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Biomedical subjects

Wen-Ming Hsu

Publications and source records attributed to Wen-Ming Hsu.

At least 19 recordsLinked to original sources

Lacrimal gland extranodal marginal zone B-cell lymphoma of MALT-type.

PURPOSE: To evaluate the clinical features and outcome of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma) in the lacrimal gland. DESIGN: Retrospective, noncomparative, observational case series in an academic referral setting. METHODS: A consecutive series of 13 histologically verified MALT lymphoma in the lacrimal gland at presentation was studied. Clinical characteristics, treatment, and prognosis were analyzed. RESULTS: Eight males and five females with a median age of 64 years and a median follow-up time of 48 months were included. All patients had no prior lymphoma and initially presented as MALT lymphoma in the lacrimal gland. Extraorbital involvement at diagnosis was noted in six patients (46.2%). Two patients had autoimmune disease, and both had Stage IV disease at presentation. Treatment consisted of surgical resection in one patient, radiotherapy in four, chemotherapy in four, and combined radiotherapy and chemotherapy in four. Complete remissions were obtained in eight patients (61.5%). Patients with bilateral disease (61.5%) had a higher rate of advanced-stage disease and a poor outcome. Recurrence was noted in two patients. At the last follow-up, eight patients were free of disease, three were alive with disease, one died of sepsis as a complication of chemotherapy, and one died of lymphoma. CONCLUSIONS: MALT lymphoma in the lacrimal gland has a high rate of extraorbital involvement and synchronous bilateral lacrimal gland involvement at presentation. The prognosis is relatively poor, especially in patients with advanced disease and bilateral involvement. Extensive staging and long-term follow-up are warranted for these patients.

Adult↗

Unnatural amino acid-substituted (hydroxyethyl)urea peptidomimetics inhibit gamma-secretase and promote the neuronal differentiation of neuroblastoma cells.

Gamma-secretase, exhibiting characteristics of aspartyl protease, mediates the intramembranous proteolysis of beta-amyloid precursor protein (APP) and Notch, and it is considered to be a prime pharmacological target in the development of therapeutics for Alzheimer's disease (AD). To identify compounds that block gamma-secretase-mediated proteolysis, we used a highly sensitive cell-based reporter gene assay for gamma-secretase in which Gal4/VP16-tagged C99-APP was expressed as the immediate substrate of gamma-secretase, and Gal4/VP16-tagged APP intracellular domain released by the gamma-secretase cleavage then activated the expression of the Gal4-driven luciferase reporter gene. Using this reporter assay, we demonstrated that the newly synthesized (hydroxyethyl)urea peptidomimetics, which contain unnatural amino acid moieties at positions P1' and/or P3', can effectively inhibit gamma-secretase activity and significantly reduce Abeta production. The gamma-secretase-dependent S3 cleavage of Notch was also consistently blocked by these (hydroxyethyl)ureas as evidenced by the decreased generation of the Notch intracellular domain, a prerequisite for the activation of Notch signaling. The inhibition of Notch signaling by active Jia compounds efficiently promotes the neuronal differentiation of neuroblastoma cells, intervening in tumorigenesis and the malignancy of neuroblastomas. Our results suggest that (hydroxyethyl)urea peptidomimetics containing unnatural amino acid substitutions could represent a novel class of gamma-secretase inhibitors with enhanced stability, providing the basis for the further development of effective therapeutics for AD and neuroblastomas.

Amino Acids↗

The immediate early 2 protein of human cytomegalovirus (HCMV) mediates the apoptotic control in HCMV retinitis through up-regulation of the cellular FLICE-inhibitory protein expression.

