Hematopoietic stem cell transplantation(HSCT)becomes a standard form of cellular therapy for patients with malignant diseases.HSCT is the first-choice of immunotherapy,although HSCT can be associated with many complic...Hematopoietic stem cell transplantation(HSCT)becomes a standard form of cellular therapy for patients with malignant diseases.HSCT is the first-choice of immunotherapy,although HSCT can be associated with many complications such as graft-versus-host disease(GVHD)which is a major cause of morbidity and mortality after allogeneic HSCT.It has been shown that certain gut microbiota could exert protective and/or regenerative immunomodulatory effects by the production of short-chain fatty acids(SCFAs)such as butyrate in the experimental models of GVHD after allogeneic HSCT.Loss of gut commensal bacteria which can produce SCFAs may worsen dysbiosis,increasing the risk of GVHD.Expression of G-protein coupled receptors such as GPR41 seems to be upre-gulated in the presence of commensal bacteria,which might be associated with the biology of regulatory T cells(Tregs).Treg cells are a suppressive subset of CD4 positive T lymphocytes implicated in the prevention of GVHD after allogeneic HSCT.Here,we discuss the current findings of the relationship between the modification of gut microbiota and the GVHD-related immunity,which suggested that tactics with certain probiotics for the beneficial symbiosis in gut-immune axis might lead to the elevation of safety in the allogeneic HSCT.展开更多
Background: A major cause of mortality and disability on a global scale is myocardial infarction (MI). These days, the most reliable way to detect and measure MI is via cardiovascular magnetic resonance imaging (CMR)....Background: A major cause of mortality and disability on a global scale is myocardial infarction (MI). These days, the most reliable way to detect and measure MI is via cardiovascular magnetic resonance imaging (CMR). Aims and Objectives: To evaluate the effectiveness of the Electrocardiogram DETERMINE Score in predicting the severity of coronary artery disease (CAD) in patients who have experienced an Acute Myocardial Infarction (AMI) & to assess improvements in left ventricular function at 6 months following coronary artery bypass grafting (CABG). Subjects and Methods: This Observational cohort study was done at the Cardiology and Radiology department and cardiac surgery department, Al-Azhar university hospitals and Helwan University hospital. The study involved 700 cases who patients diagnosed with Acute Myocardial Infarction and fulfilled specific criteria for selection. Result: There was highly statistically significant relation between Myocardial infarction size and ECG Marker Score as mean infarct size elevated When the number of ECG markers increased. There was a highly statistically significant relation between myocardial infarct segments, myocardial infarction size and improvement of cardiac function 6 months post-CABG. Conclusion: The study found that larger myocardial infarctions corresponded with higher DETERMINE Scores. It concluded that an ECG-based score better estimates infarct size than LVEF alone. Additionally, there was a significant statistical correlation between the size and segmentation of myocardial infarction and better cardiac function six months after CABG.展开更多
BACKGROUND: Graft-versus-host disease (GVHD) is associated with high mortality. Early diagnosis is essential to start treatment and to improve outcomes. Because of the inflammatory nature, we hypothesis that cytoki...BACKGROUND: Graft-versus-host disease (GVHD) is associated with high mortality. Early diagnosis is essential to start treatment and to improve outcomes. Because of the inflammatory nature, we hypothesis that cytokine profile of patients with GVHD may serve as diagnostic markers. The present study was to evaluate the role of cytokine profile in the diagnosis of GVHD. METHODS: An immunoassay was used to detect 29 cytokines simultaneously in the serum; the measuring sensitivity of all cytokines was pg/mL. Healthy subjects undergoing annual routine physical examinations served as negative controls; 23 patients with hepatocellular carcinoma (HCC) who had undergone liver transplantation (the LT group) comprised the test subjects. A total of 22 kidney recipients with biopsyconfirmed GVHD (the RT group) were included for comparison. HCC patients with radical surgery (the HCC group, n=22) served as positive control. The liver contents of the three cytokines, IL-2, IL-18, and IFN-γ, were detected with immunohistochemistry. Serum granzyme B and perforin were measured by flow cytometry.RESULTS: Of the 29 cytokines, the levels of IL-2 and IL-18 were increased significantly in liver recipients with GVHD compared with healthy controls (P〈0.05). The serum levels of these three cytokines in the healthy, HCC, LT, and RT groups were IL-2: 0.90±0.02, 4.14±0.61, 5.10±0.89, and 1.48±0.09 pg/mL; IL-18: 80.61±9.35, 109.51±10.93, 230.11±12.92, and 61.98±7.88 pg/mL; IFN-γ: 24.06±3.88, 24.84±3.21, 40.37±5.88, and 15.33±4.72 pg/mL, respectively. Immunohistochemistry showed that these 3 cytokines expressions in the liver were parallel to the serum cytokine. After standard anti-GVHD treatment, the expressions of IL-2, IL-18, and IFN-y were de- creased in the liver (P〈0.05). Serum granzyme B and perforin were significantly increased in GVHD patients (P〈0.05). CONCLUSIONS: IL-2, IL-18 and IFN-γ were from liver and might serve as biomarkers for monitoring GVHD develop- ment and the effects of anti-GVHD treatment. Granzyme B and perforin may play a role in increasing IL-2, IL-18, and IFN-y levels in GVHD patients.展开更多
Summary: Although mesenchymal stem cells (MSCs) are increasingly used to treat graft-versus-host disease (GVHD), their immune regulatory mechanism in the process is elusive. The present study aimed to investigate...Summary: Although mesenchymal stem cells (MSCs) are increasingly used to treat graft-versus-host disease (GVHD), their immune regulatory mechanism in the process is elusive. The present study aimed to investigate the curative effect of third-party umbilical cord blood-derived human MSCs (UCB-hMSCs) on GVHD patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their immune regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were treated with UCB-hMSCs. Immune cells including T lymphocyte subsets, NK ceils, Treg cells and dendritic cells (DCs) and cytokines including interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-α) were monitored before and after MSCs transfusion. The results showed that the symptoms of GVHD were alleviated significantly without increased relapse of primary disease and transplant-related complications after MSCs transfusion. The number of CD3^+, CD3+CD4^+ and CD3+CD8^+ cells decreased significantly, and that of NK cells remained unchanged, whereas the number of CD4^+ and CD8^+ Tregs increased and reached a peak at 4 weeks; the number of mature DCs, and the levels of TNF-α and IL-17 decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate GVHD and spare GVL effect via immunoregulations.展开更多
