Ethnic Differences in the Rates of Posterior Capsule Rupture and Long-Term Sequelae in Phacoemulsification Cataract Surgery.

Purpose The purpose of this study is to investigate the rates of posterior capsular rupture (PCR) and its sequelae during phacoemulsification across different ethnicities. Methods This is a retrospective cohort study of all consecutive phacoemulsification cases complicated by PCR that met the inclusion criteria over a four-year period at a single tertiary eye centre in the United Kingdom (UK). Results PCR occurred in 0.85% of cases overall (157/18,481). PCR rates were 1.8% (26/1485), 1.2% (51/4350), and 0.7% (75/10,927) in African-Caribbean, Indian subcontinent, and Caucasian patients, respectively (p < 0.001). Mean final corrected distance visual acuity improved (p < 0.05) in all ethnic groups (0.40 ± 0.57 logMAR) compared to pre-op (0.78 ± 0.61 logMAR). Post-operative cystoid macular oedema and unstable intraocular pressure rates following PCR did not statistically differ amongst ethnicities (p = 0.37 and p = 0.75, respectively). However, post-operative uveitis rates significantly differed at 11.5%, 15.7%, and 1.3% amongst the three ethnic groups, respectively (p = 0.01). Conclusion This is the first study to highlight a possible link between patient ethnicity and the risk of PCR during phacoemulsification cataract surgery. We observed significantly greater numbers of PCR cases amongst certain ethnic groups (highest in African-Caribbean eyes, then Indian subcontinental eyes, and lowest in Caucasian eyes) within the same multi-cultural urban population. Ethnicity may therefore be a contributing factor for PCR and should potentially be taken into consideration during preoperative risk stratification.

Relationship Between Obesity and Youth Athletes' Physical Activity and Exercise-Related Cardiac Symptoms.

Background: While studies have identified the negative cardiovascular effects of obesity, the effects of obesity on youth athletes are less studied. This study investigates the associations between obesity in youth athletes and exercise activity and exertional cardiac symptoms. Methods: The HeartBytes National Youth Database produced by Simon's Heart, a nonprofit that organizes adolescents' sports pre-participation examinations (PPEs), was used. This database contains demographic data, exercise-related symptoms, and electrocardiogram data obtained during PPEs. BMI was converted to percentiles, with obesity defined as BMI ≥95th percentile. Outcomes were evaluated using a chi-squared test with odds ratios (ORs) and 95% confidence intervals (CIs). Results: Of 7363 patients, there were 634 individuals with obesity. Youth athletes within normal weight ranges (5th-85th percentile) had higher exercise rates than those with underweight, overweight, or obesity (p < 0.001 for each). Athletes with obesity had higher odds of exertional symptoms overall (OR: 1.63 [CI: 1.36-1.96]; p < 0.001). However, for athletes who exercised >10 hours a week, there was no association between obesity and exertional symptoms. Athletes with obesity had higher odds of elevated blood pressure (OR: 5.35 [CI: 2.00-14.30]; p < 0.001) and hypercholesterolemia (OR: 3.84 [CI: 2.51-5.86]; p < 0.001). Conclusions: In this dataset, obesity in youth athletes is associated with decreased physical activity and increased exertional symptoms in general. Obesity is not associated with exertional symptoms in athletes who participated in higher weekly physical activity. Further studies are needed to elucidate the cause-effect relationship of these findings.

GC-MS Analysis of Persicaria bistorta: Uncovering the Molecular Basis of Its Traditional Medicinal Use.

