Total coronary occlusion in chronic coronary artery disease

The hemodynamic consequence of chronic total occlusion of a coronary artery and the association of collaterals has not been well established. To examine this, 75 patients with at least one total occlusion of a major coronary artery were identified from among 267 patients undergoing selective coronary angiography. There was evidence of previous myocardial infarction in 49 (65%) of these patients. There was no intergroup (myocardial infarction versus no infarct) difference in terms of age, chronicity of angina prior to or stability of angina at selective coronary angiography, the number and distribution of total occlusions, or the extent of coronary disease. Furthermore, there was a high prevalence of angiographically demonstrated collaterals in both myocardial infarction and noninfarct patients (96% versus 98%). However, significantly greater left ventricular dysfunction, as determined by larger end-diastolic and end-systolic volumes (p<0.001), higher left ventricular end-diastolic pressure (p<0.05), and lower ejection fraction (p<0.001) was found in the myocardial infarct group. We conclude that total occlusion of the major coronary artery occurs commonly in patients with chronic coronary disease, but is associated with myocardial infarction in only 65%. The presence of collaterals, the distribution of occlusion, and the extent of associated coronary disease do not distinguish patients with and without myocardial infarction. This suggests that the temporal course of oclusion and collateral development is a more important factor in the pathogenesis of iinfarction and its hemodynamic consequences.     

Interventional treatment for acute cerebral infarction with large vessel occlusion combined with aortic arch interruption: A case report

Rationale:Aortic arch interruption is a type of congenital vascular malformation that is often observed in childhood. Most children die of congestive heart failure due to rapid deterioration. Children can only survive to adulthood if they have extremely rich collateral circulation. Cases of acute cerebral infarction with large vessel occlusion receiving interventional treatment in adult patients with interrupted aortic arch have not been reported.Patient concerns:A 55-year-old man with a history of atrial fibrillation and smoking but without a family history of stroke was admitted to our hospital with a 5-hour history of left limb weakness and speech difficulties.Diagnoses:Emergency brain computed tomography showed a large cerebral infarction in the right frontal temporal parietal lobe. He was suspected to have aortic arch interruption in the early stage of endovascular interventional therapy through the femoral artery approach, and was converted to the transradial artery pathway. The aortic arch was disconnected, and the right internal carotid artery was occluded.Interventions:Considering the possibility of cardiogenic embolism, a middle catheter was used for thrombus aspiration of the right internal carotid artery. After removal of the dark red thrombus was removed, the right internal carotid artery was successfully recanalized.Outcomes:The patient recovered well after the operation. However, the patient and his family refused further treatment for aortic arch interruption. The modified Rankin Scale score was 0 at 3 months and 1 year of follow-up which meant that he recovered quite well.Lessons:Adult patients with acute cerebral infarction with large vessel occlusion are rarely complicated with aortic arch interruption, and emergency thrombectomy via the radial artery approach is feasible.     

Intravascular large B-cell lymphoma presenting as rapidly progressive dementia and stroke: A case report

Rationale:Intravascular large B-cell lymphoma (IVLBCL) is a rare form of large B-cell non-Hodgkin lymphoma. The diagnosis is challenging and frequently made at biopsy. Here we reported a case of IVLBCL limited to the central nervous system (CNS) presenting with progressive dementia and acute stroke, who was diagnosed by brain biopsy.Patient concerns:A 47-year-old woman was transferred to our hospital with a 6-month history of rapidly progressive dementia, and left limb weakness and numbness for 3 days. She was successively misdiagnosed with inflammatory demyelinating disease and stroke. Her condition deteriorated with elevated lactate dehydrogenase and multiple hyperintense lesions on the brain.Diagnosis:She was diagnosed with IVLBCL limited to the CNS by brain biopsy.Interventions:Bone marrow puncture and incisional random skin biopsy were not found neoplastic cells. Computed tomography scans were normal with no evidence of disease outside the CNS.Outcomes:The patient died due to rapid clinical aggravation.Lessons:IVLBCL limited to the CNS is an aggressive disease with high mortality. Making a timely and correct diagnosis is crucial for early appropriate treatment in IVLBCL patients.     

