-
Circulation Research Jun 2024Vein graft failure following cardiovascular bypass surgery results in significant patient morbidity and cost to the healthcare system. Vein graft injury can occur during...
BACKGROUND
Vein graft failure 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. Although 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 vein graft failure. 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 and spatial transcriptomics 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-carotid 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, and vascular smooth muscle cells, namely pathways responsible for cellular proliferation and migration and platelet activation across the intimal and medial layers, cytokine signaling within the adventitial layer, and ECM (extracellular matrix) remodeling throughout the vein wall. Subsequent single-nuclei RNA-sequencing analysis supported these findings and further unveiled distinct EC and fibroblast subpopulations with significant upregulation (<0.05) of markers related to endothelial injury response and cellular activation of ECs, fibroblasts, and vascular smooth muscle cells. 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 , , and , in addition to novel genes of interest, such as and . 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 spatial transcriptomics and single-nuclei RNA-sequencing data sets, we highlighted the spatial architecture of the vein graft following distension, wherein activated and mesenchymal-transitioning ECs, myeloid cells, and fibroblasts were notably enriched in the intima and media of distended veins. Finally, intercellular communication network analysis unveiled the critical roles of activated ECs, mesenchymal-transitioning ECs, protomyofibroblasts, and vascular smooth muscle cells in upregulating signaling pathways associated with cellular proliferation (MDK [midkine], PDGF [platelet-derived growth factor], VEGF [vascular endothelial growth factor]), 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.
Topics: Animals; Dogs; Transcriptome; Single-Cell Analysis; Male; Tissue and Organ Harvesting; Female; Signal Transduction; Gene Expression Profiling
PubMed: 38808504
DOI: 10.1161/CIRCRESAHA.123.323939 -
Open Veterinary Journal Apr 2024Bloody urine is classified in farm animals as hematuria, hemoglobinuria, and myoglobinuria. In small ruminants, discolored urine is reported due to several etiologies...
BACKGROUND
Bloody urine is classified in farm animals as hematuria, hemoglobinuria, and myoglobinuria. In small ruminants, discolored urine is reported due to several etiologies which is sometimes fatal. Of these causes are babesiosis, bacillary hemoglobinuria, copper toxicity, and hypophosphatemia.
AIM
This study was designed to investigate the clinical, etiological, hematobiochemical, ultrasonographic, and pathological findings in rams and bucks with red urine syndrome.
METHODS
Eighteen male animals (nine rams and nine bucks) of 6 months to 3 years were examined. Parallel, 10 healthy controls were used. They were admitted due to red urine, voiding of only urine drops, straining during the act of urination, grunting during urination, ventral abdominal edema, and abdominal distension. The duration of the disease ranged from 2 to 30 days. A history of chronic copper toxicosis was informed in two bucks and a ram. Two blood samples were collected from diseased as well as from controls in EDTA tubes (for complete blood count testing) and in plain tubes (for serum collection).
RESULTS
Hematuria was found in 11 animals (seven bucks and four rams) while hemoglobinuria was detected in seven animals (five bucks and two rams). Sonographic findings in diseased animals included ruptured urinary bladder in 3, ruptured urethra in 5, penile calculi, uroperitoneum in 6, distended urinary bladder in 7, hydronephrosis in 5, echogenic deposits in the bladder in 3, and ventral urine accumulation in four animals. Laboratory evaluation of a Geimsa-stained blood smear confirmed the infection with Babesia in three bucks and a ram. Hemolytic anemia was marked in two bucks and a ram due to chronic copper toxicity. Biochemical abnormalities included hypoalbuminemia, hyperglobulinemia, increased blood urea nitrogen and creatinine concentration, and hyperglycemia. Postmortem examination was carried out on six animals (four rams and two bucks).
CONCLUSION
Discolored urine in rams and bucks in this study resulted from hematuria due to urinary calculi and pelvic abscessation or from hemoglobinuria due to Babesia infection or due to copper toxicity. Hemolytic anemia was the outstanding hematological finding and hypoalbuminemia, hyperglobulinemia, increased blood urea nitrogen (BUN) and creatinine, and hyperglycemia were the characteristic biochemical findings. Sonography of the urinary tract was very helpful in assessing the renal parenchyma, urinary bladder, and abdominal cavity for the verification of urolithiasis, hydronephrosis, intact or ruptured urinary bladder, uroperitoneum, and perforated urethra.
