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Focal segmental glomerulosclerosis (FSGS) comprises a group of uncommon disorders that present with marked proteinuria, nephrotic syndrome, progressive renal failure and characteristic glomerular lesions on histopathology. The current standard of care for patients with FSGS include immunosuppressive drugs such as glucocorticoids followed by calcineurin inhibitors, if needed for intolerance or inadequate response to glucocorticoids. Renin-angiotensin-aldosterone (RAAS) blockers are also used to control proteinuria, an important signature of FSGS. Existing treatments, however, achieved only limited success. Despite best care, treatment failure is common and FSGS is causal in a significant proportion of end stage renal disease. Thus, an unmet need exists for novel disease modifying treatments for FSGS. We employed two widely-used murine models of FSGS to test the hypothesis that systemic inhibition of chemokine receptor CCR2 would have therapeutic benefit. Here we report that administration CCX872, a potent and selective small molecule antagonist of CCR2, achieved rapid and sustained attenuation of renal damage as determined by urine albumin excretion and improved histopathological outcome. Therapeutic benefit was present when CCX872 was used as a single therapy, and moreover, the combination of CCX872 and RAAS blockade was statistically more effective than RAAS blockade alone. In addition, the combination of CCR2 and RAAS blockade was equally as effective as endothelin receptor inhibition. We conclude that specific inhibition of CCR2 is effective in the Adriamycin-induced and 5/6 nephrectomy murine models of FSGS, and thus holds promise as a mechanistically distinct therapeutic addition to the treatment of human FSGS.

Topical antigen application is a focus of current vaccine research. This immunization route mimics natural antigen exposure across a barrier tissue and generates T cells imprinted for skin-selective homing. Soluble antigens introduced through this route require cross-presentation by DC to generate CD8 T cell responses. Here we have explored the relative contribution of various skin-derived DC subsets to cross-priming and skin-selective imprinting. In our model, DC acquire soluble Ag in vivo from immunized murine skin for cross-presentation to naïve CD8 T cells ex vivo. We find CD11b(+) migratory DC to be the relevant cross-priming DC in this model. Both Langerin(+) and Langerin(-) CD11b(+) migratory DC can cross-present antigen in our system, but only the Langerin+ subset can induce expression of the skin-selective addressin E-selectin ligand. Thus, the CD11b(+) Langerin(+) migratory DC population, comprised primarily of Langerhans cells, both cross-primes naïve CD8 T cells and imprints them with skin-homing capabilities.

A goal for developers of immunomodulatory drugs has long been a systemically administered small molecule that can selectively inhibit inflammation in specific tissues. The chemokine receptor CCR9 is an attractive target for this approach, as entry of T cells into the small intestine from blood requires interaction between CCR9 and its ligand CCL25. We have tested the ability of a small molecule CCR9 antagonist, CCX8037, to inhibit antigen-mediated T cell accumulation in the intestine. This compound prevented accumulation of gut-imprinted antigen-specific CD8 T cells within epithelium of the small intestine. Interestingly, the antagonist did not affect the robust generation of gut-imprinted CD8 T cells within mesenteric lymph nodes. To distinguish "gut-selective" from "general" T cell inhibition, we tested the drug's ability to influence accumulation of T cells within skin, a tissue in which CCR9 plays no known role, and we found no appreciable effect. This study demonstrates the feasibility of creating systemically-administered pharmaceuticals capable of tissue-selective immune modulation. This proof of concept is of utmost importance for designing effective treatments against various autoimmune disorders localized to a specific tissue.

