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  • Two-Decade Retrospective Analysis of Postoperative Endophthalmitis at

    Two-Decade Retrospective Analysis of Postoperative Endophthalmitis at

    Introduction

    Postoperative endophthalmitis is a particularly serious complication of ophthalmic surgery. Severe and irreversible visual loss can occur in a large proportion of cases, particularly if diagnosis and proper treatment are delayed. Although culture methods may fail to identify the causative pathogen, clinical signs of disease can be sufficient to recognize this condition and initiate treatment.

    The most common types of intraocular surgeries performed worldwide are cataract extraction, glaucoma filtration surgery, pars plana vitrectomy (PPV), and intravitreal injection (IVI). The reported incidence of acute-onset postoperative endophthalmitis ranges from 0.036% to 0.36% of eyes undergoing intraocular surgery.1–3 Additionally, the incidence of post-injection endophthalmitis is reportedly 0.049%–0.056%.4

    Since 2000, intraocular surgery underwent substantial changes, such as increased numbers of cataract surgeries and PPVs. Surgical advancements included small clear corneal incision cataract surgery, manual small incision cataract surgery, sutureless small-gauge PPV (instead of 20-gauge PPV), and an exponential increase in the use of intravitreal injections for ophthalmic treatment. These developments may influence the incidence of postoperative endophthalmitis.5,6

    Categorization helps to predict the causative organism and underlying etiology. According to the Endophthalmitis Vitrectomy Study, acute-onset postoperative endophthalmitis is defined as an infection arising within 6 weeks after surgery. Conversely, delayed-onset postoperative endophthalmitis is defined as an infection occurring more than 6 weeks after surgery.7

    This study was performed to evaluate the clinical features, causative organisms, treatment modalities, and visual outcomes associated with acute-onset and delayed-onset postoperative endophthalmitis during the past 20 years at a university referral center.

    Ramathibodi Hospital, a tertiary referral facility in central Thailand, receives endophthalmitis cases from local and distant areas. This single-center retrospective study focused on postoperative endophthalmitis cases from the surrounding region.

    Materials and Methods

    This study adhered to the tenets of the Declaration of Helsinki and was approved by the Mahidol University Ethics Committee for Human Research (MURA2023/888). Informed consent was waived due to the retrospective nature of the study. No identifiable patient data or images are included in this publication. A retrospective review was conducted involving the medical records of all patients who received treatment for postoperative endophthalmitis at Ramathibodi Hospital between 2001 and 2022. The study included patients with the following International Classification of Diseases and Related Health Problems-10 codes: H44.0 for purulent endophthalmitis, H44.1 for other endophthalmitis, H45.1 for endophthalmitis in diseases classified elsewhere, H59.8 for other postprocedural disorders of the eye and adnexa, such as keratoplasty-associated endophthalmitis and bleb-associated endophthalmitis, and T89.1 for unspecified procedure complications. Diagnoses of endophthalmitis were based on clinical signs and symptoms, including eye pain, vision loss, eyelid edema, conjunctival hyperemia and chemosis, anterior chamber inflammation (eg, flare, cells, hypopyon, pupillary fibrin membrane), blebitis, vitritis, and vitreous opacity on B-scan ultrasonography. In our study, follow-up was defined as the period from the initial diagnosis of endophthalmitis to at least nine months after treatment. The main outcome measurement was the evaluation at nine months post-treatment; therefore, patients who were lost to follow-up before this timepoint were excluded from the analysis.

    For all suspected cases of endophthalmitis, demographic data were recorded; these data included age, sex, underlying diseases, laterality, onset and duration, best-corrected visual acuity (VA) at initial presentation (defined as the VA measured at the patient’s first visit to our hospital at the time of endophthalmitis diagnosis) and after recovery, pathogen etiology, type of intraocular surgery and associated complications, culture results, and treatments.

    Prior to initiating treatment, vitreous and/or aqueous samples were collected for microbiological analysis in all cases. In patients undergoing intravitreal tapping, undiluted vitreous samples were aspirated using a 23-gauge needle attached to a syringe under aseptic conditions at the operating microscope. For patients treated with PPV, undiluted vitreous specimens were obtained at the start of the procedure before infusion was initiated, using the vitrectomy cutter connected to a sterile syringe or tubing. Standard 20- or 23-gauge systems were used, and all procedures were performed by experienced vitreoretinal surgeons. Collected specimens were immediately submitted for microbiological workup, which included inoculation on blood agar, chocolate agar, Sabouraud dextrose agar, and thioglycollate broth to detect aerobic and anaerobic bacteria and fungi. In some cases, molecular testing using 16S and 18S rRNA gene polymerase chain reaction (PCR) assays were performed to enhance pathogen detection. However, molecular diagnostics were not consistently available during the first five years of the study period due to laboratory limitations. Bacterial detection was performed using primers 27F and 519R, commonly applied for broad-range bacterial identification.8 For fungi, the internal transcribed spacer (ITS1–ITS2) region was amplified using ITS1 and ITS2 primers, which are widely recommended for broad fungal coverage.9 Immediate PPV was defined as surgery performed within 24 hours of endophthalmitis diagnosis, whereas delayed PPV was performed more than 24 hours after diagnosis in cases where there was no clinical improvement or worsening following primary vitreous tapping and antimicrobial injection. In cases of bacterial infection, ceftazidime and vancomycin were prescribed as empiric therapy, whereas amphotericin or voriconazole were administered in cases of fungal infection. Specific treatments for each patient were determined based on culture results.

    To facilitate statistical analysis, Snellen VA measurements were converted to logarithm of the minimum angle of resolution (logMAR) values. Poor VA measurements were assigned logMAR values of 2.0, 2.3, 2.5, 2.7, and 3.0 for counting fingers, hand motion, light projection, light perception, and no light perception, respectively. The primary outcome measure was VA assessed at nine months, which was used as the reference point for determining the final visual outcome after endophthalmitis management.10

    Statistical Analysis

    Categorical data (eg, sex, laterality, underlying diseases, prior surgeries, and treatment modalities) are shown as numbers and percentages. Continuous variables are presented as means and standard deviations; for variables with skewed distributions, medians and interquartile ranges (IQRs) are presented. Normally distributed continuous variables were analyzed using t-tests. For skewed distributions, the Mann–Whitney U-test was used. Categorical variables were analyzed using the Pearson chi-squared test or Fisher’s exact test. Multivariate logistic regression analysis was utilized to identify factors associated with poor visual prognosis. Multilevel linear random intercepts and random slope regression models were used to analyze the mean difference in VA (logMAR) from preoperative to postoperative across the three treatment groups. The models also compared the mean preoperative VA (logMAR) among the treatment groups and accounted for variations between individual participants at the preoperative stage (intercepts). Additionally, the models calculated the mean difference in the effect over time (slopes) on VA (logMAR) between preoperative and postoperative stages across the three groups. Statistical analysis was performed using STATA version 14.0 (Stata Corp LP, College Station, TX, USA). P-values <0.05 were considered statistically significant.

    Results

    This study initially included 181 patients with suspected endophthalmitis, according to their electronic medical records. After the exclusion of 18 patients (Figure 1) due to incomplete records, altered diagnoses, or loss to follow-up, 163 eyes of 163 patients were analyzed (Table 1). The participants comprised 89 men and 74 women with a mean age of 64.8±13.0 years. Endophthalmitis involved the right eye in 82 cases (50.3%). The two most prevalent underlying diseases were hypertension and diabetes mellitus, observed in 53% and 31% of cases, respectively, as presented in Table 1.

    Table 1 Demographic Data of 163 Patients with Postoperative Endophthalmitis

    Figure 1 Post-operative endophthalmitis inclusion and subgroup treatment analysis flow diagram.

    Abbreviations: EMRs, electronic medical records; ICD10, 10th revision of the International Classification of Diseases; IVI, intravitreal injection; PPV, pars plana vitrectomy.

    Notes: Bold text in the diagram indicates the total number of eyes included in the study cohort.

    All included patients had postoperative endophthalmitis; 53% of eyes (87 of 163) were acute-onset. The median intervals from surgery to presentation were 8 days (IQR, 3–14) and 730 days (IQR, 125–1753) in the acute and chronic postoperative endophthalmitis groups, respectively. Cataract surgery was the primary procedure associated with the highest incidence of postoperative endophthalmitis (94 cases, 57.7%). Eighteen eyes (11%) received vitreous tapping and intravitreal antibiotics at the referring hospital prior to presentation at our center. Of these, 14 were in the cataract surgery group, 2 in the PPV group, and 1 each in the glaucoma and IVI groups. Among these, 10 cataract cases and all PPV and glaucoma cases were culture negative.

    Microbiological investigations of vitreous fluid were performed for all patients prior to treatment. The treatment modalities utilized in this study, including intravitreal or intracameral injections, immediate PPV, delayed PPV, and enucleation, are summarized in Table 2. All PPV procedures were combined with antimicrobial intravitreal injection (IVI). Immediate PPV was the most common approach, employed in 98 eyes (60.1%), followed by vitreous tapping with IVI alone in 50 eyes (30.7%). Delayed PPV was performed in 12 eyes (7.4%) following initial IVI due to clinical deterioration. The mean time to delayed PPV after initial presentation was 3.9 days (range 2–10 days). Intracameral injection was performed in two eyes (1.2%), when the anterior and posterior chambers were considered as a single chamber, either due to prior scleral fixation of an intraocular lens procedure or the aphakic status of the patient.

    Table 2 Trends in Treatment Modalities and Antimicrobial Agents for Endophthalmitis Across Different Time Periods

    Additionally, trends in treatment modalities for endophthalmitis from 2001 to present are summarized in Table 2. A shift in management strategies was observed over the years. Immediate PPV became the predominant approach in recent years, particularly after 2016. In contrast, vitreous tapping IVI alone and delayed PPV were more frequently employed in earlier years, especially before 2010.

    Variations in drug treatment for postoperative endophthalmitis are presented in Table 2. Antimicrobial agents were administered to all patients based on suspected pathogens. The most commonly used intravitreal antibiotic regimens for bacterial infections were combinations of ceftazidime and vancomycin. Among the 163 total cases, 141 (86.5%) received systemic antibiotics, predominantly second- or third-generation fluoroquinolones, administered primarily via the oral route. Furthermore, 33 of 141 cases received intravenous antibiotics, predominantly involving a combination of ceftazidime and vancomycin.

    Table 3 presents the preoperative and postoperative VA across the three treatment groups: vitreous tapping with IVI, immediate PPV, and delayed PPV. Two eyes that received intracameral injections were included in the IVI group. The mean initial VA before treatment was 2.0 logMAR in the immediate PPV group and 1.7 logMAR in both the IVI and delayed PPV group. Significant VA improvements were observed in the immediate PPV and delayed PPV groups, with mean improvements of 0.8 logMAR (p < 0.001) and 0.9 logMAR (p = 0.001), respectively. Multilevel linear regression models with random intercepts and slopes were used to analyze the mean differences in VA changes between treatment groups. The IVI group showed significantly less VA improvement compared to the immediate PPV group (mean difference: 0.6 logMAR, p < 0.001) and the delayed PPV group (mean difference: 0.7 logMAR, p = 0.029). No statistically significant difference in VA improvement was found between the immediate and delayed PPV groups.