Human CMV (HCMV) is a widespread human pathogen that causes blindness by inducing retinitis in AIDS patients. Previously, we showed that viral immediate early 2 (IE2) protein may allow HCMV to evade the immune control by killing the Fas receptor-positive T lymphocytes attracted to the infected retina with increased secretion of Fas ligand (FasL). In this study, we further demonstrate that the secreted FasL also kills uninfected Fas-rich bystander retinal cells and that IE2 simultaneously protects the infected cells from undergoing apoptotic death, in part, by activating the expression of cellular FLIP (c-FLIP), an antiapoptotic molecule that blocks the direct downstream executer caspase 8 of the FasL/Fas pathway. c-FLIP induction requires the N-terminal 98 residues of IE2 and the c-FLIP promoter region spanning nucleotides -978 to -696. In vivo association of IE2 to this region, IE2-specific c-FLIP activation, and decrease of FasL-up-regulated activities of caspases 8 and 3 were all demonstrated in HCMV-infected human retinal cells. Moreover, c-FLIP up-regulation by IE2 appeared to involve PI3K and might also render cells resistant to TRAIL-mediated death. Finally, enhanced c-FLIP signals were immunohistochemically detected in IE-positive cells in the HCMV-infected lesions of the human retina. Taken together, these data demonstrate specific activation of c-FLIP by HCMV IE2 and indicate a novel role for c-FLIP in the pathogenesis of HCMV retinitis.

Apoptosis↗

Incidence of eyelid cancers in Taiwan: a 21-year review.

PURPOSE: To describe the epidemiologic characteristics and incidence trends of primary eyelid cancers in the Chinese population in Taiwan between 1979 and 1999. DESIGN: Retrospective population-based cancer registry data review. PARTICIPANTS: A total of 1166 primary eyelid cancers coded to International Classification of Diseases 8 or 9, site 172.1 (malignant melanoma of eyelid) and 173.1 (other malignant neoplasm of eyelid) were retrieved from the Taiwan National Cancer Registry between January 1979 and December 1999. Of these, 1121 (96.1%) were histopathologically verified and were used for analysis. METHODS: Age- and gender-specific incidence rates were calculated and were age-adjusted to the 2000 world standard population. Trends in incidence rates were estimated by calculating the annual percentage change. We further examined the effects of age, period of diagnosis, and birth cohort on incidence trends using age-period-cohort analysis. MAIN OUTCOME MEASURE: Age-standardized incidence rate. RESULTS: The mean age at diagnosis of eyelid cancers was 62.6+/-14.1 years. The average annual age-standardized incidence rate was 3.2 per million during the study period. There was an overall increase of incidence rates from 1.5 per million in 1979 to 5.1 per million in 1999, with an annual percentage change of 4.63% (P<0.001). The most common eyelid malignancy was basal cell carcinoma (BCC; 65.1%), followed by squamous cell carcinoma (12.6%), and sebaceous cell carcinoma (7.9%). The increasing rates were mainly driven by an increase in the incidence of BCC. Cohort effects were found to play a major role in terms of model fit for the incidence trends of BCC. CONCLUSIONS: These national data reveal a rapidly increasing incidence of eyelid cancers from 1979 to 1999 in Taiwan. Basal cell carcinoma dominates the incidence trends, and the significant cohort effects give a warning of increasing risk of BCC in younger birth cohorts.

Adenocarcinoma, Sebaceous↗

Fluoxetine up-regulates expression of cellular FLICE-inhibitory protein and inhibits LPS-induced apoptosis in hippocampus-derived neural stem cell.

Fluoxetine is a widely used antidepressant compound which inhibits the reuptake of serotonin in the central nervous system. Recent studies have shown that fluoxetine can promote neurogenesis and improve the survival rate of neurons. However, whether fluoxetine modulates the proliferation or neuroprotection effects of neural stem cells (NSCs) needs to be elucidated. In this study, we demonstrated that 20 microM fluoxetine can increase the cell proliferation of NSCs derived from the hippocampus of adult rats by MTT test. The up-regulated expression of Bcl-2, Bcl-xL and the cellular FLICE-inhibitory protein (c-FLIP) in fluoxetine-treated NSCs was detected by real-time RT-PCR. Our results further showed that fluoxetine protects the lipopolysaccharide-induced apoptosis in NSCs, in part, by activating the expression of c-FLIP. Moreover, c-FLIP induction by fluoxetine requires the activation of the c-FLIP promoter region spanning nucleotides -414 to -133, including CREB and SP1 sites. This effect appeared to involve the phosphatidylinositol-3-kinase-dependent pathway. Furthermore, fluoxetine treatment significantly inhibited the induction of proinflammatory factor IL-1beta, IL-6, and TNF-alpha in the culture medium of LPS-treated NSCs (p<0.01). The results of high performance liquid chromatography coupled to electrochemical detection further confirmed that fluoxentine increased the functional production of serotonin in NSCs. Together, these data demonstrate the specific activation of c-FLIP by fluoxetine and indicate the novel role of fluoxetine for neuroprotection in the treatment of depression.

