Prevalence of pterygium and outcome of pterygium surgery in hilly western Nepal

Introduction: Surgical removal is the treatment of choice for pterygium; however, prevention of recurrence is a challenge. Several techniques have been tried to reduce the fibro-vascular activity aiming to reduce rate of recurrence such as B-irradiation, conjunctival and limbal auto-grafting, anti-mitotic drugs, and amniotic membrane transplantation. This study reports the magnitude of the disease in a hilly region of western Nepal and outcome of excision and conjunctival autografting for pterygium surgery. Methods: A prospective study was done from 1st July 2015 to 31st December 2016 in which all patients with primary pterygium presented to Palpa Lions Lacoul Eye Hospital from 1st July 2015 to 30th June 2016 were treated and followed up for next six months. Patients were treated medically or surgically as indicated. Data on age, sex, visual acuity, extent of disease, treatment modality, complications, and outcome were collected and analyzed by descriptive statistics, Chi-square test, t-test, and Anova tests. P value less than 0.05 was considered significant. Results: There were 18,960 patients in total attending hospital for various conditions among which 290 (1.5%) had pterygium. There were 186 (64.1%) female and 104 (35.9%) male and this difference was significant (p<0.001). The mean age was 47.42 yrs (SD=14.23) with age ranging from 20 to 80 years. Right eye was affected more (43.1%) than left eye (33.1%); remaining 23.8% had bilateral disease. Grade-1 disease occurred in younger age compared to Grade-2 and Grade-3 disease. All grade-1 patients were managed medically; grade-2 and grade-3 patients were equally likely to be managed medically or surgically. There were no major intra or post-operative complications. Minor post-operative complications noted were subconjunctival hemorrhage, corneal scarring, suture gaping, and conjunctival cyst among others. Conclusion: Despite much advanced techniques in pterygium surgery, pterygium excision combined with conjunctival autograft is found to be a safe and effective method for treating pterygium in developing world

The Transcriptome of Human Endometrial Mesenchymal Stem Cells Under TGFβR Inhibition Reveals Improved Potential for Cell-Based Therapies

Mesenchymal stem/stromal cells (MSCs) are multipotent cells with favorable properties for cell therapies and regenerative medicine. Human endometrium harbors a small population of perivascular, clonogenic MSCs (eMSCs) identified by the SUSD2 marker. As for other MSCs, eMSCs require extensive in vitro expansion to generate clinically relevant numbers of cells, resulting in spontaneous differentiation, replicative senescence and cell death, decreasing therapeutic potency. We previously demonstrated that A83-01, a TGF-β receptor inhibitor, maintained eMSC clonogenicity, promoted proliferation, prevented apoptosis and maintained MSC function in vitro. Here we compare the transcriptome of passaged eMSCs from six women cultured with and without A83-01 for 7 days. We identified 1206 differentially expressed genes (DEG) using a false discovery rate cut-off at 0.01 and fold change >2. Significant enrichment of genes involved in anti-inflammatory responses, angiogenesis, cell migration and proliferation, and collagen fibril and extracellular matrix organization were revealed. TGF-β, Wnt and Akt signaling pathways were decreased. Anti-fibrotic and anti-apoptotic genes were induced, and fibroblast proliferation and myofibroblast related genes were downregulated. We found increased MSC potency genes (TWIST1, TWIST2, JAG1, LIFR, and SLIT2) validating the enhanced potency of A83-01-treated eMSCs, and importantly no pluripotency gene expression. We also identified eMSCs’ potential for secreting exosomes, possibly explaining their paracrine properties. Angiogenic and cytokine protein arrays confirmed the angiogenic, anti-fibrotic and immunomodulatory phenotype of A83-01-treated eMSCs, and increased angiogenic activity was functionally demonstrated in vitro. eMSCs culture expanded with A83-01 have enhanced clinically relevant properties, suggesting their potential for cell-therapies and regenerative medicine applications

Impact of sustained transforming growth factor-β receptor inhibition on chromatin accessibility and gene expression in cultured human endometrial MSC

Endometrial mesenchymal stem cells (eMSC) drive the extraordinary regenerative capacity of the human endometrium. Clinical application of eMSC for therapeutic purposes is hampered by spontaneous differentiation and cellular senescence upon large-scale expansion in vitro. A83-01, a selective transforming growth factor-β receptor (TGFβ-R) inhibitor, promotes expansion of eMSC in culture by blocking differentiation and senescence, but the underlying mechanisms are incompletely understood. In this study, we combined RNA-seq and ATAC-seq to study the impact of sustained TGFβ-R inhibition on gene expression and chromatin architecture of eMSC. Treatment of primary eMSC with A83-01 for 5 weeks resulted in differential expression of 1,463 genes. Gene ontology analysis showed enrichment of genes implicated in cell growth whereas extracellular matrix genes and genes involved in cell fate commitment were downregulated. ATAC-seq analysis demonstrated that sustained TGFβ-R inhibition results in opening and closure of 3,555 and 2,412 chromatin loci, respectively. Motif analysis revealed marked enrichment of retinoic acid receptor (RAR) binding sites, which was paralleled by the induction of RARB, encoding retinoic acid receptor beta (RARβ). Selective RARβ inhibition attenuated proliferation and clonogenicity of A83-01 treated eMSC. Taken together, our study provides new insights into the gene networks and genome-wide chromatin changes that underpin maintenance of an undifferentiated phenotype of eMSC in prolonged culture

