Original Report Research Articles

Frailty as a Prognostic Indicator in Lung Transplantation: A Comprehensive Analysis

Introduction: Frailty is a complex pathobiological process characterized by diminished physiological reserve and increased vulnerability to stressors, which has been associated with unfavorable outcomes before and after lung transplantation. Methods: We undertook an extensive narrative review, encompassing a thorough exploration of original papers, observational studies, case reports, and meta-analyses published between 1990 and July 2023, in various databases, including PubMed, Embase, Cochrane Library, Wiley Online Library databases, and Google Scholar. The search terms [frailty] AND [lung transplant] were utilized. Additionally, the reference lists of retrieved articles were examined. Inclusion criteria comprised studies written in English and involving human subjects. The identified studies were categorized into pre-transplant and post-transplant populations, and the measurement tools used to assess frailty were analyzed, along with the clinical implications reported in the studies. Results: From 1 January 1990 to 1 July 2023, a total of 10 studies on frailty and lung transplantation were identified through online sources and bibliographic searches, involving a total of 2759 patients. Among these studies, six focused on the pre-transplant population, while four examined the post-transplant population. The Fried Frailty Phenotype (FFP) and the Short Physical Performance Battery (SPPB) were the most employed tools for measuring frailty. A table presents additional frailty assessment instruments and the clinical implications described in the studies. Conclusions: Frailty is prevalent both in patients with end-stage respiratory diseases awaiting lung transplantation and in postoperative lung transplant recipients. Most transplant centers recognize the value of assessing frailty in the evaluation of potential candidates for lung transplantation. Frailty has been shown to impact mortality on the waitlist and in the post-transplant period. However, the most effective methods for measuring frailty in lung transplant candidates and recipients have yet to be determined. Strategies to reverse frailty are available and show promising results on outcomes.

Back to the future: On the typography of electronic flight deck documentation

Prompted by a series of air accidents in the 1980s, Dr Asaf Degani's 1992 report, “On the Typography of Flight Deck Documentation,” reshaped the design of documents such as manuals, maps, charts, and checklists. His report addressed key principles of typography in printed documentation and provided 19 recommendations for best practice. These are now being applied to contemporary digital documentation. Consequently, our research team, comprising of practicing type designers, revisited the original report to determine whether the suggested conventions remain applicable in a contemporary setting. The findings highlight that some recommendations were based on misconceptions due to inconsistent terminology and now obsolete technologies, which led to a generalization of isolated typographic settings. This is problematic, given that absolute guidelines can only be applied to one specific typeface at a time, due to the varying characteristics of letterforms among different typefaces. Therefore, this single-source review aims to reset the baseline of typographic understanding, rekindle the conversation about legibility in flight safety, and highlight the importance of a more comprehensive approach to typography to improve legibility and, thus, safety. It follows the original report’s structure, providing reflections on Degani’s findings and updated information as required. Further, we provide revised recommendations, directions for future research and an outlook into the future of typography, which is currently undergoing unprecedented technological changes.

Artificial Intelligence-Assisted Detection of Osteoporotic Vertebral Fractures on Lateral Chest Radiographs in Post-Menopausal Women.

Osteoporotic vertebral fractures (OVFs) are often not reported by radiologists on routine chest radiographs. This study aims to investigate the clinical value of a newly developed artificial intelligence (AI) tool, Ofeye 1.0, for automated detection of OVFs on lateral chest radiographs in post-menopausal women (>60 years) who were referred to undergo chest x-rays for other reasons. A total of 510 de-identified lateral chest radiographs from three clinical sites were retrieved and analysed using the Ofeye 1.0 tool. These images were then reviewed by a consultant radiologist with findings serving as the reference standard for determining the diagnostic performance of the AI tool for the detection of OVFs. Of all the original radiologist reports, missed OVFs were found in 28.8% of images but were detected using the AI tool. The AI tool demonstrated high specificity of 92.8% (95% CI: 89.6, 95.2%), moderate accuracy of 80.3% (95% CI: 76.3, 80.4%), positive predictive value (PPV) of 73.7% (95% CI: 65.2, 80.8%), and negative predictive value (NPV) of 81.5% (95% CI: 79, 83.8%), but low sensitivity of 49% (95% CI: 40.7, 57.3%). The AI tool showed improved sensitivity compared with the original radiologist reports, which was 20.8% (95% CI: 14.5, 28.4). The new AI tool can be used as a complementary tool in routine diagnostic reports for the reduction in missed OVFs in elderly women.

