Cellular bases of olfactory circuit assembly revealed by systematic time-lapse imaging.

Neural circuit assembly features simultaneous targeting of numerous neuronal processes from constituent neuron types, yet the dynamics is poorly understood. Here, we use the Drosophila olfactory circuit to investigate dynamic cellular processes by which olfactory receptor neurons (ORNs) target axons precisely to specific glomeruli in the ipsi- and contralateral antennal lobes. Time-lapse imaging of individual axons from 30 ORN types revealed a rich diversity in extension speed, innervation timing, and ipsilateral branch locations and identified that ipsilateral targeting occurs via stabilization of transient interstitial branches. Fast imaging using adaptive optics-corrected lattice light-sheet microscopy showed that upon approaching target, many ORN types exhibiting "exploring branches" consisted of parallel microtubule-based terminal branches emanating from an F-actin-rich hub. Antennal nerve ablations uncovered essential roles for bilateral axons in contralateral target selection and for ORN axons to facilitate dendritic refinement of postsynaptic partner neurons. Altogether, these observations provide cellular bases for wiring specificity establishment.

Coronaviruses exploit a host cysteine-aspartic protease for replication.

Highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus 2 (refs. 1,2) (SARS-CoV-2), Middle East respiratory syndrome coronavirus3 (MERS-CoV) and SARS-CoV-1 (ref. 4), vary in their transmissibility and pathogenicity. However, infection by all three viruses results in substantial apoptosis in cell culture5-7 and in patient tissues8-10, suggesting a potential link between apoptosis and pathogenesis of coronaviruses. Here we show that caspase-6, a cysteine-aspartic protease of the apoptosis cascade, serves as an important host factor for efficient coronavirus replication. We demonstrate that caspase-6 cleaves coronavirus nucleocapsid proteins, generating fragments that serve as interferon antagonists, thus facilitating virus replication. Inhibition of caspase-6 substantially attenuates lung pathology and body weight loss in golden Syrian hamsters infected with SARS-CoV-2 and improves the survival of mice expressing human DPP4 that are infected with mouse-adapted MERS-CoV. Our study reveals how coronaviruses exploit a component of the host apoptosis cascade to facilitate virus replication.

Targeted Cyclo[8]pyrrole-Based NIR-II Photoacoustic Tomography Probe for Suppression of Orthotopic Pancreatic Tumor Growth and Intra-abdominal Metastases.

Pancreatic cancer is highly lethal. New diagnostic and treatment modalities are desperately needed. We report here that an expanded porphyrin, cyclo[8]pyrrole (CP), with a high extinction coefficient (89.16 L/g·cm) within the second near-infrared window (NIR-II), may be formulated with an αvß3-specific targeting peptide, cyclic-Arg-Gly-Asp (cRGD), to form cRGD-CP nanoparticles (cRGD-CPNPs) with promising NIR-II photothermal (PT) therapeutic and photoacoustic (PA) imaging properties. Studies with a ring-array PA tomography system, coupled with analysis of control nanoparticles lacking a targeting element (CPNPs), revealed that cRGD conjugation promoted the delivery of the NPs through abnormal vessels around the tumor to the solid tumor core. This proved true in both subcutaneous and orthotopic pancreatic tumor mice models, as confirmed by immunofluorescent studies. In combination with NIR-II laser photoirradiation, the cRGD-CPNPs provided near-baseline tumor growth inhibition through PTT both in vitro and in vivo. Notably, the combination of the present cRGD-CPNPs and photoirradiation was found to inhibit intra-abdominal metastases in an orthotopic pancreatic tumor mouse model. The cRGD-CPNPs also displayed good biosafety profiles, as inferred from PA tomography, blood analyses, and H&E staining. They thus appear promising for use in combined PA imaging and PT therapeutic treatment of pancreatic cancer.

Prophylactic anti-reflux procedure for children undergoing laparoscopic gastrostomy: Rethinking of the routine practice.

