) Control, CIMT, Fasudil, or CIMT+fasudil. CIMT and/or intraperitoneal infusion of fasudil were initiated 1 day postMCAO. Skilled reach and foot fault test data were collected once before and repeatedly over 4 weeks after the operation. Infarct volumes were calculated. RESULTS: All four groups showed similar forelimb impairment before treatment. The performance of CIMT alone group was similar to that of controls on both tests. Fasudil alone facilitated recovery in the foot-fault test, but not in the skilled-reach test. Rats in the CIMT+fasudil group demonstrated enhanced recovery in both tests, including better performance over time than the Fasudil group on the foot-fault test. Infarct size did not differ significantly between the groups. CONCLUSIONS: Early CIMT promotes motor recovery after acute ischemic stroke when it is administered with fasudil pharmacotherapy, but not without it.

807C/T polymorphism of platelet glycoprotein Ia gene is associated with cerebral hemorrhage in a Chinese population.

Platelet glycoprotein (GP) mediated the role of platelet in coagulation. Platelet GP Ia 807C/T is the only GP polymorphism associated with the expression levels of GP Ia/IIa (the platelet collagen receptor). Recently, the GP Ia 807C/T polymorphism has been reported to have no association with cerebral hemorrhage (CH) in two studies pertained to Caucasian populations. The purpose of this study is to evaluate the association between platelet GP Ia 807C/T polymorphism and CH in a Han Chinese population. We performed genotype analysis for platelet GP Ia 807C/T polymorphism in a case-control study involving 195 patients with CH and 116 age- and sex-matched controls. In contrast to previous reports, we found that the frequencies of GP Ia 807C/T T allele, CT and TT genotype were much higher in CH patients than in controls (33.9% vs. 22.8%, p = 0.004; 45.5% and 11.1% vs. 40.4% and 2.6%, p = 0.022). Logistic regression analysis revealed that the presence of GP Ia 807C/T C allele and CC genotype were both associated with a decreased risk of CH compared with T allele, CT and TT genotypes, respectively (adjusted odds ratio [OR] = 0.565, 95% CI: 0.384-0.887, p = 0.005; adjusted OR = 0.172, 95% CI: 0.043-0.639, p = 0.009; adjusted OR = 0.254, 95% CI: 0.085-0.961, p = 0.041, respectively). These findings indicated that platelet GP Ia 807C/T polymorphism could be a protective factor of CH in the Chinese population.