Reconceiving vulnerabilities in relations of care how to account for and deal with carers' vulnerabilities.

While carers' vulnerability has often been neglected in the literature, the recent COVID-19 pandemic brought this issue to the fore. This article explores why it has been so often ignored and how could it be dealt with differently. It does so in the form of a philosophical and conceptual investigation illustrated by various examples and situations, related primarily, but not exclusively, to the COVID period. Criticising a property-based view, and based on examples of carers' vulnerability during the pandemic, our investigation suggests that carers' vulnerability is relationally constructed and played out on multiple interwoven dimensions that may contradict each other. Our examples also suggest that the relational construction of vulnerabilities is socially and organisationally mediated, calling for the development of social and organisational forms of mediation that may help carers deal with their vulnerabilities. Second, and rather counterintuitively with regard to the COVID-period, we question the negative valence usually associated with vulnerability and analyse how this affects ways of dealing with carers' vulnerabilities and the co-creation of care. Finally, following Gilson (2014), we propose an ambivalent, relational conception of vulnerability, considered as 'openness to affectation by' and offer some theoretical and practical implications. Theoretically, this conception also allows us to consider such openness as an ability that may nurture carers' 'response-ability'. It also allows us to develop specific relational ethics for and in care relationships. Practically, this re-conceptualisation may help carers better embrace and process their vulnerabilities, including responses to negative affectations following exposure to carees. It may also facilitate their 'reception' of carees, and help co-create and adapt responses to carees' calls, thus avoiding paternalistic responses.

Prevalence of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Spatial Association With Quarries in a Region of Northeastern France: A Capture-Recapture and Geospatial Analysis.

OBJECTIVE: Silica is an environmental substance strongly linked with autoimmunity. The aim of this study was to assess the prevalence of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and renal limited vasculitis, in a northeastern region of France and to evaluate whether there was a geospatial association between the localization of quarries in the region and the prevalence of these AAVs. METHODS: Potential AAV patients were identified using 3 sources: hospital records, immunology laboratories, and the French National Health Insurance System. Patients who resided in the Alsace region of France as of January 1, 2016 and who fulfilled the American College of Rheumatology criteria for GPA or the 2012 Chapel Hill Consensus Conference definitions for GPA or MPA were included. Incomplete case ascertainment was corrected using a capture-recapture analysis. The spatial association between the number of cases and the presence of quarries in each administrative entity was assessed using regression analyses weighted for geographic region. RESULTS: Among 910 potential AAV patients, we identified 185 patients fulfilling inclusion criteria: 120 patients with GPA, 35 patients with MPA, and 30 patients with renal limited vasculitis. The number of cases missed by any source as estimated by capture-recapture analysis was 6.4 (95% confidence interval [95% CI] 3.6-11.5). Accordingly, the estimated prevalence in Alsace in 2016 was 65.5 GPA cases per million inhabitants (95% CI 47.3-93.0), 19.1 MPA cases per million inhabitants (95% CI 11.3-34.3), and 16.8 renal limited vasculitis cases per million inhabitants (95% CI 8.7-35.2). The risk of AAV was significantly increased in communities with quarries (odds ratio 2.51 [95% CI 1.66-3.80]), and geographic-weighted regression analyses revealed a significant spatial association between the proximity to quarries and the number of GPA cases (P = 0.039). In analyses stratifying the AAV patients by ANCA serotype, a significant association between the presence of quarries and positivity for both proteinase 3 ANCAs (P = 0.04) and myeloperoxidase ANCAs (P = 0.03) was observed. CONCLUSION: In a region with a high density of quarries, the spatial association between the presence of and proximity to quarries and the prevalence of AAVs supports the idea that silica may have a role as a specific environmental factor in this disease.

Contribution of an Early Internal Medicine Rotation to the Clinical Reasoning Learning for Young Residents.

