Search

* Context.--Liver biopsy plays an important role in the clinical management of metastases and often requires workup using immunohistochemical (IHC) markers, but the approach varies among institutions. Objective.--To evaluate the utility of a morphologic pattern-based, individualized approach in the workup of hepatic metastases. Design.--All liver biopsies with metastasis between 2015 and 2018 were identified from our institutional database and were reviewed. The morphologic pattern of the metastasis and IHC markers used in each case were recorded. The final identification of primary site of the tumor was assessed based on all the available clinicopathologic data. The academic ranking and practice pattern of the pathologist signing out the case were also recorded. Results.--A total of 406 liver biopsies with metastasis were identified, and the cases were classified as adenocarcinoma (253 of 406; 62%), carcinoma not otherwise specified (12 of 406; 3%), neuroendocrine neoplasm (54 of 406; 13%), poorly differentiated carcinoma (43 of 406; 11%), nonepithelial tumor (24 of 406; 6%), and squamous cell carcinoma (20 of 406; 5%). The primary site was unknown in 39% (158 of 406) at the time of liver biopsy. A primary site was determined in 97% (395 of 406) of all cases, and only 3% (11 of 406) remained true carcinoma of unknown primary. The average number of IHC markers/ case in patients with known primary was 2.6, compared with 5.9 with an initial unknown primary and 9.5 in cases of true carcinoma of unknown primary. Conclusions.--An individualized, case-based approach seems to be highly cost-effective and uses fewer IHC markers compared with preset panels that often comprise 10 or more IHC markers. doi: 10.5858/arpa.2021-0457-OA, The liver is a common site for metastasis, and liver biopsy plays an important role in clinical management in many patients. The liver biopsy is useful for confirming the diagnosis [...]

The last decade has seen the emergence of immune checkpoint inhibitors for the treatment of a wide variety of cancer types. While these medications are generally speaking well tolerated, the full long-term side effect profiles of these medications have not been fully elucidated. We describe a case of chronic rhinosinusitis with nasal polyposis induced treatment with pembrolizumab, the first reported case. We present the case of a 48-year-old man with a background history of stage IV non-small cell lung cancer with bone metastases. He was commenced on pembrolizumab and over the course of the subsequent 5 years he developed significant nasal polyps bilaterally, and was commenced on medical therapy. Sinus CT scan demonstrated bilateral total opacification of all his sinuses and nasal cavity. He subsequently underwent bilateral functional endoscopic sinus surgery. He remains symptom-free and at his last clinical follow-up visit 1 year later. There are limited case reports of nasal polyposis occurring in patients receiving immune checkpoint inhibitors, with only one case requiring surgery. We describe the first case of severe nasal polyps due to pembrolizumab and successfully treated with polypectomy. From our review, there were no cases that required a cessation of therapy.

Abstract Background Excessive gestational weight gain (EGWG), insufficient prenatal physical activity and sleep, and poor psychological wellbeing independently increase risks for adverse maternal and infant outcomes. A novel approach to mitigate these risks is utilizing peer support in a community-based prenatal intervention. This study assessed the feasibility (acceptability, demand, implementation, and practicality) of a remotely delivered prenatal physical activity intervention called My Baby, My Move + (MBMM +) that aims to increase prenatal physical activity, enhance mood and sleep hygiene, and reduce EGWG. Methods Participants were recruited through community organizations, local clinics, and social media platforms in the Fall of 2020 and Spring of 2021. Eligible pregnant women were randomized to either the MBMM + intervention or the control group. Each group met over Zoom for 16 sessions (twice weekly for 60 min over 8 weeks) to learn either behavioral change and wellbeing knowledge and skills (MBMM +) or knowledge and skills related to parenting (control group). Multiple methods of evaluation to better understand the feasibility of the intervention were conducted. Results A total of 49 women (25 MBMM + intervention, 24 control) completed both pre- and post-survey assessments and were included in the analyses. A subsample of 19 (39%) intervention participants completed a combination of semi-structured interviews/surveys to assess acceptability, demand, implementation, and practicality. Participants expressed positive feedback regarding acceptability (satisfaction and intent to continue use) and were extremely likely or likely to recommend the program to a friend (demand). Implementation metrics were assessed by observation and feedback forms completed by peer leaders and demonstrated high-quality control. Findings suggest that the intervention was practical due to remote sessions and cost-effectiveness. Conclusion The MBMM + intervention was deemed to be a feasible intervention with high acceptability, demand, implementation, and practicality. These findings can be used to inform the scalability of the intervention and implementation of a larger efficacy trial. Trial registration 19–1366, initial date is on January 23, 2020.