AIM: Laparoscopic gastrostomy is a frequently performed procedure in children requiring long-term enteral nutrition. The role of prophylactic anti-reflux surgery during gastrostomy placements is controversial. The current study aims to evaluate the role of prophylactic anti-reflux procedures during gastrostomy placement. METHODS: A retrospective single-center analysis of all children without reflux receiving laparoscopic gastrostomy from January 2005 through December 2021 was performed. Demographics and clinical outcomes were compared between patients receiving gastrostomy placement alone and patients receiving gastrostomy with prophylactic anti-reflux surgery. RESULTS: A total of 79 patients had a confirmed absence of reflux by a 24-h pH/impedance study before operation. Thirty-six of these patients underwent prophylactic anti-reflux surgery (PAR) while 43 received gastrostomy (PG) alone. The operative time and conversion rate were significantly higher in the PAR group (140.5 ± 67.5 vs. 80.2 ± 66.8 min, p = 0.0001 and 8.3% vs. 0%, p = 0.04). There were no major complications in either group. De novo reflux was detected in five patients (11.6%) in the PG group. None of these patients progressed to require anti-reflux surgery. CONCLUSION: The occurrence of de novo reflux after laparoscopic gastrostomy was low and could be managed without anti-reflux surgery. A routine pre-operative pH study is helpful for appropriate patient selection to avoid unnecessary anti-reflux surgery, which lengthens operative time and increases the conversion rate.

Wide Resection for Pediatric Extremity Vascular Malformation-A Tertiary Hospital's Experience.

BACKGROUND: Vascular malformations of the extremities (VM) are common benign lesions that tend to grow throughout the patient's lifetime. They can cause various issues like pain, swelling, and even limb length discrepancies. Sclerotherapy was the preferred treatment choice in previous studies. However, sclerotherapy and many other treatments have the potential to result in higher recurrence rates. Surgical treatment has been shown to be effective and safe in many cases. Hence, this study aims to evaluate the suitability of wide resection surgery for VM to reduce recurrence. METHODS: Fort-seven VM cases that underwent wide resection were identified retrospectively in the institution of study. Demographics, depth of malformation, whether malformations were local or diffuse, location and size of malformations, and histology records were taken note of. Records of recurrence and postoperative function were also gathered. We utilized self-reported questionnaires, QuickDASH and Lower Extremity Functional Scale, to determine patients' postsurgical physical function. RESULTS: Out of 47 cases that underwent wide resection, we found a recurrence rate of 2.1%. No patients sustained any loss of function postsurgery, with few patients experiencing minor complications like tenderness, hypertrophic scars/keloids, as well as numbness. Good functionality posttreatment was also seen through self-reported questionnaires, with an average score of 2.12 for QuickDASH and 99.96% for LEFS. CONCLUSION: Where margins can be obtained without functional impairment, surgical-wide resection for VM is a viable treatment option to minimize recurrence. LEVEL OF EVIDENCE: Level-IV.

Improved Comfortability and Satisfaction of Hybrid-mesh Casts in the Conservative Management of Pediatric Supracondylar Humeral Fractures: A Randomized Controlled Trial.

BACKGROUND: Cast immobilization is the mainstay of treatment for stable pediatric supracondylar humeral fractures (SCHFs). In recent years, a waterproof and breathable hybrid-mesh (HM) cast has emerged and been marketed to address common complaints such as itch, skin irritation, and malodor. Hence, this randomized controlled trial seeks to assess the overall satisfaction, comfort, and clinical outcomes of using HM casts in the conservative treatment of stable pediatric SCHF. METHODS: Seventy-nine patients (age range: 1 to 10 y) with modified Gartland's classification Type I and Type IIa SCHF were recruited and randomized for immobilization with either fiberglass or HM long-arm cast for 3 weeks. During follow-up visits, patients were assessed for any loss of reduction and skin rash. The weight of casts, the presence of cast breakage, the duration of cast application, and removal were recorded. A self-reported patient comfort and satisfaction questionnaire was also administered during the same visit. RESULTS: The final analysis included 38 patients immobilized with fiberglass casts and 39 patients with HM casts. Despite the significantly longer duration required for HM cast removal (4.18±1.25 min vs. 2.25±0.55 min, P <0.001), the HM cast was significantly lighter than its fiberglass counterpart (162.82±23.94 g vs. 203.95±36.52 g, P <0.001). The HM casts have better comfort (4.05±0.887 vs. 3.47±0.951, P =0.007) and satisfaction (3.69±1.055 vs. 3.11±0.953, P =0.012) scores as compared to fiberglass casts for immobilizing pediatric SCHF without compromising clinical outcome. CONCLUSIONS: HM casts have better comfort and overall satisfaction as compared to conventional fiberglass casts for immobilizing pediatric SCHF without compromising clinical outcomes. LEVEL OF EVIDENCE: Level II-therapeutic studies-investigating the results of treatment.

