Orbital atherectomy safety and efficacy: A comparative analysis of ostial versus non-ostial calcified coronary lesions.

BACKGROUND: The safety and efficacy of coronary orbital atherectomy (OA) for treatment of ostial lesions are not yet fully established. We sought to evaluate (OA) treatment of severely calcified ostial and non-ostial lesions. METHODS: A retrospective analysis of subjects treated with OA for severely calcified ostial and non-ostial lesions, at the Mount Sinai Medical Center, Miami Beach, Florida (MSMCMB) from January 2014 to September 2020, was completed. Study baseline characteristics, lesion and vessel characteristics, procedural outcomes, and in-hospital major adverse cardiovascular events (MACE) were analyzed and compared. RESULTS: A total of 609 patients that underwent PCI with OA were identified. The majority of patients (81.9 %) had non-ostial lesions, while 16.6 % had ostial lesions (of which 2.8 % classified as aorto-ostial) and 1.5 % had unknown lesion anatomy. The mean age of the overall cohort was 74.0 ± 9.3 years, and 63.5 % were male. All patients received drug-eluting stent (DES) placement, and the overall freedom from MACE was 98.5 %, with no significant difference observed between the ostial and non-ostial groups. The freedom from cardiac death and MI was also similar between the two groups. There were low rates of bleeding complications and severe angiographic complications, and no persistent slow flow/no reflow was reported. CONCLUSIONS: This study demonstrated no significant differences in in-hospital MACE outcomes between patients with ostial versus non-ostial lesions, indicating that OA is a safe and effective treatment option for both lesion types, including those classified as aorto-ostial.

Knock-out of N-glycolylneuraminic acid attenuates antibody-mediated rejection in xenogenically perfused porcine lungs.

BACKGROUND: Antibody-mediated rejection has long been known to be one of the major organ failure mechanisms in xenotransplantation. In addition to the porcine α1,3-galactose (α1,3Gal) epitope, N-Glycolylneuraminic acid (Neu5Gc), a sialic acid, has been identified as an important porcine antigen against which most humans have pre-formed antibodies. Here we evaluate GalTKO.hCD46 lungs with an additional cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) gene knock-out (Neu5GcKO) in a xenogeneic ex vivo perfusion model METHODS: Eleven GalTKO.hCD46.Neu5GcKO pig lungs were perfused for up to 6 h with fresh heparinized human blood. Six of them were treated with histamine (H) blocker famotidine and 1-thromboxane synthase inhibitor Benzylimidazole (BIA) and five were left untreated. GalTKO.hCD46 lungs without Neu5GcKO (n = 18: eight untreated and 10 BIA+H treated) served as a reference. Functional parameters, blood, and tissue samples were collected at pre-defined time points throughout the perfusion RESULTS: All but one Neu5GcKO organs maintained adequate blood oxygenation and "survived" until elective termination at 6 h whereas two reference lungs failed before elective termination at 4 h. Human anti-Neu5Gc antibody serum levels decreased during the perfusion of GalTKO.hCD46 lungs by flow cytometry (∼40% IgM, 60% IgG), whereas antibody levels in Neu5GcKO lung perfusions did not fall (IgM p = .007; IgG p < .001). Thromboxane elaboration, thrombin generation, and histamine levels were significantly reduced with Neu5GcKO lungs compared to reference in the untreated groups (p = .007, .005, and .037, respectively); treatment with BIA+H masked these changes. Activation of platelets, measured as CD62P expression on circulating platelets, was lower in Neu5GcKO experiments compared to reference lungs (p = .023), whereas complement activation (as C3a rise in plasma) was not altered. MCP-1 and lactotransferin level elevations were blunted in Neu5GcKO lung perfusions (p = .007 and .032, respectively). Pulmonary vascular resistance (PVR) rise was significantly attenuated and delayed in untreated GalTKO.hCD46.Neu5GcKO lungs in comparison to the untreated GalTKO.hCD46 lungs (p = .003) CONCLUSION: Additional Neu5GcKO in GalTKO.hCD46 lungs significantly reduces parameters associated with antibody-mediated inflammation and activation of the coagulation cascade. Knock-out of the Neu5Gc sialic acid should be beneficial to reduce innate immune antigenicity of porcine lungs in future human recipients.