Animals↗

A novel strategy for corneal endothelial reconstruction with a bioengineered cell sheet.

Cellular organization of foreign grafts constructed from cultivated cells is critical to successful graft-host integration and tissue repair. This study described a novel human corneal endothelial cell (HCEC) therapeutic method, where cultivated adult HCEC sheet with uniform orientation was prepared and transplanted to a rabbit cornea. Having a correct morphology and intact barriers, the HCEC sheet was made by the temperature-modulated detachment of monolayered HCECs from thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm)-grafted surfaces and was delivered with proper polarity to the corneal posterior surface by a bioadhesive gelatin disc. Results of the in vivo studies, including the follow-up clinical observations and histological examinations, showed the laminated HCEC sheet was successfully integrated into rabbit cornea denuded with endothelial layer after the biodegradation of gelatin carrier. These data indicate the feasibility of the proposed procedure in cell therapy for corneal endothelial cell loss.

Acrylamides↗

Induction of vitronectin and integrin alphav in the retina after optic nerve injury.

PURPOSE: Vitronectin is a secreted glycoprotein present in blood plasma and is present in the extracellular matrix of many tissues. It was found in the retinal cDNA library that contains genes whose expression is upregulated after optic nerve injury in a previous study. The purpose of this study was to assess the temporal and spatial changes in expression of vitronectin and integrin alphav in the retina following optic nerve injury. METHODS: Adult Balb/c mice underwent crush of the optic nerve in one eye only. RT-PCR was used to determine the temporal expression of vitronectin mRNA in the retina after injury. In addition, expression at the protein level in the retina and the optic nerve of vitronectin and its major receptor subunit, integrin alphav, was analyzed by immunohistochemistry. RESULTS: Upregulation of vitronectin mRNA in the retina was detected at one day after injury, peaking at three days, and maintained up to one week. An elevated expression of vitronectin protein was also observed in the inner retina, optic nerve head, and the optic nerve after nerve crush. In the inner retina, the increased expression of vitronectin was found in retinal ganglion cells (RGCs) and its surrounding extracellular matrix. Expression of integrin alphav was also increased in the RGC layer and in the glial cells of the nerve head and the crush site. CONCLUSIONS: As vitronectin is an extracellular protein that can support cell attachment and promote neurite extension, elevated expression of vitronectin and its receptor may facilitate axonal regeneration following injury. We propose that treatment sustaining secretion of endogenous vitronectin or direct application of exogenous vitronectin may be a method to augment regeneration of the severed optic axons.

Animals↗

The influence of biologic factors on the surgical decision in advanced neuroblastoma.

BACKGROUND: Molecular markers greatly affect the outcome of neuroblastoma. This study evaluated the influence of Trk-A and myelocytomatosis viral-related oncogene, neuroblastoma-derived (MYCN) on the role of surgery in advanced neuroblastoma. METHODS: Ten stage 3 and 35 stage 4 neuroblastoma patients were included. Tumor resection was classified into gross total resection (GTR) and incomplete resection. Patients were classified into three biological risk groups according to Trk-A expression and myelocytomatosis viral-related oncogene, neuroblastoma-derived (MYCN) status in tumor tissues studied by immunohistochemistry and fluorescence in situ hybridization, respectively: low risk (positive Trk-A and normal MYCN), intermediate risk (negative Trk-A and normal MYCN), and high risk (positive or negative Trk-A and MYCN amplification). The effect of tumor resection on prognosis was studied and stratified according to the risk grouping. RESULTS: GTR was achieved in 21 patients (46.7%) with a higher complication rate (33% vs. 8% in the incomplete resection group, P = .036). GTR was easier to achieve in low-risk tumors than in intermediate- or high-risk tumors (12 of 13, 4 of 17, and 5 of 15, respectively; P < .001). GTR predicted a favorable prognosis for intermediate-risk patients (P = .037; log-rank test), but not for low- or high-risk patients because of the overall favorable and poor prognosis, respectively. CONCLUSIONS: GTR carries a potentially higher possibility of complication. Although GTR can be achieved easily in low-risk neuroblastoma patients with a favorable prognosis, surgeons should do their best to achieve GTR for intermediate-risk patients to improve outcome. Nevertheless, sacrificing vital organs to achieve GTR for high-risk patients is not justified.

