Valve in valve transcatheter aortic valve implantation (ViV-TAVI) versus redo-Surgical aortic valve replacement (redo-SAVR): A systematic review and meta-analysis.

BACKGROUND: Bioprosthetic (BP) valves have been increasingly used for aortic valve replacement over the last decade. Due to their limited durability, patients presenting with failed BP valves are rising. Valve in Valve - Transcatheter Aortic Valve Implantation (ViV-TAVI) emerged as an alternative to the gold standard redo-Surgical Aortic Valve Replacement (redo-SAVR). However, the utility of ViV-TAVI is poorly understood. METHODS: A systematic electronic search of the scientific literature was done in PubMed, EMBASE, SCOPUS, Google Scholar, and ClinicalTrials.gov. Only studies which compared the safety and efficacy of ViV-TAVI and redo-SAVR head to head in failed BP valves were included. RESULTS: Six observational studies were eligible and included 594 patients, of whom 255 underwent ViV- TAVI and 339 underwent redo-SAVR. There was no significant difference between ViV-TAVI and redo- SAVR for procedural, 30 day and 1 year mortality rates. ViV-TAVI was associated with lower risk of permanent pacemaker implantation (PPI) (OR: 0.43, CI: 0.21-0.89; P = 0.02) and a trend toward increased risk of paravalvular leak (PVL) (OR: 5.45, CI: 0.94-31.58; P = 0.06). There was no significant difference for stroke, major bleeding, vascular complications and postprocedural aortic valvular gradients more than 20 mm-hg. CONCLUSION: Our results reiterate the safety and feasibility of ViV-TAVI for failed aortic BP valves in patients deemed to be at high risk for surgery. VIV-TAVI was associated with lower risk of permanent pacemaker implantation with a trend toward increased risk of paravalvular leak.

Alpha3, a transposable element that promotes host sexual reproduction.

Theoretical models predict that selfish DNA elements require host sex to persist in a population. Therefore, a transposon that induces sex would strongly favor its own spread. We demonstrate that a protein homologous to transposases, called alpha3, was essential for mating type switch in Kluyveromyces lactis. Mutational analysis showed that amino acids conserved among transposases were essential for its function. During switching, sequences in the 5' and 3' flanking regions of the alpha3 gene were joined, forming a DNA circle, showing that alpha3 mobilized from the genome. The sequences encompassing the alpha3 gene circle junctions in the mating type alpha (MATalpha) locus were essential for switching from MATalpha to MATa, suggesting that alpha3 mobilization was a coupled event. Switching also required a DNA-binding protein, Mating type switch 1 (Mts1), whose binding sites in MATalpha were important. Expression of Mts1 was repressed in MATa/MATalpha diploids and by nutrients, limiting switching to haploids in low-nutrient conditions. A hairpin-capped DNA double-strand break (DSB) was observed in the MATa locus in mre11 mutant strains, indicating that mating type switch was induced by MAT-specific DSBs. This study provides empirical evidence for selfish DNA promoting host sexual reproduction by mediating mating type switch.

Anatomic and clinical predictors of reintervention after subclavian artery stenting.

OBJECTIVE: This study was conducted to determine long-term predictors of target lesion reintervention (TLR) after subclavian artery stenting (SAS). METHODS: This was a single-center retrospective review of patients with symptomatic atherosclerotic subclavian artery disease who underwent SAS between January 1999 and December 2013. Repeat intervention was only performed in patients with recurrent symptoms and ≥70% in-stent restenosis (ISR). TLR was defined as need for a repeat percutaneous intervention involving a previously stented area. Freedom from events (ISR and TLR) was analyzed using Kaplan-Meier curves. Cox regression analysis was used to determine the significant predictors of TLR and ISR. RESULTS: Index procedures were performed on 139 arteries in 138 patients (69.6% female). Patients were an average age of 64.5 years, with major comorbidities of hypertension (80.4%), hyperlipidemia (72.5%), and tobacco use (60.1%). Also performed during the study period were 24 TLR procedures, resulting 166 SAS interventions attempted for patients with subclavian atherosclerotic disease during a 15-year span. Of 166 procedures, 163 (98.2%) were treated successfully. Stents were placed in all but two index arteries. The main indications for SAS were subclavian steal syndrome (48.9%), arm claudication (21.6%), and coronary steal syndrome (28.8%). The average preprocedure stenosis was 87.2% ± 11.2%. For index procedures (139 arteries), duplex follow-up was available for 134 arteries (96.4%), with an overall ISR rate of 18.7% (25 of 134). Primary patency for the index procedures was 84.7% at 10 years. The overall TLR rate for the index procedures was 12.7% (17 cases). Seven patients required more than one secondary procedure. For all cases, the freedom from ISR was 91%, 77%, and 68% at 1, 5, and 10 years, respectively, and freedom from TLR was 94%, 85%, and 82% at 1, 5, and 10 years, respectively. Multivariate analysis showed the significant predictors of ISR were smoking/chronic obstructive pulmonary disease (hazard ratio [HR], 3.2; P = .001), age by decade (HR, 0.5; P < .001), discharged with statin therapy (HR, 0.3; P = .001), vessel diameter ≤7 mm (HR, 2.3; P = .028), and right-sided intervention (HR, 0.3; P = .040). The sole significant predictor of TLR was age by decade (HR, 0.6; P = .008). CONCLUSIONS: SAS has a high primary success and durability with satisfactory outcomes well beyond 10 years. ISR was more likely to develop in patients who were smokers with chronic obstructive disease or had a baseline vessel size of ≤7 mm. Younger age could be an independent risk factor for secondary intervention.

