Main Outcome measuresThe Research Articles

Receptive window might be shorter in patients with endometriosis and lesions cyclically prepare for implantation

ObjectiveTo investigate whether endometrial receptivity is affected in patients with endometriosis using podocalyxin (PCX) as a functional biomarker; to study how endometriotic lesions display PCX and the potential pathological implications. DesignWe have previously reported that PCX, an anti-adhesion glycoprotein and barrier protector, is dynamically regulated in the endometrium and acts as a key negative regulator of epithelial receptivity. Early in the cycle both luminal epithelium (LE, lining the endometrial surface) and glandular epithelium (GE, residing within the tissue) strongly express PCX, but in the receptive window PCX is selectively down-regulated in LE, switching the endometrial surface to an adhesive state for embryo attachment/implantation; meanwhile PCX expression is maintained in GE until post-receptivity. Here, we immuno-stained PCX in endometrial tissues and ectopic lesions biopsied across the menstrual cycle from patients with endometriosis (EOS, n=41), and compared to endometrium of non-endometriosis controls (Non-EOS, n=55). We further investigated how PCX changes observed in ectopic lesions may influence their adhesive capacity. SubjectsWomen without and with endometriosis. ExposureN/A. Main Outcome MeasuresThe window of endometrial receptivity might be shorter in patients with endometriosis; ectopic sites also down-regulate PCX cyclically, mirroring the eutopic endometrial cells in preparing for receptivity to increase their adhesion potential. ResultsEndometrial PCX levels were comparable between non-EOS and EOS early in the cycle, and in both groups PCX is down-regulated in LE during the expected window of receptivity, however, in EOS endometrium PCX is reduced earlier in GE as if the receptive window were shorter. In endometriotic lesions, PCX was detected in endometrial LE- and GE-like cells plus mesothelial cells enveloping peritoneal organs, but PCX was cyclically lost specifically in LE-like cells and reduced in GE-like cells as seen in the eutopic endometrium, which however may increase their adhesion potential to nearby organs (overlaid by mesothelial cells). This speculation was further corroborated in an in vitro model showing endometrial epithelial cells with lower PCX were indeed more adhesive to mesothelial cells. ConclusionEndometrial receptivity is subtly affected in patients with endometriosis with a shorter window. Cyclic down-regulation of PCX in ectopic sites may have pathological consequences.

Geometrical Features of Sub-basal Corneal Whorl-like Nerve Patterns in Dry Eye Disease: An In Vivo Confocal Microscopy Study

PurposeTo investigate the geometrical feature of the whorl-like corneal nerve in dry eye disease (DED) across different severity levels and subtypes, and to preliminarily explore its diagnostic ability. DesignCross-sectional study. ParticipantsThe study included 29 healthy subjects (51 eyes) and 62 DED patients (95 eyes). MethodsAll subjects underwent comprehensive ophthalmic examinations, dry eye tests, and in vivo confocal microscopy to visualize the whorl-like corneal nerve at the inferior whorl (IW) region and the straight nerve at the central cornea. The structure of the corneal nerve was extracted and characterized using the fractal dimension (CNDf), multi-fractal dimension (CND0), tortuosity (CNTor), fiber length (CNFL), and numbers of branching points (CNBP). Main outcome measuresThe characteristics of quantified whorl-like corneal nerve metrics in different groups of severity and subtype defined by symptoms and signs of DED. ResultsCompared to the healthy controls, the CNDf, CND0, and CNFL of the IW decreased significantly as early as grade 1 DED (P<0.05), while CNTor increased (P<0.05). These parameters did not change significantly in the straight nerve. As the DED severity increased, CNDf and CNFL in the whorl-like nerve further decreased in grade 3 DED compared to grade 1. Significant nerve fiber loss was observed in aqueous-deficient DED compared to evaporative DED (P<0.05). Whorl-like nerve metrics correlated with ocular discomfort, tear film break-up time, tear secretion and corneal fluorescein staining, respectively (P<0.05). Furthermore, merging parameters of whorl-like and linear nerve showed an area under the curve value of 0.910 in diagnosing DED. ConclusionsGeometrical parameters of IW could potentially allow optimization of the staging of DED. Reliable and objective measurements for the whorl-like cornea nerve might facilitate patient stratification and diagnosis of DED.