Human erythrocyte fragmentation during ex-vivo pig organ perfusion.

Platelet sequestration is a common process during organ reperfusion after transplantation. However, instead of lower platelet counts, when using traditional hemocytometers and light microscopy, we observed physiologically implausible platelet counts in the course of ex-vivo lung and liver xenograft organ perfusion studies. We employed conventional flow cytometry (FC) and imaging FC (AMINS ImageStream X) to investigate the findings and found platelet-sized fragments in the circulation that are mainly derived from red blood cell membranes. We speculate that this erythrocyte fragmentation contributes to anemia during in-vivo organ xenotransplant.

hEPCR.hTBM.hCD47.hHO-1 with donor clodronate and DDAVP treatment improves perfusion and function of GalTKO.hCD46 porcine livers perfused with human blood.

INTRODUCTION: Platelet sequestration, inflammation, and inappropriate coagulation cascade activation are prominent in liver xenotransplant models and are associated with poor outcomes. Here, we evaluate a cassette of six additional genetic modifications to reduce anti-pig antibody binding (α-1,3-galactosyl transferase knockout [GalTKO]) and target coagulation dysregulation (human endothelial protein C receptor [hEPRC] and thrombomodulin [hTBM]), complement pathway regulation (human membrane cofactor protein, hCD46), inflammation heme oxygenase 1 [hHO-1]), and a self-recognition receptor (integrin-associated protein [hCD47]), as well as donor pharmacologic treatments designed to blunt these phenomena. METHODS: Livers from GaltKO.hCD46 pigs ("2-gene," n = 3) and GalTKO.hCD46 pigs also transgenic for hEPRC, hTBM, hCD47, and hHO-1 ("6-gene," n = 4) were perfused ex vivo with whole human blood. Six-gene pigs were additionally pretreated with desmopressin (DDAVP) and clodronate liposomes to deplete vWF and kupffer cells, respectively. RESULTS: The average perfusion times increased from 304 (±148) min in the 2-gene group to 856 (±61) min in the 6-gene group (p = .010). The average heparin administration was decreased from 8837 U/h in the 2-gene to 1354 U/h in the 6-gene group (p = .047). Platelet sequestration tended to be delayed in the 6-gene group (p = .070), while thromboxane B2 (TXB2, a platelet activation marker) levels were lower over the first hour (p = .044) (401 ± 124 vs. 2048 ± 712 at 60 min). Thrombin production as measured by F1+2 levels tended to be lower in the 6-gene group (p = .058). CONCLUSIONS: The combination of the hEPCR.hTBM.hCD47.hHO-1 cassette along with donor pig DDAVP and clodronate liposome pretreatment was associated with prolonged function of xenoperfused livers, reduced coagulation pathway perturbations, and decreased TXB2 elaboration, and reflects significant progress to modulate liver xenograft injury in a pig to human model.

Positive Regadenoson Stress Test in a Patient on Phentermine With Normal Coronaries.

Obesity is a well-established cardiovascular (CV) risk factor with greater mortality and morbidity rates than the general population. Phentermine is a weight loss medication that is approved for short-term obesity treatment in conjunction with lifestyle modifications to decrease CV risk. A 51-year-old female with Raynaud's phenomenon who was started on phentermine one week prior presented with a one-day history of palpitations. Subsequent workup revealed non-ST elevation myocardial infarction (NSTEMI) on presentation and worsening ST segment depressions following regadenoson injection during pharmacological stress testing. Although current evidence suggests that the use of phentermine is safe and may even reduce the risk of CV disease in obese patients, it still may pose adverse CV effects. A detailed medical history, including medications used and predisposing conditions, is crucial to help identify and possibly prevent exacerbation of such CV side effects.

Humanized von Willebrand factor reduces platelet sequestration in ex vivo and in vivo xenotransplant models.

