Distal Origin Research Articles

Ventricular arrhythmias originating from different portions of the communicating vein of the left ventricular summit: electrocardiographic characteristics and catheter ablation

BackgroundIdiopathic ventricular arrhythmias (IVAs) arising from different portions of the communicating vein of the left ventricular summit (summit-CV) are not a rare phenomenon. Whereas its electrocardiographic (ECG) and electrophysiological characteristics are not fully investigated.ObjectiveThis study aimed to identify distinct ECG and electrophysiological features of IVAs originating from different portions of summit-CV.MethodsNineteen patients confirmed arising from summit-CV were included in this study.ResultsThe 19 patients were divided into proximal and distal portion groups based on their target sites in summit-CV. In the proximal portion group, 100% (11/11) VAs showed dominant negative (rs or QS) waves in lead I, while in the distal portion group, 87.5% (7/8) showed dominant positive waves (R, Rs or r) (p < 0.000). In lead V1, 100% (11/11) of the proximal portion group showed dominant positive waves (R or Rs), while 62.50% (5/8) of the distal portion group showed positive and negative bidirectional or negative waves (RS or rS) (p < 0.005). RI>4mV, SI<3.5mV, RV1<13mV, SV1>3.5mV, RI/SI>0.83, and RV1/SV1< 2.6 indicated a distal portion of summit-CV with the predictive value of 0.909, 1.000, 0.653, 0.972, 0.903, 0.966, respectively. A more positive wave in lead I and a more negative wave in lead V1 indicated more distal origin in summit-CV. Target sites in proximal and distal summit-CV groups showed similar electrophysiological characteristics during mapping.ConclusionsThere were significant differences in ECG characteristics of VAs at different portions of summit-CV, which could aid pre-procedure planning and facilitate radiofrequency catheter ablation (RFCA) procedures.

An integrated analysis of bile acid metabolism in humans with severe obesity.

Bile acids (BA) are vital regulators of metabolism. BAs are AQ6 secreted in the small intestine, reabsorbed, and transported back to the liver, where they can modulate metabolic functions. There is a paucity of data regarding the portal BA composition in humans. This study aimed to address this knowledge gap by investigating portal BA composition and the relation with peripheral and fecal BA dynamics in conjunction with the gut microbiome. Thirty-three individuals from the BARIA cohort were included. Portal plasma, peripheral plasma, and feces were collected. BA and C4 levels were measured employing mass spectrometry. FGF19 was measured using ELISA. Gut microbiota composition was determined through metagenomics analysis on stool samples. Considerable diversity in the portal BA composition was observed. The majority (n = 26) of individuals had a 9-fold higher portal than peripheral BA concentration. In contrast, 8 individuals showed lower portal BA concentration compared with peripheral and had higher levels of unconjugated and secondary BA in this compartment, suggesting more distal origin. The altered portal BA profile was associated with altered gut microbiota composition. In particular, taxa within Bacteroides were reduced in abundance in the feces of these individuals. Characterization of the portal BA composition in relation to peripheral and fecal BA increased insight into the dynamics of BA metabolism in individuals with obesity. Peripheral BA composition was much more diverse due to microbial metabolism. About 24% of the portal samples was surprisingly low in total BA; the underlying mechanism requires further exploration.

Abstract 7369: Passenger mutations link cellular origins and transcriptional identity in human lung adenocarcinoma