A validation of placental pathology reports by ethnicity in New Zealand, through systematic analysis of histological slides

IntroductionReliability studies of placental examination have shown differing interobserver agreement for certain pathological features, a lack of uniform reporting criteria and variable experience among pathologists. In previous analyses we have shown that placental pathology differs by ethnicity. This validation study was performed to investigate whether bias related to ethnicity is a feature of placental pathology reporting in New Zealand (NZ). Methods199 of 1726 eligible perinatal death cases between 2008 and 2017 were selected at random for this audit-type study, including 51 cases from South Asian, Māori and NZ European ethnicity and 46 cases from Pacific mothers. Stored histology slides were blinded and re-examined by an experienced perinatal pathologist, and linked to the corresponding original pathology report. Interobserver agreement (overall, by ethnicity and by gestational age) was described by proportional differences and kappa coefficients. ResultsTotal interobserver agreement between original placental reporting and the validation review was 89.7 %, which differed by pathological feature. There was generally more underreporting than overreporting (3.6 % and 6.7 %, respectively). There was little disagreement by ethnicity (decidual vasculopathy [p = 0.03]), although there were more differences by gestational age (villous morphology [p < 0.01], chorioamnionitis [p = 0.03], high-grade villitis of unknown etiology [p < 0.01], and placental haemorrhage [p = 0.03]). DiscussionNo systematic bias in placental pathology reporting in NZ was identified by ethnicity or gestational age, as observed differences could be related to the underlying prevalence of pathology. We identified more underreporting than overreporting of pathology in the original reports, emphasizing the importance of placental investigation by specialised perinatal pathologists.

Evaluation of CINA® LVO artificial intelligence software for detection of large vessel occlusion in brain CT angiography

ObjectiveTo systematically evaluate the ability of the CINA® LVO software to detect large vessel occlusions eligible for mechanical thrombectomy on CTA using conventional neuroradiological assessment as gold standard. MethodsRetrospectively, two hundred consecutive patients referred for a brain CTA and two hundred patients that had been subject for endovascular thrombectomy, with an accessible preceding CTA, were assessed for large vessel occlusions (LVO) using the CINA® LVO software. The patients were sub-grouped by occlusion site. The original radiology report was used as ground truth and cases with disagreement were reassessed. Two-by-two tables were created and measures for LVO detection were calculated. ResultsA total of four-hundred patients were included; 221 LVOs were present in 215 patients (54 %). The overall specificity was high for LVOs in the anterior circulation (93 %). The overall sensitivity for LVOs in the anterior circulation was 54 % with the highest sensitivity for the M1 segment of the middle cerebral artery (87 %) and T-type internal carotid occlusions (84 %). The sensitivity was low for occlusions in the M2 segment of the middle cerebral artery (13 % and 0 % for proximal and distal M2 occlusions respectively) and in posterior circulation occlusions (0 %, not included in the intended use of the software). ConclusionsLVO detection sensitivity for the CINA® LVO software differs largely depending on the location of the occlusion, with low sensitivity for detection of some LVOs potentially eligible for mechanical thrombectomy. Further development of the software to increase sensitivity to all LVO locations would increase the clinical usefulness.

Quantification and significance of extraprostatic findings on prostate MRI: a retrospective analysis and three-tier classification

ObjectivesTo quantify extraprostatic findings (EPFs) on prostate MRI, estimate the proportion of reported and unreported EPFs, assess their clinical importance, and propose standardized reporting of EPFs.Materials and methodsProstate 3-T MRI studies, reports, and clinical data from 623 patients (age 67.9 ± 8.2 years) were retrospectively analyzed and re-evaluated for the presence of EPFs and their clinical significance: E1—no finding or findings that have no clinical significance; E2—potentially significant findings; and E3—significant findings.ResultsSecondary reading identified 1236 EPFs in 593 patients (1.98 ± 1.13 EPFs per patient, no EPFs in 30 patients), from which 468 (37.8%) were mentioned in the original report. The most common findings included diverticulosis (44% of patients), hydrocele (34%), inguinal fat hernia (16%), and bladder wall trabecular hypertrophy (15%). There were 80 (6.5%) E2 EPFs and 30 (2.4%) E3 EPFs. From E3 EPFs, 10 (33%) were not originally reported. A workup was suggested in 35 (52%) of the 67 originally reported E2 and E3 findings with follow-up and performed in 20 (30%). Fourteen (21%) EPFs in 11 patients influenced their management. Four experienced radiologists originally reported 1.8 to 2.5 findings per patient (p < 0.0001).ConclusionsEPFs on prostate MRI are frequent, but only 2.4% are clinically significant (E3), and 33% of these are not reported. Only 30% of E2 and E3 findings are further explored, and 21% influence patient management. We suggest that an “E” category should be attached to the PI-RADS system to identify the presence of EPFs that require further workup.Critical relevance statementExtraprostatic findings on prostate MRI are frequent, but only 2.4% are clinically significant (E3), and 33% of these are not reported. We advocate standardized reporting of extraprostatic findings indicating their clinical significance.Key points• Extraprostatic findings on prostate MRI are frequent with an average of two findings per patient.• 2.4% of extraprostatic findings are significant, and 33% of these are not reported.• There is a significant variability among experienced radiologists in reporting extraprostatic findings.Graphical

Differences in the Development of Language and Social Independence in Children with Speech Delay and Sensorineural Hearing Loss based on Age of Early Intervention and Duration of Auditory Verbal Therapy

