Recurrent adult-onset hypophyseal Langerhans cell histiocytosis after radiotherapy: A case report

INTRODUCTION: Langerhans cell histiocytosis is a rare disease within the adult population, with very few cases reported as solitary hypophyseal lesions in adults. Of the reported cases, most have been treated successfully with surgery, radiotherapy, and/or chemotherapy. Radiotherapy has been thought to be curative at the relatively low dose of 20Gy. Here we report a case of recurrent hypophyseal Langerhans cell histiocytosis 9 months after radiotherapy with an interval period of symptomatic and radiographic response to therapy. CASE PRESENTATION: A 50-year-old Caucasian woman who had headaches, memory difficulties, and diabetes insipidus was found to have a 2.5cm suprasellar mass. Langerhans cell histiocytosis was diagnosed following stereotactic brain biopsy. Further workup revealed no other lesions. Initial radiation treatment succeeded in shrinking the tumor and relieving clinical symptoms temporarily; however, growth and recurrence of clinical symptoms was noted at 9 months. Re-irradiation was well tolerated and the patient had no acute side effects. CONCLUSION: Isolated hypophyseal involvement by Langerhans cell histiocytosis in adults is a unique presentation of a rare disease. Although radiotherapy doses as low as 20Gy have been reported to offer control, this case demonstrates that higher doses may be warranted to ensure tumor control. With modern imaging and radiotherapy techniques higher doses should offer little increased more durable risk to surrounding critical structures

Survival following gamma knife radiosurgery for brain metastasis from breast cancer

BACKGROUND: Breast cancer is the second most common cause of brain metastases in the United States. Although breast cancer induced brain metastases represent an incurable condition, some patients experience prolonged survival. In this retrospective study, we examine a cohort of patients with brain metastases from breast cancer treated with Gamma Knife stereotactic radiosurgery to identify factors that predict better outcomes. METHODS: A retrospective database of 100 patients treated for brain metastases due to breast cancer via Gamma Knife radiosurgery (GKS) from July 1998 through March 2009 was reviewed. Patients who received radiosurgery as sole treatment, as a planned boost after whole brain radiotherapy or surgical resection, or as salvage after prior whole brain radiation therapy (WBRT) or surgical resection were included. Prognostic factors identified to be significant for survival in previous brain metastasis studies were analyzed for significance by univariate and multivariate Cox analysis. RESULTS: Overall, the median brain progression-free survival time was 7.1 months and the median survival time was 12.3 months. No prognostic variables were significant for brain progression-free survival. For patients treated with a planned GKS after WBRT, GKS as sole treatment, GKS salvage after WBRT, GKS boost after surgery, or GKS for surgical salvage the median survival times (MSTs) were as follows: 12.2 months, 12.4 months, 9.5 months, 27.6 months and 33.4 months respectively. Differences between the groups were not significant (p = 0.06); however, GKS boost after surgery and GKS for salvage after surgery did have a trend toward better overall survival. The MST for patients of age <65 years was 14.5 months, compared to age ≥65 which was 7.7 months (p = 0.06) and remained a significant prognostic factor for overall survival on multivariate analysis. The MST for patients with a single lesion was 16.9 months, not significantly different than the MST of 14.5 months for patients with 2–3 lesions. However patients with >3 lesions had a MST of 5.9 months, which was significantly worse. Breast cancer subtype as approximated by biomarkers and KPS were not significant predictors of overall survival and stage at initial diagnosis was inversely associated with survival. CONCLUSION: Stereotactic radiosurgery offers good local control and prolonged survival in selected patients. Age and number of lesions are strong predictors of overall survival

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery

A High Density Integrated Genetic Linkage Map of Soybean and the Development of a 1536 Universal Soy Linkage Panel for Quantitative Trait Locus Mapping

Single nucleotide polymorphisms (SNPs) are the marker of choice for many researchers due to their abundance and the high-throughput methods available for their multiplex analysis. Only recently have SNP markers been available to researchers in soybean [Glycine max (L.) Merr.] with the release of the third version of the consensus genetic linkage map that added 1141 SNP markers to the map. Our objectives were to add 2500 additional SNP markers to the soybean integrated map and select a set of 1536 SNPs to create a universal linkage panel for high-throughput soybean quantitative trait locus (QTL) mapping. The GoldenGate assay is one high-throughput analysis method capable of genotyping 1536 SNPs in 192 DNA samples over a 3-d period. We designed GoldenGate assays for 3456 SNPs (2956 new plus 500 previously mapped) which were used to screen three recombinant inbred line populations and diverse germplasm. A total of 3000 workable assays were obtained which added about 2500 new SNP markers to create a fourth version of the soybean integrated linkage map. To create a “Universal Soy Linkage Panel” (USLP 1.0) of 1536 SNP loci, SNPs were selected based on even distribution throughout each of the 20 consensus linkage groups and to have a broad range of allele frequencies in diverse germplasm. The 1536 USLP 1.0 will be able to quickly create a comprehensive genetic map in most QTL mapping populations and thus will serve as a useful tool for high-throughput QTL mapping

