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BMC Ophthalmol ; 23(1): 154, 2023 Apr 11.
Article in English | MEDLINE | ID: mdl-37041510

ABSTRACT

PURPOSE: To identify the characteristics of asymptomatic meibomian gland dysfunction (MGD), symptomatic MGD, and MGD coexisting with dry eye disease (DED). METHODS: This cross sectional study enrolled a total of 153 eyes of 87 MGD patients. Participants filled in ocular surface disease index (OSDI) questionnaires. Age, gender, Schirmer's test, meibomian gland (MG) related parameters, lipid layer thickness (LLT) and blinking were compared among patients with asymptomatic MGD, symptomatic MGD, and MGD with DED. Multivariate regression was used to analyze the significant factor of DED in MGD. Spearman's rank correlation analysis was used to evaluate the association between the significant factors and MG function. RESULTS: There was no difference in age, Schirmer's test, lid changes, MG secretion, and MG morphology among three groups. The OSDI of asymptomatic MGD, symptomatic MGD and MGD coexisting with DED were 8.5 ± 2.9, 28.5 ± 12.8 and 27.9 ± 10.5, respectively. Patients with MGD coexisting with DED exhibited more frequent eye blinking than that of patients with asymptomatic MGD (8.1 ± 4.1 vs. 6.1 ± 3.5 blinks/20 sec, P = 0.022), and reduced LLT than that of patients with asymptomatic MGD (68.6 ± 17.2 vs. 77.6 ± 14.5 nm, P = 0.010) and symptomatic MGD (78.0 ± 17.1 nm, P = 0.015). Multivariate analysis identified LLT (per nm, OR = 0.96, 95% CI = 0.93-0.99, P = 0.002) as a significant factor associated with DED development in MGD. The number of expressible MG was positively correlated with LLT (Spearman's correlation coefficient = 0.299, P = 0.016) but negatively correlated with the number of blinking (Spearman's correlation coefficient = -0.298, P = 0.016) in MGD patients with DED, and these findings were not identified in those without DED. CONCLUSIONS: Asymptomatic MGD, symptomatic MGD, and MGD coexisting with DED share similar characteristics, including meibum secretion and morphology, but MGD patients coexisting with DED exhibited significantly reduced LLT.


Subject(s)
Dry Eye Syndromes , Meibomian Gland Dysfunction , Humans , Cross-Sectional Studies , Meibomian Glands , Blinking
3.
FASEB J ; 37(4): e22855, 2023 04.
Article in English | MEDLINE | ID: mdl-36906286

ABSTRACT

Chronic uveitis comprises heterogeneous clinical entities characterized by sustained and recurrent intraocular inflammation that is believed to be driven by autoimmune responses. The management of chronic uveitis is challenging with the limited availability of efficacious treatments, and the underlying mechanisms mediating disease chronicity remain poorly understood as the majority of experimental data are derived from the acute phase of the disease (the first 2-3 weeks post-induction). Herein, we investigated the key cellular mechanisms underlying chronic intraocular inflammation using our recently established murine model of chronic autoimmune uveitis. We demonstrate unique long-lived CD44hi IL-7R+ IL-15R+ CD4+ memory T cells in both retina and secondary lymphoid organs after 3 months postinduction of autoimmune uveitis. These memory T cells functionally exhibit antigen-specific proliferation and activation in response to retinal peptide stimulation in vitro. Critically, these effector-memory T cells are capable of effectively trafficking to the retina and accumulating in the local tissues secreting both IL-17 and IFN-γ upon adoptively transferred, leading to retinal structural and functional damage. Thus, our data reveal the critical uveitogenic functions of memory CD4+ T cells in sustaining chronic intraocular inflammation, suggesting that memory T cells can be a novel and promising therapeutic target for treating chronic uveitis in future translational studies.


Subject(s)
Autoimmune Diseases , Retinal Diseases , Uveitis , Mice , Humans , Animals , Disease Models, Animal , CD4-Positive T-Lymphocytes , Inflammation
4.
Transl Vis Sci Technol ; 11(10): 12, 2022 10 03.
Article in English | MEDLINE | ID: mdl-36201200

