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Niranjan J Sathianathen,1 Suprita Krishna,1 J Kyle Anderson,1,2 Christopher J Weight,1,2 Shilpa Gupta,2,3 Badrinath R Konety,1,2 Thomas S Griffith1,2,4,5 1Department of Urology, 2Masonic Cancer Center, 3Division of Hematology, Oncology, and Transplantation, 4Center for Immunology, 5Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota, Minneapolis, MN, USA Abstract: The management of metastatic renal-cell carcinoma (mRCC) represents an important clinical challenge. Since being approved in the early 1990s, aspecific immunotherapy has been a mainstay of treatment for mRCC and the only therapy that has demonstrated long-term cures for mRCC. However, in recent times there have been landmark advances made in the field of specific immunotherapy for a number of malignancies, including kidney cancer. This review outlines the range of immunobased agents currently available for the treatment of mRCC. Keywords: immunotherapy, cryosurgery, kidney neoplasm, vaccines, targeted therapy, immunocheckpoints

The author relates the findings of a qualitative study of the work-role transition of a clinical expert to novice nurse educator in a baccalaureate program. The information is presented in the form of a metaphor to provide a figurative way of reading research that can serve to stimulate thinking about the phenomenon while using storytelling to pique interest. [ABSTRACT FROM AUTHOR]

Use of a pharmacotherapeutic regimen incorporating a calcium channel blocker or an alpha[1]-receptor blocker and a corticosteroid can facilitate spontaneous ureteral stone passage and reduce the morbidity associated conservative approach to treatment of selected patients with ureteral stones. But important questions about this therapy remain--including stone size cut-points and optimal ureteral locations. [ABSTRACT FROM AUTHOR]

In Part I, the authors pointed out that despite the increasing focus on communication in psychosocial oncology, a comprehensive review of the literature revealed that the primary emphasis has been individuals' self-reported experiences rather than on naturally occurring interactions between cancer patients, family members, and health professionals. Thus, an empirical foundation for understanding communication activities is in its infancy. In Part II, the authors provide an overview of 'conversation analysis' as an alternative method for studying patterns of interaction during medical encounters and family interactions. Transcribed excerpts from ongoing research, focusing on how family members talk through cancer on the telephone, exemplify how 'news delivery sequences' and 'managing optimism' are crucial resources for understanding and dealing with cancer journeys. The authors conclude by discussing the need for discernment between self-report and interactional data, the usefulness of conversation analysis for oncology professionals, and the possibilities for collaborative research. [ABSTRACT FROM AUTHOR]

Although increasing attention is paid to communication in psychosocial oncology, a comprehensive review of the literature reveals that emphasis has been given to individual's self-reported experiences. Because naturally occuring interactions between cancer patients, family members, and health professionals have not received systematic attention, the authors propose that an empirical foundation for understanding communication activities is in its infancy. In this two-part article, Part I expands on how communication has been identified as central to family relationships, yet has been accessed through individuals' reports. Specific examples drawn from both qualitative and quantitative research methods illustrate the predominance and limitations of self-reports for studying communication and psychosocial oncology. Part II provides an overview of 'conversation analysis' as an alternative method for studying interactional patterns in medical encounters and family interactions. The discussion focuses on the usefulness of conversation analysis for oncology professionals and the possibilities for collaborative research. [ABSTRACT FROM AUTHOR]

Background: Andropause, the natural age-related decline in testosterone in men, has been debated in the literature. The nonsexual benefits of testosterone replacement therapy (TRT) in male hypogonadism are well documented, but whether health care professionals (HCPs) and members of the general public are aware of these benefits is not known. This study assesses the knowledge and perceptions of andropause and TRT among HCPs and members of the general public.Methods: Brief surveys were administered to HCPs and members of the general public who called a medical information telephone line. Trained clinical interviewers surveyed participants for experiences with andropause and TRT and knowledge about nonsexual effects of low testosterone in men.Results: Of 443 general public callers, 377 (85%) agreed to participate in the survey. Of these participants, 77% had heard of andropause or male menopause, and 63% had taken TRT. Of 88 HCP callers, 57 (65%) participated. Of these participants, 65% were pharmacists, 80% had encountered patients with symptoms of low testosterone, and 50% reported that patients rarely or never initiated conversations about low testosterone. Among HCPs and the general public, respectively, 98% and 91% knew that low testosterone is treatable with medication, and 60% and 57% knew that it results in osteoporosis. Only 25% of HCPs and 14% of the general public knew that low testosterone does not cause loss of urinary control.Conclusions: HCPs and members of the general public are knowledgeable about some aspects of low testosterone and have misconceptions about others. Educational initiatives are needed. [ABSTRACT FROM AUTHOR]

