Undiagnosed Behçet's Disease Complicated by Multiple Pseudoaneurysms and COVID-19 Infection.

Behcet's disease (BD) is a rare multiorgan systemic disorder characterized by recurrent episodes of acute inflammation. Involvement of the vascular system, gastrointestinal tract, and central nervous system portends a poor prognosis. We report the case of a 54-year-old man who presented with a 2-week history of symptoms attributable to infrarenal aortic and left tibioperoneal trunk pseudoaneurysms, defined by CT angiography which also revealed right lower lobe pulmonary artery (PA) and right anterior tibial arterial aneurysms. A prior history of recurrent oral ulceration, periodic fever, cerebral venous sinus thrombosis, and aseptic endocarditis with pulmonary emboli invoked a diagnosis of BD. Immunosuppression was commenced immediately, following synchronous endovascular and open arterial intervention, except the PA aneurysm. He developed a fever and cough 8 days postoperatively as a consequence of COVID-19 infection from which he recovered without complications. The management of the patient's four aneurysms in different vascular territories and postoperative COVID-19 infection in the presence of mandatory immunosuppression are discussed.

From insulin injections to islet transplantation: An overview of the journey.

When, in 1869, Paul Langerhans detected the "islands of tissue" in the pancreas, he took the first step on a journey towards islet transplantation as a treatment for type 1 diabetes. The route has embraced developments across biosciences, surgery, gene therapy and clinical research. This review highlights major milestones along that journey involving whole pancreas transplantation, islet transplantation, the creation of surrogate insulin-secreting cells and novel islet-like structures using genetic and bio-engineering technologies. To obviate the paucity of human tissue, pluripotent stem cells and non-ß-cells within the pancreas have been modified to create physiologically responsive insulin-secreting cells. Before implantation, these can be co-cultured with endothelial cells to promote vascularisation and with immune defence cells such as placental amnion cells to reduce immune rejection. Scaffolds to contain grafts and facilitate surgical placement provide further opportunities to achieve physiological insulin delivery. Alternatively, xenotransplants such as porcine islets might be reconsidered as opportunities exist to circumvent safety concerns and immune rejection. Thus, despite a long and arduous journey, the prospects for increased use of tissue transplantation to provide physiological insulin replacement are drawing ever closer.

The potential role of multifunctional human amniotic epithelial cells in pancreatic islet transplantation.

Pancreatic islet cell transplantation has proven efficacy as a treatment for type 1 diabetes mellitus, chiefly in individuals who are refractory to conventional insulin replacement therapy. At present its clinical use is restricted, firstly by the limited access to suitable donor organs but also due to factors associated with the current clinical transplant procedure which inadvertently impair the long-term functionality of the islet graft. Of note, the physical, biochemical, inflammatory, and immunological stresses to which islets are subjected, either during pretransplant processing or following implantation are detrimental to their sustained viability, necessitating repeated islet infusions to attain adequate glucose control. Progressive decline in functional beta (ß)-cell mass leads to graft failure and the eventual re-instatement of exogenous insulin treatment. Strategies which protect and/or preserve optimal islet function in the peri-transplant period would improve clinical outcomes. Human amniotic epithelial cells (HAEC) exhibit both pluripotency and immune-privilege and are ideally suited for use in replacement and regenerative therapies. The HAEC secretome exhibits trophic, anti-inflammatory, and immunomodulatory properties of relevance to islet graft survival. Facilitated by ß-cell supportive 3D cell culture systems, HAEC may be integrated with islets bringing them into close spatial arrangement where they may exert paracrine influences that support ß-cell function, reduce hypoxia-induced islet injury, and alter islet alloreactivity. The present review details the potential of multifunctional HAEC in the context of islet transplantation, with a focus on the innate capabilities that may counter adverse events associated with the current clinical transplant protocol to achieve long-term islet graft function.

An unusual presentation of acute onset Charcot arthropathy.

