-
BioRxiv : the Preprint Server For... Mar 2024Vein graft failure (VGF) following cardiovascular bypass surgery results in significant patient morbidity and cost to the healthcare system. Vein graft injury can occur...
Integrated single-nuclei and spatial transcriptomic analysis reveals propagation of early acute vein harvest and distension injury signaling pathways following arterial implantation.
BACKGROUND
Vein graft failure (VGF) following cardiovascular bypass surgery results in significant patient morbidity and cost to the healthcare system. Vein graft injury can occur during autogenous vein harvest and preparation, as well as after implantation into the arterial system, leading to the development of intimal hyperplasia, vein graft stenosis, and, ultimately, bypass graft failure. While previous studies have identified maladaptive pathways that occur shortly after implantation, the specific signaling pathways that occur during vein graft preparation are not well defined and may result in a cumulative impact on VGF. We, therefore, aimed to elucidate the response of the vein conduit wall during harvest and following implantation, probing the key maladaptive pathways driving graft failure with the overarching goal of identifying therapeutic targets for biologic intervention to minimize these natural responses to surgical vein graft injury.
METHODS
Employing a novel approach to investigating vascular pathologies, we harnessed both single-nuclei RNA-sequencing (snRNA-seq) and spatial transcriptomics (ST) analyses to profile the genomic effects of vein grafts after harvest and distension, then compared these findings to vein grafts obtained 24 hours after carotid-cartoid vein bypass implantation in a canine model (n=4).
RESULTS
Spatial transcriptomic analysis of canine cephalic vein after initial conduit harvest and distention revealed significant enrichment of pathways ( < 0.05) involved in the activation of endothelial cells (ECs), fibroblasts (FBs), and vascular smooth muscle cells (VSMCs), namely pathways responsible for cellular proliferation and migration and platelet activation across the intimal and medial layers, cytokine signaling within the adventitial layer, and extracellular matrix (ECM) remodeling throughout the vein wall. Subsequent snRNA-seq analysis supported these findings and further unveiled distinct EC and FB subpopulations with significant upregulation ( < 0.00001) of markers related to endothelial injury response and cellular activation of ECs, FBs, and VSMCs. Similarly, in vein grafts obtained 24 hours after arterial bypass, there was an increase in myeloid cell, protomyofibroblast, injury-response EC, and mesenchymal-transitioning EC subpopulations with a concomitant decrease in homeostatic ECs and fibroblasts. Among these markers were genes previously implicated in vein graft injury, including (versican), (fibrillin-1), and (vascular endothelial growth factor C), in addition to novel genes of interest such as (GLIS family zinc finger 3) and (ephrin-A3). These genes were further noted to be driving the expression of genes implicated in vascular remodeling and graft failure, such as and . By integrating the ST and snRNA-seq datasets, we highlighted the spatial architecture of the vein graft following distension, wherein activated and mesenchymal-transitioning ECs, myeloid cells, and FBs were notably enriched in the intima and media of distended veins. Lastly, intercellular communication network analysis unveiled the critical roles of activated ECs, mesenchymal transitioning ECs, protomyofibroblasts, and VSMCs in upregulating signaling pathways associated with cellular proliferation (MDK, PDGF, VEGF), transdifferentiation (Notch), migration (ephrin, semaphorin), ECM remodeling (collagen, laminin, fibronectin), and inflammation (thrombospondin), following distension.
CONCLUSIONS
Vein conduit harvest and distension elicit a prompt genomic response facilitated by distinct cellular subpopulations heterogeneously distributed throughout the vein wall. This response was found to be further exacerbated following vein graft implantation, resulting in a cascade of maladaptive gene regulatory networks. Together, these results suggest that distension initiates the upregulation of pathological pathways that may ultimately contribute to bypass graft failure and presents potential early targets warranting investigation for targeted therapies. This work highlights the first applications of single-nuclei and spatial transcriptomic analyses to investigate venous pathologies, underscoring the utility of these methodologies and providing a foundation for future investigations.
PubMed: 37961724
DOI: 10.1101/2023.10.31.564995 -
Cureus Mar 2024Budd-Chiari syndrome (BCS) is a rare constellation of conditions due to obstruction of venous flow from anatomical levels ranging from the hepatic veins to the...
