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.

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.

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.

TIMP-1 polymorphisms in a Chinese Han population with intracerebral hemorrhage.

Remodeling of extracellular matrix (ECM) and breakdown of blood-brain barrier (BBB) are crucial events in the pathogenesis of intracerebral hemorrhage (ICH). Matrix metalloproteinases (MMPs), particularly MMP-9 and MMP-2, are the most important degrading enzymes in the ECM and BBB. These proteolytic effects are controlled predominantly by tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 is the main endogenous inhibitor of MMP-9. Two polymorphisms in the TIMP-1 gene (rs4898 and rs2070584) were selected through a literature review and successfully genotyped in a study sample of 410 ICH patients and 305 controls. Differences in genotype and allele frequencies of identified polymorphisms were determined. Furthermore, the serum levels of TIMP-1 were measured in a subgroup of 96 ICH patients on days 1 after ICH onset and 76 controls. Analyses showed that C allele of rs2070584 was significantly associated with the development of ICH in male subjects (p = 0.037, OR = 1.535, 95%CI 1.025-2.300). Multiple logistic regression analysis under three genetic models demonstrated both rs4898 and rs2070584 were not risk factors for ICH in female subjects. Furthermore, serum levels of TIMP-1 were significantly higher in ICH patients than those in normal controls. However, the serum levels of TIMP-1 showed a nonsignificant decrease, depending on the alleles and genotypes of rs2070584 both in male and female cases. In conclusion, this is the first association study of the TIMP-1 gene variants with ICH. Our data suggest that C allele of rs2070584 is a risk factor for ICH development in the Chinese male population. However, the precise function of this variant needs further investigation.

[Association of ApoAI gene rs12721026 polymorphism with cerebral hemorrhage in Changsha Han population and its effect on plasma lipid levels].

OBJECTIVE: To explore the association between apolipoprotein AI (ApoAI) gene rs12721026 polymorphism and cerebral hemorrhage (CH) in Changsha Han population, and to evaluate the effect of rs12721026 polymorphism on plasma lipid levels. METHODS: A total of 273 patients with CH and 140 healthy controls were collected. The rs12721026 polymorphism of ApoAI was analyzed by SNaPshot genotyping analysis and DNA sequencing. The total cholesterol (TG), triglyceride (TC), HDL-C and LDL-C were examined by oxidase method. RESULTS: There was no significant difference in the genotype and allele frequencies of rs12721026 polymorphism between the CH group and the control group (P>0.05). Both in the CH group and in the control group, the level of HDL-C of the TT gene type of rs12721026 was significantly higher than that of the GT/GG gene type (P<0.05). There was no significant difference in the levels of TG, TC and LDL-C among different subgroups of gene types. CONCLUSION: There may be no association between apoAI gene rs12721026 polymorphism with CH in Changsha Han population, which may still influence the HDL-C levels.

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.

Genetics of intracerebral hemorrhage: Insights from candidate gene approaches.

Intracerebral hemorrhage (ICH) is a heterogeneous disease with genetic factors playing an important role. Association studies on a wide range of candidate pathways suggest a weak but significant effect for several alleles with ICH risk. Among the most widely investigated genes are those involved in the renin-angiotensin-aldosterone system (e.g., angiotensin-converting enzyme), coagulation pathway (e.g., Factor XIII, Factor VII, platelet-activating factor acetylhydrolase, Factor V Leiden, and beta1-tubulin), lipid metabolism (e.g., apolipoproteins (Apo)E, Apo(a), ApoH), homocysteine metabolism (e.g., methylenetetrahydrofolate reductase), inflammation (e.g., interleukin-6 and tumor necrosis-alpha) and other candidate pathways. To identify the robustness of the above associations with ICH, a search of Pubmed (1988 through December 2011) was performed, with searches limited to English-language studies conducted among adult human subjects. This article presents a review of the examined literature on the genetics of ICH.

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.

[Association of single nucleotide polymorphisms of kallikrein 1 gene with cerebral hemorrhage in Changsha Han Chinese].