Persicaria bistorta is a perennial herb used traditionally in treating various ailments, including diarrhea, abdominal pain, and bleeding. In this study, we used gas chromatography-mass spectrometry (GC-MS) analysis to identify the chemical composition of Persicaria bistorta. The GC-MS analysis revealed the presence of several compounds, including flavonoids, tannins, saponins, and alkaloids. Among those, the most important from medicinal points of view are ethyl oleate (3%), cyclotetradecane (4.74%), dodecanoic acid (4.69%), hexadecanoic acid (5.61%), tetradecane (5.25%), cis-13-octadecenoic acid (10.91%), and bis(2-ethylhexyl) phthalate (32%). The GC-MS analysis of ethanolic fraction of Persicaria bistorta involved in antibacterial activity showed about 18 compounds. Among those, the most important from a medicinal and nutritional point of view are bis(2-ethylhexyl) phthalate (42.20%), 6-octadecenoic acid methyl ester, (Z)- (10.37%), ethyl oleate (6.84%), hexadecanoic acid methyl ester (6.67%), and methyl ester and oleic acid (5.27%). Reported biological antibacterial activity has shown that the main compound determined in both extracts was bis(2-ethylhexyl) phthalate, which has higher peak area percentage in ethanolic extract than in ethyl acetate fraction. Some oily compounds important for health because of their cis-conformation were also revealed in the given study like ethyl oleate and oleic acid. Overall, results suggest that Persicaria bistorta may have therapeutic potential and warrant further investigation. Further research is needed to confirm the efficacy and safety of Persicaria bistorta as a natural medicine and determine its active compounds' mechanisms of action.

Left Ventricle Size Correlates with Peak Exercise Capacity in Pediatric Cancer Survivors Exposed to Anthracycline Chemotherapy.

Cancer survivors exposed to anthracycline chemotherapy are at risk for developing cardiomyopathy, which may have delayed clinical manifestation. In a retrospective cross-sectional study, we evaluated the utility of cardiopulmonary exercise testing (CPET) for detecting early cardiac disease in 35 pediatric cancer survivors by examining the associations between peak exercise capacity (measured via percent predicted peak VO2) and resting left ventricular (LV) function on echocardiography and cardiac magnetic resonance imaging (cMRI). We additionally assessed the relationships between LV size on resting echocardiography or cMRI and percent predicted peak VO2 since LV growth arrest can occur in anthracycline-exposed patients prior to changes in LV systolic function. We found reduced exercise capacity in this cohort, with low percent predicted peak VO2 (62%, IQR: 53-75%). While most patients in our pediatric cohort had normal LV systolic function, we observed associations between percent predicted peak VO2 and echocardiographic and cMRI measures of LV size. These findings indicate that CPET may be more sensitive in manifesting early anthracycline-induced cardiomyopathy than echocardiography in pediatric cancer survivors. Our study also highlights the importance of assessing LV size in addition to function in pediatric cancer survivors exposed to anthracyclines.

The prevalence of abnormal spirometry in children with CHD.

BACKGROUND: The burden of pulmonary disease in children with CHD remains under-recognised. Studies have examined children with single ventricle and two ventricle heart disease and documented a decreased forced vital capacity. Our study sought to further explore the pulmonary function of children with CHD. METHODS: A retrospective review was performed of spirometry in CHD patients over a 3-year period. Spirometry data were corrected for size, age, and gender and analysed using z-scores. RESULTS: The spirometry of 260 patients was analysed. About 31% had single ventricle (n = 80, 13.6 years (interquartile range 11.5-16.8)) and 69% had two ventricle circulation (n = 180, 14.4 years (interquartile range 12.0-17.3)). Single ventricle patients were found to have a lower median forced vital capacity z-score compared to two ventricle patients (p = 0.0133). The prevalence of an abnormal forced vital capacity was 41% in single ventricle patients and 29% in two ventricle patients. Two ventricle patients with tetralogy of Fallot and truncus arteriosus had similar low forced vital capacity comparable to single ventricle patients. The number of cardiac surgeries predicted an abnormal forced vital capacity in two ventricle patients except tetralogy of Fallot patients. CONCLUSION: Pulmonary morbidity in patients with CHD is common with a decreased forced vital capacity noted in single ventricle and two ventricle patients. Forced vital capacity is lower in patients with single ventricle circulation; however, two ventricle patients with tetralogy of Fallot or truncus arteriosus have similar lung function in comparison to the single ventricle group. The number of surgical interventions was predictive of forced vital capacity z-score in some but not all two ventricle patients and not predictive in single ventricle patients suggesting a multifactorial to pulmonary disease in children with CHD.

