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Background: Immune checkpoint inhibitors (anti-PD1 or anti-CTLA-4) are increasingly used in various cancers. Immune checkpoint inhibitors (ICI)-related renal disorders are poorly described (9 cases) and were only related to Ipilimumab. Methods: Retrospective collection of clinical charts of all the patients admitted for renal disorders following ICI in the University Hospital of Toulouse (France). Results: We report on adverse renal events that occurred in three patients treated with anti-PD1 (nivolumab or pembrolizumab) or anti-CTLA-4 (ipilimumab). Acute kidney injury occurred at 4–12 weeks after initiation of treatment, and harbored features of tubulo-interstitial nephritis (interstitial polymorphic inflammatory infiltrate with predominant CD3+ CD4+ T cells, associated with granuloma in one). Following withdrawal of ICI and steroid intake, estimated glomerular-filtration rate had improved in all patients. Conclusions: These data suggest that all ICI can lead to acute interstitial nephritis, possibly related to the presence of autoreactive clonal T cells. We recommend that patients receiving ICI should undergo renal monitoring every 2 weeks for 3–6 months.

Science and technology studies (STS) and the emerging field of data science share surprising elective affinities. At the growing intersections of these fields, there will be many opportunities and not a few thorny difficulties for STS scholars. First, I discuss how both fields frame the rollout of data science as a simultaneously social and technical endeavor, even if in distinct ways and for diverging purposes. Second, I discuss the logic of domains in contemporary computer, information, and data science circles. While STS is often agnostic about the borders between the sciences or with industry and state—occasionally taking those boundaries as an object of study—data science takes those boundaries as its target to overcome. These two elective affinities present analytic and practical challenges for STS but also opportunities for engagement. Overall, in addition to these typifications, I urge STS scholars to strategically position themselves to investigate and contribute to the breadth of transformations that seek to touch virtually every science and newly bind spheres of academy, industry, and state.

Background Systemic sclerosis (SSc) is associated with a variability of mortality rates in the literature. Objective To determine the mortality and its predictors in a long-term follow-up of a bi-centric cohort of SSc patients. Methods A retrospective observational study by systematically analyzing the medical records of patients diagnosed with SSc in Toulouse University Hospital and Ducuing Hospital. Standardized Mortality Ratio (SMR), mortality at 1, 3, 5, 10, and 15 years of disease and causes of death were described. Predictors of mortality using Cox regression were assessed. Results Three hundred seventy-five patients were included: 63 with diffuse cutaneous SSc, 279 with limited cutaneous SSc, and 33 with sine scleroderma. The SMR ratio was 1.88 (95% CI 1.46–1.97). The overall survival rates were 97.6% at 1 year, 93.4% at 3 years, 87.1% at 5 years, 77.9% at 10 years, and 61.3% at 15 years. Sixty-nine deaths were recorded. 46.4% were SSc related deaths secondary to interstitial lung disease (ILD) (34.4%), pulmonary hypertension (31.2%), and digestive tract involvement (18.8%). 53.6% were non-related to SSc: cardiovascular disorders (37.8%) and various infections (35.1%) largely distanced those from cancer (13.5%). Four significant independent predictive factors were identified: carbon monoxide diffusing capacity (DLCO) < 70% (HR=3.01; p =0.0053), C-reactive protein (CRP) >5 mg/l (HR=2.13; p =0.0174), cardiac involvement (HR=2.86; p =0.0012), and the fact of being male (HR=3.25; p =0.0004). Conclusion Long-term data confirmed high mortality of SSc. Male sex, DLCO <70%, cardiac involvement, and CRP> 5mg/l were identified as independent predictors of mortality. Highlights • Male sex, cardiac involvement, DLCO <70%, and CRP > 5 mg/l are strong predictors of mortality in systemic sclerosis. • This study shows the survival of subtypes and in particular sine scleroderma. • Sine scleroderma subtype has better survival than diffuse or limited cutaneous subtypes. • Non-systemic sclerosis-related deaths are more frequent than systemic sclerosis-related deaths. • Cardiovascular events non-systemic sclerosis-related are the main deaths.