Here,we report a case of fulminant gastrointestinal graft-versus-host disease(GI-GVHD) with cytomegalovirus(CMV) infection in 44-year-old woman.Despite the difficulties associated with the treatment of GIGVHD and GI-C...Here,we report a case of fulminant gastrointestinal graft-versus-host disease(GI-GVHD) with cytomegalovirus(CMV) infection in 44-year-old woman.Despite the difficulties associated with the treatment of GIGVHD and GI-CMV disease,the mucosal findings and the clinical course showed marked improvements during long-term clinical observation.The endoscopic findings were remarkable,with diffuse sloughing mucosa in the stomach and highly active inflammation and deep discrete ulcers throughout the colon.Changes in the CMV quantitative polymerase chain reaction results were correlated with the endoscopic mucosal findings and were useful for assessing the efficacy of the treatment.Although a definite diagnosis of GI-GVHD is generally made by endoscopy with biopsy,the gross appearance of this disease can vary depending on the endoscopy.In this paper,we also conduct a literature review of patients with GI-GVHD.展开更多
The most common approaches to prevent and treat graft-versus-host disease (GVHD) are intended to deplete or suppress the T cells capable of mediating or supporting alloresponses;however, this renders the recipients fu...The most common approaches to prevent and treat graft-versus-host disease (GVHD) are intended to deplete or suppress the T cells capable of mediating or supporting alloresponses;however, this renders the recipients functionally T cell deficient and hence highly susceptible to infections and tumor recurrence. Depletion is often accomplished through the use of broadly reactive antibodies, while functional impairment is typically achieved by pharmacological agents that require long-term administration (usually six months or more), have significant side effects, and may not result in tolerance (i.e., nonresponsiveness) of donor T cells to conditioning regimen-resistant host alloantigen-bearing cells. As our knowledge of immune system homeostasis has increased, cell populations with immune regulatory function have been identified and characterized. Although such cell populations are typically present in low frequencies, methods to isolate and expand these cells have permitted their supplementation to the donor graft or infusion late post-transplant in order to stifle GVHD. This review discusses the biology and preclinical proof of concept of GVHD models, along with GVHD outcomes that focus exclusively on immune regulatory cell therapies that have progressed to clinical testing.展开更多
This study examined the expressions of human serum tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell ...This study examined the expressions of human serum tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their clinical significance. The serum TF and TFPI levels were detected by ELISA in 28 allo-HSCT recipients before and after the transplanta-tion and the changes of TF and TFPI levels were dynamically monitored at different phases of the disease. No significant differences in the serum TF and TFPI levels were found in allo-HSCT recipi-ents in the absence of aGVHD or with gradeⅠaGVHD before and after the transplantation. The lev-els of serum TF and TFPI were substantially increased in the patients with gradeⅡ aGVHD at the peak of aGVHD (P〈0.05) and they were even higher in the patients with grade Ⅲ–Ⅳ aGVHD (P〈0.01). When the conditions became stable after treatment with immunosuppressive agents, the serum TFPI level was decreased to the baseline level (P〉0.05) and the TF level was lowered but still higher than the baseline level (P〈0.05). It was concluded that the levels of serum TF and TFPI were increased significantly in the patients with grade Ⅱ–Ⅳ aGVHD after allo-HSCT and decreased markedly after the treatment. Monitoring the levels of serum TF and TFPI in the patients with allo-HSCT is important to predict the occurrence, outcome and prognosis of aGVHD.展开更多
The surgical techniques used by Austoni and Egydio in the treatment of Peyronie's disease are based on geometric principles. The aim of this paper is to report our multicentric experience and technical changes to Aus...The surgical techniques used by Austoni and Egydio in the treatment of Peyronie's disease are based on geometric principles. The aim of this paper is to report our multicentric experience and technical changes to Austoni's original technique, focusing on several tips and tricks to make this technique easy to perform, even by less experienced practitioners. We performed operations in three different Italian institutions. We implanted a small soft Virilis I~ axial prostheses (Ф 7 Fr.), using a bovine pericardium collagen matrix patch (Hydrix) to cover the defect in the tunica albuginea. Sixty patients with a mean age of 58 years (range 44-76 years) underwent surgery between September 2005 and January 2010. After surgery, mean lengthening of the shaft was 2 cm (range 1.2-2.3 cm) with complete correction of penile recurvatum. Thirty-nine patients resumed sexual activity 60 days later, 14 after 90 days and 7 after 120 days. The international index of erectile function (IIEF) score was 15.5 before surgery and it improved to 23 at 12 and 24 months after surgery. Furthermore, the visual analogue scale (VAS) showed good results in terms of the recovery of natural sexual intercourse (over 80% of couples) and of the original length and girth of the penis. The soft implant we used takes advantage of erection that occurs spontaneously, using the residual erection of the spared cavernous tissue. The method is easy to learn and reproducible, and the use of pericardium speeds up the operation, while also covering large defects of the tunica albuginea that result from complex recurvatum.展开更多
BACKGROUND Children with acute liver failure(ALF)who meet the criteria are eligible for super-urgent transplantation,whereas children with end-stage chronic liver disease(ESCLD)are usually transplanted electively.Pedi...BACKGROUND Children with acute liver failure(ALF)who meet the criteria are eligible for super-urgent transplantation,whereas children with end-stage chronic liver disease(ESCLD)are usually transplanted electively.Pediatric liver transplantation(PLT)in ALF and ESCLD settings has been well described in the literature,but there are no studies comparing the outcomes in these two groups.AIM To determine if there is a difference in post-operative complications and survival outcomes between ALF and ESCLD in PLT.METHODS This was a retrospective observational study of all primary PLTs performed at a single center between 2000 and 2019.ALF and ESCLD groups were compared for pretransplant recipient,donor and operative parameters,and post-operative outcomes including graft and patient survival.RESULTS Over a 20-year study period,232 primary PLTs were performed at our center;195 were transplanted for ESCLD and 37 were transplanted for ALF.The ALF recipients were significantly older(median 8 years vs 5.4 years;P=0.031)and heavier(31 kg vs 21 kg;P=0.011).Living donor grafts were used more in the ESCLD group(34 vs 0;P=0.006).There was no difference between the two groups concerning vascular complications and rejection,but there were more bile leaks in the ESCLD group.Post-transplant patient survival was significantly higher in the ESCLD group:1-,5-,and 10-year survival rates were 97.9%,93.9%,and 89.4%,respectively,compared to 78.3%,78.3%,and 78.3%in the ALF group(P=0.007).However,there was no difference in 1-,5-,and 10-year graft survival between the ESCLD and ALF groups(90.7%,82.9%,77.3%vs 75.6%,72.4%,and 66.9%;P=0.119).CONCLUSION Patient survival is inferior in ALF compared to ESCLD recipients;the main reason is death in the 1st year post-PLT in ALF group.Once the ALF children overcome the 1st year after transplant,their survival stabilizes,and they have good long-term outcomes.展开更多