ABSTRACT

Purpose: To evaluate the efficacy of a pigment epithelium-derived factor (PEDF)-derived short peptide 29-mer, on the treatment and prevention of experimental dry eye (EDE). Methods: C57BL/6 mice were housed in a low humidity controlled environment chamber for 14 days to induce EDE. The 29-mer was administered topically to their eyes, for treatment or dosing, from the point of housing in the controlled environment chamber. The efficacy of the 29-mer on EDE was evaluated in terms of corneal epithelial integrity, tear secretion, and the density of conjunctival goblet cells. PEDF and inflammatory factors, including tumor necrosis factor-α, IL-1ß, IL-6, monocyte chemotactic protein (MCP)-1, matrix metalloproteinase-9, and macrophage infiltration, were examined by real-time polymerase chain reaction, Western blotting, and immunostaining. The involvement of the PEDF receptor/PNPLA2 on the 29-mer effects was evaluated by a specific inhibitor, atglistatin. Rabbit corneal epithelial cells were exposed to hyperosmotic medium to induce inflammatory responses. Results: The levels of PEDF protein increased in the corneal epithelium of EDE, compared with the nonstressed mice. The 29-mer showed a therapeutic effect on EDE and prevented the development of EDE, accompanied by amelioration of the inflammatory factors. The 29-mer effects of inflammatory relief were dramatically reversed by atglistatin. The 29-mer also suppressed the expression of matrix metalloproteinase-9 and proinflammatory cytokines in rabbit corneal epithelial cells induced by hyperosmolarity. Conclusions: Through this animal study, we provide a proof of concept of the anti-inflammatory domain of PEDF having potential to treat dry eye disease. Translational Relevance: This study shows the 29-mer has novel potential as an ophthalmic drop treatment for dry eye disease.


Subject(s)
Dry Eye Syndromes , Matrix Metalloproteinase 9 , Animals , Anti-Inflammatory Agents/therapeutic use , Cytokines/metabolism , Cytokines/therapeutic use , Disease Models, Animal , Dry Eye Syndromes/drug therapy , Dry Eye Syndromes/metabolism , Dry Eye Syndromes/pathology , Eye Proteins , Inflammation/drug therapy , Interleukin-6/therapeutic use , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/therapeutic use , Mice , Mice, Inbred C57BL , Monocyte Chemoattractant Proteins/therapeutic use , Nerve Growth Factors , Phenylurea Compounds , Rabbits , Serpins , Tumor Necrosis Factor-alpha/therapeutic use
5.
J Autoimmun ; 129: 102816, 2022 05.
Article in English | MEDLINE | ID: mdl-35395541

ABSTRACT

Effector Th17 cells, including IFN-γ-IL-17+ (eTh17) and IFN-γ+IL-17+ (eTh17/1) subsets, play critical pathogenic functions in the induction of autoimmunity. As acute inflammation subsides, a small proportion of the effectors survive and convert to memory Th17 cells (mTh17), which sustain chronic inflammation in autoimmune diseases. Herein, we investigated the differential contributions of eTh17 versus eTh17/1 to the memory pool using an experimental model of ocular autoimmune disease. Our results show that adoptive transfer of Tbx21-/- CD4+ T cells or conditional deletion of Tbx21 in Th17 cells leads to diminished eTh17/1 in acute phase and functionally compromised mTh17 in chronic phase. Further, adoptive transfer of disease-specific eTh17/1, but not eTh17, leads to generation of mTh17 and sustained ocular inflammation. Collectively, our data demonstrate that T-bet-dependent eTh17/1 cells generated during the acute inflammation are the principal effector precursors of pathogenic mTh17 cells that sustain the chronicity of autoimmune inflammation.


Subject(s)
Autoimmune Diseases , Nuclear Receptor Subfamily 1, Group F, Member 3 , Autoimmune Diseases/pathology , Humans , Inflammation/pathology , Interferon-gamma , Interleukin-17/genetics , Th1 Cells , Th17 Cells
6.
Ocul Surf ; 19: 157-168, 2021 01.
Article in English | MEDLINE | ID: mdl-32470612

ABSTRACT

Th17 cells have been implicated in the pathogenesis of numerous inflammatory and autoimmune conditions. At the ocular surface, Th17 cells have been identified as key effector cells in chronic ocular surface disease. Evidence from murine studies indicates that following differentiation and expansion, Th17 cells migrate from the lymphoid tissues to the eye, where they release inflammatory cytokines including, but not limited to, their hallmark cytokine IL-17A. As the acute phase subsides, a population of long-lived memory Th17 cells persist, which predispose hosts both to chronic inflammation and severe exacerbations of disease; of great interest is the small subset of Th17/1 cells that secrete both IL-17A and IFN-γ in acute-on-chronic disease exacerbation. Over the past decade, substantial progress has been made in deciphering how Th17 cells interact with the immune and neuroimmune pathways that mediate chronic ocular surface disease. Here, we review (i) the evidence for Th17 immunity in chronic ocular surface disease, (ii) regulatory mechanisms that constrain the Th17 immune response, and (iii) novel therapeutic strategies targeting Th17 cells.