C3 glomerulopathy (C3G) results from acquired or genetic abnormalities in the complement alternative pathway (AP). C3G with monoclonal immunoglobulin (MIg-C3G) was recently included in the spectrum of \"monoclonal gammopathy of renal significance.\" However, mechanisms of complement dysregulation in MIg-C3G are not described and the pathogenic effect of the monoclonal immunoglobulin is not understood. The purpose of this study was to investigate the mechanisms of complement dysregulation in a cohort of 41 patients with MIg-C3G. Low C3 level and elevated sC5b-9, both biomarkers of C3 and C5 convertase activation, were present in 44 and 78% of patients, respectively. Rare pathogenic variants were identified in 2/28 (7%) tested patients suggesting that the disease is acquired in a large majority of patients. Anti-complement auto-antibodies were found in 20/41 (49%) patients, including anti-FH (17%), anti-CR1 (27%), anti-FI (5%) auto-antibodies, and C3 Nephritic Factor (7%) and were polyclonal in 77% of patients. Using cofactor assay, the regulation of the AP was altered in presence of purified IgG from 3/9 and 4/7 patients with anti-FH or anti-CR1 antibodies respectively. By using fluid and solid phase AP activation, we showed that total purified IgG of 22/34 (65%) MIg-C3G patients were able to enhance C3 convertase activity. In five documented cases, we showed that the C3 convertase enhancement was mostly due to the monoclonal immunoglobulin, thus paving the way for a new mechanism of complement dysregulation in C3G. All together the results highlight the contribution of both polyclonal and monoclonal Ig in MIg-C3G. They provide direct insights to treatment approaches and opened up a potential way to a personalized therapeutic strategy based on chemotherapy adapted to the B cell clone or immunosuppressive therapy.

Data science is characterized by engaging heterogeneous data to tackle real world questions and problems. But data science has no data of its own and must seek it within real world domains. We call this search for data “prospecting” and argue that the dynamics of prospecting are pervasive in, even characteristic of, data science. Prospecting aims to render the data, knowledge, expertise, and practices of worldly domains available and tractable to data science method and epistemology. Prospecting precedes data synthesis, analysis, or visualization, and is constituted by the upstream work of discovering disordered or inaccessible data resources, thereafter to be ordered and rendered available for computation. Through this work, data science positions itself in the middle of all things—capable of engaging this, that, or any domain—and thus prospecting is a key driver of data science’s ongoing formation as a universal(izing) science.

ObjectivesSome patients with SLE or Gougerot-Sjögren’s disease (GSD) receive long-term treatment with hydroxychloroquine (HCQ), sometimes combined with immunosuppressive therapy (IS). This study sought to assess whether long-term HCQ therapy that had been initiated long before the COVID-19 pandemic had a protective or adverse effect on COVID-19 risk, severity of infection or immunity protection.MethodsThis prospective multicentre study included 547 patients with SLE, GSD, autoimmune hepatitis, primary biliary cholangitis or cured viral hepatitis C divided into four groups according to HCQ (+/−) and IS (+/−) intake prior to the pandemic: HCQ+IS+ (n=112), HCQ+IS− (n=121), HCQ−IS+ (n=115) and HCQ−IS− (n=199). When COVID-19 vaccination was possible, patients were vaccinated as recommended. Vaccination efficacy was prospectively assessed on the basis of the postvaccination antibody titre.ResultsCompared with HCQ+IS+ patients, HCQ−IS+ patients had a decreased risk of COVID-19 infection (p<0.001). Compared with HCQ+IS+ patients, HCQ−IS− patients had a decreased risk of contracting COVID-19 (p<0.001). Patients in the HCQ−IS+ or HCQ−IS− group had a lower risk of symptomatic or severe infection than HCQ+IS+ patients did (p=0.001 and p<0.001, respectively). Only patients who had two or more exposures (to vaccine and/or infection) had an increased likelihood of COVID-19 immunity after the last dose (p<0.001).ConclusionsHCQ treatment that was initiated before the pandemic did not protect against COVID-19 infection. Moreover, non-exposure to HCQ treatment (combined or not with IS) was associated with decreased risk of COVID-19 infection and of developing a symptomatic or severe infection. HCQ and IS do not influence the vaccine response. Only two or more doses of vaccine result in a good vaccine response.Trial registration numberNCT04481633.

