Safety of Immune Checkpoint Inhibitors in Patients With Advanced Chronic Kidney Disease: A Retrospective Cohort Study.

BACKGROUND: Clinical trials of immune checkpoint inhibitors (ICIs) often do not include patients with advanced chronic kidney disease (CKD). We aimed to determine the safety of ICIs in patients with cancer and advanced CKD (stages 4-5 CKD, estimated glomerular filtration rate [eGFR] <30 mL/minute/1.73 m2). PATIENTS AND METHODS: Patients with advanced CKD from the Mass General Brigham network who received ICIs (n = 91) were compared against those receiving nephrotoxic (n = 113) and non-nephrotoxic (n = 130) antineoplastic therapies, respectively. Rates of new-onset kidney failure (end-stage kidney disease or sustained eGFR ≤10 mL/minute/1.73 m2) and AKI were compared. Among ICI-treated patients, we modeled Fine-Gray subdistribution hazards to compare immune-related adverse event (irAE) risk and used Kaplan-Meier analysis to compare overall survival in patients with advanced CKD to those with eGFR ≥30 mL/minute/1.73 m2. RESULTS: Rates of new-onset kidney failure were similar at 1 year following initiation of ICIs (10.0%), nephrotoxic (6.2%), and non-nephrotoxic antineoplastic therapies (9.3%) (P = .28). AKI rates were also similar: 17.5%, 17.6%, and 20% of patients in each cohort, respectively (P = .87). Advanced CKD did not increase the risk of developing irAEs (adjusted hazard ratio [HR] 1.28, 95% CI, 0.91-1.81). However, patients with advanced CKD who received ICIs had a decreased overall survival compared with patients with eGFR ≥30 mL/minute/1.73 m2 (HR 1.30 for death, 95% CI, 1.02-1.66, P = .03). CONCLUSION: ICIs are not associated with increased risk of AKI or new-onset kidney failure compared with other antineoplastic therapies in patients with advanced CKD. Advanced CKD did not increase the risk of extra-renal irAEs, although these patients suffered from lower overall survival.

A Systematic Review of the Effects of Urban Living on Suicidality and Self-Harm in the UK and Ireland.

We conducted a systematic review to answer the following: (a) Is there any evidence to support increased prevalence of suicidality and self-harm (i.e. self-harm or suicidality) in urban versus rural environments? (b) What aspects of the urban environment pose risk for suicidality and self-harm? Thirty-five studies met our criteria. Our findings reflect a mixed picture, but with a tendency for urban living to be associated with an increased risk of suicidality and self-harm over rural living, particularly for those living in deprived areas. Further research should focus on the clustering and additive effects of risk and protective factors for suicidality and self-harm in urban environments.

UK Higher Education staff experiences of moral injury during the COVID-19 pandemic.

Jonathan Shay argued that social, relational, and institutional contexts were central to understanding moral injury and conceptualised moral injury as a normative response to the betrayal of an individual's understanding of what is right by a more senior/authoritative "other". Using the conceptual lens of moral injury, this paper investigates academic staff experiences of HE during the COVID-19 pandemic and explores the rapid transition back to face-to-face teaching that took place in autumn 2020. To collect data, we used an online survey that opened in January 2021 and ran until the end of March 2021. A total of 663 complete questionnaires were received across the survey period. The questionnaire was comprised of ten topic-related questions, each of which included follow-up sub-questions and also invited participants to write in additional information. The majority of participants felt that during the course of the COVID-19 pandemic, they had acted in ways that put their own health and wellbeing at risk. Of those who had acted in ways that put their health and wellbeing at risk, they believed that their senior management were the most responsible for them acting in such ways, followed by the UK government. Qualitative data showed a systemic absence of leadership in the sector during the time, a sense of betrayal of staff and students by senior management and the government, and feelings of compulsion to act in ways which put lives at risk. On the basis of these results, we argue that there could be synergies between the situation facing healthcare staff and academics during the pandemic. Many of the experiences of HE academic staff during the pandemic reported to us in this research are resonant with the concepts of betrayal and moral injury and resulted in affective responses which we understand here in relation to feelings of guilt, shame, and anger, leading ultimately to poor mental health and wellbeing. This paper discusses implications for the HE sector going forward.

Representations of the National Health Service (NHS) in UK print media.