Prevalence of treatment-resistant depression and associated factors among major depressive disorder follow-up patients at Saint Amanuel Mental Specialised Hospital in Ethiopia: a cross-sectional study

ObjectivesThis study aimed to assess the prevalence of treatment-resistant depression (TRD) and associated factors among patients with major depressive disorder (MDD) on follow-up at Amanuel Mental Specialised Hospital, Addis Ababa,...

Trends in Hepatocellular Carcinoma Mortality Rates in the US and Projections Through 2040

ImportanceThe burden of liver cancer varies worldwide. An upward trend in both hepatocellular carcinoma (HCC) incidence and mortality in the past 2 decades has been observed.ObjectiveTo assess observed HCC-related age-standardized mortality rates (ASMRs) in the US for 2006 to 2022 and provide ASMR projections through 2040.Design, Setting, and ParticipantsThis cross-sectional study used data from the National Vital Statistics System, which is accessible through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research website. Data on deaths attributed to HCC (from January 1, 2006, to December 31, 2022) were obtained for adults 25 years or older and were stratified by liver disease etiology, age, sex, and race and ethnicity. Etiologies included alcohol-associated liver disease (ALD), hepatitis B virus (HBV), hepatitis C virus (HCV), and metabolic dysfunction–associated steatotic liver disease (MASLD).Main Outcomes and MeasuresThe main outcomes were (1) observed ASMRs of HCC per 100 000 persons using Joinpoint regression (National Cancer Institute) to assess trends during 2006 to 2022 and (2) ASMRs projected for 2023 to 2040 using Prophet and AutoARIMA modeling.ResultsThis study included 188 280 HCC-related deaths from 2006 to 2022. Most deaths occurred among males (77.4%). The annual percentage change was 4.1% (95% CI, 2.2% to 7.7%) for 2006 to 2009 and decreased to 1.8% (95% CI, 0.7% to 2.0%) for 2009 to 2022, with an overall observed ASMR of 5.03 per 100 000 persons in 2022 and a projected ASMR of 6.39 per 100 000 persons by 2040, with consistent trends for both sexes. By etiology, ASMRs decreased for HCV- and HBV-related mortality but increased for ALD- and MASLD-related mortality. In 2022, MASLD surpassed HBV as the third-leading cause of HCC-related death and was projected to overtake HCV in 2032 as the second-leading cause; ALD was projected to be the leading cause of HCC-related death in 2026. In 2022, the ASMR was higher among individuals aged 65 years or older compared with those aged 25 to 64 years (18.37 vs 1.79 per 100 000 persons). The American Indian or Alaska Native population had the largest increase in projected ASMR by 2040 (14.71 per 100 000 persons) compared with the Asian population (3.03 per 100 000 persons).Conclusions and RelevanceIn this cross-sectional study, ASMRs for ALD- and MASLD-related HCC death increased rapidly from 2006 to 2022; ALD-related HCC was projected to be the leading cause by 2026, with MASLD as the second-leading cause by 2032. These findings may serve as a reference for public health decision-making and timely identification of groups at high risk of HCC death.

Distribution and morphologic characteristics of choroidal vortex veins in Pachychoroid disease

PurposeThis study aimed to elucidate the distribution and morphological features of choroidal vortex veins in pachychoroid disease (PCD). DesignRetrospective observational study. SubjectsPatients with PCD included from January 2022 to June 2023. MethodsWe conducted a retrospective cross-sectional analysis using wide-field indocyanine green angiography (WF-ICGA) to assess choroidal vortex veins in PCD patients, categorizing them based on location (equatorial/posterior) and morphology (absent, incomplete, complete, complete with ampulla). Main Outcome MeasuresThe incidence of different location and morphology of vortex veins in PCD. ResultsA total of 190 eyes from 99 PCD patients were examined. Notably, only 8.9 % (17/190) of eyes had posterior vortex veins. We identified 1620 vortex veins, predominantly equatorial (99 %, 1603/1620). Morphologically, the most common type was incomplete (61.9 %), followed by complete (19.5 %), absent (11.1 %), and complete with ampulla (7.5 %). The distribution of these veins varied, with the inferotemporal quadrant showing the highest prevalence at 26.9 %, followed by the superonasal (26.1 %), superotemporal (24.3 %), and inferonasal (22.7 %) quadrants. The median number of vortex veins per eye was 8, with a range from 5 to 15. ConclusionsThis study highlights that posterior vortex veins are less frequent in PCD eyes, with incomplete veins being the most prevalent. These findings provide important clinical evidence for understanding the distribution and morphologic characteristics of choroidal vortex veins in PCD, contributing to our knowledge of the pathophysiological mechanisms underlying this condition.