Charcot arthropathy is a progressive condition primarily affecting the lower limbs in patients with diabetes mellitus. It is a rare complication of diabetic neuropathy and if left untreated can lead to severe limb destruction necessitating major amputation. Here, we report the case of a 41-year-old female who presented with rapidly progressive Charcot foot over a 10-day period, necessitating open reduction and internal fixation of Lisfranc-type fracture dislocations. Her presentation with a rapidly progressing red, swollen foot with a blister on the plantar aspect prompted initial treatment on the basis of a diabetic foot infection. The report will therefore serve as a useful reminder to maintain a high index of suspicion for Charcot foot, which may present in an atypical manner.

Ultrasound Surveillance of Common Iliac Artery Aneurysms.

BACKGROUND: The surveillance of patients with common iliac artery aneurysms (CIAA) does not follow a defined protocol such as the one adopted for the management of abdominal aortic aneurysms. This study explores CIAA growth rate, and seeks to determine correlations with related parameters which may serve to influence aneurysm expansion with the view of devising an effective local surveillance protocol. METHODS: Vascular laboratories across the UK were invited to participate in an online survey. Questions were designed to assess current clinical practice in regards to the surveillance of patients with CIAA. Additionally, a retrospective audit was performed using the clinical reports of patients attending a regional vascular laboratory to undergo an aorto-iliac duplex scan (USS). Expansion rate of aneurysms was studied in patients who had ≥2 USS scans; data was recorded at 6 and/or 12 monthly intervals up to 5 years. Kaplan Meier estimates of patient mortality (all cause) and intervention rate during the surveillance period were performed. Patient age, initial CIAA diameter, bilateral/unilateral CIAA and coinciding aortic aneurysm diameter were recorded to determine if these specific features were associated with CIAA growth rates. Pearson's correlation coefficient was used to determine the strength of association between variables. RESULTS: Nine hundred and ninety-five of one thousand and sixty patient records were suitable for review: 21.6% (215/995) of patients had a CIAA. Isolated CIAA accounted for 23% (50/215). Mean CIAA growth was 1.5 ± 0.3 mm/year. A strong correlation was found between CIAA diameter versus time from diagnosis (r = 0.820; P = 0.004); CIAA with smaller initial diameters (15-20 mm) expanded more rapidly than those of larger diameter at diagnosis (r = 0.871; P = 0.005). CIAA measured at >30 mm demonstrated an unpredictable growth trajectory which was also evident in those CIAA coinciding with larger AAA (>50 mm; r = 0.208; P = 0.655). CONCLUSIONS: The results obtained in this study may form the basis for a dedicated CIAA surveillance protocol.

Rotational culture and integration with amniotic stem cells reduce porcine islet immunoreactivity in vitro and slow xeno-rejection in a murine model of islet transplantation.

BACKGROUND: Pre-transplant modification of porcine islets may improve their suitability for clinical use in diabetes management by supporting graft function and reducing the potential for xeno-rejection. The present study investigates intra-graft incorporation of stem cells that secrete beta (ß)-cell trophic and immunomodulatory factors to preserve function and alter immune cell responsiveness to porcine islets. METHODS: Isolated porcine islets were maintained in a three-dimensional rotational cell culture system (RCCS) to facilitate aggregation with human amniotic epithelial cells (AECs). Assembled islet constructs were assessed for functional integrity and ability to avoid xeno-recognition by CD4+ T-cells using mixed islet:lymphocyte reaction assays. To determine whether stem cell-mediated modification of porcine islets provided a survival advantage over native islets, structural integrity was examined in a pig-to-mouse islet transplant model. RESULTS: Rotational cell culture system supported the formation of porcine islet:AEC aggregates with improved insulin-secretory capacity compared to unmodified islets, whilst the xeno-response of purified CD4+ T-cells to AEC-bearing grafts was significantly (P < 0.05) attenuated. Transplanted AEC-bearing grafts demonstrated slower rejection in immune-competent recipients compared to unmodified islets. CONCLUSIONS/INTERPRETATION: Rotational culture enables pre-transplant modification of porcine islets by integration with immunomodulatory stem cells capable of subduing xeno-reactivity to CD4+ T-cells. This reduces islet rejection and offers translational potential to widen availability and improve the clinical effectiveness of islet transplantation.