Glaesserella parasuis es habitualmente encontrada en el tracto respiratorio de cerdos, aunque existen cepas asociadas a enfermedades sistémicas severas, causantes de pérdidas económicas a nivel mundial. Existen 15 serotipos caracterizados asociados a diferentes grados de virulencia. En Paraguay, se desconocen los serotipos circulantes. El objetivo de este trabajo fue identificar serotipos de G. parasuis presentes en el Departamento de Itapúa. Se incluyeron 62 cerdos con síntomas respiratorios provenientes de cinco granjas productoras de porcinos de Itapúa durante el mes de febrero del 2022 a marzo del 2023. Los aislados se realizaron a partir de muestras de pulmón y de cornetes colectadas en necropsias e hisopados nasales en animales vivos. Las muestras se cultivaron en Agar Chocolate + NAD, tras 48 hs de incubación a 37°C se realizaron pruebas bioquímicas a las colonias sospechosas, posteriormente se realizó la extracción de ADN a las confirmadas, seguido de PCR multiplex utilizando cebadores para cada uno de los serotipos y un par específico de la especie. En todas las granjas se identificó la presencia de G. parasuis, un total de 12 cepas, entre las que se encontraban el Serotipo 2 (1), Serotipo 3 (3), Serotipo 7 (1), Serotipo 8 (1) y otras Serotipo no determinado (6), identificándose la presencia del gen de virulencia VtaA en todas las cepas aisladas, excepto la correspondiente al Ser8. De esta manera, este trabajo se convierte en el primer reporte de serotipos de G. parasuis en Itapúa-Paraguay.

Abstract Background To support public health researchers and advocates seeking to challenge the influence of powerful commercial actors on health, it is necessary to develop a deeper understanding of corporate political activities. This project explores political science scholarship analysing lobbying to identify new datasets and research methods that can be applied to public health and stimulate further research and advocacy. Methods We undertook a systematic scoping review of peer-reviewed and grey literature reports analysing the practice of lobbying. Titles and abstracts of 4533 peer-reviewed and 285 grey literature reports were screened, with 233 peer-reviewed and 280 grey literature reports assessed for eligibility. We used a two-stage process for data extraction. In stage 1, we collected two pieces of information from all included studies: data sources and indicators used to measure lobbying. For the second stage, data extraction was limited to 15 studies that focused on meetings. Results The most common indicators used to measure lobbying activity were: registrations of active lobbyists; expenditure on lobbying; meetings; written comments and submissions made to government consultations; bills; and committee participation. A range of different data sources were used to analyse lobbying, including from governments, not-for-profits and commercial sources. All 15 studies analysing lobbyist meetings were from high-income contexts. The studies analysed three key variables: the types of government actors targeted by lobbying; the policies of interest; and the lobbyists and/or their clients. The studies used a range of taxonomies to classify policy issues and the types of actors engaged in lobbying. All studies discussed challenges with accessing and analysing lobbying data. Conclusions There is enormous potential for public health research and advocacy concerned with commercial lobbying to learn from political science scholarship. This includes both conceptual frameworks and sources of empirical data. Moreover, the absence of good quality transparency internationally emphasises the importance of advocacy to support policy change to improve the quality of political transparency to make it easier to monitor commercial lobbying.