    Table 3 Mean VA (Log MAR) Value and Mean Difference of Participants From Initial and Final Visual Acuity of Three Different Treatment Groups

    Among acute-onset cases, 60 of 87 eyes (69%) underwent immediate PPV with IVI, whereas in delayed-onset cases, 38 of 76 eyes (50%) underwent the same treatment. One patient with a prior history of corneal transplantation required immediate enucleation due to severe infection. During the follow-up period, five additional eyes required enucleation due to inadequate response to treatment. For patients who retained their eye, the median final VA was 20/200, corresponding to 0.9 (0.3, 2.3) logMAR. VA improved by more than five letters in 61.2% of cases, remained stable in 11.5%, and declined by more than five letters in 27.4%.

    Prior Intraocular Surgeries

    We analyzed the relationships between prior intraocular surgeries and postoperative endophthalmitis (Table 4). Our results showed that cataract surgery was the most common procedure among the 94 eyes (57.7%) with postoperative endophthalmitis. Within this group, complicated surgeries involving posterior capsular rupture occurred in 12 eyes (12.8%). Other procedures included glaucoma surgeries (trabeculectomy and glaucoma drainage devices) in 23 eyes (14.1%), vitrectomy in 16 eyes (9.8%), corneal transplantation (penetrating keratoplasty and keratoprosthesis implantation) in 10 eyes (6.1%), and IVI in eight eyes (4.9%). Twelve eyes (7.4%) had undergone combined cataract surgery with other procedures, such as vitrectomy and trabeculectomy.

    Table 4 Different Prior Intraocular Surgeries with Their Associated Factors and Visual Outcomes

    The median age at presentation for patients undergoing glaucoma surgery was 61 years, the lowest among all surgical groups. Conversely, the highest median age at presentation was 70 years, observed in the corneal transplantation group. The interval between surgery and endophthalmitis diagnosis varied among procedures. Most patients with cataract surgery–, combined cataract surgery–, or intravitreal injection–related postoperative endophthalmitis presented with acute disease. Conversely, most patients who underwent prior glaucoma surgeries or corneal transplantation presented with chronic disease.

    Furthermore, we examined variations in globe salvage rates across surgical groups. The lowest rate was observed in the prior glaucoma surgery group (87%), whereas the highest rates were observed in the IVI and combined cataract surgery groups (100%). After the exclusion of cases requiring enucleation, the most favorable visual outcomes were achieved in the cataract and vitrectomy groups: median (IQR) VA of 0.5 (0.2–2.0) logMAR and 0.5 (0.5–2.3) logMAR, respectively. In subgroup analysis focusing on cataract surgery, the final median (IQR) VA after endophthalmitis treatment was less favorable in cases involving complicated cataract surgery (1.15 [IQR 0.60–2.15] logMAR) than in non-complicated cases (0.40 [IQR 0.20–2.0] logMAR). However, this difference in VA was not statistically significant (p=0.06). The least favorable visual outcome was observed in the prior corneal transplantation group, with a median (IQR) VA of 3.0 (2.0–3.0) logMAR.

    Causative Microorganisms

    Positive cultures were obtained in 52 of 163 eyes (31.9%). Bacteria were isolated in 42 eyes (80.7%), fungi were isolated in five eyes (9.6%), multiple bacterial organisms were isolated in one eye (2.0%), and mixed causative organisms in four eyes (7.7%). Notably, seven bacterial infections were identified through 16S rRNA analysis and negative culture methods, whereas two fungal infections were identified through 18S rRNA analysis and negative culture methods. The specific causative organisms, classified according to onset timing, and their visual outcomes are presented in Table 5. When considering the previous surgical procedures, the positive-culture rate was highest in the glaucoma surgery group (52.2%) and lowest in the vitrectomy group (25.0%). In acute postoperative endophthalmitis, positive cultures were obtained in 26 of 87 eyes (29.9%). The most frequently identified microorganism was coagulase-negative Staphylococcus (CoNS; 15/26, 57.7%), followed by Enterococcus faecalis (4/26, 15.9%).

    Table 5 Culture-Positive Pathogen Results According to Onset, Ocular-Related Surgeries and Visual Acuity

    Among cases of delayed-onset postoperative endophthalmitis, positive cultures were obtained in 22 of 76 eyes (29.0%). CoNS was again the most frequently identified microorganism (4/22, 18.2%). Most culture-positive delayed-onset postoperative endophthalmitis cases were associated with glaucoma surgery (11/21, 52.4%), and Streptococcus species were the predominant organisms in three cases. Pseudomonas aeruginosa infection was the most virulent organism, causing final VA of no light perception in all three affected patients. Staphylococcus aureus and CoNS were comparatively less virulent, with the best median final VA.

    Among five eyes with culture-proven fungal endophthalmitis, three were infected with Aspergillus spp., one with Penicillium, and one with Rigidoporus. Based on initial treatment modality, one eye received IVI (amphotericin and voriconazole) without vitrectomy and achieved successful infection control (Penicillium). Two eyes underwent immediate PPV (Aspergillus) and both were successfully salvaged. The remaining two eyes received only IVI as delayed PPV was not feasible due to uncontrolled infection and poor corneal clarity; both subsequently required enucleation (Aspergillus and Rigidoporus). The remaining three cases with preserved eyes, the median VA was 2.4 logMAR. All fungal infection cases exhibited delayed onset, with mean and median intervals from surgery (two keratoprostheses, one trabeculectomy, one phacoemulsification, and one scleral fixation of an intraocular lens) to diagnosis of 96.6 and 56.4 weeks, respectively.

    Subsequently, participants were categorized into two groups based on visual outcomes, as determined by the median final VA (Table 6). These groups had VA better than 20/200 and VA equal to or less than 20/200; six enucleation cases were excluded from the analysis. Univariate analysis revealed that diabetes mellitus, initial VA of 20/200 or worse, hypopyon at initial presentation, and delayed-onset postoperative endophthalmitis were factors significantly associated with poor visual outcomes. No significant differences in visual outcomes were observed based on other factors, such as sex, immunocompetence, end-stage renal disease status, culture results, and vitrectomy status. Stepwise logistic regression analysis confirmed significant associations of poor visual outcomes with diabetes mellitus (odds ratio [OR]=2.65; 95% confidence interval [CI], 1.17–5.96), VA at initial presentation of 20/200 or worse (OR=35.87; 95% CI, 7.15–179.89), and delayed-onset postoperative endophthalmitis (OR=3.9; 95% CI, 1.79–8.50).

    Table 6 Factors Associated with Final Visual Outcome After Treatment of Postoperative Endophthalmitis by Univariate and Multivariate Analysis (Enucleation Eyes Were Excluded)

    In this study, six patients underwent enucleation due to uncontrolled infection after treatment, representing a globe salvage rate of 96.3%. The infections occurred after three postoperative trabeculectomies, one phacoemulsification, one vitrectomy with scleral fixation, and one keratoprosthesis implantation.

    Discussion

    In cases of postoperative endophthalmitis, intraocular fluid smears and cultures remain the gold standard for identifying causative organisms. The culture-positive rate in our study was lower than typically reported in the literature, where postoperative endophthalmitis culture yields generally range from 40% to 70%.11–13 Several factors may explain this finding. Eighteen eyes (11%) had received intravitreal antibiotics prior to referral, potentially suppressing organism growth by the time of sample collection. Additionally, limited vitreous volume in some cases and the use of conventional culture methods without molecular diagnostics could have reduced detection sensitivity. Culture-positive rates also varied by prior surgery type, with higher rates in the glaucoma group and lower rates in the cataract and PPV groups. This may be partly due to pre-referral treatment: 14 of the 18 pretreated eyes were in the cataract group (10 culture-negative), and all pretreated PPV and glaucoma cases were also culture-negative. Differences in sample size across surgical subgroups may also have contributed to the variability in culture positivity.

    The Endophthalmitis Vitrectomy Study (1995) showed that early vitrectomy significantly improved outcomes in patients with light perception vision, with a threefold greater chance of achieving 20/40 vision.14 Since then, advances in surgical techniques have increased the success of PPV, which has become more widely adopted in managing endophthalmitis.5 The Complete and Early Vitrectomy for Endophthalmitis (CEVE) approach is now recommended as a primary treatment, especially when the fundus view is obscured or macular involvement cannot be excluded.15 We compared VA at initial presentation among three groups: IVI alone, immediate PPV with IVI, and delayed PPV with IVI. Initial VA was generally better in the IVI and delayed PPV groups, likely reflecting clinical decisions to reserve immediate PPV for eyes with more severe vitritis.

    Post-treatment outcomes showed significant visual improvement in both the immediate and delayed PPV groups, while the IVI group showed no significant change. Visual improvement was also significantly greater in the PPV groups compared to the IVI group. These findings suggest that PPV—whether performed initially or after IVI—offers superior visual outcomes, particularly in patients with poor baseline vision or severe vitritis. This aligns with previous studies reporting that immediate PPV results in better visual outcomes compared to IVI alone in cases of postoperative endophthalmitis presenting with poor vision or severe vitritis.15,16

    The limited improvement in the IVI group may be due to the absence of mechanical clearance of infectious and inflammatory material. Additionally, less severe initial presentations in this group may have led to smaller observed gains in visual acuity. The difference in outcomes between immediate and delayed PPV was not statistically significant, likely due to the small sample size in the delayed PPV group. These findings underscore the need for individualized treatment based on disease severity, with close monitoring to allow timely surgical intervention when needed.

    Intravitreal antibiotics are essential for initial management of postoperative endophthalmitis and are often combined with topical and systemic agents. Vancomycin and ceftazidime are commonly used due to their broad-spectrum coverage. Vancomycin targets gram-positive bacteria, including methicillin-resistant strains, while ceftazidime is preferred for gram-negative coverage and is safer than amikacin.17 The use of topical and systemic antibiotics alongside intravitreal therapy in postoperative endophthalmitis depends on disease severity and patient factors. The EVS recommends systemic antibiotics in cases with severe presentation, such as dense hypopyon or poor initial vision. The 2013 ESCRS guidelines also advise that if systemic antibiotics are used for severe acute-onset cases, they should align with the spectrum of intravitreal agents.18 In our study, systemic antibiotics were used in 87% of cases, primarily via oral administration. Intravenous antibiotics were given in 20%, typically for more severe presentations. While intravenous antibiotics may be perceived as beneficial in advanced cases, their efficacy remains uncertain, especially in milder disease, as existing studies have not shown a clear advantage.