Background: Internationally, over one-third of women experience birth trauma, leading to adverse mental health outcomes. Poor communication with healthcare professionals is a primary contributing factor. Paramedics attend various clinical presentations, including childbirth, yet their potential impact on women's birth experiences has been largely overlooked., Methods: A systematic literature search was conducted following the Joanna Briggs Institute methodological framework. The search identified 1015 potentially suitable articles, and 5 articles met the inclusion criteria. Data was analysed using reflexive thematic analysis from a feminist standpoint., Results: Three themes were generated: 1. First Impressions Count: paramedic demeanour impacted the woman's sense of safety and perception of paramedic clinical competence. 2. Choice as a Pathway to Control: when paramedics involved women in decision-making, it led to empowerment, while non-involvement led to women becoming passive participants. 3. Exposed, Violated and Disempowered: some paramedics disrespected and abused women, treating them solely as objects for the purpose of producing a baby., Conclusions: This review highlights the influence of paramedic communication on women's birth experiences. While some paramedics communicated respectfully, other paramedics were the perpetrators of Obstetric Violence. Future research should inform paramedic education and improve outcomes for birthing women., Competing Interests: Declaration of competing interest The authors confirm there are no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Acquired amegakaryocytic thrombocytopenia (AATP) is a rare disorder in which severely low platelet levels occur due to reduced or complete absence of megakaryocytes in the bone marrow. The pathophysiology of this disease is not fully understood, although anti-thyroid peroxidase antibodies (anti-TPO) binding to cellular-myeloproliferative leukemia (c-mpl) receptors is a proposed mechanism. Currently, no standard published guideline for treatment exists, but immunosuppressive therapies have been used based on the proposed mechanism and associated conditions. We present a case of a 57-year-old male who presented to the hospital with a 3-day history of progressive weakness and dysphagia. He had recently been discharged from an outside health system after evaluation for suspected gastrointestinal bleeding, although esophagogastroduodenoscopy and colonoscopy did not uncover a source of bleeding. Fifteen days later, he was admitted to our hospital for septic shock and acute renal failure with suspected lower gastrointestinal bleeding (melena on presentation). He was found to have a rapidly declining platelet count with a nadir of 0. Due to severe thrombocytopenia, filgrastim was administered. A bone marrow biopsy revealed findings consistent with amegakaryocytosis with otherwise preserved cell lines. Hematologic labs improved with the initiation of appropriate treatment for severe sepsis. After performing an extensive workup, the likely etiology of transient AATP in this case was severe sepsis-induced immune dysregulation and bone marrow suppression., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Barker et al.)