The mechanisms that underlie the critical dendritic cell (DC) function in maintainance of peripheral immune tolerance are incompletely understood, although the β-catenin signaling pathway is critical for this role. The molecular details by which β-catenin signaling is regulated in DCs are unknown. Mechanical disruption of murine bone marrow-derived DC (BMDC) clusters activates DCs while maintaining their tolerogenic potential and this activation is associated with β-catenin signaling, providing a useful model with which to explore tolerance-associated β-catenin signaling in DCs. In this report, we demonstrate novel molecular features of the signaling events that control DC activation in response to mechanical stimulation. Non-canonical β-catenin signaling is an essential component of this tolerogenic activation and is modulated by adhesion molecules, including integrins. This unique β-catenin-dependent signaling pathway is constitutively active at low levels, suggesting that mechanical stimulation is not necessarily required for induction of this unique activation program. We additionally find that the immunomodulatory cytokine TGF-β antagonizes β-catenin in DCs, thereby selectively suppressing signaling associated with tolerogenic DC activation while having no impact on LPS-induced, β-catenin-independent immunogenic activation. These findings provide new molecular insight into the regulation of a critical signaling pathway for DC function in peripheral immune tolerance.

Abstract The infiltration of chronic lymphocytic leukemia (CLL) cells into lymphoid organs correlates with disease severity. CXCL12 is a key chemotactic factor for the trafficking of CLL. Tissue factor pathway inhibitor (TFPI) is a serine protease inhibitor and plays a role in CXCL12-mediated hematopoietic stem cell homing. We aim to explore the role of TFPI in CXCL12-mediated migration of CLL cells. In this study, plasma TFPI concentrations were measured by ELISA. CLL cells were isolated from patients and used for trans-endothelial migration (TEM) assays. Quantitative RT-PCR and Western blotting were used to detect the expression of CXCR7, CXCR4 and β-catenin. Immunofluorescence and co-immunoprecipitation was used to detect the binding of TFPI and glypican-3 (GPC3). We found that plasma TFPI levels in CLL patients were higher than in healthy controls, particularly in the patients with advanced disease. TFPI enhanced CXCL12-mediated TEM of CLL cells by increasing the expression of the CXCL12 receptor CXCR7, but not of the CXCL12 receptor CXCR4. The effect of TFPI on TEM was abolished by the CXCR7 inhibitor, CCX771, while the CXCR4 inhibitor AMD3100 strongly increased TEM. TFPI co-localized with GPC3 on the cell surface. An antibody to GPC3, HS20, decreased CXCR7 expression and abolished the effect of TFPI on TEM. TFPI activated β-catenin and the Wnt/β-catenin inhibitor IWP4 repressed the effect of TFPI on CXCR7 expression and TEM. We conclude that TFPI may contribute to organ infiltration in CLL patients.

Cancer associated fibroblasts (CAFs) have been suggested to regulate cancer cell metabolism, but the mechanisms are not completely elucidated. Here, the authors show that low FAK expression in stromal cells correlates with poor prognosis in breast and pancreatic cancer patients and that FAK-silencing in CAFs promotes tumourigenesis by the paracrine regulation of cancer cell metabolism.

While it has long been established that the chemokine receptor CCR9 and its ligand CCL25 are essential for the movement of leukocytes into the small intestine and the development of small-intestinal inflammation, the role of this chemokine-receptor pair in colonic inflammation is not clear. Toward this end, we compared colonic CCL25 protein levels in healthy individuals to those in patients with ulcerative colitis. In addition, we determined the effect of CCR9 pharmacological inhibition in the mdr1a−/− mouse model of ulcerative colitis. Colon samples from patients with ulcerative colitis had significantly higher levels of CCL25 protein compared to healthy controls, a finding mirrored in the mdr1a−/− mice. In the mdr1a−/− mice, CCR9 antagonists significantly decreased the extent of wasting and colonic remodeling and reduced the levels of inflammatory cytokines in the colon. These findings indicate that the CCR9:CCL25 pair plays a causative role in ulcerative colitis and suggest that CCR9 antagonists will provide a therapeutic benefit in patients with colonic inflammation.