Abstract B cells are known to contribute to the anti-tumor immune response, especially in immunogenic tumors such as melanoma, yet humoral immunity has not been characterized in these cancers to detail. Here we show comprehensive phenotyping in samples of circulating and tumor-resident B cells as well as serum antibodies in melanoma patients. Memory B cells are enriched in tumors compared to blood in paired samples and feature distinct antibody repertoires, linked to specific isotypes. Tumor-associated B cells undergo clonal expansion, class switch recombination, somatic hypermutation and receptor revision. Compared with blood, tumor-associated B cells produce antibodies with proportionally higher levels of unproductive sequences and distinct complementarity determining region 3 properties. The observed features are signs of affinity maturation and polyreactivity and suggest an active and aberrant autoimmune-like reaction in the tumor microenvironment. Consistent with this, tumor-derived antibodies are polyreactive and characterized by autoantigen recognition. Serum antibodies show reactivity to antigens attributed to autoimmune diseases and cancer, and their levels are higher in patients with active disease compared to post-resection state. Our findings thus reveal B cell lineage dysregulation with distinct antibody repertoire and specificity, alongside clonally-expanded tumor-infiltrating B cells with autoimmune-like features, shaping the humoral immune response in melanoma.

David J Cangemi, Brian E Lacy Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USACorrespondence: David J Cangemi, Division of Gastroenterology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, USA, 32224, Email cangemi.david@mayo.eduAbstract: Gastroparesis (GP), a historically vexing disorder characterized by symptoms of nausea, vomiting, abdominal pain, early satiety, and/or bloating, in the setting of an objective delay in gastric emptying, is often difficult to treat and carries a tremendous burden on the quality of patients’ lives, as well as the healthcare system in general. Though the etiology of GP has been fairly well defined, much work has been done recently to better understand the pathophysiology of GP, as well as to identify novel effective and safe treatment options. As our understanding of GP has evolved, many myths and misconceptions still abound in this rapidly changing field. The goal of this review is to identify myths and misconceptions regarding the etiology, pathophysiology, diagnosis, and treatment of GP, in the context of the latest research findings which have shaped our current understanding of GP. Recognition and dispelling of such myths and misconceptions is critical to moving the field forward and ultimately advancing the clinical management of what will hopefully become a better understood and more manageable disorder in the future.Keywords: gastroparesis, functional dyspepsia, nausea, vomiting, abdominal pain

Abstract Overall survival estimates from diagnosis are valuable for guiding treatment, but do not consider the years already survived. Conditional survival (CS) provides dynamic survival predictions over time. This study was conducted to estimate CS at 1–8 years from diagnosis and the impact of baseline prognostic factors on CS in multiple myeloma (MM) patients. This is a retrospective study including 2556 MM patients diagnosed between 2004 and 2019. CS (t | s) was defined as the probability of surviving t years given survival of s years. Median age was 64 years. Median follow-up was 6.2 years and median overall survival from diagnosis was 7.5 years. The 5-year CS estimates at s = 0, 1, 2, 3, and 5 years were 0.64, 0.61, 0.61, 0.61, and 0.58, respectively. On multivariate analysis, age ≥ 65 and proteasome inhibitor+immunomodulatory-based induction were associated with decreased survival and increased survival, respectively, retained at 5 years. The adverse impact of 1q gain/amplification, high-risk IgH translocation, and ISS-3 was significant at 1 and 3 years but not 5 years. Chromosome 17 abnormality was associated with decreased survival only at 1 year. Among MM patients, 5-year CS was stable at 1–5 years from diagnosis. The prognostic impact of high-risk cytogenetic factors decreased with additional years survived.

