OCULAR DELIVERY OF NATAMYCIN SOLID LIPID NANOPARTICLE LOADED MUCOADHESIVE GEL: FORMULATION, CHARACTERIZATION AND IN VIVO STUDY

Objective: This study aimed to develop a novel topical ocular system of natamycin (NAT) by formulating and evaluating of NAT-solid lipid nanoparticle (SLN) loaded on mucoadhesive gels to improve its therapeutic activity and reduce the frequency of dosage to assist patient compliance. Methods: SLNs were prepared using lipids and Tween 80 or Pluronic F127 as stabilizers via modified high shear homogenization and ultrasound techniques. The prepared SLNs were characterized for particle size (PS), zeta potential (ZP), polydispersity index (PI), and entrapment efficiency percentage (EE %). The morphological examination for chosen SLNs was done using a transmission electron microscope (TEM). Carbapol 940 and Hydroxypropyl methylcellulose (HPMC) was incorporated with selected NAT-SLNs to form mucoadhesive gels. The prepared NAT-SLN gels were evaluated for drug content, mucoadhesion force, release study, and in vitro microbiological activity. In vivo study for the chosen formulae was done to evaluate its efficacy against keratitis in rabbits. Results: NAT-SLNs exhibited high EE % up to 99.167% and PS ranging from 128.35 to 1719.5 nm, with negatively charged ZP that confirmed the stability of SLNs. The NAT-SLN gels provided the high mucoadhesive force with a controlled release manner compared with the marketed-product MP. The in vivo experimental studies and histopathological examination showed the superiority of G2 (NAT-SLN (5% Pluronic F127 and 1:1 mixed lipid) 4% HPMC) over MP against Candida keratitis. Conclusion: According to the obtained results, G2 provided an effective pharmaceutical system against fungal keratitis in a controlled release manner compared with MP for reducing dosage frequency

Early and delayed suture adjustments after adjustable suture strabismus surgery: a randomized controlled trial

Background: Adjustable sutures increase the success rate of strabismus surgery. However, the optimal timing of postoperative suture adjustment remains controversial. This trial was aimed at comparing the surgical outcomes and pain scores of early or 2 – 4 h and delayed or 24 h postoperative suture adjustment in adult patients undergoing strabismus surgery. Methods: An open-label, prospective, randomized, comparative interventional study was performed in consecutive adult patients scheduled for eye muscle surgery. Patients were randomized into two groups: the early group, with suture adjustment 2 – 4 h postoperatively, and the delayed group, with suture adjustment 24 h postoperatively. Subjective pain scores during the adjustment were also analyzed. The angles of misalignment at 1 and 3 months and the success rate at 3 months postoperatively were compared. Results: Forty-five (90%) patients completed the follow-up, including 23 (92%) in the early adjustment group and 22 (88%) in the delayed adjustment group, with a mean (standard deviation) age of 25.6 (9.5) years and a male-to-female ratio of 46.7:53.3. Thirty patients (66.7%) had exotropia, and 15 (33.3%) patients had esotropia. Both groups had comparable baseline characteristics (all P > 0.05). The mean pain scores during adjustment did not differ significantly between groups (P > 0.05). The postoperative angles of alignment were comparable between the groups before suture adjustment and at the 1- and 3-month follow-ups (all P > 0.05). The success rate in the early adjustment group was slightly higher (87.0% versus 63.6%), but the difference was not statistically significant (P > 0.05). The success rate was comparable between the groups in patients with esotropia or exotropia (both P > 0.05). Conclusions: Although the early adjustment group had a slightly higher success rate, the difference was not significant. Both groups had comparable subjective pain scores during adjustment. Future clinical trials should be performed different time intervals for postoperative suture adjustment, and subjective and objective outcomes, such as diplopia and stereopsis, should be compared between patients with a first strabismus surgery and those who underwent reoperation. This could better resolve the persistent controversy related to the optimal time for suture adjustment

In depth characterisation of the biomolecular coronas of polymer coated inorganic nanoparticles with differential centrifugal sedimentation

Advances in nanofabrication methods have enabled the tailoring of new strategies towards the controlled production of nanoparticles with attractive applications in healthcare. In many cases, their characterisation remains a big challenge, particularly for small-sized functional nanoparticles of 5 nm diameter or smaller, where current particle sizing techniques struggle to provide the required sensitivity and accuracy. There is a clear need for the development of new reliable characterisation approaches for the physico-chemical characterisation of nanoparticles with significant accuracy, particularly for the analysis of the particles in the presence of complex biological fluids. Herein, we show that the Differential Centrifugal Sedimentation can be utilised as a high-precision tool for the reliable characterisation of functional nanoparticles of different materials. We report a method to correlate the sedimentation shift with the polymer and biomolecule adsorption on the nanoparticle surface, validating the developed core–shell model. We also highlight its limit when measuring nanoparticles of smaller size and the need to use several complementary methods when characterising nanoparticle corona complexes

