Nevin Manimala

Graefes Arch Clin Exp Ophthalmol. 2023 Jan 21. doi: 10.1007/s00417-022-05963-5. Online ahead of print.

ABSTRACT

PURPOSE: Data from healthy eyes is needed to interpret optical coherence tomography angiography (OCTA) findings. However, very little normative data is available for wide-field swept-source OCTA (WF SS-OCTA), particularly 12 × 12-mm and disc-centered angiograms. Therefore, we aim to report quantitative metrics in a large sample of control eyes.

METHODS: In this cross-sectional observational study, 482 eyes of 375 healthy adults were imaged on the 100 kHz Zeiss PLEX® Elite 9000 using protocols centered on the fovea (3 × 3, 6 × 6, and 12 × 12-mm) and optic disc (6 × 6 and 12 × 12-mm) between December 2018 and January 2022. The ARI Network (Zeiss Portal v5.4) was used to calculate vessel density (VD) and vessel skeletonized density (VSD) in the superficial capillary plexus, deep capillary plexus, and whole retina, as well as foveal avascular zone (FAZ) parameters. Mixed-effect multiple linear regression models were used for statistical analysis.

RESULTS: The subjects’ median age was 55 (38-63) years, and 201 (53.6%) were female. Greater age and worse best-corrected visual acuity (BCVA) were associated with significantly lower VD and VSD (p < 0.05). VD and VSD differed based on race and cataract status, but not sex, on some scan protocols (p < 0.05). FAZ circularity decreased with age, and FAZ dimensions differed based on race and ethnicity in certain scan protocols.

CONCLUSIONS: We report a large database of parafoveal and peripapillary vascular metrics in several angiogram sizes. In referencing these values, researchers must consider characteristics such as age, race, and BCVA, but will have a valuable point of comparison for OCTA measurements in pathologic settings.

PMID:36680613 | DOI:10.1007/s00417-022-05963-5

Graefes Arch Clin Exp Ophthalmol. 2023 Jan 21. doi: 10.1007/s00417-022-05914-0. Online ahead of print.

ABSTRACT

PURPOSE: The following is a comparative analysis on the treatment outcomes of corneal perforations using amniotic membrane transplantation (AMT) or penetrating keratoplasty (PK).

METHODS: This monocentric retrospective study was performed at the Department of Ophthalmology, University Hospital Ulm, Germany. A total of 78 eyes of 78 patients were included. Thirty-nine eyes received an AMT, and 39 patients were treated with a PK. Primary outcome was recurrence of perforation. Secondary outcomes were patient mortality and visual acuity.

RESULTS: No statistically significant difference was observed with regard to a recurrence of perforation between the two groups (26% in AMT vs 23% in PK, p > 0.99). The time of recurrences was within the first two years and did not differ statistically (p = 0.97). In addition, a proportional hazards model with cox regression regarding recurrent perforation showed no significant differences (p = 0.5). After AMT, 41% and after KP, 28% of the patients died during follow-up (p = 0.2), respectively. The Charlson Comorbidity Index (p < 0.0001) and the age at the time of surgery (p = 0.0002) were statistically significantly higher in those who were deceased. A mean follow-up of 485 ± 517 days was recorded.

CONCLUSION: Both surgical methods show good results and no statistically significant difference regarding recurrent perforation rate. About a third of the patients died during the follow-up period. The decision regarding the appropriate method should therefore be based on a combination of all factors.

PMID:36680612 | DOI:10.1007/s00417-022-05914-0

Graefes Arch Clin Exp Ophthalmol. 2023 Jan 21. doi: 10.1007/s00417-023-05976-8. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to assess the association between hormone replacement therapy (HRT) and the prevalence of nonarteritic anterior ischemic optic neuropathy (NAION) in menopausal women using national data from the entire Korean population.

METHODS: The health screening data of 1,381,605 women between 40 and 90 years of age collected by the National Health Insurance Service (NHIS) of Korea between January 1, 2009, and December 31, 2018, were retrospectively reviewed. Before data analysis, the potential cofounders were adjusted for among all participants. Based on HRT use and its duration (classified into four groups), the hazard ratio (HR) and 95% confidence interval (CI) of NAION development were calculated via a Cox proportional hazards regression analysis using the nonuser group as a reference.