Subject(s)
Autoimmune Diseases , Th17 Cells , Animals , Cell Differentiation , Cytokines , Eye , Mice
7.
Mucosal Immunol ; 14(1): 177-186, 2021 01.
Article in English | MEDLINE | ID: mdl-32327706

ABSTRACT

Long-lived memory T-helper 17 (Th17) cells actively mediate the chronic inflammation in autoimmune disorders, including dry eye disease (DED). The mechanisms responsible for the maintenance and reactivation of these cells in autoimmunity have been subject of investigation. However, the process through which memory Th17 are generated from their effector precursors remains to be elucidated. Herein, using our murine model of DED, we detect a linear transition from effector-to-memory Th17 cells during the abatement phase of acute inflammation, which is accompanied by persistently high levels of IL-23 and diminished levels of IL-2. In addition, in vitro culture of effector Th17 cells derived from the DED animals with IL-23, but not IL-2, leads to significant generation of memory Th17 cells, along with upregulated expression levels of IL-7R and IL-15R by these cells. Furthermore, supplementation of IL-2 abolishes and blockade of IL-2 enhances IL-23-induced generation of memory Th17 cells in vitro. Finally, in vivo blockade of IL-23 signaling during the contraction phase of primary response inhibits the generation of memory Th17 cells from their effector precursors. Together, our data demonstrate a new dichotomy between IL-23 and IL-2 in driving effector Th17 cells into the memory pool in autoimmune-mediated ocular surface inflammation.


Subject(s)
Autoimmunity , Dry Eye Syndromes/etiology , Dry Eye Syndromes/metabolism , Immunologic Memory , Interleukin-23/metabolism , Interleukin-2/metabolism , Th17 Cells/immunology , Th17 Cells/metabolism , Animals , Apoptosis/genetics , Apoptosis/immunology , Autoimmune Diseases/etiology , Autoimmune Diseases/metabolism , Autoimmune Diseases/pathology , Biomarkers , Disease Models, Animal , Disease Susceptibility , Dry Eye Syndromes/pathology , Humans , Interleukin-2/genetics , Interleukin-23/genetics , Mice , Signal Transduction
8.
Am J Pathol ; 191(3): 425-437, 2021 03.
Article in English | MEDLINE | ID: mdl-32966818

ABSTRACT

Autoimmune uveitis is a sight-threatening intraocular inflammatory disease. For >30 years, the mouse model of experimental autoimmune uveitis has been employed to investigate disease mechanisms and test immunotherapeutic approaches. However, inflammation in this model is self-limited, and does not replicate the chronic, insidious nature prevalent in the human disease. Herein, a robust and reliable model of chronic autoimmune uveitis was developed and characterized in two strains of wild-type mice by modifying interphotoreceptor retinoid-binding protein dose and peptide fragments from conventional experimental autoimmune uveitis models. In both of these murine strains, immunization with our modified protocols resulted in a slowly progressive uveitis, with retinal scars and atrophy observed in the chronic stage by fundoscopy. Optical coherence tomography demonstrated decreased retinal thickness in chronic autoimmune uveitis mice, and electroretinography showed significantly reduced amplitudes of dark-adapted a- and b-waves and light-adapted b-waves. Histologic examination revealed prominent choroiditis with extensive retinal damage. Flow cytometry analysis showed substantially increased numbers of CD44hiIL-17+IFN-γ- memory T-helper 17 (Th17) cells in the retina, cervical lymph nodes, inguinal lymph nodes, and spleen. These data establish new modified protocols for inducing chronic uveitis in wild-type mice, and demonstrate a predominant memory Th17 cell response, suggesting an important role for memory Th17 cells in driving chronic inflammation in autoimmune uveitis.


Subject(s)
Autoimmune Diseases/immunology , Immunity/immunology , Inflammation/immunology , Retinal Degeneration/physiopathology , Th17 Cells/immunology , Uveitis/immunology , Animals , Autoimmune Diseases/metabolism , Autoimmune Diseases/pathology , Chronic Disease , Disease Models, Animal , Inflammation/metabolism , Inflammation/pathology , Mice , Mice, Inbred C57BL , Uveitis/metabolism , Uveitis/pathology
9.
J Microbiol Immunol Infect ; 53(2): 274-282, 2020 Apr.
Article in English | MEDLINE | ID: mdl-30082145

