Relationship of PIEZO1 and PIEZO2 vascular expression with diabetic neuropathy.

Introduction: Diabetic distal symmetric polyneuropathy (DDSP) is the most prevalent form of diabetic peripheral neuropathy, and 25% of patients develop pain in their toes. DDSP is associated with increased cutaneous microvessel density (MVD), reduced skin blood flow, endothelial dysfunction, and impaired fluid filtration with vasodilation. The Piezo family of mechanosensitive channels is known to be involved in the control of vascular caliber by converting mechanical force into intracellular signals. Furthermore, Piezo2 is particularly involved in peripheral pain mechanisms of DDSP patients. To date, very little is known about the number, structure, and PIEZO expression in cutaneous blood vessels (BVs) of individuals with DDSP and their relation with pain and time span of diabetes. Methods and results: We studied microvessels using endothelial markers (CD34 and CD31) and smooth cell marker (α-SMA) by indirect immunohistochemical assay in sections of the glabrous skin of the toes from patients and controls. MVD was assessed through CD34 and CD31 immunoreaction. MVD determined by CD34 is higher in short-term DDSP patients (less than 15 years of evolution), regardless of pain. However, long-term DDSP patients only had increased BV density in the painful group for CD31. BVs of patients with DDSP showed structural disorganization and loss of shape. The BVs affected by painful DDSP underwent the most dramatic structural changes, showing rupture, leakage, and abundance of material that occluded the BV lumen. Moreover, BVs of DDSP patients displayed a Piezo1 slight immunoreaction, whereas painful DDSP patients showed an increase in Piezo2 immunoreaction. Discussion: These results suggest that alterations in the number, structure, and immunohistochemical profile of specific BVs can explain the vascular impairment associated with painful DDSP, as well as the temporal span of diabetes. Finally, this study points out a possible correlation between increased vascular Piezo2 immunostaining and pain and decreased vascular Piezo1 immunostaining and the development of vasodilation deficiency.

Involvement of Cutaneous Sensory Corpuscles in Non-Painful and Painful Diabetic Neuropathy.

Distal diabetic sensorimotor polyneuropathy (DDSP) is the most prevalent form of diabetic neuropathy, and some of the patients develop gradual pain. Specialized sensory structures present in the skin encode different modalities of somatosensitivity such as temperature, touch, and pain. The cutaneous sensory structures responsible for the qualities of mechanosensitivity (fine touch, vibration) are collectively known as cutaneous mechanoreceptors (Meissner corpuscles, Pacinian corpuscles, and Merkel cell-axonal complexes), which results are altered during diabetes. Here, we used immunohistochemistry to analyze the density, localization within the dermis, arrangement of corpuscular components (axons and Schwann-like cells), and expression of putative mechanoproteins (PIEZO2, ASIC2, and TRPV4) in cutaneous mechanoreceptors of subjects suffering clinically diagnosed non-painful and painful distal diabetic sensorimotor polyneuropathy. The number of Meissner corpuscles, Pacinian corpuscles, and Merkel cells was found to be severely decreased in the non-painful presentation of the disease, and almost disappeared in the painful presentation. Furthermore, there was a marked reduction in the expression of axonal and Schwann-like cell markers (with are characteristics of corpuscular denervation) as well as of all investigated mechanoproteins in the non-painful distal diabetic sensorimotor polyneuropathy, and these were absent in the painful form. Taken together, these alterations might explain, at least partly, the impairment of mechanosensitivity system associated with distal diabetic sensorimotor polyneuropathy. Furthermore, our results support that an increasing severity of DDSP may increase the risk of developing painful neuropathic symptoms. However, why the absence of cutaneous mechanoreceptors is associated with pain remains to be elucidated.

Immunological Aspects Involved in the Degeneration of Cryopreserved Arterial Allografts.