Biomarkers, Tumor↗

Factors predicting intraocular pressure control after phacoemulsification in angle-closure glaucoma.

OBJECTIVES: To investigate whether the presence of glaucomatous optic neuropathy affects the reduction of intraocular pressure (IOP) after phacoemulsification in postiridotomy eyes with primary narrow angles, and to evaluate the preoperative factors associated with postoperative IOP control in primary angle-closure glaucoma (PACG). METHODS: Patients with PACG undergoing phacoemulsification were prospectively enrolled and received a complete ophthalmic examination. Diurnal IOP was measured 1 day before and 3 months after surgery. For comparison, patients with primary angle closure or angle closure suspect (PAC/S) undergoing phacoemulsification were also enrolled. RESULTS: Postoperative reduction of IOP was significant in the PACG group (n = 29; P = .001) and in the PAC/S group (n = 28; P<.001), with no significant difference between the groups. The number of glaucoma medications used decreased in both groups (both, P<.001). Multiple regression analysis for the PACG group showed that there was a positive correlation between postoperative IOP and preoperative factors of mean IOP (P = .001) and the anterior chamber depth (P = .03). CONCLUSIONS: The reduction of IOP 3 months after phacoemulsification is significant and is similar in extent in postiridotomy eyes with and without glaucomatous optic neuropathy. A higher postoperative IOP in PACG is associated with a higher preoperative IOP and with a deeper preoperative anterior chamber depth.

Aged↗

Bioengineered human corneal endothelium for transplantation.

OBJECTIVE: To investigate whether the bioengineered human corneal endothelial cell (HCEC) monolayers harvested from thermoresponsive culture supports could be used as biological tissue equivalents. METHODS: Untransformed adult HCECs derived from eye bank corneas were cultivated on a thermoresponsive poly-N-isopropylacrylamide-grafted surface for 3 weeks at 37 degrees C. Confluent cell cultures with a phenotype and cell density similar to HCECs in vivo were detached as a laminated sheet by lowering the culture temperature to 20 degrees C. In vitro characteristics of the HCEC sheets were determined evaluating their viability and by scanning electron microscopy, immunohistochemistry, and histological studies. RESULTS: After separation from culture surfaces via a thermal stimulus, the HCEC sheets remained viable. Polygonal cell morphology and multiple cellular interconnections were observed throughout the HCEC sheets. Immunolocalization of zonula occludens-1 and Na+,K+-adenosine triphosphatase (ATPase) indicated the formation of tight junctions and the distribution of ionic pumps at the cell boundary. In addition, we ascertained that cultured HCECs have a monolayered architecture that mimics native corneal endothelium. CONCLUSION: These data suggest that a well-organized and functional HCEC monolayer can feasibly be used as tissue equivalents for replacing compromised endothelium.Clinical Relevance Bioengineered human corneal endothelium fabricated from thermoresponsive supports can potentially offer a new therapeutic strategy for corneal endothelial cell loss.

Aged↗

Propionibacterium acnes DNA from an explanted intraocular lens detected by polymerase chain reaction in a case of chronic pseudophakic endophthalmitis.

We report a case of Propionibacterium acnes DNA from the explanted intraocular lens (IOL) a 76-year-old man with delayed-onset chronic endophthalmitis. The detection was by polymerase chain reaction (PCR). Slitlamp microscopic examination showed cells and flare in the anterior chamber, keratic precipitates on the endothelium, and multiple white plaques on both surfaces of the IOL. Propionibacterium acnes DNA was found in both the aqueous humor and the explanted IOL by PCR. Scanning electron microscopy showed diphtheroid particles, a coating of biofilm-like deposits, as well as scattered crystals on the surface of the explanted IOL and supported the possibility of P acne colonies on the IOL.

Aged↗

Retinoblastoma with spinal recurrence presenting as spinal cord compression.

