tbuckley/cabot-search huggingface dataset:
Estimating the magnitude and healthcare costs of melanoma <i>in situ</i> and thin invasive melanoma overdiagnosis in Australia
Authors: Daniel Lindsay, Katy J L Bell, Catherine M Olsen, David C Whiteman, Thanya Pathirana, Louisa G Collins
Journal: British Journal of Dermatology (2024)

Abstract Background Research suggests that a high proportion of melanoma in situ (MIS) may be overdiagnosed, potentially contributing to overtreatment, patient harm and inflated costs for individuals and healthcare systems. However, Australia-wide estimates of the magnitude of melanoma overdiagnosis are potentially outdated and there has been no estimation of the cost to the healthcare system. Objectives To estimate the magnitude and cost of overdiagnosed MIS and thin invasive melanomas in Australia. Methods Using two different methods to calculate lifetime risk, we used routinely collected national-level data to estimate overdiagnosed MIS and thin invasive melanomas (stage IA) in Australia in 2017 and 2021, separately for men and women. We multiplied the number of overdiagnosed melanomas by the estimated annual cost of a MIS or thin invasive melanoma, to quantify the financial burden of melanoma overdiagnosis to the Australian healthcare system in the year following diagnosis. Results We estimated that 67–70% of MIS were overdiagnosed in 2017, rising to 71–76% in 2021, contributing to between 19 829 [95% confidence interval (CI) 19 553–20 105] and 20 811 (95% CI 20 528–21 094) cases of overdiagnosed MIS. In 2021, the estimated costs in Australia ranged between $17.7 million Australian dollars (AUD; 95% CI 17.4–17.9 million) and AUD$18.6 million (95% CI 18.3–18.8 million). We estimated that 22–29% of thin invasive melanomas were overdiagnosed in 2017, rising to 28–34% in 2021, contributing to between 2831 (95% CI 2726–2935) and 3168 (95% CI 3058–3279) overdiagnosed thin invasive melanomas. In 2021, the estimated costs from thin invasive melanoma overdiagnoses ranged between AUD$2.5 million (95% CI 2.4–2.6 million) and AUD$2.8 million (95% CI 2.7–2.9 million). Conclusions Melanoma overdiagnosis is a growing clinical and public health problem in Australia, producing significant economic costs in the year following overdiagnosis. Limiting melanoma overdiagnosis may prevent unnecessary healthcare resource use and improve financial sustainability within the Australian healthcare system.
A nonsense variant in <i>KRT31</i> is associated with autosomal dominant monilethrix
Authors: Xing Xiong, Nicole Cesarato, Yasmina Gossmann, Maria Wehner, Sheetal Kumar, Holger Thiele, Stephanie Demuth, Vinzenz Oji, Matthias Geyer, Henning Hamm, F Buket Basmanav, Regina C Betz
Journal: British Journal of Dermatology (2024)

Abstract Background Monilethrix is a rare hereditary hair disorder that is characterized by a beaded hair shaft structure and increased hair fragility. Patients may also present with keratosis pilaris and nail changes. Research has identified three genes responsible for autosomal dominant monilethrix (KRT81, KRT83, KRT86) and one responsible for the autosomal recessive form (DSG4). Objectives To investigate the genetic basis of autosomal dominant monilethrix in families with no pathogenic variants in any of the known monilethrix genes, and to understand the mechanistic basis of variant pathogenicity using a cellular model. Methods Nine affected individuals from four unrelated families were included. A clinical diagnosis of monilethrix was assigned based on clinical examination and/or trichoscopy. Exome sequencing was performed in six individuals to identify pathogenic variants; Sanger sequencing was used for co-segregation and haplotype analyses. Cell culture experiments [immunoblotting, immunofluorescence and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) analyses] were used to confirm variant pathogenicity, to determine the expression and subcellular localization of proteins, and to identify possible nonsense-mediated mRNA decay. Results In six affected individuals with clinically suggested monilethrix, exome sequencing led to the identification of the nonsense variant c.1081G&amp;gt;T; p.(Glu361*) in KRT31, which was subsequently identified in other affected members of these families by Sanger sequencing. This variant led to the abolition of both the last three amino acids of the 2B subdomain and the complete C-terminal tail domain of keratin 31. Immunoblotting demonstrated that when co-expressed with its binding partner keratin 85, the truncated keratin 31 was still expressed, albeit less abundantly than the wildtype protein. Immunofluorescence revealed that p.(Glu361*) keratin 31 had an altered cytoskeletal localization and formed vesicular-like structures in the cell cytoplasm near the cell membrane. RT-qPCR analysis did not generate evidence for nonsense-mediated decay of the mutant transcript. Conclusions This study is the first to identify pathogenic variants in KRT31 as a cause of autosomal dominant monilethrix. This highlights the importance of hair keratin proteins in hair biology, and will increase the molecular diagnostic yield for rare ectodermal phenotypes of hair and nail tissues.
Emerging opportunities to target inflammation: myocardial infarction and type 2 diabetes
Authors: Tafadzwa T J Kufazvinei, Jason Chai, Katherine A Boden, Keith M Channon, Robin P Choudhury
Journal: Cardiovascular Research (2024)