Effects of connective tissue massage on physical and emotional symptoms, insomnia, and quality of life in postmenopausal women: A randomized, sham-controlled trial

ObjectivesConnective tissue massage is a therapeutic approach with local, reflex, and systemic effects. This study evaluated the effects of connective tissue massage on postmenopausal symptoms, menopause-specific quality of life, and insomnia. Study designA total of 57 postmenopausal women were randomly allocated to either the massage group (n = 28) or the control group (sham therapeutic ultrasound) (n = 29). Participants received massage or the sham intervention in 3 sessions per week for 4 weeks, each session lasting 15 min. The Wilcoxon test was used for within-group comparisons, and the independent groups t-test, Mann-Whitney U test, or Pearson chi-square test were used for between-group comparisons. Statistical significance was set as p ≤ .05. Main outcome measuresThe primary outcome was menopausal symptom severity, assessed by the Menopause Rating Scale. Secondary outcomes included hot flash frequency, hot flash score (frequency × severity), menopause-specific quality of life, emotional status, insomnia, and satisfaction with the intervention. ResultsData from 52 of the 57 participants were included in the final analysis. There was a greater improvement in the massage group compared with the control group in all primary and secondary outcome measures except insomnia severity (p ≤ .05). ConclusionsConnective tissue massage can be offered as a first-line approach to improve physical and emotional health in the short term for postmenopausal women. Further studies are needed to determine the long-term effects.Clinical trial registration number: NCT05293860

SGLT-2 inhibitors and mortality among patients with heart failure with reduced ejection fraction: linked database study

ObjectiveTo investigate the association between sodium-glucose cotransporter-2 (SGLT-2) inhibitor use and risk of all cause mortality among patients with heart failure with reduced ejection fraction.DesignLinked database study.SettingNational registers in Denmark,...

Development and Preliminary Evaluation of a Food Literacy Measure for Use With Young People in Canada

BackgroundThis article presents the culmination of a multiyear research project aimed at creating a comprehensive food literacy framework and corresponding measure. Specifically, this article documents the development and validation of a food literacy measure for young people facing social inequities. ObjectivesThis study aimed to identify items to measure 12 attributes of food literacy; test the measure with the identified target groups, considering attribute, face, and content validity, inter-rater reliability and test-retest reliability; and refine the measure. DesignThe study’s design consisted of a 5-phase approach that included drafting the food literacy measure, expert review, cognitive interviews, pilot testing, and validity and reliability testing. Participants and settingSeven international experts provided feedback on the measure and 25 individuals aged 16 to 25 years participated in cognitive interviews. Two hundred fifty-five young people completed the test survey and 147 completed a retest survey 2 weeks later. These surveys identified food literacy factors. To further evaluate the validity of these factors. One hundred ninety-three participants completed a confirmatory test that was used for confirmatory factor analysis to assess the final model’s fit. Interview participants were recruited from local programs and services from across Ontario, Canada, whereas survey participants were recruited from across Canada via social media. The research study was conducted between January 2018 and December 2019. Main outcome measuresThe main outcome measures were validity and reliability scores for a food literacy measurement tool that consisted of 50 questions across 10 attributes of food literacy. Statistical analyses performedInterview analyses were guided by the four stages of cognitive processing. Exploratory factor analysis was used to identify the factors that improved the Cronbach alpha of the food literacy measure. Test-retest reliability was assessed using percent agreement, Cohen kappa, and weighted kappa. Confirmatory factor analysis was used to produce an acceptable final model with a root mean square error of approximation estimate. ResultsThe final food literacy measure consisted of 50 questions addressing 10 food literacy attributes. Exploratory factor analysis showed an improvement in Cronbach alpha when compared with the initial attribute construction. Test-retest reliability showed percent agreement ranging from 64% to 97%, with most items having fair (0.21 to 0.40) to moderate (0.41 to 0.60) kappa values. Confirmatory factor analysis produced an acceptable final model with a root mean square error of approximation estimate of 0.0437. ConclusionsThe food literacy measure is a comprehensive tool for assessing food literacy among young people. Additional research is needed to explore the measure's modularity, its use as an evaluation tool, and its suitability for use with diverse samples, including individuals from varied gender, geographic locations, ethnicities, and cultural backgrounds.

