Analysis of Aortic Growth Rates in Uncomplicated Type B Dissection.

BACKGROUND: Uncomplicated type B dissections have historically been treated medically with hemodynamic control. Early progression of the disease and late aneurysmal dilation have been considered as indications for intervention. The aim of this study is to analyze growth rate patterns of type B dissections based on computed tomography (CT) measurements over time. METHODS: We conducted a retrospective review of patients with acute type B dissection from 2008 to 2014 who had at least 2 follow-up CT scans. Patients with rapid progression requiring interventions were also included. Using M2S software (M2S, Lebanon, NH), we calculated the mean centerline diameter of the true and false lumens at 3 different sites of the descending aorta. Growth rate was calculated as the change in maximal diameter between the first interval and last available CT scans. Primary outcome was to compare the growth rate pattern between the 2 time intervals. Secondary outcomes included early and delayed aortic intervention and overall mortality (OM). RESULTS: A total of 108 patients were included. Average age of patients was 58.7 years. Median follow-up time was 3 months for the first CT and 32 months for the second. OM was 27.8% (n = 30), whereas the disease-specific mortality was 11.1% (n = 12). Thirty-seven percent (n = 40) required operative intervention (18 open and 22 endovascular repair): 20 at 30 days, 12 at 12 months, and 8 patients at >1 year. Mean aortic growth rate was higher in the first time interval compared with the second: 0.89 vs. 0.19 mm/month (P < 0.05) at the proximal descending aorta, 1.01 vs. 0.18 mm/month (P < 0.05) at the mid-descending aorta, and 0.65 vs. 0.28 mm/month; (P < 0.05) at the distal descending aorta. Those who underwent intervention had a higher aortic growth rate at early and late interval (P < 0.05). Age and number of comorbidities were associated with OM. Thrombosis of the false lumen did not affect the mortality and intervention rate. CONCLUSIONS: Type B dissection is associated with aortic growth over time. The overall growth rate was not linear with a more prominent initial phase. Faster aortic growth rate is associated with an increased intervention rate, whereas advanced age and number of comorbidities are associated with increased mortality. Prospectively designed studies are needed to identify the subgroup of patients who may benefit from early intervention based on growth rate measurements.

Endovascular Treatment of a Traumatic Thoracic Aortic Injury in an Eight-Year Old Patient: Case Report and Review of Literature.

Traumatic aortic injuries in children and adolescents are rare. Although endovascular repair has become the preferred approach for such injuries in adults, open repair has endured as the gold standard in children owing mainly to the smaller aortic and access vessel diameter and the scarcity of long-term follow-up data. We report a successful endovascular repair of a traumatic thoracic aortic injury in an 8-year-old girl using a Zenith Alpha thoracic endograft (Cook Medical, Bloomington, IN). We also review the literature on endovascular treatment of traumatic aortic injuries in the pediatric population.

Endovascular recanalization of total occlusions of the mesenteric and celiac arteries.

OBJECTIVE: To evaluate our experience with the endovascular treatment of total occlusions of the mesenteric and celiac arteries. METHODS: We performed a retrospective review of endovascular stenting of 27 nonembolic total occlusions of the superior mesenteric artery (SMA) and celiac artery (CA) between July 2004 and July 2011 (26 patients, 16 females; mean age, 62 ± 13 years). A variety of demographic, lesion-related and procedure-related variables were evaluated for potential impact of technical success and patency. The follow-up protocol included clinical assessment, and color and spectral Doppler evaluation of the stented vessel(s). RESULTS: The clinical presentation was chronic mesenteric ischemia in 12 patients, acute mesenteric vascular syndromes in 10 patients, foregut ischemia/ischemic pancreatitis in three patients, and prior to endovascular repair of aortic aneurysm in one patient. The treated vessel was SMA in 22 procedures, CA in three, and both SMA and CA in one. Technical success was achieved in 23 of the 27 attempted recanalizations (85%). Three patients who failed the attempt underwent open bypass, and another one underwent retrograde recanalization and stenting of the SMA. Procedure success was only significantly related to patient age <70 years or procedure performance after the year 2006. Notably, the presence of a stump, ostial plaque, extensive vascular calcification, recanalization route (intraluminal vs subintimal), occlusion length, and vessel diameter had no significant impact on procedure success. Traditional duplex criteria proved unreliable in predicting restenosis. Life table analysis of freedom from symptom recurrence showed a primary and assisted rates of 58% and 80% at 1 year, and 33% and 60% at 2 years, respectively. Clinical recurrences developed in six patients (four presented with abdominal angina and weight loss, two presented with abdominal catastrophe). There were six access-related complications and no procedural deaths. Four delayed deaths occurred during follow-up (two cardiac causes, two due to abdominal sepsis). CONCLUSIONS: Endovascular recanalization of mesenteric artery occlusion is both feasible and successful, provided careful planning is used.