Perfusion image guided mechanical thrombectomy combined with tirofiban successfully revascularize systemic lupus erythematosus related acute large vessel occlusion: A case report

Rationale:Systemic lupus erythematosus (SLE) is an important cause of stroke, more than a half the cases present as acute ischemic stroke. Thrombolysis is an effective choice in most cases, but for large vessel occlusion, mechanical thrombectomy is more effective. Here we reported a case of SLE-related stroke with left middle cerebral artery (MCA) occlusion, who was successfully treated by MT and tirofiban.Patient concern:A 38-year-old female suffered from right hemiplegia and aphasia for 8 hours. She was diagnosed with SLE 20 years ago, and neuropsychiatric SLE was considered 8 months before this onset. One month ago, glucocorticoids were discontinued by herself because of deterioration of bilateral femoral head osteonecrosis.Diagnosis:Left MCA occlusion was confirmed by computed tomography perfusion.Intervention:Immediate mechanical thrombectomy was performed and tirofiban was given to prevent re-occlusion of left MCA. Twenty fourhours later oral antiplatelet was given after intracranial hemorrhage was ruled out.Outcomes:Her neurological symptom improved several days later, and she was transferred to further rehabilitation. At 4 months follow-up she can live independently with mild hypophrasia. There was no further events of ischemic stroke in 1-year follow-up.Lessons:Mechanical thrombectomy is a highly effective and indispensable treatment for SLE related large vessel occlusion. In addition, tirofiban may reduce vessel reocclusion in special cases such as SLE and artery stenosis.     

Central Nervous System-related Graft-versus-host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hemopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for refractory hematological malignancies. However, there are many treatment-related complications, including organ disorders, graft-versus-host disease (GVHD), and infectious diseases. Furthermore, there are many unclear points regarding central nervous system (CNS) complications, and the prognosis in patients with CNS complications is extremely poor. We herein report a 49-year-old woman who developed CNS-GVHD after a second transplantation for therapy-related myelodysplastic syndrome. CNS-GVHD in this case was refractory to all treatments, including steroids, and progressed. We also present a review of the literature about the symptoms, diagnosis, and treatment of CNS-GVHD.     

The pathophysiology of chronic graft-versus-host disease

Chronic graft-versus-host disease (GVHD) still remains the most significant complication after allogeneic hematopoietic stem cell transplantation. The disease usually appears after day 100 and is characterized by signs and symptoms similar to autoimmune diseases. The pathophysiology of chronic GVHD is poorly understood because of the lack of highly satisfactory animal models and basic studies in patients. It has not been clearly determined whether the disease is a distinct entity or a continuation of acute GVHD. In experimental and clinical studies of chronic GVHD, thymic atrophy, lymphocyte depletion, and autoantibody formation have been described. Conditioning regimens and acute GVHD may disrupt thymic function and dysregulate the negative selection process of potentially autoreactive T-lymphocytes. Disruption of thymic apoptosis and failure to eliminate the majority of self-reactive lymphocytes may lead to impairment of lymphocyte homeostasis and self tolerance. Expansion and effector functions of autoreactive T-cells will then promote autoreactive B-cell activation and production of autoantibodies with target-organ damage. Chronic GVHD requires continuous CD4+ T-cell help for B-cells and is known as T-helper 2 (Th2) disease. Murine models have demonstrated the roles of interleukin (IL)-12 and IL-18 in chronic GVHD. IL-12 may cause an increase in donor CD8+ cytotoxic T-cells leading to conversion of chronic GVHD to an acute form. In contrast, IL-18 prevents chronic GVHD by decreasing numbers of CD4+ (Th2) cells and host-reactive B-cell activation and reducing alloantigen-specific immune response. Mouse and human cellular genomics coupled with advances in cell biology in donor-recipient tolerance will improve our understanding of transplantation immunology and may offer new approaches to the challenge of ameliorating chronic GVHD.     