Ixr1 is required for the expression of the ribonucleotide reductase Rnr1 and maintenance of dNTP pools.

The Saccharomyces cerevisiae Dun1 protein kinase is a downstream target of the conserved Mec1-Rad53 checkpoint pathway. Dun1 regulates dNTP pools during an unperturbed cell cycle and after DNA damage by modulating the activity of ribonucleotide reductase (RNR) by multiple mechanisms, including phosphorylation of RNR inhibitors Sml1 and Dif1. Dun1 also activates DNA-damage-inducible genes by inhibiting the Crt1 transcriptional repressor. Among the genes repressed by Crt1 are three out of four RNR genes: RNR2, RNR3, and RNR4. The fourth RNR gene, RNR1, is also DNA damage-inducible, but is not controlled by Crt1. It has been shown that the deletion of DUN1 is synthetic lethal with the deletion of IXR1, encoding an HMG-box-containing DNA binding protein, but the reason for this lethality is not known. Here we demonstrate that the dun1 ixr1 synthetic lethality is caused by an inadequate RNR activity. The deletion of IXR1 results in decreased dNTP levels due to a reduced RNR1 expression. The ixr1 single mutants compensate for the reduced Rnr1 levels by the Mec1-Rad53-Dun1-Crt1-dependent elevation of Rnr3 and Rnr4 levels and downregulation of Sml1 levels, explaining why DUN1 is indispensible in ixr1 mutants. The dun1 ixr1 synthetic lethality is rescued by an artificial elevation of the dNTP pools. We show that Ixr1 is phosphorylated at several residues and that Ser366, a residue important for the interaction of HMG boxes with DNA, is required for Ixr1 phosphorylation. Ixr1 interacts with DNA at multiple loci, including the RNR1 promoter. Ixr1 levels are decreased in Rad53-deficient cells, which are known to have excessive histone levels. A reduction of the histone gene dosage in the rad53 mutant restores Ixr1 levels. Our results demonstrate that Ixr1, but not Dun1, is required for the proper RNR1 expression both during an unperturbed cell cycle and after DNA damage.

Repeat Revascularization Post Coronary Artery Bypass Grafting: Comparing Minimally Invasive and Traditional Sternotomy Techniques in 1468 Cases.

BACKGROUND: Traditional open sternotomy coronary artery bypass grafting (CABG) utilizes highly invasive techniques that lead to several serious complications. In response, minimally invasive cardiac surgery CABG (MICS-CABG) was developed. MICS-CABG is safe, reproducible, and with fewer complications, while allowing for better postoperative recovery periods. There is a paucity of data exploring rates of repeat revascularization in patients post MICS-CABG compared to post traditional sternotomy CABG. METHODS: This was a retrospective billing database review examining 1468 CABG patients at a large university medical center from January 2005 to December 2017. The primary objective was to compare the rate of repeat revascularization events between MICS-CABG and traditional open sternotomy CABG over an eight-year follow-up period. RESULTS: Our study population consisted of 1468 patients, of whom 513 had MICS-CABG and 955 had traditional CABG. The number of patients undergoing repeat revascularization within the eight-year surveillance was 99 for MICS-CABG and 75 for traditional CABG. The Kaplan-Meier survival probability estimates for eight years were 0.86 for MICS-CABG and 0.91 for traditional CABG. The mean time until a repeat revascularization event was 84.1 months for MICS-CABG and 88.5 months for traditional CABG. CONCLUSIONS:  Traditional CABG was found to have a statistically significantly longer time to repeat revascularization than MICS-CABG. Despite the technical challenges associated with MICS-CABG, the time to repeat revascularization was different by only about four months, which may not hold large clinical significance. This suggests that MICS-CABG may have a role to play due to previous findings showing a reduction in complications while allowing for better postoperative recovery periods.