Impact of Volumetric Dosimetry on the Projected Cost of Radiation-Related Late Effects Screening After Childhood Cancer: A Real-World Cohort Analysis.

BACKGROUND: Screening guidelines for childhood cancer survivors treated with radiation currently rely on broad anatomic irradiated regions (IR) to determine risk for late effects. However, contemporary radiotherapy techniques use volumetric dosimetry (VD) to define organ-specific exposure, which supports more specific screening recommendations that could be less costly. PATIENTS AND METHODS: This was a cross-sectional study of 132 patients treated with irradiation at Children's Hospital Los Angeles from 2000 to 2016. For 5 key organs (cochlea, breast, heart, lung, and colon), radiation exposure was determined retrospectively using both IR and VD methods. Under each method, Children's Oncology Group Long-Term Follow-Up Guidelines were used to identify organs flagged for screening and recommended screening tests. Projected screening costs incurred under each method were computed through age 65 using insurance claims data. RESULTS: Median age at the end of treatment was 10.6 years (range, 1.4-20.4). Brain tumor was the most common diagnosis (45%) and head/brain the most common irradiated region (61%). For all 5 organs, use of VD rather than IR resulted in fewer recommended screening tests. This led to average cumulative estimated savings of $3769 (P = .099), with significant savings in patients with CNS tumors (P = .012). Among patients with savings, average savings were $9620 per patient (P = .016) and significantly more likely for females than males (P = .027). CONCLUSION: Use of VD to enhance precision of guideline-based screening for radiation-related late effects permits fewer recommended screening tests and generates cost-savings.

Feature issue introduction: ultrafast optical imaging.

This feature issue of Optics Express collects 20 articles that report the most recent progress of ultrafast optical imaging. This review provides a summary of these articles that cover the spectrum of ultrafast optical imaging, from new technologies to applications.

Large-scale fabrication of an ultrathin broadband absorber using quasi-random dielectric Mie resonators.

Ultrathin broadband absorber maintaining a near-uniform low reflectivity over a broadband wavelength is essential for many optical applications, such as light harvesting and nanoscale imaging. Recently, there has been considerable interest in employing arrays of high-index dielectric Mie resonators on surfaces to trap light and reduce the reflectivity. For such Mie-resonant metasurfaces, however, antireflection properties featuring both a flat low reflectance curve and a wide bandwidth are hard to be satisfied simultaneously, and an efficient large-scale nanofabrication technique rarely exists. Here, we present a high-throughput laser interference induced quasi-random patterning (LIIQP) technique to fabricate quasi-random Mie resonators in large scale. Mie resonators with feature sizes down to sub-100 nm have been fabricated using a 1064 nm laser source. Each Mie resonator concentrates light at its shape-dependent resonant frequency, and all such resonators are arranged quasi-randomly to provide both rich (with broadband Fourier components) and strong (with large intensities) Fourier spectra. Specifically, a near-uniform broadband reflectivity over 400-1100 nm spectrum region has been confined below 3% by fabricating a large-scale ultrathin (around 400 nm) absorber. Our concept and high-throughput fabrication technique allows the rapid production of quasi-random dielectric Mie-resonant metasurfaces in a controllable way, which can be used in various promising applications including thin-film solar cells, display, and imaging.

Observation of modulation instability Kerr frequency combs in a fiber Fabry-Pérot resonator.