Background It is still controversial whether percutaneous coronary intervention with drug-eluting stent (DES) is safe and effective compared to coronary artery bypass graft surgery (CABG) for unprotected left main...Background It is still controversial whether percutaneous coronary intervention with drug-eluting stent (DES) is safe and effective compared to coronary artery bypass graft surgery (CABG) for unprotected left main coronary artery (ULMCA) disease at long-term follow up (≥3 years). Methods Eligible studies were selected by searching PubMed, EMBASE, and Cochrane Library up to December 6, 2016. The primary endpoint was a composite of death, myocardial infarction (MI) or stroke during the longest follow-up. Death, cardiac death, MI, stroke and repeat revascularization were the secondary outcomes. Results Four randomized controlled trials and twelve adjusted observational studies involving 14,130 patients were included. DES was comparable to CABG regarding the occurrence of the primary endpoint (FIR = 0.94, 95% CI: 0.86-1.03). Besides, DES was significantly associated with higher incidence of MI (HR = 1.56, 95% CI: 1.09-2.22) and repeat revascularization (HR = 3.09, 95% CI: 2.33-4.10) compared with CABG, while no difference was found between the two strategies regard as the rate of death, cardiac death and stroke. Furthermore, DES can reduce the risk of the composite endpoint of death, MI or stroke (HR = 0.80, 95% CI: 0.67-0.95) for ULMCA lesions with SYNTAX score ≤32. Conclusions Although with higher risk of repeat revascularization, PCI with DES appears to be as safe as CABG for ULMCA disease at long-term follow up. In addition, treatment with DES could be an alternative interventional strategy to CABG for ULMCA lesions with low to intermediate anatomic complexity.展开更多
Most studies focus on the adaptive immune cells in the GVHD pathogenesis,while little is known about innate immune cells in GVHD occurrence and development,especially macrophages.Meanwhile,a higher incidence of graft ...Most studies focus on the adaptive immune cells in the GVHD pathogenesis,while little is known about innate immune cells in GVHD occurrence and development,especially macrophages.Meanwhile,a higher incidence of graft versus host disease(GVHD)is also found in the elderly patients.Though advances have been made in the modification of macrophages influenced by the inflamm-ageing,there is still no review on the role of macrophages in GVHD and the association between GVHD and the altered macrophages by inflamm-ageing.In this review,we focus on the potential age-related modifications of macrophage in GVHD,which contributes to the change of morbidity and mortality of GVHD.Via literature review,we found that the infiltration of macrophages is associated with GVHD and macrophages are modified in inflamm-ageing state,including the proliferation,migration,phagocytosis,antigen presentation,interaction with other immune cells,and pro-fibrosis.We suppose that altered macrophage functions in inflamm-ageing state contribute to GVHD in elderly patients.展开更多
Allogeneic hematopoietic stem cell transplantation(aHSCT)is a standard validated therapy for patients suffering from malignant and nonmalignant hematological diseases.However,aHSCT procedures are limited by potentiall...Allogeneic hematopoietic stem cell transplantation(aHSCT)is a standard validated therapy for patients suffering from malignant and nonmalignant hematological diseases.However,aHSCT procedures are limited by potentially life-threatening complications,and one of the most serious complications is acute graft-versus-host disease(GVHD).During the last decades,DNA sequencing technologies were used to investigate relationship between composition or function of the gut microbiome and disease states.Even if it remains unclear whether these microbiome alterations are causative or secondary to the presence of the disease,they may be useful for diagnosis,prevention and therapy in aHSCT recipients.Here,we summarized the most recent findings of the association between human gut microbiome changes and acute GVHD in patients receiving aHSCT.展开更多
Several studies have shown that coronary artery bypass graft surgery (CABG) is superior to percutaneous coronary intervention (PCI) in patients with diabetes and multi-vessel disease. Whether this advantage of CAB...Several studies have shown that coronary artery bypass graft surgery (CABG) is superior to percutaneous coronary intervention (PCI) in patients with diabetes and multi-vessel disease. Whether this advantage of CABG over PCI is confined to diabetics who require insulin is unknown. We review the published literature comparing CABG with PCI in diabetics including 8 cohorts and 4,786 patients. There was a lower rate for all-cause mortality (Relative risk (RR): 0.78, 95% confidence interval (CI): 0.62-0.99), and for major adverse cardiac and cerebrovascular events (MACCE, RR: 0.59, 95% CI: 0.47-0.75) for CABG compared to PCI. Composite outcome of mortality, myocardial infarction and stoke was similar between CABG and PCI (RR: 0.87, 95% CI: 0.54-1.42). Visual inspection of the forest plots showed that in most analyses, the point estimates of the RR are similar between the insulin requiring group and non-insulin requiring group. On meta-regression, there was no interaction between status of insulin requirement and revascularization strategies (P 〉 0.05 for all). The pre- sented data on the still unpublished analysis of the FREEDOM trial showed similar results. Thus, in the current era, CABG is superior to PCI with lower mortality and MACCE rates, but the state of insulin requirement had no effect on the outcomes from the two revascularization strategies.展开更多
Allogenic haematological stem cell transplantation (allo-SCT) from a human leukocyte antigen (HLA) matched related or unrelated donor is used as a curative therapy for a large number of malignant and non-malignant hae...Allogenic haematological stem cell transplantation (allo-SCT) from a human leukocyte antigen (HLA) matched related or unrelated donor is used as a curative therapy for a large number of malignant and non-malignant haematological diseases. The curative effect of allo-SCT is achieved by graft versus leukaemia effect while the downside of the graft versus patient activity is the graft-versus-host-disease (GVHD), a major reason for mortality and morbidity. The search of articles for this review had been accomplished using Ovid, Medline, Embase, Pubmed and was supplemented by retrieving cross references also. Electronic literature search for English language articles with full text access was performed using graft versus host disease, ocular, management, dry eyes as key words. This review has been intended to explicate the classification, pathogenesis, risk factors and management of ocular graft versus host disease.展开更多