Background: At least half of all young people who die by suicide have previously self-harmed and most of those who self-harm will not seek help from health services for self-harming behaviours. By default, schools, colleges and universities necessarily play a key role in identifying those who self-harm and supporting them to access help., Methods: We conducted a systematic review (PROSPERO ID: CRD42021243692) of five databases (Medline, PsycINFO, ASSIA, ERIC and BEI) for quantitative studies evaluating interventions to reduce self-harm among students in schools, colleges and universities., Results: We identified six eligible studies that reported interventions. Two interventions used mindfulness-based approaches and the remaining four interventions focused on in-classroom education. Three interventions reported a significant reduction in self-harm, all three used in-classroom education. Of the six studies, one study was rated methodologically moderate, while the remaining five were weak., Conclusion: In summary, the evidence base is limited in size and quality. Most current interventions to address self-harm in schools focus on training staff in awareness, with a significant gap in direct support for students., (© 2022 The Authors. Child and Adolescent Mental Health published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Introduction: Hospital-acquired infections (HAIs) after stroke are associated with additional morbidity and mortality, but whether HAIs increase long-term cognitive decline in stroke patients is unknown. We hypothesized that older adults with incident stroke with HAI experience faster cognitive decline than those having stroke without HAI and those without stroke., Methods: We performed a longitudinal analysis in the population-based prospective Cardiovascular Health Study. Medicare-eligible participants aged ≥65 years with and without incident stroke had cognition assessed annually. HAIs were assessed by hospital discharge codes. Global cognitive function was assessed annually by the Modified Mini-Mental State Examination (3MSE) and executive function by the Digit Symbol Substitution Test (DSST). We used linear mixed models to estimate the mean decline and 95% confidence intervals (95% CI) for 3MSE and DSST scores by incident stroke and HAI status, adjusted for demographics and vascular risk factors., Results: Among 5,443 participants ≥65 years without previous history of stroke, 393 participants had stroke with HAI (SI), 766 had a stroke only (SO), and 4,284 had no stroke (NS) throughout a maximum 9-year follow-up. For 3MSE, compared with NS participants, SO participants had a similar adjusted mean decline (additional 0.08 points/year, 95% CI: -0.15, 0.31), while SI participants had a more rapid decline (additional 0.28 points/year, 95% CI: 0.16, 0.40). Adjusted mean decline was 0.20 points/year faster (95% CI: -0.05, 0.45) among SI than SO participants. For DSST, compared with NS participants, SO participants had a faster adjusted mean decline (additional 0.17 points/year [95% CI: 0.003, 0.33]), as did SI participants (additional 0.27 points/year [95% CI: 0.19, 0.35])., Conclusion: Stroke, when accompanied by HAI, leads to a faster long-term decline in cognitive ability than in those without stroke. The clinical and public health implications of the effect of infection on post-stroke cognitive decline warrant further attention., (© 2023 S. Karger AG, Basel.)