Anatomic bifurcated reconstruction of chronic bilateral innominate-superior vena cava occlusion using the Y-stenting technique.

This article presents the case of a 42-year-old man who presented with superior vena cava (SVC) syndrome due to fibrosing mediastinitis with multiple failed attempts at recanalization. We initially treated him with unilateral sharp needle recanalization of the right innominate vein into the SVC stump followed by stenting. Although his symptoms improved immediately, they did not completely resolve. Six months later, he returned with worsening symptoms, and venography revealed in-stent restenosis. The patient requested simultaneous treatment on the left side. The right stent was dilated, and a 3-cm-long occlusion of the left innominate vein was recanalized, again using sharp needle technique, homing into the struts of the right-sided stent. Following fenestration of the stent, a second stent was deployed from the left side into the SVC, and the two Y limbs were sequentially dilated to allow a true bifurcation anatomy (figure). The patient had complete resolution of his symptoms and continues to do well 6 months later.

Lower extremity aneurysmal degeneration of great saphenous venous allograft bypass in an adolescent boy.

Chronic limb-threatening ischemia in the pediatric population is a rare phenomenon. When open repair is necessitated, an autogenous conduit is preferred. However, venous grafts are prone to their own long-term complications. We have presented the case of a 10-year-old boy with chronic limb-threatening ischemia due to popliteal artery thrombosis that was treated with an ipsilateral great saphenous vein bypass. Seven years after the initial procedure, the venous graft had developed aneurysmal degeneration with acute thrombosis, necessitating bypass revision. Through the present case, we have discussed the surgical approach and highlighted the importance of long-term postoperative surveillance after open repair in the pediatric population.

Protein Kinase C Epsilon Overexpression Is Associated With Poor Patient Outcomes in AML and Promotes Daunorubicin Resistance Through p-Glycoprotein-Mediated Drug Efflux.

The protein kinase C (PKC) family of serine/threonine kinases are pleiotropic signaling regulators and are implicated in hematopoietic signaling and development. Only one isoform however, PKCϵ, has oncogenic properties in solid cancers where it is associated with poor outcomes. Here we show that PKCϵ protein is significantly overexpressed in acute myeloid leukemia (AML; 37% of patients). In addition, PKCϵ expression in AML was associated with a significant reduction in complete remission induction and disease-free survival. Examination of the functional consequences of PKCϵ overexpression in normal human hematopoiesis, showed that PKCϵ promotes myeloid differentiation, particularly of the monocytic lineage, and decreased colony formation, suggesting that PKCϵ does not act as an oncogene in hematopoietic cells. Rather, in AML cell lines, PKCϵ overexpression selectively conferred resistance to the chemotherapeutic agent, daunorubicin, by reducing intracellular concentrations of this agent. Mechanistic analysis showed that PKCϵ promoted the expression of the efflux pump, P-GP (ABCB1), and that drug efflux mediated by this transporter fully accounted for the daunorubicin resistance associated with PKCϵ overexpression. Analysis of AML patient samples also showed a link between PKCϵ and P-GP protein expression suggesting that PKCϵ expression drives treatment resistance in AML by upregulating P-GP expression.

RUNX3 overexpression inhibits normal human erythroid development.

RUNX proteins belong to a family of transcription factors essential for cellular proliferation, differentiation, and apoptosis with emerging data implicating RUNX3 in haematopoiesis and haematological malignancies. Here we show that RUNX3 plays an important regulatory role in normal human erythropoiesis. The impact of altering RUNX3 expression on erythropoiesis was determined by transducing human CD34+ cells with RUNX3 overexpression or shRNA knockdown vectors. Analysis of RUNX3 mRNA expression showed that RUNX3 levels decreased during erythropoiesis. Functionally, RUNX3 overexpression had a modest impact on early erythroid growth and development. However, in late-stage erythroid development, RUNX3 promoted growth and inhibited terminal differentiation with RUNX3 overexpressing cells exhibiting lower expression of glycophorin A, greater cell size and less differentiated morphology. These results suggest that suppression of RUNX3 is required for normal erythropoiesis. Overexpression of RUNX3 increased colony formation in liquid culture whilst, corresponding RUNX3 knockdown suppressed colony formation but otherwise had little impact. This study demonstrates that the downregulation of RUNX3 observed in normal human erythropoiesis is important in promoting the terminal stages of erythroid development and may further our understanding of the role of this transcription factor in haematological malignancies.