Abstract The global threat of antimicrobial resistance (AMR) varies regionally. This study explores whether geospatial analysis and data visualization methods detect both clinically and statistically significant variations in antibiotic susceptibility rates at a neighborhood level. This observational multicenter geospatial study collected 10 years of patient-level antibiotic susceptibility data and patient addresses from three regionally distinct Wisconsin health systems (UW Health, Fort HealthCare, Marshfield Clinic Health System [MCHS]). We included the initial Escherichia coli isolate per patient per year per sample source with a patient address in Wisconsin (N = 100,176). Isolates from U.S. Census Block Groups with less than 30 isolates were excluded (n = 13,709), resulting in 86,467 E. coli isolates. The primary study outcomes were the results of Moran’s I spatial autocorrelation analyses to quantify antibiotic susceptibility as spatially dispersed, randomly distributed, or clustered by a range of − 1 to + 1, and the detection of statistically significant local hot (high susceptibility) and cold spots (low susceptibility) for variations in antibiotic susceptibility by U.S. Census Block Group. UW Health isolates collected represented greater isolate geographic density (n = 36,279 E. coli, 389 = blocks, 2009–2018), compared to Fort HealthCare (n = 5110 isolates, 48 = blocks, 2012–2018) and MCHS (45,078 isolates, 480 blocks, 2009–2018). Choropleth maps enabled a spatial AMR data visualization. A positive spatially-clustered pattern was identified from the UW Health data for ciprofloxacin (Moran’s I = 0.096, p = 0.005) and trimethoprim/sulfamethoxazole susceptibility (Moran’s I = 0.180, p

Abstract Background: Inpatient behavioral health units (BHUs) had unique challenges in implementing interventions to mitigate coronavirus disease 2019 (COVID-19) transmission, in part due to socialization in BHU settings. The objective of this study was to identify the transmission routes and the efficacy of the mitigation strategies employed during a COVID-19 outbreak in an inpatient BHU during the Omicron surge from December 2021 to January 2022. Methods: An outbreak investigation was performed after identifying 2 COVID-19-positive BHU inpatients on December 16 and 20, 2021. Mitigation measures involved weekly point prevalence testing for all inpatients, healthcare workers (HCWs), and staff, followed by infection prevention mitigation measures and molecular surveillance. Whole-genome sequencing on a subset of COVID-19-positive individuals was performed to identify the outbreak source. Finally, an outbreak control sustainability plan was formulated for future BHU outbreak resurgences. Results: We identified 35 HCWs and 8 inpatients who tested positive in the BHU between December 16, 2021, and January 17, 2022. We generated severe acute respiratory coronavirus virus 2 (SARS-CoV-2) genomes from 15 HCWs and all inpatients. Phylogenetic analyses revealed 3 distinct but genetically related clusters: (1) an HCW and inpatient outbreak likely initiated by staff, (2) an HCW and inpatient outbreak likely initiated by an inpatient visitor, and (3) an HCW-only cluster initiated by staff. Conclusions: Distinct transmission clusters are consistent with multiple, independent SARS-CoV-2 introductions with further inpatient transmission occurring in communal settings. The implemented outbreak control plan comprised of enhanced personal protective equipment requirements, limited socialization, and molecular surveillance likely minimized disruptions to patient care as a model for future pandemics.

Sustainability implementation efforts, relevant to all Sustainable Development Goals (SDG), can succeed or fail based on how the program activities effectively align with local community norms. Conflict arises when implementers incorrectly assume the ways in which local communities and other stakeholders share their world views. A novel approach was applied to identify conflicts between stakeholder norms through the example of wildlife conservation. This case is based on 62 systematically collected interviews involving law enforcement staff (wildlife police officers [WPOs]) and local community members in four of Zambia's Game Management Areas. Cultural consensus analysis (CCA) was used to extract and compare cultural models across groups. Discordant cultural norms were identified for resource protection, which reflected frailty of collaborative strategies. Concordant norms were relevant to shared understandings of the disproportionate burdens to GMA-based communities from conservation and some potential benefits of collaboration. This case shows exemplar application of CCA to capture and compare stakeholder norms associated with livelihoods and conservation, allowing better program design that reduces conflict and builds on shared values to better support SDGs, especially SDG15 (Life on Land).