Biliary fistula and late recurrence of liver hydatid cyst: Role of cysto-biliary communication: A prospective multicenter study

Background: Hydatid cyst disease (HCD) is common in certain locations. Surgery is associated with postoperative biliary fistula (POBF) and recurrence. The primary aim of this study was to identify whether occult cysto-biliary communication (CBC) can predict recurrent HCD. The secondary aim was to assess the role of cystic fluid bilirubin and alkaline phosphatase (ALP) levels in predicting POBF and recurrent HCD. Aim: To identify whether occult CBC can predict recurrent HCD. The secondary aim was to assess the role of cystic fluid bilirubin and ALP levels in predicting POBF and recurrent HCD. Methods: From September 2010 to September 2016, a prospective multicenter study was undertaken involving 244 patients with solitary primary superficial stage cystic echinococcosis 2 and cystic echinococcosis 3b HCD who underwent laparoscopic partial cystectomy with omentoplasty. Univariable logistic regression analysis assessed independent factors determining biliary complications and recurrence. Results: There was a highly statistically significant association (P ≤ 0.001) between cystic fluid biochemical indices and the development of biliary complications (of 16 patients with POBF, 15 patients had high cyst fluid bilirubin and ALP levels), where patients with high bilirubin-ALP levels were 3405 times more likely to have biliary complications. There was a highly statistically significant association (P ≤ 0.001) between biliary complications, biochemical indices, and the occurrence of recurrent HCD (of 30 patients with recurrent HCD, 15 patients had high cyst fluid bilirubin and ALP; all 16 patients who had POBF later developed recurrent HCD), where patients who developed biliary complications and high bilirubin-ALP were 244.6 and 214 times more likely to have recurrent hydatid cysts, respectively. Conclusion: Occult CBC can predict recurrent HCD. Elevated cyst fluid bilirubin and ALP levels predicted POBF and recurrent HCD

Intraoperative endomanometric laparoscopic Nissen fundoplication improves postoperative outcomes in large sliding hiatus hernia with severe gastroesophageal reflux disease. A retrospective cohort study

Background: Laparoscopic Nissen Fundoplication (LNF) is the gold standard surgical intervention for gastroesophageal reflux disease (GERD). LNF can be followed by recurrent symptoms or complications affecting patient satisfaction. The aim of this study is to assess the value of the intraoperative endomanometric evaluation of esophagogastric competence and pressure combined with LNF in patients with large sliding hiatus hernia (> 5 cm) with severe GERD (DeMeester score >100). Materials and methods: This is a retrospective, multicenter cohort study. Baseline characteristics, postoperative dysphagia and gas bloat syndrome, recurrent symptoms, and satisfaction were collected from a prospectively maintained database. Outcomes analyzed included recurrent reflux symptoms, postoperative side effects, and satisfaction with surgery. Results: 360 patients were stratified into endomanometric LNF (180 patients, LNF+) and LNF alone (180 patients, LNF). Recurrent heartburn (3.9% vs. 8.3%) and recurrent regurgitation (2.2% vs. 5%) showed a lower incidence in the LNF+ group (P=0.012). Postoperative score III recurrent heartburn and score III regurgitations occurred in 0% vs. 3.3% and 0% vs. 2.8% cases in the LNF+ and LNF groups, respectively (P=0.005). Postoperative persistent dysphagia and gas bloat syndrome occurred in 1.75% vs. 5.6% and 0% vs. 3.9% of patients (P=0.001). Score III postoperative persistent dysphagia was 0% vs. 2.8% in the two groups (P=0.007). There was no redo surgery for dysphagia after LNF+. Patient satisfaction at the end of the study was 93.3% vs. 86.7% in both cohorts, respectively (P=0.05). Conclusions: Intraoperative high-resolution manometry (HRM) and endoscopic were feasible in all patients, and the outcomes were favorable from an effectiveness and safety standpoint

Safety and efficacy of percutaneous nephrolithotripsy in comorbid patients: A 3 years prospective observational study