Increased expression of RUNX3 inhibits normal human myeloid development.

RUNX3 is a transcription factor dysregulated in acute myeloid leukemia (AML). However, its role in normal myeloid development and leukemia is poorly understood. Here we investigate RUNX3 expression in both settings and the impact of its dysregulation on myelopoiesis. We found that RUNX3 mRNA expression was stable during hematopoiesis but decreased with granulocytic differentiation. In AML, RUNX3 mRNA was overexpressed in many disease subtypes, but downregulated in AML with core binding factor abnormalities, such as RUNX1::ETO. Overexpression of RUNX3 in human hematopoietic stem and progenitor cells (HSPC) inhibited myeloid differentiation, particularly of the granulocytic lineage. Proliferation and myeloid colony formation were also inhibited. Conversely, RUNX3 knockdown did not impact the myeloid growth and development of human HSPC. Overexpression of RUNX3 in the context of RUNX1::ETO did not rescue the RUNX1::ETO-mediated block in differentiation. RNA-sequencing showed that RUNX3 overexpression downregulates key developmental genes, such as KIT and RUNX1, while upregulating lymphoid genes, such as KLRB1 and TBX21. Overall, these data show that increased RUNX3 expression observed in AML could contribute to the developmental arrest characteristic of this disease, possibly by driving a competing transcriptional program favoring a lymphoid fate.

A natural history of aortic aneurysm hygroma.

A 56-year-old man with a family history of aortic aneurysm underwent routine repair in 2003. A postoperative computed tomography scan showed a 6-cm perigraft hygroma. Sudden onset of abdominal pain 12 months later revealed a larger hygroma, with an additional anterior fluid collection suggestive of contained rupture. The bilobed hygroma remained stable until 2010, when he presented with chills and severe abdominal pain. A computed tomography scan demonstrated free rupture of the sister hygroma, with air pockets observed within the sac. Conservative management was elected. Air pockets as well as the hygroma eventually resolved, and the patient remains well.

Supraclavicular Versus Transaxillary First Rib Resection for Thoracic Outlet Syndrome.

Background: Thoracic outlet syndrome (TOS) results from compression of neurovascular structures supplying the upper extremity as they exit the thoracic outlet. Depending on the clinical presentation, surgical decompression may be required. Objectives: Transaxillary (TA) and supraclavicular (SC) approaches are both widely utilized and deemed effective. Our objective was to review the outcomes for both approaches at our institution. Methods: A retrospective review was conducted on patients who underwent thoracic outlet decompression between 2010 and 2015. Data on demographics, comorbidities, presenting symptoms, and type of TOS (neurogenic, venous, or arterial) were collected. Operative times, length of hospital stay, perioperative complications, and outcomes were also studied. Results: A total of 82 thoracic outlet decompression procedures were performed during the study period: 42% neurogenic TOS, 46% venous TOS, and 12% arterial TOS. In total, 49% underwent TA approach and 51% underwent SC approach. Adjunct procedures were performed in 13% of patients. There were no significant differences in average operative time (151.3 ± 54.1 minutes versus 126.1 ± 36.1 minutes, P = .11) or hospital stay (2.3 ± 1.9 days versus 2.4 ± 1.4 days, P = .23) between both groups, respectively. Minor complications were seen in 6% of patients with no significant difference in both groups, whereas 6% had major complications. No perioperative or 30-day mortalities were observed. In total, 49% of patients had complete resolution of symptoms, 46% had partial improvement, and 5% had no improvement. There was no difference in symptom resolution between either group. Conclusions: TA and SC approaches are equally safe and effective for the treatment of TOS. SC decompression allows for adjunct procedures and vascular reconstructions.

The impact of the COVID-19 pandemic on cardiology services.

OBJECTIVE: The COVID-19 pandemic resulted in prioritisation of National Health Service (NHS) resources to cope with the surge in infected patients. However, there have been no studies in the UK looking at the effect of the COVID-19 work pattern on the provision of cardiology services. We aimed to assess the impact of the pandemic on cardiology services and clinical activity. METHODS: We analysed key performance indicators in cardiology services in a single centre in the UK in the periods prior to and during lockdown to assess reduction or changes in service provision. RESULTS: There has been a greater than 50% drop in the number of patients presenting to cardiology and those diagnosed with myocardial infarction. All areas of cardiology service provision sustained significant reductions, which included outpatient clinics, investigations, procedures and cardiology community services such as heart failure and cardiac rehabilitation. CONCLUSIONS: As ischaemic heart disease continues to be the leading cause of death nationally and globally, cardiology services need to prepare for a significant increase in workload in the recovery phase and develop new pathways to urgently help those adversely affected by the changes in service provision.