    Cataract surgery was the most common procedure among the 94 eyes with endophthalmitis. Previous studies have identified posterior capsule rupture as a significant risk factor for post-cataract endophthalmitis.13,19–26 In our study, we were unable to calculate the true incidence of posterior capsule rupture; therefore, we could not analyze its relationship with endophthalmitis. Of the 94 cataract cases, 82 (87.2%) were uncomplicated and 12 (12.8%) were complicated. Final median VA was poorer in the complicated group (1.15 logMAR) compared to the uncomplicated group (0.40 logMAR), though this difference was not statistically significant.

    In our cohort, the median time from surgery to presentation in the chronic group was 730 days, which is longer than the typical duration of two to three months but remains plausible given that delayed-onset chronic endophthalmitis can present months to years after surgery. These indolent cases may remain subclinical for prolonged periods before eventually manifesting with signs of inflammation, as described in previous reports.27–29 The timing of endophthalmitis onset varied by procedure. Acute-onset cases were more common after cataract surgery, combined cataract procedures, and IVI, while delayed-onset cases occurred more frequently after glaucoma surgery or corneal transplantation. Our findings align with prior reports indicating that bleb-associated endophthalmitis occurs in 0.2% to 9.6% of glaucoma filtering surgeries, typically presenting more than one month postoperatively.30–32 Delayed-onset cases often have poor outcomes despite infection control and 22% requiring enucleation or evisceration.30,32

    Our study included 10 cases of delayed-onset post-keratoplasty endophthalmitis, with one requiring enucleation. The remaining cases had a median final VA of 3.0 logMAR, reflecting poor outcomes. Similarly, Tran et al reported unfavorable visual outcomes in patients with delayed-onset endophthalmitis following penetrating keratoplasty.33

    In this study, the spectrum of endophthalmitis isolates predominantly comprised gram-positive microorganisms, such as CoNS (Staphylococcus epidermidis), E. faecalis and Staphylococcus aureus. In culture-positive acute-onset cases, CoNS was the most common isolate (57.7%). This aligns with their known role as common skin and ocular surface flora, which may be introduced during intraocular procedures. Although consistent with prior studies,34–36 our data underscore the continued predominance of CoNS in postoperative endophthalmitis and highlight the need for meticulous perioperative aseptic precautions to minimize contamination risk.

    Delayed-onset postoperative endophthalmitis is typically caused by Propionibacterium spp., CoNS, and fungi.37–39 In the present study, CoNS remained the predominant microorganisms among cases of delayed-onset postoperative endophthalmitis (18.18% of culture-positive cases); our findings reinforce previous reports that CoNS constitute common pathogens in chronic cases of postoperative endophthalmitis. We also identified three cases each of S. aureus, E. faecalis, and fungal isolates. Notably, over half of delayed-onset culture-positive cases followed glaucoma surgery, with Streptococcus spp. being the most frequent, aligning with previous findings in bleb-associated infections.30 The prevalence of other bacterial species can vary in delayed-onset endophthalmitis, highlighting the importance of understanding the microbial profile to ensure effective treatment.

    All five cases of fungal postoperative endophthalmitis in our study presented with delayed onset. Two required enucleations, while the remaining eyes were salvaged but had poor final visual acuity. This aligns with prior reports that fungal endophthalmitis often results in poor visual outcomes.40 Aspergillus is known for its aggressive course and high risk of vision loss, whereas data on Penicillium and Rigidoporus remain limited. Current strategies involve PPV, intravitreal amphotericin (5–10 mg/0.1 mL) or voriconazole, and systemic antifungal therapy.41,42 Given the indolent nature of delayed-onset fungal infections, prolonged systemic treatment (6 weeks to 6 months) may be warranted to improve outcomes.42

    Importantly, clinical outcomes vary among bacterial species. P. aeruginosa infections were associated with the worst visual outcomes, as indicated by the absence of light perception in all three affected patients. Similarly, Lin et al43 reported dismal visual outcomes in cases of P. aeruginosa endophthalmitis, such that nearly all patients experienced final VA of counting fingers or worse; additionally, the rate of evisceration was high. In contrast, S. aureus and CoNS exhibited less virulence, resulting in better median final VA. These findings emphasize the importance of identifying specific microbial profiles to predict clinical outcomes and tailor treatment strategies.

    Retinal detachment (RD) was identified in a small proportion of eyes with postoperative endophthalmitis (4.9%), though underreporting may have contributed to this low rate. All culture-positive RD cases involved bacterial pathogens and had poor visual outcomes (median final VA: 2.3 logMAR). Zhang et al44 also reported worse prognosis and higher complication rates in eyes with RD. At our center, silicone oil is routinely used in eyes with concurrent RD for its antimicrobial and tamponade properties, which may help reduce RD recurrence. Other studies have shown that the risk of RD is reduced in eyes with adjuvant silicone oil implantation.45,46

    In this study, several factors were identified as significantly influencing visual outcomes in postoperative endophthalmitis. These factors included diabetes mellitus (OR=2.7), VA at initial presentation of 20/200 or worse (OR=35.9) and delayed-onset postoperative endophthalmitis (OR=3.9). Diabetic patients may be more susceptible to infection due to impaired neutrophil function and hyperglycemia-related immune dysfunction.47,48 An additional reported risk factor is renal disease.16 Despite the significant morbidity associated with infectious endophthalmitis, this study highlights the potential benefits for microbiological analysis and prompt, tailored antimicrobial and/or surgical interventions in improving visual outcomes, even in cases with poor initial VA.

    Conclusions

    Postoperative endophthalmitis most commonly followed cataract surgery. Coagulase-negative Staphylococcus species were the leading causative microorganisms in both acute- and delayed-onset cases. Immediate PPV with intravitreal injection was the most frequent treatment, yielding significant improvements in VA, with a median final VA of 20/200 and a globe salvage rate of 96.3%. Visual improvement was achieved in most cases, though factors such as diabetes mellitus, poor VA at initial presentation and delayed-onset endophthalmitis were significantly associated with worse outcomes. These findings underscore the importance of timely and appropriate management to optimize visual and anatomical outcomes.

    Abbreviations

    CI, confidence interval; CoNS, coagulase-negative Staphylococcus; ESCRS, European Society of Cataract and Refractive Surgeons; EVS, Endophthalmitis Vitrectomy Study; IQR, interquartile range; IVI, intravitreal injection; logMAR: logarithm of the minimum angle of resolution; OR, odd ratio; PPV, pars plana vitrectomy; RD, retinal detachment; RNA, ribonucleic acid; rRNA, ribosomal RNA; VA, visual acuity.

    Funding

    There is no funding to report.

    Disclosure

    The authors report no conflicts of interest in this work.

    References

    1. Kamalarajah S, Silvestri G, Sharma N, et al. Surveillance of endophthalmitis following cataract surgery in the UK. Eye. 2004;18(6):580–587. doi:10.1038/sj.eye.6700645

    2. Lundström M, Wejde G, Stenevi U, Thorburn W, Montan P. Endophthalmitis after cataract surgery: a nationwide prospective study evaluating incidence in relation to incision type and location. Ophthalmology. 2007;114(5):866–870. doi:10.1016/j.ophtha.2006.11.025

    3. Patwardhan A, Rao GP, Saha K, Craig EA. Incidence and outcomes evaluation of endophthalmitis management after phacoemulsification and 3-piece silicone intraocular lens implantation over 6 years in a single eye unit. J Cataract Refract Surg. 2006;32(6):1018–1021. doi:10.1016/j.jcrs.2006.02.034

    4. Sachdeva MM, Moshiri A, Leder HA, Scott AW. Endophthalmitis following intravitreal injection of anti-VEGF agents: long-term outcomes and the identification of unusual micro-organisms. J Ophthalmic Inflammation Infection. 2016;6:1–7. doi:10.1186/s12348-015-0069-5

    5. Barry P, Seal DV, Gettinby G, et al. ESCRS study of prophylaxis of postoperative endophthalmitis after cataract surgery: preliminary report of principal results from a European multicenter study. J Cataract Refract Surg. 2006;32(3):407–410. doi:10.1016/j.jcrs.2006.02.021

    6. Scott IU, Harry W, Flynn J, et al. Endophthalmitis after 25-gauge and 20-gauge pars plana vitrectomy: incidence and outcomes. Retina. 2008;28(1):138–142. doi:10.1097/IAE.0b013e31815e9313

    7. Johnson MW, Doft BH, Kelsey SF, et al. The endophthalmitis vitrectomy study: relationship between clinical presentation and microbiologic spectrum. Ophthalmology. 1997;104(2):261–272. doi:10.1016/S0161-6420(97)30326-1

    8. Varliero G, Lebre PH, Stevens MI, Czechowski P, Makhalanyane T, Cowan DA. The use of different 16S rRNA gene variable regions in biogeographical studies. Environ Microbio Rep. 2023;15(3):216–228. doi:10.1111/1758-2229.13145

    9. Pryce T, Palladino S, Kay I, Coombs G. Rapid identification of fungi by sequencing the ITS1 and ITS2 regions using an automated capillary electrophoresis system. Med Mycol. 2003;41(5):369–381. doi:10.1080/13693780310001600435

    10. Vitrectomy E. Results of the endophthalmitis vitrectomy study. Arch Ophthalmol. 1995;113:1479–1496.

    11. Choi JA, Chung SK. Postoperative endophthalmitis following cataract surgery in Asia. Int Scholarly Res Notices. 2011;2011(1):917265.

    12. Wong TY, Chee S-P. The epidemiology of acute endophthalmitis after cataract surgery in an Asian population. Ophthalmology. 2004;111(4):699–705. doi:10.1016/j.ophtha.2003.07.014

    13. Lalitha P, Rajagopalan J, Prakash K, Ramasamy K, Prajna NV, Srinivasan M. Postcataract endophthalmitis in South India: incidence and outcome. Ophthalmology. 2005;112(11):1884–1889. doi:10.1016/j.ophtha.2005.05.020

    14. Doft B, Nakamura T, Walonker A, Doft BH, Karenchak LM. Results of the endophthalmitis vitrectomy study: a randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Am J Ophthalmol. 1995;119:62–64. doi:10.1016/s0002-9394(14)73814-0

    15. Dib B, Morris RE, Oltmanns MH, Sapp MR, Glover JP, Kuhn F. Complete and early vitrectomy for endophthalmitis after cataract surgery: an alternative treatment paradigm. Clin Ophthalmol. 2020;Volume 14:1945–1954. doi:10.2147/OPTH.S253228

    16. Peng K-L, Kung Y-H, Tsai H-S, Wu -T-T. Treatment outcomes of acute postoperative infectious endophthalmitis. BMC Ophthalmology. 2021;21:1–9. doi:10.1186/s12886-021-02144-6

    17. Rahmani S, Eliott D. Postoperative endophthalmitis: a review of risk factors, prophylaxis, incidence, microbiology, treatment, and outcomes. Seminars Ophthalmol. 2017;33:1–7. doi:10.1080/08820538.2017.1353826

    18. Barry P, Cordovés L, Gardner S. ESCRS guidelines for prevention and treatment of endophthalmitis following cataract surgery: data, dilemmas and conclusions. Eur Soci Cataract Refractive Surg. 2013;1–44.