Budd-Chiari syndrome (BCS) is a rare constellation of conditions due to obstruction of venous flow from anatomical levels ranging from the hepatic veins to the confluence of the inferior vena cava (IVC) and right atrium. The resulting retrograde flow of blood leads to hepatomegaly, ascites, and liver failure among other features. Our case highlights the clinical features, diagnostic challenges, and management of a patient with a tumor thrombus from a metastatic prostate adenocarcinoma in a 67-year-old male leading to BCS. This patient, with a past history of prostate adenocarcinoma and aortic valve replacement on chronic warfarin anticoagulation, presented with acutely worsening abdominal pain and a distended abdomen, and imaging revealed an IVC filling defect. Subsequent imaging with a piflufolastat prostate-specific PET showing increased uptake in the IVC elucidated the diagnosis of tumor thrombosis. Management considerations include aggressive therapy and optimization of quality of life. The patient was offered both options, and options including surgical shunting, bypasses, and anticoagulation were discussed. After shared decision-making, the patient and family opted to choose the pathway of palliative radiation and anticoagulation.
PubMed: 38562314
DOI: 10.7759/cureus.55330 -
Topics in Companion Animal Medicine 2024Canine strongyloidosis by Strongyloides stercoralis is a parasitic disease emerging in Europe, which represents both a veterinary clinical issue and a public health...
Canine strongyloidosis by Strongyloides stercoralis is a parasitic disease emerging in Europe, which represents both a veterinary clinical issue and a public health challenge because of the zoonotic potential. The disease, not yet frequent in Europe, could induce severe clinical signs in dogs; thus, an early diagnosis and appropriate treatment are desirable. The aim of the present work is to retrospectively investigate the clinical and paraclinical findings in sick dogs naturally infected by S. stercoralis, with particular attention to ultrasound (US) changes at the gastrointestinal level. Twelve dogs were included in the study. The diagnosis was made by means of larval morphological identification on faecal samples and PCR. Most dogs presented with gastrointestinal signs; diarrhea and weight loss were the most common presenting complaint. Only one dog showed respiratory signs, associated to a parasitic cutaneous nodule. Hypoproteinaemia, anaemia, leucocytosis and an increase in alpha2-globulin fraction at serum protein electrophoresis were common (>50%) but not constant findings. The most reported US picture was a fluid-filled, distended, atonic small intestine mostly associated with altered wall layering, while the wall thickness commonly associated with chronic enteritis was only rarely reported. These changes, associated with other clinical and paraclinical alterations, could increase the suspicion of canine strongyloidosis and may direct clinicians to include strongyloidosis in the differential diagnosis of dogs with diarrhea. The histological examination at the intestinal level, available in five dogs, revealed the presence of parasites from the full-thickness biopsy, but not from the endoscopic biopsy. The critical points of diagnosis in clinical practice are also discussed.
Topics: Animals; Dogs; Dog Diseases; Strongyloidiasis; Male; Female; Retrospective Studies; Feces; Strongyloides stercoralis; Ultrasonography; Diarrhea
PubMed: 38184143
DOI: 10.1016/j.tcam.2024.100845 -
Radiology Case Reports Nov 2023An imperforate hymen is a rare malformation present at birth; however, in most cases, diagnosis is missed until adolescence, when hematocolpometra and its symptoms...
An imperforate hymen is a rare malformation present at birth; however, in most cases, diagnosis is missed until adolescence, when hematocolpometra and its symptoms develop. At this stage, every further delay in diagnosis and treatment will negatively affect the quality of life of young females. It may also be one of the causes of endometriosis and its consequences, such as subfertility. Sonography of the pelvis and physical examination are the diagnostic modalities of choice for diagnosing hematocolpometra and imperforate hymen. We present a case of a 14-year-old patient admitted to the obstetrics and gynecology clinic with complaints of lower abdominal pain and urinary retention following dysuria. The patient was previously examined by a family doctor who misidentified the issue and treated it as a urinary infection. After the symptoms worsened, the patient was referred to a gynecologist. An ultrasound examination showed a distended vagina and uterus, suggesting hematocolpometra, and after further inspection, it was revealed to be caused by an imperforate hymen. A hymenectomy was performed, and about 900 mL of blood was drained. Symptoms and complaints ceased, and the patient was discharged the next day.
PubMed: 37732002
DOI: 10.1016/j.radcr.2023.08.098 -
Cureus Mar 2024A 36-year-old man presented with abdominal pain, vomiting, and diarrhea. On arrival, his vital signs were remarkable for fever (39.3 °C) and tachycardia (127 beats/min,...