Application of a physiologically based pharmacokinetic model in predicting captopril disposition in children with chronic kidney disease.

Over the last several decades, angiotensin-converting enzyme inhibitors (ACEIs) have been a staple in the treatment of hypertension and renovascular disorders in children. One of the ACEIs, captopril, is projected to have all the benefits of traditional vasodilators. However, conducting clinical trials for determining the pharmacokinetics (PK) of a drug is challenging, particularly in pediatrics. As a result, modeling and simulation methods have been developed to identify the safe and effective dosages of drugs. The physiologically based pharmacokinetic (PBPK) modeling is a well-established method that permits extrapolation from adult to juvenile populations. By using SIMCYP simulator, as a modeling platform, a previously developed PBPK drug-disease model of captopril was scaled to renally impaired pediatrics population for predicting captopril PK. The visual predictive checks, predicted/observed ratios (ratiopred/obs), and the average fold error of PK parameters were used for model evaluation. The model predictions were comparable with the reported PK data of captopril in mild and severe chronic kidney disease (CKD) patients, as the mean ratiopred/obs Cmax and AUC0-t were 1.44 (95% CI 1.07 - 1.80) and 1.26 (95% CI 0.93 - 1.59), respectively. The successfully developed captopril-CKD pediatric model can be used in suggesting drug dosing in children diagnosed with different stages of CKD.

Baerveldt Aqueous Shunt with or without Mitomycin C Augmentation: A Retrospective Comparison Study.

OBJECTIVE: To evaluate if intraoperative mitomycin C (MMC) influences the success of Baerveldt aqueous shunts. DESIGN: Retrospective comparative case series. PARTICIPANTS: The study population consisted of 88 patients. Fifty-five received intraoperative MMC and 33 did not (controls). METHODS: The medical records of consecutive patients who underwent standalone Baerveldt aqueous shunts at Birmingham Midland Eye Centre, United Kingdom, were retrospectively reviewed. Patients in the MMC group received 0.2 to 0.4 mg/mL of MMC intraoperatively whereas controls did not. MAIN OUTCOME MEASURES: Primary outcome was survival, which was defined as an intraocular pressure (IOP) > 6 mmHg and ≤ 21 mmHg or ≤ 18 mmHg and > 20% IOP reduction from baseline. Further analysis of patients who required medications (qualified) or no medications (complete) was undertaken. Secondary outcomes were IOP, number of glaucoma medications, complications, intraluminal ripcord removal (IRR), and interventions. RESULTS: Average follow-up was 4.7 ± 1.4 years. At year 5, complete success with the ≤ 21 mmHg threshold was significantly higher in MMC vs controls (39.3% vs 17.8%; log rank P = 0.016). Final complete success with the ≤ 18 mmHg threshold was higher in patients with MMC shunts vs controls (38% vs 15.6%; log rank P = 0.0042). Qualified success was not different between patients with MMC shunts and controls with ≤ 21 mmHg (82% vs 93%; log rank P = 0.29) and ≤ 18 mmHg thresholds (70.3% vs 79.3%; log rank P = 0.44). Uveitic patients were also more likely to achieve complete success at both 21 and 18 mmHg thresholds among the patients receiving MMC compared with controls. Mitomycin C was correlated with lower number of medications between month 3 and year 2 post operatively (P < 0.001) and with a lower rate of IRR at all timepoints (P < 0.001). There were no significant differences in the incidence of prolonged hypotony, although MMC cases had higher transient hypotony at year 1 (P = 0.049). CONCLUSIONS: Mitomycin C provides a significant advantage in Baerveldt aqueous shunt survival when considering medication-free success but not in qualified success. Control patients required more medications to control IOP. This study suggests that intraoperative MMC augmentation of Baerveldt aqueous shunt surgery may be advantageous in achieving IOP control without the need for medication but that it may be associated with more transient hypotony episodes. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

COVID-19 Vaccine Booster Hesitancy (VBH) among Healthcare Professionals of Pakistan, a Nationwide Survey.