We report the experimental observation of a modulation instability induced Kerr frequency comb in an all fiber Fabry-Pérot resonator. We fully characterized, in intensity and phase, the frequency comb using a commercial 10 MHz resolution heterodyne detection system to reveal more than 125 comb teeth within each of the modulation instability sidelobes. Moreover, we were able to reveal the fine temporal structure in phase and intensity of the output Turing patterns. The experimental results are generally in good agreement with numerical simulations.

A comprehensive review of 30 years of pediatric clinical trial radiotherapy dose constraints.

BACKGROUND: Radiation therapy normal tissue dose constraints are critical when treating pediatric patients. However, there is limited evidence supporting proposed constraints, which has led to variations in constraints over the years. In this study, we identify these variations in dose constraints within pediatric trials both in the United States and in Europe used in the past 30 years. PROCEDURE: All pediatric trials from the Children's Oncology Group website were queried from inception until January 2022 and a sampling of European studies was included. Dose constraints were identified and built into an organ-based interactive web application with filters to display data by organs at risk (OAR), protocol, start date, dose, volume, and fractionation scheme. Dose constraints were evaluated for consistency over time and compared between pediatric US and European trials RESULTS: One hundred five closed trials were included-93 US trials and 12 European trials. Thirty-eight separate OAR were found with high-dose constraint variability. Across all trials, nine organs had greater than 10 different constraints (median 16, range 11-26), including serial organs. When comparing US versus European dose tolerances, the United States constraints were higher for seven OAR, lower for one, and identical for five. No OAR had constraints change systematically over the last 30 years. CONCLUSION: Review of pediatric dose-volume constraints in clinical trials showed substantial variability for all OAR. Continued efforts focused on standardization of OAR dose constraints and risk profiles are essential to increase consistency of protocol outcomes and ultimately to reduce radiation toxicities in the pediatric population.

Outcome and learning curve for laparoscopic intra-corporeal inguinal hernia repair in children.

BACKGROUND: Laparoscopic inguinal hernia repair is one of the procedures most commonly performed by paediatric surgeons. Current research on the learning curve for laparoscopic hernia repair in children is scarce. This study aims to evaluate the clinical outcome and learning curve of laparoscopic intra-corporeal inguinal hernia repair in children. METHODS: A retrospective single-centre analysis of all paediatric patients who underwent laparoscopic intra-corporeal inguinal hernia repair between 2010 and 2019 was performed. The clinical outcomes were analysed. The data on the achievement of the learning curve by surgical trainees were evaluated with the CUSUM technique, focusing on operative time. RESULTS: There were 719 patients with laparoscopic intra-corporeal inguinal hernia repair (comprising 1051 sides) performed during the study period. The overall ipsilateral recurrence rate was 1.8% without other complications detected. CUSUM analysis showed that there were 3 phases of training, for which the trainees underwent initial learning phase (Phase 1) for the first 7 cases. After mastering of the skills and extrapolating the skills to male patients with smaller body size (Phase 2), they then achieved performance comparable to that of the senior surgeons after 18 procedures (Phase 3). CONCLUSIONS: 18 procedures seem to be the number required to reach the learning curve plateau in terms of operative time by surgical trainees. The clinical outcomes show that laparoscopic intra-corporeal inguinal hernia repair is a safe and transferrable technique, even in the hands of trainees, with adequate supervision and careful case selection. It also provides skill acquisition for minimally invasive surgery.

Analysing Factors Prolonging Hospital Stay After Excision of Choledochal Cyst-A Pathway Towards Enhanced Recovery After Surgery.