Successful use of the impella ventricular assist device for management of reverse Takotsubo Cardiomyopathy in the setting of acute intracranial hemorrhage.

Reverse Takotsubo Cardiomyopathy (rTTC) is a rare variant of Takotsubo Cardiomyopathy (TTC) that is characterized by hypokinesis of the base and sparing of the mid to apical wall of the left ventricle best seen on echocardiogram. Intracranial hemorrhage (ICH) has been identified as a risk factor rTTC. Nearly around 10% of the patients with TTC develop cardiogenic shock. We hereby report the successful use of the Impella Ventricular Assist Device (Impella CP®) for management of rTTC in the setting of acute ICH. Our patient is a young female who presented with loss of consciousness after an acute headache and imaging studies revealed left posterior cerebral artery aneurysm with intraventricular hemorrhage. Subsequently the patient developed hypoxia, severe hypotension and cardiac arrest. After resuscitation, an echocardiogram showed that the patient had rTTC and a cardiac angiogram showed patent coronary arteries. The Impella CP® was successfully inserted followed by immediate cerebral angiography and aneurysmal coiling. Systemic anticoagulation was started during coiling. In the next three days, the patient's left ventricular function recovered, and she was discharged home. Up to our knowledge, this is the first case report to mark the successful placement of the Impella CP® with delayed initial anticoagulation for management of rTTC. Our patient was challenging as there are no current guidelines in the management of cardiogenic shock secondary to rTTC in the setting of acute ICH.

Long-Term Progression-Free Survival in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer Patient Treated With Crizotinib.

Lung cancer is the second most common cancer worldwide. Non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) gene rearrangements constitutes 3-5%. Crizotinib was approved for the first-line therapy of advanced ALK-positive NSCLC patients. We present a female patient with advanced ALK-positive NSCLC who was kept on crizotinib as first-line therapy and showed progression-free survival (PFS) of 48 months despite the data suggesting that the majority of patients on crizotinib show relapse within 1 year. Further studies should focus on the molecular and biological factors and the possible effect of the long-term use of this drug.

Cdc25B cooperates with Cdc25A to induce mitosis but has a unique role in activating cyclin B1-Cdk1 at the centrosome.

Cdc25 phosphatases are essential for the activation of mitotic cyclin-Cdks, but the precise roles of the three mammalian isoforms (A, B, and C) are unclear. Using RNA interference to reduce the expression of each Cdc25 isoform in HeLa and HEK293 cells, we observed that Cdc25A and -B are both needed for mitotic entry, whereas Cdc25C alone cannot induce mitosis. We found that the G2 delay caused by small interfering RNA to Cdc25A or -B was accompanied by reduced activities of both cyclin B1-Cdk1 and cyclin A-Cdk2 complexes and a delayed accumulation of cyclin B1 protein. Further, three-dimensional time-lapse microscopy and quantification of Cdk1 phosphorylation versus cyclin B1 levels in individual cells revealed that Cdc25A and -B exert specific functions in the initiation of mitosis: Cdc25A may play a role in chromatin condensation, whereas Cdc25B specifically activates cyclin B1-Cdk1 on centrosomes.

Complete atrioventricular block caused by pulmonary embolism: A case report and review of literature.

INTRODUCTION: Acute electrocardiogram abnormalities are common in patients afflicted with pulmonary embolism (PE). Rarely, a patient with acute pulmonary embolism and electrocardiogram changes may have an underlying conduction abnormality that complicates their course. CASE PRESENTATION: We describe a patient with known history of left bundle branch block who presented with acute PE and developed a right bundle branch block, which devolved into complete third degree heart block without ventricular escape rhythm and led to concomitant hemodynamic compromise. DISCUSSION: Given the rarity of this clinical scenario, we call for clinicians to be aware of PE-associated conduction pathology as well as the possibility that malignant cardiac conduction blocks may occur in the setting of PE particularly if the patient is known to have underlying conduction system disease. We emphasize the importance of continuous telemetry monitoring in patients presenting with PE as these types of arrhythmic complications and hemodynamic decompensation has been observed.