Abstract Lineage plasticity hinders identification of cellular origin of cancers, as malignant cells cease to resemble benign cells from which they presumably evolved. Lung adenocarcinoma (LUAD), the most common primary lung cancer in United States is thought to arise from alveolar type II (AT2) cells. However recent mouse models have shown that LUADs may also arise from other cell types such as basal and club. Although such mouse models are considered to be gold standard for identifying cell of origin for cancers, they are generally limited to a specific genetic context and lack all cell types that are present in human lung. Thus, to better understand the cellular origins of LUAD, we utilized a publicly available lung scRNA-seq atlas from Human Cell Atlas, spanning over 584,000 cells from 107 individuals to investigate cell type specific passenger mutational footprints of transcriptional coupled repair process (a sub-pathway of nucleotide excision repair that preferentially corrects mutations in highly expressed genes) across 295 lung cancer WGS profiles. As most mutations in self-renewing tissues are thought to occur prior to the onset of tumorigenesis, genes that are most highly transcribed in the cell of origin would have fewer somatic single nucleotide variants (SNV). To test this hypothesis, our study correlated somatic mutational density with gene expression profiles of cell types to identify Alveolar Type 0 (AT0, newly identified cell type) cells to be most strongly associated with LUAD mutation density, suggesting that the ancestor of LUAD cells in tumor spent most of their non-cancerous time in AT0 state. Interestingly studies have shown that following DNA damage in AT2 cells, transition to AT1 occurs to repair the damage. However, if the damage is detrimental, the transition of AT2 to AT1 is stalled and the cells remain in AT0 (i.e., a transitionary) state. We propose that such stalling for a long period of time can give rise to LUAD. Further our study identified a subset of LUAD patients with non-AT2 (i.e., proximal) origin. In particular, we observed significantly higher KRAS mutations in distal origin LUAD patients compared to those in proximal origin LUADs. Finally, a subset of LUAD patients with distal cell of origin adopted a more proximal transcriptional identity. Extending our analysis to lung squamous cell carcinoma (LUSC) patients, we observed basal resting cells to be the Cell of Origin (COO) for LUSC. Our study provides a novel approach for identifying cell of origin for cancers and points to a complex interplay between origin and identify in lung adenocarcinoma evolution. Citation Format: Sukanya Panja, Padmaja Mantri, Juan Andrade Martinez, Marcin Imielinski. Passenger mutations link cellular origins and transcriptional identity in human lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7369.

Long-term exposure to traffic noise and risk of incident colon cancer: A pooled study of eleven Nordic cohorts

BackgroundColon cancer incidence is rising globally, and factors pertaining to urbanization have been proposed involved in this development. Traffic noise may increase colon cancer risk by causing sleep disturbance and stress, thereby inducing known colon cancer risk-factors, e.g. obesity, diabetes, physical inactivity, and alcohol consumption, but few studies have examined this.ObjectivesThe objective of this study was to investigate the association between traffic noise and colon cancer (all, proximal, distal) in a pooled population of 11 Nordic cohorts, totaling 155,203 persons.MethodsWe identified residential address history and estimated road, railway, and aircraft noise, as well as air pollution, for all addresses, using similar exposure models across cohorts. Colon cancer cases were identified through national registries. We analyzed data using Cox Proportional Hazards Models, adjusting main models for harmonized sociodemographic and lifestyle data.ResultsDuring follow-up (median 18.8 years), 2757 colon cancer cases developed. We found a hazard ratio (HR) of 1.05 (95% confidence interval (CI): 0.99–1.10) per 10-dB higher 5-year mean time-weighted road traffic noise. In sub-type analyses, the association seemed confined to distal colon cancer: HR 1.06 (95% CI: 0.98–1.14). Railway and aircraft noise was not associated with colon cancer, albeit there was some indication in sub-type analyses that railway noise may also be associated with distal colon cancer. In interaction-analyses, the association between road traffic noise and colon cancer was strongest among obese persons and those with high NO2-exposure.DiscussionA prominent study strength is the large population with harmonized data across eleven cohorts, and the complete address-history during follow-up. However, each cohort estimated noise independently, and only at the most exposed façade, which may introduce exposure misclassification. Despite this, the results of this pooled study suggest that traffic noise may be a risk factor for colon cancer, especially of distal origin.

GATA3 Is a Useful Immunohistochemical Marker to Differentiate Variants of Renal Tubular Lesions from Different Segments of Renal Tubules