BACKGROUND: To evaluate factors affecting length of stay (LOS) after choledochal cyst resection in paediatric patients. METHODS: This was a retrospective study on patients operated between 2004 and 2021. Associations between clinical factors and LOS were evaluated by bivariate analysis, multiple regression, and equivalence test. RESULTS: Sixty-two patients were included. Twenty-four underwent hepaticoduodenostomy as biliary reconstruction. Five suffered from major complications. The median (25th-75th percentile) operation time was 279 (182-378) min. Median LOS, time to enteral feeding, and time to abdominal drain removal were 8(6-10), 2(1-3), and 5(4-7) days, respectively. Seven factors were found significantly associated with a shorter LOS in bivariate analysis and were included in multiple regression. It revealed that early abdominal drain removal (p < 0.001), early enteral feeding (p = 0.042), and the absence of major complications (p < 0.001) were significantly associated with shorter LOS. Equivalence test suggested that age and preoperative cholangitis had no practical effect on LOS. CONCLUSIONS: Early enteral feeding, early drain removal, and avoidance of major complications are associated with a shorter LOS.

Prognostic and predictive biomarkers with therapeutic targets in breast cancer: A 2022 update on current developments, evidence, and recommendations.

OBJECTIVE: To evaluate and validate the recent and emerging data for prognostic and predictive biomarkers with therapeutic targets in breast cancer. DATA SOURCES: A literature search from January 2015 to March 2022 was performed using the key terms breast cancer, clinical practice guidelines, gene mutations, genomic assay, immune cancer therapy, predictive and/or prognostic biomarkers, and targeted therapies. STUDY SELECTION AND DATA EXTRACTION: Relevant clinical trials, meta-analyses, seminal articles, and published evidence- and consensus-based clinical practice guidelines in the English language were identified, reviewed and evaluated. DATA SYNTHESIS: Breast cancer is a biologically heterogeneous disease, leading to wide variability in treatment responses and survival outcomes. Biomarkers for breast cancer are evolving from traditional biomarkers in immunohistochemistry (IHC) such as estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor type 2 (HER2) to genetic biomarkers with therapeutic implications (e.g. breast cancer susceptibility gene 1/2 [BRCA1/2], estrogen receptor α [ESR1] gene mutation, HER2 gene mutation, microsatellite instability [MSI], phosphatidylinositol 3-kinase catalytic subunit 3Cα [PIK3CA] gene mutation, neurotrophic tyrosine receptor kinase [NTRK] gene mutation). In addition, current data are most robust for biomarkers in immunotherapy (e.g. programmed cell death receptor ligand-1 [PD-L1], microsatellite instability-high [MSI-H] or deficient mismatch repair [dMMR]). Oncotype DX assay remains the best validated gene expression assay that is both predictive and prognostic whereas MammaPrint is prognostic for genomic risk. CONCLUSIONS: Biomarker-driven therapies have the potential to confer greater therapeutic advantages than standard-of-care therapies. The purported survival benefits associated with biomarker-driven therapies should be weighed against their potential harms.

The nutrient sensor OGT regulates Hipk stability and tumorigenic-like activities in Drosophila.

Environmental cues such as nutrients alter cellular behaviors by acting on a wide array of molecular sensors inside cells. Of emerging interest is the link observed between effects of dietary sugars on cancer proliferation. Here, we identify the requirements of hexosamine biosynthetic pathway (HBP) and O-GlcNAc transferase (OGT) for Drosophila homeodomain-interacting protein kinase (Hipk)-induced growth abnormalities in response to a high sugar diet. On a normal diet, OGT is both necessary and sufficient for inducing Hipk-mediated tumor-like growth. We further show that OGT maintains Hipk protein stability by blocking its proteasomal degradation and that Hipk is O-GlcNAcylated by OGT. In mammalian cells, human HIPK2 proteins accumulate posttranscriptionally upon OGT overexpression. Mass spectrometry analyses reveal that HIPK2 is at least O-GlcNAc modified at S852, T1009, and S1147 residues. Mutations of these residues reduce HIPK2 O-GlcNAcylation and stability. Together, our data demonstrate a conserved role of OGT in positively regulating the protein stability of HIPKs (fly Hipk and human HIPK2), which likely permits the nutritional responsiveness of HIPKs.

The impact of pre-operative cholecystostomy on laparoscopic excision of choledochal cyst in paediatric patients.