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma; data indicate that blastoid and pleomorphic variants have a poor prognosis. We report characteristics and outcomes of patients with blastoid/pleomorphic variants of MCL. We retrospectively studied adults with newly diagnosed MCL treated from 2000 to 2015. Primary objectives were to describe progression-free survival (PFS) and overall survival (OS). Secondary objectives included characterization of patient characteristics and treatments. Of the 1029 patients with MCL studied, a total of 207 neoplasms were blastoid or pleomorphic variants. Median follow-up period was 82 months (range, 0.1-174 months); median PFS was 38 months (95% confidence interval [CI], 28-66) and OS was 68 months (95% CI, 45-96). Factors associated with PFS were receipt of consolidative autologous hematopoietic transplantation (auto-HCT; hazard ratio [HR], 0.52; 95% CI, 0.31-0.80; P < .05), MCL International Prognostic Index (MIPI) intermediate (HR, 2.3; 95% CI, 1.2-4.3; P < .02) and high (HR, 3.8; 95% CI, 2.0-7.4; P < .01) scores, and complete response to induction (HR, 0.29 (95% CI, 0.17-0.51). Receipt of auto-HCT was not associated with OS (HR, 0.69; 95% CI, 0.41-1.16; P = .16) but was associated with MIPI intermediate (HR, 5.7; 95% CI, 2.5-13.2; P < .01) and high (HR, 10.8; 95% CI, 4.7-24.9; P < .01) scores. We report outcomes in a large cohort of patients with blastoid/pleomorphic variant MCL. For eligible patients, receipt of auto-HCT after induction was associated with improved PFS but not OS. Higher MIPI score and auto-HCT ineligibility were associated with worse survival., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Purpose: There is a critical need for reliable diagnostic biomarkers as well as surrogate markers of disease progression in multiple system atrophy (MSA). Neurofilament light chain (NfL) has been reported to potentially meet those needs. We therefore sought to explore the value of NfL in plasma (NfL-p) in contrast to cerebrospinal fluid (NfL-c) as a diagnostic marker of MSA, and to assess NfL-p and NfL-c as markers of clinical disease progression., Methods: Well-characterized patients with early MSA (n = 32), Parkinson's disease (PD; n = 21), and matched controls (CON; n = 15) were enrolled in a prospective, longitudinal study of synucleinopathies with serial annual evaluations. NfL was measured using a high-sensitivity immunoassay, and findings were assessed by disease category and relationship with clinical measures of disease progression., Results: Measurements of NfL-c were highly reproducible across immunoassay platforms (Pearson, r = 0.99), while correlation between NfL-c and -p was only moderate (r = 0.66). NfL was significantly higher in MSA compared with CON and PD; the separation was essentially perfect for NfL-c, but there was overlap, particularly with PD, for NfL-p. While clinical measures of disease severity progressively increased over time, NfL-c and -p remained at stable elevated levels within subjects across serial measurements. Neither change in NfL nor baseline NfL were significantly associated with changes in clinical markers of disease severity., Conclusions: These findings confirm NfL-c as a faithful diagnostic marker of MSA, while NfL-p showed less robust diagnostic value. The significant NfL elevation in MSA was found to be remarkably stable over time and was not predictive of clinical disease progression., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Children and young people (CYP) with comorbid physical and/or mental health conditions often struggle to receive a timely diagnosis, access specialist mental health care, and more likely to report unmet healthcare needs. Integrated healthcare is an increasingly explored model to support timely access, quality of care and better outcomes for CYP with comorbid conditions. Yet, studies evaluating the effectiveness of integrated care for paediatric populations are scarce., Aim and Methods: This systematic review synthesises and evaluates the evidence for effectiveness and cost-effectiveness of integrated care for CYP in secondary and tertiary healthcare settings. Studies were identified through systematic searches of electronic databases: Medline, Embase, PsychINFO, Child Development and Adolescent Studies, ERIC, ASSIA and British Education Index., Findings: A total of 77 papers describing 67 unique studies met inclusion criteria. The findings suggest that integrated care models, particularly system of care and care coordination, improve access and user experience of care. The results on improving clinical outcomes and acute resource utilisation are mixed, largely due to the heterogeneity of studied interventions and outcome measures used. No definitive conclusion can be drawn on cost-effectiveness since studies focused mainly on costs of service delivery. The majority of studies were rated as weak by the quality appraisal tool used., Conclusions: The evidence of on clinical effectiveness of integrated healthcare models for paediatric populations is limited and of moderate quality. Available evidence is tentatively encouraging, particularly in regard to access and user experience of care. Given the lack of specificity by medical groups, however, the precise model of integration should be undertaken on a best-practice basis taking the specific parameters and contexts of the health and care environment into account. Agreed practical definitions of integrated care and associated key terms, and cost-effectiveness evaluations are a priority for future research., (© 2023 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: School-based mental health literacy interventions aim to prevent mental disorders and promote mental wellbeing through improving the knowledge and understanding of mental health, mental disorders, and reducing stigma. Evidence suggests that good mental health literacy helps young people recognise mental health difficulties in themselves and in others, and seek help for mental health problems. Improved help-seeking can allow for early intervention, which prevents the progression of mental disorders and ultimately reduces the burden of mental disorders. The aim of this review is to identify and synthesise evidence on the effectiveness of school-based mental health literacy interventions in improving help-seeking outcomes., Methods: We searched MEDLINE, Embase, PsycINFO, ERIC, Child Development and Adolescent Studies, British Education Index and ASSIA (June 2020). Additional searches were conducted a year later to identify any new publications (June 2021). We included randomised controlled trials (RCTs) assessing the effectiveness or cost-effectiveness of school-based interventions to improve help-seeking outcomes for children and young people aged 4-18 years. Included studies were critically appraised., Results: We identified 11 studies investigating help-seeking outcomes of school-based mental health literacy interventions including a total of 7066 participants from 66 secondary schools. Overall, there is no strong evidence for the effectiveness of school-based mental health literacy interventions in improving help-seeking outcomes, including general attitudes towards help-seeking, personal intentions to seek help, knowledge of when and how to seek help for mental disorders, confidence to seek help, and actual help-seeking behaviours. None of the studies investigated the cost-effectiveness of the interventions., Conclusion: The lack of standardised measures with established reliability and validity for help-seeking outcomes, and the incomprehensive consideration of the multi-faceted concepts of MH literacy and MH stigma have contributed to the scarcity of evidence for the effectiveness. Future research should focus on developing standardised measurement tools and including economic evaluations to understand pragmatic and financial aspects of school-based mental health literacy interventions., (© 2022 The Authors. Child and Adolescent Mental Health published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: The steadily increasing prevalence of mental disorders in children and adolescents presents itself as a public health challenge, especially given the health, social and economic burden of mental disorders. School-based interventions aimed at improving mental health literacy and reducing mental health stigma have the potential to prevent mental disorders and promote mental well-being, thus reducing the burden of mental disorders. This review identified and synthesised evidence on the effectiveness of school-based interventions designed to improve mental health literacy and reduce mental health stigma., Methods: Electronic bibliographic databases including MEDLINE, Embase, PsycINFO, Education Resources Information Center (ERIC), Child Development and Adolescent Studies, British Education Index and Applied Social Sciences Index and Abstracts (ASSIA) were searched. Randomised controlled trials (RCTs) were included if they assessed the effectiveness or cost-effectiveness of school-based intervention aimed at improving mental health literacy and reducing mental health stigma for children and young people aged 4-18 years. Quality of studies was appraised using the EPHPP tool. A numerical summary and a narrative description of the findings in relation to the research questions were synthesised. This systematic review was registered with PROSPERO (CRD42020191265)., Results: We identified 21 studies describing 20 unique school-based mental health interventions. Overall, there is moderate evidence suggesting that school-based mental health interventions can be effective in improving mental health literacy and reducing mental health stigma defined as attitudes and beliefs regarding mental disorders. However, there is less evidence for their long-term effectiveness, as most studies did not include follow-ups., Conclusions: Despite exclusively including studies with randomised designs, intervention and methodological heterogeneity poses uncertainties to any conclusions made. Future research should focus on resolving methodological issues concerning how outcomes are assessed and include process evaluations to better inform the design of an intervention in term of its delivery and implementation., (© 2022 The Authors. Child and Adolescent Mental Health published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: This scoping review aimed to overview studies that used administrative data linkage in the context of child maltreatment to improve our understanding of the value that data linkage may confer for policy, practice, and research., Methods: We searched MEDLINE, Embase, PsycINFO, CINAHL, and ERIC electronic databases in June 2019 and May 2020 for studies that linked two or more datasets (at least one of which was administrative in nature) to study child maltreatment. We report findings with numerical and narrative summary., Results: We included 121 studies, mainly from the United States or Australia and published in the past decade. Data came primarily from social services and health sectors, and linkage processes and data quality were often not described in sufficient detail to align with current reporting guidelines. Most studies were descriptive in nature and research questions addressed fell under eight themes: descriptive epidemiology, risk factors, outcomes, intergenerational transmission, predictive modelling, intervention/service evaluation, multi-sector involvement, and methodological considerations/advancements., Conclusions: Included studies demonstrated the wide variety of ways in which data linkage can contribute to the public health response to child maltreatment. However, how research using linked data can be translated into effective service development and monitoring, or targeting of interventions, is underexplored in terms of privacy protection, ethics and governance, data quality, and evidence of effectiveness.