Highlights :1. This original research report provides information to the public about the importance of early detection, the use of hearing technology and the advantages of Auditory Verbal Therapy in delayed speech children with sensorineural hearing loss, where this therapy makes it easier for children to achieve language development on par with other children their age.2. Auditory Verbal Therapy as part of the process of learning to speak and hear deaf children is still quite new and unfamiliar among the community, so based on this study it can be seen that AVT has a positive impact on child development. AbstractSpeech delay with sensorineural hearing loss is a delay in a child's speech process compared to normal children of the same age, mostly caused by hearing loss. It can give may affect the development of language and social independence of children. Auditory Verbal Therapy (AVT) as early intervention maximizes the use of residual hearing with hearing aids or a cochlear implant for sound detection. Therapy that is routinely and periodically conducted may affect language development to support children's independence. This study aims to analyze differences in the development of language and social independence of children with delayed speech and sensorineural hearing loss based on the age of early intervention and duration of auditory verbal therapy. This study used an analytical-observational study design with a cross-sectional approach. The samples were obtained by total sampling from all children who underwent routine AVT once a week at the Aurica Surabaya Foundation, with a total sample of 29 children. The instrument used Developmental Pre-Screening Questionnaire. Method of data analysis was bivariate analysis with the Chi-Square (p-value) proportions different test using SPSS . The results regarding language development based on the age of early intervention and the duration of AVT obtained p = value 0.013 (p &lt; 0.05) and p = 0.019 (p &lt; 0.05), while the results of the chi-square test analysis of the development of social independence based on the age of early intervention and duration of AVT obtained p value = 0.229 (p &gt; 0.05) and p-value = 0.111 (p &gt; 0.05). In conclusion, there was a difference between language development based on the age of early intervention and the duration of AVT, but no difference was found between the development of social independence based on the age of early intervention and the duration of AVT.

Development and validation of open-source deep neural networks for comprehensive chest x-ray reading: a retrospective, multicentre study

Artificial intelligence (AI) systems for automated chest x-ray interpretation hold promise for standardising reporting and reducing delays in health systems with shortages of trained radiologists. Yet, there are few freely accessible AI systems trained on large datasets for practitioners to use with their own data with a view to accelerating clinical deployment of AI systems in radiology. We aimed to contribute an AI system for comprehensive chest x-ray abnormality detection. In this retrospective cohort study, we developed open-source neural networks, X-Raydar and X-Raydar-NLP, for classifying common chest x-ray findings from images and their free-text reports. Our networks were developed using data from six UK hospitals from three National Health Service (NHS) Trusts (University Hospitals Coventry and Warwickshire NHS Trust, University Hospitals Birmingham NHS Foundation Trust, and University Hospitals Leicester NHS Trust) collectively contributing 2 513 546 chest x-ray studies taken from a 13-year period (2006-19), which yielded 1 940 508 usable free-text radiological reports written by the contemporary assessing radiologist (collectively referred to as the "historic reporters") and 1 896 034 frontal images. Chest x-rays were labelled using a taxonomy of 37 findings by a custom-trained natural language processing (NLP) algorithm, X-Raydar-NLP, from the original free-text reports. X-Raydar-NLP was trained on 23 230 manually annotated reports and tested on 4551 reports from all hospitals. 1 694 921 labelled images from the training set and 89 238 from the validation set were then used to train a multi-label image classifier. Our algorithms were evaluated on three retrospective datasets: a set of exams sampled randomly from the full NHS dataset reported during clinical practice and annotated using NLP (n=103 328); a consensus set sampled from all six hospitals annotated by three expert radiologists (two independent annotators for each image and a third consultant to facilitate disagreement resolution) under research conditions (n=1427); and an independent dataset, MIMIC-CXR, consisting of NLP-annotated exams (n=252 374). X-Raydar achieved a mean AUC of 0·919 (SD 0·039) on the auto-labelled set, 0·864 (0·102) on the consensus set, and 0·842 (0·074) on the MIMIC-CXR test, demonstrating similar performance to the historic clinical radiologist reporters, as assessed on the consensus set, for multiple clinically important findings, including pneumothorax, parenchymal opacification, and parenchymal mass or nodules. On the consensus set, X-Raydar outperformed historical reporter balanced accuracy with significance on 27 of 37 findings, was non-inferior on nine, and inferior on one finding, resulting in an average improvement of 13·3% (SD 13·1) to 0·763 (0·110), including a mean 5·6% (13·2) improvement in critical findings to 0·826 (0·119). Our study shows that automated classification of chest x-rays under a comprehensive taxonomy can achieve performance levels similar to those of historical reporters and exhibit robust generalisation to external data. The open-sourced neural networks can serve as foundation models for further research and are freely available to the research community. Wellcome Trust.

Overcoming Obstacles: The Legacy of Fidel Pagés, Founder of the Epidural, 100 Years After His Passing.