After myocardial infarction (MI), patients with type 2 diabetes have an increased rate of adverse outcomes, compared to patients without. Diabetes confers a 1.5-2-fold increase in early mortality and, importantly, this discrepancy has been consistent over recent decades, despite advances in treatment and overall survival. Certain assumptions have emerged to explain this increased risk, such as differences in infarct size or coronary artery disease severity. Here, we re-evaluate that evidence and show how contemporary analyses using state-of-the-art characterization tools suggest that the received wisdom tells an incomplete story. Simultaneously, epidemiological and mechanistic biological data suggest additional factors relating to processes of diabetes-related inflammation might play a prominent role. Inflammatory processes after MI mediate injury and repair and are thus a potential therapeutic target. Recent studies have shown how diabetes affects immune cell numbers and drives changes in the bone marrow, leading to pro-inflammatory gene expression and functional suppression of healing and repair. Here, we review and re-evaluate the evidence around adverse prognosis in patients with diabetes after MI, with emphasis on how targeting processes of inflammation presents unexplored, yet valuable opportunities to improve cardiovascular outcomes in this vulnerable patient group.
High prevalence of undiagnosed and undertreated psoriasis in a UK urban population: results from the observational COPPACA study
Authors: Stephanie R Harrison, Fiona Campbell, Hannah Bennett, Gabriele De Marco, Philip S Helliwell, Rebecca Golenya, Dennis G McGonagle, Cleone Pardoe, Pavan Sambi, Kave Shams, David Wright, Helena Marzo-Ortega, Philip M Laws
Journal: British Journal of Dermatology (2024)

Community Psoriasis: Phenotype and Comorbidity Assessment (COPPACA) was a study of the point prevalence and burden of untreated psoriasis in the Leeds urban area. There were high rates of undiagnosed psoriasis (41.1% of patients were newly diagnosed by the study team), and all patients (newly diagnosed or otherwise) reported significant psychosocial comorbidity [median Psoriasis Area and Severity Index (PASI) = 3 (interquartile range 1.7–6.8), PASI &amp;gt; 5 = 34%, mean Dermatology Life Quality Index (DLQI) = 8.45, DLQI ≥ 10 = 34.8%]. This highlights a significant unmet need for improved access to, and communication between, primary and secondary care dermatology in our area to improve patients’ physical and mental wellbeing.
21-Gene Recurrence Score and Survival Outcomes in the Phase III Multicenter TAILORx Clinical Trial
Authors: Sherry X. Yang, John Yu, Molin Wang
Journal: Journal of the National Comprehensive Cancer Network (2024)

Recurrence score (RS) based on a 21-gene genomic assay is frequently used to estimate risk of distant recurrence for choice of adjuvant chemotherapy in breast cancer. It remains unclear whether RS is an independent prognostic factor for breast cancer-specific survival (BCSS) and overall survival (OS) in the TAILORx trial population.
NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2024
Authors: Susan M. Swetter, Douglas Johnson, Mark R. Albertini, Christopher A. Barker, Sarah Bateni, Joel Baumgartner, Shailender Bhatia, Christopher Bichakjian, Genevieve Boland, Sunandana Chandra, Bartosz Chmielowski, Dominick DiMaio, Roxana Dronca, Ryan C. Fields, Martin D. Fleming, Anjela Galan, Samantha Guild, John Hyngstrom, Giorgos Karakousis, Kari Kendra, Maija Kiuru, Julie R. Lange, Ryan Lanning, Theodore Logan, Daniel Olson, Anthony J. Olszanski, Patrick A. Ott, Merrick I. Ross, Luke Rothermel, April K. Salama, Rohit Sharma, Joseph Skitzki, Emily Smith, Katy Tsai, Evan Wuthrick, Yan Xing, Nicole McMillian, Sara Espinosa
Journal: Journal of the National Comprehensive Cancer Network (2024)

The NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.
A nanomedicine approach for the treatment of long-lasting pain
Authors: Hadjer Hazam, Lucas Prades, Catherine Cailleau, Julie Mougin, Jiao Feng, Dan Benhamou, Frédéric Gobeaux, Leïla Hamdi, Patrick Couvreur, Philippe Sitbon, Sinda Lepetre-Mouelhi
Journal: Journal of Controlled Release (2024)
Drugs need to be formulated with scale-up in mind
Authors: Kurt D Ristroph
Journal: Journal of Controlled Release (2024)

Formulation scale-up remains a major hurdle in drug development in part because preliminary formulation research efforts rarely consider the challenges of scaling up production for commercialization. This Perspective outlines considerations around scalability that can be incorporated into formulation design work in order to increase the chances of successful translation. Both technical (unit operations, excipient selection, scaling principles) and non-technical (funding, publications, and personnel) considerations are discussed, with a focus on lab-scale work by academic researchers.
Inhibition of PERK-mediated unfolded protein response acts as a switch for reversal of residual senescence and as senolytic therapy in glioblastoma
Authors: Madhura Ketkar, Sanket Desai, Pranav Rana, Rahul Thorat, Sridhar Epari, Amit Dutt, Shilpee Dutt
Journal: Neuro-Oncology (2024)

Abstract Background Glioblastoma due to recurrence is clinically challenging with 10–15 months overall survival. Previously we showed that therapy-induced senescence (TIS) in glioblastoma reverses causing recurrence. Here, we aim to delineate the TIS reversal mechanism for potential therapeutic intervention to prevent glioblastoma (GBM) recurrence. Methods Residual senescent (RS) and end of residual senescence (ERS) cells were captured from GBM patient-derived primary-cultures and cell lines mimicking clinical scenarios. RNA-sequencing, transcript/protein validations, knock-down/inhibitor studies, ChIP RT-PCR, biochemical assays, and IHCs were performed for the mechanistics of TIS reversal. In vivo validations were conducted in GBM orthotopic mouse model. Results Transcriptome analysis showed co-expression of endoplasmic reticulum (ER) stress-unfolded protein response (UPR) and senescence-associated secretory phenotype (SASP) with TIS induction and reversal. Robust SASP production and secretion by RS cells could induce senescence, Reactive oxygen specis (ROS), DNA damage, and ER stress in paracrine fashion independent of radiation. Neutralization of most significantly enriched cytokine from RS-secretome IL1β, suppressed SASP, and delayed senescence reversal. Mechanistically, with SASP and massive protein accumulation in ER, RS cells displayed stressed ER morphology, upregulated ER stress markers, and PERK pathway activation via peIF2α-ATF4-CHOP which was spontaneously resolved in ERS. ChIP RT-PCR showed CHOP occupancy at CXCL8/IL8, CDKN1A/p21, and BCL2L1/BCLXL aiding survival. PERK knockdown/inhibition with GSK2606414 in combination with radiation led to sustained ER stress and senescence without SASP. PERKi in RS functioned as senolytic via apoptosis and prevented recurrence in vitro and in vivo ameliorating overall survival. Conclusion We demonstrate that PERK-mediated UPR regulates senescence reversal and its inhibition can be exploited as a potential seno-therapeutic option in glioblastoma.
Risk factors for breast cancer subtypes by race and ethnicity: a scoping review
Authors: Amber N Hurson, Thomas U Ahearn, Hela Koka, Brittany D Jenkins, Alexandra R Harris, Sylvia Roberts, Sharon Fan, Jamirra Franklin, Gisela Butera, Renske Keeman, Audrey Y Jung, Pooja Middha, Gretchen L Gierach, Xiaohong R Yang, Jenny Chang-Claude, Rulla M Tamimi, Melissa A Troester, Elisa V Bandera, Mustapha Abubakar, Marjanka K Schmidt, Montserrat Garcia-Closas
Journal: JNCI Journal of the National Cancer Institute (2024)