Immunotoxicity is the critical endpoint used by some regulatory agencies to establish toxicity values for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). However, the hypothesis that exposure to certain per- and polyfluoroalkyl substances (PFAS) causes immune dysregulation is subject to much debate. An independent, international expert panel was engaged utilizing methods to reduce bias and "groupthink". The panel concluded there is moderate evidence that PFOS and PFOA are immunotoxic, based primarily on evidence from animal data. However, species concordance and human relevance cannot be well established due to data limitations. The panel recommended additional testing that includes longer-term exposures, evaluates both genders, includes other species of animals, tests lower dose levels, assesses more complete measures of immune responses, and elucidates the mechanism of action. Panel members agreed that the Faroe Islands cohort data should not be used as the primary basis for deriving PFAS risk assessment values. The panel agreed that vaccine antibody titer is not useful as a stand-alone metric for risk assessment. Instead, PFOA and PFOS toxicity values should rely on multiple high-quality studies, which are currently not available for immune suppression. The panel concluded that the available PFAS immune epidemiology studies suffer from weaknesses in study design that preclude their use, whereas available animal toxicity studies provide comprehensive dataset to derive points of departure (PODs) for non-immune endpoints. The panel recommends accounting for potential PFAS immunotoxicity by applying a database uncertainty factor to POD values derived from animal studies for other more robustly supported critical effects.

Competing Interests: We declare no competing interests.