The transplantation of organs across species offers the potential to solve the shortage of human organs. While activation of human platelets by human von Willebrand factor (vWF) requires vWF activation by shear stress, contact between human platelets and porcine vWF (pvWF) leads to spontaneous platelet adhesion and activation. This non-physiologic interaction may contribute to the thrombocytopenia and coagulation pathway dysregulation often associated with xenotransplantation of pig organs in nonhuman primates. Pigs genetically modified to decrease antibody and complement-dependent rejection (GTKO.hCD46) were engineered to express humanized pvWF (h*pvWF) by replacing a pvWF gene region that encodes the glycoprotein Ib-binding site with human cDNA orthologs. This modification corrected for non-physiologic human platelet aggregation on exposure to pig plasma, while preserving in vitro platelet activation by collagen. Organs from pigs with h*pvWF demonstrated reduced platelet sequestration during lung (p ≤ .01) and liver (p ≤ .038 within 4 h) perfusion ex vivo with human blood and after pig-to-baboon lung transplantation (p ≤ .007). Residual platelet sequestration and activation were not prevented by the blockade of canonical platelet adhesion pathways. The h*pvWF modification prevents physiologically inappropriate activation of human or baboon platelets by porcine vWF, addressing one cause of the thrombocytopenia and platelet activation observed with xenotransplantation.

Factitious Disorder Masquerading as a Life-Threatening Anaphylaxis.

Factitious disorder is a psychiatric disorder in which sufferers intentionally fabricate physical or psychological symptoms in order to assume the role of the patient, without any obvious gain. We present a case of a 23-year-old female with chronic urticaria who presented with dyspnea, dysphasia, mild generalized erythema, abdominal cramps, and headache. She was tachypneic and hypotensive. This was her third admission with similar symptoms within the last 7 months. Tryptase, complement, anti-SM/RNP, Sjogren, Scl-70, C3, and C4 were negative. Computed tomography-guided bone marrow biopsy showed no mast cells. Flow cytometry did not show any immunophenotypic reaction. Other possible differentials including pregnancy, autoimmune disorders, and infections including hepatitis, thyroid disorder, and age-related malignancies were ruled out. After a thorough review, malingering disorder was ruled out, but we noticed the patient's intent of assuming a sick role. Later, the patient was diagnosed with major depressive disorder. Factitious anaphylaxis can present with multiple presentations including a life-threatening condition that mimics true anaphylaxis. A better approach would be thorough clinical evaluation and early multidisciplinary involvement. This case highlights the importance of further evidence-based studies in factitious disorder to decrease the disease burden and reduce the health care cost.

Delayed Presentation of Acute Generalized Exanthematous Pustulosis Following Treatment with Cefepime in a Patient with COVID-19 without the Use of Hydroxychloroquine.

BACKGROUND Acute generalized exanthematous pustulosis (AGEP) is a rare exanthem characterized by the abrupt onset of numerous small, non-follicular, sterile pustules arising on an erythematous base. AGEP is often associated with medications; however, it has also been connected to various viral infections including cytomegalovirus, parvovirus B19, and Epstein-Barr virus. Coronavirus disease 2019 (COVID-19) has been associated with a variety of skin findings, including erythematous or patchy rash, urticaria, hives, blisters, petechiae, livedo reticularis, and even AGEP in a patient undergoing treatment with hydroxychloroquine. CASE REPORT A 78-year-old man with a past medical history of benign prostatic hyperplasia, coronary artery disease, and atrial fibrillation presented with septic shock secondary to a urinary tract infection. On day 7 of treatment with cefepime, he became febrile and developed a pustular rash and persistent hypotension without any respiratory symptoms. Subsequently, he was diagnosed with COVID-19. Skin biopsy of the rash revealed AGEP. CONCLUSIONS AGEP is an uncommon cutaneous eruption often triggered by medications and viruses. AGEP is thought to be mediated by pro-inflammatory cells and cytokines. This report describes an unusual presentation of AGEP following treatment with cefepime for a urinary tract infection in a 78-year-old man who was found to be positive for SARS-CoV-2 infection, but was not treated with hydroxychloroquine. Although AGEP has been described in association with some viral infections, it is more commonly a drug-associated dermatosis, commonly seen during treatment with antibiotics. As in this case, AGEP usually resolves after discontinuation of the offending antibiotic.