Breast cancer consists of distinct molecular subtypes. Studies have reported differences in risk factor associations with breast cancer subtypes, especially by tumor estrogen receptor (ER) status, but their consistency across racial and ethnic populations has not been comprehensively evaluated.
Breast Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology
Authors: William J. Gradishar, Meena S. Moran, Jame Abraham, Vandana Abramson, Rebecca Aft, Doreen Agnese, Kimberly H. Allison, Bethany Anderson, Janet Bailey, Harold J. Burstein, Nan Chen, Helen Chew, Chau Dang, Anthony D. Elias, Sharon H. Giordano, Matthew P. Goetz, Rachel C. Jankowitz, Sara H. Javid, Jairam Krishnamurthy, A. Marilyn Leitch, Janice Lyons, Susie McCloskey, Melissa McShane, Joanne Mortimer, Sameer A. Patel, Laura H. Rosenberger, Hope S. Rugo, Cesar Santa-Maria, Bryan P. Schneider, Mary Lou Smith, Hatem Soliman, Erica M. Stringer-Reasor, Melinda L. Telli, Mei Wei, Kari B. Wisinski, Kay T. Yeung, Jessica S. Young, Ryan Schonfeld, Rashmi Kumar
Journal: Journal of the National Comprehensive Cancer Network (2024)

Breast cancer is treated with a multidisciplinary approach involving surgical oncology, radiation oncology, and medical oncology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget’s disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of systemic therapy (preoperative and adjuvant) options for nonmetastatic breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org .
“Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study.” John P. Corcoran, Ioannis Psallidas, Stephen Gerry, Francesco Piccolo, Coenraad F. Koegelenberg, Tarek Saba, Cyrus Daneshvar, Ian Fairbairn, Richard Heinink, Alex West, Andrew E. Stanton, Jayne Holme, Jack A. Kastelik, Henry Steer, Nicola J. Downer, Mohammed Haris, Emma H. Baker, Caroline F. Everett, Justin Pepperell, Thomas Bewick, Lonny Yarmus, Fabien Maldonado, …
Journal: European Respiratory Journal (2020)
Patient‑reported outcome measures for assessing health‑related quality of life in patients with differentiated thyroid cancer: a systematic review
Authors: Lujing Xiong, Lei Liu, Yuqing Xiang, Chao Li, Wei Dai, Jinchuan Hu, Chunyan Shui, Yuqiu Zhou, Xu Wang, Yongcong Cai
Journal: International Journal of Surgery (2024)

Background: Patient-reported outcome measures (PROMs) have become important tools for evaluating health-related quality of life (HRQOL) in patients with differentiated thyroid cancer (DTC). While there are many PROMs available to measure HRQOL, there is a lack of a comprehensive overview of these PROMs. Therefore, we aimed to systematically review and categorize all PROMs that have been used to measure HRQOL in patients with DTC. Materials and methods: After determining the search strategy and identifying inclusion and exclusion criteria, articles were searched in PubMed and EMBASE from January 1900 to September 2023. Information on PROMs from the included studies, such as development language, target population, (sub)scales name, number of items per (sub)scale, completion time, and validation, was extracted and synthesized. The frequency with which PROMs were utilized in the included studies was also graphed. After innovatively classifying PROMs as five categories, all of the included PROMs were allocated to their respective categories. Results: A total of 330 articles fulfilled all of the criteria, and they utilized 96 different PROMs to measure HRQOL in DTC patients. The 96 PROMs were classified into five categories, namely universal PROMs (16/96), DTC-related PROMs (11/96), radioiodine-related PROMs (4/96), operation-related PROMs (37/96), and psychology-related PROMs (28/96). Among them, some PROMs were the frequently employed PROMs to assess diverse aspects of HRQOL in patients with DTC. Conclusion: A large number of PROMs are available for patients with DTC, which evaluate all aspects of HRQOL. Combining the relevant information and frequency of PROMs utilization, it can provide convenience and reference for researchers to select PROMs across different categories. However, a more detailed critical appraisal of the PROMs used in various clinical scenarios is required. Additionally, PROMs usage frequency in previous studies can indirectly indicate the comprehensiveness or gaps in HRQOL aspects studied, guiding further review or research.
Letter to the editor: Severe parvovirus B19 infections in the immunocompetent population
Authors: Marta Giovanetti, Francesco Branda, Fabio Scarpa, Massimo Ciccozzi, Giancarlo Ceccarelli
Journal: Eurosurveillance (2024)