Sirolimus in combination with tacrolimus and corticosteroids for the treatment of resistant chronic graft-versus-host disease

Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality in haematopoietic transplant recipients. Sirolimus is a macrocyclic triene antibiotic with immunosuppressive, antifungal and antitumour properties, that has activity in the prevention and treatment of acute GVHD. We conducted a phase II trial of sirolimus combined with tacrolimus and methylprednisolone in patients with steroid-resistant cGVHD. Thirty-five patients who developed GVHD after day 100 post-transplant were studied. Six patients had a complete response and 16 a partial response with an overall response rate of 63%. Major adverse events related to the combination of tacrolimus and sirolimus were hyperlipidaemia, renal dysfunction and cytopenias. Four patients had thrombotic microangiopathy (TMA) and 27 (77%) had infectious complications. The median survival for the whole group was 15 months. A significantly better outcome was observed in patients with a platelet count > or = 100 x 10(9)/l, as well as in those with true chronic manifestations of GVHD compared to those with acute GVHD beyond day 100. Controlled trials comparing this approach with alternative strategies to determine which can best achieve the goal of GVHD-free survival are warranted.     

The management and outcome of chronic graft-versus-host disease

Chronic graft-versus-host disease (cGVHD) is a common complication following allogeneic haematopoietic cell transplantation (HCT). It is the leading cause of non-relapse mortality in transplant survivors and has a significant impact upon their functional status and quality of life. Despite significant advances being made in the field of HCT over the past 25 years, there has been little change in the incidence, morbidity and mortality of cGVHD. This is partly because of a lack of understanding about the pathogenesis of the disorder but also because a lack of well validated grading systems and outcome measures has hindered clinical research. Strategies for prophylaxis have largely been unsuccessful and may compromise the graft-versus-leukaemia (GVL) effect. Standard primary treatment remains a combination of corticosteroids and calcineurin inhibitors. There is no standard therapy for those who fail to respond to corticosteroids. Many agents have been studied but there is an urgent need for systematic research to compare the efficacy of different approaches. Infection is the leading cause of death among patients with cGVHD so antimicrobial prophylaxis is mandatory. A multidisciplinary approach to the care of patients with cGVHD is essential to adequately address its effects on both physical and psychological functioning.     

Diagnosis and clinical management of chronic graft-versus-host disease

Chronic graft-versus-host disease (GVHD) occurs in approximately 60% of patients who survive for more than 100 days after receiving an allogeneic marrow or peripheral blood stem cell transplant without T-cell depletion of the graft. Chronic GVHD represents a major cause of morbidity and mortality among hematopoietic stem cell transplant recipients. Risk factors for the development of chronic GVHD and for mortality among patients who develop this complication have been defined, but the pathogenesis of chronic GVHD is not well understood. This review discusses the clinical manifestations that lead to a diagnosis of chronic GVHD and outlines an approach for therapy with glucocorticoids and extended administration of a calcineurin inhibitor. The judicious use of glucocorticoids at the lowest effective dose and alternate-day administration can minimize steroid-related side effects. Antibiotic prophylaxis to prevent infection and supportive care to minimize morbidity and prevent disability are critically important components in the management of patients with chronic GVHD. Approximately 50% of patients with chronic GVHD are able to discontinue immunosuppressive treatment within 5 years after the diagnosis, and 10% require continued treatment beyond 5 years. The remaining 40% die or develop recurrent malignancy before the chronic GVHD resolves. An improved understanding of the pathogenesis of the disease is needed to develop more effective therapy.     

Photopheresis in paediatric patients with drug-resistant chronic graft-versus-host disease

Photopheresis (ECP) is a new type of photochemotherapy, used for the treatment of oncological and autoimmune diseases. Lymphocytes are drawn from the patients by leukapheresis, treated with 8-methoxypsoralen (8-MOP) and ultraviolet light A (UVA) in an extracorporeal system and then reinfused. Skin exposure to 8-MOP and UVA (PUVA) has been shown to relieve cutaneous symptoms of graft-versus-host disease (GVHD) in bone marrow transplant (BMT) recipients. ECP, which is similar in some ways to PUVA, has been used in this study to treat four paediatric patients who developed chronic GVHD following BMT and in whom GVHD had failed to respond to conventional immunosuppressive therapy. Following ECP, skin lesions cleared almost completely and pulmonary function tests improved in two of three patients with cutaneous and lung involvement. Serum bilirubin and transaminases gradually normalized, and γGT decreased considerably in the remaining patient who had a severe cholestatic hepatopathy. The Karnofsky performance score increased to 90% in the three patients with positive responses to ECP and remained unchanged (40%) in the patient who did not respond. Immunosuppressive therapy was reduced in three patients and eventually discontinued in two. No significant side-effects were observed during the treatment. Our results suggest that ECP is a non-aggressive treatment that may benefit patients with chronic GVHD who do not respond to standard immunosuppressive therapy.     