Hepatitis B virus (HBV) whole genome sequencing (WGS) is currently limited as the DNA viral loads (VL) of many clinical samples are below the threshold required to generate full genomes using current sequencing methods. We developed two pan-genotypic viral enrichment methods, using probe-based capture and tiled amplicon PCR (HEP-TILE) for HBV WGS. We demonstrate using mock samples that both enrichment methods are pan-genotypic (genotypes A-J). Using clinical samples, we demonstrate that HEP-TILE amplification successfully amplifies full genomes at the lowest HBV VL tested (30 IU/ml), and the PCR products can be sequenced using both Nanopore and Illumina platforms. Probe-based capture with Illumina sequencing required VL > 300,000 IU/ml to generate full length HBV genomes. The capture-Illumina and HEP-TILE-Nanopore pipelines had consensus sequencing accuracy of 100% in mock samples with known DNA sequences. Together, these protocols will facilitate the generation of HBV sequence data, enabling a more accurate and representative picture of HBV molecular epidemiology, cast light on persistence and pathogenesis, and enhance understanding of the outcomes of infection and its treatment., Competing Interests: Competing interests: Chris Kent has received an honorarium from Illumina for a talk on PrimalScheme3. No other authors declare competing interests., (© 2025. The Author(s).)

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and is the leading cause of death. Bacillus Calmette-Guérin (BCG) is the only licensed TB vaccine. Preclinical studies have shown that in adults intravenous administration of BCG improves protection against TB. We hypothesize that intradermal administration of BCG to the human newborn leads to low grade BCG bacteraemia and that this systemic dissemination improves protection against Mtb infection. This hypothesis is based on supporting observations including animal and human studies. It is a testable hypothesis and offers to deliver immediately actionable insight to advance the global efforts against TB., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Recent interest in the diverse ecosystem of bacteria, fungi, parasites, and viruses that make up the skin microbiome has led to several studies investigating the microbiome in healthy skin and in a variety of dermatological conditions. An imbalance of the normal skin flora can cause some skin diseases, and current culture techniques are often unable to detect a microorganism to further our understanding of the clinical-microbiological correlates of disease and dysbiosis. Atopic dermatitis and rosacea are presentations that GPs often manage that may have an infective or microbiological component and can be challenging to treat. We aim to discuss the implications of the skin microbiome including the impact of dysbiosis on conditions such as these. We will also discuss some clinical pearls for initial and future directions of the management of conditions such as atopic dermatitis, rosacea, and hidradenitis suppurativa. Further research using culture-independent techniques is needed for conditions involving microbial dysbiosis to advance our knowledge of skin disease pathophysiology and guide future management.

Rare diseases affect over three hundred million individuals globally. Investment in research and development remains incommensurate with the challenges rare diseases pose. Further investment in information sharing platforms to promote common and standardized network technologies for rare disease is needed. Rare disease R&D generates information and assets that spill over in other ways, providing benefits that may not be apparent to investors ex ante. Analytical and computational methods recently applied at scale are promising. One important way of achieving efficiencies of scale in R&D is clustering rare diseases into groups with similar traits., Competing Interests: Author CPR was employed by Binera, Inc. consulting for United States Department of Health and Human Services. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Runge, Campbell and Runge.)