Atypical presentation of an elderly male with autoimmune encephalitis: anti-LG1 limbic encephalitis.

INTRODUCTION: We present a case of an elderly male with anti-LG1 limbic encephalitis involving hypothalamus presenting with acute changes in mental status and persistent hyperthermia. CASE REPORT: A 74-year-old male presented to the hospital with fever and chills. He had also been evaluated by his PCP for changes in his mental status, trouble remembering things, and following directions while driving. A lumbar puncture was performed, and empiric meningitis coverage was initiated. His LP results were not suggestive for any infectious process. An MRI showed bilateral hippocampal edema. As an infectious workup was non-revealing and other causes were ruled out, with the concern for paraneoplastic or autoimmune encephalitis, patient was started on high dose steroids and plasma exchange while results of antibodies for autoimmune and paraneoplastic encephalitis were awaited. After plasmapheresis and a course of steroids, the patient's mental status began to slowly improve. He was discharged from the hospital and on subsequent neurology office visit, his serum autoimmune encephalitis panel returned positive for anti-LGI 1 antibodies. Further management consisted of outpatient rituximab infusion. DISCUSSION: Diagnosis of limbic encephalitis can be challenging and can present with symptoms of limbic dysfunction. A modest index of suspicion of limbic encephalitis should be kept in adults with altered mental changes. Early recognition and initiation of therapy can be crucial in the management of patients with autoimmune encephalitis and can prevent permanent cognitive impairment and damage.

A 31-Year-Old Man with COVID-19-Associated Empyema and Lupus Anticoagulant.

BACKGROUND COVID-19 was declared a pandemic in March 2020 in the United States. It has been associated with high mortality and morbidity all over the world. COVID-19 can cause a significant inflammatory response leading to coagulopathy and this hypercoagulable state has been associated with worse clinical outcomes in these patients. The published data regarding the presence of lupus anticoagulant in critically ill COVID-19-positive patients is limited and indicates varying conclusions so far. CASE REPORT Here, we present a case of a 31-year-old man who was admitted to the hospital with COVID-19 pneumonia, complicated with superadded bacterial empyema and required video-assisted thoracoscopic surgery with decortication. This patient also had prolonged prothrombin time on preoperative labs, which was not corrected with mixing study. Further workup detected positive lupus anticoagulant and anti-cardiolipin IgM along with alteration in other coagulation factor levels. The patient was treated with fresh frozen plasma and vitamin K before surgical intervention. He had an uneventful surgical course. He received prophylactic-dose low molecular weight heparin for venous thromboembolism prophylaxis and did not experience any thrombotic events while hospitalized. CONCLUSIONS COVID-19 infection creates a prothrombotic state in affected patients. The formation of micro-thrombotic emboli results in significantly increased mortality and morbidity. Routine anticoagulation with low molecular weight heparin can prevent thrombotic events and thus can improve patient outcomes. In patients with elevated prothrombin time, lupus anticoagulant/anti-cardiolipin antibody-positivity should be suspected, and anticoagulation prophylaxis should be continued perioperatively for better outcomes.

Metformin Associated Lactic Acidosis in the Intensive Care Unit: A Rare Condition Mimicking Sepsis.