Abstract Introduction/Objective GATA3 is found in glomerular mesangial cells, and the distal tubules &amp; collecting ducts in metanephros and eventual kidneys, but not associated with the proximal tubules and loops of Henle. We hypothesize that GATA3 can be used as a marker to identify the origin of tubular differentiation in most renal tumors. Methods/Case Report Ten negative controls and 43 renal mass lesions (RCC, papillary, clear cell papillary, and chromophobe carcinomas, oncocytoma, and polycystic kidney disease). GATA3 nuclear stain was graded as negative (absent stain), equivocal and positive (&amp;lt; 5 and &amp;gt; 5% cells, respectively). Details of their GATA3 nuclear expression was analyzed for identifying their tubular segmental origins. Results (if a Case Study enter NA) In 10 normal renal parenchyma, GATA3 was positive in mesangial cells, distal tubules, and collecting ducts, but was negative in the proximal tubules and loop of Henle. The cystic lining of glomerulocystic renal disease was stained negatively for GATA3 (proximal tubular origin), whereas pediatric and adult variants of polycystic kidney diseases was positive for GATA3 staining (distal tubular origin). 1/10 ten clear cell RCC and papillary RCC showed focal positive GATA3 stain. GATA3 showed weakly positive staining in some oncocytomas (4/11) and some chromophobe RCC (4/11), indicating that they might be derived from the junctional segment between the loop of Henle and the distal tubules. By contrast, all clear cell papillary RCC (distal tubule origin) were diffusely positive. Conclusion Our results indicate that GATA3 is a useful immunohistochemical marker to determine the developmental origin in the specific renal tubular segment for the majority of renal mass lesions. Thus, it may be useful for routine differential diagnosis of these lesions.

AMPK differentially alters sulphated glycosaminoglycans under normal and high glucose milieu in proximal tubular cells.

Glycosaminoglycans (GAGs) and AMP-activated protein kinase (AMPK) are two critical molecular players involved in cellular homeostasis. Both of them are altered due to hyperglycaemia in the kidney, leading to the pathogenesis of diabetic nephropathy. Here, we have looked into the effect of AMPK modulation on sulphated GAG (sGAG) levels of tubular cells of proximal and distal origin to understand the mechanism of hyperglycaemia-mediated pathogenesis of the diabetic nephropathy. In MDCK cells (distal tubular cell) and NRK-52E (proximal tubular cell), AMPK inhibition resulted in increased sGAG levels under normal glucose conditions characteristically of heparan sulphate class, whereas AMPK activation did not have any effect. High glucose (HG) condition did not alter sGAG levels in MDCK cell despite a decrease in AMPK phosphorylation. Subjecting NRK-52E cells to HG milieu significantly decreased sGAG levels more so of chondroitin/dermatan sulphate, which is significantly prevented when HG is co-treated with AMPK activator. Interestingly, knockdown of AMPK by AMPKα1/α2 siRNA showed increased sGAG levels in NRK-52E. Our results suggest that changes in sGAG level, in particular, as a result of AMPK modulation is differentially regulated and is dependent on cell type as well as its physiological status. Furthermore, activation of AMPK is beneficial in preventing the HG-mediated decrease in sGAGs in proximal tubular cells.

Isolation and Enrichment of Human Lung Epithelial Progenitor Cells for Organoid Culture.

Epithelial organoid models serve as valuable tools to study the basic biology of an organ system and for disease modeling. When grown as organoids, epithelial progenitor cells can self-renew and generate differentiating progeny that exhibit cellular functions similar to those of their in vivo counterparts. Herein we describe a step-by-step protocol to isolate region-specific progenitors from human lung and generate 3D organoid cultures as an experimental and validation tool. We define proximal and distal regions of the lung with the goal of isolating region-specific progenitor cells. We utilized a combination of enzymatic and mechanical dissociation to isolate total cells from the lung and trachea. Specific progenitor cells were then fractionated from the proximal or distal origin cells using fluorescence associated cell sorting (FACS) based on cell type-specific surface markers, such as NGFRfor sorting basal cells and HTII-280 for sorting alveolar type II cells. Isolated basal or alveolar type II progenitors were used to generate 3D organoid cultures. Both distal and proximal progenitors formed organoids with a colony forming efficiency of 9-13% in distal region and 7-10% in proximal region when plated 5000 cell/well on day 30. Distal organoids maintained HTII-280+ alveolar type II cells in culture whereas proximal organoids differentiated into ciliated and secretory cells by day 30. These 3D organoid cultures can be used as an experimental tool for studying the cell biology of lung epithelium and epithelial mesenchymal interactions, as well as for the development and validation of therapeutic strategies targeting epithelial dysfunction in a disease.

Study of Anatomical Variations of 1,2 Intercompartmental Supraretinacular Artery-Based Vascularized Bone Graft in Cadavers.

