Clinicopathological features of corneal invasion by filtering bleb.

PURPOSE: To describe the clinicopathological characteristics and explore the possible etiology of cornea invasion by filtering bleb (CIFB) after filtering surgery. METHODS: We reviewed 22 patients treated for CIFB between March 2005 and March 2022. The patients were followed up for more than 1 year. Slit-lamp examination, optical coherence tomography (OCT), ultrasound biomicroscopy, and histopathological examination were performed to observe the morphology of the bleb and depth of corneal invasion. Depending on the severity of the lesion, treatments consisting of local massage, acupuncture separation, or surgical resection were administered. RESULTS: The mean age of the patients was 56.3 ± 8.8 years. All patients underwent filtering surgery in the moderate or advanced stage of glaucoma. The filtering bleb was closely connected with the cornea, and its posterior boundary was locally adhered. Forward displacement of the internal opening of the filtering bleb was found in 4 of 7 surgically treated patients. OCT and pathological examination showed that the filtering blebs invaded the corneal stroma. Removal of the adhesion of the posterior boundary of the filtering bleb by different treatment methods successfully improved the patients' conditions. CONCLUSION: Filtering blebs can invade the corneal stroma. Adhesion of the posterior boundary and forward displacement of the internal opening of the filtering bleb are the possible causes of CIFB. Removal of the adhesion of the posterior boundary of the filtering bleb can halt the progression of CIFB.

ROS-responsive liposomes as an inhaled drug delivery nanoplatform for idiopathic pulmonary fibrosis treatment via Nrf2 signaling.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease with pathophysiological characteristics of transforming growth factor-ß (TGF-ß), and reactive oxygen species (ROS)-induced excessive fibroblast-to-myofibroblast transition and extracellular matrix deposition. Macrophages are closely involved in the development of fibrosis. Nuclear factor erythroid 2 related factor 2 (Nrf2) is a key molecule regulating ROS and TGF-ß expression. Therefore, Nrf2 signaling modulation might be a promising therapy for fibrosis. The inhalation-based drug delivery can reduce systemic side effects and improve therapeutic effects, and is currently receiving increasing attention, but direct inhaled drugs are easily cleared and difficult to exert their efficacy. Therefore, we aimed to design a ROS-responsive liposome for the Nrf2 agonist dimethyl fumarate (DMF) delivery in the fibrotic lung. Moreover, we explored its therapeutic effect on pulmonary fibrosis and macrophage activation. RESULTS: We synthesized DMF-loaded ROS-responsive DSPE-TK-PEG@DMF liposomes (DTP@DMF NPs). DTP@DMF NPs had suitable size and negative zeta potential and excellent capability to rapidly release DMF in a high-ROS environment. We found that macrophage accumulation and polarization were closely related to fibrosis development, while DTP@DMF NPs could attenuate macrophage activity and fibrosis in mice. RAW264.7 and NIH-3T3 cells coculture revealed that DTP@DMF NPs could promote Nrf2 and downstream heme oxygenase-1 (HO-1) expression and suppress TGF-ß and ROS production in macrophages, thereby reducing fibroblast-to-myofibroblast transition and collagen production by NIH-3T3 cells. In vivo experiments confirmed the above findings. Compared with direct DMF instillation, DTP@DMF NPs treatment presented enhanced antifibrotic effect. DTP@DMF NPs also had a prolonged residence time in the lung as well as excellent biocompatibility. CONCLUSIONS: DTP@DMF NPs can reduce macrophage-mediated fibroblast-to-myofibroblast transition and extracellular matrix deposition to attenuate lung fibrosis by upregulating Nrf2 signaling. This ROS-responsive liposome is clinically promising as an ideal delivery system for inhaled drug delivery.

Design and Methodology of a Multi-Centre Clinical Trial of Low Dose Laser Cycloplasty for the Treatment of Malignant Glaucoma in China.

PURPOSE: To summarize the design and methodology of a trial designed to evaluate the efficacy and safety of low dose laser cycloplasty (LCP) in treating malignant glaucoma. METHODS: Prospective, multicentre, non-controlled clinical trial. Subjects were recruited from eight ophthalmic centers in China. The target sample size was 34. Patients aged >18 years with a clinical diagnosis of malignant glaucoma inadequately controlled on medical therapy or malignant glaucoma recurrence after topical cycloplegics withdrawal were enrolled. All patients underwent LCP under retrobulbar anesthesia or sub-Tenon anesthesia. LCP is a treatment adopting few laser points (1100-2000 mW energy, 2000 milliseconds duration) that cauterizes and remodels the ciliary body over two clock hour-positions, which may relieve the ciliary ring block. Follow-up is planned for a period of 12 months. The primary outcome is the resolution of malignant glaucoma which is defined as central anterior chamber deepening after LCP. CONCLUSION: The Malignant Glaucoma Treatment trial (MGTT) will be the first prospective trial providing evidence of a treatment for malignant glaucoma. It intends to provide clinicians an optional, easy and convenient treatment for malignant glaucoma patients. Detailed morphological and biometric information collected during the study period will also help provide experience for the outcomes of malignant glaucoma. TRIAL REGISTRATION NUMBER: ChiCTR1800017960.