PURPOSE: This aim of this study was to identify the pre-operative risk factors for conversion during laparoscopic excision of choledochal cyst in paediatric patients. METHODS: A retrospective single-centre study was carried out. All paediatric patients (< 18 years) who had undergone laparoscopic excision of choledochal cyst between 2004 and 2021 were reviewed. The outcome was conversion to open surgery and pre-operative factors that affected the conversion rate were analyzed. RESULTS: Sixty-one patients were included. Conversion was required in 24 cases (39.3%). There was no difference in the conversion rate between the first (before 2012, n = 30) and second (after 2012, n = 31) half of the series (36.7% vs. 42.0%, p = 0.674). Majority was type 1 cyst (86.8%) and the median cyst size was 4.6 cm (IQR: 2.2-6.4 cm). Antenatal diagnosis was available in 18 patients (29.5%). The median age at operation was 23.0 months (IQR: 8.0-72.0 months). Pre-operatively, 19 patients (31.1%) suffered from cholangitis and 5 (8.2%) of them required cholecystostomy. Comparing patients with successful laparoscopic surgery (L) and converted cases (C), there were no differences in the age at operation (p = 0.74), cyst size (p = 0.35), availability of antenatal diagnosis (p = 0.23) and cholangitic episodes (p = 0.40). However, a higher percentage of patients required cholecystostomy in the converted group (L vs. C = 2.7% vs. 16.7%, p = 0.05). Using logistic regression analysis, it was also a risk factor for conversion (OR = 3.5 [1.37-5.21], p = 0.05). CONCLUSION: Pre-operative cholecystostomy is a potential risk factor for conversion during laparoscopic excision of choledochal cyst in children.

Primary anastomosis is the preferred surgical approach for proximal intestinal atresia: a retrospective 20-year analysis.

PURPOSE: We aimed to compare the outcomes of primary anastomosis (PA) and enterostomy as treatments for intestinal atresia in neonates to identify the factors influencing the choice of modality. METHODS: We conducted a retrospective single-centre analysis of all neonates with intestinal atresia between 2000 and 2020 and measured the clinical outcomes. We performed logistic regression to identify factors that influenced the choice of surgical approach. RESULTS: Of 62 intestinal atresia neonates, 71% received PA. There were no significant differences in gestation, gender, age at operation, birth weight, or body weight at operation between the PA and enterostomy groups. PA reoperation was not required for 78% of patients, and the PA group had shorter hospital stays. Complications, operative time, duration on parenteral nutrition, time to full enteral feeding were comparable in both groups. Upon multivariate regression analysis, surgeons favoured PA in proximal atresia [Odds ratio (OR) 38.5, 95% Confidence Interval (CI) 2.558-579] while enterostomy in smaller body size [OR 2.75, CI 0.538-14.02] and lower Apgar score [OR 1.1, CI 0.07-17.8]. Subgroup analysis in these patient groups demonstrated comparable outcomes with both surgical approaches. CONCLUSION: Both surgical approaches achieved comparable outcomes, but PA was associated with short hospital stays and the avoidance of stoma-related complications, and reoperation was generally not required. This surgical approach was suitable for patients with proximal atresia, but enterostomy remained a sensible choice for patients with smaller body sizes and lower Apgar scores.

C-reactive protein of ≥ 20 mg/L and ultrasound finding of an effusion ≥ 7 mm has a high specificity and sensitivity in diagnosing paediatric hip septic arthritis.