The aim of this study is to describe the anatomy of the 1,2 intercompartmental supraretinacular artery (1,2 ICSRA), including the location of the perforators, number of perforators, and proximal and distal origins of the artery. The study was done by dissecting both wrists of 11 fresh-frozen cadavers. In each specimen, skin incision and dissections were done in the forearm by the Henry approach. Radial artery was identified and cannulated and dye was injected. The dye consisted of the mixture of polyvinyl chloride and acetone in the ratio of 1:4, to which red-colored resin was added. The artery of interest 1,2 ICSRA was dissected and its anatomical characteristics such as distal origin, proximal origin, number of perforators, and largest perforator were measured. Of the 22 wrists dissected, only in 19 wrists we were able to recognize the perforators. Average number of perforators seen was 3.05 (range 1-5). Average distance of the largest perforator from the radial styloid was 11.79 mm (range 6-19 mm). The average distance of the distal origin of 1,2 ICSRA from the radial styloid was 6.71 mm distal to radial styloid. It ranged from 16 mm distal to styloid process to 6 mm proximal to the styloid process. The average distance of proximal origin of 1,2 ICSRA from the radial styloid was 40.52 mm proximal to the radial styloid (range 25-66 mm). The maximum density of perforators of 2.84 was noticed to be in the region of 6-18 mm from the distal articular margin. The distal origin of 1,2 ICSRA in our study was much more distal in comparison to the western population. The detailed anatomy of the 1,2 ICSRA presented in this study may guide in planning and dissection to maximize the vascularity of a pedicled bone graft based on this vessel for the management of scaphoid nonunions and other carpal pathologies.

Tectono-metamorphic evolution of an evaporitic décollement as recorded by mineral and fluid geochemistry: The “Nappe des Gypses” (Western Alps) case study

Evaporites play a major role on the structuration of collisional orogens especially when they act as décollement units. However, their exact pressure-temperature-deformation (P-T-d) paths are poorly documented. In this study, the first direct P-T-d constraints of the “Nappe des Gypses” formation (western French Alps) have been established. An innovative association of structural geology, petrography, crystallochemistry, and detailed study of both fluid inclusions and stable isotopes (C, O) analysis has been applied to this evaporitic facies. Geochemical analysis shows that the “Nappe des Gypses” formation has recorded the three typical metamorphic and deformational events of the Alps (namely D1, D2 and D3). These different constraints allow the determination of the first P-T path determination for this unit. Metamorphic peak conditions of the “Nappe des Gypses” are at 16.6 ± 2.3 kbar and 431 °C ± 28 °C. This formation was buried at similar conditions than the oceanic units. During the exhumation path, the D1-D2 transition is reached at 350 °C ± 20 °C and 6.5 ± 1.8 kbar and the D2-D3 transition is assumed to be at 259 °C ± 24 °C and 2.0 ± 1.0 kbar (Strzerzynski et al., 2012). Peak P-T conditions overlap those of the median Liguro-Piemontese units but are different from those of the Briançonnais units. It implies 1) an active and crucial role of the “Nappe des Gypses” during the exhumation of the Alpine oceanic complex, and 2) confirms the allochthonous and more distal origin of the European Tethyan passive margin of the “Nappe des Gypses” formation. Consideration of sulfates dehydration probably between 15.0 and 16.6 kbar and 200 and 300 °C, allows to discuss pore pressure excess and its mechanical consequences on the exhumation process. This process is very likely to amplify the “décollement” effect of the evaporites and allow the nappe stack formation.This illustrates the role of this formation as a décollement surface. This difference of evolution highlights the major role of the evaporitic formations on the exhumation and structuration of a collisional chain. Such methodology could contribute to decipher the role of evaporites in the structural context of other collisional chains such as Himalaya, Pyrenees or Zagros.

The Vastus Medialis Insertion Is More Proximal and Medial in Patients With Patellar Instability: A Magnetic Resonance Imaging Case-Control Study.