A 36-year-old man presented with abdominal pain, vomiting, and diarrhea. On arrival, his vital signs were remarkable for fever (39.3 °C) and tachycardia (127 beats/min, regular). His abdomen was distended, and a blood test showed elevations of inflammatory markers. Contrast-enhanced computed tomography revealed a superior mesenteric artery thrombus, ischemic colitis, ascites, and infarctions in the spleen and right kidney. He was diagnosed with bowel necrosis due to acute mesenteric ischemia (AMI). An emergent laparotomy was performed. The following day, was identified in the blood culture. In addition, transthoracic echocardiography revealed vegetation on the mitral valve leaflet. These findings were suggestive of infective endocarditis (IE) caused by ( endocarditis); thus, the patient underwent surgical mitral valve replacement with the administration of antifungal therapy. Following postoperative intensive care and a prolonged course of antifungal treatment, he achieved a full recovery. AMI is only rarely caused by IE, and this case is the first reported instance of AMI secondary to endocarditis. When encountering patients with AMI without any risk factors for thromboembolism, clinicians should be aware that IE may cause AMI.
PubMed: 38523876
DOI: 10.7759/cureus.56747 -
International Journal of Surgery Case... Mar 2024Necrotizing fasciitis (NF) is a rare and rapidly progressing soft tissue infection. The commonly involved body parts are the extremities and trunk. Necrotizing fasciitis...
INTRODUCTION
Necrotizing fasciitis (NF) is a rare and rapidly progressing soft tissue infection. The commonly involved body parts are the extremities and trunk. Necrotizing fasciitis (NF) involving the retroperitoneum is very uncommon but associated with higher morbidity and mortality. There are only a few patients survived according to the report.
PRESENTATION OF CASE
This is a 19-year-old male patient presented with abdominal pain, high-grade fever, vomiting and abdominal distension for 3 days. On physical examination, he was hypotensive, tachycardic and febrile. He had a distended, tender abdomen, and hypoactive bowel sound. There were no significant pertinent findings on the other systems. Laboratory tests showed leukocytosis, thrombocytopenia, and elevated liver enzymes. After optimizing with resuscitation and initiating antibiotics, a laparotomy was performed. The finding was 300 ml of hemorrhagic fluid, ischemic cecum and ascending colon, and retroperitoneal necrosis. Subsequently, multiple debridement and right hemicolectomy with stoma was performed. Despite the close monitoring in the ICU, the patient died of uncontrolled sepsis.
CLINICAL DISCUSSION
Necrotizing fasciitis (NF) is a rapidly progressing infectious condition that requires urgent intervention. While it is rare for the retroperitoneum to be affected by NF, it is associated with a high mortality rate. The symptoms of retroperitoneal NF are not specific, making it difficult to diagnose. Here, we present a case of retroperitoneal NF with signs and symptoms of generalized peritonitis, resembling perforated appendicitis.
CONCLUSION
When patients are presented with a case of generalized peritonitis, it is important to include retroperitoneal NF as a potential differential diagnosis.
PubMed: 38382145
DOI: 10.1016/j.ijscr.2024.109412 -
World Journal of Clinical Cases Oct 2023Although intestinal obstruction is one of the most common surgical emergencies in an infant, it is difficult to diagnose neonatal enteric duplication cysts (EDC)...
BACKGROUND
Although intestinal obstruction is one of the most common surgical emergencies in an infant, it is difficult to diagnose neonatal enteric duplication cysts (EDC) preoperatively owing to their rarity as a cause of intestinal obstruction. We describe a case report of a neonatal EDC presenting intestinal obstruction and shock.
CASE SUMMARY
A 32-d-old male infant with a prenatal sonographic finding of bladder distension was admitted to our hospital for a severely distended abdomen, fever, and oliguria. The first diagnostic hypothesis was septic shock and intestinal obstruction. The patient's symptoms worsened; following an emergency surgical exploratory laparotomy and histopathological findings, the final diagnosis of cecal duplication cyst was confirmed. The patient's postoperative course was uneventful, and on the fifth postoperative day, oral feeding restarted. Twenty days later, the patient was discharged from the hospital.
CONCLUSION
Although EDC located in the cecum is exceptional, it should be considered when evaluating suspected intestinal obstruction and shock.