RESULTS: Overall, 7824 NAION diagnoses were made during the mean follow-up of 8.22 years (standard deviation: 1.09 years) in 1,381,605 post-menopausal women. NAION was more common in the HRT group than in the non-HRT group (HR [95% CI]: 1.268 [1.197-1.344]). Furthermore, the risk of NAION increased along with increased HRT duration (p < 0.0001). In the multivariate analysis, the adjusted HRs of the < 2-year HRT group, the 2-5-year HRT group, and the ≥ 5-year HRT group were 1.19 (95% CI: 1.10-1.28), 1.3 (95% CI: 1.17-1.45), and 1.473 (95% CI: 1.31-1.65), respectively. Compared to women younger than 65 years, the HR of HRT for NAION was significantly higher than that of women older than 65 years (p < 0.0001).

CONCLUSION: Our population-based cohort study found that HRT was significantly associated with increased incidence of NAION. The incidence of NAION also increased with the duration of HRT.

PMID:36680611 | DOI:10.1007/s00417-023-05976-8

J Cancer Res Clin Oncol. 2023 Jan 21. doi: 10.1007/s00432-023-04588-3. Online ahead of print.

ABSTRACT

BACKGROUND: The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies.

OBJECTIVE: Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness.

MATERIALS AND METHODS: Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500 mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study’s main outcome, while the secondary endpoint was a clinical benefit.

RESULTS: Of the 354 patients enrolled, 253 initially responded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7% versus 2%, respectively) per the Chevallier classification (Class1 + Class2) (p = 0.1464) and 3% versus 10% assessed per Sataloff Classification (TA, NA/NB) (p = 0.3108). Palbociclib did not increase the rate of complete pathological response.

CONCLUSION: Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.

PMID:36680581 | DOI:10.1007/s00432-023-04588-3

Neuroradiology. 2023 Jan 21. doi: 10.1007/s00234-022-03111-8. Online ahead of print.

ABSTRACT

PURPOSE: This study assessed the position of the termination of the conus medullaris (the point where the spinal cord tapers to an end) and thecal sac (the sheath of dura mater that surrounds the spinal cord and caudal nerve roots) in a large pediatric population, to characterise the nature of the pediatric Gaussian distribution and assess whether age affected the distribution. The study further aimed to assess the effect of gender on termination positions.

METHODS: A total of 520 MRI spine studies of children aged between 1 month and 19 years old were collected from two pediatric tertiary referral centres in the UK and Italy. Studies with pathological findings were excluded, and normal scans were found using keyword search algorithms on a database of radiologists’ reports. The reported scans were individually assessed and reviewed by two experienced neuroradiologists. The termination points of the conus medullaris and thecal sac were determined for each study. Local IRB approvals were sought.

RESULTS: The results showcased a Gaussian distribution in both conus medullaris (r=0.8997) and thecal sac termination levels (r=0.9639). No statistically significant results were noted with increasing age for the termination positions of the conus medullaris or thecal sac (p = 0.154, 0.063). No statistical significance was observed with gender variation with either anatomical landmark. A weak positive correlation was observed between the termination levels of the conus medullaris and the thecal sac (r=0.2567) CONCLUSION: Termination levels across all pediatric age range followed a Gaussian distribution. Knowledge of normal termination levels has relevant clinical implications, including the assessment of patients with suspected spinal dysraphism.

PMID:36680571 | DOI:10.1007/s00234-022-03111-8

Inflamm Bowel Dis. 2023 Jan 21:izac273. doi: 10.1093/ibd/izac273. Online ahead of print.

ABSTRACT

BACKGROUND: Inflammatory bowel disease (IBD) is associated with an increased risk of osteoporosis and bone fracture. The aims of this study were to (1) confirm the association between IBD and low bone density and (2) test for shared risk variants across diseases.

METHODS: The study cohort included patients from the Michigan Genomics Initiative. Student’s t tests (continuous) and chi-square tests (categorical) were used for univariate analyses. Multivariable logistic regression was performed to test the effect of IBD on osteoporosis or osteopenia. Publicly available genome-wide association summary statistics were used to identify variants that alter the risk of IBD and bone density, and Mendelian randomization (MR) was used to identify causal effects of genetically predicted IBD on bone density.