Background:The anatomy and function of the quadriceps muscle play a role in patellofemoral stability. Few studies have evaluated anatomic differences in the vastus medialis between patients with and without patellar instability.Purpose:To compare the anatomy of the vastus medialis using magnetic resonance imaging in patients with patellar instability to a control group.Study Design:Cross-sectional study; Level of evidence, 3.Methods:A group of patients with patellar instability were sex-matched with a control group with anterior cruciate ligament tears, meniscal injuries, or sprains; patients younger than 15 years were excluded. The anatomy of the vastus medialis was examined by the distance between the distal origin of the vastus medialis in the femur and the medial femoral condyle, the distance from the proximal pole of the patella to the most distal insertion of the muscle and its ratio to the length of the articular surface of the patella, and a qualitative description of the insertion position of the muscle fibers (directly in the patella or the medial retinaculum).Results:Both groups comprised 78 knees (48 female; 61.5%). The mean age in the control and patellar instability groups was 30.2 ± 7.8 years and 25.6 ± 7.5 years, respectively (P = .001). The distance from the vastus origin to the condyle was 27.52 ± 3.49 mm and 26.59 ± 3.43 mm, respectively (P = .041); the distance from the proximal pole of the patella to the most distal muscle insertion was 17.59 ± 5.54 mm and 15.02 ± 4.18 mm, respectively (P < .001); and the ratio of this distance to the joint surface was 0.586 ± 0.180 and 0.481 ± 0.130, respectively (P < .001). In 75.6% of knees in the patellar instability group, the insertion of the vastus was into the medial retinaculum and not into the patella compared with 52.6% in the control group (P = .003; odds ratio, 2.8).Conclusion:The distal insertion of the vastus medialis differed in knees with patellar instability, with a more proximal insertion and less patellar coverage relative to controls, and was more frequently found in the retinaculum instead of directly in the patella.

Simultaneous SFA Angioplasty/Stent Plus Popliteal Distal Bypass for Limb Salvage

Introduction: Treatment of severe critical limb ischemia (CLI) due to Superficial Femoral Artery (SFA) and below-the-knee (BTK) vessels' involvement could be compromised by the lack of a Great Saphenous Vein (GSV) suitable in its entire length. The purpose of this study is to assess the efficacy of a hybrid endovascular and open lower limbs arterial reconstruction in these patients with multilevel, advanced CLI. We combined two different techniques, each one largely validated for different level of intervention (endovascular for SFA, surgical for BTK), and we aimed to assess the efficacy of such an hybrid arterial reconstruction in patients with multilevel CLI in the lack of suitable autologous vein. Methods: From 2005 to 2019, we performed hybrid endovascular and surgical treatment for limb salvage in SFA-BTK CLI. This consisted of percutaneous transluminal angioplasty (PTA) with or without stenting of the SFA, along with distal origin vein graft bypass. Inclusion criteria were: Rutherford category 5 or 6, lack of a suitable GSV, patency of the popliteal artery, steno-obstructive lesions of the SFA, lesions of the three crural vessels > 5 cm in length each. The follow-up was performed with duplex scan surveillance of both the bypass graft and PTA sites. Results: The hybrid treatment was performed in 34 patients. 56% of the SFA steno-obstructive lesions were treated with simple PTA, except for the application of a bare metal stent in one patient (3%), while in all the SFA occlusions PTA was completed with covered stents (41%). Thirty-four popliteal-to-distal vein bypass grafts have been performed. There were no perioperative PTA or bypass graft failures. Clinical improvement was achieved in 26 (76%) patients. Overall, primary, assisted primary and secondary patency, limb salvage, and survival rates were 65%, 70%, 68%, and 75% at 5 years, respectively (Graph 1 and Graph 2). Conclusion: A hybrid strategy in multilevel SFA-BTK CLI is a well established approach. Additional studies are warranted to validate these results.Graph 2View Large Image Figure ViewerDownload Hi-res image Download (PPT) Disclosure: Nothing to disclose

Simultaneous Superficial Femoral Artery Angioplasty/Stent Plus Popliteal Distal Bypass for Limb Salvage