Generating negative news coverage of state welfare provision has been identified as a strategy designed to create public support for radical policies aimed to reduce such provision. To date, research of this kind has focused on scandals and crises. However, little is known about the complex relationship between media representations of specific events, and those of media representations in the lead up to these events, what we refer to as periphery representations. Employing a content and frame analysis, this paper analyses the frequency and intensity of peripheral representations of the National Health Service (NHS) in the British print media for 1 week a month before and for 1 week during three key events in recent NHS history: the official consultation period for the Health and Social Care Act; the publication of Five-Year Forward View, and the first Junior Doctor Strike. This article finds that negative NHS representations in articles that are peripheral to particular topical issues of controversy evidence fluctuations, amplifications and intensities across time periods, depending on the particular context. The paper concludes by arguing that repetition of negative themes in news helps to build a sensibility of 'inadequacy' of vital services. We hope that this focus on the ways in which amplifications and de-amplifications in negative intensity of peripheral NHS representations across time and content, helps to contribute to debate about the complex interplay between public health services, media representation and policy consent.

Exploring the Experiences of Male Forensic Inpatients' Relationships with Staff within Low, Medium and High Security Mental Health Settings.

Therapeutic relationships within psychiatric settings are highlighted as important throughout the literature. However, research from the forensic inpatient perspective is limited. We address this gap by exploring the patient-staff relationships within forensic mental health inpatient services, from the patient's perspective. Thirty adult male forensic inpatients were interviewed about their experiences on the ward and their interactions with staff. Our analysis examines inpatients experiences of respectful and reciprocal relationships, relationships that empower, a disinterest in their patients' and authoritarian relationships. This study concludes by highlighting the need to prioritise the development of reciprocal relationships within forensic services.

A perineal cystic hamartoma causing constipation in an intact female Irish water spaniel.

A perineal fluid-filled structure was discovered in a 6-year-old intact female Irish water spaniel suffering from intermittent constipation. Diagnostic tests revealed the structure was immediately caudal to the vagina and compatible with a cyst. Surgical excision was required for resolution of clinical signs. Histology confirmed the structure was a cyst. The exact origin is unknown; however, the variety of lining epithelia, including sections with mucin production, and a well-differentiated smooth muscle layer, were most consistent with development from the lower hindgut or urogenital sinus during embryonic growth. The histologic and anatomical similarities with human retrorectal cystic hamartomas were key in establishing the diagnosis of a perineal cystic hamartoma. Following removal, constipation resolved, and the cyst did not recur.

Hamartome kystique périnéal causant de la constipation chez une femelle intacte de race épagneul d'eau irlandais. Une structure périnéale remplie de liquide fut découverte chez une chienne intacte de race épagneul d'eau irlandais âgée de 6 ans souffrant de constipation intermittente. Les tests diagnostiques ont révélé que la structure était immédiatement caudale au vagin et était compatible avec un kyste. L'excision chirurgicale était requise pour la résolution des signes cliniques. L'histologie confirma que la structure était un kyste. L'origine exacte est inconnue; toutefois, la diversité de l'épithélium de couverture, incluant des sections avec production de mucine, et une couche bien différenciée de muscle lisse, étaient plus cohérentes avec un développement à partir du tractus digestif postérieur ou du sinus urogénital lors de la croissance embryonnaire. Les similarités histologique et anatomique avec l'hamartome rétro-rectal humain étaient critiques pour établir le diagnostic d'hamartome kystique périnéal. À la suite du retrait, la constipation s'est résolue, et il n'y a pas eu de récurrence du kyste.(Traduit par Dr Serge Messier).

Onchocerca lupi Nematodes in Dogs Exported from the United States into Canada.

The Onchocerca lupi nematode is an emerging helminth capable of infecting pets and humans. We detected this parasite in 2 dogs that were imported into Canada from the southwestern United States, a region to which this nematode is endemic. We discuss risk for establishment of O. lupi in Canada.

Cutaneous Phaeohyphomycosis Caused by Exophiala attenuata in a Domestic Cat.

A 7-year-old female-spayed, domestic short-haired cat was presented to her veterinarian with a mass on the hind paw. Histopathologic examination of a tissue biopsy revealed nodular pyogranulomatous panniculitis with intralesional pigmented fungal hyphae. A dematiaceous fungal isolate was isolated with a micromorphological phenotype consistent with the anamorphic genus Exophiala: budding cells, torulose mycelium and annellidic conidiogenesis from simple conidiophores consisting of terminal and lateral cells that tapered to a short beak at the apex. Sequence homology of the internal transcribed spacer region of the rDNA gene confirmed the identification of the isolate as Exophiala attenuata. Reported here is the first confirmed case of feline phaeohyphomycosis caused by E. attenuata in North America. Similar to historical cases of feline phaeohyphomycosis caused by Exophiala spp., there was no history or postmortem evidence to suggest the patient was in an immunocompromised state (e.g., suffering from FeLV or FIV). Although aggressive surgical excision of local lesions is recommended prior to drug treatment when dealing with subcutaneous phaeohyphomycosis, surgery followed by itraconazole treatment did not resolve the E. attenuata infection in this cat.