Fidel Pagés, a Spanish surgeon, tragically died in 1923 at the age of 37, just 2 years after his publication "Anestesia Metamérica," the first description of human thoracolumbar epidural anesthesia. In the intervening 100 years, epidural anesthesia has faced countless obstacles, starting with the dissemination of his initial report, which was not widely read nor appreciated at the time. However, the merits of the technique have fueled innovations to meet these challenges over the years. Even today, while epidural anesthesia is widely embraced, particularly in obstetric and chronic pain medicine, the pressures of the operating room for efficiency and a low tolerance for failure, pose modern-day challenges. Here, we revisit Pagés' original report and highlight the key innovations that have allowed for the evolution of this essential anesthesia technique.

The importance of weekly Radiology-General Surgery Multi-Disciplinary Meetings (MDMs) in the management of Emergency General Surgery (EGS) patients

Abstract Aims Most patients in Emergency-General-Surgery (EGS) require radiological investigations as part of their management plan. However, unlike cancer services where structured multi-disciplinary-meetings (MDMs) form an integral part of patient management, MDMs are not commonly practised in EGS. Having a weekly Radiology-General Surgery-MDM leads to better outcome in management of EGS-patients, &amp; also improves learning of surgeons &amp; junior-doctors. Methods A prospective study of weekly 1-hour Radiology-GeneralSurgery-MDMs over 10-weeks during May2023-September2023 was performed. These MDMs were led by a consultant radiologist who discussed the scans with consultant surgeons &amp; other junior-doctors. Factors taken into consideration were clinical presentation, original scan report, any missed findings not mentioned in original scan report, any changes recommended in management plan that would lead to better patient outcome. The scans were also discussed with junior-doctors to improve their knowledge of interpretation of scans. Results A total of 70 cases were discussed during the study period, 25 (35.71%) initially reported by the out-of-hours reporting system. Few had missed findings that were noted as result of Radiology-GeneralSurgery-MDM, &amp; 27(38.57%) had change in management plan. The informal feedback collected after these MDMs noted over 85% junior-doctors agreed that these MDMs had significant impact on their understanding of interpretation of radiological-scans in EGS. Conclusion Weekly Radiology-GeneralSurgery-MDMs for EGS-admissions has been seen to improve patient outcome as a result of having an expert 2nd-opinion, &amp; also recommending change in management plan in significant proportion of patients. It also had an impact on learning the clinical correlation of radiological-scans by junior-doctors who regularly attended these meetings.

Medium-chain triglycerides (8:0 and 10:0) increase muscle mass and function in frail older adults: a combined data analysis of clinical trials.

Three clinical trials have examined the chronic effects of medium-chain triglycerides (MCTs) on muscle mass and function in frail older adults (mean age 85 years old). However, significant increases in muscle mass and some muscle function relative to long-chain triglycerides (LCTs) have yet to be shown, possibly due to the small number of participants in each trial. We re-analyzed these previous clinical trials to clarify whether MCT supplementation can increase muscle mass and function. After adding post hoc tests to the original report, we compared changes in measurement between the MCT and LCT groups in the first 2 trials and conducted a combined data analysis. In a combined data analysis, changes from baseline in measurements at the 3 months intervention in the MCTs- and LCTs-containing groups were assessed by analysis of covariance adjusted for baseline values of each measurement, age, sex, BMI, allocation to trial, habitual intakes in energy, protein, leucine, octanoic acid, decanoic acid, and vitamin D during the baseline period. The Mann-Whitney U test was used to analyze data on right and left knee extension times. MCT supplementation for 3 months increased muscle function relative to LCT supplementation with and without an L-leucine (1.2 g) and vitamin D (cholecalciferol, 20 μg)-enriched supplement. In a combined data analysis (n = 29 in MCTs, n = 27 in LCTs), relative to supplementation with 6 g LCTs/day, supplementation with 6 g MCTs/day at dinner for 3 months significantly increased body weight (adjusted mean change from baseline: MCTs 1.2 vs. LCTs 0.2 kg, p = 0.023), right arm muscle area (MCTs 1.4 vs. LCTs-0.7 cm2, p = 0.002), left calf circumference (p = 0.015), right-hand grip strength (MCTs 1.6 vs. LCTs 0.3 kg, p = 0.017), right knee extension time (p = 0.021), left knee extension time (p = 0.034), walking speed (p = 0.002), and number of iterations in leg open and close test (p < 0.001) and decreased right triceps skinfold thickness (p = 0.016). In frail older adults, supplementation for 3 months with a low dose (6 g/day) of MCTs (C8:0 and C10:0) increased muscle mass and function. These findings indicate the potential for the practical use of MCTs in daily life in treating sarcopenia.