PubMed: 37901014
DOI: 10.12998/wjcc.v11.i28.6931 -
Circulation Journal : Official Journal... May 2024The gold standard graft for coronary artery bypass grafting (CABG) is the internal thoracic artery (ITA), and the second recommendation is the radial artery. However,... (Review)
Review
The gold standard graft for coronary artery bypass grafting (CABG) is the internal thoracic artery (ITA), and the second recommendation is the radial artery. However, complete revascularization with arterial grafts alone is often difficult, and the saphenous vein (SV) is the most commonly used autologous graft for CABG, because it is easier to use without restriction for the length of the graft. On the other hand, the patency of SV grafts (SVGs) is poor compared with that of arterial grafts. The SVG is conventionally harvested as a distended conduit with surrounding tissue removed, a procedure that may cause vascular damage. A no-touch technique of SVG harvesting has been reported to result in improved long-term patency in CABG comparable to that when using the ITA for grafting. Possible reasons for the excellent long-term patency of no-touch SVGs are the physical support provided by preserved surrounding perivascular adipose tissue, preservation of the vascular wall structure including the vasa vasorum, and production of adipocyte-derived factors. In this review, we discuss recent strategies aimed at improving the performance of SVGs, including no-touch harvesting, minimally invasive harvesting and mechanical support using external stents.
Topics: Humans; Coronary Artery Bypass; Saphenous Vein; Adipose Tissue; Vascular Patency; Tissue and Organ Harvesting; Graft Occlusion, Vascular; Stents
PubMed: 37914280
DOI: 10.1253/circj.CJ-23-0581 -
Cureus Apr 2024A 19-year-old girl with a short stature and presenting low intelligence quotient, illegible speech, and a greatly distended abdomen was seen at the gynecological...
A 19-year-old girl with a short stature and presenting low intelligence quotient, illegible speech, and a greatly distended abdomen was seen at the gynecological outpatient department. She underwent investigation and was found to have large abdominopelvic multicystic ovaries with no malignant features and CA125 levels within the normal range for premenopausal women. Her thyroid-stimulating hormone (TSH) was markedly elevated. She received a diagnosis of untreated severe hypothyroidism with benign giant ovarian cysts, posing a grave risk of cyst rupture and imminent complications. The parents were counseled, and they accepted the risk, agreeing to conservative therapy. Levothyroxine replacement therapy was initiated, and after one month, her TSH levels normalized. Follow-up ultrasonography after one month of her therapy revealed a marked decrease in ovarian cyst size. Thyroid replacement therapy was continued, and at the end of three months, the cysts disappeared, and the ovaries, much smaller, showed polycystic ovarian morphology. Careful analysis of clinical signs, investigations, and appropriate therapy helped avoid unnecessary surgery.
PubMed: 38784352
DOI: 10.7759/cureus.58837 -
Materials Today. Bio Oct 2023Ferrocene-based nanoparticles have garnered interest as reactive oxygen species (ROS)-responsive nanocarriers of anticancer drugs and imaging agents. However, their...
Ferrocene-based nanoparticles have garnered interest as reactive oxygen species (ROS)-responsive nanocarriers of anticancer drugs and imaging agents. However, their biomedical applications remain limited due to their poor physiological stability. PEGylation of nanocarriers improves their stability and biocompatibility. In this study, we aimed to develop novel PEG-ferrocene nanoparticles (PFNPs) with enhanced stability and ROS responsiveness for the delivery of paclitaxel (PTX) and imaging agents. PEGylation improved the stability of ferrocene nanoparticles, inhibiting their ROS-responsive destruction. Several PEG-ferrocene polymers containing different molar ratios of methacrylic acid and poly (ethylene glycol) methyl ether methacrylate was designed for optimization. ROS-responsive polymers with optimal monomer ratios were self-assembled into PFNPs with enhanced stability. The PFNPs distended, effectively releasing encapsulated PTX and imaging agents within 8 h in the presence of ROS. Furthermore, they remained stable, with no changes in their hydrodynamic diameters or polydispersity indexes after storage in an aqueous solution and biological buffer. The accumulation of PFNPs in a tumor model was 15-fold higher than a free dye. PTX-loaded PFNPs showed a substantial tumor-suppression effect, reducing tumor size to approximately 18% of that in the corresponding control group. These findings suggest a promising application of ROS-responsive PFNPs in tumor treatment as biocompatible nanocarriers of anticancer drugs and imaging agents.
PubMed: 37664795
DOI: 10.1016/j.mtbio.2023.100774