Coupling of black hole mass to the cosmic expansion has been suggested as a possible path to understanding the dark energy content of the Universe. We test this hypothesis by comparing the supermassive black hole (SMBH) mass density at z = 0 to the total mass accreted in active galactic nuclei (AGN) since z = 6, to constrain how much of the SMBH mass density can arise from cosmologically coupled growth, as opposed to growth by accretion. Using an estimate of the local SMBH mass density of ≈1.0 × 10 ^6 M _⊙ Mpc ^−1 , a radiative accretion efficiency, η , in the range 0.05 < η < 0.3, and the observed AGN luminosity density at z ≈ 4, we constrain the value of the coupling constant between the scale size of the Universe and the black hole mass, k , to lie in the range 0 < k ≲ 2, below the value of k = 3 needed for black holes to be the source term for dark energy. Initial estimates of the gravitational-wave background (GWB) using pulsar timing arrays, however, favor a higher SMBH mass density at z = 0. We show that if we adopt such a mass density at z = 0 of ≈7.4 × 10 ^6 M _⊙ Mpc ^−1 , this makes k = 3 viable even for low radiative efficiencies, and may exclude nonzero cosmological coupling. We conclude that, although current estimates of the SMBH mass density based on the black hole mass–bulge mass relation probably exclude k = 3, the possibility remains open that, if the GWB is due to SMBH mergers, k > 2 is preferred.

Abstract Molecular tools are increasingly applied for assessing and monitoring biodiversity and informing conservation action. While recent developments in genetic and genomic methods provide greater sensitivity in analysis and the capacity to address new questions, they are not equally available to all practitioners: There is considerable bias across institutions and countries in access to technologies, funding, and training. Consequently, in many cases, more accessible traditional genetic data (e.g., microsatellites) are still utilized for making conservation decisions. Conservation approaches need to be pragmatic by tackling clearly defined management questions and using the most appropriate methods available, while maximizing the use of limited resources. Here we present some key questions to consider when applying the molecular toolbox for accessible and actionable conservation management. Finally, we highlight a number of important steps to be addressed in a collaborative way, which can facilitate the broad integration of molecular data into conservation.

Summary: Background: The protection of fourth dose mRNA vaccination against SARS-CoV-2 is relevant to current global policy decisions regarding ongoing booster roll-out. We aimed to estimate the effect of fourth dose vaccination, prior infection, and duration of PCR positivity in a highly-vaccinated and largely prior-COVID-19 infected cohort of UK healthcare workers. Methods: Participants underwent fortnightly PCR and regular antibody testing for SARS-CoV-2 and completed symptoms questionnaires. A multi-state model was used to estimate vaccine effectiveness (VE) against infection from a fourth dose compared to a waned third dose, with protection from prior infection and duration of PCR positivity jointly estimated. Findings: 1298 infections were detected among 9560 individuals under active follow-up between September 2022 and March 2023. Compared to a waned third dose, fourth dose VE was 13.1% (95% CI 0.9 to 23.8) overall; 24.0% (95% CI 8.5 to 36.8) in the first 2 months post-vaccination, reducing to 10.3% (95% CI −11.4 to 27.8) and 1.7% (95% CI −17.0 to 17.4) at 2–4 and 4–6 months, respectively. Relative to an infection >2 years ago and controlling for vaccination, 63.6% (95% CI 46.9 to 75.0) and 29.1% (95% CI 3.8 to 43.1) greater protection against infection was estimated for an infection within the past 0–6, and 6–12 months, respectively. A fourth dose was associated with greater protection against asymptomatic infection than symptomatic infection, whilst prior infection independently provided more protection against symptomatic infection, particularly if the infection had occurred within the previous 6 months. Duration of PCR positivity was significantly lower for asymptomatic compared to symptomatic infection. Interpretation: Despite rapid waning of protection, vaccine boosters remain an important tool in responding to the dynamic COVID-19 landscape; boosting population immunity in advance of periods of anticipated pressure, such as surging infection rates or emerging variants of concern. Funding: UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, Bristol, and others.