Acquired multiple acyl-CoA dehydrogenase deficiency and marked selenium deficiency causing severe rhabdomyolysis in a horse.

This report describes a case of severe rhabdomyolysis in a pregnant mare associated with histopathologic and biochemical features of both selenium deficiency and acquired multiple acyl-CoA dehydrogenase deficiency (MADD) due to seasonal pasture myopathy (SPM). This case highlights the importance of assessing plasma selenium levels in horses with clinical signs of pasture myopathy as this deficiency may be a contributing or exacerbating factor.

Déficience multiple acquise de déshydrogénase acyl-CoA et carence en sélénium marquée causant une rhabdomyolyse grave chez un cheval. Ce rapport décrit le cas d'une rhabdomyolyse grave chez une jument gravide associée à des caractéristiques histopathologiques et biochimiques de la carence en sélénium et d'une carence multiple acquise de déhydrogénase acyl-CoA (MADD) causées par la myopathie saisonnière des pâturages (SPM). Ce cas souligne l'importance d'évaluer les niveaux de sélénium dans le plasma des chevaux manifestant des signes cliniques de myopathie du pâturage car cette carence peut être un facteur contributif ou aggravant.(Traduit par Isabelle Vallières).

Sarcopenia, adiposity and large discordance between cystatin C and creatinine-based estimated glomerular filtration rate in patients with cancer.

BACKGROUND: Creatinine-based estimated glomerular filtration rate (eGFRCRE) may overestimate kidney function in patients with sarcopenia. While cystatin C-based eGFR (eGFRCYS) is less affected by muscle mass, it may underestimate kidney function in patients with obesity. We sought to evaluate the relationship between body composition defined by computed tomography (CT) scans and discordance between creatinine, eGFRCRE and eGFRCYS in adult patients with cancer. METHODS: This study is a cross-sectional study of consecutive adults with cancer with an abdominal CT scan performed within 90 days of simultaneous eGFRCRE and eGFRCYS measurements between May 2010 and January 2022. Muscle and adipose tissue cross-sectional areas were measured at the level of the third lumbar vertebral body using a validated deep-learning pipeline. CT-defined sarcopenia was defined using independent sex-specific cut-offs for skeletal muscle index (<39 cm2/m2 for women and <55 cm2/m2 for men). High adiposity was defined as the highest sex-specific quartile of the total (visceral plus subcutaneous) adiposity index in the cohort. The primary outcome was eGFR discordance, defined by eGFRCYS > 30% lower than eGFRCRE; the secondary outcome was eGFRCYS > 50% lower than eGFRCRE. The odds of eGFR discordance were estimated using multivariable logistic regression modelling. Unadjusted spline regression was used to evaluate the relationship between skeletal muscle index and the difference between eGFRCYS and eGFRCRE. RESULTS: Of the 545 included patients (mean age 63 ± 14 years, 300 [55%] females, 440 [80.7%] non-Hispanic white), 320 (58.7%) met the criteria for CT-defined sarcopenia, and 136 (25%) had high adiposity. A total of 259 patients (48%) had >30% eGFR discordance, and 122 (22.4%) had >50% eGFR discordance. After adjustment for potential confounders, CT-defined sarcopenia and high adiposity were both associated with >30% eGFR discordance (adjusted odds ratio [aOR] 1.90, 95% confidence interval [CI] 1.12-3.24; aOR 2.01, 95% CI 1.15-3.52, respectively) and >50% eGFR discordance (aOR 2.34, 95% CI 1.21-4.51; aOR 2.23, 95% CI 1.19-4.17, respectively). A spline model demonstrated that as skeletal muscle index decreases, the predicted difference between eGFRCRE and eGFRCYS widens considerably. CONCLUSIONS: CT-defined sarcopenia and high adiposity are both independently associated with large eGFR discordance. Incorporating valuable information from body composition analysis derived from CT scans performed as a part of routine cancer care can impact the interpretation of GFR estimates.

Sialolipoma of a minor salivary gland in a dog.