Central nervous system (CNS) involvement is not rare in extraocular retinoblastoma, and it is not surprising to find it in view of its route of spread. However, although spinal recurrence presenting as spinal cord compression (SCC) is a form of CNS involvement, it is extremely rare. This report describes two patients with unilateral retinoblastoma with spinal recurrence presenting as SCC. The first patient developed erythematous swelling of the right foot and weakness of the bilateral lower limbs at 7 months after left enucleation. Examination revealed pitting edema of bilateral feet and muscle power of 2+ to 3+, with intact sensory function. The second patient developed weakness of the bilateral lower limbs, and defecative and urinary difficulty for 2 days at 8 months after left enucleation. Examination revealed pitting edema of bilateral feet and muscle power of 2+, with defective sensory function. Both patients received surgery and local irradiation after SCC. The first patient refused chemotherapy and survived only 4 months due to disease progression. The second patient received systemic and intrathecal chemotherapy, and survived 19.5 months without disease progression. Spinal recurrence with SCC should be suspected when leg weakness or bowel or bladder disturbance occurs in patients with retinoblastoma.

Child, Preschool↗

Congenital hemangiopericytoma in a neonate.

Hemangiopericytoma is a rare malignant vascular tumor that usually occurs in adults. The occurrence of these tumors in infants, known as congenital or infantile hemangiopericytoma, is even rarer and their behavior may be more benign than the adult type. We describe a 1-day-old female neonate with congenital hemangiopericytoma, presenting with a right inguinal mass at birth. At the time of surgery, lymphangioma was suspected because of its appearance, fluid-filled multicystic content, and the high incidence of this disease in pediatric patients. Tumor excision was performed and hemangiopericytoma was diagnosed by histology. There was no tumor recurrence during 12 months of follow-up.

Abdominal Neoplasms↗

Corneal lesion as the initial manifestation of tyrosinemia type II.

Tyrosinemia type II (Richner-Hanhart syndrome) is a rare autosomal recessive disease with deficiency of tyrosine aminotransferase and subsequently increasing level of serum tyrosine. We report the case of a 2-year-old girl who was referred due to bilateral corneal lesions. Slit-lamp examination showed small granular white deposits arranged in a dendritic pattern in the superficial central cornea of both eyes. Physical examination revealed painful, non-pruritic, hyperkeratotic plaques on the soles, palms and fingertips. Mental evaluation demonstrated developmental delay for her age. Blood examination revealed serum tyrosine level to be 1868 microM (normal range, 30-110 microM), which decreased to 838 microM with 2-month diet on tyrosine and phenylalanine restriction. The corneal and skin lesions resolved completely. However, the corneal deposits recurred a month later as her mother failed to strictly control the diet because the little girl was losing weight and activity. With specific formula and adjusted diet regimen, the corneal lesions decreased again. Corneal pseudodendritic deposits may be the initial manifestation in patients with tyrosinemia type II. Early diagnosis and intervention with diet control are crucial for preventing permanent visual and developmental deficits. Corneal deposits can be one of the parameters in monitoring the efficacy of diet control.

Child, Preschool↗

Preseptal and orbital cellulitis: a 10-year review of hospitalized patients.

BACKGROUND: Preseptal and orbital cellulitis range in severity from minor to potentially severe complications. The purpose of this study is to describe the clinical features of patients with preseptal or orbital cellulitis in one medical center in Taiwan, and to assess the effectiveness of treatments and the complications. METHODS: Patients admitted between 1996 and 2005 to Taipei Veterans General Hospital under the diagnosis of preseptal or orbital cellulitis were retrospectively reviewed. The demographics, administrative history, past history, clinical presentations, treatments, and complications were analyzed. RESULTS: In total, 94 patients fulfilling the diagnostic criteria for preseptal or orbital cellulitis were identified (67 had preseptal cellulitis, 27 had orbital cellulitis). While paranasal sinus disease was the most common predisposing cause in orbital cases, skin lesions in children and dacryocystitis in adults were the most common in preseptal cases. Microbiologic investigations showed variable results, but the most common pathogen isolated was Staphylococcus aureus. Cultures from eye swabs and local abscesses gave the highest positive yield. Blood cultures were taken in some patients, but the positive rate was extremely low. Treatments included intravenous antibiotics alone, or intravenous antibiotics combined with surgical drainage. Only one case had permanent ocular motility impairment after removal of the orbital foreign body. CONCLUSION: Despite the past history of potential morbidity and even mortality from orbital cellulitis, early diagnosis and prompt treatment with proper antibiotics and/or surgical intervention can achieve a good prognosis.