Introduction: Cryopreserved arterial allografts have remained an option in patients requiring distal revascularization or associated with vascular infection, in the absence of a valid autogenous saphenous vein. The objective of this study is to describe the different clinical, anatomopathological, and immunological findings related to vascular transplant rejection. Methods: In a prospective trial, 35 patients who underwent cryopreserved allogeneic arterial bypass were studied, including demographics and conduit patency. Anti-HLA antibody production was stablished prior to the surgery, 7 days, 1, 3 months, and every 3 months since. Clinical and ultrasound evaluation was added after the first month. Donor HLA-typing was retrieved whenever available, allowing for the characterization and quantification of donor specific antibodies. Cytotoxic crossmatch test was also performed. A second group of patients with allograft degenerations registered during the follow up period was studied. In this group, exclusively for aneurysm description and histopathological analysis, they were included those degenerated vascular transplants from the original series, but also those implanted prior to the beginning of the study and degraded during follow up. Results: All patients studied displayed an increase in anti-HLA antibodies one month after the intervention, regarding bypass patency. In total, 14 patients fulfilled requirements for the study of donor specific antibodies, equally showing IgG production detectable one month after surgery. The presence of complement-fixing antibodies was also confirmed. Antibody levels were not related to graft degeneration. No specific immune markers able to predict aneurysmal development and evolution were found. From the original group, 3 patients suffered aneurysmal degeneration during follow up, together with 9 bypasses previously implanted. Average time until the first degeneration was 33 ± 19.7 months, with 30.6 ± 17.7 and 54.5 ± 2.5 months for a second and third degeneration, when occurring. Therefore, subsequent vascular transplants frequently augmented the time for new degenerations, despite increasing sensibilization. Samples from eight degenerated allografts were available for analysis, unexpectedly showing inflammatory infiltrate in only four cases and immune complex deposition in 7. Conclusions: Immune response against vascular transplants was confirmed in all cases, but chronic rejection did not necessarily provoke bypass degradation or reduced the time for new aneurysms to develop in subsequent allografts.

Debranching aortic surgery.

Conventional open surgery still remains as the gold standard of care for aortic arch and thoracoabdominal pathology. In centers of excellence, open repair of the arch has been performed with 5% immediate mortality and a low rate of complications; however overall mortality rates are around 15%, being up to 40% of all patients rejected for treatment due to their age or comorbidities. For thoracoabdominal aortic pathology, data reported from centers of excellence show immediate mortality rates from 5% to 19%, spinal cord ischemia from 2.7% to 13.2%, and renal failure needing dialysis from 4.6% to 5.6%. For these reasons, different alternatives that use endovascular techniques, including debranching procedures, have been developed. The reported results for hybrid debranching procedures are controversial and difficult to interpret because series are retrospective, heterogenic and including a small number of patients. Clearly, an important selection bias exists: debranching procedures are performed in elderly patients with more comorbidities and with thoracoabdominal aortic aneurysms that have more complex and extensive disease. Considering this fact, debranching procedures still remain a useful alternative: for aortic arch pathology debranching techniques can avoid or reduce the time of extracorporeal circulation (ECC) or cardiac arrest which may be beneficial in high-risk patients that otherwise would be rejected for treatment. And compared to pure endovascular techniques, they can be used in emergency cases with applicability in a wide range of anatomies. For thoracoabdominal aortic aneurysms, they are mainly useful when other lesser invasive endovascular options are not feasible due to anatomical limitations or when they are not available in cases where delaying the intervention is not an option.

Complex Aortic Aneurysm: A Current Indication for Debranching.

Conventional open repair of thoracoabdominal aortic aneurysms is still associated with severe complications and shows immediate mortality rates up to 20%. Although there is an increasing number of cases treated exclusively by an endovascular approach, renovisceral debranching still represents a valid alternative in high-risk patients for open surgery and in those patients where endovascular procedures are not feasible due to anatomic limitations or are not available when patients cannot wait for treatment. Herein we report the case of a patient with multiple surgical interventions and an extensive aortic aneurysm, complicated with a chronic contained rupture of the renovisceral aorta, who was successfully treated by means of a hybrid technique involving renovisceral debranching after discarding a pure endovascular management due to anatomical criteria.

Aneurisma humeral verdadero en relación con acceso vascular en paciente trasplantado renal: a propósito de 2 casos clínicos / True brachial artery aneurism following vascular access for haemodialysis in renal trasplant patient. Two case reports

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Rotura de un aneurisma gigante de arteria hepática / Ruptured giant hepatic artery aneurysm

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"Lower limbs revascularization from supraceliac and thoracic aorta".

Revascularization of femoral arteries from descending thoracic or supraceliac aorta is an uncommon procedure, in part because of the popularization of the technically easier extra-anatomic bypasses. However, using those aortic levels as the source of the bypass inflow is a useful alternative in selected patients with aortoiliac disease, with excellent results. We report long-term results in 4 patients with revascularization from thoracic aorta and another 2 cases from aorta at supraceliac level. This technique should be considered as a good alternative in patients with adverse abdominal conditions or with a severely diseased infrarenal aorta due to heavy calcification.