AIM: To investigate appropriate therapeutic strategies for graft-vs-host disease (GVHD) following liver transplantation. METHODS: Four patients who developed GVHD after liver transplantation in West China Hospital wer...AIM: To investigate appropriate therapeutic strategies for graft-vs-host disease (GVHD) following liver transplantation. METHODS: Four patients who developed GVHD after liver transplantation in West China Hospital were included in this study. Therapeutic strategies with augmentation or withdrawal of immunosuppressants combined with supportive therapy were investigated in these patients. In addition, a literature review of patients who developed GVHD after liver transplantation was performed. RESULTS: Although a transient response to initial treatment was detected, all four patients died of complications from GVHD: one from sepsis with multiple organ failure, one from gastrointestinal bleeding, and the other two from sepsis with gastrointestinal bleeding. Few consensuses for the treatment of GVHD after liver transplantation have been reached.CONCLUSION: New and effective treatments are re-quired for GVHD after liver transplantation to improve the prognosis of patients with this diagnosis.展开更多
AIM: To evaluate the incidence and severity of ocular graft versus host disease(o GVHD) in patients who underwent allogeneic stem cell transplant(SCT) in King Abdul-Aziz Medical City, Saudi Arabia.METHODS: This is a r...AIM: To evaluate the incidence and severity of ocular graft versus host disease(o GVHD) in patients who underwent allogeneic stem cell transplant(SCT) in King Abdul-Aziz Medical City, Saudi Arabia.METHODS: This is a retrospective cohort study conducted in King Abdul Aziz Medical City on patients who underwent allogeneic hematopoietic cell transplant(allo-HCT) from 2010 to 2017. The ocular examination findings including visual acuity, meibomian gland dysfunction, corneal and conjunctival staining with severity, corneal scarring, tear film meniscus and breakup time, anterior and posterior segment examination findings, intraocular pressure, treatment given, punctual plugs used or not, and follow up response were collected.RESULTS: The five years cumulative incidence of o GVHD among post-transplant patients was 56.98%(95%CI 38.6%-71.7%). The potential risk factors assessed for developing ocular manifestation were age, gender, donor’s age, donor gender mismatch CD3 and CD34 infusion, while none of the correlates were identified as statistically significant risk factors of developing ocular manifestation. However, the incidence was statistically significantly different betweenpatients diagnosed with acute myelocytic leukemia and acute lymphocytic leukemia(P=0.038). The mean latent period to develop ocular symptoms was 20.5 mo. All patients had variable degree of dry eyes. None of the patients developed any posterior segment complication.CONCLUSION: The incidence of o GVHD is low in King Abdul-Aziz Medical City. This can be attributed to the preconditioning and immunosuppressive regime.展开更多
BACKGROUND The lack of space,as an indication for a native unilateral nephrectomy for positioning a future kidney graft in the absence of other autosomal dominant polycystic kidney disease-related symptoms,remains con...BACKGROUND The lack of space,as an indication for a native unilateral nephrectomy for positioning a future kidney graft in the absence of other autosomal dominant polycystic kidney disease-related symptoms,remains controversial.AIM To evaluate the surgical comorbidity and the impact on graft survival of an associated ipsilateral native nephrectomy during isolated kidney transplantation in patients with autosomal dominant polycystic kidney disease.METHODS One hundred and fifty-four kidney transplantations performed between January 2007 and January 2019 of which 77 without(kidney transplant alone(KTA)group)and 77 with associated ipsilateral nephrectomy(KTIN group),were retrospectively reviewed.Demographics and surgical variables were analyzed and their respective impact on surgical comorbidity and graft survival.RESULTS Creation of space for future graft positioning was the main reason(n=74,96.1%)for associated ipsilateral nephrectomy.No significant difference in surgical comorbidity(lymphocele,wound infection,incisional hernia,wound hematoma,urinary infection,need for blood transfusion,hospitalization stay,Dindo Clavien classification and readmission rate)was observed between the two study groups.The incidence of primary nonfunction and delayed graft function was comparable in both groups[0%and 2.6%(P=0.497)and 9.1%and 16.9%(P=0.230),respectively,in the KTA and KTIN group].The 1-and 5-year graft survival were 94.8%and 90.3%,and 100%and 93.8%,respectively,in the KTA and KTIN group(P=0.774).The 1-and 5-year patient survival were 96.1%and 92.9%,and 100%and 100%,respectively,in the KTA and KTIN group(P=0.168).CONCLUSION Simultaneous ipsilateral native nephrectomy to create space for graft positioning during kidney transplantation in patients with autosomal dominant polycystic kidney disease does not negatively impact surgical comorbidity and short-and long-term graft survival.展开更多
We report a case of a 56-year-old woman with a history of allogenic bone marrow transplantation for two years,complaining with dysphagia and weight loss. Upper endoscopy revealed esophageal stenosis and extensive muco...We report a case of a 56-year-old woman with a history of allogenic bone marrow transplantation for two years,complaining with dysphagia and weight loss. Upper endoscopy revealed esophageal stenosis and extensive mucosa sloughing. Biopsies confirmed the diagnosis of graft-vs-host disease(GVHD). Balloon dilation,corticosteroids and cyclosporin resulted in marked clinical improvement. Gastrointestinal tract is involved in the majority of patients with chronic GVHD. Esophageal manifestations are rare and include vesiculobullous disease,ulceration,esophageal webs,casts or strictures. Sloughing esophagitis along with severe stenosis requiring endoscopic dilation has never been reported in this context.展开更多
Parkinson's disease(PD) is a neurodegenerative condition which causes a characteristic movement disorder secondary to loss of dopaminergic neurons in the substanitia nigra.The motor disorder responds well to dopami...Parkinson's disease(PD) is a neurodegenerative condition which causes a characteristic movement disorder secondary to loss of dopaminergic neurons in the substanitia nigra.The motor disorder responds well to dopamine-replacement therapies,though these result in significant adverse effects due to non-physiological release of dopamine in the striatum,and off-target effects.Cell-based regenerative treatments offer a potential means for targeted replacement of dopamine,in a physiological manner.Dopaminergic neurons for cell-based therapies can be obtained from several sources.Fetal ventral mesencephalon tissue contains dopaminergic neuron progenitors,and has been transplanted into the striatum of PD patients with good results in a number of cases.However,the ethical implications and logistical challenges of using fetal tissue mean that fetal ventral mesencephalon is unlikely to be used in a widespread clinical setting.Induced pluripotent stem cells can be used to generate dopaminergic neurons for transplantation,providing a source of autologous tissue for grafting.This approach means that challenges associated with allografts,such as the potential for immune rejection,can be circumvented.However,the associated cost and difficulty in producing a standardized product from different cell lines means that,at present,this approach is not commercially viable as a cell-based therapy.Dopaminergic neurons derived from embryonic stem cells offer the most promising basis for a cell-based therapy for Parkinson's disease,with trials due to commence in the next few years.Though there are ethical considerations to take into account when using embryonic tissue,the possibility of producing a standardized,optimized cell product means that this approach can be both effective,and commercially viable.展开更多
