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Performance of spleen stiffness measurement to rule out high-risk varices in patients with porto-sinusoidal vascular disorder.
No full textBACKGROUND AIMS
Baveno VII consensus suggests that screening endoscopy can be spared in patients with compensated cirrhosis when spleen stiffness measurement (SSM) by vibration-controlled transient elastography (VCTE) is ≤40 kPa as they have a low probability of high-risk varices (HRV). Conversely, screening endoscopy is required in all patients with porto-sinusoidal vascular disorder (PSVD). This study aimed to evaluate the performance of SSM-VCTE to rule out HRV in patients with PSVD and signs of portal hypertension.
APPROACH RESULTS
We retrospectively included patients with PSVD, ≥1 sign of portal hypertension, without history of variceal bleeding, who underwent a SSM-VCTE within 2 years before or after an upper endoscopy in 21 VALDIG centers, divided into a derivation and a validation cohort. 154 patients were included in the derivation cohort; 43% had HRV. By multivariable logistic regression analysis, SSM-VCTE >40 kPa and serum bilirubin ≥1 mg/dL were associated with HRV. SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL had a sensitivity of 96% to rule out HRV, and could spare 38% of screening endoscopies, with 4% of HRV missed, and a 95% negative predictive value (NPV). In the validation cohort, including 155 patients, SSM combined with bilirubin could spare 21% of screening endoscopies, with 4% of HRV missed and a 94% NPV.
CONCLUSION
This study gathering a total of 309 PSVD patients showed that SSM-VCTE ≤40 kPa combined with bilirubin <1 mg/dL identifies patients with PSVD and portal hypertension with a probability of HRV <5%, in whom screening endoscopy can be spared
Spatial heterogeneity of immune regulators drives dynamic changes of local immune responses, affecting disease outcomes in pancreatic cancer.
No full textPURPOSE
Pancreatic ductal adenocarcinoma (PDAC) is considered a low immunogenic tumor with "cold" tumor microenvironment (TME) and is mostly unresponsive to immune checkpoint blockade therapies. Here we decipher the impact of intratumoral heterogeneity of immune determinants on antitumor response.
EXPERIMENTAL DESIGN
We performed spatial proteomic and transcriptomic analyses and multiplexed immunofluorescence on multiple tumor regions, including tumor center (TC) and invasive front (IF), from 220 PDAC-patients, classified according to their transcriptomic immune signaling into high-immunogenic (HI-PDACs, n=54) and low-immunogenic tumors (LI-PDACs, n=166). Spatial compartments (tumor: Pancytokeratin+/CD45- and leukocytes: Pancytokeratin-/CD45+) were defined by fluorescent imaging.
RESULTS
HI-PDACs exhibited higher densities of cytotoxic T lymphocytes with upregulation of T-cell priming-associated immune determinants, including CD40, ITGAM, GITR, CXCL10, GZMB, IFNG and HLA-DR, which was significantly more prominent at the IF than the TC. In contrast, LI-PDACs exhibited immune evasive TMEs with downregulation of immune determinants and a negative gradient from TC to IF. Patients with HI-PDACs had significantly better outcomes; however, they showed more frequently exhausted immune phenotypes.
CONCLUSIONS
Our results indicate strategic differences in the regulation of immune determinants, which lead to different levels of effectiveness of antitumor responses between high- and low-immunogenic tumors and dynamic spatial changes, which affect the evolution of immune evasion and patient outcomes. This supports coevolution of tumor and immune cells and may help define therapeutic vulnerabilities to improve antitumor immunity and harness the responsiveness to immune checkpoint inhibitors in PDAC patients
Velocity and pattern of growth of intracranial meningiomas.
No full textOBJECTIVE
The authors' aim was to assess the velocity and pattern of growth of meningiomas and to correlate the kinetics of tumor growth with their previously reported two-item radiological risk stratification and CNS WHO grade (5th edition, 2021).
METHODS
The authors performed a serial volumetric analysis of meningiomas diagnosed radiologically at their institution between 2003 and 2015. The primary endpoint was velocity of diametric expansion (VDE), which represents the slope of the linear regression of the mean tumor diameter against time. For the secondary analysis, they categorized the growth patterns as linear or exponential by fitting time-volume curves to a linear and exponential function. Three radiological risk categories based on T2-weighted iso/hyperintensity and absence of calcifications were compared: low risk (T2-weighted hypointense), intermediate-risk (T2-weighted iso/hyperintense with calcifications), and high-risk (T2-weighted iso/hyperintense without calcifications) tumors.
RESULTS
For the entire cohort of 240 meningiomas, the median (IQR) VDE was 0.33 (0.00-0.71) mm/year. Distribution of VDE differed significantly among radiological risk categories (0.49 vs 0.35 vs 0.05 mm/year, p < 0.001). High-risk and intermediate-risk tumors more frequently tended to grow exponentially compared to low-risk tumors (43.8% vs 37.0% vs 8.3%, p = 0.067). The authors found no correlation of growth velocity with CNS WHO grade in their cohort (1.30 mm/year for CNS WHO grade 1 vs 4.01 mm/year for CNS WHO grade 2, p = 0.185).