ABSTRACT

BACKGROUND: Mycobacterial infections are important and potentially life-threatening complications after organ transplantations. Notably, for the recipients of allogeneic hematopoietic stem cell transplantation (HSCT), there are a few supporting results to explore post-transplant mycobacterial infections. Taiwan is a high endemic area of the infection. We aim to investigate the incidence, risk factors, and survival of post-transplant mycobacterial infections, including mycobacterium tuberculosis (MTB) and non-tuberculous mycobacterium (NTM). METHODS: We included 422 adult patients undergoing allogeneic HSCT at an Asian tertiary medical center between January 2003 and December 2014. A total 26 subjects developed post-transplant mycobacterial infections. Risk factors, clinical features, and survival for post-transplant mycobacterial infections were collected and analyzed. RESULTS: Post-transplant mycobacterial infections occurred in 26 (6.2%) of 422 HSCT patients. Two-year cumulative incidences in MTB and NTM were 1.4% and 5.4%. In the multivariate analysis, being age >45 years (adjusted HR 2.21, 95% CI 1.01-4.83) and extensive chronic graft-versus-host disease (cGVHD) (adjusted HR 4.95, 95% CI 2.14-11.46) were identified as independent risk factors of infections. There was a trend as a risk factors in relapsed patients (P = 0.088). For patients with cGVHD, there was a significant difference of post-transplant survival between mycobacterial infections and none (P = 0.036). Pneumonia contributed most to mortality (n = 11, 42.3%). CONCLUSION: Mycobacterial infections are worth to note in a high endemic area. Once a high-risk group is identified, much effort is required to target new approaches for prevention, early detection and treatment of infections.


Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Mycobacterium Infections/complications , Mycobacterium Infections/epidemiology , Adult , Cohort Studies , Female , Graft vs Host Disease , Humans , Incidence , Male , Middle Aged , Mycobacterium , Mycobacterium Infections/diagnosis , Mycobacterium Infections/physiopathology , Retrospective Studies , Risk Factors , Taiwan/epidemiology
10.
Can J Ophthalmol ; 54(6): 735-740, 2019 12.
Article in English | MEDLINE | ID: mdl-31836108

ABSTRACT

OBJECTIVE: To analyze the relationship between dry eye symptoms and modern dry eye tests, including the Schirmer I test, lipid layer thickness (LLT), and blinking pattern by LipiView interferometer. DESIGN: Cross-sectional study. PARTICIPANTS: 115 dry eye outpatients. METHODS: Dry eye symptoms were quantified by questionnaire scores, such as Ocular Surface Disease Index (OSDI) and Standard Patient Evaluation of Eye Dryness (SPEED). LLT, complete, and incomplete blinking rate were recorded by the LipiView interferometer. RESULTS: 115 patients (229 eyes, mean age = 60.5 ± 13.6 years) were enrolled in this study. The mean value of the SPEED and OSDI scores was 9.5 and 10.2, respectively. A total of 44.3% of all subjects had severe dry eye syndrome (SPEED, OSDI ≥ 10). LLT (mean = 71.2 nm) was inversely correlated with both the SPEED and OSDI (p = 0.003 and 0.004, respectively). The incomplete-to-complete ratio of blinking rate (i/c ratio) was correlated with both the SPEED and OSDI (p = 0.0048 and 0.0234, respectively). Patients with LLT less than 69 nm were more likely to have severe dry eye syndrome. There was no significant relationship between the Schirmer I test and the SPEED or OSDI. However, LLT was inversely related to the Schirmer I test (linear regression, p = 0.0002, r = -0.1857). CONCLUSIONS: LLT and the i/c ratio were significantly correlated to dry eye symptoms. Eyes with thinner LLT are more likely to have better aqueous tear production. The role of the reciprocal influence between each tear component in the maintenance of tear function warrants further investigation.


Subject(s)
Blinking/physiology , Dry Eye Syndromes/diagnosis , Lipid Metabolism/physiology , Adult , Aged , Cross-Sectional Studies , Dry Eye Syndromes/metabolism , Dry Eye Syndromes/physiopathology , Female , Humans , Interferometry , Male , Middle Aged , Surveys and Questionnaires , Tears/metabolism , Young Adult
11.
Sci Rep ; 9(1): 11795, 2019 08 13.
Article in English | MEDLINE | ID: mdl-31409884