Coronary Artery Diffuse Aneurysmal Dilation in an Acute Myocardial Infarction Patient.

Coronary artery aneurysm (CAA) is a rare disease that is associated with dangerous dormant complications. It is associated with atherosclerotic heart disease in half of the cases during a coronary angiogram. Currently, there are no guidelines for the management of such cases. We present a case of acute ST-segment elevation myocardial infarction in a male patient who was found to have diffuse aneurysmal dilation of the coronary arteries along with 100% occlusion of the right coronary artery. The complexity of the lesions caused him not to be a candidate for either percutaneous or surgical intervention. This raises an important question regarding treatment options in such a rare case.

Reverse Takotsubo Cardiomyopathy Following Exploratory Laparotomy.

Reverse takotsubo cardiomyopathy is an uncommon cardiomyopathy characterized by reversible regional wall motion abnormalities in the basilar segment of the left ventricle. This happens in the absence of any coronary artery pathology. Although it shares some pathogenic mechanisms with its more common variant, takotsubo cardiomyopathy, differences exist in terms of echocardiographic features, demographics, clinical manifestations, laboratory features, and prognosis. Cases of postoperative reverse takotsubo cardiomyopathy are less described in the literature. Herein, we report a case of reverse takotsubo cardiomyopathy in a 44-year-old woman occurring after exploratory laparotomy.

Long-term Outcome after Percutaneous Coronary Intervention Compared with Minimally Invasive Coronary Artery Bypass Surgery in the Elderly.

BACKGROUND: Elderly patients with unstable coronary artery disease (CAD) have better outcomes with coronary revascularization than conservative treatment. With the improvement in percutaneous coronary intervention (PCI) techniques using drug eluting-stents, this became an attractive option in elderly. Minimally invasive coronary artery bypass grafting (MICS-CABG) is a safe and effective alternative to conventional CABG. We aimed to explore the long-term outcomes after PCI vs MICS-CABG in ≥75 year-old patients with severe CAD. METHODS: A total of 1454 elderly patients (≥75 year-old patients) underwent coronary artery revascularization between January 2005 and December 2009. Patients were selected in the study if they have one of the Class-I indications for CABG. Groups were divided according to the type of procedure, PCI or MICS-CABG, and 5 year follow-up. RESULTS: Among 175 elderly patients, 109 underwent PCI and 66 had MICS-CABG. There was no significant difference observed in both groups with long-term all-cause mortality (31 PCI vs 21% MICS-CABG, p=0.151) and the overall 5 year survival was similar on Kaplan-Meier curve (Log rank p=0.318). The average length of stay in hospital was significantly shorter in the PCI than in the MICS-CABG group (4.3 vs 7.8 days, p<0.001). Only 4.7% of the PCI group were discharged to rehabilitation facility compared with 43.9% of the MICS-CABG group (p<0.001). The rate of repeat revascularization was significantly higher in the PCI group than in the MICS-CABG group (15 vs 3%, p=0.014). CONCLUSION: Among elderly patients, long-term all-cause mortality is similar after PCI and MICS-CABG. However, there is a significantly higher rate of repeat revascularization after PCI.

A multicenter, phase II study of the RAF-kinase inhibitor sorafenib in patients with advanced renal cell carcinoma.

The treatment of advanced renal cell carcinoma (RCC) has advanced significantly over the last two decades. This multicenter study was designed with the primary objective to evaluate the efficacy and safety of sorafenib as first-line treatment in patients with advanced or metastatic RCC in the Middle East, who were considered to be ineligible for other approved first-line therapies. A total of 75 eligible patients from 8 centers in the Middle East were included in this study. The patients comprised 48 men and 27 women, with a median age of 52 years (range, 19-78 years). A total of 50 patients had clear cell carcinoma, 17 had papillary carcinoma and 8 had other pathological subtypes. At enrollment, 55 of the 75 patients had undergone previous nephrectomy. A total of 67 patients presented with metastatic disease, while 8 patients had regional residual lesions or local recurrence. The patients were treated with 400 mg oral sorafenib twice daily on a continuous basis as a single agent. Treatment was discontinued upon disease progression, prohibitive toxicity, surgical complications, loss to follow-up, or refusal to continue therapy. The median treatment duration was 21 weeks (range, 1-137 weeks). Sorafenib was tolerated by the majority of the patients. Grade 3/4 hand-foot syndrome occurred in 17 patients; diarrhea, elevated liver enzymes and fatigue were observed in 3 patients each; and grade 3/4 vomiting, hypertension and anemia, in 1 patient each. Of the 75 patients included in this study, 60 were evaluable for response. One patient achieved a complete response for 91 weeks and 6 patients exhibited a partial response (median duration of 23 weeks) with an overall response rate of 11.7%. Disease stabilization occurred in 37 patients (61.7%). Thus, disease control was achieved in 44 of the 60 patientrs (73%). At a median follow-up period of 53.5 weeks (range, 8.5-192 weeks), an intention-to-treat analysis demonstrated a median time-to-disease progression of 25.7 weeks, with a median overall survival of 54.8 weeks. In conclusion, sorafenib was found to be tolerable and effective as first-line therapy in patients with advanced RCC.