Immune Checkpoint Blockade Therapy May Be a Feasible Option for Primary Pulmonary Lymphoepithelioma-like Carcinoma.

Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype of non-small cell lung cancer (NSCLC) for which there is currently no recognized treatment. Recently, favorable immune checkpoint blockade responses have been observed in PPLELC. This study aimed to review the effects of this regimen in patients with advanced PPLELC. PPLELC patients treated with immune checkpoint inhibitors at West China Hospital between January 2008 and December 2019 were retrospectively identified. Demographic parameters and antitumor treatment details were retrieved and reviewed. Among 128 patients diagnosed with PPLELC, 5 who received immune checkpoint inhibitors at advanced stages were included in the analysis. All of these patients were female nonsmokers with a median age of 55.6 (range 53-58) years at diagnosis. Their median PD-L1 expression was 40% (range, 30-80%). Although the patients underwent surgeries, chemotherapy and radiotherapy, all the treatments failed. Immune checkpoint inhibitors were administered palliatively, and three patients responded favorably, with the best overall response being partial remission (PR). Thus, immune checkpoint inhibitors may be a promising treatment for advanced PPLELC, and large clinical trials are warranted to obtain more evidence regarding this regimen.

Clinical features of asthma with comorbid bronchiectasis: A systematic review and meta-analysis.

BACKGROUND: This meta-analysis aimed to systematically estimate the prevalence of comorbid bronchiectasis in patients with asthma and to summarize its clinical impact. METHODS: Embase, PubMed, and Cochrane Library electronic databases were searched to identify relevant studies published from inception until March 2020. STUDY SELECTION: Studies were included if bronchiectasis was identified by high-resolution computed tomography. Outcomes included the prevalence of bronchiectasis and its association with demographic characteristics and indicators of asthma severity, including results of lung function tests and the number of exacerbations. RESULTS: Five observational studies with 839 patients were included. Overall, the mean prevalence of bronchiectasis in patients with asthma was 36.6% (307/839). Patients with comorbid bronchiectasis had lower forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) (MD: -2.71; 95% CI: -3.72 to -1.69) and more frequent exacerbations (MD: 0.68; 95% CI: 0.03 to 1.33) than those with asthma alone, and there was no significant difference of sex, duration of asthma and serum levels of immunoglobulin(Ig)Es between asthmatic patients with or without bronchiectasis. CONCLUSION: The presence of bronchiectasis in patients with asthma was associated with greater asthma severity. There are important therapeutic implications of identifying bronchiectasis in asthmatic patients.

Clinical characteristics, rates of blindness, and geographic features of PACD in China.

OBJECTIVE: To analyze the rates of blindness with the demographics and clinical characteristics of patients with primary angle-closure disease (PACD) to provide a comprehensive epidemiologic reference in China. METHODS: A retrospective analysis was conducted in the Chinese Glaucoma Study Consortium database, which is a national multicenter glaucoma research alliance of 111 hospitals participating between December 21, 2015 and September 9, 2018. The diagnosis of PACD was made by qualified physicians through examination. Comparison of sex, age, family history, subtypes of PACD, and blindness were analyzed. RESULTS: A total of 5762 glaucoma patients were included, of which 4588 (79.6%) had PACD. Of PACD patients, 72.1% were female with the sex ratio (F/M) of 2.6, and the average age of patients was 63.8±9.3 years with the majority between 60 and 70 years. Additionally, 30% of these patients had low vision in one eye, 8.8% had low vision in both eyes, 1.7% had blindness in one eye, and 0.3% had blindness in both eyes. There were statistical differences with regards to age between male and female patients with PACD, with male patients being older on average. Primary angle-closure glaucoma was more commonly diagnosed in males (60%) compared to females (35.9%), whereas acute primary angle closure (APAC) was more commonly diagnosed in females (54.3%) compared to males (37.7%). The visual acuity in APAC patients was lower and the rate of low vision and blindness was higher than other subtypes. CONCLUSION: PACD was the major type of glaucoma in Chinese hospitals. There were more female patients with PACD, mostly between 60 and 70 years old, with higher rates of APAC in women. APAC resulted in the worst visual outcomes of all PACD subtypes.

A prediction model to evaluate the pretest risk of malignancy in solitary pulmonary nodules: evidence from a large Chinese southwestern population.