PURPOSE: Differentiating septic arthritis (SA) from transient synovitis (TS) in children remains a diagnostic challenge. Several algorithms have been developed to diagnose SA including Kocher's criteria and its subsequent modifications, but reports show variable efficacy. This study aims to examine the diagnostic utility of a novel method only using C-reactive protein (CRP) and ultrasound (US) findings of effusion in differentiating SA from TS, determine the optimal values for these predictors and validate this method against existing clinical predictors. METHODS: A 5-year retrospective study was performed including all paediatric patients with acute, non-traumatic hip pain with a suspicion of SA. All patients were evaluated using Kocher's criteria, Caird's criteria, and the novel method. Multivariate logistic regression was performed to identify independent clinical predictors of SA. The degree of agreement between the various methods were assessed using Cohen's kappa (k). Receiver operating characteristics (ROC) curves were used to examine the diagnostic accuracy of this novel method as well as to determine optimal cut-offs for US effusion and CRP in diagnosing SA. RESULTS: Hundred and one patients were recruited. CRP and effusion on US were found to be independent predictors of SA. Both Kocher's and Caird's method showed good specificity (98.9%) but extremely poor sensitivity for SA (0%). When Kocher's four clinical predictors were present, probability of SA was only 59.16%. The k for both Kocher's and Caird's methods, was -0.017 indicating poor agreement. However the k in the novel method was 0.641, indicating good agreement. CONCLUSION: Our study showed that the novel method using CRP (≥ 20 mg/L) and US finding of effusion (≥ 7 mm) has a high specificity (97%) and sensitivity (71%) in diagnosing SA.

Single or double? A comparison of evisceration techniques.

PURPOSE: We compared the rates of implant exposure and extrusion after evisceration with single and double scleral closure techniques. METHODS: This retrospective cohort study included all patients who underwent evisceration with an implant insertion over the past 18 years at Tung Wah Eastern Hospital and Pamela Youde Nethersole Eastern Hospital. Clinical documents and operation records were reviewed. RESULTS: A total of 81 ethnic Chinese patients (44 male) who underwent evisceration with primary implant insertion were reviewed. 39 (48%) patients underwent the double scleral closure technique with an implant placed posterior to the posterior sclera, and 42 (52%) patients underwent the single scleral closure technique with an implant inserted in the intra-scleral cavity. The follow-up interval was 70 months. The surgical indications were endophthalmitis (35%), painful blind eye (23%), traumatic disfigured globe (22%) and phthisis bulbi (20%). Silicone was the most used implant material (69%). The patients who underwent double scleral closure had a larger size of the implant (19.7 vs 17.9 mm, p < 0.05). Both implant exposure (26% vs 3%, p < 0.05) and implant extrusion (26% vs 0%, p < 0.05) were more common in patients who underwent single scleral. CONCLUSIONS: Double scleral closure technique allows a larger implant, and it is associated with a lower rate of implant exposure and extrusion. The double scleral closure technique is a superior technique of choice in these patients with primary implant placement.

Gut microbiota composition is associated with SARS-CoV-2 vaccine immunogenicity and adverse events.

OBJECTIVE: The gut microbiota plays a key role in modulating host immune response. We conducted a prospective, observational study to examine gut microbiota composition in association with immune responses and adverse events in adults who have received the inactivated vaccine (CoronaVac; Sinovac) or the mRNA vaccine (BNT162b2; BioNTech; Comirnaty). DESIGN: We performed shotgun metagenomic sequencing in stool samples of 138 COVID-19 vaccinees (37 CoronaVac and 101 BNT162b2 vaccinees) collected at baseline and 1 month after second dose of vaccination. Immune markers were measured by SARS-CoV-2 surrogate virus neutralisation test and spike receptor-binding domain IgG ELISA. RESULTS: We found a significantly lower immune response in recipients of CoronaVac than BNT162b2 vaccines (p<0.05). Bifidobacterium adolescentis was persistently higher in subjects with high neutralising antibodies to CoronaVac vaccine (p=0.023) and their baseline gut microbiome was enriched in pathways related to carbohydrate metabolism (linear discriminant analysis (LDA) scores >2 and p<0.05). Neutralising antibodies in BNT162b2 vaccinees showed a positive correlation with the total abundance of bacteria with flagella and fimbriae including Roseburia faecis (p=0.028). The abundance of Prevotella copri and two Megamonas species were enriched in individuals with fewer adverse events following either of the vaccines indicating that these bacteria may play an anti-inflammatory role in host immune response (LDA scores>3 and p<0.05). CONCLUSION: Our study has identified specific gut microbiota markers in association with improved immune response and reduced adverse events following COVID-19 vaccines. Microbiota-targeted interventions have the potential to complement effectiveness of COVID-19 vaccines.