Topics: Animals; Male; Goat Diseases; Sheep Diseases; Sheep; Goats; Ultrasonography; Hematuria; Hemoglobinuria
PubMed: 38808288
DOI: 10.5455/OVJ.2024.v14.i4.13 -
Microorganisms Apr 2024Enrofloxacin is a broad-spectrum synthetic antimicrobial drug widely used in veterinary medicine. The present study aimed to determine the effective enrofloxacin dose...
Enrofloxacin is a broad-spectrum synthetic antimicrobial drug widely used in veterinary medicine. The present study aimed to determine the effective enrofloxacin dose for treating and infection in and isolates were verified using selective differential media and biochemically using the Vitek 2 test. Bacterial isolates were virulent for with LD equal to 2.03 × 10 and 2.22 × 10 CFU fish for and , respectively. Infected fish suffered from decreased feed intake followed by off-food, tail erosion, darkening of the external body surface, exophthalmia, ascites, and loss of escape reflex. Internally, congested hemorrhagic hepatopancreas with engorged distended gall bladder were dominant. The posterior kidney was congested with enlarged spleen, and empty elementary tract. Pathologically, severe degenerative changes were dominant in the hepatopancreas, posterior kidney, spleen, stomach, and gills of infected fish. Antimicrobial sensitivity test indicated the high susceptibility of and to enrofloxacin with MIC estimated at 1 and 0.0625 µg/mL, respectively. Enrofloxacin effectively protected against and infection when used with medicated feed at doses of 10 and 20 mg kg body weight.
PubMed: 38792731
DOI: 10.3390/microorganisms12050901 -
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 -
International Journal of Surgery Case... Jun 2024Intestinal intussusception is rare in adults, involving telescoping of one intestinal segment into another. Commonly associated with colonic lesions, it presents as...
INTRODUCTION AND IMPORTANCE
Intestinal intussusception is rare in adults, involving telescoping of one intestinal segment into another. Commonly associated with colonic lesions, it presents as acute obstruction. Diagnosis relies on CT. We report a rare case of colorectal intussusception due to a polyp, managed by endoscopic polypectomy.
CASE PRESENTATION
We present a case of a 74-year-old man with chronic constipation, who presented with acute abdominal pain, vomiting, and cessation of bowel movements. Hemodynamically stable, he had a distended abdomen. We diagnosed acute bowel obstruction secondary to colorectal intussusception via CT scan. Surgery was planned after resuscitation. However, after induction of general anesthesia, the procedure was postponed due to a significant diarrheal episode and resolution of the abdominal distension. A subsequent colonoscopy revealed a 10 mm polyp, which was excised endoscopically. The patient's recovery was smooth, with no recurrence after a one-year follow-up.
CLINICAL DISCUSSION
Intestinal intussusception, rare in adults, primarily affects the small intestine but may involve the colon, often associated with organic lesions or postoperative adhesions. While colocolonic intussusceptions, mostly malignant, may stem from benign causes occasionally, symptoms are nonspecific, with common pain. Diagnosis relies on CT scans, with surgery typically required, except in select cases.
CONCLUSION
Colorectal intussusception, rare in adults, may necessitate laparotomy. Spontaneous symptom resolution enables conservative management. Clinician awareness is vital to prevent unnecessary and risky surgeries, given its rarity and potential for favorable outcomes sans intervention.
PubMed: 38781843
DOI: 10.1016/j.ijscr.2024.109790 -
Cureus Apr 2024Secondary tumors of the ampulla of Vater are exceedingly rare and associated with relatively poor prognosis. Tumors of the ampulla are classified into four distinct...