Listeria Infected Pseudoaneurysm of the Superficial Femoral Artery.

We present a unique case of listeria-infected pseudoaneurysm of the superficial femoral artery. Listeria monocytogenes, a gram positive, intracellular bacterium, is widespread in the environment. The manifestation of infection in humans ranges from mild gastroenteritis to life-threatening listeriosis. The incidence in the healthy population is low (0.7 per 100,000) but rises sharply in pregnancy, the immunocompromised and patients with malignancy. Listeria rarely causes mycotic aneurysm formation, with fewer than 40 cases reported in the literature. Further investigation revealed the patient to be diagnosed with a hepatocellular carcinoma. It is likely that the two pathologies were linked. Hence, we would advocate investigation for underlying malignancy in patients presenting with a mycotic aneurysm, particularly those resulting from Listeria infection.

Low gravity rotational culture and the integration of immunomodulatory stem cells reduce human islet allo-reactivity.

Modification of human islets prior to transplantation may improve long-term clinical outcome in terms of diabetes management, by supporting graft function and reducing the potential for allo-rejection. Intragraft incorporation of stem cells secreting beta (ß)-cell trophic and immunomodulatory factors represents a credible approach, but requires suitable culture methods to facilitate islet alteration without compromising integrity. This study employed a three-dimensional rotational cell culture system (RCCS) to achieve modification, preserve function, and ultimately influence immune cell responsiveness to human islets. Islets underwent intentional dispersal and rotational culture-assisted aggregation with amniotic epithelial cells (AEC) exhibiting intrinsic immunomodulatory potential. Reassembled islet constructs were assessed for functional integrity, and their ability to induce an allo-response in discrete T-cell subsets determined using mixed islet:lymphocyte reaction assays. RCCS supported the formation of islet:AEC aggregates with improved insulin secretory capacity compared to unmodified islets. Further, the allo-response of peripheral blood mononuclear cell (PBMC) and purified CD4+ and CD8+ T-cell subsets to AEC-bearing grafts was significantly (p < 0.05) attenuated. Rotational culture enables pre-transplant islet modification involving their integration with immunomodulatory stem cells capable of subduing the allo-reactivity of T cells relevant to islet rejection. The approach may play a role in achieving acute and long-term graft survival in islet transplantation.

Accelerated development of mesenteric and renal artery calcific atherosclerosis following radiotherapy for testicular cancer.

We present a case of a 61-year-old male presenting with post-prandial epigastric pain and marked weight loss. Investigation revealed calcific atherosclerosis of the abdominal aorta, coeliac axis, superior mesenteric (SMA) and renal arteries. He had undergone radiotherapy for testicular teratoma 34 years previously. Percutaneous mesenteric revascularization by primary stenting of the SMA proved successful. Radiotherapy for intra-abdominal malignancy has the potential to induce both acute and chronic enteritis and an accelerated atherosclerotic process in the arteries within the field of beam.

Isolated dissecting aneurysms of the abdominal aorta and the superior mesenteric artery. A case report and literature review.

Supracoeliac abdominal aortic dissections are rare and require complex interventions for repair. Superior mesenteric artery (SMA) dissections are also rare and even less frequently reported to involve aneurysmal change. We present the case of a 65-year-old man with a dissecting supracoeliac aortoiliac aneurysm and a separate dissecting aneurysm of the SMA The surgical intervention performed and a review of the literature on the management of SMA dissection in the endovascular era are presented.

An unusual presentation of thoracoacromial artery pseudoaneurysm following shoulder arthroplasty.