The unprecedented and multi-faceted challenges health and care workers faced during the COVID-19 pandemic inspired the world's health ministers to call for a new Global Health and Care Worker Compact at the 74th World Health Assembly in 2021. The Care Compact identifies key areas where governments can use law and policy to prevent harm, provide support, ensure inclusivity, and safeguard rights of health and care workers toward improving population health. Using policy surveillance methods, we conducted an empirical analysis of the national law and policy environments on health and care workers' protection and rights in 182 countries. Across 10 indicators, 1,262 laws and policies were identified and analyzed for their alignment with the international legal standards. Analysis shows significant gaps. 62% of all national laws are aligned. Nearly every country has multiple areas where national laws are not yet aligned with the Care Compact. Though alignment is feasible. In 5 of 6 regions at least one country has laws aligned on all indicators. Geographic region was not a significant predictor of alignment, while income level was only weakly associated. Comparing the key legal issues facing health and care workers, well over half of countries studied are fully aligned with the Care Compact on occupational health and safety, fair remuneration, enabling work environments, freedom of association, and collective bargaining. Approximately 50% of countries studied are fully aligned on protections against violence and harassment in the workplace and whistleblower protections. But less than 25% are fully aligned on access to health services in occupational settings and equal treatment and non-discrimination. Together this analysis highlights the need for, and opportunity of, law reform in countries throughout the world to elevate and protect the rights and well-being of health and care workers and, in doing so, improve health systems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kavanagh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for several hematological diseases. Prospective and retrospective studies have associated myeloablative conditioning regimens with increased non-relapse mortality and less intense regimens with disease relapse, leading to similar overall survival rates. Objectives: Analyze the experience with the different RIC schemes in patients transplanted for AML/MDS in our program. Methods: We retrospectively analyzed our program's reduced-intensity conditioning regimens (RIC) between 2012 and 2022 in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Results: During this period, 450 allogeneic stem cell transplantations were performed, of which 52 patients were treated with RIC for AML, mostly in men. The 3-year overall survival/progression-free survival rates were 52/53%, 51/57%, and 57/55% in the fludarabine-reduced intensity with total-body irradiation, Melphalan, and Busulfan, respectively ( p = 0.89). The composite incidences of aGVHD III-IV, cGVHD, and admission to the critical patient unit were 21%, 25%, and 30%, respectively, without statistically significant differences according to the type of conditioning, but with a trend of greater ICU admission in patients who used melphalan-based conditioning. Conclusion: Our study found no differences in overall survival, progression-free survival, and complications between the most commonly used reduced-intensity conditioning regimens.

Allogeneic transplantation (HSCT) is a curative option for several hematological diseases. Our center has privileged the use of identical family donors (IFD) or haploidentical (HD) donors. However, the chances of finding family donors may be challenging in small families or unsuitable donors. In these cases, there is the possibility of obtaining hematopoietic precursors from unrelated donors (URD) with complete or almost complete HLA compatibility., Aim: this work analyzes the results of a historical cohort of patients with allogeneic transplantation in our institution., Methods: a retrospective analysis of data base and clinical records of patients with allogeneic transplantation in our adult transplantation program., Results: between 2005 and 2023, 370 TPH were performed, of which 150 were IFD (40%), 167 HD (45%) and 53 URD (15%). The median age of the patients was 37 years (range 16-76), the majority were transplanted for acute leukemia (60%) and 41% were women. With a median follow-up of 8 years, the overall survival was 64, 67, and 65% for IFD, HD or URD. Subgroup analysis showed more severe cases of graft versus host disease in HD group (p= 0.001)., Conclusion: our experience shows that the results of DNR, DFI, and DFH are similar. 15% of patients were transplanted with URD because of the absence of suitable family donors.

The aim of the work presented in this paper was development of a thermodynamically consistent constitutive model for orthotopic metals and determination of its parameters based on standard characterisation methods used in the aerospace industry. The model was derived with additive decomposition of the strain tensor and consisted of an elastic part, derived from Helmholtz free energy, Hill's thermodynamic potential, which controls evolution of plastic deformation, and damage orthotopic potential, which controls evolution of damage in material. Damage effects were incorporated using the continuum damage mechanics approach, with the effective stress and energy equivalence principle. Material characterisation and derivation of model parameters was conducted with standard specimens with a uniform cross-section, although a number of tests with non-uniform cross-sections were also conducted here. The tests were designed to assess the extent of damage in material over a range of plastic deformation values, where displacement was measured locally using digital image correlation. The new model was implemented as a user material subroutine in Abaqus and verified and validated against the experimental results for aerospace-grade aluminium alloy 2024-T3. Verification was conducted in a series of single element tests, designed to separately validate elasticity, plasticity and damage-related parts of the model. Validation at this stage of the development was based on comparison of the numerical results with experimental data obtained in the quasistatic characterisation tests, which illustrated the ability of the modelling approach to predict experimentally observed behaviour. A validated user material subroutine allows for efficient simulation-led design improvements of aluminium components, such as stiffened panels and the other thin-wall structures used in the aerospace industry.