    19. Hatch WV, Cernat G, Wong D, Devenyi R, Bell CM. Risk factors for acute endophthalmitis after cataract surgery: a population-based study. Ophthalmology. 2009;116(3):425–430. doi:10.1016/j.ophtha.2008.09.039

    20. Ng JQ, Morlet N, Bulsara MK, Semmens JB. Reducing the risk for endophthalmitis after cataract surgery: population-based nested case-control study: endophthalmitis population study of Western Australia sixth report. J Cataract Refract Surg. 2007;33(2):269–280. doi:10.1016/j.jcrs.2006.10.067

    21. Wallin T, Parker J, Jin Y, Kefalopoulos G, Olson RJ. Cohort study of 27 cases of endophthalmitis at a single institution. J Cataract Refract Surg. 2005;31(4):735–741. doi:10.1016/j.jcrs.2004.10.057

    22. Wong T, Chee S. Risk factors of acute endophthalmitis after cataract extraction: a case-control study in Asian eyes. Br J Ophthalmol. 2004;88(1):29–31. doi:10.1136/bjo.88.1.29

    23. Mayer E, Cadman D, Ewings P, et al. A 10 year retrospective survey of cataract surgery and endophthalmitis in a single eye unit: injectable lenses lower the incidence of endophthalmitis. Br J Ophthalmol. 2003;87(7):867–869. doi:10.1136/bjo.87.7.867

    24. Norregaard JC, Thoning H, Bernth-Petersen P, Andersen TF, Javitt JC, Anderson GF. Risk of endophthalmitis after cataract extraction: results from the international cataract surgery outcomes study. Br J Ophthalmol. 1997;81(2):102–106. doi:10.1136/bjo.81.2.102

    25. Javitt JC, Vitale S, Canner JK, et al. National outcomes of cataract extraction: endophthalmitis following inpatient surgery. Arch Ophthalmol. 1991;109(8):1085–1089. doi:10.1001/archopht.1991.01080080045025

    26. Kamalarajah S, Ling R, Silvestri G, et al. Presumed infectious endophthalmitis following cataract surgery in the UK: a case–control study of risk factors. Eye. 2007;21(5):580–586. doi:10.1038/sj.eye.6702368

    27. Clark WL, Kaiser PK, Flynn HW Jr, Belfort A, Miller D, Meisler DM. Treatment strategies and visual acuity outcomes in chronic postoperative Propionibacterium acnes endophthalmitis. Ophthalmology. 1999;106(9):1665–1670. doi:10.1016/S0161-6420(99)90348-2

    28. Poon E, Poon A, McKelvie P, Levitz L, Zamir E. Delayed bacterial endotheliitis and endophthalmitis 11 years after cataract surgery. Case Rep Ophthalmol. 2023;14(1):376–381. doi:10.1159/000531501

    29. Lazzarini TA, Al-Khersan H, Patel NA, et al. Chronic, recurrent bacterial endophthalmitis caused by Achromobacter xylosoxidans: clinical features and management. Int Med Case Rep Jo. 2020;Volume 13:265–269. doi:10.2147/IMCRJ.S259899

    30. Kangas TA, Greenfield DS, Flynn JHW, Parrish IIRK, Palmberg P. Delayed-onset endophthalmitis associated with conjunctival filtering blebs. Ophthalmology. 1997;104(5):746–752. doi:10.1016/S0161-6420(97)30238-3

    31. Phillips WB, Wong TP, Bergren RL, Friedberg MA, Benson WE. Late onset endophthalmitis associated with filtering blebs. Slack Incorporated Thorofare. 1994;88–91.

    32. Song A, Scott IU, Flynn MHW, Budenz DL. Delayed-onset bleb-associated endophthalmitis: clinical features and visual acuity outcomes. Ophthalmology. 2002;109(5):985–991. doi:10.1016/S0161-6420(02)00965-X

    33. Tran KD, Yannuzzi NA, Si N, et al. Clinical features, antimicrobial susceptibilities, and treatment outcomes of patients with culture positive endophthalmitis after penetrating keratoplasty. Am J Ophthalmol Case Rep. 2018;9:62–67. doi:10.1016/j.ajoc.2018.01.011

    34. Gentile RC, Shukla S, Shah M, et al. Microbiological spectrum and antibiotic sensitivity in endophthalmitis: a 25-year review. Ophthalmology. 2014;121(8):1634–1642. doi:10.1016/j.ophtha.2014.02.001

    35. Benz MS, Scott IU, Flynn HW Jr, Unonius N, Miller D. Endophthalmitis isolates and antibiotic sensitivities: a 6-year review of culture-proven cases. Am J Ophthalmol. 2004;137(1):38–42. doi:10.1016/S0002-9394(03)00896-1

    36. Recchia FM, Busbee BG, Pearlman RB, Carvalho-Recchia CA, Ho AC. Changing trends in the microbiologic aspects of postcataract endophthalmitis. Archives of Ophthalmol. 2005;123(3):341–346. doi:10.1001/archopht.123.3.341

    37. Maalouf F, Abdulaal M, Hamam RN. Chronic postoperative endophthalmitis: a review of clinical characteristics, microbiology, treatment strategies, and outcomes. Int J Inf. 2012;2012:1–6. doi:10.1155/2012/313248

    38. Shirodkar AR, Pathengay A, Flynn HW Jr, et al. Delayed-versus acute-onset endophthalmitis after cataract surgery. Am J Ophthalmol. 2012;153(3):391–398.e2. doi:10.1016/j.ajo.2011.08.029

    39. Fox GM, Joondeph BC, Flynn HW, Pflugfelder SC, Roussel TJ. Delayed-onset pseudophakic endophthalmitis: reply. Am J Ophthalmol. 1991;111(5):656–657. doi:10.1016/S0002-9394(14)73723-7

    40. Narang S, Gupta A, Gupta V, et al. Fungal endophthalmitis following cataract surgery: clinical presentation, microbiological spectrum, and outcome. Am J Ophthalmol. 2001;132(5):609–617. doi:10.1016/S0002-9394(01)01180-1

    41. Weishaar PD, Flynn HW Jr, Murray TG, et al. Endogenous Aspergillus endophthalmitis: clinical features and treatment outcomes. Ophthalmology. 1998;105(1):57–65. doi:10.1016/S0161-6420(98)71225-3

    42. Chakrabarti A, Shivaprakash MR, Singh R, et al. Fungal endophthalmitis: fourteen years’ experience from a center in India. Retina. 2008;28(10):1400–1407. doi:10.1097/IAE.0b013e318185e943

    43. Lin J, Huang S, Liu M, Lin L, Gu J, Duan F. Endophthalmitis caused by pseudomonas aeruginosa: clinical characteristics, outcomes, and antibiotics sensitivities. Journal of Ophthalmol. 2022;2022:1–6. doi:10.1155/2022/1265556

    44. Zhang WF ZX, Meng LH, Chen H, Chen YX, Chen Y-X. Endophthalmitis at a tertiary referral center: characteristics and treatment outcomes over three decades. Front Cell Dev Biol. 2022;10:952375. doi:10.3389/fcell.2022.952375

    45. Nagpal M, Jain P, Nagpal K. Pars plana vitrectomy with or without silicone oil endotamponade in surgical management of endophthalmitis. Asia-Pac J Ophthalmol. 2012;1:216–221. doi:10.1097/APO.0b013e31826000cd

    46. Do T, Hon D, Aung T, Hien N, Cowan C. Bacterial endogenous endophthalmitis in Vietnam: a randomized controlled trial comparing vitrectomy with silicone oil versus vitrectomy alone. Clin Ophthalmol. 2014;8:1633–1640. doi:10.2147/OPTH.S67589

    47. Pozzilli P, Leslie RD. Infections and diabetes: mechanisms and prospects for prevention. Diabet Med. 1994;11(10):935–941. doi:10.1111/j.1464-5491.1994.tb00250.x

    48. Geerlings S, Hoepelman A. Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol med microbio. 2000;26:259–265. doi:10.1111/j.1574-695X.1999.tb01397.x

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  • A Machine learning Model Integrating Preoperative Blood-Based Indices

    A Machine learning Model Integrating Preoperative Blood-Based Indices

    Introduction

    Endometrial cancer (EC) is a common gynecologic malignancy affecting women’s health, its incidence rising in many countries over recent decades. According to the 2022 cancer statistics from the National Cancer Center of China, the incidence rate of EC stands at 6.84 per 100,000, with a mortality rate of 1.05 per 100,000.1 This increase is hypothesized to be associated with the increasing prevalence of obesity and changes in female reproductive patterns.2,3 EC develops through a multistep progression originating from normal or hyperplastic endometrium. Endometrial hyperplasia (EH), is histologically characterized by an abnormal increase in the gland-to-stroma ratio accompanied by architectural irregularities in glandular morphology, including variations in both shape and size. This pathological transformation is predominantly driven by prolonged exposure to unopposed estrogen stimulation.4 Clinical evidence indicates that untreated EH carries a significant risk of malignant transformation.5 The prognosis of EC is critically dependent on the disease stage at diagnosis. Although approximately 70% of early-stage EC cases are detected due to abnormal vaginal bleeding, nearly 30% of patients present with advanced-stage disease due to the asymptomatic, resulting in significantly poorer clinical outcomes.6,7 Consequently, early detection of EC is important for improving patient prognosis and survival rates.

    Recent studies have shown that both in the treatment and screening of EC, it is recommended to minimize damage for patients and non-invasive,8 but the absence of a simple, non-invasive screening protocol for EC represents a significant clinical challenge. While hysteroscopy and diagnostic curettage remain the most frequently utilized methods for evaluating endometrial lesions, these approaches are associated with several substantial limitations: invasive, procedural complexity and substantial healthcare costs. Furthermore, repeated applications of these techniques may increase the risk of lesion metastasis and induce intrauterine adhesions –that are particularly relevant for young, nulliparous women. Although fine-needle aspiration offers a minimally invasive method, its diagnostic reliability is compromised, which typically evaluates less than 50% of the uterine cavity. Transvaginal ultrasound (TVUS) remains the first-line imaging modality for evaluating endometrial abnormalities, offering high sensitivity for detecting hyperplasia or polyps. However, its specificity for differentiating benign lesions from early-stage malignancies remains suboptimal. Magnetic resonance imaging (MRI), while superior in assessing myometrial invasion and tumor staging, is cost-prohibitive for routine screening. These limitations underscore the need for complementary non-invasive tools to refine preoperative risk stratification.9 Previous studies has identified several biomarkers associated with EC clinical features and prognosis;7,10,11 however, their diagnostic performance remains suboptimal when used in isolation. These diagnostic limitations present substantial challenges in differentiating between endometrial hyperplasia (EH) and early-stage EC. In densely populated nations such as China, there is an urgent need to develop robust, quantitative and cost-efficient predictive models for EC. Such advancements could facilitate timely intervention, and ultimately improve patient outcomes through personalized risk stratification.