Graft vs host disease(GVHD) is a complication of patients who are treated by hematopoietic cell transplantation.National Institutes of Health in 2005 by Working Group on Diagnosis and Staging Consensus Development Pro...Graft vs host disease(GVHD) is a complication of patients who are treated by hematopoietic cell transplantation.National Institutes of Health in 2005 by Working Group on Diagnosis and Staging Consensus Development Project on Criteria for Clinical Trials in Chronic GVHD(cGVHD) established 2 principal categories of oral GVHD, acute and chronic. The oral mucosa may be the first site of manifestation of the disease. Clinical diagnosis needs to be confirmed by a biopsy of oral mucosa and minor salivary glands. Microscopic results have played a major role in the diagnosis and management of acute and chronic oral GVHD. Development of second malignancies is the greatest risk of oral cGVHD patients, mostly regarding squamous cell carcinoma. The focus of oral GVHD therapy is to improve symptoms and maintain oral function. The aim of this review article is to update the information on the oral GVHD in its clinical, microscopic features and their complications.展开更多
文摘Hematopoietic stem cell transplantation(HSCT)becomes a standard form of cellular therapy for patients with malignant diseases.HSCT is the first-choice of immunotherapy,although HSCT can be associated with many complications such as graft-versus-host disease(GVHD)which is a major cause of morbidity and mortality after allogeneic HSCT.It has been shown that certain gut microbiota could exert protective and/or regenerative immunomodulatory effects by the production of short-chain fatty acids(SCFAs)such as butyrate in the experimental models of GVHD after allogeneic HSCT.Loss of gut commensal bacteria which can produce SCFAs may worsen dysbiosis,increasing the risk of GVHD.Expression of G-protein coupled receptors such as GPR41 seems to be upre-gulated in the presence of commensal bacteria,which might be associated with the biology of regulatory T cells(Tregs).Treg cells are a suppressive subset of CD4 positive T lymphocytes implicated in the prevention of GVHD after allogeneic HSCT.Here,we discuss the current findings of the relationship between the modification of gut microbiota and the GVHD-related immunity,which suggested that tactics with certain probiotics for the beneficial symbiosis in gut-immune axis might lead to the elevation of safety in the allogeneic HSCT.
文摘Background: A major cause of mortality and disability on a global scale is myocardial infarction (MI). These days, the most reliable way to detect and measure MI is via cardiovascular magnetic resonance imaging (CMR). Aims and Objectives: To evaluate the effectiveness of the Electrocardiogram DETERMINE Score in predicting the severity of coronary artery disease (CAD) in patients who have experienced an Acute Myocardial Infarction (AMI) & to assess improvements in left ventricular function at 6 months following coronary artery bypass grafting (CABG). Subjects and Methods: This Observational cohort study was done at the Cardiology and Radiology department and cardiac surgery department, Al-Azhar university hospitals and Helwan University hospital. The study involved 700 cases who patients diagnosed with Acute Myocardial Infarction and fulfilled specific criteria for selection. Result: There was highly statistically significant relation between Myocardial infarction size and ECG Marker Score as mean infarct size elevated When the number of ECG markers increased. There was a highly statistically significant relation between myocardial infarct segments, myocardial infarction size and improvement of cardiac function 6 months post-CABG. Conclusion: The study found that larger myocardial infarctions corresponded with higher DETERMINE Scores. It concluded that an ECG-based score better estimates infarct size than LVEF alone. Additionally, there was a significant statistical correlation between the size and segmentation of myocardial infarction and better cardiac function six months after CABG.
基金supported by grants from the National Natural Science Foundation of China(81372425,8157295481421062,91542205 and 81401319)
文摘BACKGROUND: Graft-versus-host disease (GVHD) is associated with high mortality. Early diagnosis is essential to start treatment and to improve outcomes. Because of the inflammatory nature, we hypothesis that cytokine profile of patients with GVHD may serve as diagnostic markers. The present study was to evaluate the role of cytokine profile in the diagnosis of GVHD. METHODS: An immunoassay was used to detect 29 cytokines simultaneously in the serum; the measuring sensitivity of all cytokines was pg/mL. Healthy subjects undergoing annual routine physical examinations served as negative controls; 23 patients with hepatocellular carcinoma (HCC) who had undergone liver transplantation (the LT group) comprised the test subjects. A total of 22 kidney recipients with biopsyconfirmed GVHD (the RT group) were included for comparison. HCC patients with radical surgery (the HCC group, n=22) served as positive control. The liver contents of the three cytokines, IL-2, IL-18, and IFN-γ, were detected with immunohistochemistry. Serum granzyme B and perforin were measured by flow cytometry.RESULTS: Of the 29 cytokines, the levels of IL-2 and IL-18 were increased significantly in liver recipients with GVHD compared with healthy controls (P〈0.05). The serum levels of these three cytokines in the healthy, HCC, LT, and RT groups were IL-2: 0.90±0.02, 4.14±0.61, 5.10±0.89, and 1.48±0.09 pg/mL; IL-18: 80.61±9.35, 109.51±10.93, 230.11±12.92, and 61.98±7.88 pg/mL; IFN-γ: 24.06±3.88, 24.84±3.21, 40.37±5.88, and 15.33±4.72 pg/mL, respectively. Immunohistochemistry showed that these 3 cytokines expressions in the liver were parallel to the serum cytokine. After standard anti-GVHD treatment, the expressions of IL-2, IL-18, and IFN-y were de- creased in the liver (P〈0.05). Serum granzyme B and perforin were significantly increased in GVHD patients (P〈0.05). CONCLUSIONS: IL-2, IL-18 and IFN-γ were from liver and might serve as biomarkers for monitoring GVHD develop- ment and the effects of anti-GVHD treatment. Granzyme B and perforin may play a role in increasing IL-2, IL-18, and IFN-y levels in GVHD patients.