Background: The waning vaccine immunity and emergence of new variants of SARS-CoV-2 led health authorities across the globe to administer booster doses (BDs) of the COVID-19 vaccine. Hence, the current study aimed to assess the COVID-19 vaccine booster hesitancy (VBH) amongst Pakistani healthcare professionals (HCPs). Methods: A nationwide survey-based study was carried out from April 2022 to May 2022. The online self-administered questionnaire was utilized to collect data regarding demographics (age, gender, marital status, profession, residential area, and province), COVID-19 infection history (infection history, onset, and clinical severity of disease), previous COVID-19 vaccination (type of vaccination and the number of doses), attitudes towards BDs (acceptance, rejection, and hesitancy), and psychological drivers of VBH (perceived effectiveness, vaccine safety, risk/benefit ratio, and vaccine type preference). We assessed the association between the dependent variable attitudes of study participants, regarding BDs and independent variables (demographics, COVID-19 infection history, previous COVID-19 vaccination, and psychological drivers of VBH), by using the Chi-square test/Fisher exact test. Results: Among the 1164 study participants, 51.4% were male, and 80.4% were medical professionals. The half of study participants (52.1%) agreed to take the COVID-19 vaccine BD or had already taken it, while the rest of them refused (34.7%) or hesitated (24.2%) to take it. These attitudes of the participants were significantly associated (p < 0.001) with psychological divers about the COVID-19 vaccine BD. Conclusion: This study revealed that Pakistani HCPs hesitant to take the COVID-19 vaccine BD had concerns about the safety, efficacy, and risk/benefits ratio of the vaccine's BD. To eliminate the hesitancy, regarding BD in HCPs, certain educational strategies should be implemented by health authorities to address the concerns of HCPs.

Bilateral Panuveitis and Exudative Retinal Detachments Associated with Alpelisib.

We report a case of alpelisib-induced uveitis. A 68-year-old female who had recently been given alpelisib for metastatic breast cancer presented with a 2-week history of bilateral worsening vision with a corresponding acute hypermetropic shift. Her unaided visual acuity was 6/60 in both eyes, with bilateral anterior uveitis, non-granulomatous keratic precipitates, posterior synechiae, and limited fundal view. There was also a mild iris bombe configuration, although the intraocular pressures were normal. Ocular ultrasound revealed bilateral uveal effusion, ciliary body congestion, dense vitreous cells, and exudative retinal detachments. These findings were also confirmed on multimodal imaging with widefield fundus photography (Optos) and optical coherence tomography. Based on the clinical features above, a diagnosis of alpelisib-induced panuveitis was diagnosed. She was then admitted and treated with a 3-day course of intravenous methylprednisolone and intensive topical steroids. Her clinical signs and symptoms started to improve, and she was discharged 4 days later. At 1 week of follow-up, her best-corrected visual acuity was 6/12 in both eyes, with broken posterior synechiae and resolution of exudative retinal detachments. This case highlights the importance of early ophthalmology involvement by the oncology team as oncology therapy can have potential unexpected ocular manifestations.

Gonioscopy-Assisted Transluminal Trabeculotomy Following Failed iStent Surgery.

We describe 4 cases of eyes initially treated with phacoemulsification and iStent trabecular microbypass (Glaukos Corporation). These patients subsequently required further surgery and were successfully treated with the removal of the iStent device followed by gonioscopy-assisted transluminal trabeculotomy (GATT), using the iTrack catheter (Ellex Medical Lasers Ltd). Three of the cases had prior first-generation iStent (G1), and 1 had prior second-generation iStent (G2). This case series demonstrates that in selected cases, a further angle procedure in the form of a GATT can show efficacy and durability in the medium term. Our patients had controlled intraocular pressures (IOPs) at 1-year post-GATT: 2 on IOP-lowering therapy and 2 without any IOP-lowering medications. Three patients had transient hyphema and 2 with high IOP in the immediate postoperative period. No patients experienced a decrease in best-corrected visual acuity postoperatively. To the best of our knowledge, there is no prior literature describing this surgical strategy. This series demonstrates that GATT could potentially be an effective procedure in the case of a failed initial iStent microtrabecular bypass.