Women’s autonomy in healthcare decision making: a systematic review

ObjectivesAlthough there are calls for women’s empowerment and gender equity globally, there are still large disparities regarding women’s autonomy in healthcare decision making. The autonomy of women is believed to be crucial in improving their health-related outcomes. This review discusses factors that influence autonomy among women in healthcare decision making.DesignSystematic review.Data sourcesPubMed, Web of Science and Scopus were searched from 2017–2022.Eligibility criteriaThe inclusion criteria include original articles, case studies and reports that has been written in the English Language, while manuscripts with no full article, reviews, newspaper reports, grey literatures, and articles that did not answer the review objectives were excluded.Data extraction and synthesisWe carried out data extraction using a standardized data extraction form, that has been organized using Microsoft Excel. A narrative synthesis was carried out to combine the findings of all included articles.ResultsA total of 70 records were identified and 18 were reviewed, yielding eight articles to be included in the accepted list of studies. All studies were conducted in developing countries and most of the studies were cross sectional. Factors that were associated with women’s autonomy in healthcare decision making were age, women’s education and occupation, husbands’/partners’ education and occupation, residential location or region of residence, household wealth index as well as culture and religion.ConclusionsIdentification of these factors may help stakeholders in improving women’s autonomy in healthcare decision making. Policymakers play a crucial role in healthcare decision making by enacting laws and policies that protect women's rights, promoting gender-sensitive healthcare services, ensuring access to comprehensive information, promoting health education, and supporting vulnerable populations. These efforts ensure women's autonomy including able to access to unbiased and effective healthcare services.

Physical Inactivity Prevalence in the Islamic World: An Updated Analysis of 47 Countries.

Physical inactivity prevalence estimates for youth and adults have been published on a global scale and for various geographical and geopolitical permutations. Only one such study has presented estimates for adults in Muslim countries, and it is nearly 10years old. I conducted an update of this study by incorporating newer data, refining methods, and including youth estimates. I identified 47 Muslim countries with physical inactivity data for youth, adults, or both. Data were extracted by country primarily from global estimates reported by Guthold etal in 2018 and 2020 and from World Health Organization surveillance data repositories. Weighted prevalence calculations for total prevalence and by sex, ethnicity (Arab vs non-Arab), and country income group accounted for country population, study sample size, and a country's proportion of Muslims. Z tests and chi-square tests, and follow-up odds ratios and percentage deviations, respectively, were used to determine differences by sex, ethnicity, and country income group. Overall physical inactivity prevalence was 84.2% (youth) and 29.6% (adults). Gaps favoring males over females were observed for youth (5.6% lower prevalence) and adults (9.6% lower prevalence). Gaps favoring non-Arabs over Arabs were observed for youth (3.9% lower) and adults (3.8% lower). No pattern emerged for country income group for youth; however, prevalence for adults trended upward across income groups from low (22.7%) to high (62.0%). Gaps by sex and ethnicity have narrowed since the original report and prevalence values are somewhat higher than current global estimates.

Association between military service identified through public data tracing and Alzheimer’s disease neuropathology at autopsy

AbstractBackgroundMilitary veterans face increased risk of Alzheimer’s disease and related dementias (ADRD) compared to the general population, but the association between the military exposome and ADRD pathology is poorly understood. Existing biobanks rarely collect military service information, complicating efforts to characterize military risk factors. Public data tracing methods linking the military exposome to existing neuropathological data have the potential to catalyze research on the mechanisms driving brain health disparities.MethodSubjects were decedents from two Alzheimer’s Disease Research Center brain banks who died between 1986‐2018 and were characterized on neurofibrillary tangle burden (NFT‐B score, n = 1154). Military service was characterized through public data tracing (Figure 1): systematic extractions from public records including obituaries, newspapers, and enlistment records (Figure 2). NFT‐B score, per National Institute of Aging and Alzheimer’s Association guidelines for neuropathologic change, was extracted from the standardized Neuropathology Dataset form or from original autopsy reports. Generalized ordered logistic regression with site‐level clustered standards errors was used to model NFT‐B score, adjusting for age, sex, and year of death.ResultPublic data tracing identified 373 decedents (32% of the sample) with a history of military service. After adjusting for age, sex, and year of death, decedents with a history of military service had a 12% greater odds (OR = 1.12, 95% CI: 1.11–1.13) of a more severe NFT burden compared to those without a history of military service, which was proportional when comparing the odds at each increasing B score level (B score = (1,2, or 3), vs (0), B score = (2,3) vs (0,1) and B score = (3) vs (0,1,2)) (Table 1).ConclusionPublic data tracing offers a promising way to retrospectively add the military exposome into brain tissue biomarkers research. Military service was associated with more severe neurofibrillary tangle pathology, one of the primary neuropathological features of Alzheimer’s disease. Future research should explore the feasibility and validity of public data tracing for more detailed characterization of military service, such as length and branch of service, involvement in specific conflicts, or exposure to environmental toxins, which may elucidate mechanisms underlying its association with ADRD pathology.

Per-patient Negative Predictive Value of the CT and MRI Liver Imaging Reporting and Data System Version 2018 Treatment Response Algorithm for Hepatocellular Carcinoma.