Self-Assembling Proteins as High-Performance Substrates for Embryonic Stem Cell Self-Renewal.

The development of extracellular matrix mimetics that imitate niche stem cell microenvironments and support cell growth for technological applications is intensely pursued. Specifically, mimetics are sought that can enact control over the self-renewal and directed differentiation of human pluripotent stem cells (hPSCs) for clinical use. Despite considerable progress in the field, a major impediment to the clinical translation of hPSCs is the difficulty and high cost of large-scale cell production under xeno-free culture conditions using current matrices. Here, a bioactive, recombinant, protein-based polymer, termed ZTFn , is presented that closely mimics human plasma fibronectin and serves as an economical, xeno-free, biodegradable, and functionally adaptable cell substrate. The ZTFn substrate supports with high performance the propagation and long-term self-renewal of human embryonic stem cells while preserving their pluripotency. The ZTFn polymer can, therefore, be proposed as an efficient and affordable replacement for fibronectin in clinical grade cell culturing. Further, it can be postulated that the ZT polymer has significant engineering potential for further orthogonal functionalization in complex cell applications.

ECM1 expression in thyroid tumors--a comparison of real-time RT-PCR and IHC.

BACKGROUND: Increased extracellular matrix 1 (ECM1) expression, as determined by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), has been recently proposed as a novel and independent diagnostic marker for malignant thyroid nodules. However ECM1 protein expression has not been previously evaluated in thyroid tumors. Real-time RT-PCR is not widely available and this has important implications for the widespread use of the expression of this gene for diagnosis. The purpose of the current study is to evaluate and compare ECM1 expression by real-time RT-PCR with immunohistochemistry (IHC) as diagnostic aids in thyroid neoplasms. MATERIALS AND METHODS: ECM1 expression was studied in normal thyroid tissues (n = 14) and primary thyroid tumors (19 benign, 30 malignant) using both techniques. The performance characteristics of ECM1 expression were examined with receiver operating characteristic curves and the resulting area under the curve. RESULTS: ECM1 was highly expressed in thyroid carcinomas, compared with benign thyroid tissues, both at the mRNA (P < 0.01) and protein (P = 0.06) levels. However, ECM1 mRNA expression appeared to be a more sensitive marker of thyroid malignancy than IHC (AUC = 0.77 and 0.65, respectively). ECM1 expression by both methods was useful in identifying malignant follicular, but not Hürthle cell neoplasms. CONCLUSIONS: We confirm that ECM1 expression has potential utility as an independent diagnostic marker for thyroid cancer, although, performance characteristics were lower than previously published. Furthermore, IHC was not as sensitive as real-time RT-PCR in identifying malignant lesions. Prospective studies are needed to further clarify the role of ECM1 expression as a diagnostic marker.

Suprarenal clamping is a safe method of aortic control when infrarenal clamping is not desirable.

We evaluated the safety of suprarenal aortic clamping in patients with abdominal aortic aneurysm (AAA) treated by open aortic replacement by retrospectively reviewing all patients who underwent elective AAA replacement at a university hospital from 1993 until 2003. We reviewed 249 patient charts and divided them into three groups according to the clamp location during aortic replacement: group 1, infrarenal clamp group (n = 185); group 2, suprarenal clamp group (n = 52); and group 3, supraceliac clamp group (n = 12). Groups 1 and 2 were compared with respect to risk factors, intraoperative events, and postoperative events. Statistical analysis was done using Wilcoxon's rank-sum test, chi-squared test, and Fisher's exact test. Risk factors were comparable in groups 1 and 2 except for weight, which was higher in group 1. Intraoperative urine output, hypotensive episodes, and use of renal protective drugs were comparable in the two groups. Operation time, blood loss, and use of IV fluids were all significantly higher in group 2, while total aortic clamp time was higher in group 1. Postoperative events were comparable except for postoperative peak creatinine, intensive care unit length of stay, and postoperative length of stay, which were higher in group 2; however, discharge creatinine was comparable without a significant difference. Suprarenal clamping is a safe method of aortic control during open AAA replacement surgery. The selection of clamping site should be individualized according to the intraoperative anatomy. Supraceliac clamping is not necessarily the preferable method of aortic control when the infrarenal location is not suitable for clamping.