    Uncontrolled inflammation plays a pivotal role in both the initiation and progression of tumors, with the inflammatory state often reflected in alterations of serum inflammatory markers.12 Beyond traditional markers such as white blood cells, lymphocytes, and platelets, emerging indices including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), as well as the more recently developed systemic immune-inflammation index (SII)13 and systemic inflammatory response index (SIRI)14 have been recognized as valuable indicators of systemic inflammatory response.15 These peripheral blood-based markers have demonstrated significant roles in systemic inflammation and cancer biology, encompassing cancer prediction, progression, and survival prognosis.16–20 While these biomarkers have been studied as prognostic indicators in EC,17 their potential utility in the diagnosis and prediction of EC remains underexplored.

    Machine Learning (ML) algorithms have increasingly been integrated into the medical field for disease prediction, offering significant advantages over traditional statistical methods. ML algorithm is capable of processing large and complex datasets, identifying implicit relationships among various relevant features, and thereby enabling more accurate disease risk prediction.21 The current landscape of EC risk assessment reveals a paucity of robust predictive models that base on real-world data. Our objective is to develop a non-invasive preoperative tool utilizing peripheral blood indices and ultrasound to predict EC risk, reduce the need for the invasive diagnostic interventions.

    Materials and Methods

    Study Participants

    The study included women treated at the Third Affiliated Hospital of SYSU between January 2014 to August 2024, who were diagnosed by histopathology.

    Inclusion Criteria:

    1. Patients diagnosed with EH or EC confirmed by diagnostic curettage or surgical pathology.

    2. Patients with complete clinical information and data.

    Exclusion Criteria:

    1. Patients with severe dysfunction of the heart, liver, kidney, or other major organs.

    2. Patients with other malignant tumors or conditions affecting serum tumor marker and inflammatory marker levels.

    3. Patients without complete blood cell count data available one week prior to surgery.

    4. Patients with a history of fertility-preserving treatment for EC who were receiving hormone therapy.

    Data Collection

    Feature selection was guided by evidence-based approach: (1) established clinical relevance (eg, age, BMI, and menopausal status as known EC risk factors); (2) systematic review of biomarkers implicated in EC (eg, HE4, CA-125); and (3) relevant frontier guidelines research and literature (eg, NLR).

    The clinical pathological data of patients were obtained through the hospital electronic medical record database:

    1. Basic information: including age, height, weight, comorbidities, etc.; Body mass index (BMI) is calculated as the patient’s weight (kg) divided by the square of the height (m).

    2. Preoperative serum examinations including WBC, neutrophil count, lymphocyte count, monocyte count, platelet count;

    3. Preoperative tumor markers including Serum carbohydrate antigen 125 (CA-125) and human epididymis protein 4(HE4).

    Neutrophil-to-lymphocyte ratio (NLR) is calculated as: neutrophil count/lymphocyte count; Monocyte-to-lymphocyte ratio (MLR) is calculated as: monocyte count/lymphocyte count; Platelet-to-lymphocyte ratio (PLR) is calculated as: platelet count/lymphocyte count; Systemic immune-inflammation index (SII) is calculated as: platelet count × neutrophil count/lymphocyte count; Systemic inflammatory response index (SIRI) is calculated as: neutrophil count × monocyte count/lymphocyte count.

    Pre-Processing and Model Development, Evaluation

    To mitigate the issue of class imbalance between two groups, we implemented a comprehensive data preprocessing strategy combining the Synthetic Minority Oversampling Technique (SMOTE) with random under sampling. Subsequently, all features were standardized using Standard Scaler to prevent potential bias from features with larger numerical ranges.

    The dataset was strategically partitioned through random stratified sampling into a training set (80%, n = 686) and a validation set (20%, n = 171). The training set was exclusively used for model development, while the validation set served as an independent cohort for performance evaluation. Six machine learning algorithms including Random Forest (RF), Extreme Gradient Boosting (XGBoost), Support Vector Mac (SVM), Gradient Boosting Machine Model (GBDT), Logistic Regression (LR) and Multilayer Perceptron (MLP) were used to construct the prediction model of EC. Among them, the RF classifier is a popular machine learning algorithm implemented in the Python package RF. The RF classification algorithm can be run without tuning the parameters and can give an approximate estimate of the importance of the features. Boosting refers to the use of a series of linear combinations of models to complete model tasks. It includes gradient boosting, there is a technique called GBDT. MLP is one of the simplest artificial neural networks, which consists of three layers—an input layer, an output layer, and a hidden layer.22 LR is a member of the general linear model family.23 Model performance was comprehensively evaluated using multiple metrics, with particular emphasis on the area under the receiver operating characteristic curve (AUC)as the primary indicator of discriminative ability. Brier score is a measure of the degree of deviation between the predicted and actual results, with lower values indicating better alignment between predicted probabilities and actual outcomes. Sensitivity and specificity were analyzed as complementary performance measures.

    To elucidate feature contributions, SHapley Additive exPlanations (SHAP) values were employed to quantify and interpret feature importance in the best predictive performance model. The algorithm provides a measure of feature importance across the model.

    Statistics

    The Shapiro–Wilk normality test was performed to assess the data normality. Continuous variables are reported as mean (SD) or medians with interquartile ranges (IQRs) for skewed distributed variables and were compared using an unpaired, Mann–Whitney U-test. Categorical variables are reported as whole numbers and proportions (n [%]) and were compared using the χ2 test. Statistical significance was defined as a p-value <0.05. The strength of associations among modeling variables was assessed using Spearman correlation analysis.

    All statistical analyses were performed using IBM SPSS Statistics 22 (SPSS Inc., Chicago, IL, USA). The predictive model construction and graphical representations were implemented using Python V3.7 (Python Software Foundation) and Prism 10.0 (GraphPad Software, San Diego, CA, USA), respectively.

    Ethics

    The study reporting adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines and has obtained informed consent from all participants. This study was approved by the ethics committee of the Third Affiliated Hospital of Sun Yat-sen University (No. II2023-008-02). Our research strictly adheres to the principles of the Declaration of Helsinki.

    Results

    A retrospective cohort of 948 patients diagnosed with endometrial lesions was identified from the electronic medical records of the Third Affiliated Hospital of Sun Yat-sen University between January 1, 2014 and August 31, 2024.According to the inclusion and exclusion criteria,857 patients were included in the final analysis (Figure 1).

    Figure 1 Flowchart of the study population.

    Characteristics of the Participants

    The study cohort included 857 patients, stratified into two groups based on histopathological diagnosis: 208 patients in EH group and 649 patients in EC group (Table 1). Demographic analysis revealed significant between-group differences in median age (EH group: 46 years [IQR 41.3–50] vs EC group: 53 years [IQR 47–59]; p<0.001). Furthermore, statistically significant differences were observed in menopausal status, hypertension, diabetes mellitus and endometrial thickness between the two groups. Among EC patients: Stage I (n=524, 80.7%), Stage II (n=44, 6.8%), Stage III (n=68, 10.5%), and Stage IV (n=13, 2.0%).

    Table 1 Baseline Characteristics and Serum Inflammatory Markers of the Participants

    Performed Spearman’s rank correlation analysis to quantify the strength of associations among these differential variables, with the results visualized in a heatmap (Figure 2). These variables may play important roles in cancer pathogenesis and progression.

    Figure 2 The overall correlation between parameters in EC patients.

    Construction and Evaluation of Prediction Model

    The predictive performance of these selected features was evaluated using six ML model: Random Forest (RF), Extreme Gradient Boosting (XGBoost), Support Vector Machine (SVM), Gradient Boosting Decision Tree (GBDT), Logistic Regression (LR), and Multilayer Perceptron (MLP). As detailed in Table 2, the GBDT model demonstrated superior discriminative performance, achieving an AUC of 0.95 (95% CI: 0.93–0.97), with specificity of 0.90, and F1-score of 0.90. Subsequent validation in an independent cohort confirmed the model’s performance. With the lowest integrated Brier score (0.06), the GBDT model demonstrated significant advantages in predicting EC compared to other models. The ROC curves for all six models are presented in Figure 3A and B, providing a comprehensive comparison of their predictive capabilities across different models.

    Table 2 Predictive Performances of the Six ML Models for EC

    Figure 3 Receiver operating characteristic curves for the 6 machine learning models. (A). Comparison of area under the curve. (B). Receiver operating characteristic curves.

    Importance of Features Interpreted by SHAP Value

    To elucidate feature contributions and interpret model predictions, we implemented SHAP analysis, a robust game-theoretic approach that quantifies the relative importance of each predictive feature (Figure 4A and B). The higher the SHAP value of a feature, the higher your log odds of risk. Red to blue represents the eigenvalue from large to small. The thickness of the line represents the sample distribution. In the optimal performing GBDT model, the top three predictive features for EC identification were HE4 (0.03), CA-125 (0.02) and SIRI (0.02).

    Figure 4 SHAP interpretation of the GBDT model. (A). Importance score ranking of the model prediction characteristics. (B). Every feature’s impact on the model’s output.

    Discussion

    This study represents an advancement in EC prediction by developing and validating a machine learning (ML) model that integrates baseline characteristics with non-invasive biomarkers. Among six ML models, the GBDT model demonstrated superior predictive performance, achieving an AUC of 0.95, Brier score of 0.06. SHAP interpretability analysis identified HE4, CA-125 and SIRI as key contributors to the model’s predictions. These findings provide a novel technical pathway for EC risk prediction.

    EC has emerged as the most prevalent gynecological malignancy globally, surpassing cervical cancer in disease burden. Late-stage diagnosis is associated with poor clinical outcomes. Among gynecologic tumors, cervical and ovarian cancers can be screened early and non-invasively. The significant reduction in cervical cancer incidence and mortality rates has been largely attributed to the implementation of population-based screening programs and the development of robust risk-prediction algorithms.,24,25 EC lacks effective early detection tools. Early identification and management of high-risk precancerous lesions remain the most cost-effective strategy for reducing cancer-related morbidity and mortality.

    The management of EH, particularly atypical hyperplasia, presents significant clinical challenges. That may progressively evolve into EC if left undetected or untreated. While current clinical guidelines recommend periodic endometrial surveillance via diagnostic curettage or hysteroscopic sampling,26,27 these invasive procedures carry inherent risks of iatrogenic endometrial damage, including irreversible basal layer injury and intrauterine adhesions—complications particularly detrimental to young patients with fertility preservation requirements. Therefore, developing cost-effective, non-invasive methods for EC prediction is crucial for improving risk stratification and guiding conservative management strategies.