CONCLUSIONS
A radiological risk assessment using two parameters-T2-weighted signal iso/hyperintensity and absence of calcifications-allows estimation of growth velocity and characteristics of untreated intracranial meningiomas. Only high-risk tumors exhibit the potential for rapid growth. However, rapid tumor growth does not indicate a higher CNS WHO grade per se
Magnetic resonance imaging to monitor disease activity in giant cell arteritis treated with ultra-short glucocorticoids and tocilizumab.
No full textOBJECTIVES
MRI is well established for diagnosing GCA. Its role in monitoring disease activity has yet to be determined. We investigated vascular and musculoskeletal inflammation using MRI in the patients of the GUSTO trial to assess the utility of MRI in monitoring disease activity.
METHODS
Eighteen patients with newly diagnosed GCA received 500 mg methylprednisolone intravenously for 3 consecutive days followed by tocilizumab monotherapy from day 3 until week 52. Cranial, thoracic and abdominal MRI exams were performed at baseline (active, new-onset disease), and at weeks 24, 52 (remission on-treatment), and 104 (remission off-treatment). MRI findings typical for PMR as well as extent and severity of vasculitic disease were rated.
RESULTS
In total, 673 vascular segments and 943 musculoskeletal regions in 55 thoracic/abdominal MRI and 490 vascular segments in 49 cranial MRI scans of 18 patients were analysed. Vasculitic vessels were still detectable in one in four cranial segments at week 24. At weeks 52 and 104, no cranial vascular segment showed a vasculitic manifestation. Large vessels, except for the ascending aorta, and PMR displayed little or no decrease in inflammatory findings over time.
CONCLUSION
Vasculitic manifestations in the cranial vessels normalised after 52 weeks of treatment, whereas large vessel and PMR findings persisted despite lasting full remission. The dynamics of cranial vessel signals suggest that MRI of these arteries might qualify as a potential diagnostic tool for monitoring disease activity and for detecting relapse after 52 weeks of treatment
The effects of combustible cigarettes and electronic nicotine delivery systems on immune cell-driven inflammation and mucosal healing in ulcerative colitis.
No full textINTRODUCTION
The effects of combustible cigarettes (CCs) and electronic nicotine delivery systems (ENDS) on immune cell-driven colon inflammation and intestinal healing of patients with ulcerative colitis (UC) are still unknown and, therefore, were examined in this study.
METHODS
Intracellular staining and flow cytometry analysis of immune cells isolated from UC patients who used ENDS (UCENDS), CCs (UCCC) and who were non-smokers (UCAIR) were performed to elucidate cellular mechanisms which were responsible for CCs and ENDS-dependent modulation of immune response during UC progression. Additionally, dextran sulfate sodium (DSS)-colitis was induced in ENDS/CC/air-exposed mice (DSSENDS/ DSSCC/DSSAIR groups) to support clinical findings.
RESULTS
Significantly increased number of immunosuppressive, IL-10, TGF-β and IL-35-producing, FoxP3-expressing CD3+CD4+T regulatory cells (Tregs) was observed in the blood of UCENDS patients while reduced presence of inflammatory, TNF-α and IFN-γ-producing, Tbx21-expressing CD3+CD4+ Th1, IL-4-producing Gata3-expresing Th2 and IL-17, IL-22-producing, RORγT, IL-23R-expressing Th17 cells were noticed in the blood of UCCC patients. Exposure to either CCs or ENDS was associated with enhanced mucosal healing, ameliorated spontaneous recovery and improved survival of DSS-treated mice. An expansion of immunosuppressive cells (IL-10-producing tolerogenic CD11c+ dendritic cells, alternatively activated CD206, Arginase 1-expressing, IL-10-producing F4/80+macrophages, IL-10-producing FoxP3-expressing Tregs) was noticed in the colons of DSSENDS-treated mice, while reduced number of inflammatory, IL-17- and IL-4-producing T lymphocytes was observed in the colons of DSSCC-compared to DSSAIR-treated mice.
CONCLUSIONS
Despite different mechanisms of action, both ENDS and CCs attenuated on-going colon inflammation, enhanced healing and ameliorated recovery of injured intestines of DSS-treated mice and UC patients.
IMPLICATIONS
This is the first study that compared the effects of CCs and ENDS on immune cells of patients suffering from ulcerative colitis, providing new information about molecular and cellular mechanisms which were responsible for ENDS and CCs-dependent modulation of immune cell-driven colon injury and inflammation. Obtained results showed that both ENDS and CCs had capacity to attenuate detrimental immune response, enhanced healing and ameliorated recovery of injured intestines
Effectiveness of music therapy, aromatherapy, and massage therapy on people in palliative care with end-of-life needs: A systematic review.