Metformin-associated lactic acidosis (MALA) is a rare but serious complication of metformin use, associated with high mortality. MALA can occur any time a patient on metformin suffers disruption in renal function resulting in the accumulation of metformin. A 63-year-old man with a history of non-insulin-dependent type 2 diabetes mellitus, alcohol abuse, and hypothyroidism was brought to the emergency department with altered mental status, nausea, vomiting, and abdominal pain. He was found to be in respiratory distress, was hypotensive and hypoglycemic (48 mg/dL), and required emergent intubation. Blood work was significant for pH<6.69, undetectable bicarbonate, anion gap 37.2 mEq/L, lactate >12 mmol/L, creatinine 15.95 mg/dL, blood urea nitrogen (BUN) 112 mg/dL, glomerular filtration rate (GFR), 3 ml/min/1.73sqm, and potassium 7 mmol/L. He suffered cardiac arrest, underwent cardiopulmonary resuscitation (CPR), and was admitted to the intensive care unit (ICU) where he required multiple vasopressors, bicarbonate infusion, and bicarbonate pushes. He was started on continuous renal replacement therapy with a high flux membrane. A high dose of pre- and post- filter fluids was used to improve conductive clearance. His pH corrected to normal in less than 24 hours, and hemodialysis was initiated the following day for a total of four days. Head/chest/abdomen/pelvis CT, urine, and blood cultures did not reveal any pathology that would explain lactic acidosis. The patient's dose of metformin was 1 gr twice daily and sitagliptin, 100 mg daily. Blood metformin that had been tested on admission was 29 mcg/ml (therapeutic range, 1-2 mcg/ml). Methanol, ethanol, ethylene glycol, propylene glycol, and isopropanol levels were negative. He had been started on lisinopril 5 mg and amitriptyline 25 mg four weeks prior to admission and had normal creatinine at that time. He was discharged to an acute rehabilitation facility on day seven of hospitalization. MALA generally presents with nausea, vomiting, and fatigue-often mimicking sepsis. It is possible that our patient progressively developed alcoholic ketoacidosis and acute renal failure from dehydration and excessive drinking in the setting of newly started Angiotensin-converting-enzyme (ACE) inhibitor. Recommendations for the optimal treatment of MALA mostly depend on expert opinion and case reports. Treatment is restricted to supportive measures, although hemodialysis may offer a protective effect. Our case demonstrates that even in extreme cases of MALA, prompt and adequate supportive measures can produce a favorable outcome.

Takotsubo Cardiomyopathy in a Nonagenarian With Urosepsis.

Takotsubo cardiomyopathy (TCM) is a rare but reversible myocardial left ventricular (LV) dysfunction, which mimics acute coronary syndrome (ACS) without the presence of significant coronary artery disease (CAD). Emotional stressors may include the death of kin or a life-threatening medical diagnosis whereas physical stressors include infections, endoscopic procedures, exacerbation of asthma, or systemic disorders. A 90-year-old female presented to the ED with nausea, intermittent chest heaviness, and generalized weakness for a duration of three days. Her troponin-I was elevated and an electrocardiogram (EKG) showed T-wave inversions in leads V2-V6 and no ST-segment changes. An echocardiogram (ECHO) revealed an ejection fraction (EF) of 35%-40% with anteroapical hypokinesis. She underwent cardiac catheterization showing nonobstructive CAD. She was diagnosed with pan-sensitive Escherichia coli urosepsis and started on ceftriaxone. She improved clinically and was discharged. A repeat ECHO done a month later showed normal EF. Urosepsis-induced TCM has rarely been reported in the literature. Physicians should have a high index of suspicion of TCM in patients with symptoms mimicking ACS in the presence of a physical stressor like an infection. We report the case of TCM, which resulted from a urinary tract infection (UTI) in an elderly female.

Opioid antidote induced pulmonary edema and lung injury.

INTRODUCTION: Opioid overdose emergencies are increasing every year, naloxone is the antidote for the treatment of opioid overdose. Naloxone is being dispensed to even lay persons through some programs to prevent opioid overdose deaths. CASE: 23 year old patient presented with naloxone treated opioid overdose complained of chest pain, pink frothy sputum production and shortness of breath. Physical exam showed tachycardia, tachypnea and coarse breath sounds. Imaging of the lungs showed diffuse pulmonary edema. Within an hour after the administration of naloxone patient developed pulmonary edema and lung injury. Patient was managed with non-invasive positive pressure ventilation which improved patient's symptoms in less than 6 hours confirmed by radiological improvement in 24-36 hrs. DISCUSSION: There are no specific observation guidelines post naloxone treatment in opiate overdose patients. We recommend early treatment of naloxone induced pulmonary complications during the observation period with non-invasive positive pressure ventilation to reduce the morbidity.