Treatment of severe critical limb ischemia (CLI) due to superficial femoral artery (SFA) and below-the-knee (BTK) vessels' involvement could be compromised by the lack of a great saphenous vein (GSV) suitable in its entire length. The purpose of this study is to assess the efficacy of a hybrid endovascular and open lower limbs arterial reconstruction in these patients with multilevel, advanced CLI. From 2005 to 2019, we performed hybrid endovascular and surgical treatment for limb salvage in SFA-BTK CLI. This consisted of percutaneous transluminal angioplasty (PTA) with or without stenting of the SFA, along with distal origin vein graft bypass. Inclusion criteria were Rutherford category 5 or 6, lack of a suitable GSV, patency of the popliteal artery, steno-obstructive lesions of the SFA, lesions of the 3 crural vessels >5cm in length each. The follow-up was performed with duplex scan surveillance of both the bypass graft and PTA sites. The hybrid treatment could be performed in 34 patients. Fifty-six percent of the SFA steno-obstructive lesions were treated with simple PTA, except for the application of a bare metal stent in one patient (3%), while in all the SFA occlusions PTA was completed with covered stents (41%). Thirty-four popliteal-to-distal vein bypass grafts bypass grafts have been performed. There were no perioperative PTA or bypass graft failures. Clinical improvement was achieved in 26 (76%) patients. Overall, primary and secondary patency, limb salvage, and survival rates were 65%, 68%, 75%, and 75% at 5years, respectively. A hybrid strategy in multilevel SFA-BTK CLI is a well-established approach. Additional studies are warranted to validate these results.

The First Mantidfly (Neuroptera: Mantispidae) from the Early Eocene Green River Formation

Protonolima mantispinoformis gen. et sp. nov. (Neuroptera: Mantispidae) is described from the early Eocene Green River Formation. It likely belongs to Calomantispinae, on the basis of the very distal origin of posterior radius and the basal crossvein between media and cubitus (1m-cu) connecting radius + media and anterior cubitus; if so, it would be the only fossil representative of the subfamily. Protonolima gen. nov. is probably most closely related to the extant American genus Nolima.

Abstract 730: Genomic characterization of hereditary leiomyomatosis and renal cell carcinoma (HLRCC), a rare and aggressive kidney cancer

Abstract Background Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) is a rare autosomal-dominant syndromic disorder associated with germline FH mutations. Affected individuals have a predisposition to cutaneous and uterine leiomyoma’s, and are at increased risk of developing a renal cell carcinoma (HLRCC- associated RCC) with aggressive clinical outcome. However, aside from FH bi-allelic loss, additional genomic features of HLRCC are currently poorly understood. Method Five cases of HLRCC-associated RCC were characterized using integrated next generation sequencing (NGS) technology. This included an index case where multiple tumor sites (kidney, lung, liver, lymph node, skin, and uterine) from a single patient were characterized. For integrative analysis, in-house data were combined with five RCC cases with FH bi-allelic loss from The Cancer Genome Atlas Study. Single cell sequencing was carried out on normal human kidney to study the cell of origin for HLRCC- associated RCC. Results: Integrative NGS profiling and analysis of HLRCC-associated RCC tumors (n=10) revealed several important observations such as 1) a high frequency loss of whole chromosomes, which is reminiscent of tumors arising from the distal nephron, 2) low mutational burden similar to that observed in other kidney tumors and, 3) a HLRCC specific gene expression signature and discovery of a novel therapeutic candidate (HLRCC-TC1). Importantly, among renal tumors, HLRCC-TC1 was specifically expressed in HLRCC and other RCCs with poor clinical outcome. Application of siRNAs and neutralizing antibodies to HLRCC-TC1 reduced cell proliferation of the HLRCC cell line UOK262, but did not for that of control cell lines. Conclusion: The observed FH bi-allelic mutation along with recurrent chromosome-wide losses and integrative analysis with human kidney single cell sequencing data support a distal nephron origin for HLRCC- associated RCC. In addition, our study provides evidence for nominating HLRCC-TC1 as a novel cancer-specific therapeutic target. Further studies are needed to conduct an in-depth characterization of HLRCC-TC1. Citation Format: Pankaj Vats, Yuping Zhang, Sarvana Mohan Dhanashekaran, Narayanan Sathiya Pandi, Xuhong Cao, Fengyun Su, Sudhanshu Shukla, Rui Wang, Marcin Cieslik, Jincheng Pan, Christopher J. Ricketts, Prem Kumar Kumpati, Ajjai Alva, Marston W. Linehan, Rohit Mehra, Arul M. Chinnaiyan. Genomic characterization of hereditary leiomyomatosis and renal cell carcinoma (HLRCC), a rare and aggressive kidney cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 730.

Occluded mammary graft post-coronary bypass surgery: do we need to look for the second one? A case report.