Full text linkBACKGROUND
Music therapy, aromatherapy and massage therapy are widely used in palliative care in patients near end-of-life with the aim to reduce symptom burden and improve quality of life (QoL). Recent research shows an increase in popularity and use of complementary and integrative medicine however a more thorough evidence base about their usefulness is required.
OBJECTIVES
The aim of this study was to evaluate the available evidence on the use of music therapy, aromatherapy and massage therapy in palliative and hospice care and summarize findings.
METHODS
A defined search strategy was used in reviewing literature from two major databases, MEDLINE and Embase for the period between 2010 and 2022. Studies were selected for further evaluation based on intervention type and relevancy. After evaluation using quality assessment tools, findings were summarised, and potential benefits were identified.
RESULTS
Out of 1261 studies initially identified, 26 were selected for further evaluation. 16 evaluated music therapy, 4 aromatherapy and massage therapy. The most represented outcomes were pain, anxiety, well-being and QoL. Many studies demonstrated a short-term benefit in symptom improvement. Qualitative studies showed that these complementary methods are highly valued.
CONCLUSION
Main results found that music and massage therapy had the most potential benefits on a range of outcome parameters, including pain and QoL. Future studies may consider using more qualitative and/or mixed methods to provide a more comprehensive evaluation of treatment
East Anglian English in the English Dialects App: Regional variation in East Anglian English based on evidence from a smartphone-based survey
No full textEast Anglian English was the first British variety of English to be subject to dialectological scrutiny using sociolinguistic techniques (Trudgill, 1974, and his subsequent work) and since then has been subject to only sporadic investigation (e.g. Britain, 1991, 2014a, 2014b, 2015; Kingston, 2000; Straw, 2006; Amos, 2011; Potter, 2012, 2018; Butcher, 2015). Recent research has suggested that, in those few locations that have been investigated, East Anglian English is gradually losing some of its traditional dialect features, in favour of forms from the South East more generally. Kingston (2000), Britain (2014a) and Potter (2018) all found, for example, a rather steep decline in the use of East Anglia's traditional third-person present-tense zero. Furthermore, we are aware of the arrival into East Anglia of linguistic innovations from the South East of England, such as TH fronting (Trudgill, 1988; Britain, 2005; Potter, 2012) and /l/ vocalisation (Johnson & Britain, 2007; Potter, 2014), but we only know about their success in a few parts of the region – Norwich, East Suffolk and the Fens. Since Trudgill's investigations across East Anglia in the 1970s, however (e.g. Trudgill & Foxcroft, 1978), and despite a few multilocality studies (Britain, 1991, 2014a; Potter, 2018) no research has been able to provide a picture of the state of the traditional dialect across the whole region. We have therefore only a patchy understanding of the extent to which traditional dialect obsolescence, dialect levelling and innovation diffusion have impacted the dialect landscape of this region as a whole
Narratives about distributed health literacy during the COVID-19 pandemic.
Full text linkThe promotion of health literacy was a key public health strategy during the COVID-19 pandemic. However, the role of social networks and relationships for support with health literacy-related tasks in the context of the COVID-19 pandemic is scarcely understood. Moving beyond traditional notions of health literacy, which focus on individual skills and knowledge, this study uses the concept of distributed health literacy to explore how individuals make meaning of and respond to health literacy and make their literacy skills available to others through their relational and socially situated and lived experiences of the COVID-19 pandemic. Drawing on 89 semi-structured interviews conducted in three European countries (Italy, Portugal, and Switzerland) between October and December 2021, we found narratives of stabilization, hybridization, and disruption that show how health literacy concerning COVID-19 is a complex social construct intertwined with emotional, cognitive, and behavioral responses distributed among individuals, communities, and institutions within socioeconomic and political contexts that affect their existence. This paper opens new empirical directions to understand the critical engagement of individuals and communities toward health information aimed at making sense of a complex and prolonged situation of uncertainty in a pandemic
Challenging Patriarchy, Class, and Imperialism. The Philippine Women’s Movements (1970-1992)
No full textBuilding on the work of feminist and decolonial scholars this article traces transnational feminisms
in the Philippine nationalist democratic women’s movements between 1970 and 1992. Considering the activists’ visions of the future as relevant political acts, I explore how feminism was articulated amidst self-determination and class struggles and how this was tied to transnational entanglements. The article rejects a monolithic Western view of feminism and aims to provide a differentiated historical perspective on transnational feminisms. Based on non-state sources and oral history interviews, I argue for two theses: first, Filipina militant women reappropriated the meaning of feminism into their contexts by connecting women, class, and national struggle. Second, by creating shared future visions of liberation, the Philippine women’s movements built transnational networks of solidarity that shaped their activism financially, politically, and ideologically. Through international exchange, they increasingly located their struggle in a global «Third-World» context. Overall, the visions of the Philippine women’s movements were not only ideas – of peace, women’s emancipation, and national sovereignty – but also practices: of resistance, networking, and solidarity. In sum, the article contributes to a relational and historically informed understanding of feminism and women’s movements and illustrates how «Third World women» have been an important source of feminist thought and action
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