ACR Appropriateness Criteria® Recurrent Hodgkin Lymphoma

This topic addresses the management of recurrent Hodgkin lymphoma. While autologous stem cell transplantation may be appropriate for select cases of recurrent disease following comprehensive combined-modality therapy, other options exist for patients treated with lower-dose therapy for early-stage disease. Additionally, innovative targeted therapies provide newer salvage options to consider. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation, or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. By combining the most recent medical literature and expert opinion, this revised guideline can aid clinicians in the complex decisionmaking associated with the management of recurrent Hodgkin lymphoma

Effective refractive error coverage in adults: a systematic review and meta-analysis of updated estimates from population-based surveys in 76 countries modelling the path towards the 2030 global target

Background: In 2024, WHO included effective refractive error coverage (eREC) into the results framework of the 14th General Programme of Work, which sets a road map for global health and guides WHO's work between 2025 and 2028. eREC is a measure of both the availability and quality of refractive correction in a population. This study aimed to model global and regional estimates of eREC as of 2023 and evaluate progress towards the WHO global target of a 40 percentage-point absolute increase in eREC by 2030. Methods: For this systematic review and meta-analysis, the Vision Loss Expert Group analysed data from 237 population-based eye surveys conducted in 76 countries since 2000, comprising 815 273 participants, to calculate eREC (met need / met need + undermet need + unmet need]) and the relative quality gap between eREC and REC ([REC – eREC] / REC × 100, where REC = [met + undermet need] / [met need + undermet need + unmet need]). An expert elicitation process was used to choose covariates for a Bayesian logistic regression model used to estimate eREC by country–age–sex grouping among adults aged 50 years and older. Country–age–sex group estimates were aggregated to provide estimates according to Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) super-regions. Findings: Global eREC was estimated to be 65·8% (95% uncertainty interval [UI] 64·7–66·8) in 2023, 6 percentage points higher than in 2010 (eREC 59·8% [59·4–60·2]). There were marked differences in eREC between GBD super-regions in 2023, ranging from 84·0% (95% UI 83·0–85·0) in high-income countries to 28·3% (26·4–30·4) in sub-Saharan Africa. In all super-regions, eREC was lower in females than males, and decreased with increasing age among adults aged ≥50 years. Since 2000, the relative increase in eREC was 60·2% in sub-Saharan Africa, 45·7% in North Africa and the Middle East, 41·5% in southeast Asia, east Asia and Oceania, 40·3% in south Asia, 16·2% in Latin America and the Caribbean, 8·3% in central Europe, eastern Europe and central Asia, and 6·8% in the high-income super-region. The relative quality gap ranged from 2·9% to 78·3% across studies, with larger gaps characteristically in regions of lower eREC. Globally, the percentage of those with a refractive need that was undermet reduced between 2000 and 2023, from 10·0% (95% UI 9·5–10·5) to 5·3% (5·1–5·5). Interpretation: The current trajectory of improvement in eREC and the relative quality gap are insufficient to meet the 2030 target. Global efforts to equitably increase spectacle coverage, such as the WHO SPECS 2030 initiative, and to address equity failings associated with geography, age, and sex, are crucial to accelerating progress towards the 2030 targets. No region is close to achieving universal coverage. Funding: WHO, Sightsavers, The Fred Hollows Foundation, Fondation Thea, University of Heidelberg, German Federal Ministry for Education and Research. Translations: For the French, Chinese and Spanish translations of the abstract see Supplementary Materials section

Innate immunity in ocular Chlamydia trachomatis infection: contribution of IL8 and CSF2 gene variants to risk of trachomatous scarring in Gambians

Background: Trachoma, a chronic keratoconjunctivitis caused by Chlamydia trachomatis, is the world's commonest infectious cause of blindness. Blindness is due to progressive scarring of the conjunctiva (trachomatous scarring) leading to in-turning of eyelashes (trichiasis) and corneal opacification. We evaluated the contribution of genetic variation across the chemokine and cytokine clusters in chromosomes 4q and 5q31 respectively to risk of scarring trachoma and trichiasis in a large case-control association study in a Gambian population. Methods: Linkage disequilibrium (LD) mapping was used to investigate risk effects across the 4q and 5q31 cytokine clusters in relation to the risk of scarring sequelae of ocular Ct infection. Disease association and epistatic effects were assessed in a population based study of 651 case-control pairs by conditional logistic regression (CLR) analyses. Results: LD mapping suggested that genetic effects on risk within these regions mapped to the pro-inflammatory innate immune genes interleukin 8 (IL8) and granulocyte-macrophage colony stimulatory factor (CSF2) loci. The IL8-251 rare allele (IL8-251 TT) was associated with protection from scarring trachoma (OR = 0.29 p = 0.027). The intronic CSF2_27348 A allele in chromosome 5q31 was associated with dose dependent protection from trichiasis, with each copy of the allele reducing risk by 37% (p = 0.005). There was evidence of epistasis, with effects at IL8 and CSF2 loci interacting with those previously reported at the MMP9 locus, a gene acting downstream to IL8 and CSF2 in the inflammatory cascade. Conclusion: innate immune response SNP-haplotypes are linked to ocular Ct sequelae. This work illustrates the first example of epistatic effects of two genes on trachoma