Longitudinal Goal Attainment With Repeat Injections of AbobotulinumtoxinA in Adults With Lower Limb Spasticity: Results From a Prospective Observational Study

ObjectiveTo assess longitudinal goal attainment with repeat abobotulinumtoxinA (AboBoNT-A) injections for lower limb spasticity (LLS) over 16 months. DesignProspective, longitudinal, international, multicenter, observational study (NCT04050527). SettingSpecialist neurorehabilitation centers. ParticipantsAmbulatory adults with unilateral LLS able to take ≥5 steps with/without assistance (effectiveness population, N=384). InterventionsParticipants received ≥1 AboBoNT-A treatment cycle administered in accordance with local prescribing guidelines to achieve individualized treatment goals. Main Outcome MeasuresThe primary endpoint was goal attainment as assessed using the cumulated Goal Attainment Scaling-Leg (GAS-leg) T score, across all treatment cycles for each patient. ResultsOverall, participants underwent a median of 5 lower limb injection cycles (median dose 600U, range 100-1475U) with a mean±SD injection interval of 18.3±6.1 weeks. Participants generally achieved their goals as expected over repeated cycles; the mean (95% CI) GAS-leg T score at cycle 1 baseline was 38.0 (37.7, 38.3) and the mean cumulated GAS-leg T score at 16 months was 48.2 (47.4, 48.9) (mean change from a baseline of 9.9 [9.1, 10.7]). Participants injected with a guidance technique at baseline were more likely to attain their cycle 1 primary treatment goals (odds ratio: 1.9 [95% CI 1.1, 3.1], P=.02). Overall, 56 (13.5%) participants reported ≥1 adverse event, of which 6 participants (1.4%) had a treatment-related adverse event. ConclusionsFindings from this large, international study provide evidence for the benefit of repeated cycles of AboBoNT-A for LLS. Multivariate analyses indicated that goal attainment during the first cycle was better with those injected using injection guidance than those injected without guidance.

Surgical Costs of Enucleation vs. Plaque Brachytherapy for Intraocular Malignancy: A Time-Driven Activity-Based Costing Approach

ObjectiveTo compare costs between enucleation and plaque brachytherapy procedures for the treatment of intraocular malignancies. DesignRetrospective economic analysis using a time-driven activity-based costing (TDABC) methodology. SubjectsPatients undergoing plaque brachytherapy and enucleation procedures for the treatment of intraocular malignancy performed at the University of Michigan Kellogg Eye Center from 2021-2022. MethodsData inputs were obtained from the Electronic Health Record (EHR) and prior literature. Associated expenses were determined using TDABC, a method for cost calculation that correlates the cost rate of each resource used in a procedure with the amount of time that the resource is used. Main Outcome MeasuresThe primary outcome was the difference in total cost associated with enucleation versus plaque brachytherapy procedures. Secondary outcomes included length of surgery (in minutes), total day-of-surgery costs, and number of follow-up visits. Results145 cases were included, with 41 enucleations and 104 courses of plaque brachytherapy.. Between all enucleation and plaque brachytherapy procedures, plaque brachytherapy was significantly more costly ($10,140.95 vs. $6,127.70, P < 0.01), with total difference in cost of $4013 (95% confidence interval $3352.02 to $4674.47). There was no significant difference in OR time between enucleation and plaque brachytherapy. Plaque brachytherapy required significantly more follow-up visits than enucleation (1.02 visits vs. 0.59 visits, P < 0.01). ConclusionsThrough TDABC cost analysis, we determined that the surgical course of plaque brachytherapy is more costly than enucleation, with the primary cost drivers being cost of the radiotherapy plaque and radiation oncology-related expenses.