RESULTS: There were 51 405 individuals in the Michigan Genomics Initiative cohort including 10 378 (20.2%) cases of osteoporosis or osteopenia and 1404 (2.7%) cases of IBD. Patients with osteoporosis or osteopenia were more likely to be older (64 years of age vs 56 years of age; P < .001), female (67% vs 49%; P < .001), and have a lower body mass index (29 kg/m2 vs 30 kg/m2; P < .001). IBD patients with (odds ratio, 4.60; 95% confidence interval, 3.93-5.37) and without (odds ratio, 1.77; 95% confidence interval, 1.42-2.21) steroid use had a significantly higher risk of osteoporosis or osteopenia. Twenty-one IBD variants associated with reduced bone mineral density at P ≤ .05 and 3 IBD risk variants associated with reduced bone mineral density at P ≤ 5 × 10-8. Of the 3 genome-wide significant variants, 2 increased risk of IBD (rs12568930-T: MIR4418;ZBTB40; rs7236492-C: NFATC1). MR did not reveal a causal effect of genetically predicted IBD on bone density (MR Egger, P = .30; inverse variance weighted, P = .63).

CONCLUSIONS: Patients with IBD are at increased risk for low bone density, independent of steroid use. Variants in or near ZBTB40 and NFATC1 are associated with an increased risk of IBD and low bone density.

PMID:36680554 | DOI:10.1093/ibd/izac273

Dev Sci. 2023 Jan 21:e13373. doi: 10.1111/desc.13373. Online ahead of print.

ABSTRACT

Recent years have seen a flourishing of Natural Language Processing models that can mimic many aspects of human language fluency. These models harness a simple, decades-old idea: It is possible to learn a lot about word meanings just from exposure to language, because words similar in meaning are used in language in similar ways. The successes of these models raise the intriguing possibility that exposure to word use in language also shapes the word knowledge that children amass during development. However, this possibility is strongly challenged by the fact that models use language input and learning mechanisms that may be unavailable to children. Across three studies, we found that unrealistically complex input and learning mechanisms are unnecessary. Instead, simple regularities of word use in children’s language input that they have the capacity to learn can foster knowledge about word meanings. Thus, exposure to language may play a simple but powerful role in children’s growing word knowledge. Highlights Natural Language Processing (NLP) models can learn that words are similar in meaning from higher-order statistical regularities of word use. Unlike NLP models, infants and children may primarily learn only simple co-occurrences between words. We show that infants’ and children’s language input is rich in simple co-occurrence that can support learning similarities in meaning between words. We find that simple co-occurrences can explain infants’ and children’s knowledge that words are similar in meaning. This article is protected by copyright. All rights reserved.

PMID:36680539 | DOI:10.1111/desc.13373

Health Inf Manag. 2023 Jan 21:18333583221144662. doi: 10.1177/18333583221144662. Online ahead of print.

ABSTRACT

BACKGROUND: Healthcare data frequently lack the specificity level needed to achieve clinical and operational objectives such as optimising bed management. Pneumonia is a disease of importance as it accounts for more bed days than any other lung disease and has a varied aetiology. The condition has a range of SNOMED CT concepts with different levels of specificity.

OBJECTIVE: This study aimed to quantify the importance of the specificity of an SNOMED CT concept, against well-established predictors, for forecasting length of stay for pneumonia patients.

METHOD: A retrospective data analysis was conducted of pneumonia admissions to a tertiary hospital between 2011 and 2021. For inclusion, the primary diagnosis was a subtype of bacterial or viral pneumonia, as identified by SNOMED CT concepts. Three linear mixed models were constructed. Model One included known predictors of length of stay. Model Two included the predictors in Model One and SNOMED CT concepts of lower specificity. Model Three included the Model Two predictors and the concepts with higher specificity. Model performances were compared.

RESULTS: Sex, ethnicity, deprivation rank and Charlson Comorbidity Index scores (age-adjusted) were meaningful predictors of length of stay in all models. Inclusion of lower specificity SNOMED CT concepts did not significantly improve performance (ΔR² = 0.41%, p = .058). SNOMED CT concepts with higher specificity explained more variance than each of the individual predictors (ΔR² = 4.31%, p < .001).