    In the non-invasive screening of tumors, tumor markers have emerged as pivotal tools for the early detection of malignancies. While tumor markers like HE4 and CA125 have been evaluated for EC detection,28 our study revealed significant limitations: 72% of EC patients showed CA125 levels below the diagnostic threshold, and 67% had subthreshold HE4 levels, despite significant. These results align with multicenter studies,29,30 emphasizing the insufficiency of single-marker strategies. Using ultrasound alone for prediction also has the problem of low sensitivity.31

    The intricate relationship between inflammation and cancer, initially posited by Virchow in 1863,32 extensive research has elucidated the role of inflammatory cells and cytokines in tumorigenesis and progression. These inflammatory cells are implicated in tumor growth, progression, and metastasis.33 Among inflammatory cells, leukocytes constitute the largest group, with neutrophils contributing to tumor progression through the release of tumor necrosis factor, interleukin-1, and interleukin-6.34 Lymphocytes and Monocytes play a crucial role in tumor-specific immune responses by inducing cytotoxic cell death and inhibiting tumor cell proliferation and migration.35 Platelets influence the metastatic potential of cancer cells via multiple biological pathways.36 A single blood parameter as a marker may not adequately reflect the inflammatory state, composite markers such as NLR, PLR, MLR, SII and SIRI can sometimes provide more information. Markers derived from peripheral blood serum can provide predictive information when evaluated preoperatively, and their analysis is cost-effective and readily accessible.

    Machine learning models have gained significant traction in disease prediction due to their ability to handle complex datasets and uncover intricate patterns. The field of EC detection lacks validated machine learning-based prediction models utilizing real-world clinical data, which is essential to improve the screening and diagnostic precision for EC. Previous studies, such as those by Li, Vetter and Su et al,37–39 utilized traditional statistical logistic regression methods to construct prediction models in postmenopausal populations. Qiu et al40 employed genetic data for predictive modeling, which is less feasible for widespread clinical application. While Erdemoglu et al41 used the artificial intelligence in EC prediction, their model’s performance was suboptimal (F1 score: 0.59), potentially due to only demographic data and ultrasonic endometrial thickness were used for modeling. Our investigation addresses these critical limitations through a comprehensive approach that: (1) including pre- and post-menopausal populations; (2) employs advanced machine learning algorithms to identify complex, nonlinear interactions among multidimensional clinical features; and (3) using clinical data and blood markers thereby enhancing model generalizability. Unlike previous studies that predominantly focused on single-type indicators, our research combines demographic characteristics (age, menopausal status, hypertension, etc), imaging metrics (endometrial thickness), tumor markers (CA-125, HE4), and inflammatory markers (PLR, SIRI, etc) to construct a highly discriminative prediction model. Among the six ML models developed, the GBDT demonstrated the highest predictive performance, with an AUC of 0.95, outperforming the other five models.

    To improve the interpretability and intuitiveness of the ML approach, we applied SHAP values to the model, facilitating a better understanding of the impact of key features. SHAP values are widely recognized in ML, particularly in medical applications, for their ability to quantify the contribution of each feature to the model’s output. SHAP decision plots provide clinicians with an intuitive grasp of the results. Our analysis revealed that HE4, CA-125 and SIRI are the primary influencing factors of EC.

    During the clinical application process, the data characteristics of patients are collected and input into the model for risk prediction, when patients are identified as high-risk for EC, timely invasive procedures such as hysteroscopy and curettage can be performed to confirm the diagnosis and facilitate referral to gynecologic oncologists. Conversely, for patients deemed low-risk, non-invasive screening and predictive methods can be employed for regular monitoring.

    Strengths and Limitations

    Our study has demonstrated a satisfactory predictive capability of the model, indicating that the GBDT model could be utilized in the future to assess the risk of EC, offering a non-invasive approach particularly suitable for the long-term follow-up of younger patients. Secondly, the findings of this study can be applied in clinical settings, assisting physicians in managing patients with endometrial lesions more effectively, especially in resource-limited environments.

    However, our study has several limitations. Firstly, the research was conducted in China, with participant selection primarily based on the local population. Consequently, extrapolating these results to a global population may introduce potential biases.42 Secondly, the retrospective single-center design may inherently introduce selection bias,43 and healthy patients were not included in the development of the current model, which limits the generalization of the model to asymptomatic women. Fortunately, compared to previously published studies, our sample size is relatively large.38,39 Future research should involve multicenter, large-sample, prospective studies to further optimize the model.

    Conclusion

    This study establishes a GBDT model integrating preoperative blood-based indices and endometrial thickness achieves high accuracy in predicting endometrial cancer risk. The SHAP- analysis identified three principal determinants: HE4, CA-125, and SIRI, aligning with their established roles in oncogenesis and inflammation. This non-invasive tool holds promise for preoperative risk stratification, particularly in reducing unnecessary invasive procedures. Future prospective studies are warranted to confirm its generalizability in asymptomatic populations and diverse clinical settings.

    Data Sharing Statement

    The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

    Disclosure

    The authors report no conflicts of interest in this work.

    References

    1. Xia C, Dong X, Li H, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J. 2022;135:584–590.

    2. Ninimiya SY, Ansu-Mensah M, Bawontuo V, Kuupiel D. Mapping evidence on ovarian, endometrial, vaginal, and vulva cancer research in Africa: a scoping review protocol. Syst Rev. 2021;10:108. doi:10.1186/s13643-021-01654-0

    3. Raglan O, Kalliala I, Markozannes G, et al. Risk factors for endometrial cancer: an umbrella review of the literature. Int, J, Cancer. 2019;145:1719–1730. doi:10.1002/ijc.31961

    4. Barakat A, Ismail A, Chattopadhyay S, Davies Q. Endometrial cancer incidence in patients with atypical endometrial hyperplasia according to mode of management. Cancer Diagn Progn. 2022;2(5):564–568. doi:10.21873/cdp.10143

    5. Ring KL, Mills AM, Modesitt SC. Endometrial hyperplasia. Obstet Gynecol. 2022;140:1061–1075. doi:10.1097/AOG.0000000000004989

    6. Bell DW, Ellenson LH. Molecular genetics of endometrial carcinoma. Annu Rev Pathol. 2019;14:339–367. doi:10.1146/annurev-pathol-020117-043609

    7. Brooks RA, Fleming GF, Lastra RR, et al. Current recommendations and recent progress in endometrial cancer. CA Cancer J Clin. 2019;69:258–279. doi:10.3322/caac.21561

    8. Bogani G, Di Donato V, Papadia A, et al. Evaluating long-term outcomes of three approaches to retroperitoneal staging in endometrial cancer. Gynecol Oncol. 2022;166:277–283. doi:10.1016/j.ygyno.2022.06.007

    9. Braun MM. Diagnosis and management of endometrial cancer. Endometrial Cancer. 2016;93:468–474.

    10. Espiau Romera A, Cuesta Guardiola T, Benito Vielba M, De Bonrostro Torralba C, Coronado Martín PJ, Baquedano Mainar L HE4 tumor marker as a predictive factor for lymphatic metastasis in endometrial cancer. Int J Gynaecol Obstet. 2020;149(3):265–268. doi:10.1002/ijgo.13140

    11. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–249. doi:10.3322/caac.21660

    12. Arneth B. Tumor microenvironment. Med Kaunas Lith. 2019;56:15.

    13. Zhang Y, Chen B, Wang L, Wang R, Yang X. Systemic immune-inflammation index is a promising noninvasive marker to predict survival of lung cancer: a meta-analysis. Medicine. 2019;98:e13788. doi:10.1097/MD.0000000000013788

    14. Wang L, Zhou Y, Xia S, et al. Prognostic value of the systemic inflammation response index (SIRI) before and after surgery in operable breast cancer patients. Cancer Biomark Sect Dis Markers. 2020;28:537–547. doi:10.3233/CBM-201682

    15. Zhong J-H, Huang D-H, Chen Z-Y. Prognostic role of systemic immune-inflammation index in solid tumors: a systematic review and meta-analysis. Oncotarget. 2017;8:75381–75388. doi:10.18632/oncotarget.18856

    16. Zheng L, Zou K, Yang C, et al. Inflammation-based indexes and clinicopathologic features are strong predictive values of preoperative circulating tumor cell detection in gastric cancer patients. Clin Transl Oncol. 2017;19:1125–1132. doi:10.1007/s12094-017-1649-7

    17. Song H, Jeong MJ, Cha J, et al. Preoperative neutrophil-to-lymphocyte, platelet-to-lymphocyte and monocyte-to-lymphocyte ratio as a prognostic factor in non-endometrioid endometrial cancer. Int J Med Sci. 2021;18:3712–3717. doi:10.7150/ijms.64658

    18. Takahashi R, Mabuchi S, Kawano M, et al. Prognostic significance of systemic neutrophil and leukocyte alterations in surgically treated endometrial cancer patients: a monoinstitutional study. Gynecol Oncol. 2015;137:112–118. doi:10.1016/j.ygyno.2015.02.006

    19. Cong R, Kong F, Ma J, et al. Combination of preoperative neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and monocyte-lymphocyte ratio: a superior prognostic factor of endometrial cancer. BMC Cancer. 2020;20(1):464. doi:10.1186/s12885-020-06953-8

    20. Xu M, Wu Q, Cai L, et al. Systemic inflammatory score predicts overall survival in patients with cervical cancer. J Cancer. 2021;12:3671–3677. doi:10.7150/jca.56170

    21. Rajula HSR, Verlato G, Manchia M, Antonucci N, Fanos V. Comparison of conventional statistical methods with machine learning in medicine: diagnosis, drug development, and treatment. Med Kaunas Lith. 2020;56:455.