RCT testing Sources of Strength impact on suicide attempts and moderation by sexual violence

IntroductionYouth suicide rates have risen steadily in recent decades, with suicide attempts representing a significant risk factor for future mortality. Sexual violence (SV) exposure further elevates this risk. This study investigated the efficacy of Sources of Strength, a school-based peer led program, for reducing suicide attempts school-wide, as well as specifically among youth with recent SV exposure. Study DesignCluster randomized controlled trial (RCT) was conducted 2017-2019, contrasting 22 schools paired and then randomized to either Sources of Strength intervention (n=11) for two school years or wait-listed condition (n=11). Two control schools dropped out prior to completing baseline assessments. Setting/participantsParticipants were 6,539 students in 20 high schools across four assessment waves: baseline prior to random assignment and 6-, 12-, and 18-month follow-ups. InterventionIn schools assigned to immediate Sources of Strength implementation, student peer leaders (n=348) receiving training in the program's multidimensional healthy coping framework in fall of both school years, and peer leaders conducted school-wide campaigns with ongoing mentoring from staff adult advisors (n=122). Main outcome measuresThe primary outcome was any new suicide attempt reported at waves 3 and 4. Recent SV history was also assessed at baseline. Analyses were conducted in 2023. ResultsSources of Strength significantly reduced new suicide attempts by 29%, even after accounting for student characteristics and recent SV history. Moderation analyses showed this overall intervention effect may not have extended to students with more severe SV victim histories. ConclusionsSources of Strength effectively reduced suicide attempts in high school students overall, suggesting its potential for population-level impact. This is especially important in the face of steadily rising suicide attempt and fatality rates among adolescents and young adults. However, a cautious interpretation of the evidence suggests that Sources of Strength may not prevent attempts among students with recent SV contact victimization, highlighting the need for additional intervention work for this high-risk group.

Association between Semaglutide and Non-Arteritic Anterior Ischemic Optic Neuropathy: A Multinational Population-Based Real-World Study

ObjectiveTo investigate whether semaglutide increases the risk of non-arteritic anterior ischemic optic neuropathy (NAION) in the general population. DesignThis retrospective cohort study utilized a de-identified global electronic medical records database. The enrollment period was extended from January 2017 to August 2023, with observations concluding in August 2024. ParticipantsThis study included individuals with type 2 diabetes mellitus (T2DM) or obesity. They were further categorized into T2DM-only, obesity-only, and T2DM with obesity groups to assess the differences among these subgroups. The effects of semaglutide were compared with those of glucose-lowering or weight loss medications other than glucagon-like peptide receptor agonists. MethodsPatient data were obtained from 160 healthcare organizations across 21 countries. Outcomes were evaluated at one, two, and three years of follow-up. A 1:1 propensity score matching was performed to balance age, sex, body mass index, hemoglobin A1C, medications, and underlying comorbidities. Cox regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI). Main Outcome MeasuresThe occurrence of NAION. ResultsThe final analysis included 37,245 participants with T2DM-only, 33,537 participants with obesity-only, and 64,989 participants with both T2DM and obesity. The results indicated that the administration of semaglutide was not associated with the development of NAION in the T2DM-only group (1 year follow-up: HR, 2.32; 95% CI, 0.60–8.97; 2 years: HR, 2.31; 95% CI, 0.86–6.17; 3 years: HR, 1.51; 95% CI, 0.71–3.25), the obesity-only group (1 year follow-up: HR, 0.25; 95% CI, 0.03–2.28; 2 years: HR, 0.44; 95% CI, 0.09–2.21; 3 years: HR, 0.44; 95% CI, 0.09–2.21), and the T2DM with obesity group (1 year follow-up: HR, 0.81; 95% CI, 0.42–1.57; 2 years: HR, 1.2; 95% CI, 0.74–1.94; 3 years: HR, 1.19; 95% CI, 0.78–1.82). ConclusionsThe findings suggest that semaglutide may not be associated with an increased risk of NAION in the general population. Therefore, avoidance of semaglutide based solely on concerns regarding the risk of NAION may not be warranted, as its potential benefits for blood glucose control and cardiovascular health likely outweigh its potential risks.