ObjectiveThe association of immune-mediated thrombotic thrombocytopenic purpura (iTTP) and SLE was previously described, but patients with iTTP with coexistent SLE remain poorly characterised.MethodsWe compared the clinical presentation and the outcome of patients with iTTP with coexistent SLE (SLE-iTTP) to an age-sex matched cohort of patients with idiopathic iTTP without SLE.ResultsDuring the study period, 1409 patients with iTTP were recruited in our registry. Of these, 79 (6%) had a prior or concurrent diagnosis of SLE at the time of iTTP diagnosis, and 437 (31%) had detectable ANAs without other clinical features of SLE. When compared with idiopathic iTTP, patients with SLE-iTTP had more severe renal involvement, and cardiac involvement was more prevalent, whereas central nervous system involvement was less common. Patients with SLE-iTTP received more immunosuppressive agents. There was no difference in response categories during the acute phase. During follow-up, SLE-iTTP had superior ADAMTS13 relapse-free survival than idiopathic iTTP. Among patients with ANAs without other clinical features of SLE, 33 (8%) were diagnosed with SLE 27 months (IQR: 7–65 months) following iTTP diagnosis; 32 additional patients (7%) developed another systemic autoimmune disease. No patient from the idiopathic iTTP group developed clinical SLE during follow-up.ConclusionPatients with iTTP are prone to develop autoimmune features, and patients with SLE-iTTP have distinct clinical features and outcome. Relapse-free survival seems better in patients with SLE-iTTP, underscoring the need for tailored management strategies in this population, including a specific follow-up to assess early features suggestive of SLE.Trial registration numberNCT00426686.

Aims Advances have been made over the last decade in the management of cardiac amyloidosis (CA), but a delayed diagnosis is still common. The aim of this study was to describe the journey to CA diagnosis from initial clinical and to analyse time to diagnosis. Methods and results Between January 2001 and May 2019, 270 consecutive patients with CA diagnosed at Toulouse University Hospital were retrospectively included in this cross‐sectional study: 111 (41%) light chain amyloidosis, 122 (45%) wild‐type transthyretin amyloidosis, and 37 (14%) hereditary transthyretin amyloidosis. CA onset occurred mostly with dyspnoea (50%) or systematic follow‐up (10%). The cardiologist was the first line specialist in 68% of patients, followed by the nephrologist (9%) and neurologist (8%). Patients encountered a median (minimum–maximum) number of two (1–7) physician specialists and performed a median (minimum–maximum) number of three (1–8) tests before diagnosis. Median delay between symptom onset and CA diagnosis was 8 [IQR 5–14], 10 [IQR 3–34], and 18 [IQR 4–49] months, respectively, in light chain amyloidosis, wild‐type transthyretin amyloidosis, and hereditary transthyretin amyloidosis subgroups (P = .060). Having performed electromyography or spirometry was associated with a longer delay in diagnosis in the overall population: odds ratio = 1.13; 95% confidence interval 1.02 to 1.24; and odds ratio = 1.13; 1.03 to 1.24, respectively, probably due to non‐specific initial symptoms. Conclusions CA is a protean disease with various first line specialists causing a diagnostic wandering despite increasing medical community awareness. It requires a multidisciplinary specialist care networks to educate and manage symptoms and therapies.

The logic of domains has become a key organizing principle for contemporary computing projects and in broader science policy. The logic parses collectives of expertise into ‘domains’ that are to be studied or engaged in order to inform computational advancements and/or interventions on the domains themselves. The concept of a domain is set against a proposition that there is a more general, domain independent or agnostic technique that can serve to intermediate the domains. This article contrasts instances of this discourse, organizing and techne, drawing from cases in artificial intelligence, software engineering, and science policy to illustrate three ongoing figurations of the logic as i) experimental research, ii) formalization in method and software tools, and iii) a de facto organizing principle for science policy and technology development.

A defining concern for information systems (IS) is how to theorize its primary object of study, the digital artifact. Historically, approaches in IS have oscillated between technological determinist and social determinist ones. Bruno Latour’s works contributed to recalibrating a more symmetrical treatment of the two, and he played a distinctive role in stimulating the evolution of empirically committed, process-oriented theorizing in the IS field. We commemorate Latour’s work by revisiting his early influence on IS research and discuss some of the direct and indirect influences on contemporary IS, such as infrastructure studies and sociomateriality. With the interest in agentic technologies via AI, Latour’s perspectives on technological agency are more relevant than ever. In addition, we explore ideas that are relevant to IS but have yet to be taken up, thus representing untapped theoretical and methodological potential for future IS research—for example, approaching data as circulating reference or how his work could contribute to sustainability discussions in IS.