Skin scar formation following Bacille Calmette-Guérin (BCG) or smallpox (Vaccinia) vaccination is an established marker of successful vaccination and 'vaccine take'. Potent pathogen-specific (tuberculosis; smallpox) and pathogen-agnostic (protection from diseases unrelated to the intentionally targeted pathogen) effects of BCG and smallpox vaccines hold significant translational potential. Yet despite their use for centuries, how scar formation occurs and how local skin-based events relate to systemic effects that allow these two vaccines to deliver powerful health promoting effects has not yet been determined. We review here what is known about the events occurring in the skin and place this knowledge in the context of the overall impact of these two vaccines on human health with a particular focus on maternal-child health., (© 2024. The Author(s).)

With the emergence of the COVID-19 pandemic, the absence of established evidence-based treatment protocols led healthcare professionals and the public to explore experimental treatments, including high doses of vitamin D supplements. This study aimed to assess changes in serum 25-hydroxyvitamin D levels during the pandemic, employing a retrospective cohort analysis of data from Charleston Area Medical Center (CAMC). The study analyzed serum 25-hydroxyvitamin D levels in a cohort of 35,556 patients treated at CAMC in 2019, a representative pre-pandemic period, to 2021, a representative pandemic period. Our findings revealed a significant increase in mean serum 25-hydroxyvitamin D levels as compared with 2019 (37 ± 21 vs. 31 ± 15 ng/mL, p ≤ 0.001). Additionally, in 2021, there were significantly more patients exhibiting serum levels in the highest quintiles, specifically >100 ng/mL (1.6% vs. 0.2%), 75-100 ng/mL (4.6% vs. 1.2%), and 50-75 ng/mL (16.0% vs. 8.4%), p ≤ 0.001. This upsurge suggests increased intake of vitamin D supplements, potentially fueled by widespread discussions that were taking place largely on the internet regarding the efficacy of vitamin D against COVID-19. Our findings underscore the critical need for evidence-based public health messaging, especially during health crises, to prevent unnecessary health risks and ensure patient safety.