基金supported by grants from the National Natural Science Foundation of China(No.81172826)Collaborative Innovation Center of Hematology,China
文摘Summary: Although mesenchymal stem cells (MSCs) are increasingly used to treat graft-versus-host disease (GVHD), their immune regulatory mechanism in the process is elusive. The present study aimed to investigate the curative effect of third-party umbilical cord blood-derived human MSCs (UCB-hMSCs) on GVHD patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their immune regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were treated with UCB-hMSCs. Immune cells including T lymphocyte subsets, NK ceils, Treg cells and dendritic cells (DCs) and cytokines including interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-α) were monitored before and after MSCs transfusion. The results showed that the symptoms of GVHD were alleviated significantly without increased relapse of primary disease and transplant-related complications after MSCs transfusion. The number of CD3^+, CD3+CD4^+ and CD3+CD8^+ cells decreased significantly, and that of NK cells remained unchanged, whereas the number of CD4^+ and CD8^+ Tregs increased and reached a peak at 4 weeks; the number of mature DCs, and the levels of TNF-α and IL-17 decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate GVHD and spare GVL effect via immunoregulations.
基金Supported by Grant from the National Center for Global Health and Medicine
文摘Here,we report a case of fulminant gastrointestinal graft-versus-host disease(GI-GVHD) with cytomegalovirus(CMV) infection in 44-year-old woman.Despite the difficulties associated with the treatment of GIGVHD and GI-CMV disease,the mucosal findings and the clinical course showed marked improvements during long-term clinical observation.The endoscopic findings were remarkable,with diffuse sloughing mucosa in the stomach and highly active inflammation and deep discrete ulcers throughout the colon.Changes in the CMV quantitative polymerase chain reaction results were correlated with the endoscopic mucosal findings and were useful for assessing the efficacy of the treatment.Although a definite diagnosis of GI-GVHD is generally made by endoscopy with biopsy,the gross appearance of this disease can vary depending on the endoscopy.In this paper,we also conduct a literature review of patients with GI-GVHD.
基金supported by grants from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (R37 AI34495)National Heart, Lung, and Blood Institute, National Institutes of Health (R01 HL56067 and R01 HL11879)National Cancer Institute, National Institutes of Health (P01 CA142106 and P01 CA065493)
文摘The most common approaches to prevent and treat graft-versus-host disease (GVHD) are intended to deplete or suppress the T cells capable of mediating or supporting alloresponses;however, this renders the recipients functionally T cell deficient and hence highly susceptible to infections and tumor recurrence. Depletion is often accomplished through the use of broadly reactive antibodies, while functional impairment is typically achieved by pharmacological agents that require long-term administration (usually six months or more), have significant side effects, and may not result in tolerance (i.e., nonresponsiveness) of donor T cells to conditioning regimen-resistant host alloantigen-bearing cells. As our knowledge of immune system homeostasis has increased, cell populations with immune regulatory function have been identified and characterized. Although such cell populations are typically present in low frequencies, methods to isolate and expand these cells have permitted their supplementation to the donor graft or infusion late post-transplant in order to stifle GVHD. This review discusses the biology and preclinical proof of concept of GVHD models, along with GVHD outcomes that focus exclusively on immune regulatory cell therapies that have progressed to clinical testing.
文摘This study examined the expressions of human serum tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their clinical significance. The serum TF and TFPI levels were detected by ELISA in 28 allo-HSCT recipients before and after the transplanta-tion and the changes of TF and TFPI levels were dynamically monitored at different phases of the disease. No significant differences in the serum TF and TFPI levels were found in allo-HSCT recipi-ents in the absence of aGVHD or with gradeⅠaGVHD before and after the transplantation. The lev-els of serum TF and TFPI were substantially increased in the patients with gradeⅡ aGVHD at the peak of aGVHD (P〈0.05) and they were even higher in the patients with grade Ⅲ–Ⅳ aGVHD (P〈0.01). When the conditions became stable after treatment with immunosuppressive agents, the serum TFPI level was decreased to the baseline level (P〉0.05) and the TF level was lowered but still higher than the baseline level (P〈0.05). It was concluded that the levels of serum TF and TFPI were increased significantly in the patients with grade Ⅱ–Ⅳ aGVHD after allo-HSCT and decreased markedly after the treatment. Monitoring the levels of serum TF and TFPI in the patients with allo-HSCT is important to predict the occurrence, outcome and prognosis of aGVHD.
文摘The surgical techniques used by Austoni and Egydio in the treatment of Peyronie's disease are based on geometric principles. The aim of this paper is to report our multicentric experience and technical changes to Austoni's original technique, focusing on several tips and tricks to make this technique easy to perform, even by less experienced practitioners. We performed operations in three different Italian institutions. We implanted a small soft Virilis I~ axial prostheses (Ф 7 Fr.), using a bovine pericardium collagen matrix patch (Hydrix) to cover the defect in the tunica albuginea. Sixty patients with a mean age of 58 years (range 44-76 years) underwent surgery between September 2005 and January 2010. After surgery, mean lengthening of the shaft was 2 cm (range 1.2-2.3 cm) with complete correction of penile recurvatum. Thirty-nine patients resumed sexual activity 60 days later, 14 after 90 days and 7 after 120 days. The international index of erectile function (IIEF) score was 15.5 before surgery and it improved to 23 at 12 and 24 months after surgery. Furthermore, the visual analogue scale (VAS) showed good results in terms of the recovery of natural sexual intercourse (over 80% of couples) and of the original length and girth of the penis. The soft implant we used takes advantage of erection that occurs spontaneously, using the residual erection of the spared cavernous tissue. The method is easy to learn and reproducible, and the use of pericardium speeds up the operation, while also covering large defects of the tunica albuginea that result from complex recurvatum.
文摘BACKGROUND Children with acute liver failure(ALF)who meet the criteria are eligible for super-urgent transplantation,whereas children with end-stage chronic liver disease(ESCLD)are usually transplanted electively.Pediatric liver transplantation(PLT)in ALF and ESCLD settings has been well described in the literature,but there are no studies comparing the outcomes in these two groups.AIM To determine if there is a difference in post-operative complications and survival outcomes between ALF and ESCLD in PLT.METHODS This was a retrospective observational study of all primary PLTs performed at a single center between 2000 and 2019.ALF and ESCLD groups were compared for pretransplant recipient,donor and operative parameters,and post-operative outcomes including graft and patient survival.RESULTS Over a 20-year study period,232 primary PLTs were performed at our center;195 were transplanted for ESCLD and 37 were transplanted for ALF.The ALF recipients were significantly older(median 8 years vs 5.4 years;P=0.031)and heavier(31 kg vs 21 kg;P=0.011).Living donor grafts were used more in the ESCLD group(34 vs 0;P=0.006).There was no difference between the two groups concerning vascular complications and rejection,but there were more bile leaks in the ESCLD group.Post-transplant patient survival was significantly higher in the ESCLD group:1-,5-,and 10-year survival rates were 97.9%,93.9%,and 89.4%,respectively,compared to 78.3%,78.3%,and 78.3%in the ALF group(P=0.007).However,there was no difference in 1-,5-,and 10-year graft survival between the ESCLD and ALF groups(90.7%,82.9%,77.3%vs 75.6%,72.4%,and 66.9%;P=0.119).CONCLUSION Patient survival is inferior in ALF compared to ESCLD recipients;the main reason is death in the 1st year post-PLT in ALF group.Once the ALF children overcome the 1st year after transplant,their survival stabilizes,and they have good long-term outcomes.