Secondary tumors of the ampulla of Vater are exceedingly rare and associated with relatively poor prognosis. Tumors of the ampulla are classified into four distinct subtypes based on the location and involvement of surrounding structures. Most reported cases are of renal cell or malignant skin melanoma primary with only five previously reported cases of breast primary found in a literature review. We present a 72-year-old woman with metastatic breast cancer to the ampulla of Vater as well as multiple bones. She had a history of breast cancer status post bilateral mastectomy and chemo 27 years prior. She presented to the hospital with altered mental status and was found to have an acute liver injury. Magnetic resonance cholangiopancreatography revealed a distended gallbladder and an indeterminate left retroperitoneal mass concerning for cystic or necrotic lymphadenopathy. Endoscopy then showed an edematous and erythematous periampullary region, which was biopsied and returned positive for carcinoma. Immunohistochemical staining of the retroperitoneal mass returned positive for keratin, estrogen receptor, GATA3, and MOC31 and negative for progesterone receptor, WT1, calretinin, and E-cadherin. The periampullary region's immunohistochemistry returned positive for pankeratin (AE1/AE3) and CD138 and negative for CD45 and S100, supporting a diagnosis of primary breast carcinoma. The average time from diagnosis of breast cancer to metastasis was found to be 2.5 years. Endoscopic visual presentation of metastatic cancer to the ampulla is indistinguishable from that of primary cancers. Thus, a biopsy with cytology and immunohistochemical analysis is necessary for diagnosis. Management of secondary ampullary tumors requires a multidisciplinary team, including gastroenterology, surgery, oncology, and often palliative care. Secondary tumors have been found to be treated by any combination of Whipple's resections, chemotherapy, drainage/stenting, and endoscopic ampullectomy.
PubMed: 38756323
DOI: 10.7759/cureus.58396 -
Animals : An Open Access Journal From... Apr 2024The effects of parity and somatic cell count in milk (SCC) threshold on the udder morphology, milkability traits, and milk composition was evaluated in 41 Canarian goats...
The effects of parity and somatic cell count in milk (SCC) threshold on the udder morphology, milkability traits, and milk composition was evaluated in 41 Canarian goats in mid-lactation. The animals were divided according to parity (1st, 2nd, and 3rd), and a SCC threshold of 2000 × 10 cells/mL in milk was set to evaluate the effect of this factor on the different measured parameters. Results showed that primiparous goats had the udder smaller and less distended than multiparous goats, but no differences were detected on milk flow parameters. Furthermore, SCC and total bacterial count (TBC) tended to be higher when the parity increased. On the other hand, goats with SCC ≤ 2000 × 10 had higher cistern-floor distance (CF) and lower TBC values compared with those goats with a count above the predetermined threshold. The results suggest that a reduction in SCC can be achieved by a selection of udder morphological traits. Moreover, milk flow parameters do not seem to be a tool to determine the udder health status in Canarian goats, but long-term studies are needed to verify it.
PubMed: 38731266
DOI: 10.3390/ani14091262 -
Turkish Journal of Surgery Dec 2023Adult idiopathic hypertrophic pyloric stenosis (AIHPS) is a rare entity first described by Cruveilhier in 1835. There are only approximately 200 cases reported in the...
Adult idiopathic hypertrophic pyloric stenosis (AIHPS) is a rare entity first described by Cruveilhier in 1835. There are only approximately 200 cases reported in the English literature to date. Histologically, it may be mistaken for spindle cell neoplasms such as gastrointestinal stromal tumour (GIST). Patients with AIHPS usually present with early satiety, abdominal fullness, postprandial vomiting, epigastric pain, and eructations. Adult intussusception is rare and only accounts for 5% of all intussusceptions. Gastroduodenal intussusception is one of the rare types of adult intussusception. This is more likely to occur when a benign or malignant stomach lesion acts as a lead point. We report a case of AIHPS in a 70-year-old lady presenting with gastroduodenal intussusception. An oesophagogastroduodenoscopy (OGDS) was performed, and it revealed a diffusely thickened and narrowed pyloric antrum. A contrasted computed tomography (CECT) of the thorax and abdomen showed a distended stomach with circumferential thickening of the pylorus. The pre-pyloric antrum was intussuscepting into the pylorus, and the apex is seen within the first part of duodenum. She underwent distal gastrectomy with a Roux-en-y reconstruction via laparoscopic approach and was discharged well. AIHPS is a rare condition and should be a differential in adults presenting with gastric outlet obstruction. We believe in cases of AIHPS presenting with gastroduodenal intussusception, a distal gastrectomy with reconstruction is a reasonable approach. A multidisciplinary approach is essential to obtain the best outcome.