Background: To investigate the impacts of the COVID-19 pandemic on the health workforce, we aimed to develop a framework that synergizes natural language processing (NLP) techniques and human-generated analysis to reduce, organize, classify, and analyze a vast volume of publicly available news articles to complement scientific literature and support strategic policy dialogue, advocacy, and decision-making., Objective: This study aimed to explore the possibility of systematically scanning intelligence from media that are usually not captured or best gathered through structured academic channels and inform on the impacts of the COVID-19 pandemic on the health workforce, contributing factors to the pervasiveness of the impacts, and policy responses, as depicted in publicly available news articles. Our focus was to investigate the impacts of the COVID-19 pandemic and, concurrently, assess the feasibility of gathering health workforce insights from open sources rapidly., Methods: We conducted an NLP-assisted media content analysis of open-source news coverage on the COVID-19 pandemic published between January 2020 and June 2022. A data set of 3,299,158 English news articles on the COVID-19 pandemic was extracted from the World Health Organization Epidemic Intelligence through Open Sources (EIOS) system. The data preparation phase included developing rules-based classification, fine-tuning an NLP summarization model, and further data processing. Following relevancy evaluation, a deductive-inductive approach was used for the analysis of the summarizations. This included data extraction, inductive coding, and theme grouping., Results: After processing and classifying the initial data set comprising 3,299,158 news articles and reports, a data set of 5131 articles with 3,007,693 words was devised. The NLP summarization model allowed for a reduction in the length of each article resulting in 496,209 words that facilitated agile analysis performed by humans. Media content analysis yielded results in 3 sections: areas of COVID-19 impacts and their pervasiveness, contributing factors to COVID-19-related impacts, and responses to the impacts. The results suggest that insufficient remuneration and compensation packages have been key disruptors for the health workforce during the COVID-19 pandemic, leading to industrial actions and mental health burdens. Shortages of personal protective equipment and occupational risks have increased infection and death risks, particularly at the pandemic's onset. Workload and staff shortages became a growing disruption as the pandemic progressed., Conclusions: This study demonstrates the capacity of artificial intelligence-assisted media content analysis applied to open-source news articles and reports concerning the health workforce. Adequate remuneration packages and personal protective equipment supplies should be prioritized as preventive measures to reduce the initial impact of future pandemics on the health workforce. Interventions aimed at lessening the emotional toll and workload need to be formulated as a part of reactive measures, enhancing the efficiency and maintainability of health delivery during a pandemic., (©Anita Pienkowska, Mathieu Ravaut, Maleyka Mammadova, Chin-Siang Ang, Hanyu Wang, Qi Chwen Ong, Iva Bojic, Vicky Mengqi Qin, Dewan Md Sumsuzzman, Onyema Ajuebor, Mathieu Boniol, Juana Paola Bustamante, James Campbell, Giorgio Cometto, Siobhan Fitzpatrick, Catherine Kane, Shafiq Joty, Josip Car. Originally published in JMIR Formative Research (https://formative.jmir.org), 13.06.2024.)

Background: Malaria elimination in Senegal requires accurate diagnosis of all Plasmodium species. Plasmodium falciparum is the most prevalent species in Senegal, although Plasmodium malariae, Plasmodium ovale, and recently Plasmodium vivax have also been reported. Nonetheless, most malaria control tools, such as Histidine Rich Protein 2 rapid diagnosis test (PfHRP2-RDT,) can only diagnose P. falciparum. Thus, PfHRP2-RDT misses non-falciparum species and P. falciparum infections that fall below the limit of detection. These limitations can be addressed using highly sensitive Next Generation Sequencing (NGS). This study assesses the burden of the four different Plasmodium species in western and eastern regions of Senegal using targeted PCR amplicon sequencing., Methods: Three thousand samples from symptomatic and asymptomatic individuals in 2021 from three sites in Senegal (Sessene, Diourbel region; Parcelles Assainies, Kaolack region; Gabou, Tambacounda region) were collected. All samples were tested using PfHRP2-RDT and photoinduced electron transfer polymerase chain reaction (PET-PCR), which detects all Plasmodium species. Targeted sequencing of the nuclear 18S rRNA and the mitochondrial cytochrome B genes was performed on PET-PCR positive samples., Results: Malaria prevalence by PfHRP2-RDT showed 9.4% (94/1000) and 0.2% (2/1000) in Diourbel (DBL) and Kaolack (KL), respectively. In Tambacounda (TAM) patients who had malaria symptoms and had a negative PfHRP2-RDT were enrolled. The PET-PCR had a positivity rate of 23.5% (295/1255) overall. The PET-PCR positivity rate was 37.6%, 12.3%, and 22.8% in Diourbel, Kaolack, and Tambacounda, respectively. Successful sequencing of 121/295 positive samples detected P. falciparum (93%), P. vivax (2.6%), P. malariae (4.4%), and P. ovale wallikeri (0.9%). Plasmodium vivax was co-identified with P. falciparum in thirteen samples. Sequencing also detected two PfHRP2-RDT-negative mono-infections of P. vivax in Tambacounda and Kaolack., Conclusion: The findings demonstrate the circulation of P. vivax in western and eastern Senegal, highlighting the need for improved malaria control strategies and accurate diagnostic tools to better understand the prevalence of non-falciparum species countrywide., (© 2024. The Author(s).)