Background: In a reverse total shoulder arthroplasty, the altered glenohumeral joint center of rotation subjects the glenoid baseplate to increased shear forces and potential loosening., Methods: This study examined glenoid baseplate micromotion and initial fixation strength with the application of direct shear force in a Sawbone model. The reverse total shoulder arthroplasty systems examined were the DJO Reverse® Shoulder Prosthesis, the Exactech Equinoxe® Reverse System, and the Tornier Aequalis TM Reverse Shoulder Prosthesis. Specimens were cyclically tested with increasing shear loads until 150 µm of displacement between the implant and glenoid was achieved, and subsequently until failure, classified as either 1 cm of implant/glenoid displacement or fracture., Results: The average load withstood for the 150 µm threshold for DJO, Tornier, and Exactech was 460 ± 88 N, 525 ± 100 N, and 585 ± 160 N, respectively. The average total load at device failure for DJO, Tornier, and Exactech was 980 ± 260 N, 1260 ± 120 N, and 1350 ± 230 N, respectively., Discussion: The Exactech implant design trended toward requiring more load to induce micromotion at each threshold and to induce device failure, most commonly seen as inferior screw pull out. This study proposes design features that may enhance fixation and suggests little risk of initial micromotion or failure during initial post-operative recovery., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2021 The British Elbow & Shoulder Society.)

Laparoscopic donor nephrectomy (LDN) offers advantages to the donor. The reported incidence of testicular pain after LDN varies in the literature ranging from 3% to 55%., Methods: A survey was sent to 322 male LDN patients who donated from February 5, 2009, to February 5, 2019. The survey assessed if the donor had testicular pain or saw an additional medical professional after donation., Results: Of the 322 surveyed, 147 (46%) responses were received. Of those who had a left nephrectomy, 39% had testicular pain; 23.8% of those patients had testicular swelling in addition. Of those who had pain, laterality of kidney donated did not impact if the patient had pain, pain onset, pain level, or pain duration. Of those who donated their right kidney, 35% had testicular pain, and 16.7% of those patients reported testicular swelling in addition. Twenty-seven symptomatic patients sought additional medical care for the testicular symptoms postdonation. Seven (25%) had hydroceles, 2 (7%) had testicular cysts, 1 had a urinary tract infection, and 16 (59%) had reassurance or no additional procedures provided., Conclusions: Our results suggest that orchialgia is not as uncommon as previously thought and may be one of the most common minor complications experienced by male donors., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