    22. Etemad L, Wu T-H, Heiner P, et al. Machine learning from clinical data sets of a contemporary decision for orthodontic tooth extraction. Orthod Craniofac Res. 2021;24:193–200. doi:10.1111/ocr.12502

    23. Montolío A, Martín-Gallego A, Cegoñino J, et al. Machine learning in diagnosis and disability prediction of multiple sclerosis using optical coherence tomography. Comput Biol Med. 2021;133:104416. doi:10.1016/j.compbiomed.2021.104416

    24. Bumrungthai S, Ekalaksananan T, Kleebkaow P, et al. Mathematical modelling of cervical precancerous lesion grade risk scores: linear regression analysis of cellular protein biomarkers and human papillomavirus E6/E7 RNA staining patterns. Diagnostics. 2023;13:1084. doi:10.3390/diagnostics13061084

    25. Tisler A, Võrk A, Tammemägi M, et al. Nationwide study on development and validation of a risk prediction model for CIN3+ and cervical cancer in Estonia. Sci Rep. 2024;14:24589. doi:10.1038/s41598-024-75697-3

    26. Concin N, Matias-Guiu X, Vergote I, et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int J Gynecol Cancer. 2021;31:12–39. doi:10.1136/ijgc-2020-002230

    27. Yang B, Xu Y, Zhu Q, et al. Treatment efficiency of comprehensive hysteroscopic evaluation and lesion resection combined with progestin therapy in young women with endometrial atypical hyperplasia and endometrial cancer. Gynecol Oncol. 2019;153:55–62. doi:10.1016/j.ygyno.2019.01.014

    28. Liu J, Han L, Sun Q, Li Y, Niyazi M. Meta-analysis of the diagnostic accuracy of HE4 for endometrial carcinoma. Eur J Obstet Gynecol Reprod Biol. 2020;252:404–411. doi:10.1016/j.ejogrb.2020.07.015

    29. Ginath S, Menczer J, Fintsi Y, et al. Tissue and serum CA125 expression in endometrial cancer. Int J Gynecol Cancer off J Int Gynecol Cancer Soc. 2002;12:372–375. doi:10.1136/ijgc-00009577-200207000-00007

    30. Dotters DJ. Preoperative CA 125 in endometrial cancer: is it useful? Am J Obstet Gynecol. 2000;182:1328–1334. doi:10.1067/mob.2000.106251

    31. Opolskiene G, Sladkevicius P, Valentin L. Prediction of endometrial malignancy in women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm. Ultrasound Obstet Gynecol. 2011;37(2):232–240. doi:10.1002/uog.8871

    32. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow?. Lancet. 2001;357(9255):539–45 doi:10.1016/S0140-6736(00)04046-0

    33. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140:883–899. doi:10.1016/j.cell.2010.01.025

    34. Cupp MA, Cariolou M, Tzoulaki I, Aune D, Evangelou E, Berlanga-Taylor AJ. Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies. BMC Med. 2020;18(1):360. doi:10.1186/s12916-020-01817-1

    35. Patel A, Ravaud A, Motzer RJ, et al. Neutrophil-to-lymphocyte ratio as a prognostic factor of disease-free survival in postnephrectomy high-risk locoregional renal cell carcinoma: analysis of the S-TRAC trial. Clin Cancer Res. 2020;26:4863–4868. doi:10.1158/1078-0432.CCR-20-0704

    36. Song M, Graubard BI, Rabkin CS, Engels EA. Neutrophil-to-lymphocyte ratio and mortality in the United States general population. Sci Rep. 2021;11:464. doi:10.1038/s41598-020-79431-7

    37. Vetter MH, Smith B, Benedict J, et al. Preoperative predictors of endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia or complex atypical hyperplasia. Am J Obstet Gynecol. 2020;222(1):e60.1–e60.7. doi:10.1016/j.ajog.2019.08.002

    38. Su J, She L, Fan Y, et al. Model predicting the risk of endometrial hyperplasia developing into endometrial cancer. J Inflamm Res. 2024:6159–6171—.

    39. Li X, Wang H, Wang T, et al. Combining demographic data and transvaginal ultrasonography: a predictive model for endometrial carcinoma in postmenopausal patients. BMC Women’s Health. 2024;24(1):539. doi:10.1186/s12905-024-03374-8

    40. Sang Q, Yang L, Zhao H, et al. Risk prediction model of uterine corpus endometrial carcinoma based on immune-related genes. BMC Women’s Health. 2024;24(1):429. doi:10.1186/s12905-024-03237-2

    41. Erdemoglu E. Artificial intelligence for prediction of endometrial intraepithelial neoplasia and endometrial cancer risks in pre- and postmenopausal women. AJOG Glob Rep. 2023;3:100154.doi: 10.1016/j.xagr.2022.100154

    42. Shi Y, Zhang G, Ma C, et al. Machine learning algorithms to predict intraoperative hemorrhage in surgical patients: a modeling study of real-world data in shanghai, China. BMC Med Inf Decis Mak. 2023;23:156. doi:10.1186/s12911-023-02253-w

    43. de Ron J, Fried EI, Epskamp S. Psychological networks in clinical populations: investigating the consequences of berkson’s bias. Psychol Med. 2021;51:168–176. doi:10.1017/S0033291719003209

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  • Dame Stephanie ‘Steve’ Shirley, technology pioneer, dies aged 91

    Dame Stephanie ‘Steve’ Shirley, technology pioneer, dies aged 91

    BBC Dame Stephanie Shirley poses infront of the sea in a white suit covered in drawings of children and a Star of David necklace at the unveiling of a memorial to Kindertransport on the quayside at Harwich in 2022BBC

    To many women in tech, myself included, Dame Stephanie Shirley was inspirational.

    Her pioneering and controversial decision to hire exclusively women coders and data inputters, working from home, was way ahead of its time and changed many lives.

    She had a difficult life, and it made her tough.

    She was stoic about grief and showed – publicly at least – extraordinary strength in the face of a number of traumatic experiences.

    She was from a generation whose childhoods were shaped by the atrocities of World War 2.

    She died on 9 August aged 91, her family said in an Instagram post on Monday.

    AFP via Getty Images Dame Stephanie Shirley wearing a purple hat, matching purple dress, and a pearl necklace, smiles at the camera while holding a medal outside Buckingham Palace after she was made a member of the Order of the Companions of Honour AFP via Getty Images

    Born Vera Buchthal in the German city of Dortmund in 1933, Dame Stephanie’s Jewish father was a judge.

    He had hoped that being in a position of power would protect his family, but as the Nazi government increased its persecution of German Jews, they fled to the Austrian capital Vienna.

    She was one of thousands of Jewish children fleeing the Nazis and came to Britain aged five as part of the Kindertransport – a British rescue effort in the months preceding World War 2 which brought 10,000 children to the UK – where she was brought up by loving foster parents.

    She went on to become a computer industry and women’s rights pioneer in the 1950s and 1960s.

    She founded the software company Freelance Programmers, which shook up the tech industry by almost exclusively hiring women, and in later life donated almost £70m to help those with autism and to IT projects.

    She was very smart and truly formidable, even adopting the name “Steve” to help her in a male-dominated tech world.

    Dame Stephanie Shirley In a black and white photograph a young Dame Stephanie is pictured to the left of her parents and sister wearing a pale dress while her family also pose with neutral expressions in smart clothesDame Stephanie Shirley

    Dame Stephanie (left) and her sister, pictured with their German father and Austrian mother, who put them on a Kindertransport train to escape Nazi-occupied Austria

    Dame Stephanie was determined not to be defined by her traumatic childhood.

    After starting out as a scientific civil servant, in 1962 she founded Freelance Programmers – later known as FI Group, later still Xansa – something which was almost unheard of for a woman to do in the 1960s.

    She designed the company to provide jobs for women with children.

    It changed the landscape for women working in technology by offering flexible working practices.

    Of the first 300 staff, 297 were female.

    The success of the company left Dame Stephanie with a fortune of about £150m, most of which she donated to good causes.

    Her late son Giles was autistic and she was an early member of the National Autistic Society, with her charity the Shirley Foundation funding many projects particularly related to autism.

    She founded Autism at Kingwood, a service which now supports autistic adults in Berkshire, Oxfordshire and Buckinghamshire.

    She also helped set up Prior’s Court – a school for autistic young people in Thatcham, Berkshire.

    Dame Stephanie Shirley Dame Stephanie is pictured in a black and white photograph looking down and wearing a shirt and blazer with technological equipment in the backgroundDame Stephanie Shirley

    Dame Stephanie was at the forefront of UK computing advances

    “Steve was an absolute legend, and an incredible friend and role model for me over the last 30 years,” Professor Sue Black told the BBC.

    “Before the likes of Steve Jobs and Mark Zuckerberg, Steve Shirley was innovating and solving problems with tech in the UK.”

    And Dame Wendy Hall, one of the world’s leading computer scientists said Dame Shirley was “inspirational”.

    “She was my mentor and my friend and she will be hugely missed,” she said.

    “She did so much for the computer science community to encourage women into that community, and of course, for the world of autism.”

    The last time I saw her, I introduced her at an event on stage. She was frail, but as always extremely glamorous and totally captivating.

    She said she knew she was coming to the end of her life and she reflected candidly on what she felt she had learned.

    She had a strong moral compass and believed in using her wealth for good. And she never stopped standing up to sexism.

    She spent her whole life refusing to conform to society’s many gender stereotypes and clichés.

    Much time has passed since Dame Stephanie started signing letters as Steve in order to get the attention of the male business contacts she was messaging.

    But Tech continues to be a male dominated industry and women still have to shout loud to be heard.

    Steve was one of the first, and she shouted the loudest.

    Additional reporting by Charlotte Edwards

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  • Impulse Space selected by NASA to deliver orbital transfer vehicle studies – Engineering.com

    1. Impulse Space selected by NASA to deliver orbital transfer vehicle studies  Engineering.com
    2. NASA Selects Six Companies to Provide Orbital Transfer Vehicle Studies  Universe Today
    3. NASA Awards OTV Study Contracts to Firefly, Rocket Lab, and Others  Via Satellite
    4. Blue Origin and five other companies study how orbital transfer vehicles can aid NASA  GeekWire
    5. NASA Selects Blue Origin of Merritt Island Among Six Companies to Provide Orbital Transfer Vehicle Studies  Space Coast Daily

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  • Amazfit on track with latest flagship wearable, Balance 2

    Amazfit on track with latest flagship wearable, Balance 2

    Amidst a competitive summer of athletics, Amazfit‘s latest flagship wearable, the Balance 2, is endeavouring to support elite athletic performance from training through recovery.

    Gabby Thomas, an established Amazfit partner and the most decorated US track and field athlete of the 2024 Paris Olympics, is among several elite athletes leveraging a number of Amazfit track-specific features – alongside athletes such as Morgan Pearson and Yeman Crippa.

    The Amazfit Balance 2 includes Track Run Mode, which delivers real-time performance metrics – from VO₂ Max to stride cadence – to analyse aerobic and anaerobic effort throughout a session. With the updated technology, runners can choose which data to monitor, customising each session to their specific needs. This data includes post-training and recovery insights such as ATL, CTL, HRV, and mental and physical fatigue.

    Leveraging Amazfit’s BioTracker technology, the device also captures advanced biometric data and parameters, using what the brand cites as the latest generation biometric sensor. Available data includes cadence, stride, running power – all seen as vital for sprinters and long-distance runners aiming to optimize efficiency and speed.

    Post-session insights via the Zepp App provide an overview of athletic performance, including training load, training effect, recovery time, and detailed performance charts.

    www.amazfit.com

     

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  • Scientists may have discovered a new mineral on Mars

    Scientists may have discovered a new mineral on Mars

    Researchers have pinpointed a previously unknown mineral on Mars, indicating the red planet’s surface may be more actively changing than previously believed.  While scientists have a solid understanding of Mars’ surface appearance, uncovering its precise composition remains a challenge.

    Recently, a team of researchers believes they have identified a completely new mineral, derived from an unusual layer of iron sulfate exhibiting a distinctive spectral signature. In a paper published on August 5 in Nature Communications, astrobiologists led by Janice Bishop from the SETI Institute detailed the detection of an uncommon ferric hydroxysulfate mineral near Valles Marineris, a colossal canyon that runs along Mars’ equator. The region, thought to have once hosted flowing water, could hold vital clues about the natural forces that shaped the planet’s surface and whether microbes once inhabited Mars.