PubMed: 38694524
DOI: 10.47717/turkjsurg.2023.4552 -
Open Veterinary Journal Mar 2024Urolithiasis in dogs is a disorder of the urinary tract caused by the development of crystals. These crystals are composed of minerals such as phosphates, oxalates,...
BACKGROUND
Urolithiasis in dogs is a disorder of the urinary tract caused by the development of crystals. These crystals are composed of minerals such as phosphates, oxalates, urates, cystine, carbonates, and silica. It can be fatal if the diagnosis and treatment are inaccurate. This report aims to report a case of urolithiasis in a Toy Poodle dog.
CASE DESCRIPTION
A 2-year-old male Toy Poodle dog weighing 4.2 kg with black hair, and having trouble urinating was presented to Prof. Soeparwi Animal Hospital, Universitas Gadjah Mada, Indonesia. The dog is examined physically and, in the laboratory, diagnosed and continued with operative therapy. The history and physical examination revealed that the dog had been experiencing hematuria, stranguria, and oliguria for 2 months, with the last few days accompanied by decreased appetite. The dog exhibited decreased skin turgor, a capillary refill time (CRT) of less than 2 seconds, signs of pain and distress during urination, and palpation of distended urinary vesicles. Ultrasound scans revealed uroliths in the urinary vesica, which were identified by an acoustic shadow. Blood tests indicated a decrease in hematocrit and erythrocytes along with an increase in leukocytes. Urolithiasis was diagnosed in the case dog based on anamnesis, physical examination, hematological examination, and ultrasonography. Subsequently, a cystotomy was performed, and uroliths located in urinary vesicles were removed. The dog received ceftriaxone injections at 15 mg/kg body weight and vitamin B-complex injections at a concentration of 10 mg/kg body weight for 5 days. Four days post-surgery, the case dog was able to successfully urinate and pass clean urine.
CONCLUSION
The Toy Poodle dog was diagnosed with silica urolithiasis in the urinary vesicles and the urolith is quite large. Cystotomy was performed to remove the urolith. Postoperative care were included the administration of antibiotics and vitamins to facilitate the healing process. The condition of the Poodle toy dog improved.
Topics: Animals; Dogs; Dog Diseases; Male; Urolithiasis; Indonesia
PubMed: 38682149
DOI: 10.5455/OVJ.2024.v14.i3.23 -
Radiology Case Reports Jul 2024Computer tomography colonography (CTC) is a non-invasive procedure which has replaced barium enema. CTC uses helical images of a cleansed and gas-distended colon for the...
Computer tomography colonography (CTC) is a non-invasive procedure which has replaced barium enema. CTC uses helical images of a cleansed and gas-distended colon for the diagnosis and treatment of colonic neoplasms. This case study compares 2 patients: one with positive pathology (patient A) and another as comparator (patient B) with a similar pathology to discuss and debate possible treatment pathways. Patient (A) CTC showed 2 polyps: 6 mm and 10 mm, which the colorectal surgeons thought only needed follow-up. Our comparator (patient B) displayed a similar pathology which measured 9 mm. In this case (patient B), there was mutual agreement with the surgeons for polypectomy but without haematology involvement which was atypical of the usual pathway. The surgeons did not see the 9 mm polyp at polypectomy which could be due to observer error or radiology reporter error. Given that conventional colonoscopy is more sensitive in detecting polyps; a repeat of both tests could confirm the presence of polyp, however, the surgeons gave patient (B) a virtual appointment and requested a repeat CTC in 12 months. In colorectal medicine there can be variations in the treatment of patients with polyps. While a repeat of both tests could confirm the presence of polyp in patient (B), the surgeons' decisions regarding the patient's treatment reflected a balance of confidence in clinical assessment and use of diagnostic imaging which can reduce unnecessary requests and use of diagnostic tests.
PubMed: 38680738
DOI: 10.1016/j.radcr.2024.03.066