An expert panel was convened to provide insight and guidance on per- and polyfluoroalkyl substances (PFAS) grouping for the purposes of protecting human health from drinking water exposures, and how risks to PFAS mixtures should be assessed. These questions were addressed through multiple rounds of blind, independent responses to charge questions, and review and comments on co-panelists responses. The experts agreed that the lack of consistent interpretations of human health risk for well-studied PFAS and the lack of information for the vast majority of PFAS present significant challenges for any mixtures risk assessment approach. Most experts agreed that "all PFAS" should not be grouped together, persistence alone is not sufficient for grouping PFAS for the purposes of assessing human health risk, and that the definition of appropriate subgroups can only be defined on a case-by-case manner. Most panelists agreed that it is inappropriate to assume equal toxicity/potency across the diverse class of PFAS. A tiered approach combining multiple lines of evidence was presented as a possible viable means for addressing PFAS that lack analytical and/or toxicological studies. Most PFAS risk assessments will need to employ assumptions that are more likely to overestimate risk than to underestimate risk, given the choice of assumptions regarding dose-response model, uncertainty factors, and exposure information., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the accuracy of manufacturer models and difference in ice ball dimensions from the first to second freeze cycles during cryoablation of renal cell carcinoma (RCC)., Methods: All patients who underwent cryoablation for RCC and had either a uniform type of needle placed in a pattern consistent with manufacturer provided data (n = 48) or computed tomography performed during the first and second freeze cycles (n = 28) were retrospectively reviewed. Ice ball measurements were made in relationship to the cryoablation probes. Factors which may affect the manufacturer prediction or change in the size of the ice ball from first to second freeze cycles were evaluated., Results: The visualized ice ball was significantly smaller than predicted in the long axis (LA) (Visualized: 29 mm ± 8; Predicted: 54 mm ± 7; p < 0.001), perpendicular transverse (PTR) (Visualized: 31 mm ± 7; Predicted: 52 mm ± 6; p < 0.001) and perpendicular craniocaudal (PCC) (Visualized: 30 mm ± 8; Predicted: 50 mm ± 7; p < 0.001). Furthermore, in the LA, PTR and PCC directions the achieved ice ball size was significantly closer to the predicted size as the total number of probes increased (p = 0.006, p = 0.048 and p = 0.023, respectively). The ice ball was significantly larger in the LA (3 mm (range: -7, 14 mm), p < 0.001), PTR (3 mm (range: -4, 11 mm), p < 0.001), and PCC (3 mm (range: 0, 26 mm), p < 0.001) dimensions on the second as compared to the first freeze cycle., Conclusion: The manufacturer provided model overestimates the size of the visualized Ice ball and Ice balls formed on the second freeze are significantly larger (median 3 mm) than those formed on the first freeze., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To assess the efficacy and safety of upadacitinib (UPA), an oral Janus kinase inhibitor, as monotherapy or in combination with non-biologic DMARDs (nbDMARDs) in patients with PsA., Methods: Pooled data were analysed from patients with prior inadequate response or intolerance to one or more nbDMARD (SELECT-PsA 1) or one or more biologic DMARD (SELECT-PsA 2) who received placebo, UPA 15 mg once daily (QD) or UPA 30 mg QD as monotherapy or in combination with two or fewer nbDMARDs for 24 weeks. Efficacy outcomes included achievement of ACR responses, Psoriasis Area and Severity Index responses, minimal disease activity and change from baseline and clinically meaningful improvement in the HAQ Disability Index. Adverse events (AEs) were summarized., Results: A total of 1916 patients were included; 574 (30%) received monotherapy and 1342 (70%) received combination therapy. Placebo-subtracted treatment effects for a 20% improvement in ACR criteria at week 12 were 33.7% (95% CI 24.4, 43.1) and 34.0% (95% CI 27.9, 40.1) for UPA 15 mg QD monotherapy and combination therapy, respectively, and 45.7% (95% CI 36.9, 54.5) and 39.6% (95% CI 33.7, 45.5) for UPA 30 mg QD monotherapy and combination therapy, respectively. Treatment effects for other outcomes were consistent between monotherapy and combination therapy. AE frequency was generally similar for UPA monotherapy and combination therapy, although hepatic disorders and creatine phosphokinase elevation were more common with combination therapy vs monotherapy., Conclusion: The efficacy and safety of UPA were generally consistent when administered as monotherapy or in combination with nbDMARDs through 24 weeks, supporting the use of UPA with or without nbDMARDs in PsA., Trial Registration: ClinicalTrials.gov (https://clinicaltrials.gov): SELECT-PsA 1 (NCT03104400), SELECT-PsA 2 (NCT03104374)., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Per- and polyfluoroalkyl substances (PFASs) are a major priority for many federal and state regulatory agencies charged with monitoring levels of emerging contaminants in environmental media and setting health-protective benchmarks to guide risk assessments. While screening levels and toxicity reference values have been developed for numerous individual PFAS compounds, there remain important data gaps regarding the mode of action for toxicity of PFAS mixtures. The present study aims to contribute whole-mixture toxicity data and advance the methods for evaluating mixtures of two key components of aqueous film-forming foams: perfluorooctanesulfonic acid (PFOS), and 6:2 fluorotelomer sulfonic acid (6:2 FTS). Wildtype (AB) zebrafish embryos were exposed to PFOS and 6:2 FTS, both as individual components and as binary mixtures, from 2 to 122 h post-fertilization. Five treatment levels were selected to encompass environmentally relevant exposure levels. Experimental endpoints consisted of mortality, hatching, and developmental endpoints, including swim bladder inflation, yolk sac area, and larval body length. Results from dose-response analysis indicate that the assumption of additivity using conventional points of departure (e.g., NOAEL, LOAEL) is not supported for critical effect endpoints with these PFAS mixtures, and that the interactions vary as a function of the dose range. Alternative methods for quantifying relative potency are proposed, and recommendations for additional investigations are provided to further advance assessments of the toxicity of PFAS mixtures to aquatic organisms.