CONCLUSION: SNOMED CT concepts with higher specificity explained more variance in length of stay than a range of well-studied predictors.

IMPLICATIONS: Accurate and specific clinical documentation using SNOMED CT can improve predictive modelling and the generation of actionable insights. Resources should be dedicated to optimising and assuring clinical documentation quality at the point of recording.

PMID:36680531 | DOI:10.1177/18333583221144662

Pediatr Int. 2023 Jan;65(1):e15359. doi: 10.1111/ped.15359.

ABSTRACT

BACKGROUND: This non-randomized intervention study aimed to evaluate the effect of supplementing infant formula with biotin on biotin metabolism and on development.

METHODS: We enrolled healthy Japanese infants (n = 84) and assigned them to groups offered Formula A (total biotin, 0.5 μg/100 kcal) or Formula B (total biotin, 2.4 μg/100 kcal) until they were 6 months of age, and completed an additional follow up to age 36 months. Urinary biotin concentrations were measured at 1 and 6 months, and were compared among breast-fed, Formula A-fed, and Formula B-fed infants at each age. In a follow-up subgroup analysis, we compared scores on the Ages and Stages Questionnaire, version 3 (ASQ-3), from 9 to 36 months among infants continuously fed Formula A, Formula B, or breastmilk.

RESULTS: No adverse events occurred during the intervention period. At 1 month, urinary biotin concentrations were highest in Formula B-fed infants and lowest in Formula A-fed infants. At 6 months, Formula B-fed infants retained higher biotin levels than Formula A-fed and breast-fed infants. Both differences were statistically significant (P < 0.05). The breast-fed, Formula A-fed, and Formula B-fed groups had similar ASQ scores at 9-36 months.

CONCLUSIONS: Biotin supplementation of infant formula contributed to improving biotin status in formula-fed infants. The results support the official approval of the use of biotin in infant formula by the government of Japan in 2014.

PMID:36680523 | DOI:10.1111/ped.15359

Med Phys. 2023 Jan 21. doi: 10.1002/mp.16232. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) detection with B-mode and contrast-enhanced ultrasound (CUS) imaging often varies between subjects, especially in patients with background cirrhosis. Various factors contribute to this variability, including the tumor blood flow, tumor size, internal echoes, and its location in livers with diffuse fibro-cirrhotic changes OBJECTIVE: Towards improving lesion detection, this study evaluates a vasodilator, hydralazine, to enhance the visibility of HCC by reducing its blood flow relative to the surrounding liver tissue.

METHODS: HCC were analyzed for tumor visibility measured for B-mode, CUS, and hydralazine-augmented-contrast ultrasound (HyCUS) in an autochthonous HCC rat model. 21 tumors from 12 rats were studied. B-mode and CUS images were acquired before hydralazine injection. Rats received an intravenous hydralazine injection of 5 mg/kg, then images were acquired 20 min later. Four rats were used as controls. The difference in echo intensity of the lesion and the surrounding tissue was used to determine the visibility index (VI).

RESULTS: The visibility index for HCC was found to be significantly improved with the use of HyCUS imaging compared to traditional B-mode and CUS imaging. The visibility index for HCC was 16.5 ± 2.8 for HyCUS, compared to 5.3 ± 4.8 for B-mode and 4.1 ± 3.8 for CUS. The differences between HyCUS and the other imaging modalities were statistically significant, with p-values of 0.001 and 0.02, respectively. Additionally, when compared to control cases, HyCUS showed higher discrimination of HCC (VI = 6.4 ± 1.2) with a p-value of 0.003, while B-mode (VI = 6.7 ± 1.4, p = 0.5) and CUS (VI = 6.4 ± 1.2, p = 0.3) showed lower discrimination.

CONCLUSION: Vascular blood flow modulation by hydralazine enhances the visibility of HCC. HyCUS offers a potential problem-solving method for detecting HCC when B-mode and CUS are unsuccessful, especially with background fibro-cirrhotic liver disease. Future evaluation of the approach in humans will determine its translatability for clinical applications. This article is protected by copyright. All rights reserved.

PMID:36680519 | DOI:10.1002/mp.16232