Crucial role of hematopoietic JAK2V617F in the development of aortic aneurysms

JAK2V617F is the most frequent driver mutation in myeloproliferative neoplasms (MPNs) and is associated with vascular complications. However, the impact of hematopoietic JAK2V617F on the aortic aneurysms (AAs) remains unknown. Our cross-sectional study indicated that 9 (23%) out of 39 MPN patients with JAK2V617F exhibited the presence of AAs. Next, to clarify whether the hematopoietic JAK2V617F contributes to the AAs, we applied a bone marrow transplantation (BMT) with the donor cells from Jak2V617F transgenic (JAK2V617F) mice or control wild-type (WT) mice into lethally irradiated apolipoprotein E-deficient mice. Five weeks after BMT, the JAK2V617F-BMT mice and WT-BMT mice were subjected to continuous angiotensin II infusion to induce AA formation. Four weeks after angiotensin II infusion, the abdominal aorta diameter in JAK2V617F-BMT mice was significantly enlarged compared to that in the WT-BMT mice. Additionally, the abdominal AA-free survival rate was significantly lower in the JAK2V617F-BMT mice. Hematopoietic JAK2V617F accelerated aortic elastic lamina degradation as well as activation of matrix metalloproteinase (MMP)-2 and MMP-9 in the abdominal aorta. The numbers of infiltrated macrophages were significantly upregulated in the abdominal aorta of the JAK2V617F-BMT mice accompanied by STAT3 phosphorylation. The accumulation of BM-derived hematopoietic cells carrying JAK2V617F in the abdominal aorta was confirmed by use of reporter GFP-transgene. BM-derived macrophages carrying JAK2V617F showed increases in mRNA expression levels of Mmp2, Mmp9, and Mmp13. Ruxolitinib decreased the abdominal aorta diameter and the incidence of abdominal AA in the JAK2V617F-BMT mice. Our findings provide a novel feature of vascular complications of AAs in MPNs with JAK2V617F.

Evaluation of Fluid Therapy by Point-of-Care Ultrasound in Hyperglycemic Emergencies

Aim: Diabetic ketoacidosis (DKA) and Hyperosmolar hyperglycemic state (HHS) are among the cases where total body fluid deficit is high. Although it is known that dehydration is one of the main determinants of mortality and morbidity, it is difficult to determine and follow up fluid treatment in patients with multiple comorbidities. Measurement of the respiratory variability of the vena cava inferior diameter and vena cava inferior / aortic diameter measurement can be performed easily and quickly at the bedside and have a high objectivity compared to physical examination. In this study, we evaluated the follow-up of fluid therapy by POCUS with vena cava inferior diameter and vena cava inferior diameter / abdominal aortic diameter ratio in patients presenting with hyperglycemic emergencies (DKA, HHS, severe hyperglycemia). Methodology: 56 patients diagnosed with severe hyperglycemia, DKA and HHS according to the American Diabetes Association (ADA) diagnostic criteria were included in the study. Vital signs, laboratory tests(venous blood gas analysis, complete urinalysis, osmolarity, fingertip blood glucose level), fluid volume and bedside ultrasonographic measurements [vena cava inferior inspiration and expiration (iVCI and eVCI) diameter,vena cava inferior colapsiability index (VCI index), abdominal aorta diameter and ratio of vena cava inferior to abdominal aorta diameter (VCI/Ao)] were recorded. Results: Of the 56 patients, 21.4% were diagnosed with DKA 8.9%, HHS and 69.6% with severe hyperglycemia. There was a significant difference in osmolarity and although pH values ​​were not statistically significant, it tended to improve with the amount of fluid given. There was a significant difference in iVCI, VCI index and VCI/Ao. Conclusion: We believe that planning and monitoring fluid treatment with bedside ultrasonographic VCI diameter and VCI/Ao ratio measurements will reduce the undesirable complications, the intensity of emergency services, long waiting time and follow-up periods and will contribute to patient benefit and emergency departments.

Endovascular approach in isolated abdominal aortic dissections

Background Here, we report the mid-term results of endovascular treatment of isolated dissection of the abdominal aorta, which is a very rare pathology. Materials and methods A total of 11 patients (4 males (36.3%) and 7 females (63.6%)) aged 42–72 (mean, 60.3 ± 10.45) years with isolated dissection of the abdominal aorta underwent endovascular stent-graft treatment at our institution between August 2010 and September 2015. Eight patients were symptomatic, and the remaining three were asymptomatic. The asymptomatic patients had aortic aneurysms coexisting with dissection. Eight patients without aneurysm had spontaneous dissections, and the most common symptom was unresponsive abdominal pain. Results The mean abdominal aorta diameter was 46.7 ± 20.6 (range, 31.2–100.9) mm and the mean dissection length was 71.1 ± 47.3 (range, 17–162) mm. Aorto-bi-iliac stent grafts were used in all patients, and were placed successfully under spinal anesthesia in all but one (90.9%) patient. Occlusion developed in one patient due to compression of the aorto-bi-iliac graft. Right–left femoral–femoral bypass was performed in this patient, who could not be placed on the opposite side. In addition, the graft was placed in one patient using the left renal artery chimney technique. No intraoperative mortality occurred, and open surgery was not required. In addition, no death occurred and no additional intervention was required during the mean follow-up period of 25.5 ± 17.1 (range, 6–60) months. Conclusion Limited data regarding endovascular treatment of isolated dissection of the abdominal aorta are available in the literature. Based on data obtained in a limited number of patients, we consider endovascular aortic repair to be a good alternative to surgery due to its low morbidity and mortality rates.