Clinical reasoning is the cornerstone of medical practice, and achieving this competence depends on a large number of factors. Internal medicine departments provide junior doctors with plentiful and varied patients, offering a comprehensive basis for learning clinical reasoning. In order to evaluate the usefulness of an early rotation at internal medicine departments, we compared, via script concordance tests, the evolution of residents' clinical reasoning after an initial internal medicine rotation compared to rotations through other medical specialties. Twenty-two residents were tested after six months of their internal medicine rotation and compared to twenty-five residents that had the first rotation in another specialty (control). We showed a significant difference in the improvement of the script concordance tests scores (p=0.015) between the beginning and the end of their first rotation between the internal medicine and the control groups, and this implies the lower improvement of clinical reasoning skills and spontaneous learning slope of the junior doctors in other departments.

History and Outcome of Febrile Neutropenia Outside the Oncology Setting: A Retrospective Study of 76 Cases Related to Non-Chemotherapy Drugs.

BACKGROUND: Despite major advances in its prevention and treatment, febrile neutropenia remains a most concerning complication of cancer chemotherapy. Outside the oncology setting, however, only few data are currently available on febrile neutropenia related to non-chemotherapy drugs. We report here data on 76 patients with febrile neutropenia related to non-chemotherapy drugs, followed up in a referral center within a university hospital. PATIENTS AND METHODS: Data from 76 patients with idiosyncratic drug-induced febrile neutropenia were retrospectively reviewed. All cases were extracted from a cohort study on agranulocytosis conducted at the Strasbourg University Hospital (Strasbourg, France). RESULTS: Mean patient age was 52.2 years old (range: 18-93) and gender ratio (F/M) 1.6, with several comorbidities present in 86.8% of patients. The most common causative drugs were: antibiotics (37.4%), antithyroid drugs (17.2%), neuroleptic and anti-epileptic agents (13.1%), non-steroidal anti-inflammatory agents and analgesics (8%), and platelet aggregation inhibitors (8%). Main clinical presentations upon hospitalization included isolated fever (30%), sore throat, acute tonsillitis and sinusitis (18.4%), documented pneumonia (18.4%), septicemia (14.5%), and septic shock (6.6%). Mean neutrophil count at nadir was 0.13 × 10(9)/L (range: 0-0.48). While in hospital, 22 patients (28.9%) worsened clinically and required intensive care unit placement. All patients were promptly treated with broad-spectrum antibiotics, and 45 (59.2%) with hematopoietic growth factors. Mean duration of hematological recovery (neutrophil count ≥1.5 × 10(9)/L) was 7.5 days (range: 2-21), which was reduced to 0.7 days (range: 2-16) (p = 0.089) with hematopoietic growth factors. Outcome was favorable in 89.5% of patients, whereas eight died. CONCLUSIONS: Like in oncology and myelosuppressive chemotherapy settings, idiosyncratic febrile neutropenia is typically serious, about 40% of patients exhibiting severe pneumonia, septicemia, and septic shock, with a mortality rate of 10%. Like in febrile, chemotherapy-related neutropenia, modern and timely management (immediate broad spectrum antibiotherapy, hematopoietic growth factors) may reduce infection-related mortality. All practitioners should be aware of this potential side-effect that may even occur in the event of "daily medication" exposure.

Idiosyncratic drug-induced neutropenia & agranulocytosis.