Pseudoaneurysms of peripheral arteries are not an uncommon condition presenting to vascular surgeons. Perioperative injury and infection are two of the commonest causes. We describe a case of an 82-year-old lady, who presented 10 years following right shoulder joint replacement, with a sharply marginated erythematous cutaneous eruption over the right shoulder. Subsequent angiography revealed a pseudoaneurysm of the acromial branch of the thoracoacromial artery. Planned intervention was superseded by a further embolic episode, which prompted immediate percutaneous translumninal embolisation of the aneurysm. The aetiology of a pseudoaneurysm 10 years following shoulder arthroplasty is discussed.

Pre-transplant signal induction for vascularisation in human islets.

Human islet transplant success is partially impaired by slow revascularisation. Our study investigated the potential for rotational cell culture (RC) of human islets combined with thiazolidinedione (TZD) stimulation of peroxisome proliferator-activated receptor gamma (PPARγ) to upregulate vascular endothelial growth factor (VEGF) expression in the islets. Four groups of human islets were studied: static culture (SC) with and without 25 mmol/L TZD and RC with and without 25 mmol/L TZD. These were assessed for insulin secretion and soluble VEGF-A release. Both proteins were quantified by enzyme-linked immunosorbent assay (ELISA), supported with qualitative immunofluorescence staining. RC + TZD increased insulin secretion by >20% (p < 0.05-0.001) in response to 16.7 mmol/L glucose and 16.7 mmol/L glucose + 10 mmol/L theophylline (G + T). This effect was seen at all time intervals compared with SC and without addition of TZD. Soluble VEGF-A release was significantly augmented by RC and TZD exposure with an increased effect of >30% (p < 0.001) at 72 h under both SC and RC conditions. RC supplemented with a TZD enhances and prolongs the release of insulin and soluble VEGF-A by isolated human islets.

Spontaneous rupture of the adrenal artery successfully treated using the endovascular approach: a report of 2 cases.

UNLABELLED: Adrenal artery rupture is a rare cause of retroperitoneal hemorrhage. We describe 2 cases of spontaneous rupture of the adrenal artery successfully treated using endovascular coil embolization. CASE REPORT: Two patients presented with sudden onset abdominal pain and hemodynamic compromise. In both the cases computed tomography (CT) showed a large retroperitoneal hemorrhage. Aortography confirmed bleeding from the right inferior adrenal artery in the first patient and the left inferior adrenal artery in the second patient. Both patients were treated with endovascular coil embolization. Subsequent CT scans demonstrated a reduction in the size of the retroperitoneal hematoma with no active bleeding. CONCLUSION: Endovascular treatment of a ruptured adrenal artery is effective, safe, and permits organ preservation.

Endovascular repair for left common iliac artery occlusion following blunt trauma without associated bony injury: image in vascular surgery.

Common iliac artery injury (CIAI), commonly associated with pelvic fractures may present with a potentially fatal combination of haemorrhage and limb ischaemia. We report a case of isolated CIAI from blunt trauma without bony injury treated successfully using endovascular repair.

Human amniotic epithelial cells induce localized cell-mediated immune privilege in vitro: implications for pancreatic islet transplantation.

Chronic systemic immunosuppression in cell replacement therapy restricts its clinical application. This study sought to explore the potential of cell-based immune modulation as an alternative to immunosuppressive drug therapy in the context of pancreatic islet transplantation. Human amniotic epithelial cells (AEC) possess innate anti-inflammatory and immunosuppressive properties that were utilized to create localized immune privilege in an in vitro islet cell culture system. Cellular constructs composed of human islets and AEC (islet/AEC) were bioengineered under defined rotational cell culture conditions. Insulin secretory capacity was validated by glucose challenge and immunomodulatory potential characterized using a peripheral blood lymphocyte (PBL) proliferation assay. Results were compared to control constructs composed of islets or AEC cultured alone. Studies employing AEC-conditioned medium examined the role of soluble factors, and fluorescence immunocytochemistry was used to identify putative mediators of the immunosuppressive response in isolated AEC monocultures. Sustained, physiologically appropriate insulin secretion was observed in both islets and islet/AEC constructs. Activation of resting PBL proliferation occurred on exposure to human islets alone but this response was significantly (p < 0.05) attenuated by the presence of AEC and AEC-conditioned medium. Mitogen (phytohaemagglutinin, 5 µg/ml)-induced PBL proliferation was sustained on contact with isolated islets but abrogated by AEC, conditioned medium, and the islet/AEC constructs. Immunocytochemical analysis of AEC monocultures identified a subpopulation of cells that expressed the proapoptosis protein Fas ligand. This study demonstrates that human islet/AEC constructs exhibit localized immunosuppressive properties with no impairment of ß-cell function. The data suggest that transplanted islets may benefit from the immune privilege status conferred on them as a consequence of their close proximity to human AEC. Such an approach may reduce the need for chronic systemic immunosuppression, thus making islet transplantation a more attractive treatment option for the management of insulin-dependent diabetes.