Preview this article: Letter to the editor: Severe parvovirus B19 infections in the immunocompetent population, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/29/29/eurosurv-29-29-6-1.gif
Increase in candidemia cases and emergence of fluconazole-resistant Candida parapsilosis and C. auris isolates in a tertiary care academic hospital during the COVID-19 pandemic, Greece, 2020 to 2023
Authors: Maria Siopi, Panagiota-Christina Georgiou, Paschalis Paranos, Maria-Ioanna Beredaki, Aikaterini Tarpatzi, Eleni Kalogeropoulou, Sofia Damianidou, Alexandra Vasilakopoulou, Polyxeni Karakosta, Spyros Pournaras, Joseph Meletiadis
Journal: Eurosurveillance (2024)

Background The COVID-19 pandemic and the emergence of Candida auris have changed the epidemiological landscape of candidaemia worldwide. Aim We compared the epidemiological trends of candidaemia in a Greek tertiary academic hospital before (2009–2018) and during the early COVID-19 (2020–2021) and late COVID-19/early post-pandemic (2022–2023) era. Methods Incidence rates, species distribution, antifungal susceptibility profile and antifungal consumption were recorded, and one-way ANOVA or Fisher’s exact test performed. Species were identified by MALDI-ToF MS, and in vitro susceptibility determined with CLSI M27-Ed4 for C. auris and the EUCAST-E.DEF 7.3.2 for other Candida spp. Results In total, 370 candidaemia episodes were recorded during the COVID-19 pandemic. Infection incidence (2.0 episodes/10,000 hospital bed days before, 3.9 during the early and 5.1 during the late COVID-19 era, p &lt; 0.0001), C. auris (0%, 9% and 33%, p &lt; 0.0001) and fluconazole-resistant C. parapsilosis species complex (SC) (20%, 24% and 33%, p = 0.06) infections increased over time, with the latter not associated with increase in fluconazole/voriconazole consumption. A significant increase over time was observed in fluconazole-resistant isolates regardless of species (8%, 17% and 41%, p &lt; 0.0001). Resistance to amphotericin B or echinocandins was not recorded, with the exception of a single pan-echinocandin-resistant C. auris strain. Conclusion Candidaemia incidence nearly tripled during the COVID-19 era, with C. auris among the major causative agents and increasing fluconazole resistance in C. parapsilosis SC. Almost half of Candida isolates were fluconazole-resistant, underscoring the need for increased awareness and strict implementation of infection control measures.
A pilot project harnessing surveillance systems to support clinicians providing clinical care for people diagnosed with hepatitis C in Victoria, Australia, September 2021 to 31 March 2022
Authors: Mielle Abbott, Jennifer H MacLachlan, Nicole Romero, Nicole Matthews, Nasra Higgins, Alvin Lee, Mark Stoove, Tafireyi Marukutira, Brendan Quinn, Nicole L Allard, Benjamin C Cowie
Journal: Eurosurveillance (2024)

Background Active follow-up of chronic hepatitis C notifications to promote linkage to care is a promising strategy to support elimination. Aim This pilot study in Victoria, Australia, explored if the Department of Health could follow-up on hepatitis C cases through their diagnosing clinicians, to assess and support linkage to care and complete data missing from the notification. Methods For notifications received between 1 September 2021 and 31 March 2022 of unspecified hepatitis C cases (i.e. acquired &gt; 24 months ago or of unknown duration), contact with diagnosing clinicians was attempted. Data were collected on risk exposures, clinical and demographic characteristics and follow-up care (i.e. HCV RNA test; referral or ascertainment of previous negative testing or treatment history). Reasons for unsuccessful doctor contact and gaps in care provision were investigated. Advice to clinicians on care and resources for clinical support were given on demand. Results Of 513 cases where information was sought, this was able to be obtained for 356 (69.4%). Reasons for unsuccessful contact included incomplete contact details or difficulties getting in touch across three attempts, particularly for hospital diagnoses. Among the 356 cases, 307 (86.2%) had received follow-up care. Patient-management resources were requested by 100 of 286 contacted diagnosing clinicians. Conclusions Most doctors successfully contacted had provided follow-up care. Missing contact information and the time taken to reach clinicians significantly impeded the feasibility of the intervention. Enhancing system automation, such as integration of laboratory results, could improve completeness of notifications and support further linkage to care where needed.