BACKGROUD: Few data is currently available on neutropenia and agranulocytosis related to drug intake. We report here data on 203 patients with established idiosyncratic drug-induced agranulocytosis, followed up in a referral centre within a university hospital. PATIENTS AND METHODS: Data from 203 patients with idiosyncratic drug-induced agranulocytosis were retrospectively reviewed. All cases were extracted from a cohort study on agranulocytosis in the Strasbourg University Hospital (Strasbourg, France) RESULTS: : The mean age was 61.6 years old (range: 18-95), the gender ratio (F/M) was 1.3. Several comorbidities were present in 63.5%. The most frequent causative drugs were: antibiotics (49.3%), especially ß-lactams and cotrimoxazole; antithyroid drugs (16.7%); neuroleptic and anti-epileptic agents (11.8%); antiviral agents (7.9%); and platelet aggregation inhibitors as ticlopidine and acid acetylsalicylic (6.9%). The main primary clinical manifestations during hospitalization included: isolated fever (26.3%); septicaemia (13.9%); documented pneumonia (13.4%); sore throat and acute tonsillitis (9.3%); and septic shock (6.7%). The mean neutrophil count at nadir was 0.148 x 109/L (range: 0-0.48). All febrile patients were treated with broad-spectrum antibiotics and 107 (52.7%) with hematopoietic growth factors. The mean duration of haematological recovery (neutrophil count ≥1.5 x 109/L) was 7.8 (range: 2-20). This mean duration was reduced to 2.1 days (range: 2-16) (p = 0.057) with hematopoietic growth factors. Outcome was favourable in 91.6% of patients; seventeen died. Thirty-seven patients (18.2%) required intensive care. CONCLUSIONS: The present study demonstrated that idiosyncratic drug-induced agranulocytosis is a relative rare events; that antibiotics, antithyroid, neuroleptic and anti-epileptic agents, and platelet aggregation inhibitors are the main incriminated drug classes; that agranulocytosis typically serious, with at least 50% exhibiting severe sepsis and a mortality rate <10%; and that modern management of such disorder may reduce the infection-related mortality.

The Absent Interpreter in Administrative Detention Center Medical Units.

The particular situation of the French administrative detention center (ADC) medical units appears to be an exemplary case to study the difficulties facing medical practice. Indeed, the starting point of our inquiry was an amazing observation that needed to be addressed and understood: why are professional interpreters so seldom requested in ADC medical units, where one would expect that they would be "naturally" present? Aiming to fully explore the meanings of the "absent interpreter", this article takes into account the possible meanings of this situation: the recourse to professional interpreters in France is far from expected given cumulative evidence of its benefits; perceptions of illegal immigrants and medical habitus itself may both hamper the use of a third party; the ADCs are a very stressful place for healthcare professionals, with conflicting missions, political issues enmeshed with medical goals, and heavy affective burden that may lead to self-protection. Silencing voices of suffering others might be seen as the hidden indecent truth of the "absent interpreter". These reflections open a window to a larger issue with regard to the full range of medicine: what are the place, the role and the function of patient's words and narratives in contemporary medicine? The highly invested somatic perspective and its political corollary giving primacy to bare life harbor potential risks of obscuring speeches and undervaluing narratives.

Systemic capillary leak syndrome and autoimmune diseases: A case series.

OBJECTIVES: Systemic capillary leak syndrome (Clarkson's disease) is a rare entity characterized by recurrent and unpredictable attacks of capillary leakage of plasma fluid and proteins throughout the endothelium. Some cases are secondary. We describe the rare association between secondary capillary leak syndrome (SCLS) and autoimmune diseases. METHODS: We conducted a nationwide, retrospective, observational, and collaborative study throughout the hospital units of the Club des Rhumatismes et Inflammations network (CRI) between March and August 2015. Inclusion criteria were patients with (1) capillary leakage episodes characterized by edema and elevated hematocrit, low albumin count without proteinuria, or other cause of protein loss; and (2) definite autoimmune diseases according to international classification criteria. RESULTS: The clinical and biological data of five patients (three women) were reviewed. Median age was 43.2 (17-55) years. Four patients had Sjögren syndrome. One of them also fulfilled the criteria for systemic sclerosis (n = 1). The fifth patient had polymyositis. During the 37.2 months of median follow-up (5.4-201), we recorded a total of 24 attacks, yielding an attack incidence of 91/100 patient-years. Laboratory tests revealed that three patients had anti-SSA/Ro antibodies. Only one patient had a monoclonal blood component (IgGκ). Three patients needed ICU support; one died during a flare. CONCLUSIONS: We reported the first case series of a rare association of SCLS and autoimmune diseases, supporting the idea of some immune mediation in the pathogenesis of the former disease.