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

Comparing the Effect of TGF-β Receptor Inhibition on Human Perivascular Mesenchymal Stromal Cells Derived from Endometrium, Bone Marrow and Adipose Tissues

Rare perivascular mesenchymal stromal cells (MSCs) with therapeutic properties have been identified in many tissues. Their rarity necessitates extensive in vitro expansion, resulting in spontaneous differentiation, cellular senescence and apoptosis, producing therapeutic products with variable quality and decreased potency. We previously demonstrated that A83-01, a transforming growth factor beta (TGF-&beta;) receptor inhibitor, maintained clonogenicity and promoted the potency of culture-expanded premenopausal endometrial MSCs using functional assays and whole-transcriptome sequencing. Here, we compared the effects of A83-01 on MSCs derived from postmenopausal endometrium, menstrual blood, placenta decidua-basalis, bone marrow and adipose tissue. Sushi-domain-containing-2 (SUSD2+) and CD34+CD31&minus;CD45&minus; MSCs were isolated. Expanded MSCs were cultured with or without A83-01 for 7 days and assessed for MSC properties. SUSD2 identified perivascular cells in the placental decidua-basalis, and their maternal origin was validated. A83-01 promoted MSC proliferation from all sources except bone marrow and only increased SUSD2 expression and prevented apoptosis in MSCs from endometrial-derived tissues. A83-01 only improved the cloning efficiency of postmenopausal endometrial MSCs (eMSCs), and expanded adipose tissue MSCs (adMSCs) underwent significant senescence, which was mitigated by A83-01. MSCs derived from bone marrow (bmMSCs) were highly apoptotic, but A83-01 was without effect. A83-01 maintained the function and phenotype in MSCs cultured from endometrial, but not other, tissues. Our results also demonstrated that cellular SUSD2 expression directly correlates with the functional phenotype

Culture Expansion of Undifferentiated Human Mesenchymal Stem/Stromal Cells for Management of Gynaecological Diseases

Mesenchymal stem cells are a type of adult stem cell which can be isolated from one’s own tissues such as the endometrium or uterine lining, menstrual blood, placenta, bone marrow and fat. They have the potential to be used for treating a wide range of diseases, but because they are rare it is necessary to grow them in the laboratory to generate the large number of cells required. In my PhD, I identified a drug that keeps these cells fit and healthy during culturing. Therefore, the cells remain potent and will do their job more effectively when given to patients

Comparison of Phacotrabeculectomy and Phacotrabeculectomy with Subconjunctival 5-Fluorouracil

Introduction: Glaucoma is the second leading cause of blindness worldwide. Phacotrabeculectomy is a technique in which glaucoma and cataract surgery performed. &#13; Methods: Prospective study was carried out in the department of glaucoma at Lumbini Eye Institute, Bhairahawa.100 patients who underwent phacotrabeculectomy within a period of two years. Patients were divided into two groups those who received 5FU (n=47) and no antifibrotic agent (n= 53). &#13; Results: The age range was from 38 to 80 years; mean age of 62.97±9.14 SD. 55% were male and 45% were female.The postoperative IOP reduction in last follow- up group A was mean=13.08±1.57SD and mean=13.23±1.73SD in group B. This was statically significant with P &lt;0.001. Bleb survival was almost similar in two groups 3.17(78.31%) in group A and 3.20 (78.93%) in group B. 85% visual acuity was improved in both groups. &#13; Conclusions: Phacotrabeculectomy and phacotrabeculectomy with inj. 5FU, both were equally effective surgical techniques in terms of visual acuity, IOP control and bleb survival.There was no significant statistical difference vis-à-vis the success of Phacotrabeculectomy using of either these two techniques. &#13; Keywords: glaucoma; 5FU; intraocular pressure; phacotrabeculectomy

Scleral Fixation of Intraocular Lens with Ab Interno Technique

Introduction: Implantation of scleral fixation intraocular lens for the surgical management of aphakia cases without capsular support is a safe procedure. Methods: Prospective study was carried out at Lumbini Eye Institute, Bhairahawa. A total of 32 patients underwent scleral fixation intraocular lens implantation within a period of two years from February 2014 to February 2016. Results: The age range was from 15 to 79 years; mean age was 47.56±20.16 SD. Among them 14 (43.75%) were male and 18 (56.25%) were female. The follow-up lasted for 24 months. The postoperative characteristics of the patients are listed in the tables below. Conclusions: SFIOL for the surgical management of aphakia in the absence of capsular support is a safe procedure. The long-term follow-up is needed for an accurate evaluation of outcomes. Keywords: double armed prolene suture; intraocular pressure; scleral fixation intraocular lens; scleral tunnel. [PubMed