A national survey to assess breast cancer awareness among the female university students of Pakistan.

The incidence of breast cancer is increasing in Pakistan as well as globally. Awareness of women about breast cancer plays a cornerstone role in its early detection, better management, and prevention. Keeping this in mind, a cross-sectional study was carried out to assess the awareness of female university students about breast cancer's risk factors, signs and symptoms, and breast cancer examination. The data was collected from female university students studying in Pakistan. A total of 774 participants completed the survey and recorded their responses on an online pre-tested self-administered questionnaire. Only 29.8% of the participants have identified breast cancer history in their first-degree relatives as a risk factor. Moreover, 14.1% of the participant considered that the use of oral contraceptives for more than 5 years can increase the risk of developing breast cancer. In addition, inward pulled nipple, wounds around the nipple, and abrupt changes in the breast size were considered as the sign and symptoms of breast cancer by 25.2%, 25.7%, and 31.7% of the participants, respectively. Moreover, only 20.9% of the participants identified the correct year for starting breast cancer examination and 44.4% of the respondents marked that mammography should be initiated after 40 years. Overall, the university female students of Pakistan were poorly aware of breast cancer's risk factors, signs and symptoms, and breast examination. This study has highlighted the need for initiation of aggressive strategies regarding breast cancer awareness in both the literate and illiterate female population of Pakistan.

Knowledge, Attitude, Practice, Behavior and Risk Perception of COVID-19 Pandemic among Medical and non-Medical University Students.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) pandemic has substantially affected students around the globe due to the closure of educational institutes. However, student involvements and contributions are important in combating the disease; for this reason, the current study was designed to assess the knowledge-attitude-practice (KAP), preventive behavior, and risk perception among university students. METHODS: A cross-sectional survey-based study was conducted among medical and non-medical university students, from April 1 to June 30, 2020. The 68-item questionnaire was used to evaluate responses using statistical approaches (Student's t-test, regression-analysis, and co-relation analysis) by considering a P-value <0.05 as statistically significant. RESULTS: A total of 503 university students (medical and nonmedical) were selected, where majority of participants were females (83%) and 64.5% were of age ranged from 16 to 21 years old. The participants (80%) reported good disease knowledge with a mean score of 12.06 ± 1.75, which substantially higher among medical students (P < 0.05). Most of the respondents (72%) believed that COVID-19 will be effectively controlled through precautionary measures. In correlation subgroup analysis, a significant relationship (P = 0.025) between knowledge and positive attitude were indicated. Fear and knowledge of COVID-19 emerged as strong predictors (P < 0.001) of preventive behaviors towards disease. CONCLUSION: This study demonstrated satisfactory knowledge, positive attitudes, and suitable practices among students toward COVID-19. University students can be involved in public education to aid the health authorities in achieving the targets of educational campaigns with maximum population coverage.

Reduced Forced Vital Capacity and the Number of Chest Wall Surgeries are Associated with Decreased Exercise Capacity in Children with Congenital Heart Disease.

Low forced vital capacity (FVC) is associated with decreased exercise capacity in CHD. Multiple prior cardiac surgeries have been associated with low FVC. We seek to understand the relationship between low FVC, number of cardiac surgeries and cardiopulmonary response leading to decreased exercise capacity. Retrospective chart review of demographics, surgical history and exercise testing including spirometry was performed in patients with CHD. Single ventricle patients were excluded. Low FVC was defined as a Z-score below the lower limit of normal. Exercise parameters were expressed as a percent of predicted. There were 93 patients with 2 ventricle CHD identified over 34 months with cardiopulmonary exercise testing. The FVC Z-score directly correlated with peak V̇O2% (R2 = 0.07, p < 0.05), and the O2 pulse% (R2 = 0.25, p < 0.0001). The VE/VCO2 was inversely related to the FVC Z-score (R2 = 0.11, p < 0.01). Patients with minimum three prior surgeries had decreased peak VO2% (63.7 vs. 72.8, p < 0.05), decreased peak O2 pulse% (80.8 vs. 97.9, p < 0.01) and a lower mean FVC Z-score (- 1.9 vs - 0.38, p < 0.01). The FVC Z-score and number of surgeries both predicted peak V̇O2% in multivariate analysis. Our study demonstrated that low FVC and three or more prior cardiac surgeries were associated with lower exercise capacity and lower stroke volume response. More cardiac surgeries were also associated with low FVC. However, both low FVC and the number of surgeries were independent predictors of exercise capacity.