文摘Background It is still controversial whether percutaneous coronary intervention with drug-eluting stent (DES) is safe and effective compared to coronary artery bypass graft surgery (CABG) for unprotected left main coronary artery (ULMCA) disease at long-term follow up (≥3 years). Methods Eligible studies were selected by searching PubMed, EMBASE, and Cochrane Library up to December 6, 2016. The primary endpoint was a composite of death, myocardial infarction (MI) or stroke during the longest follow-up. Death, cardiac death, MI, stroke and repeat revascularization were the secondary outcomes. Results Four randomized controlled trials and twelve adjusted observational studies involving 14,130 patients were included. DES was comparable to CABG regarding the occurrence of the primary endpoint (FIR = 0.94, 95% CI: 0.86-1.03). Besides, DES was significantly associated with higher incidence of MI (HR = 1.56, 95% CI: 1.09-2.22) and repeat revascularization (HR = 3.09, 95% CI: 2.33-4.10) compared with CABG, while no difference was found between the two strategies regard as the rate of death, cardiac death and stroke. Furthermore, DES can reduce the risk of the composite endpoint of death, MI or stroke (HR = 0.80, 95% CI: 0.67-0.95) for ULMCA lesions with SYNTAX score ≤32. Conclusions Although with higher risk of repeat revascularization, PCI with DES appears to be as safe as CABG for ULMCA disease at long-term follow up. In addition, treatment with DES could be an alternative interventional strategy to CABG for ULMCA lesions with low to intermediate anatomic complexity.
基金the topnotch innovative talents project and the project of Fujian Science and Technology Department(Grant 2016Y9025&2016J06018&2017I0004)Fujian Medical University teaching reform project(Y17005)Fujian Provincial Health and Family planning Commission Youth Research Project(2017-1-6)to LI.URL:http://kjt.fujian.gov.cn/。
文摘Most studies focus on the adaptive immune cells in the GVHD pathogenesis,while little is known about innate immune cells in GVHD occurrence and development,especially macrophages.Meanwhile,a higher incidence of graft versus host disease(GVHD)is also found in the elderly patients.Though advances have been made in the modification of macrophages influenced by the inflamm-ageing,there is still no review on the role of macrophages in GVHD and the association between GVHD and the altered macrophages by inflamm-ageing.In this review,we focus on the potential age-related modifications of macrophage in GVHD,which contributes to the change of morbidity and mortality of GVHD.Via literature review,we found that the infiltration of macrophages is associated with GVHD and macrophages are modified in inflamm-ageing state,including the proliferation,migration,phagocytosis,antigen presentation,interaction with other immune cells,and pro-fibrosis.We suppose that altered macrophage functions in inflamm-ageing state contribute to GVHD in elderly patients.
文摘Allogeneic hematopoietic stem cell transplantation(aHSCT)is a standard validated therapy for patients suffering from malignant and nonmalignant hematological diseases.However,aHSCT procedures are limited by potentially life-threatening complications,and one of the most serious complications is acute graft-versus-host disease(GVHD).During the last decades,DNA sequencing technologies were used to investigate relationship between composition or function of the gut microbiome and disease states.Even if it remains unclear whether these microbiome alterations are causative or secondary to the presence of the disease,they may be useful for diagnosis,prevention and therapy in aHSCT recipients.Here,we summarized the most recent findings of the association between human gut microbiome changes and acute GVHD in patients receiving aHSCT.
文摘Several studies have shown that coronary artery bypass graft surgery (CABG) is superior to percutaneous coronary intervention (PCI) in patients with diabetes and multi-vessel disease. Whether this advantage of CABG over PCI is confined to diabetics who require insulin is unknown. We review the published literature comparing CABG with PCI in diabetics including 8 cohorts and 4,786 patients. There was a lower rate for all-cause mortality (Relative risk (RR): 0.78, 95% confidence interval (CI): 0.62-0.99), and for major adverse cardiac and cerebrovascular events (MACCE, RR: 0.59, 95% CI: 0.47-0.75) for CABG compared to PCI. Composite outcome of mortality, myocardial infarction and stoke was similar between CABG and PCI (RR: 0.87, 95% CI: 0.54-1.42). Visual inspection of the forest plots showed that in most analyses, the point estimates of the RR are similar between the insulin requiring group and non-insulin requiring group. On meta-regression, there was no interaction between status of insulin requirement and revascularization strategies (P 〉 0.05 for all). The pre- sented data on the still unpublished analysis of the FREEDOM trial showed similar results. Thus, in the current era, CABG is superior to PCI with lower mortality and MACCE rates, but the state of insulin requirement had no effect on the outcomes from the two revascularization strategies.
文摘Allogenic haematological stem cell transplantation (allo-SCT) from a human leukocyte antigen (HLA) matched related or unrelated donor is used as a curative therapy for a large number of malignant and non-malignant haematological diseases. The curative effect of allo-SCT is achieved by graft versus leukaemia effect while the downside of the graft versus patient activity is the graft-versus-host-disease (GVHD), a major reason for mortality and morbidity. The search of articles for this review had been accomplished using Ovid, Medline, Embase, Pubmed and was supplemented by retrieving cross references also. Electronic literature search for English language articles with full text access was performed using graft versus host disease, ocular, management, dry eyes as key words. This review has been intended to explicate the classification, pathogenesis, risk factors and management of ocular graft versus host disease.
文摘AIM: To investigate appropriate therapeutic strategies for graft-vs-host disease (GVHD) following liver transplantation. METHODS: Four patients who developed GVHD after liver transplantation in West China Hospital were included in this study. Therapeutic strategies with augmentation or withdrawal of immunosuppressants combined with supportive therapy were investigated in these patients. In addition, a literature review of patients who developed GVHD after liver transplantation was performed. RESULTS: Although a transient response to initial treatment was detected, all four patients died of complications from GVHD: one from sepsis with multiple organ failure, one from gastrointestinal bleeding, and the other two from sepsis with gastrointestinal bleeding. Few consensuses for the treatment of GVHD after liver transplantation have been reached.CONCLUSION: New and effective treatments are re-quired for GVHD after liver transplantation to improve the prognosis of patients with this diagnosis.