Continued lumbar spinal erosion after repair of chronic contained rupture of a mycotic abdominal aortic aneurysm.

INTRODUCTION: Mycotic aneurysm of the aorta is a rare, dangerous condition. We report a case of an abdominal aortic aneurysm (AAA) caused by Candida albicans. METHODS: Case report and review of pertinent English-language literature. CASE REPORT: A 48 year-old man presented with an acute exacerbation of long-standing back pain. Examination revealed a pulsatile epigastric mass, and radiologic examinations confirmed a 9 cm chronic contained rupture of an inflammatory infrarenal AAA. At operation, no posterior aneurysm sac was found, and lumbar vertebral erosion was noted. Lower limb vascularity was secured with left axillo-bifemoral bypass. The patient presented 12 months later with severe non-mechanical back pain. Imaging confirmed continuing vertebral erosion. At laparotomy, an autologous fibula strut was used for spinal stabilization. CONCLUSION: Aggressive multimodality therapy of infected AAA and associated vertebral osteomyelitis is necessary for a successful outcome.

Chronic type B dissecting aortoiliac aneurysm repair complicated by congenital pelvic kidney.

Although the association between abdominal aortic aneurysm and pelvic kidney is rare, previous reports have described various methods of repair with successful preservation of pelvic kidney function. We describe a unique case complicated by aortic dissection. Successful intra-operative perfusion of the kidney was maintained via a temporary axillorenal shunt.

Human islet isolation: semi-automated and manual methods.

Large yields of high-viability human islets are necessary to service the expanding programmes of islet transplantation worldwide; similarly, there is an increasing demand from diabetes researchers for a reliable and cost-effective supply of human islets. The two main isolation methods are semi-automated and manual. Both methods rely on prompt and careful removal and transfer of the donor pancreas to allow isolation to commence, preferably within eight hours. Each method involves exocrine digestion with high-activity collagenase (Liberase). The semi-automated method is standardised, generally provides higher islet yields and is used for clinical transplant purposes, although it is not suitable for all donor pancreata. The manual method is less expensive and more adaptable and enables islets to be isolated for research from most donor pancreata.

Preservation of glucose responsiveness in human islets maintained in a rotational cell culture system.

The diminution of glucose responsiveness in isolated human islets maintained under conventional static culture (CSC) conditions represents a major limitation for the long-term storage of islet tissue and precludes extensive study of beta (beta)-cell biology. In the present investigation, we examined the effect of culturing primary human islets in a rotational cell culture system (RCCS) to determine its' ability to sustain both the structural integrity and functional viability of these fragile cell constructs. Over a 10-day culture period both structural integrity and glucose-stimulated insulin release (GSIR) were preserved in islets maintained within the RCCS whilst those held under CSC conditions exhibited progressive fragmentation and rapid loss of secretory function. In addition, intentionally dissociated islet cells maintained within the RCCS demonstrated the ability to re-aggregate and form tight islet-like structures with enhanced secretory capacity compared to whole islets maintained in static culture. These findings suggest a novel use for the RCCS and illustrate its potential as an experimental tool for in vitro study of human islet/beta-cell physiology.