    Sulfur, a common element on both Mars and Earth, frequently bonds with other elements to create sulfate minerals. These sulfates dissolve readily in water, but because Mars has been dry for so long, these minerals likely remained on the surface since the planet lost its liquid water. Examining these minerals can reveal crucial insights into Mars’ early environmental conditions.

    The research team focused on sulfate-rich zones near Valles Marineris, targeting areas that displayed unusual spectral signals from orbit, as well as layered sulfate deposits and notable geological features, Bishop explained in a statement.

    In one region, they discovered layered deposits of polyhydrated sulfates, beneath which lay monohydrated and ferric hydroxysulfates.

    Laboratory experiments showed that the ferric hydroxysulfate observed on Mars could only have formed in the presence of oxygen, with the formation process releasing water. These conditions also suggest it formed at high temperatures, pointing to volcanic activity as a likely source. The mineral’s unique structure and thermal properties indicate it may be entirely new to science.

    Bishop explained that the material we produced in the lab seems to be a new mineral due to its unique crystal structure and thermal stability. However, we must find this mineral on Earth first before we can officially recognize it as a new mineral species.

    This is not the first time researchers have potentially discovered new minerals on Mars. Back in March 2025, Roger Wiens, a Mars exploration expert and a professor of earth, atmospheric, and planetary sciences at Purdue University in Indiana, directed NASA’s Perseverance rover to target some unusually pale rocks on the Martian surface with its laser. He and his team found that these rocks contain unusually high levels of aluminum linked to the mineral kaolinite. This finding was notable on its own, but what truly made it remarkable is that kaolinite typically forms only in very warm and wet conditions. Their discovery, published in Nature Communications Earth & Environment, indicates that Mars might have been more Earth-like—warmer, wetter, and more complex—than scientists previously believed.


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  • Karma Amaris, The World’s First Hybrid EREV Luxury Coupé, Takes Center Stage at Monterey Car Week

    Karma Amaris, The World’s First Hybrid EREV Luxury Coupé, Takes Center Stage at Monterey Car Week

    As the world’s first Hybrid EREV performance luxury coupé, Amaris fully delivers the exceptional driving dynamics and sheer speed promised by its purposeful stance and dramatic proportions. Packing 708 horsepower and 676 ft. lbs. torque, Amaris will launch from 0-60mph in less than 3.5 seconds, continuing-on to an electronically governed top speed of 165mph. Its Hybrid EREV powertrain consists of two electric motors driving the rear wheels, powered by a 41.5 kw/H battery which is maintained by a 4-Cylinder turbocharged ICE generator. This Hybrid EREV powertrain delivers over 100 miles of electric-only driving range, and over 400 miles of combined driving range (electric and ICE).

    Amaris begins production in Q4/2026, and will be priced from approximately $200,000USD.

    “Amaris delivers all the joys and indulgences of a thoroughbred performance coupe – staggering pace, exuberant style and opulent interior appointments – balanced with an ultra-low emissions Hybrid EREV powertrain which offers the freedom to refuel with gasoline or recharge with electricity, whichever is more convenient,” says Marques McCammon, President and Chief Executive, Karma Automotive. “Amaris delivers pure desire paired with eco-conscious driving like no other vehicle in the world.”

    The powerful yet timelessly elegant carbon fiber and aluminum body of the Amaris, specified for Monterey Car Week in Solar Blaze Red paintwork, features the latest evolution of the Comet Line design language first established with the upcoming Karma Kaveya super-coupe. With Amaris, the Comet Line originates in the sculpted cowl aft of the nose, continuing rearward in an arc across the sides of the hood, descending rearward to amplify the wide, aggressive rear track. 22″ Constellation wheels, crafted in forged aluminum, fully-establish the purposeful, fluid stance of the Amaris. The voluptuous clamshell hood – incorporating Karma’s Target Lighting signature – creates a seamless transition and visual flow to the front fenders. The Backslash design element punctuates the space between the front wheels and the “swan doors,” which gracefully pivot upwards to dramatic effect. Its sleek rear glass profile concludes with an aero pass-through spoiler that reduces aerodynamic drag while creating rear axle downforce for increased stability at high speeds. The Americana-inspired side exhaust further signals performance and capability. 

    Inside, the cabin of the Amaris is specified in Crimson Orbit leather and suede, with carbon fiber and piano black accents. Like the Kaveya super-coupe, Amaris features an electro-chromatically adjustable full glass roof; and “orbits” which visually define the driver and passenger environments. Amaris is shown in its 2-seater configuration, with its rear compartment sculpted to accommodate travel bags.

    Carbon fiber adorns the doors, center console and rear support brace, creating the visual effect of an exposed carbon fiber monocoque with floating leather and suede panels. The door panel forms are drawn forward, descending from shoulder height towards the footwells, creating a sense of speed and acceleration. This same dynamic effect applies to the center console, which houses the gear selector and—concealed beneath a hinged leather ignition cover to further heighten anticipation for the driving experience ahead—the “Start” button.

    Following Karma Automotive’s “reductionary” approach, non-essential features remain hidden until called upon, including the co-pilot’s display which illuminates once the passenger is seated; and cupholders that are concealed by the wireless phone charger until it is retracted with a gentle touch. The interior environment also hides atmospheric lighting that can be adjusted by the user, or changes according to the drive mode selected.

    About Karma Automotive

    Karma Automotive is America’s only full-line ultra-luxury vehicle manufacturer, and a pioneer of EREV (Extended-Range Electric) vehicles which it manufactures at its Karma Innovation and Customization Center (KICC) in Moreno Valley, CA. Its Executive, Product Development, and Design headquarters are located in nearby Irvine, CA. The Karma portfolio embodies California’s spirit of innovation and entrepreneurial boldness, reflected by the signature Comet Line which is the central hallmark of Karma’s new design language. Sales of the 3rd Generation Karma Revero sport sedan, the world’s first luxury Hybrid EREV, are now underway in the USA and EU, offering luxury balanced with conscientiousness delivered without compromise. Sales of Revero’s ultra-exclusive, performance-tuned stablemate, Karma Invictus, are also now underway, to be followed by the Gyesera Hybrid EREV four-seater in Q4 2025, and the Amaris coupe in Q4 2026. The Karma Kaveya super-coupe, with up to 1,000HP and butterfly-doors, will arrive in 2027, and the Karma Ivara GT-UV will arrive in 2028: both will incorporate SDVA (Software-Defined Vehicle Architecture) developed with the world’s leading technology companies. Further, Karma Automotive will provide Tier 1’s and Original Equipment Manufacturers (OEMs) with business-to-business SDVA solutions, as it does today with Karma Connect, its proprietary Vehicle Data Management and Over-the-Air services platform, which presently provides services to the world’s second largest OEM. Karma Automotive’s dealer network spans North America, Europe, South America and the Middle East. (www.karmaautomotive.com) 

    Media Contact:                                                                                                                                                         
              Joe Richardson, (917) 716-6617                                                                           
              [email protected]

    SOURCE Karma Automotive

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  • Israeli jazz bassist in NYC comes home to compose North African sounds

    Israeli jazz bassist in NYC comes home to compose North African sounds

    When Israeli Andalusian Orchestra Ashdod performs a new jazz work composed by acclaimed jazz bassist Omer Avital later this month, it will be a collaboration decades in the making.

    The orchestra, under the artistic direction of Elad Levi, will perform “North African Dream,” composed and conducted by Avital.

    The work will be performed on August 27 at Elma in Zichron Yaakov, on August 28 at the Jerusalem YMCA, and on August 29 at the Tel Aviv Museum of Art.

    Avital, a classically trained jazz musician, collaborated with Elad Levi, artistic director of the Andalusian orchestra, first composing a piece for the orchestra at last year’s Ashdod jazz festival.

    “I knew everybody involved,” said Avital. “It was like a Moroccan synagogue.”

    Now they’ll perform it again in August, followed by another series of performances in November and then take it on the road to Paris in November, with a tour planned for spring 2026 in the US.

    It’s a poignant piece of music in four movements — Piyut / Father, The Dream, Eastern Melancholy, The Return of the African Jew — that yearns and pines for the almost lost cultural traditions of past generations of Avital’s family.

    These days, Avital looks for opportunities to come to Israel, particularly after the Hamas terrorist attack of October 7 and the concurrent burst of anti-Israel sentiment and antisemitism in his hometown of New York as the Gaza war drags on.

    “People who I thought were on my side or were my friends are now on the other side,” said Avital. “But life goes on, and I think making music in Israel is my calling right now. I love working with Israelis. I think we’re very talented people, and at the moment, the jazz scene in Israel is one of the more bubbling scenes in the world.”

    “People are on fire with their music in Israel,” added Avital. “We say what we need to say musically.”

    New York has become a more complicated place for Avital, who said he isn’t worried about his personal safety but feels the growing hatred for Jews and Israelis around him.

    At the same time, he’s happy to have excuses to come home to Israel.

    When he was younger and growing up in Israel, Avital focused on studying classical music, learning the masters with Russian instructors. It was during a stint in Israel in the early 2000s that he spent time studying Jewish Arabic music, including his family’s Yemenite and Moroccan sounds.

    “It’s our music, it’s Jewish Arabic music,” he said. “When I was growing up, we didn’t talk about being Mizrachi, about our music, so this was a welcome renaissance.”

    Each time he has returned to Israel over the last two decades, Avital has engaged more with local music and helped create a new trend in music, combining Arab Jewish music with jazz elements.

    Avital wasn’t the only one.

    With several generations of Israeli-born jazz musicians, alongside a surge of curiosity in traditional Jewish Arabic music, such as the Andalusian tunes, there has long been a trend of melding classical strings with Middle Eastern instruments, creating a new melange of Israeli sound.

    As Avital, 53, traveled back and forth between Israel and the US, he saw how the younger generation of musicians knew and recognized jazz. The current Andalusian Orchestra is comprised of musicians in their late 20s who grew up on jazz as well as the modern music of North Africa.

    “The time was ripe to come back and work with this orchestra that can do anything,” said Avital.

    The Ashdod orchestra, founded nearly 30 years ago in the southern port city, initially included some 30 musicians who were mostly of Tunisian, Moroccan and Russian origin, and focused solely on traditional Andalusian music and liturgical poetry, playing on a variety of instruments that range from the violin to the oud.

    Now the orchestra includes younger, more mainstream Israeli musicians who are very used to melding modern sound with ancient liturgical poetry and instruments.

    “When I started doing it, it was still very strange,” said Avital. “People wondered why we were mixing jazz with liturgical singers?”

    But he — along with other musicians such as the orchestra’s Elad Levi, conductor Tom Cohen, Yemen Blues’ Ravid Kahalani — began exploring this new sound, and it stuck.

    “I’ve realized that this is my real music,” said Avital. “I learned jazz, but I’m Israeli, and I can bring my knowledge into this classical Israeli music and help make it the future music of Israel.”


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