ABSTRACT

Post-transplant thoracic air-leak syndrome (ALS) is rare but potentially life-threatening in patients receiving allogeneic haematopoietic stem cell transplantation (HSCT). Nevertheless, papers on thoracic ALS are limited, and this complication remains largely unknown. We reviewed 423 adult patients undergoing allogeneic HSCT from 2003 to 2014. Risk factors, clinical features and survival for thoracic ALS were collected and analysed. Thirteen out of 423 patients (3.1%) developed post-transplant thoracic ALS, including two ALS patients in the early phase. The median age at HSCT was 33 years among 13 patients with thoracic ALS. Male patients were predominant (69%). The median onset time was 253 days (range: 40-2680) after HSCT. Multivariate analysis revealed that grade III-IV acute graft-versus-host disease (GVHD) (p = 0.017), extensive chronic GVHD (cGVHD) (p = 0.019) and prior history of pulmonary invasive fungal infection (p = 0.007) were significant risk factors for thoracic ALS. In patients with cGVHD, those with thoracic ALS had a significantly worse survival than those without thoracic ALS (p = 0.04). Currently, published data analysing and exploring post-transplant thoracic ALS are limited. Our study employed a large patient cohort and determined the risk factors and clinical features for post-transplant thoracic ALS.


Subject(s)
Graft vs Host Disease/pathology , Hematopoietic Stem Cell Transplantation/adverse effects , Invasive Fungal Infections/microbiology , Transplantation, Homologous/adverse effects , Adult , Female , Graft vs Host Disease/etiology , Graft vs Host Disease/microbiology , Humans , Invasive Fungal Infections/etiology , Invasive Fungal Infections/pathology , Lung/microbiology , Lung/pathology , Male , Middle Aged , Risk Factors , Thoracic Neoplasms/etiology , Thoracic Neoplasms/microbiology , Thoracic Neoplasms/pathology
12.
J Cell Mol Med ; 23(7): 4759-4769, 2019 07.
Article in English | MEDLINE | ID: mdl-31066230

ABSTRACT

Expansion of limbal epithelial stem cells (LSCs) is crucial for the success of limbal transplantation. Previous studies showed that pigment epithelium-derived peptide (PEDF) short peptide 44-mer could effectively expand LSCs and maintain them in a stem-cell state, but the mechanism remained unclear. In the current study, we found that pharmacological inhibition of Sonic Hedgehog (SHh) activity reduced the LSC holoclone number and suppressed LSC proliferation in response to 44-mer. In mice subjected to focal limbal injury, 44-mer facilitated the restoration of the LSC population in damaged limbus, and such effect was impeded by the SHh or ATGL (a PEDF receptor) inhibitor. Furthermore, we showed that 44-mer increased nuclear translocation of Gli1 and Gli3 in LSCs. Knockdown of Gli1 or Gli3 suppressed the ability of 44-mer to induce cyclin D1 expression and LSC proliferation. In addition, ATGL inhibitor suppressed the 44-mer-induced phosphorylation of STAT3 at Tyr705 in LSC. Both inhibitors for ATGL and STAT3 attenuated 44-mer-induced SHh activation and LSC proliferation. In conclusion, our data demonstrate that SHh-Gli pathway driven by ATGL/STAT3 signalling accounts for the 44-mer-mediated LSC proliferation.


Subject(s)
Eye Proteins/pharmacology , Hedgehog Proteins/metabolism , Limbus Corneae/cytology , Nerve Growth Factors/pharmacology , Peptides/pharmacology , Serpins/pharmacology , Signal Transduction , Stem Cells/cytology , Animals , Cell Proliferation/drug effects , Epithelial Cells/drug effects , Gene Knockdown Techniques , Lipase/metabolism , Mice, Inbred BALB C , Mitogens/pharmacology , Rabbits , STAT3 Transcription Factor/metabolism , Signal Transduction/drug effects , Stem Cells/drug effects , Transcription Factors/metabolism
13.
Exp Eye Res ; 185: 107678, 2019 08.
Article in English | MEDLINE | ID: mdl-31129251

ABSTRACT

Age-related meibomian gland (MG) atrophy, characterized by decreased meibocyte proliferation, is one of the causes of meibomian gland dysfunction (MGD), which leads to dry eye disease. Currently, there is no available treatment effectively preventing or reversing the decreased cell proliferation and acinar tissue atrophy. In this study, we investigated the therapeutic effects of a pigment epithelium-derived factor (PEDF) peptide in treating this condition. We found abundant expression of PEDF in the nucleus of acinar basal cells, but not in mature meibocytes, and that the expression levels were significantly decreased in the aged mice. We next treated the aged mice (15-month old) with atrophic MGs using a synthetic PEDF-derived peptide 29-mer (residues 93-121). We found that 29-mer effectively stimulated acinar basal cell proliferation and the following mature meibocyte proliferation in the atrophied MGs. In addition, the treatment increased ΔNp63 and Lrig1 expressions in acinar basal cells. Finally, the aged mice receiving the treatment showed MG growth and improved tear film break-up time. In conclusion, the 29-mer treatment is effective in promoting MG acinar basal cell proliferation and enlarging the acinar size of MG, as well as improving MG function in aged mice, suggesting a therapeutic potential of the PEDF-derived short peptide in ameliorating age-related MGD.