Idiosyncratic Drug-Induced Severe Neutropenia and Agranulocytosis in Elderly Patients (≥75 years): A Monocentric Cohort Study of 61 Cases.

BACKGROUND: Little data is currently available in the literature on neutropenia and agranulocytosis in the elderly, and, to our knowledge, idiosyncratic drug-induced agranulocytosis is particularly poorly covered, or not at all. OBJECTIVE: We herein describe the clinical picture and outcome of patients aged ≥75 years with established idiosyncratic drug-induced agranulocytosis. PATIENTS AND METHODS: Data from 61 patients over 75 years old with idiosyncratic drug-induced agranulocytosis were retrospectively reviewed. All cases were extracted from a cohort study on agranulocytosis (n = 203) in the Strasbourg University Hospitals (Strasbourg, France), a referral center. RESULTS: The mean age was 84.9 years (range 75-95), the gender ratio (F/M) was 2.4. Underlying diseases were present in 74 %. The most frequent causative drugs were antibiotics (43.8 %), antithyroid drugs (15.8 %), neuroleptic and anti-epileptic agents (12.3 %), and antiaggregant platelet agents (10.5 %). The primary clinical features during hospitalization included isolated fever (27.6 %), septicemia or septic shock (24.1 %), and pneumonia (20.7 %). The mean neutrophil count at nadir was 0.15 × 109/L (range 0-0.4). All febrile patients were treated with broad-spectrum antibiotics and 36 with hematopoietic growth factors. Outcome was favorable in 85.3 % of patients; nine patients died. Two elderly patients (3.3 %) died of uncontrolled septic shock relating to the depth of the neutropenia. Comparison of mortality between <75- and ≥75-year-old patients revealed a statistical difference: 4.2 % versus 14.8 % (p = 0.023). CONCLUSIONS: Our study demonstrates that 30 % of idiosyncratic drug-induced agranulocytosis concerned elderly patients. Antibiotic, antithyroid, neuroleptic, anti-epileptic, and antiaggregant platelet agents are the primary causative drug classes. Idiosyncratic drug-induced agranulocytosis is typically serious in this frail population of elderly patients, with at least 50 % suffering from severe sepsis and with a mortality rate of approximately 15 %. Modern management of agranulocytosis may reduce the infection-related mortality (3.3 %).

Breast metastasis as the first clinical manifestation of ileal neuroendocrine tumor. A challenging diagnosis with relevant clinical implications.

Ileal neuroendocrine tumors are slow-growing grade 1 or, more rarely, grade 2 neuroendocrine tumors which, however, are frequently metastatic to regional lymph nodes and the liver. A few cases of ileal neuroendocrine tumors that are metastatic to the breast have also been reported in the medical literature. The knowledge of this uncommon clinical presentation is of great importance because it needs to be differentiated from primary breast carcinomas with neuroendocrine features, which represent completely different entities with a different therapeutic approach. The diagnosis of a breast metastasis from an ileal neuroendocrine tumor and its distinction from a well-differentiated primary neuroendocrine tumor of the breast is a challenging task for clinicians and pathologists. This workup is particularly difficult when the breast lesion is the first sign of malignancy. In the present paper, we describe the clinicopathological features of an ileal neuroendocrine tumor first presenting with a breast metastasis in a 50-year-old woman and we discuss the key diagnostic features for the differential diagnosis with primary well-differentiated neuroendocrine tumor of the breast. Moreover, we have reviewed the medical literature to give the reader a comprehensive overview on this topic.

Towards a new procreation ethic: the exemplary instance of cleft lip and palate.