BackgroundAnatomic variations of the left internal mammary artery (LIMA) can influence coronary artery bypass surgical technique as well as posing definite difficulties in the interpretation of angiographic findings. We present an unusual anatomic variant of two LIMAs originating from the left subclavian artery discovered post-coronary artery bypass grafting surgery.Case summaryA 60-year-old man post-LIMA grafting of the left anterior descending (LAD) coronary artery underwent diagnostic cardiac catheterization. Selective angiography revealed occluded LIMA; therefore, it was decided to proceed with percutaneous coronary intervention (PCI) to the occluded native LAD. Once antegrade flow in the LAD was restored, retrograde filling of a vessel corresponding to the previously grafted LIMA was also detected. Additional contrast injection in the left subclavian artery (LSCA) showed a second patent LIMA originating from the distal segment of the LSCA.DiscussionThis patient has an unusual anatomic variant of two LIMAs originating from the LCSA. The proximal rudimentary LIMA was misinterpreted as an occluded arterial graft while the second, well-developed LIMA connected to the LAD had an unusually distal origin and had therefore been overlooked. This anatomical variant should be kept in mind when the internal mammary graft seems to be occluded.

Iliolumbar Vein: Anatomy and Surgical Importance During Lateral Transpsoas and Oblique Approaches to Lumbar Spine

Safe surgical approaches to the anterolateral lumbar spine require a good working knowledge of the anatomy and anatomic variations of this region. As the iliolumbar vein is in the vicinity of both oblique and lateral transpsoas approaches to the lower lumbar spine, the following study was performed to better elucidate its anatomy, variations, and position during such surgical procedures. Fifteen (30 sides) fresh frozen adult cadavers underwent dissection of the iliolumbar vein (ILV). The origin, course, variants, relations, and morphometrics of each vein were documented. Fluoroscopy of the vessels was performed. Lastly, anterior oblique and lateral transpsoas approaches to the lumbar spine were carried out in order to evaluate for potential ILV injury. An ILV was found on all but 2 sides (93.3%). It arose as a common trunk from the common iliac vein on 14 sides. Left ILVs tended to have a more distal origin than right ILVs. ILVs had a mean length of 3.7 cm and a mean width of 0.9 cm and were significantly larger on right versus left sides (P < 0.05). Left-sided ILVs tended to have more branches than right-sided veins. The majority of vertical branches of the ILV traveled anterior to the ventral rami of the lumbar spinal nerves, most commonly L4. The ILV and, in particular, its vertical branches coursed next to the L4 and L5 vertebrae. The ILV should be considered during both oblique and lateral transpsoas approaches to the lumbar spine.

In This Issue: November

In This Issue: November

Catheter Ablation of Idiopathic Left Posterior Fascicular Ventricular Tachycardia: Predicting the Site of Origin via Mapping and Electrocardiography.

We report the 12-lead ECG morphology of left posterior fascicular ventricular tachycardia (LPF-VT) and the relationship between His-ventricular (HV) interval and site of origin in LPF-VT. We studied 41 patients who underwent successful catheter ablation of LPF-VT with HV interval >0 ms (n=8; proximal-LPF group), HV interval 0 to -15 ms (n=15; middle-LPF group), and HV interval <-15 ms (n=18; distal-LPF group). The earliest mapped presystolic potential (PP)-QRS interval was 34.1±4.2, 24.5±3.2, and 19.4±2.8 ms in proximal-, middle-, and distal-LPF groups. The earliest PP ratio (PP-QRS interval during VT/HV interval during sinus rhythm) was 0.59±0.05, 0.45±0.07, and 0.31±0.05 in the proximal-, middle-, and distal-LPF groups. There were statistically significant differences between the 3 groups in earliest PP ratio, and there was close correlation between the HV interval during LPF-VT and earliest PP ratio. The QRS duration in the proximal-LPF group (114±6 ms) was significantly narrower compared with the middle-LPF group (128±5 ms) and distal-LPF group (140±6 ms). In leads I and V6, the ratio of R/S tended to be greater in the proximal-LPF group compared with the other 2 groups. QRS duration, the ratio of R/S in leads V6, and lead I could predict a proximal or distal origin site of LPF-VT with high sensitivity and specificity. The HV interval and 12-lead ECG morphology of LPF-VT may help predict the successful site of origin and prove useful in guiding an effective ablation strategy.