Lactobacillus rhamnosus Bacteremia in an Immunocompromised Renal Transplant Patient.

Conventionally, Lactobacillus species are considered as low virulence organisms and rarely cause infection in immunocompetent individuals. However, it might be an opportunistic infection source in immunocompromised patients and can cause invasive serious infections. To our knowledge, there are only a handful of cases in the literature reporting primary bloodstream infection caused by Lactobacilli spp. in transplant recipients. Here, we report a case of a kidney transplant recipient with Lactobacillus rhamnosus bacteremia.

Thromboxane and histamine mediate PVR elevation during xenogeneic pig lung perfusion with human blood.

BACKGROUND: Elevated pulmonary vascular resistance (PVR), platelet adhesion, coagulation activation, and inflammation are prominent features of xenolung rejection. Here, we evaluate the role of thromboxane and histamine on PVR, and their contribution to other lung xenograft injury mechanisms. METHODS: GalTKO.hCD46 single pig lungs were perfused ex vivo with fresh heparinized human blood: lungs were either treated with 1-Benzylimidazole (1-BIA) combined with histamine receptor blocker famotidine (n = 4) or diphenhydramine (n = 6), 1-BIA alone (n = 6) or were left untreated (n = 9). RESULTS: Six of the nine control experiments (GalTKO.hCD46 untreated), "survived" until elective termination at 4 hours. Without treatment, initial PVR elevation within the first 30 minutes resolved partially over the following hour, and increased progressively during the final 2 hours of perfusion. In contrast, 1-BIA, alone or in addition to either antihistamine treatment, was associated with low stable PVR. Combined treatments significantly lowered the airway pressure when compared to untreated reference. Although platelet and neutrophil sequestration and coagulation cascade activation were not consistently altered by any intervention, increased terminal wet/dry weight ratio in untreated lungs was significantly blunted by combined treatments. CONCLUSION: Combined thromboxane and histamine pathway blockade prevents PVR elevation and significantly inhibits loss of vascular barrier function when GalTKO.hCD46 lungs are perfused with human blood. Platelet activation and platelet and neutrophil sequestration persist in all groups despite efficient complement regulation, and appear to occur independent of thromboxane and histamine antagonism. Our work identifies thromboxane and histamine as key mediators of xenolung injury and defines those pathways as therapeutic targets to achieve successful xenolung transplantation.

Interleukin-8 mediates neutrophil-endothelial interactions in pig-to-human xenogeneic models.

BACKGROUND: Human neutrophils are sequestered by pig lung xenografts within minutes during ex vivo perfusion. This phenomenon is not prevented by pig genetic modifications that remove xeno-antigens or added human regulatory molecules intended to down-regulate activation of complement and coagulation pathways. This study investigated whether recipient and donor interleukin-8 (IL-8), a chemokine known to attract and activate neutrophils during inflammation, is elaborated in the context of xenogeneic injury, and whether human or pig IL-8 promote the adhesion of human neutrophils in in vitro xenograft models. METHODS: Plasma levels of pig, human or non-human primate (NHP) IL-8 from ex vivo pig lung perfusion experiments (n = 10) and in vivo pig-to-baboon lung transplantation in baboons (n = 22) were analysed by ELISA or Luminex. Human neutrophils stimulated with human or pig IL-8 were analysed for CD11b expression, CD18 activation, oxidative burst and adhesion to resting or TNF-activated endothelial cells (EC) evaluated under static and flow (Bioflux) conditions. For some experiments, human neutrophils were incubated with Reparixin (IL-8/CXCL8 receptor blocker) and then analysed as in the in vitro experiments mentioned above. RESULTS: Plasma levels of pig IL-8 (~6113 pg/mL) increased more than human (~1235 pg/mL) between one and four hours after initiation of ex vivo lung perfusion. However, pig IL-8 levels remained consistently low (<60 pg/mL) and NHP IL-8 plasma levels increased by ~2000 pg/mL after four hours in a pig-to-baboon lung xenotransplantation. In vitro, human neutrophils' CD11b expression, CD18 activation and oxidative burst all increased in a dose-dependent manner following exposure to either pig or human IL-8, which also were associated with increased adhesion to EC in both static and flow conditions. Reparixin inhibited human neutrophil activation by both pig and human IL-8 in a dose-dependent fashion. At 0.1 mg/mL, Reparixin inhibited the adhesion of IL-8-activated human neutrophils to pAECs by 84 ± 2.5%. CONCLUSIONS: Pig IL-8 increased in an ex vivo model of pig-to-human lung xenotransplantation but is not detected in vivo, whereas human or NHP IL-8 is elevated to a similar degree in both models. Both pig and human IL-8 activate human neutrophils and increase their adhesion to pig aortic ECs, a process significantly inhibited by the addition of Reparixin to human neutrophils. This work implicates IL-8, whether of pig or human origin, as a possible factor mediating in lung xenograft inflammation and injury and supports the evaluation of therapeutic targeting of this pathway in the context of xenotransplantation.