Longer WIC participation is associated with higher diet quality and consumption of WIC-eligible foods among children 2-5 years old

BackgroundFew studies have evaluated trends in diet quality across early childhood including the extent to which foods and beverages available in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) Food Package contribute to children’s diets. ObjectiveThe objective was to examine across ages 2-5 years: (1) trends in Healthy Eating Index-2020 (HEI-2020) total and component scores; (2) differences in mean HEI-2020 scores by WIC participation duration; and (3) contributions of the top 5 contributing foods or beverages to HEI-2020 component scores by WIC duration. DesignThis was a secondary analysis of a nationally representative sample of the WIC Infant and Toddler Feeding Practices Study-2 (WIC ITFPS-2) conducted between 2013-2019. Participants/setting: 980 WIC ITFPS-2 participants (weighted n=403,726) were included. Main Outcome MeasuresThe outcomes were HEI-2020 scores and top contributing foods to HEI-2020 components. Statistical AnalysesMultivariate regression was conducted to examine HEI-2020 scores by WIC duration (high, intermediate, and low groups). The top 5 contributors to HEI-2020 components were averaged across ages 2-5 and compared across WIC duration groups. ResultsFor all participants combined, the mean HEI-2020 total scores were similar across ages 2 through 5. Children with high WIC duration had higher total HEI-2020 scores compared to children with low WIC duration from ages 2-5 (mean±SE, 58.1±0.7 vs. 55.6±1.1, p=0.03). The percentage contributions of many of the WIC-eligible foods to HEI-2020 components were higher in the high WIC duration group compared to low WIC duration group, including higher intake of dried beans, unsweetened breakfast cereals, whole grain breads, and 1% milk; the high WIC duration group also had lower intake of sweetened breakfast cereals and 2% milk. ConclusionFindings illustrate how WIC-eligible foods contribute to higher diet quality scores: when children participate in WIC longer, their diets are better aligned with national dietary guidelines.

Treatment patterns of childhood glaucoma in the United States: Analysis of IRIS® Registry (Intelligent Research in Sight)

PurposeTo investigate treatment patterns of childhood glaucoma in the United States. DesignRetrospective clinical cohort study SubjectsPatients under 18 years of age with a diagnosis code for glaucoma between January 1, 2013, and December 31, 2020, in the IRIS® Registry (Intelligent Research in Sight). MethodsPatient demographic information and clinical characteristics were extracted. A Cox regression model was used to determine predictors of undergoing incisional glaucoma surgery. Main Outcome MeasuresThe primary outcomes were the percentage of childhood glaucoma eyes that underwent glaucoma-related procedures and those receiving intraocular pressure (IOP)-lowering medications. Our secondary outcomes were hazard ratios (HRs) of demographic and clinical factors for undergoing incisional surgeries. ResultsA total of 5017 eyes of 3069 patients were included in this study. Based on billing codes, 208 eyes (4.1%) had primary congenital glaucoma (PCG), 1911 eyes (38.1%) had juvenile open-angle glaucoma (JOAG), 999 eyes (19.9%) had glaucoma following cataract surgery (GFCS), and 1646 (32.8%) had secondary glaucoma other than GFCS. Out of 5017 eyes with childhood glaucoma, 808 eyes (16.1%) underwent glaucoma-related procedures, and 4698 eyes (93.6%) received antiglaucoma medications. Angle surgery was the most common first-recorded procedure for PCG, and tube shunt surgery for GFCS and secondary glaucoma. Laser trabeculoplasty was mainly performed for JOAG by non-glaucoma subspecialists. Factors associated with higher likelihood of incisional surgeries were PCG (vs. JOAG, HR 5.40, 95% confidence interval [CI] 1.55–18.84, p = 0.008), increase in IOP (HR 1.06 per mmHg, CI 1.05–1.08, p<0.001), and index date at age < one year (vs. ages 11–15 years, HR 6.08, CI 1.51 – 24.44, p = 0.011). Being cared for by a non-glaucoma subspecialist was associated with a lower likelihood of undergoing incisional surgery (HR: 0.32 (95%CI: 0.23 – 0.44, p<0.001). ConclusionsWe found that 1 in 6 childhood glaucoma eyes underwent glaucoma-related procedures, and nearly all received antiglaucoma medications. The choice of first-recorded procedure differed across age and diagnosis. Type of glaucoma, baseline IOP, age, and type of treating subspecialist were predictors for undergoing incisional glaucoma surgery.