Subject(s)
Aging/physiology , Eye Proteins/therapeutic use , Meibomian Glands/drug effects , Nerve Growth Factors/therapeutic use , Serpins/therapeutic use , Acinar Cells/drug effects , Acinar Cells/metabolism , Acinar Cells/pathology , Animals , Atrophy/drug therapy , Atrophy/metabolism , Atrophy/pathology , Cell Proliferation/drug effects , Conjunctiva/drug effects , Dry Eye Syndromes/drug therapy , Dry Eye Syndromes/metabolism , Dry Eye Syndromes/pathology , Eye Proteins/metabolism , Female , Fluorescent Antibody Technique, Indirect , Immunohistochemistry , Injections, Intraocular , Meibomian Glands/metabolism , Meibomian Glands/pathology , Membrane Glycoproteins/metabolism , Mice , Mice, Inbred C57BL , Nerve Growth Factors/metabolism , Nerve Tissue Proteins/metabolism , Serpins/metabolism , Tears/physiology , Trans-Activators/metabolism
14.
Ann Hematol ; 96(9): 1533-1540, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28710648

ABSTRACT

Bloodstream nontyphoidal salmonella (NTS) infection is rare, but its associated characteristics and microbiological features in immunocompromised patients are worth paying attention to, particularly for those receiving allogeneic hematopoietic stem cell transplantation (SCT). No studies so far have analyzed post-transplant bloodstream NTS infection. Therefore, we reviewed 423 adult patients undergoing allogeneic hematopoietic SCT from 2003 to 2014. Nine out of four hundred twenty-three patients (2.13%) developed post-transplant bloodstream NTS infection, including two patients who had subsequent or combined metastatic infections. The median age at SCT was 35 years (interquartile range, 29-46) among the nine patients with bloodstream NTS infection. Male patients were predominant (78%). The median onset of bloodstream NTS infection was at 315 days after SCT (range, 207-629). Multivariate analysis revealed that extensive chronic graft-versus-host disease (GVHD) (OR 8.054, p = 0.003) and nonmyeloablative transplant conditioning (OR 4.604, p = 0.037) were significant associated characteristics for NTS infection. Currently, there are no published data analyzing and exploring post-transplant bloodstream NTS infections in adult allogeneic hematopoietic SCT. Our study determined the associated characteristics and microbiological features for this infection.


Subject(s)
Hematopoietic Stem Cell Transplantation , Salmonella Infections , Salmonella , Transplantation Conditioning , Adult , Allografts , Female , Graft vs Host Disease/blood , Graft vs Host Disease/etiology , Graft vs Host Disease/microbiology , Humans , Male , Middle Aged , Salmonella Infections/blood , Salmonella Infections/etiology , Salmonella Infections/microbiology , Sex Factors
15.
PLoS One ; 11(11): e0167129, 2016.
Article in English | MEDLINE | ID: mdl-27902756

ABSTRACT

BACKGROUND: To investigate the incidence, risk factors and survival of conjunctival acute graft-versus-host disease (aGVHD) in adult patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: This retrospective study included a total of 139 patients undergoing allogeneic HSCT between January 2012 and December 2014 at a tertiary referral hospital. Patients with ocular complaints after allogeneic HSCT or first donor lymphocyte infusion were evaluated by ophthalmologists. The risk factors for conjunctival aGVHD were analyzed using the Cox proportional hazards model. The overall survival was evaluated using Kaplan-Meier estimates. RESULTS: Thirteen (9.4%) patients developed conjunctival aGVHD, including eight patients with pseudomembranous conjunctivitis. The cumulative incidence of conjunctival aGVHD was 2.1 cases per 10,000 person-day. The median age at HSCT was 47 years (range, 18 to 66) in all patients and 42 years (range, 24 to 58) in the 13 patients with conjunctival aGVHD. Median time of follow-up after allogeneic HSCT was 353 days (range, 11 to 1184). In univariate analysis, grades II-IV skin aGVHD (P = 0.002) and advanced systemic aGVHD except skin aGVHD (overall grades III-IV) (P = 0.001) were significant predictors for conjunctival aGVHD. In multivariate analysis, grades II-IV skin aGVHD was a significant risk factor (P = 0.04). The severity of conjunctival aGVHD was generally correlated with the systemic aGVHD (P = 0.001). Overall survival was significantly shorter in patients with grades II-IV aGVHD compared to those with grade 0-I (P = 0.01). Survival in patients with conjunctival aGVHD did not differ significantly from those without this complication (P = 0.94). In the subgroup analysis of patients with grades III-IV aGVHD, survival was significantly longer in patients with conjunctival involvement than those without (P = 0.03). CONCLUSIONS: The severity of conjunctival aGVHD is correlated with systemic aGVHD, but not with inferior overall survival.