Background The Liver Imaging Reporting and Data System version 2018 (LI-RADS) treatment response algorithm (TRA) is a high-specificity, lower-sensitivity grading system to diagnose hepatocellular carcinoma (HCC) and recurrence after local-regional therapy. However, the emphasis on specificity can result in disease understaging, potentially leading to poorer posttransplant outcomes. Purpose To determine the negative predictive value (NPV) of pretransplant CT and MRI assessment for viable HCC on a per-patient basis using the LI-RADS TRA, considering explant pathology as the reference standard. Materials and Methods Patient records from 218 consecutive adult patients from a single institution with HCC who underwent liver transplant from January 2011 to November 2017 were retrospectively reviewed. Two readers blinded to the original report reviewed immediate (within 90 days) pretransplant imaging and characterized observations according to the LI-RADS TRA. Based on this, patients with LR-4, LR-5, or LR-TR (treatment response) viable tumors were designated as viable tumor; patients with solely LR-3 or LR-TR equivocal tumors were designated as equivocal; and patients with only LR-TR nonviable lesions were designated as no viable disease. Patients were designated as within or outside the Milan criteria. These per-patient designations were compared with the presence of viable disease at explant pathology. Fisher exact test was used to compare the differences between CT and MRI. Weighted κ values were used to calculate interreader reliability. Results Final study sample consisted of 206 patients (median age, 61 years [IQR, 57-65 years]; 157 male patients and 49 female patients). Per-patient LI-RADS TRA assessment of pretransplant imaging had an NPV of 32% (95% CI: 27, 38) and 26% (95% CI: 20, 33) (readers 1 and 2, respectively) for predicting viable disease. Seventy-five percent (reader 1) and 77% (reader 2) of patients deemed equivocal had residual tumors at explant pathology. Weighted interreader reliability was substantial (κ = 0.62). Conclusion Patient-based stratification of viable, equivocal, and nonviable disease at pretransplant CT or MRI, based on LI-RADS TRA, demonstrated low negative predictive value in excluding HCC at explant pathology. © RSNA, 2023 See also the editorial by Tamir and Tau in this issue.

Immunohistochemical Tumor Expression Predicts Response to CD3xCD20 Bispecific Antibodies in Patients with Relapsed/Refractory B Cell Lymphoma

Introduction Several studies show that CD3xCD20 bispecific antibodies show promising results in relapsed or refractory B-cell lymphomas and may have a milder adverse effect profile compared to chimeric antigen receptor T cell therapy (CAR-T). Tumor loss of antibody target (i.e. CD19 or PD1) have shown to negatively affect treatment outcomes in CD19-CAR-T cell therapy in DLBCL, and anti-PD1 therapy in Hodgkin lymphoma. It has, to our knowledge, not been reported how loss of CD20 expression and other immunohistochemical (IHC) expression patterns affects treatment outcomes in patients treated with CD3xCD20 antibodies. Methods We collected data on all patients in Denmark who received CD3xCD20 bispecific antibodies from 2017 to 2023. Electronic health records were assessed for general baseline characteristics and response according to Lugano criteria. Pathology reports on pre- and post-CD3xCD20 therapy lymphoma samples were collected and assessed on IHC analysis of CD20, Ki67, CD10, Bcl2, Bcl6, MUM1, germinal center B-cell (GCB) subtype and non-germinal center B-cell subtypes (non-GCB) according to Hans algorithm, as well as reports on cytogenetic FISH analysis regarding MYC with BCL2 and/or BCL6 rearrangements. To determine whether an expression was weak, negative, or strong the assessment of the original pathology reports was used. Results Pre-treatment IHC assessments were available in 122 patients. These were distributed across 81 patients with DLBCL, 32 with FL and 9 with other lymphoid neoplasms (MZL, HL, CLL). Of these, 109 had a strong CD20 expression, 10 had a weak CD20 expression, while 3 had no expression of CD20. Patients with a weak CD20 expression before treatment had an overall survival (OS) rate after 12 months at 40% (95% CI, 9.5-70) compared to 69% in patients with strong CD20 expression (95% CI, 45-61) (Figure 1, p=0.08). In a univariable Cox regression, we found that negative CD20 expression and higher Ki67 was significantly associated with inferior OS (Table 1, respectively HR=2.11 and HR=1.02 (per %-change in Ki67)). Worse performance status and a higher number of previous lines of treatment were also significantly associated with inferior overall survival (respectively HR=1.85 and HR=1.20). Surprisingly, BCL6 rearrangement was significantly associated with superior OS (HR=0.46). In a multivariable cox regression using OS as the endpoint, weak and negative IHC expression of CD20 was significantly associated with inferior OS (respectively HR=3.29, 95% CI 1.32-8.23, p=0.011 and HR=6.79 95% CI 1.25-36.76, p=0.026). Positive BCL6 compared to negative was associated with increased OS (HR =0.48, 95% CI 0.24 - 0.94, p=0.032). Analyzing only patients with DLBCL (n=81), weak and negative IHC expression of CD20 were the only factors to remain significantly associated with inferior overall survival (respectively HR=3.01, 95% CI 1.10-8.28, p=0.032 and HR=7.26, 95% CI 1.35-43.35, p=0.026). BCL6 rearrangement was associated with an increased overall survival, however only borderline statistically significant (HR=0.53, 95% CI 0.26-1.08, p=0.082). With regards to treatment response weak CD20 expression, worse performance status, higher Ki67 and a higher number of prior lines of treatment was in univariable analysis significantly associated with not being in a complete remission (CR) (respectively HR=2.28, HR=1.73, HR=1.01(per %-change in Ki67), HR=1.23 (per prior line of treatment). In a multivariable cox regression only weak and negative CD20 expression remained significantly associated with not being in CR (respectively HR=2.40, 95% CI 1.1-5.25, p=0.028 and HR=5.7 95% CI 1.14-28.58, p=0.034). Of the 48 patients who had biopsy-confirmed relapse, 29 had a weak or negative IHC CD20 expression (24 with a negative expression and 5 with a weak expression). Of these 29 patients, 24 had a strong pre-treatment IHC CD20 expression. Conclusions To our knowledge, we here present the first long-term analysis of the prognostic effect of tumor immunohistochemistry properties in patients treated with CD3xCD20 bispecific antibodies. We find that CD20 expression before treatment is an important prognostic factor, as patients with lymphomas with weak CD20 expression yield significantly poorer responses and decreased overall survival. Additionally, we find that BCL6 rearrangement is associated with superior overall survival in patients treated with CD3XCD20 bispecific antibodies.