The improvement of ultrasound scan techniques is enabling ever earlier prenatal diagnosis of developmental anomalies. In France, apart from cases where the mother's life is endangered, the detection of "particularly serious" conditions, and conditions that are "incurable at the time of diagnosis" are the only instances in which a therapeutic abortion can be performed, this applying up to the 9th month of pregnancy. Thus numerous conditions, despite the fact that they cause distress or pain or are socially disabling, do not qualify for therapeutic abortion, despite sometimes pressing demands from parents aware of the difficulties in store for their child and themselves, in a society that is not very favourable towards the integration and self-fulfilment of people with a disability. Cleft lip and palate (CLP), although it can be completely treated, is one of the conditions that considerably complicates the lives of child and parents. Nevertheless, the recent scope for making very early diagnosis of CLP, before the deadline for legal voluntary abortion, has not led to any wave of abortions. CLP in France has the benefit of a exceptional care plan, targeting both the health and the integration of the individuals affected. This article sets out, via the emblematic instance of CLP, to show how present fears of an emerging "domestic" or liberal eugenic trend could become redundant if disability is addressed politically and medically, so that individuals with a disability have the same social rights as any other citizen.

[Advantages and weaknesses of the tumor board meeting in validating prophylactic mastectomy]. / La réunion de concertation pluridisciplinaire de cancérologie pour valider la mastectomie prophylactique : atouts et faiblesses.

The evolution of our health care system strengthens multidisciplinary collaboration in medical practice. Today, the tumor board meeting (TBM) has become mandatory for treatment decision-making in oncology. Experts recommend that such a multidisciplinary tool be extended to prophylactic mastectomy. We will discuss the relevance of this extension on the basis of a survey with female patients and health professionals confronted with prophylactic mastectomy. Health professionals find the TBM necessary because it allows more reasoned and consensual proposals to be made, reduces the burden of difficult decisions, and promotes a comprehensive view of those who receive care. However, this approach has also drawn criticism. Unlike medical consultation, which focuses on a patient's singularity, the TBM seems poorly suited to take into account psychosocial factors governing the decision-making process. It may be easier for a group to reach a complex decision, but it does not mean that the TBM allows for decisions to be adapted on a singular basis. Therefore, we suggest to modify the TBM so that it better suits the needs of patients susceptible to breast cancer. The referring physician, who knows the patient best, should guide the content of multidisciplinary deliberations and put the focus on individual criteria raised during medical consultations.

Plateable cryopreserved human hepatocytes for the assessment of cytochrome P450 inducibility: experimental condition-related variables affecting their response to inducers.

UNLABELLED: 1. RATIONALE: The aim of the present study was to assess the stability of cryopreserved human hepatocytes over 5 years and to explore experimental condition-related variables such as seeding density, culture matrix and medium, start and duration of treatment that could potentially affect the quality of cultures and their response to cytochrome P450 (CYP) inducers. 2. RESULTS: 63/125 batches of cryopreserved human hepatocytes were plateable after thawing. Of those, 17 batches showed reproducible recovery, viability and plateability (less than 5% intra-batch variability) up to 5 years. When cultured in collagen home-coated 48-well plates at a seeding density allowing 70% confluence, cryopreserved human hepatocytes display activities equivalent to fresh counterparts. Their response to CYP inducers is maximal and equivalent to fresh counterpart for an incubation of 72 h starting at Day 2 or Day 3 after plating when cultured in modified Hepatocyte Maintenance Medium (HMM). The number of cryopreserved human hepatocytes can be further reduced by using a cocktail of CYP substrates for the assessment of their inducibility. 3. CONCLUSIONS: Experimental condition-related variables, such as seeding density, culture matrix and medium, start and duration of treatment, affecting the response of plateable thawed cryopreserved human hepatocytes to cytochrome P450 inducers can be reduced by optimizing critical steps of the protocols.

Pleasure in medical practice.