Clinical Evaluation of a Novel CRISPR-Cas12a-Based RID-MyC Assay for the Diagnosis of Fungal Endophthalmitis

ObjectiveThis study evaluates the RID-MyC (Rapid Identification of Mycoses using CRISPR) assay, a CRISPR/Cas12a-based diagnostic tool, for its efficacy in diagnosing fungal endophthalmitis (FE), comparing it with panfungal PCR and culture methods. DesignA comparative cross-sectional study assessing the performance of the RID-MyC assay against established diagnostic modalities for FE. SubjectsThe study included 133 intraocular samples from 117 patients with suspected microbial endophthalmitis. MethodsThe study compared the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the RID-MyC assay against panfungal PCR and culture. The Limit of Detection (LoD) for Aspergillus flavus and Candida albicans was determined for both RID-MyC and panfungal PCR across three different media: nuclease-free water (NFW), aqueous humor (AH), and vitreous humor (VH). Discrepancy analysis was conducted for discordant results, incorporating clinical outcomes and responses to antifungal treatment. Main Outcome MeasuresThe study primarily assessed the sensitivity, specificity, PPV, and NPV for clinical samples. Time to diagnosis was also evaluated. ResultsThe RID-MyC assay demonstrated a sensitivity of 88.24% (CI: 63.56% to 98.54%) and specificity of 93.1% (CI: 86.86% to 96.98%), with PPV and NPV of 65.22% (CI: 48.45% to 78.91%) and 98.18% (CI: 93.62% to 99.50%), respectively. Discrepancy analysis enhanced sensitivity to 90.48% (CI: 69.62% to 98.83%) and specificity to 96.43% (CI: 91.11% to 99.02%). The RID-MyC assay was 10 to 1000-fold more sensitive than panfungal PCR in detecting Aspergillus flavus and Candida albicans in intraocular specimens. The time to diagnosis with the RID-MyC assay was consistently under two hours. ConclusionsThe RID-MyC assay may advance the rapid and precise diagnosis of FE, with possible relevance to other invasive fungal conditions.

Ipsilesional 5 Hz Repetitive Transcranial Magnetic Stimulation for Motor Dysfunction in Subacute Intracerebral Hemorrhage: An Exploratory Trial

ObjectiveTo explore whether ipsilesional 5 Hz repetitive transcranial magnetic stimulation (rTMS) therapy can improve motor function in patients with intracerebral hemorrhage (ICH) and observe any adverse reactions. DesignA 4-week randomized, controlled, single-blind (evaluator) trial with a 1-month follow-up. SettingA tertiary hospital rehabilitation center. ParticipantsForty-nine patients with first ICH were recruited and randomly separated into an experimental (n=25; 19 men, 6 women) or control group (n=24; 17 men, 7 women), with age range of 30 to 75 years, and mean duration after hemorrhage onset of 47 (range 17-86) days. InterventionsThe experimental group received ipsilesional 5 Hz rTMS therapy and conventional rehabilitation training. The hot spot of the abductor pollicis brevis and tibialis anterior muscles on the affected hemisphere of the brain received 1500 pulses of stimulation each day, for a total of 3000 pulses. The stimulations applied to the affected abductor pollicis brevis and tibialis anterior hot spots were separated by >2 hours. The stimulation frequency was 5 Hz, each sequence lasting 2 seconds, with a sequence interval of 5 seconds, for a total duration of 36 minutes every day. The control group only received conventional rehabilitation training. Main Outcome MeasuresThe primary endpoint was the change in Brunnstrom stage. Secondary endpoints included Fugl-Meyer Assessment, Barthel Index, and Berg Balance Scale. All assessments were performed at baseline, after intervention (day 29) and 1 month after intervention (day 60). ResultsImprovements over baseline in all scores at day 29 and 60 were significantly greater in the 5 Hz rTMS group than in the control group. No significant side effects were reported during the experiment and 1 month after the experiment. ConclusionsApplying 5 Hz high-frequency rTMS to the affected hemisphere within 3 months after the onset of ICH appears safe and may significantly improve motor function and activities of daily living.