The bromodomain inhibitor (+)-JQ1 is a highly validated chemical probe; however, it exhibits poor in vivo pharmacokinetics. To guide efforts toward improving its pharmacological properties, we identified the (+)-JQ1 primary metabolite using chemical catalysis methods. Treatment of (+)-JQ1 with tetrabutylammonium decatungstate under photochemical conditions resulted in selective formation of an aldehyde at the 2-position of the thiophene ring [(+)-JQ1-CHO], which was further reduced to the 2-hydroxymethyl analog [(+)-JQ1-OH]. Comparative LC/MS analysis of (+)-JQ1-OH to the product obtained from liver microsomes suggested (+)-JQ1-OH as the major metabolite of (+)-JQ1. The 2-thienyl position was then substituted to generate a trideuterated (-CD 3 , (+)-JQ1-D) analog having half-lives that were 1.8- and 2.8-fold longer in mouse and human liver microsomes, respectively. This result unambiguously confirmed (+)-JQ1-OH as the major metabolite of (+)-JQ1. These studies demonstrate an efficient process for studying drug metabolism and identifying the metabolic soft spots of bioactive compounds., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Introduction: Hodgkin Lymphoma (HL) is a prevalent hematological cancer in the world and Chile., Objectives: Show the experience of 10 years treating HL in a Chilean academic center. Additionally, it exposes the diagnostic performance of PET CT and Bone Marrow Biopsy., Material and Methods: We conducted a retrospective cohort study to collect data and outcomes of patients treated in our center., Results: 82 patients were analyzed (Average age, 35 years old; the ratio between men and women was 1.9:1). Progression-free survival was 88.6% and 66.4% for localized and advanced stages, respectively. PET as a staging strategy had better sensitivity than Marrow Biopsy., Conclusions: The clinical results of the patients treated in this Chilean teaching center were comparable to the international literature. Additionally, PET CT proved to be a superior tool in diagnosis and staging compared to biopsy in our patients.

Background: During the COVID-19 pandemic, and recognising the sacrifice of health and care workers alongside discrimination, violence, poor working conditions and other violations of their rights, health and safety, in 2021 the World Health Assembly requested WHO to develop a global health and care worker compact, building on existing normative documentation, to provide guidance to 'protect health and care workers and safeguard their rights'., Methods: A review of existing international law and other normative documents was conducted. We manually searched five main sets of international instruments: (1) International Labour Organization conventions and recommendations; (2) WHO documents; (3) United Nations (UN) human rights treaties and related documents; (4) UN Security Council and General Assembly resolutions and (5) the Geneva Conventions and Additional Protocols. We included only legal or other normative documents with a global or regional focus directly addressing or relevant to health and care workers or workers overall., Results: More than 70 documents met our search criteria. Collectively, they fell into four domains, within which we identified 10 distinct areas: (1) preventing harm, encompassing (A) occupational hazards, (B) violence and harassment and (C) attacks in situations of fragility, conflict and violence; (2) inclusivity, encompassing (A) non-discrimination and equality; (3) providing support, encompassing (A) fair and equitable remuneration, (B) social protection and (C) enabling work environments and (4) safeguarding rights, encompassing (A) freedom of association and collective bargaining and (B) whistle-blower protections and freedom from retaliation., Discussion: A robust legal and policy framework exists for supporting health and care workers and safeguarding their rights. Specific human rights, the right to health overall, and other binding and non-binding legal documents provide firm grounding for the compact.However, these existing commitments are not being fully met. Implementing the compact will require more effective governance mechanisms and new policies, in partnership with health and care workers themselves., Competing Interests: Competing interests: All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare: AF, EAF, LG and SW were part of a grant in 2021 from the Federal Ministry of Health of Germany that was administered by WHO and provided to the O’Neill Institute for National and Global Health Law (via Georgetown University) to identify the evidence base for the global health and care worker compact and to develop a draft of the compact; the Federal Ministry of Health of Germany had no role in the conceptualisation and drafting of the manuscript. AF, EAF, LG and SW are part of a current (2023) grant from the Federal Ministry of Health of Germany that is administered by WHO and provided to the O’Neill Institute for National and Global Health Law (via Georgetown University). The firt installment of the grant has been provided by WHO to the O’Neill Institute (via Georgetown University) for follow-on work on the global health and care worker compact to support monitoring and implementation of the compact, with further installments to be provided; the Federal Ministry of Health of Germany had no role in the conceptualisation and drafting of the manuscript. LG is the Director of the WHO Collaborating Centre on Global Health Law. AF, EAF, LG and SW have no other conflicts of interest to declare. RB, CB, JC, GC and CK have no interests to declare, including no other support from any organisation for the submitted work other than that described for AF, EAF, LG and SW; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years other than that described for AF, EAF, LG and SW; and no other relationships or activities that could appear to have influenced the submitted work other than that described for LG., (© World Health Organization 2023. Licensee BMJ.)