PURPOSE: Lung cancer is the leading cause of cancer death and there have been clinical prediction models. This study aimed to evaluate the diagnostic performance of published models and create new models to evaluate the probability of malignant solitary pulmonary nodules (SPNs) in Chinese population. METHODS: We consecutively enrolled 2061 patients with SPNs from West China Hospital between January 2008 and December 2016, each SPN was pathologically confirmed. First, four published prediction models, Mayo clinic model, Veterans Affairs (VA) model, Brock model and People's Hospital of Peking University (PEH) model were validated in our patients. Then, utilizing logistic regression, decision tree and random forest (RF), we developed three new models and internally validated them. RESULTS: Area under the receiver operating characteristic curve (AUC) values of four published models were as follows: Mayo 0.705 (95% CI 0.658-0.752, n = 726), VA 0.64 6 (95% CI 0.598-0.695, n = 800), Brock 0.575 (95% CI 0.502-0.648, n = 550) and PEH 0.675 (95% CI 0.627-0.723, n = 726). Logistic regression model, decision tree model and RF model were developed, AUC values of these models were 0.842 (95% CI 0.778-0.906), 0.734 (95% CI 0.647-0.821), 0.851 (95% CI 0.789-0.914), respectively. CONCLUSION: The four published lung cancer prediction models do not apply to our population, and we have established new models that can be used to predict the probability of malignant SPNs.

Prognostic performance of the FACED score and bronchiectasis severity index in bronchiectasis: a systematic review and meta-analysis.

BACKGROUND: Bronchiectasis is a multidimensional lung disease characterized by bronchial dilation, chronic inflammation, and infection. The FACED (Forced expiratory volume in 1 s (FEV1), Age, Chronic colonization, Extension, and Dyspnea) score and Bronchiectasis Severity Index (BSI) are used to stratify disease risk and guide clinical practice. This meta-analysis aimed to quantify the accuracy of these two systems for predicting bronchiectasis outcomes. METHODS: PubMed, Embase, and the Cochrane Database of Systematic Reviews were searched for relevant studies. Quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) criteria. Pooled summary estimates, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. Summary receiver operating characteristic curves were constructed, and the area under the curve (AUC) was used to evaluate prognostic performance. RESULTS: We analyzed 17 unique cohorts (6525 participants) from ten studies. FACED scores with a cut-off value ≥ 5 predicted all-cause mortality better than BSI with a cut-off value ≥ 9, based on pooled sensitivity (0.34 vs 0.7), specificity (0.94 vs 0.66), PLR (4.76 vs 2.05), NLR (0.74 vs 0.48), DOR (6.67 vs 5.01), and AUC (0.87 vs 0.75). Both FACED scores with a cut-off value ≥ 5 (AUC = 0.82) and BSI scores with a cut-off value ≥ 5 or 9 (both AUC = 0.80) help to predict hospitalization. CONCLUSIONS: At a cut-off value ≥ 5, FACED scores can reliably predict all-cause mortality and hospitalization, while BSI scores can reliably predict hospitalization with a cut-off of ≥5 or ≥9. Further studies are essential to validate the prognostic performance of these two scores.

Dasatinib-induced chylothorax: report of a case and review of the literature.

Dasatinib is a tyrosine kinase inhibitor for the treatment of BCR-ABL-positive chronic myeloid leukaemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL). Although fluid retention is a common adverse event associated with dasatinib, chylothorax is exceptionally rare. The pathological mechanism, clinical manifestation and management of dasatinib-induced chylothorax are completely unclear. A 71-year-old man treated with dasatinib for CML was admitted for progressive dyspnea. Computed tomography (CT) showed a pleural effusion that was more prominent on the right thoracic cavity. Thoracentesis showed thick milky pleural fluid, which was then confirmed as chylothorax by chylum qualitative tests and triglyceride measurements. Radionuclide lymphoscintigraphy yielded an obstruction at the end segment of the thoracic duct, but no leakage points were found. After excluding common causes, drug-induced chylothorax was presumed. Then, dasatinib was withdrawn, and 1 week later, chylothorax resolved. To further elucidate the relationship between the medication and chylothorax, dasatinib was resumed tentatively for 2 days. As expected, pleural effusion recurred soon. Based on these clinical manifestations, the diagnosis of dasatinib-induced chylothorax was identified. The patient was suggested to stop dasatinib and use an alternative drug as recommended by the haematologist. Pleural effusion is the common adverse reaction of dasatinib, but chylothorax is rare. Only six cases of dasatinib-induced chylothorax have been reported, and our patient is the seventh case. Once a patient with dasatinib treatment develops chylothorax, dasatinib should be considered one of the possible causes. If no other definitive aetiological factor is identified, dasatinib discontinuation might be the optimum scheme.

Management strategies in malignant glaucoma secondary to antiglaucoma surgery.