Subject(s)
Conjunctival Diseases/etiology , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Acute Disease , Adolescent , Adult , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Survival Analysis , Transplantation, Homologous/adverse effects , Young Adult
16.
Stem Cells Int ; 2016: 5143071, 2016.
Article in English | MEDLINE | ID: mdl-27123006

ABSTRACT

The cure of hematologic disorders by allogeneic hematopoietic stem cell transplantation (HSCT) is often associated with major complications resulting in poor outcome, including graft-versus-host disease (GVHD), relapse, and death. A novel composite endpoint of GVHD-free/relapse-free survival (GRFS) in which events include grades 3-4 acute GVHD, chronic GVHD requiring systemic therapy, relapse, or death is censored to completely characterize the survival without mortality or ongoing morbidity. In this regard, studies attempting to identify the prognostic factors of GRFS are quite scarce. Thus, we reviewed 377 adult patients undergoing allogeneic HSCT between 2003 and 2013. The 1- and 2-year GRFS were 40.8% and 36.5%, respectively, significantly worse than overall survival and disease-free survival (log-rank p < 0.001). European Group for Blood and Marrow Transplantation (EBMT) risk score > 2 (p < 0.001) and hematologic malignancy (p = 0.033) were poor prognostic factors for 1-year GRFS. For 2-year GRFS, EBMT risk score > 2 (p < 0.001), being male (p = 0.028), and hematologic malignancy (p = 0.010) were significant for poor outcome. The events between 1-year GRFS and 2-year GRFS predominantly increased in relapsed patients. With prognostic factors of GRFS, we could evaluate the probability of real recovery following HSCT without ongoing morbidity.

17.
Cornea ; 35(5): 596-601, 2016 May.
Article in English | MEDLINE | ID: mdl-26967107

ABSTRACT

PURPOSE: To report the long-term outcomes of topical ganciclovir (GCV) and corticosteroids as a maintenance therapy for cytomegalovirus (CMV) corneal endotheliitis. METHODS: This retrospective study included 10 eyes of 9 patients diagnosed with CMV corneal endotheliitis with a minimum 1-year follow-up at a tertiary referral hospital between 2008 and 2014. CMV corneal endotheliitis was defined by corneal edema associated with typical keratic precipitates (KPs) and a positive CMV polymerase chain reaction from aqueous humor taps. Patients receiving long-term topical 0.5% GCV and topical corticosteroids without discontinuation were included. The final corneal condition and endothelial cell density (ECD) were reported. RESULTS: The mean age was 45.6 ± 11.7 years. The mean follow-up duration was 48 ± 25 months. All patients exhibited typical coin-shaped and/or linear KPs. A significant resolution of corneal edema and decreased KPs were achieved within 1 month in all patients after initiating topical 0.5% GCV every 2 hours and topical corticosteroids twice a day. The dose frequency was gradually tapered to GCV 4 times and corticosteroids once or twice a day as a maintenance therapy. All 10 eyes had a clear graft or corneas at the end of this study. The mean ECD was 1630 ± 699 cells per millimeter square before treatment and 1776 ± 834 cells per millimeter square at the end of the study period. CONCLUSIONS: Topical 0.5% GCV and corticosteroids as a maintenance regimen without interruption effectively preserved long-term corneal endothelial function.