Adolescent↗

Effects of bimatoprost 0.03% on ocular hemodynamics in normal tension glaucoma.

PURPOSE: The aim of this study was to investigate the effects of bimatoprost 0.03% on ocular hemodynamics in patients with normal tension glaucoma (NTG). METHODS: Twenty-two (22) patients with NTG were consecutively recruited. After basic eye examination and diurnal intraocular pressure (IOP) measurement, color Doppler imaging was used to measure the peak systolic and end diastolic velocities and resistive index of the central retinal, lateral posterior ciliary, and medial posterior ciliary arteries. Patients received bimatoprost 0.03% for 4 weeks, and these measurements were then repeated. The worse eye of each NTG patient was used in the statistical analysis. RESULTS: Bimatoprost 0.03% significantly reduced mean IOP from 15.1 +/- 3.8 mmHg at baseline to 12.0 +/- 2.9 mmHg after treatment in our sample of NTG patients (P < 0.001). No significant changes in blood velocities or resistance indices were observed in the retrobulbar vessels after the 4-week treatment. CONCLUSIONS: Topical bimatoprost 0.03% significantly reduced IOP in our NTG patients without causing significant hemodynamic changes in the retrobulbar vessels.

Aged↗

Corneal injury by anti-misting agent in swim goggles: a case report.

PURPOSE: To report a case of corneal injury by swim goggle anti-misting agent. METHODS: Case report. RESULTS: A 47-year-old man presented with ocular injury caused by swim goggle anti-misting agent. Two weeks previously, the patient felt sudden ocular pain and grit after pool water flooded his goggles while swimming. Before the patient's swim, a copious amount of anti-misting agent was sprayed inside his goggles. On examination, severe corneal epithelial defect and stroma edema of the right eye were noted. Best-corrected visual acuity (BCVA) was 20/40. Right eye corneal thickness was 625 microm. Topical corticosteroids, antibiotic eye drops, and oral tetracycline were started. After 1 week of treatment, the epithelial defect of his right cornea improved slightly. Stromal edema decreased mildly. Epithelial defect persisted at 1 month follow-up. Right eye BCVA remained 20/40. Three months after treatment, the right eye epithelial defect healed completely. Mild diffuse superficial stromal opacity was noted. BCVA improved to 20/20. At 1-year follow-up, right eye corneal thickness was 547 microm, which was thinner than the left eye. Right eye corneal endothelial cell density measured approximately 1500 cells/mm2, which was less than the left eye at 2300 cells/mm2. The faint, diffuse stromal opacity disappeared; however, white subepithelial plaques were noted in the cornea centers. After 1 month of treatment with topical corticosteroids, the plaques subsided completely. The corneas remained clear at 2-year follow-up. CONCLUSION: Anti-misting agent can cause severe corneal injuries, including persistent epithelial defects, stromal edema and opacity, endothelial cell loss, and subepithelial plaque.

Anti-Bacterial Agents↗

Long-term prognosis of patients with biliary atresia: a 25 year summary.

OBJECTIVE: The purpose of this study was to delineate the long-term prognosis of biliary atresia (BA) in Taiwan. STUDY DESIGN: From 1976 to 2000, 185 children were diagnosed with BA, 22 underwent exploratory laparotomy without Kasai operation, and 163 underwent Kasai operation, of which 141 cases had long-term follow-up and formed the basis of this study. The outcome was analyzed. RESULTS: Among the 141 BA children studied who underwent Kasai operation, 115 (81.6%) had recoloration of stools, and 86 (61.0%) became jaundice-free (bilirubin <34 micromol/L) [corrected]. The resolution of jaundice and the absence of repeated cholangitis contributed to better outcome. Five and 10 year survival rates with native liver were 35% and 31%, respectively. Liver transplantation was performed in 19 patients (all but 2 with a living-related donor), and 15 (79%) survived. Five and 10 year overall survival rates for BA patients were 41.9% and 40.2%, respectively. CONCLUSIONS: The study delineated the long-term outcome of BA in an Asian country other than Japan. Survival with native liver after a Kasai operation in Taiwan was similar to that in the American and European series. Limited donors for liver transplantation in the years of the study accounted for the poor overall prognosis of BA patients in this series.

Adolescent↗