Effects of Hydroxyurea on Fertility in Sickle Cell Disease; A Systemic Review and Meta-Analysis

Background: Hydroxyurea (HU) remains a widely available and clinically effective therapy for sickle cell disease (SCD). Whilst a substantial body of evidence documents the benefits of HU with acceptable short- and long-term toxicity profiles, concerns regarding its safety persist, particularly regarding fertility. Methods: This systemic review and meta-analysis evaluated fertility parameters in males and females with SCD receiving HU therapy. Articles published from inception to July 2023 were searched in PubMed and EMBASE. Terms used in the research for primary endpoints were “”sickle cell disease“ and ”infertility“ and ”hydroxyurea“; ”sickle cell disease“ and ”fertility“ and ”hydroxyurea“; ”sickle cell anaemia“ and ”hydroxyurea“ and ”infertility“; ”sickle cell disease“ and ”hydroxycarbamide“ and ”infertility“; and combination of the terms ”sickle cell anaemia“ and ”hydroxycarbamide“ and ”infertility“. Our research focused on primary fertility outcomes stratified by male or female gender. Inclusion criteria were as follows: (i) Studies published in English from inception to the present day; (ii) Studies subjects (aged ≥ 6 years), prospective and retrospective cohort studies reporting frequency of outcomes of interests (semen parameters and female infertility events) stratified by HU therapy. Case reports, reviews, animal studies, duplications and studies on very young patients (aged &amp;lt; 6 years) were excluded . The Newcastle-Ottawa Scale was used to assess the quality and risk of bias of the included studies. Results: A total of 160 articles were initially retrieved from PubMed and Embase. After applying the exclusion criteria, the full texts of 32 potentially relevant studies were reviewed. A total of 25 were excluded due to lack of relevant research (n=11), non-human research (n=4), not original research (n=6), case reports (n=3) and articles not in English (n=1). In total, 7 were finally included for meta-analysis (Figure). Four studies were included that evaluated the effects of HU on sperm parameters in males. Three studies were included that assessed anti-mullerian hormone (AMH) levels and ovarian reserves in females. Changes from baseline were used to identify compromised fertility. Amongst males, HU treatment negatively impacted the concentration of spermatozoa (MD= -15.48 million/mL; 95% CI: [-20.69, -10.26]; p&amp;lt; 0.001) which continued following treatment cessation (MD= -20.09 million/mL; 95% CI: [-38.78, -1.40]; P= 0.04). HU treatment also led to lower total sperm counts (MD= -105.87 million; 95% CI: [-140.61, -71.13]; P&amp;lt; 0.001) which persisted after treatment cessation (MD= -53.05 million; 95% CI: [-104.96, -1.14]; P= 0.05). Sperm volume, initial forward motility and morphology were unaffected by HU treatment. In females, HU treatment did not impact the mean AMH levels 2.01 (95% CI [1.58, 2.44] and a total of 67% patients treated with HU showed normal ovarian reserves (95% CI [53%, 82%]). The fertility of 33% of patients was however negatively impacted by HU therapy. Conclusions: Our findings suggest that the use of HU for SCD impacts seminal fluid parameters in males and diminishes ovarian reserves in a significant number of females. Fertility preservation counselling should be considered in patients with SCD in both genders of reproductive age prior to HU therapy. Our study highlights the need for long-term multi-centric studies using consistent HU doses and outcome assessments to fully understand the impact of HU on fertility in SCD patients.