Subject(s)
Cytomegalovirus Infections/drug therapy , Cytomegalovirus/isolation & purification , Endothelium, Corneal/physiology , Eye Infections, Viral/drug therapy , Ganciclovir/therapeutic use , Glucocorticoids/therapeutic use , Keratitis/drug therapy , Administration, Topical , Adult , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , Aqueous Humor/virology , Corneal Edema/drug therapy , Corneal Edema/physiopathology , Corneal Edema/virology , Cytomegalovirus Infections/physiopathology , Cytomegalovirus Infections/virology , DNA, Viral/genetics , Drug Combinations , Eye Infections, Viral/physiopathology , Eye Infections, Viral/virology , Female , Follow-Up Studies , Ganciclovir/administration & dosage , Glucocorticoids/administration & dosage , Humans , Keratitis/physiopathology , Keratitis/virology , Male , Middle Aged , Ophthalmic Solutions , Polymerase Chain Reaction , Prednisolone/administration & dosage , Prednisolone/analogs & derivatives , Prednisolone/therapeutic use , Retrospective Studies
18.
J Microbiol Immunol Infect ; 49(4): 567-74, 2016 Aug.
Article in English | MEDLINE | ID: mdl-25735797

ABSTRACT

BACKGROUND: To investigate the incidence and risk factors for the occurrence of proven or probable invasive fungal infection (IFI) in adult patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: We retrospectively analyzed 421 patients undergoing HSCT between 2002 and 2013 in our hospital. The risk factors for the occurrence of IFI were analyzed using Cox regression models. RESULTS: Thirty-one patients with the median age of 42 years (range, 19-60 years) developed IFI after HSCT. The post-HSCT IFI incidence was 7.4% and median time from HSCT to the diagnosis of IFI was 139 days (range, 2-1809 days). Of the pretransplant factors, European Group for Blood and Marrow Transplantation (EBMT) risk score > 2 (p = 0.001) and prior history of IFI (p = 0.006) or type 2 diabetes mellitus (DM; p = 0.042) were the significant predictors for post-HSCT IFI in univariate analyses. In multivariate analysis, EBMT risk score > 2 (p = 0.015) and prior history of IFI (p = 0.006) retained significance. Of the post-transplant factors, acute graft-versus-disease (GVHD) overall Grade III-IV (p < 0.001), extensive chronic GVHD (p = 0.002), development of post-transplant lymphoproliferative disorders (p = 0.005), and the use of high-dose steroids (p < 0.001) were statistically significant in univariate analyses. After multivariate analysis, high-dose steroids (p < 0.001) and acute GVHD overall Grade III-IV (p = 0.045) retained significance. CONCLUSION: These results suggest that risk group stratification prior to HSCT and monitoring of IFI in patients with severe GVHD receiving high-dose steroids is mandatory to reduce the mortality and morbidity of post-HSCT IFI, especially in those with prior history of IFI.


Subject(s)
Aspergillosis/epidemiology , Hematopoietic Stem Cell Transplantation/adverse effects , Immunocompromised Host , Invasive Fungal Infections/epidemiology , Adult , Aged , Aspergillosis/microbiology , Diabetes Mellitus, Type 2/epidemiology , Female , Graft vs Host Disease/prevention & control , Humans , Invasive Fungal Infections/microbiology , Male , Methylprednisolone/adverse effects , Methylprednisolone/therapeutic use , Middle Aged , Retrospective Studies , Risk Factors , Transplantation, Homologous/adverse effects , Treatment Outcome , Young Adult
19.
Br J Haematol ; 169(5): 737-45, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25818840

ABSTRACT

Pericardial effusion (PE) is a rare but potentially life-threatening complication for allogeneic haematopoietic stem cell transplantation (HSCT) recipients. The risk factors, aetiology, incidence and therapy are largely unclear. To investigate this issue, we reviewed 391 adult patients undergoing allogeneic HSCT between January 2003 and December 2013. Twelve out of 391 patients (3·1%) developed PE of moderate to large amounts, including 9 out of 12 patients (75%) identified as late-onset PE. Two out of the nine patients with late-onset PE experienced recurrent effusion. The median age at HSCT was 44·5 years (range: 22-63 years) among the 12 patients with PE and 47 years in the late-onset patients. Multivariate analysis revealed that multiple transplant procedures was a significant risk factor for PE (P = 0·036) and a trend as risk factor in patients aged>50 years (P = 0·066). For late-onset PE, pre-transplant age>50 years (P = 0·032) and extensive chronic graft-versus-host disease (cGVHD) (P = 0·006) remained statistically significant on multivariate analysis. Currently, there are no published data exploring the risk factors for post-transplant PE in adult patients of allogeneic HSCT. Our study determined the risk factors and incidence for the post-transplant PE, especially in the late-onset group.


Subject(s)
Pericardial Effusion/epidemiology , Pericardial Effusion/etiology , Adolescent , Adult , Aged , Female , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Incidence , Male , Middle Aged , Patient Outcome Assessment , Pericardial Effusion/mortality , Retrospective Studies , Risk Factors , Transplantation Conditioning/adverse effects , Transplantation, Homologous , Young Adult
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