OBJECTIVE: To explore the association between single nucleotide polymorphisms (SNPs) of KLK1 gene and cerebral hemorrhage in Changsha Han Chinese. METHODS: Two hundred and seventy-three cerebral hemorrhage (CH) patients and 140 healthy controls were collected. The SNPs of rs5516 and rs5517 loci of KLK1 gene were analyzed by SNaPshot methods and direct sequencing. RESULTS: (1)Genotype and allele frequencies in rs5516 locus had no difference between the CH patients and controls (P> 0.05). However, the A allele frequency of the rs5517 locus in CH patients was higher than that in the control group (0.419, 0.321 respectively, P< 0.05). (2)In the control group,the levels of diastolic blood pressure (DBP) of the GA and AA genotype carriers of the rs5517 locus were significantly higher than those of the GG genotype (P< 0.05), while the levels of blood pressure were not significantly different among different genotypes of the rs5516 polymorphism in both CH patients and the control group(P> 0.05). CONCLUSION: Author's preliminary results suggested that the rs5517 polymorphism was associated with cerebral hemorrhage, while the rs5516 polymorphism was not in Changsha Han Chinese.

[Relationship between T704C polymorphism of angiotensinogen gene and cerebral hemorrhage in Han people in Changsha].

OBJECTIVE: To investigate the relationship between T704C polymorphism of angiotensinogen (AGT) gene and cerebral hemorrhage and its impact on the levels of blood pressure in Han people in Changsha. METHODS: A total of 273 cerebral hemorrhage patients (the cerebral hemorrhage group) and 140 normal controls (the control group) were collected from Jan. 2005 to Jan. 2009. DNA was extracted from their peripheral blood samples. The polymorphism of AGT-T704C was analyzed by SNaPshot and direct DNA sequencing. The possible risk factors of cerebral hemorrhage were investigated at the same time. Each group was divided into 2 subgroups (a high blood pressure subgroup and a normal blood pressure subgroup) according to whether they had essential hypertension. Logistic regression analysis was used to detect the relationship between cerebral hemorrhage and all its possible risk factors and AGT-T704C polymorphism. RESULTS: The drinking history, coronary heart disease history, essential hypertension history, and blood levels of lipids were shown significant difference between the cerebral hemorrhage group and the control group (P<0.05). Logistic regression analysis showed that hypertension history, systolic blood pressure level, and high density lipoprotein cholesterol level were independent risk factors for cerebral hemorrhage in Han people in Changsha. The genotype C/C, C/T, and T/T frequencies of AGT-T704C polymorphism in the cerebral hemorrhage group and the control group were 0.692, 0.279, 0.029 and 0.629, 0.350, 0.021, respectively. The allele C and T frequencies of AGT-T704C polymorphism in the 2 groups were 0.832, 0.168 and 0.804, 0.196, respectively. The frequencies of all the genotypes and alleles had no significant difference between the 2 groups and their subgroups (P>0.05). CONCLUSION: The polymorphism of AGT-T704C may not be associated with cerebral hemorrhage and not related to the levels of lipids and blood pressure in Han people in Changsha. Hypertension history, systolic blood pressure level, and high density lipoprotein cholesterol level are the main risk factors of cerebral hemorrhage in Han people in Changsha.

[Association between polymorphism of rs3212855 and rs5515 of KLK1 gene with cerebral hemorrhage in Changsha Han population].

OBJECTIVE: To explore the association between single nucleotide polymorphism (SNPs) of KLK1 gene and cerebral hemorrhage in Changsha Han population. METHODS: We enrolled 273 patients with cerebral hemorrhage and 140 normal people. The SNPs (including rs3212855 and rs5515) of KLK1 gene were analyzed by Snapshot method and direct sequencing. RESULTS: We found rs5515 was not a polymorphic site in Changsha Han population. Genotype and allele frequency in rs3212855 were not different between patients with cerebral hemorrhage and the controls (P>0.05). The blood pressure level was not different between the genotype subgroups. CONCLUSION: Neither rs5515 nor rs3212855 is associated with cerebral hemorrhage.

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.

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.

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.

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.

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).

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.