Smoking cessation interventions and implementations across multiple settings in Japan: a scoping review and supplemental survey

BackgroundSmoking is the leading risk factor for death worldwide. In Japan, although several evidence-based interventions (EBIs) for smoking cessation have been disseminated or adopted, there is a gap between scientific evidence and the actual implementation. This scoping review aimed to describe the knowledge gaps in local-level smoking cessation interventions in Japan, their implementation outcomes, implementation barriers and facilitators, and the use of implementation strategies.MethodsThis study comprised two approaches: (1) a comprehensive scoping review of primary and grey literature, and (2) a supplemental survey of organizations in the grey literature. For the scoping review, we included original studies or reports on smoking cessation interventions targeting adults aged 18 years and older, or providers of cessation support at various settings (community, workplace, school, and clinical settings) in Japan. The extracted data included basic characteristics, intervention categories, implementation outcomes, factors influencing implementation, and implementation strategies for each intervention. Responses to the supplemental survey were extracted same used for the scoping review. To gain a deeper understanding, semi-structured interviews were conducted with some of the organizations in the survey.ResultsA total of 600 interventions with 691 intervention components, based on EBIs in the 2020 US Surgeon General Report, from 498 articles were included in the data extraction; 32 of the 88 organizations responded to the survey. Regarding the overall knowledge about smoking cessation intervention components, behavioral counseling, and cessation medication in clinical settings were mostly reported (34.7%). Implementation outcomes were measured in 18 articles (3.0%) and penetration was mostly reported. Regarding influential factors, “available resources,” and “knowledge and beliefs about the intervention” for barriers, and “relative priority” for facilitators were mostly reported. Implementation strategies were measured in 29 articles (4.8%), and “Train and educate stakeholders” was mostly reported.ConclusionsMost EBIs reported in the Japanese literature included smoking cessation treatments in clinical settings. While a few articles focused on the implementation indicators in Japan, significant knowledge and experience were extracted from the grey literature, especially in the workplace and community settings. Future research should focus more on implementation to reduce the knowledge gap regarding smoking cessation interventions.

Genetic Patterns of Selected Muscular Dystrophies in the Muscular Dystrophy Surveillance, Tracking, and Research Network.

To report the genetic etiologies of Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy (LGMD), congenital muscular dystrophy (CMD), and distal muscular dystrophy (DD) in 6 geographically defined areas of the United States. This was a cross-sectional, population-based study in which we studied the genes and variants associated with muscular dystrophy in individuals who were diagnosed with and received care for EDMD, LGMD, CMD, and DD from January 1, 2008, through December 31, 2016, in the 6 areas of the United States covered by the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). Variants of unknown significance (VUSs) from the original genetic test reports were reanalyzed for changes in interpretation. Among 243 individuals with definite or probable muscular dystrophy, LGMD was the most common diagnosis (138 cases), followed by CMD (62 cases), DD (22 cases), and EDMD (21 cases). There was a higher proportion of male individuals compared with female individuals, which persisted after excluding X-linked genes (EMD) and autosomal genes reported to have skewed gender ratios (ANO5, CAV3, and LMNA). The most common associated genes were FKRP, CAPN3, ANO5, and DYSF. Reanalysis yielded more definitive variant interpretations for 60 of 144 VUSs, with a mean interval between the original clinical genetic test of 8.11 years for all 144 VUSs and 8.62 years for the 60 reclassified variants. Ten individuals were found to have monoallelic pathogenic variants in genes known to be primarily recessive. This study is distinct for being an examination of 4 types of muscular dystrophies in selected geographic areas of the United States. The striking proportion of resolved VUSs demonstrates the value of periodic re-examinations of these variants. Such re-examinations will resolve some genetic diagnostic ambiguities before initiating repeat testing or more invasive diagnostic procedures such as muscle biopsy. The presence of monoallelic pathogenic variants in recessive genes in our cohort indicates that some individuals with muscular dystrophy continue to face incomplete genetic diagnoses; further refinements in genetic knowledge and diagnostic approaches will optimize diagnostic information for these individuals.

Retracted] miR‑216b inhibits glioma cell migration and invasion through suppression of FoxM1.

Following the publication of the above article, a concerned reader reported that certain of the cell invasion assay data shown in Fig. 2D, and the mouse images shown in Fig. 6A, were strikingly similar to data that appeared in the following (subsequently published) article: Li C, Zheng H, Hou W, BaoH, Xiong J, Che W, Gu Y, Sun H and Liang P: Long non-coding RNA linc00645 promotes TGF-β-induced epithelial-mesenchymal transition by regulating miR-205-3p-ZEB1 axis in glioma. Cell Death Dis 10: 717, 2019. The authors regret that the data in question featured in the original Oncology Reports article had been re-used, and accept the Editor's decision to retract this article; furthermore, the authors and the Editor apologize to the readership of the Journal for any inconvenience caused. [Oncology Reports 38: 1751‑1759, 2017; DOI: 10.3892/or.2017.5824].