Fundamental Biomaterial Considerations in the Development of a 3D Model Representative of Primary Open Angle Glaucoma.

Glaucoma is a leading cause of irreversible blindness globally, with primary open angle glaucoma (POAG) being the most common subset. Raised intraocular pressure is an important risk factor for POAG and is caused by a reduction in aqueous humour (AqH) outflow due to dysfunctional cellular and matrix dynamics in the eye's main drainage site, the trabecular meshwork (TM) and Schlemm's canal (SC). The TM/SC are highly specialised tissues that regulate AqH outflow; however, their exact mechanisms of AqH outflow control are still not fully understood. Emulating physiologically relevant 3D TM/S in vitro models poses challenges to accurately mimic the complex biophysical and biochemical cues that take place in healthy and glaucomatous TM/SC in vivo. With development of such models still in its infancy, there is a clear need for more well-defined approaches that will accurately contrast the two central regions that become dysfunctional in POAG; the juxtacanalicular tissue (JCT) region of the TM and inner wall endothelia of the Schlemm's canal (eSC). This review will discuss the unique biological and biomechanical characteristics that are thought to influence AqH outflow and POAG progression. Further consideration into fundamental biomaterial attributes for the formation of a biomimetic POAG/AqH outflow model will also be explored for future success in pre-clinical drug discovery and disease translation.

Comparison of 1-year surgical outcomes of combined cataract surgery and gonioscopy-assisted transluminal trabeculotomy (GATT) versus cataract surgery and iStent Inject.

PURPOSE: Evaluate the efficacy, safety, and complication rates of phacoemulsification cataract surgery when combined with either gonioscopy-assisted transluminal trabeculotomy (GATT) or iStent Inject. METHODS: This is a retrospective case-control study to compare the surgical outcomes of combined phacoemulsification cataract surgery with either GATT (phaco-GATT) or iStent Inject (phaco-iStent). Both groups had at least 1-year follow-up. The primary outcome measures were IOP and number of glaucoma medications (NGMs) at 1 year. Secondary outcomes measures were best corrected visual acuity (BCVA) and intra- or postoperative complications within the first year of follow-up. Success was defined as intraocular pressure (IOP) < 21 mmHg and ≥ 20% reduction in IOP at 1 year regardless of the NGM. RESULTS: Each group included 37 patients. The median baseline IOP (24 vs 17) and NGM (3 vs 2) were higher in the phaco-GATT group (p < 0.001). Phaco-GATT achieved a 38% (p < 0.0001) reduction in IOP compared to 13.2% (p < 0.001) in the phaco-iStent group at 1-year follow-up. The reduction in IOP and NGM was significantly higher in the phaco-GATT group (p < 0.01). After adjusting for baseline IOP, the reduction in IOP at 12 months was still significantly higher in the phaco-GATT group (p = 0.042). At 1 year, 86.4% of patients in the phaco-GATT group met the success criteria compared to 35.1% in the phaco-iStent group. Safety outcomes were slightly favourable in the phaco-iStent group. CONCLUSION: Phaco-GATT and phaco-iStent showed a significant reduction in IOP and NGM, with phaco-GATT having a significantly higher reduction. Phaco-iStent appears to have a higher safety profile and is probably preferable in monocular patients and those with a high risk of bleeding.

Current knowledge of Chagas-related heart disease among pediatric cardiologists in the United States.