Background: Hematopoietic autologous stem cell transplantation (ASCT) is a validated therapeutic strategy for lymphoma treatment and precise well-tolerated conditioning. Several conditioning methods are available, but the most commonly used are CVB, BEAM, and ICE, which are conventionally administered in 6 to 7 days. Since 2015, our program has moved toward noncryopreserved platforms that require concise times; therefore, we have modified the conditioning by reducing it to 4 to 5 days. In this study, we show our experience., Methods: We compared ASCT performed in our program before and after 2015 in lymphoma patients. Between 2000 and 2014 and from 2015 to 2022, we performed 46 and 61 ASCT procedures, respectively., Results: Since 2015, we observed a greater number of infused stem cells, fewer episodes of febrile neutropenia (60% vs. 37% P = .008), shorter hospitalizations (30 vs. 18 days P = .001), faster engraftment (20 vs. 14 days P = .001) and better progression-free survival (72 vs. 44 months P = .002). Additionally, a prolonged overall survival was observed at these results, and this prolonged survival is difficult to interpret due to the short follow-up., Conclusion: In conclusion, conditioning adjusted for a noncryopreserved strategy offers at least similar or even better results than the cryopreserved strategy. Prospective studies are warranted., Competing Interests: Disclosure The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Algorithms have been developed to identify rheumatoid arthritis-interstitial lung disease (RA-ILD) in administrative data with positive predictive values (PPVs) between 70 and 80%. We hypothesized that including ILD-related terms identified within chest computed tomography (CT) reports through text mining would improve the PPV of these algorithms in this cross-sectional study., Methods: We identified a derivation cohort of possible RA-ILD cases (n = 114) using electronic health record data from a large academic medical center and performed medical record review to validate diagnoses (reference standard). ILD-related terms (e.g., ground glass, honeycomb) were identified in chest CT reports by natural language processing. Administrative algorithms including diagnostic and procedural codes as well as specialty were applied to the cohort both with and without the requirement for ILD-related terms from CT reports. We subsequently analyzed similar algorithms in an external validation cohort of 536 participants with RA., Results: The addition of ILD-related terms to RA-ILD administrative algorithms increased the PPV in both the derivation (improvement ranging from 3.6 to 11.7%) and validation cohorts (improvement 6.0 to 21.1%). This increase was greatest for less stringent algorithms. Administrative algorithms including ILD-related terms from CT reports exceeded a PPV of 90% (maximum 94.6% derivation cohort). Increases in PPV were accompanied by a decline in sensitivity (validation cohort -3.9 to -19.5%)., Conclusions: The addition of ILD-related terms identified by text mining from chest CT reports led to improvements in the PPV of RA-ILD algorithms. With high PPVs, use of these algorithms in large data sets could facilitate epidemiologic and comparative effectiveness research in RA-ILD., (Copyright © 2023. Published by Elsevier Inc.)