Evaluation of Morphology of Premature Ventricular Contraction on 12-Lead Electrocardiogram

Background-Evaluation of different morphology of premature ventricular contraction (PVC) in 12-lead ECG might reflect the presence or absence of myocardial diseases and determine PVC foci. It is important for ablation procedure and it can help in pre-procedural planning and potentially may improve ablation outcome.Methods and Results-In this study, 12-lead Electrocardiogram (ECG) of 50 patients with or without structural cardiac diseases, who had experienced PVC, were obtained. PVC QRS duration, contour, pattern, unifocal or multifocaland different morphology in various lead were evaluated. PVC-QRS morphology of 50 ECGs showed QRSd d” 140ms was 60%, &gt;140ms was 24%, &gt;160ms was 16%. QRS notching &lt;40ms was 42%, &gt;40ms was 16%, smooth contour was 42%. The morphology of PVCs in lead V1, RBBB morphology was 36%, LBBB morphology was 64%; in lead V1 &amp; V2, high r 8%, low r 4%. QRS wave polarity in lead I negative (QS, Qr, or rS wave pattern) 28%, positive (R-wave pattern) 52%; in lead II, III, avF, positive 76%. Of these RR’ or Rr’ pattern 20%, R pattern 56%. Negative 24%. QRS transition in chest lead, 16% transition occur at V4 –V5, 48% at V3-V4, 4% at V2-V3, 36% at V1-V2 level. The pattern of PVCs were bigeminy 24%, trigeminy 6%, couplet 4%, salvos 12%, R on T 2%, VT 6%. Of the 32 PVCs originating from the RVOT, 8 were classified as of free-wall origin, 24 of septal, 14 of left, 26 of right, 4 of proximal, and 2 of distal origin. Of the 6 PVCs originating from the LVOT, 4 were originated from the LVOT close to the left coronary cusp and 2 were originated from the LVOT close to the right coronary cusp. Of the 12 PVCs originated from LV fascicle, 12 of posterior fascicle origin and none from anterior fascicle origin.Conclusion-12-lead ECG is a simple, inexpensive and noninvasive tool to detect PVCs and facilitate their localization. By evaluating morphology of PVC, we can also predict the structural and functional state of heart.Bangladesh Heart Journal 2016; 31(2) : 75-79

High-resolution anatomic correlation of cyclic motor patterns in the human colon: Evidence of a rectosigmoid brake.

Colonic cyclic motor patterns (CMPs) have been hypothesized to act as a brake to limit rectal filling. However, the spatiotemporal profile of CMPs, including anatomic origins and distributions, remains unclear. This study characterized colonic CMPs using high-resolution (HR) manometry (72 sensors, 1-cm resolution) and their relationship with proximal antegrade propagating events. Nine healthy volunteers were recruited. Recordings were performed over 4 h, with a 700-kcal meal given after 2 h. Propagating events were visually identified and analyzed by pattern, origin, amplitude, extent of propagation, velocity, and duration. Manometric data were normalized using anatomic landmarks identified on abdominal radiographs. These were mapped over a three-dimensional anatomic model. CMPs comprised a majority of detected propagating events. Most occurred postprandially and were retrograde propagating events (84.9 ± 26.0 retrograde vs. 14.3 ± 11.8 antegrade events/2 h, P = 0.004). The dominant sites of initiation for retrograde CMPs were in the rectosigmoid region, with patterns proximally propagating by a mean distance of 12.4 ± 0.3 cm. There were significant differences in the characteristics of CMPs depending on the direction of travel and site of initiation. Association analysis showed that proximal antegrade propagating events occurred independently of CMPs. This study accurately characterized CMPs with anatomic correlation. CMPs were unlikely to be triggered by proximal antegrade propagating events in our study context. However, the distal origin and prominence of retrograde CMPs could still act as a mechanism to limit rectal filling and support the theory of a "rectosigmoid brake."NEW & NOTEWORTHY Retrograde cyclic motor patterns (CMPs) are the dominant motor patterns in a healthy prepared human colon. The major sites of initiation are in the rectosigmoid region, with retrograde propagation, supporting the idea of a "rectosigmoid brake." A significant increase in the number of CMPs is seen after a meal. In our study context, the majority of CMPs occurred independent of proximal propagating events, suggesting that CMPs are primarily controlled by external innervation.