Long-term mortality in minimally invasive compared with sternotomy coronary artery bypass surgery in the geriatric population (75 years and older patients).

OBJECTIVES: Ischaemic heart disease is the leading cause of death in the elderly population. Coronary artery bypass graft (CABG) surgery via sternotomy remains the standard of care for patients with multivessel coronary artery disease (CAD). Minimally invasive cardiac surgery (MICS)-CABG via left thoracotomy has been used as an alternative to sternotomy. The aim of our study was to assess the overall survival after MICS-CABG and sternotomy-CABG in elderly patients with CAD. METHODS: This observational study included patients who underwent coronary bypass from 2005 to 2008. Patients 75 years and older (n = 159) were included in the final analysis. Each arm was further divided into the MICS-CABG group or sternotomy-CABG group. Primary outcome and overall survival were obtained from our records and the social security death index. RESULTS: Among patients 75 years and older (159 patients), MICS-CABG had a significantly lower 5-year all-cause mortality than sternotomy-CABG (19.7 vs 47.7%, P < 0.001). Similarly, Kaplan-Meier curves showed significantly higher overall survival in the MICS-CABG group compared with sternotomy-CABG (log-rank P = 0.014). After adjusting for confounders, MICS-CABG demonstrated a lower mortality than sternotomy-CABG (HR 0.51, 95% confidence interval 0.26-0.97, P = 0.04). For patients less than 75 years old, MICS and sternotomy groups had similar survival according to both uni- and multivariate analyses. CONCLUSIONS: The adjusted models demonstrated that MICS-CABG has a significantly better long-term survival than sternotomy-CABG despite slightly differing baseline characteristics. Further studies are needed to compare the short- and long-term outcomes of the two approaches among the elderly population.

Rare case of coronary to pulmonary vein fistula with coronary steal phenomenon.

Coronary artery fistulas are abnormal connections between coronary artery territories and cardiac chambers or major vessels, most of them are congenital. Patients with coronary artery fistula can be asymptomatic or present with different symptoms like angina. Cardiac computed tomography (CT) is one of the best modalities for diagnosis. We present an elderly patient that presented with angina symptoms, non invasive stress test was positive for ischemic heart disease, coronary angiogram could not reveal any obstructive lesions, but an abnormal branch of the left descending coronary artery (LAD), cardiac CT showed fistula that connect left anterior descending coronary artery to left superior pulmonary vein. Our case is extremely rare as most of the reported cases were fistulas between LAD and pulmonary artery, but in our case the fistula between LAD and left superior pulmonary vein. In addition, our patients' symptoms resolved with anti-ischemic medical treatment without any surgical intervention.

Cardiac resynchronization therapy in acute pulmonary edema: A case report.

We are reporting a case of 71-year old lady with a dual chamber demand pacemaker, who developed acute pulmonary edema due to an acute left ventricular (LV) dysfunction and worsening in mitral valve regurgitation after atrioventricular nodal ablation for uncontrolled atrial fibrillation. This was attributed to right ventricular apical pacing leading to LV dyssynchronization. Patient dramatically improved within 12-24 h after upgrading her single chamber pacemaker to biventricular pacing. Our case demonstrates that biventricular pacing can be an effective modality of treatment of acute congestive heart failure. In particular, it can be used when it is secondary to LV dysfunction and severe mitral regurgitation attributed to significant dyssynchrony created by right ventricular pacing in patients with atrioventricular nodal ablation for chronic atrial fibrillation.

Unique presentation of Twiddler's syndrome.

We present a rare case of Twiddler's syndrome diagnosed in an asymptomatic patient on a routine follow up. This case reiterates the need for frequent monitoring of the implanted device. In addition, it was detected 4 years after implantation of an automatic implantable cardioverter defibrillator. This late representation is extremely uncommon.