颅内大动脉慢性闭塞血管内再通的可行性和安全性分析

目的探讨血管内介入再通颅内大动脉慢性闭塞的可行性和安全性。方法回顾性分析2009年1月至2017年1月首都医科大学宣武医院神经外科血管内介入再通的15例颅内大动脉慢性闭塞患者的临床和影像学资料。12例为椎动脉V4段闭塞,3例为颈内动脉颅内段闭塞。术前采用全脑DSA评估闭塞长度和位置,用高分辨率MRI评估闭塞性质和再通可行性;术中双侧股动脉置鞘13例,一侧用于再通置入支架,另一侧通过侧支循环代偿充盈闭塞动脉远端作为参考路径图,增加再通可行性。术后根据脑梗死溶栓(TICI)分级系统评估再通后的顺向血流,定义≥2b级为血管成功再通。结果 15例患者首次症状发作到再通时间中位数为50(18~365)d。再通成功13例,2例椎动脉颅内段再通失败。13例再通成功患者中,12例再通后复查造影正向血流恢复至TICI 3级,1例TICI 2b级;7例症状好转,4例症状无变化,1例术后出现短暂性脑缺血发作、1例出现卒中。11例患者随访中位数时间39(3~89)个月后,改良Rankin量表评分中位数为1(0~2)分。结论颅内大动脉慢性闭塞再通,术前采用高分辨率MRI评估以及术中双侧置鞘技术,可能会增加开通率和降低围手术期并发症。     

Study design and endpoints in graft-versus-host disease

The design of clinical trials for prevention or treatment of acute or chronic graft-versus-host disease poses many challenges. These challenges include the selection of primary and secondary endpoints that demonstrate clinical benefit, and the identification of measures indicating success both for individual patients and groups. Assessment of response in treatment trials should ideally encompass the prior trajectory of change before treatment. The criteria, timing and duration of response should be specified, and the potential effects of concomitant treatment and complications other than GVHD should be taken into account in assessing outcomes. A crucial element in clinical trial design is the pre-specification of the hypothesis to be tested in quantitative terms. Potential barriers to enrollment should be carefully considered in order to ensure timely completion of the trial.     

Role of extracorporeal photochemotherapy in patients with refractory chronic graft-versus-host disease

Recent studies suggest that extracorporeal photochemotherapy (ECP) may be beneficial in patients with steroid-refractory chronic graft-versus-host disease (cGvHD). However, it is not yet clear whether certain conditions, such as age, mode of onset of cGvHD etc., influence clinical response and whether certain affected organs are more sensitive to ECP than others. We analysed the main clinical and laboratory parameters related to evolution of the disease in 32 steroid-refractory cGvHD patients, to identify any useful response predictors to ECP. ECP affected the course of the disease positively in 78% (25/32) of our cases.     

Transfusion-associated graft-versus-host disease in fludarabine-treated B-chronic lymphocytic leukaemia

Summary. Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but serious complication of blood component therapy in patients with haematological malignancies. B-chronic lymphocytic leukaemia (B-CLL), however, has rarely been associated with TA-GVHD. We report three patients with advanced B-CLL who developed TA-GVHD. All these had been treated with fludarabine. Suppression of T cells by fludarabine may have contributed to an increased susceptibility to TA-GVHD. The use of irradiated blood products to prevent this complication should be considered for patients with advanced B-CLL treated with fludarabine or other purine analogues.     

Treatment of steroid refractory acute and chronic graft-versus-host disease with daclizumab

Competitive inhibition of interleukin 2-dependent lymphocytes by daclizumab demonstrates some beneficial effects in the treatment of graft-versus-host disease (GVHD). Sixteen patients with steroid refractory GVHD received daclizumab (1 mg/kg BW) on d 1, 2 (-5), 7, 14 and 21. Twelve patients suffered from grade III-IV acute GVHD and four patients from extensive chronic GVHD. Responses were observed in nine patients (six acute, three chronic GVHD). Fourteen out of 16 patients acquired infections during daclizumab treatment and three deaths were infection related. Daclizumab demonstrates limited activity and is associated with an increased incidence of infectious complications.