BACKGROUND: Chagas disease is a pathogenic parasitic infection with approximately 8 million cases worldwide and greater than 300,000 cases in the United States (U.S.). Chagas disease can lead to chronic cardiomyopathy and cardiac complications, with variable cardiac presentations in pediatrics making it difficult to recognize. The purpose of our study is to better understand current knowledge and experience with Chagas related heart disease among pediatric cardiologists in the U.S. METHODS: We prospectively disseminated a 19-question survey to pediatric cardiologists via 3 pediatric cardiology listservs. The survey included questions about demographics, Chagas disease presentation and experience. RESULTS: Of 139 responses, 119 cardiologists treat pediatric patients in the U.S. and were included. Most providers (87%) had not seen a case of Chagas disease in their practice; however, 72% also had never tested for it. The majority of knowledge-based questions about Chagas disease cardiac presentations were answered incorrectly, and 85% of providers expressed discomfort with recognizing cardiac presentations in children. Most respondents selected that they would not include Chagas disease on their differential diagnosis for presentations such as conduction anomalies, myocarditis and/or apical aneurysms, but would be more likely to include it if found in a Latin American immigrant. Of respondents, 87% agreed that they would be likely to attend a Chagas disease-related lecture. CONCLUSIONS: Pediatric cardiologists in the U.S. have seen very few cases of Chagas disease, albeit most have not sent testing or included it in their differential diagnosis. Most individuals agreed that education on Chagas disease would be worth-while.

ILB® resolves inflammatory scarring and promotes functional tissue repair.

Fibrotic disease is a major cause of mortality worldwide, with fibrosis arising from prolonged inflammation and aberrant extracellular matrix dynamics. Compromised cellular and tissue repair processes following injury, infection, metabolic dysfunction, autoimmune conditions and vascular diseases leave tissues susceptible to unresolved inflammation, fibrogenesis, loss of function and scarring. There has been limited clinical success with therapies for inflammatory and fibrotic diseases such that there remains a large unmet therapeutic need to restore normal tissue homoeostasis without detrimental side effects. We investigated the effects of a newly formulated low molecular weight dextran sulfate (LMW-DS), termed ILB®, to resolve inflammation and activate matrix remodelling in rodent and human disease models. We demonstrated modulation of the expression of multiple pro-inflammatory cytokines and chemokines in vitro together with scar resolution and improved matrix remodelling in vivo. Of particular relevance, we demonstrated that ILB® acts, in part, by downregulating transforming growth factor (TGF)ß signalling genes and by altering gene expression relating to extracellular matrix dynamics, leading to tissue remodelling, reduced fibrosis and functional tissue regeneration. These observations indicate the potential of ILB® to alleviate fibrotic diseases.

Only eye study 2 (OnES 2): 'Am I going to be able to see when the patch comes off?' A qualitative study of patient experiences of undergoing high-stakes only eye surgery.

OBJECTIVES: Ocular surgery is a source of significant concern for many patients, especially in high-stakes circumstances. The purpose of this study was to explore patient experiences of undergoing surgery on their only-seeing eye. DESIGN: A qualitative investigation using semistructured face-to-face interviews. Transcripts were analysed using thematic analysis. SETTING: Hospital eye service in the UK. PARTICIPANTS: Twelve participants with a diagnosis of glaucoma with worse eye visual acuity <3/60± end-stage visual field loss. All participants had experience of undergoing surgery on their better-seeing (ie, 'only') eye. RESULTS: Data were coded into three key themes relating to (1) emotional impact of surgery, (2) burden of visual loss and (3) coping with surgery. Patients reported depressive symptoms at all stages of their surgical journey; concern about poor visual outcomes was a common feature. Only eye surgery imposes an emotional burden due to the uncertainty regarding individuals' ability to continue daily activities and maintaining social roles. Burden extended to the inconvenience of frequent hospital visits and difficulties with follow-up care. Participants' ability to cope effectively with surgery appeared to be linked to extent of support from healthcare professionals. Key areas in developing trust and support were an open and transparent dialogue between surgeons and patients, continuity of care, patient inclusion in decision-making, and observable empathy. CONCLUSIONS: The findings indicate a need for an enhanced model of care in only eye surgery to better target patient preferences and allay concerns inherent with these procedures.