文摘AIM: To evaluate the incidence and severity of ocular graft versus host disease(o GVHD) in patients who underwent allogeneic stem cell transplant(SCT) in King Abdul-Aziz Medical City, Saudi Arabia.METHODS: This is a retrospective cohort study conducted in King Abdul Aziz Medical City on patients who underwent allogeneic hematopoietic cell transplant(allo-HCT) from 2010 to 2017. The ocular examination findings including visual acuity, meibomian gland dysfunction, corneal and conjunctival staining with severity, corneal scarring, tear film meniscus and breakup time, anterior and posterior segment examination findings, intraocular pressure, treatment given, punctual plugs used or not, and follow up response were collected.RESULTS: The five years cumulative incidence of o GVHD among post-transplant patients was 56.98%(95%CI 38.6%-71.7%). The potential risk factors assessed for developing ocular manifestation were age, gender, donor’s age, donor gender mismatch CD3 and CD34 infusion, while none of the correlates were identified as statistically significant risk factors of developing ocular manifestation. However, the incidence was statistically significantly different betweenpatients diagnosed with acute myelocytic leukemia and acute lymphocytic leukemia(P=0.038). The mean latent period to develop ocular symptoms was 20.5 mo. All patients had variable degree of dry eyes. None of the patients developed any posterior segment complication.CONCLUSION: The incidence of o GVHD is low in King Abdul-Aziz Medical City. This can be attributed to the preconditioning and immunosuppressive regime.
文摘BACKGROUND The lack of space,as an indication for a native unilateral nephrectomy for positioning a future kidney graft in the absence of other autosomal dominant polycystic kidney disease-related symptoms,remains controversial.AIM To evaluate the surgical comorbidity and the impact on graft survival of an associated ipsilateral native nephrectomy during isolated kidney transplantation in patients with autosomal dominant polycystic kidney disease.METHODS One hundred and fifty-four kidney transplantations performed between January 2007 and January 2019 of which 77 without(kidney transplant alone(KTA)group)and 77 with associated ipsilateral nephrectomy(KTIN group),were retrospectively reviewed.Demographics and surgical variables were analyzed and their respective impact on surgical comorbidity and graft survival.RESULTS Creation of space for future graft positioning was the main reason(n=74,96.1%)for associated ipsilateral nephrectomy.No significant difference in surgical comorbidity(lymphocele,wound infection,incisional hernia,wound hematoma,urinary infection,need for blood transfusion,hospitalization stay,Dindo Clavien classification and readmission rate)was observed between the two study groups.The incidence of primary nonfunction and delayed graft function was comparable in both groups[0%and 2.6%(P=0.497)and 9.1%and 16.9%(P=0.230),respectively,in the KTA and KTIN group].The 1-and 5-year graft survival were 94.8%and 90.3%,and 100%and 93.8%,respectively,in the KTA and KTIN group(P=0.774).The 1-and 5-year patient survival were 96.1%and 92.9%,and 100%and 100%,respectively,in the KTA and KTIN group(P=0.168).CONCLUSION Simultaneous ipsilateral native nephrectomy to create space for graft positioning during kidney transplantation in patients with autosomal dominant polycystic kidney disease does not negatively impact surgical comorbidity and short-and long-term graft survival.
文摘We report a case of a 56-year-old woman with a history of allogenic bone marrow transplantation for two years,complaining with dysphagia and weight loss. Upper endoscopy revealed esophageal stenosis and extensive mucosa sloughing. Biopsies confirmed the diagnosis of graft-vs-host disease(GVHD). Balloon dilation,corticosteroids and cyclosporin resulted in marked clinical improvement. Gastrointestinal tract is involved in the majority of patients with chronic GVHD. Esophageal manifestations are rare and include vesiculobullous disease,ulceration,esophageal webs,casts or strictures. Sloughing esophagitis along with severe stenosis requiring endoscopic dilation has never been reported in this context.
基金Medical Research CouncilWellcome Trust Stem Cell Institute(Cambridge)+2 种基金NIHR Cambridge Biomedical Research Centerthe Biotechnology and Biological Sciences Research Councilthe Engineering and Physical Sciences Research Council
文摘Parkinson's disease(PD) is a neurodegenerative condition which causes a characteristic movement disorder secondary to loss of dopaminergic neurons in the substanitia nigra.The motor disorder responds well to dopamine-replacement therapies,though these result in significant adverse effects due to non-physiological release of dopamine in the striatum,and off-target effects.Cell-based regenerative treatments offer a potential means for targeted replacement of dopamine,in a physiological manner.Dopaminergic neurons for cell-based therapies can be obtained from several sources.Fetal ventral mesencephalon tissue contains dopaminergic neuron progenitors,and has been transplanted into the striatum of PD patients with good results in a number of cases.However,the ethical implications and logistical challenges of using fetal tissue mean that fetal ventral mesencephalon is unlikely to be used in a widespread clinical setting.Induced pluripotent stem cells can be used to generate dopaminergic neurons for transplantation,providing a source of autologous tissue for grafting.This approach means that challenges associated with allografts,such as the potential for immune rejection,can be circumvented.However,the associated cost and difficulty in producing a standardized product from different cell lines means that,at present,this approach is not commercially viable as a cell-based therapy.Dopaminergic neurons derived from embryonic stem cells offer the most promising basis for a cell-based therapy for Parkinson's disease,with trials due to commence in the next few years.Though there are ethical considerations to take into account when using embryonic tissue,the possibility of producing a standardized,optimized cell product means that this approach can be both effective,and commercially viable.
文摘Graft vs host disease(GVHD) is a complication of patients who are treated by hematopoietic cell transplantation.National Institutes of Health in 2005 by Working Group on Diagnosis and Staging Consensus Development Project on Criteria for Clinical Trials in Chronic GVHD(cGVHD) established 2 principal categories of oral GVHD, acute and chronic. The oral mucosa may be the first site of manifestation of the disease. Clinical diagnosis needs to be confirmed by a biopsy of oral mucosa and minor salivary glands. Microscopic results have played a major role in the diagnosis and management of acute and chronic oral GVHD. Development of second malignancies is the greatest risk of oral cGVHD patients, mostly regarding squamous cell carcinoma. The focus of oral GVHD therapy is to improve symptoms and maintain oral function. The aim of this review article is to update the information on the oral GVHD in its clinical, microscopic features and their complications.