The role of sialic acids in the immune recognition of xenografts.

Presentation of sialic acid (Sia) varies among different tissues and organs within each species, and between species. This diversity has biologically important consequences regarding the recognition of cells by "xeno" antibodies (Neu5Gc vs Neu5Ac). Sia also plays a central role in inflammation by influencing binding of the asialoglycoprotein receptor 1 (ASGR-1), Siglec-1 (Sialoadhesin), and cellular interactions mediated by the selectin, integrin, and galectin receptor families. This review will focus on what is known about basic Sia structure and function in association with xenotransplantation, how changes in sialylation may occur in this context (through desialylation or changes in sialyltransferases), and how this fundamental pathway modulates adhesive and cell activation pathways that appear to be particularly crucial to homeostasis and inflammation for xenografts.

Vascularized Thymosternal Composite Tissue Allo- and Xenotransplantation in Nonhuman Primates: Initial Experience.

BACKGROUND: Vascularized composite allotransplantation is constrained by complications associated with standard immunosuppressive strategies. Vascularized thymus and bone marrow have been shown to promote prolonged graft survival in composite organ and soft-tissue vascularized composite allotransplantation models. We report development of a nonhuman primate vascularized thymosternal composite tissue transplant model as a platform to address donor-specific immune tolerance induction strategies. METHODS: Vascularized thymosternal allograft (skin, muscle, thymus, sternal bone) was transplanted between MHC-mismatched rhesus monkeys (feasibility studies) and baboons (long-term survival studies), with end-to-side anastomoses of the donor aorta and SVC to the recipient common femoral vessels. A male allograft was transplanted to a female's lower abdominal wall, and clinically applicable immunosuppression was given. Skin biopsies and immunological assays were completed at regular intervals, and chimerism was quantified using polymerase chain reaction specific for baboon Y chromosome. RESULTS: Four allo- and 2 xenotransplants were performed, demonstrating consistent technical feasibility. In 1 baboon thymosternal allograft recipient treated with anti-CD40-based immunosuppression, loss of peripheral blood microchimerism after day 5 was observed and anticipated graft rejection at 13 days. In the second allograft, when cutaneous erythema and ecchymosis with allograft swelling was treated with anti-thymocyte globulin starting on day 6, microchimerism persisted until immunosuppression was reduced after the first month, and the allograft survived to 87 days, 1 month after cessation of immunosuppression treatment. CONCLUSIONS: We established both allo- and xeno- composite vascularized thymosternal transplant preclinical models, which will be useful to investigate the role of primarily vascularized donor bone marrow and thymus.

Spontaneous Superficial Femoral Artery Pseudoaneurysm in Behcet's Disease.

Behcet's disease is an autoimmune multisystemic disorder on vasculitis base. Cardiovascular involvement is the most important predictor of morbidity and mortality. The treatment should be planned carefully for pathologies requiring interventions. In our report, we present a 45-year-old patient with spontaneous superficial femoral artery pseudoaneurysm, our treatment strategy, and circumstances we faced.