AIM: To assess the outcomes of various interventions for malignant glaucoma (MG). METHODS: A retrospective, comparative analysis of case series were performed on 38 eyes of 35 MG patients treated in Aier Eye Hospital of Wuhan between Jan. 2009 and Dec. 2012. Numerous treatments were administered including medical therapy, neodymium: yttrium- aluminium-garnet (Nd:YAG) laser posterior capsulotomy and hyaloidotomy as well as 3 surgical options. The characteristic, treatment option and outcome of MG in every individual patient were reviewed and analyzed among all patients who were followed up for an average of 27.1±9.1mo. RESULTS: Four eyes of 3 patients achieved complete resolution with medical therapy. Nd:YAG laser posterior capsulotomy and hyaloidotomy were performed on 2 eyes, both of which achieved resolution after initial intervention. Thirty-two eyes were given surgical treatments with anterior vitrectomy- reformation of anterior chamber in 13 eyes, phacoemulsification- intraocular lens implantation in 10 eyes and phacoemulsification- intraocular lens implantation- anterior vitrectomy in 9 eyes. Resolution of MG was seen in almost all patients. The mean intraocular pressure decreased from 41.87±9.44 mm Hg at presentation to 15.84±3.73 mm Hg at the last visit. The mean anterior chamber depth improved from 0.28±0.27 mm to 2.28±0.19 mm. Twenty eyes with preoperative visual acuity better than counting figure/ 50 cm had various visual improvements. Complications occurred in 3 eyes of 3 patients including bleeding at the entry site of vitrectomy into vitreous cavity, corneal endothelial decompensation and allergic to atropine respectively. CONCLUSION: MG occurs as a result of multiple mechanisms involved simultaneously or sequentially.Medical therapy is advocated as the initial treatment, laser therapy is beneficial in pseudophakic eyes, and different surgical regimen is recommended based on different pathogenesis of MG when non-response occurs to nonsurgical management. MG can be managed successfully by appropriate and timely interventions with good visual outcome.

[The early postoperative complications and cost-effectiveness analysis of non-penetrating trabecular surgery in patients with primary open angle glaucoma].

OBJECTIVE: To compare the early postoperative complications of non-penetrating trabecular surgery (NPTS) and modified trabeculectomy (MT) in patients with primary open angle glaucoma, and to analyze the cost-effectiveness of NPTS to prevent adverse events as well. METHODS: One hundred and forty seven consecutive cases (215 eyes) with primary open angle glaucoma from the glaucoma division, Zhongshan Ophthalmic Center, were involved. One hundred and four eyes underwent NPTS; while 111 eyes underwent MT. Visual acuity, intraocular pressure and complications occurred while staying in the hospital, were recorded. Number of need to treat (NNT) was used to analyze the cost-effective for NPTS. RESULTS: (1) Visual acuity decrease over 2 lines occurred in 25 eyes (24.0%) in NPTS group and 26 eyes (23.4%) in MT group. The difference of visual changes between these two groups was not statistically significant (P > 0.05). (2) One day after the operation, hypotension [IOP less or equal to 5 mm Hg (1 mm Hg = 0.133 kPa)] occurred in 39 eyes in NPTS group (38.2%), and 10 eyes in MT group (9.2%). The difference was significant (P < 0.01). On the day of discharge, the incidence of hypotension was 27.5% in NPTS group and 17.3% in MT group, respectively. The difference was still significant (P < 0.05). (3) Hyphema was found in 20 eyes (19.2%) in NPTS group and ten eyes (9.0%) in MT group. In either group, a surgical procedure was needed in two eyes to evacuate the blood. (4) Two eyes of grade II degrees and five eyes of grade I degrees shallow chamber were found in NPTS group. Five eyes of grade II degrees and five eyes of grade I shallow chamber were found in MT group. The difference of incidence of shallow chamber between these two groups was not statistically significant (P > 0.05). (5) Other complications: In the NPTS group, trabeculo-descemetic membrane rupture occurred in one eye, pupil dilated to 7 mm observed in six eyes; in the MT group, acute elevated IOP occurred in one eye, peripheral anterior synechia at inner incision occurred in one eye, hypotensive macular edema occurred in one eye. (6) The absolute risk ratio (ARR) of NPTS for adverse event was 3.0%, (NNT = 33.2), it costs additional RMB yen 116, 100 for preventing one adverse event. For serious adverse event, ARR = 1.8% (NNT = 55.5), and it costs additional RMB yen 194, 000 to prevent one serious adverse event. CONCLUSIONS: Although the NPTS may reduce the incidence of serious adverse event in comparing with MT, the cost of NPTS is very high, therefore, it is not an optimal procedure in China. Ophthalmologists in the general hospital should familiar with the MT procedure to save the medical expenses.