Purpose: To report the result of percutaneous nephrolithotripsy (PCNL) via standard nephrostomy tract in a single training institution. The perioperative complications in relation to the comorbid state are particularly assessed. Patients and methods: A prospective interventional study between January 2019 to November 2022, included 210 patients scheduled for PCNL. The average age was 40.3 ± 11.8 years (range 18- 67 years). Patients were categorized into two groups. The first group comprised 146 cases (69 .5%) with no associated co-morbidities while the second group 64 (30.5%) had co-morbidities such as obesity in 4 cases (1.9%), hypertension (HTN) in 24 cases (11.4%) cases, diabetes mellitus (DM) in 17 (8.1%) cases, history of recurrent stone surgery in 11 (5.2%) cases and more than one in 8 cases (3.8%). Co-morbidities, stone burden, location of stone, time of surgery, stay in the hospital, further operations, and negative events were among the reported data. Complications and the stone-free rate were the main outcome indicators. Results: Intraoperative complications were reported in 40 (18.8%) patients (18 group 1 and 22 group 2) during PCNL. Bleeding occurred in 22 (10.5%) patients (9 group 1 and 13 group 2), blood transfusions were needed in 4 (1.9%) (2 group 1 and 2 group 2), extravasation was observed in 11 patients (5.2%) (6 group 1 and 5 group 2) and cardiac arrhythmia in 3 (1.4%) (1 group 1 and 2 group 2) patients. Postoperative complications occurred in 61 patients (29%) (24 group 1 and 37 group 2) in the form of fever in 10 patients (4.8 %) (3 group 1 and 7 group 2) and prolonged leakage in 50 patients (23.8%) (21 group 1 and 29 group 2). One patient of group 2 died from postoperative sepsis. Extravasation and postoperative leakage were higher in diabetic patients than in non-diabetics. Stonefree rate was 60.5% (127 of 210). Clinically significant residual fragments (CSRFs) found in 70 cases (33.3%) (33 group 1 and 37 group 2). In 13 cases (6.2%) (5 group 1 and 8 group 2), clinically insignificant residual fragments (CIRFs) were found. In 8 (3 group 1 and 5 group 2) of the 13 cases, spontaneous stone passage was observed within 4-6 weeks of surgery. Residual stones in three cases (1 group 1 and 2 group 2) were asymptomatic and 4 mm or less, whereas stones increased in two cases of group 2. Among all factors studied, stone burden was significantly correlated to both intraoperative and postoperative complications. The occurrence of postoperative fever increased with large stone burden. Conclusions: PCNL is a therapeutic modality that is effective, feasible, and safe for a wide range of patients with concurrent medical issues. A steep curve is required to reduce intraoperative and postoperative complications

Development and Implementation of the AIDA International Registry for Patients With Still's Disease

Objective: Aim of this paper is to present the design, construction, and modalities of dissemination of the AutoInflammatory Disease Alliance (AIDA) International Registry for patients with systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD), which are the pediatric and adult forms of the same autoinflammatory disorder. Methods: This Registry is a clinical, physician-driven, population- and electronic-based instrument implemented for the retrospective and prospective collection of real-world data. The collection of data is based on the Research Electronic Data Capture (REDCap) tool and is intended to obtain evidence drawn from routine patients' management. The collection of standardized data is thought to bring knowledge about real-life clinical research and potentially communicate with other existing and future Registries dedicated to Still's disease. Moreover, it has been conceived to be flexible enough to easily change according to future scientific acquisitions. Results: Starting from June 30th to February 7th, 2022, 110 Centers from 23 Countries in 4 continents have been involved. Fifty-four of these have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 175 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry collects baseline and follow-up data using 4449 fields organized into 14 instruments, including patient's demographics, history, clinical manifestations and symptoms, trigger/risk factors, therapies and healthcare access. Conclusions: This international Registry for patients with Still's disease will allow a robust clinical research through collection of standardized data, international consultation, dissemination of knowledge, and implementation of observational studies based on wide cohorts of patients followed-up for very long periods. Solid evidence drawn from "real-life " data represents the ultimate goal of this Registry, which has been implemented to significantly improve the overall management of patients with Still's disease. NCT 05200715 available at

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Automated Settings of Overcurrent Relays Considering Transformer Phase Shift and Distributed Generators Using Gorilla Troops Optimizer

The relative protective devices are cascaded in a proper sequence with a proper min/max coordination time margin (CTM) to minimize the outage area of the network in case of fault condition. This manuscript addresses a new methodology based on the gorilla troops optimizer (GTO) to produce the best automated settings for overcurrent relays. In the GTO, the exploration and exploitation phases are realized using five methodologies. Three of them are used in the exploration phase and the other two in the exploitation phase. In the exploration phase, all gorillas are considered as candidate solutions and the best one is considered as the silverback gorilla. Then again, the exploitation phase comprises two steps: (i) the first one is the follow of silverback gorilla, and (ii) the second one is the competition for adult females. The latter mentioned offers an added advantage to the GTO framework to move forward steadily to global minima and to avoid trapping into local minima. Two test cases under numerous scenarios are demonstrated comprising an isolated real distribution network with distributed generations for the Agiba Petroleum company which is in the Western Desert of Egypt. The relay coordination problem is adapted as an optimization problem subject to a set of predefined constraints which is solved using the GTO including fixed and varied inverse IEC curves, in which the practical constraints including transformer phase shift and other scenarios for min/max fault conditions are dealt with. In due course, this current effort aims at proving the best strategy for achieving the smoothest coordination of overcurrent relays (OCRs), with the least obtained value of CTMs for the studied cases being established via the automated relay settings. At last, it can be pointed out that the GTO successfully dealt with this problem and was able to produce competitive answers compared to other competitors