It is time to challenge the issue of pleasure associated with the core of medical practice. Its importance is made clear through its opposite: unhappiness--something which affects doctors in a rather worrying way. The paper aims to provide a discussion on pleasure on reliable grounds. Plato's conception of techne is a convenient model that offers insights into the unique practice of medicine, which embraces in a single purposive action several heterogeneous dimensions. In Aristotle's Ethics, pleasure appears to play a central role for action's assessment and intensification. Pleasure is also tightly associated with the Kantian faculty of reflective judgment, which operates at the heart of clinical reasoning. Indeed, practicing medicine means to deal with the particular and the manifold, requiring clinical judgment, but also relying on embodied habitus. With Bourdieu's notion of habitus, pleasure is the mark of a happy practice, which presupposes a deep involvement in one's field. Throughout our inquiry, the question of pleasure comes to offer a critical reappraisal of real medical practice and leads to consider ethics more as a component of techne than as a separate realm of concern.

Chronic meningococcaemia and immunoglobulin A deficiency.

Chronic meningococcaemia is an unusual clinical presentation of Neisseria meningitidis infection. We describe the case of a patient, who presented with total IgA deficiency and partial IgM deficiency with a low switched memory B cells count, suggestive of a borderline form of common variable immunodeficiency (CVID). The role of IgA in the protection against Neisseria meningitidis, and the link between IgA deficiency and CVID are discussed.

Allelotyping analyses of synchronous primary and metastasis CIN colon cancers identified different subtypes.

In colorectal cancer, the molecular alterations that lead to metastasis are not clearly established, probably because of their high genetic complexity. To identify combinations of genetic changes involved in tumor progression and metastasis, we focused on chromosome instable (CIN) colon cancers. We compared by allelotyping of 33 microsatellites, the genomic alterations of 38 primary colon tumors with the synchronously resected matched liver metastases (CLM). We observed that (i) the number of patients with alterations at certain loci did not differ significantly between the whole primary tumor and the paired CLM, (ii) a group of patients had fewer alterations in the metastasis when compared with the matched primary tumor. A 2-way hierarchical unsupervised clustering of the allelotyping data revealed 2 tumor subtypes that have different levels of CIN (CIN-High, CIN-Low). Both subtypes have a minimal common set of alterations at chromosomes 8p, 17p and 18q, but does not include alteration at 5q or mutation at K-Ras. These 2 subtypes were also observed using a collection of 104 independent primary CIN colon tumors. In addition, we found a third subtype, consisting of tumors with a very low number of alterations not associated with specific loci (CIN-Very Low). We found that colon carcinogenesis may require a minimal set of alterations and that, in contrast to the current hypothesis, the level of CIN does not correlate with tumor progression. Therefore, our results suggest that metastasis potential could be present at very early stages of tumor development.

Puffy hand syndrome due to drug addiction: a case-control study of the pathogenesis.

AIM: We studied the pathogenesis of puffy hand syndrome of intravenous drug use. We hypothesized that injections of high-dose sublingual buprenorphine, instead of the recommended sublingual administration, could play an important role in lymphatic obstruction and destruction. DESIGN AND PARTICIPANTS: We set up a case-control study in substitution centres, recruiting intravenous drug addicts with and without puffy hands, respectively. The subjects were asked to answer anonymously a questionnaire of 40 items comprising social and demographic status, history of illicit drugs use, buprenorphine misuse and injection practices. FINDINGS: We included 33 cases and 33 controls, mean age of 34 years. They were past heroin users, mainly methadone-substituted. In multivariate analysis, sex (women) (OR = 8.9, P = 0.03), injections in the hands (OR = 5.9, P = 0.03), injections in the feet (OR = 6.5, P = 0.01) and the absence of tourniquet (OR = 7.0, p = 0.02) were significant risk factors for puffy hand syndrome. In 69.7% of the cases and 59.4% of the controls, respectively, there was a high-dose sublingual buprenorphine misuse, although it appeared not to be a significant risk factor for puffy hand syndrome. CONCLUSIONS: Injection practices are likely to cause puffy hands syndrome, but buprenorphine misuse should not be considered as a significant risk factor. However, intravenous drug users must still be warned of local and systemic complications of intravenous drug misuse.