A 10-year-old golden retriever dog was presented for evaluation of progressive panting, inspiratory stridor, and gagging. Oropharyngeal examination revealed a soft, nonulcerated, pedunculated mass arising from the right tonsillar fossa. The mass was completely excised and histopathology was consistent with a sialolipoma. No regrowth of the mass was evident 6 months after surgery.

Lipome salivaire d'une glande salivaire mineure chez un chien. Un chien Golden retriever âgé de 10 ans a été présenté pour l'évaluation d'un halètement progressif, d'un stridor respiratoire et des haut-le-cœur. Un examen oropharyngien a révélé une petite masse molle non ulcérée et pédonculée se dressant sur la fosse de l'amygdale droite. La masse a été entièrement excisée et l'histopathologie était conforme à un lipome salivaire. Six mois après la chirurgie, aucune repousse de la masse n'a été constatée.(Traduit par Isabelle Vallières).

The shaping of moral injury among UK military veterans of the wars in Afghanistan and Iraq.

OBJECTIVE: Research on 'moral injury'-the psychological wound experienced by military personnel and other 'functionaries' whose moral values are violated-has proliferated in recent years. Many psychological researchers, including those in the UK, have subscribed to an increasingly individualised operationalisation of moral injury, with medicalised criteria that closely mirrors PTSD. This trend carries assumptions that have not been comprehensively verified by empirical research. This study aims to explore UK military veterans' experiences of, and challenges to, their moral values in relation to their deployment experiences, without prematurely foreclosing exploration of wider systemic influences. METHOD: Twelve UK military veterans who served in Afghanistan and/or Iraq were interviewed, and the data were analysed thematically and reflexively. RESULTS: Three inter-related themes were generated: (1) 'you've been undermined', (2) 'how am I involved in this?' and (3) 'civilianised'. CONCLUSIONS: The analysis suggests that several assumptions privileged in moral injury research may be empirically contradicted, at least in relation to the experiences of UK military veterans. These assumptions include that moral injury is exclusively driven by individual, episodic acts of commission and omission, invariably leads to guilt and necessarily bifurcates into variants of either perpetration or betrayal. Instead, participants understood the moral violations they experienced as socially contingent. Rather than 'treating' moral injury as a disorder of thinking and feeling located within an individual, the socially contextualised understanding of moral injury indicated by this study's findings may prompt the development of psychological and social interventions that understand moral injury as the fallout of what occurs between people and within systems.

A narrative exploration of identity in adults with de novo scoliosis.

Adult de novo scoliosis is a chronic health condition characterised by a curvature in the ageing spine. It can cause debilitating back pain and significant visible differences. Yet there has been very limited research on the psychological effects of this condition, particularly around identity. Therefore, we undertook semi-structured interviews to explore the ways in which individuals with scoliosis understood their identity. Findings from narrative analysis highlight the ways in which individuals negotiate their identity in relation to their social roles, their ability to control their condition and things around them, the extent to which their condition is visible and the extent to which they experienced physical pain from their condition. This article concludes by highlighting the relationship between identity and scoliosis and offers practical implications and suggestions for future research.

Characterization of PLA Sheets Prepared by Stretching under Different Conditions: Influence of Reprocessing and Establishing Optimal Conditions.

Polylactide (PLA) is one of the most commonly used biomaterials nowadays, with many recognized benefits, particularly in the packaging and single-use products industries. However, little research has been conducted on its stretching behavior. This work investigates the optimal conditions of biaxial stretching of injection-molded PLA samples produced under different processing conditions (pressure, drying, and pre-processing by extrusion, to simulate a recycling step). The injection-molded samples were characterized to determine their mechanical, thermal and thermo-mechanical behavior, water absorption, thermal behavior, and crystallization kinetics. The extruded samples showed reduced thermal stability, lower viscosity, decreased mechanical properties, and higher crystallization rates due to thermal degradation. However, the stretched samples provided similar properties regardless of the materials pre-processing. Regarding the assessment of the biaxial stretching process, processing at lower temperatures provides the films with a higher yield and breaking strength, while the time and strain rates have little influence on such properties. It was then determined that 82 °C is the optimal temperature for stretching the PLA samples. An increase in the stretch ratio provided a higher elastic modulus and higher values of opacity due to an increased crystallinity induced by stress during the process. Films as thin as 50 µm can be obtained by biaxially stretching injection-molded preforms, producing a deformation over 150% and acquiring good mechanical properties: about 90 MPa for the yield and a breaking strength and elastic modulus of 4000 MPa.