Multimodal Deep Learning for Differentiating Bacterial and Fungal Keratitis Using Prospective, Representative Data

ObjectiveThis study develops and evaluates multimodal machine learning models for differentiating bacterial and fungal keratitis using a prospective, representative dataset from South India. DesignMachine learning classifier training and validation study. Participants599 subjects diagnosed with acute infectious keratitis at Aravind Eye Hospital in Madurai, India. MethodsWe developed and compared three prediction models to distinguish bacterial and fungal keratitis using a prospective, consecutively-collected, representative dataset gathered over a full calendar year (the MADURAI dataset). These models included a clinical data model, a computer vision model using the EfficientNet architecture, and a multimodal model combining both imaging and clinical data. We partitioned the MADURAI dataset into 70% train/validation and 30% test sets. Model training was performed with 5-fold cross-validation. We also compared the performance of the MADURAI-trained computer vision model against a model with identical architecture but trained on a pre-existing dataset collated from multiple prior bacterial and fungal keratitis randomized clinical trials (the RCT-trained computer vision model). Main Outcome MeasuresThe primary evaluation metric was the area under the precision-recall curve (AUPRC). Secondary metrics included area under the receiver operating curve (AUROC), accuracy, and F1 score. ResultsThe MADURAI-trained computer vision model outperformed the clinical data model and the RCT-trained computer vision model on the hold-out test set, with an AUPRC 0.94 (95% CI: 0.92-0.96), AUROC 0.81 (0.76-0.85), accuracy 77%, and F1 score 0.85. The multimodal model did not substantially improve performance compared to the computer vision model. ConclusionsThe best-performing machine learning classifier for infectious keratitis was a computer vision model trained using the MADURAI dataset. These findings suggest that image-based deep learning could significantly enhance diagnostic capabilities for infectious keratitis, and emphasize the importance of using prospective, consecutively-collected, representative data for machine learning model training and evaluation.

Analysis of the impact of a rhinologist-assisted endoscopic approach on a single neurosurgeon’s outcomes in transsphenoidal resection of pituitary adenomas

ObjectivesDetermine the improvements in outcomes of transsphenoidal pituitary adenoma resection following addition of a skull base rhinologist to the neurosurgical team. DesignAll patients that underwent transsphenoidal resection of pituitary adenoma were identified. Demographic data, Otolaryngology (ENT) involvement, initial adenoma size, extent of resection, hormonal secretion status, visual field exam, post-operative DI, CSF leak, recurrence, need for nasoseptal flap (NSF), re-operation rate were all collected. A linear-regression model adjusteds for confounders. SettingA single academic institution Participants271 patients who underwent transsphenoidal surgery between 2015 and 2020.Main Outcome MeasuresThe main outcome measures were Extent of Resection and Endocrinologic remission. ResultsOf the 271 patients identified, 228 (84 %) patients had macroadenomas, one-third of patients presented with bitemporal hemianopsia, and 27 % (72) were hormonally active. For these and demographics there were no statistically significant differences between the microscopic or endoscopic approach (EEA) groups. For patients with cavernous sinus invasion of >50 %, EEA was more likely to achieve gross total resection (GTR) (OR 2.6; p<0.001). For patients who had prior sellar surgery, EEA was 2.5x more likely to get a GTR (p=0.05). The EEA approach resulted in an extra hospital day (1–2 vs 2–3 p<0.05) and surgery lasted an additional hour (1.17 vs 2.5, p<0.05), but did not require fat grafts or lumbar drains on a routine basis. ConclusionsWhile the operating time and LOS were longer, the EEA approach performed by two specialized co-surgeons demonstrates superior value for adenomas that have had a prior surgical attempt or with significant cavernous sinus invasion.

Prevalence of hazardous alcohol consumption and associated factors among HIV-positive pregnant women attending public hospitals in Northwest Ethiopia: a multicentred cross-sectional study

BackgroundAlcohol is a major public health problem in pregnant women due to its harmful effects on pregnancy and adverse birth outcomes. Therefore, assessing the prevalence and the factors associated with...

Intensive chemotherapy versus standard chemotherapy among patients with high risk, operable, triple negative breast cancer based on integrated mRNA-lncRNA signature (BCTOP-T-A01): randomised, multicentre, phase 3 trial

ObjectiveTo evaluate the feasibility of using a multigene signature to tailor individualised adjuvant therapy for patients with operable triple negative breast cancer.DesignRandomised, multicentre, open label, phase 3 trial.Setting7 cancer centres...