Possible genetic component to the etiology of perigraft hygromas.

Perigraft hygroma is a known complication of prosthetic graft implantation. The specific etiology of perigraft hygromas is still unknown. We report 2 brothers who underwent open abdominal aortic aneurysm repairs with polytetrafluoroethylene grafts that developed progressively enlarging perigraft hygromas. This is the first case report of 2 brothers developing sac hygromas after open abdominal aortic aneurysm repair. This case demonstrates that there could be a genetic component associated with the development of perigraft hygromas and further investigation of genetic etiologies should be considered.

Combined direct repair and inline inflow stenting in the management of aortoiliac disease extending into the common femoral artery.

PURPOSE: Describe a hybrid approach to simplify management of complex aortoiliac occlusive disease (AIOD) extending into the common femoral artery (CFA). METHODS: Retrospective review of 56 patients who underwent hybrid management of AIOD extending into CFA between January 2003 and February 2007. Two distinct hybrid approaches were compared: Inline (iliac stenting continuous with an open CFA reconstruction, 38 limbs in 37 patients) and tandem (noncontiguous stenting of an upstream iliac segment, 20 limbs in 19 patients). The median follow-up duration was 15 ± 12 months in the inline group and 24 ± 12 months in the tandem group. RESULTS: Technical success was achieved in all but 1 procedure. Clinical and hemodynamic responses to the interventions and limb loss rates were comparable in both groups. Survival table analysis showed no significant difference between inline and tandem reconstructions. CONCLUSIONS: Inline stenting represents a lesser invasive revascularization choice in complex AIOD with contiguous involvement of the CFA.

Impact of aggressive endovascular recanalization techniques on success rate in chronic total arterial occlusions (CTOs).

PURPOSE: To report experience with aggressive recanalization approaches in chronic total arterial occlusion (CTO). METHODS: Chronic total arterial occlusion recanalization was attempted on 112 limbs in 99 consecutive patients between January 1999 and December 2006. RESULTS: There were 63 iliac arteries, 45 femoropopliteal arteries, and 4 occluded stents. Mean occlusion length was 8.7 ± 4.7 cm. Conventional recanalization was attempted first and was successful in 71 limbs (70%). Probing with the guidewire's stiff end was attempted in 33 of the 41 procedures where conventional techniques failed and was successful in 18 (54%), improving the overall procedural success rate to 80%. For the remaining 15 limbs, home-made directional sharp needle recanalization was attempted in 11 and was successful in 9 (82%), further improving the overall recanalization success to 88%. Procedural complications were self-limited or managed nonoperatively. CONCLUSIONS: Aggressive recanalization techniques in CTO following failure of traditional means are safe and can substantially improve procedural success rates.

RIZ1 is epigenetically inactivated by promoter hypermethylation in thyroid carcinoma.

BACKGROUND: Allelotype studies have suggested that chromosome 1p is frequently lost in thyroid cancers, thus suggesting that there is an important tumor suppressor at this location. RIZ1 (PRDM2), located on 1p36, is a recently described tumor suppressor gene and is a member of the protein methyltransferase superfamily. RIZ1 expression is lost in a variety of tumors, primarily by means of epigenetic mechanisms that involve promoter hypermethylation. METHODS: RIZ1 expression was examined in a panel of thyroid tumor cell lines and primary thyroid tissues (14 normal, 19 benign, and 31 cancerous) by using real-time polymerase chain reaction (PCR). Methylation status of the RIZ1 promoter was studied using bisulfite sequencing and methylation-specific PCR. RESULTS: The authors demonstrated that RIZ1 expression is lost in thyroid tumor cell lines and is also significantly reduced in thyroid carcinomas, when compared with normal thyroid tissues (P < .0001) and benign tumors (P = .0003). The current study results also showed that loss of RIZ1 is mediated by aberrant cytosine methylation of the RIZ1 promoter. One hundred percent of carcinomas were methylated, compared with 33% of normal thyroid tissues (P = .001). RIZ1 mRNA expression was significantly higher (P = .02) in unmethylated (1.22 +/- 1.2, mean +/- standard deviation [SD]), compared with methylated tissues (0.37 +/- 0.42, mean +/- SD). Last, treatment with a DNA methyltransferase inhibitor led to reactivation of RIZ1 expression in cell lines that had negligible RIZ1 expression at baseline. CONCLUSIONS: The current study suggested an important role for RIZ1 expression in thyroid tumorigenesis and identified a potential novel therapeutic target for tumors unresponsive to other therapies.