Incomplete thymic involution in systemic sclerosis and rheumatoid arthritis

ObjectiveThe thymus plays a crucial role in immune system homeostasis. Thymic abnormalities have been reported in many autoimmune diseases, but data for systemic sclerosis (SSc) and rheumatoid arthritis (RA) are sparse. The aim of this study was to evaluate the prevalence and correlates of radiological incomplete involution of the thymus in SSc and RA patients, and in a non-autoimmune group of controls.MethodsAll patients were at least 40 years old: 96 SSc patients (median age 59 years, 80% women) and 65 RA patients (median age 57 years, 88% women) were compared with 32 control individuals (median age 63 years, 62% women). Pulmonary CT-scans performed for lung assessment were available for all individuals. For the purpose of our study, complete involution of the thymus was defined as the absence of a residual thymus or a gland thickness, corresponding to the short axis on the axial slice, of less than 7 mm. We defined incomplete involution of the thymus as a residual thymic tissue more than 7 mm thick.ResultsThe frequency of incomplete thymus involution was significantly higher in SSc and RA patients (respectively 15 and 14%) than in the control group (0%; P < 0.05). Incomplete thymus involution was associated with pulmonary restrictive syndrome in SSc patients, and with biotherapy and an absence of antinuclear antibodies in RA patients.ConclusionOur findings show that two autoimmune diseases, SSc and RA, are associated with incomplete thymus involution.     

Soins intensifs à domicile : modèles internationaux et niveau de preuve

Introduction

Despite recent legislation favouring home treatment services, international literature contrasts with its development in France, where those programs stay rare. They were implemented since the deinstitutionalization movement of the 1970s, to provide care to severe mentally ill outpatients, who used to stay in long-term inpatient wards. Those home treatment programs can be divided in two groups: Assertive Community Treatment and crisis interventions teams.

Objectives

This article first aims to describe those two types of programs, and then to review their evidence level. Finally, we will discuss the actual controversy about effectiveness of home treatment.

Method

This article is a literature review of international research about home treatment programs for adults’ severe mental illness. It excluded children psychiatry, addictology and elderly psychiatry. We selected reviews and research articles taken from international publications, using a PubMed research.

Results

This article concerns home treatment programs, belonging to “mobile teams”, which is a group of psychiatric teams including varied goals: Improving continuity of care, community assessment, avoiding admissions to psychiatric hospital, improving skills in community living, and supporting families. Those programs practice assertive outreach. Some provide care and others only assess and direct people to other services. Only the first ones are concerned by this article. We distinguish two types of home treatments: Assertive Community Treatment (ACT) and Crisis Intervention teams. Assertive Community Treatment, also named Assertive Outreach teams or Intensive Case Management, is a very well described model which aims to keep people with severe mental illness in the community. It is an intensive kind of Case Management. It is specially addressed to high services users, with frequent admissions. ACT consists in visiting people at home, providing cares and social support, developing skills to cope with daily living. It is provided by a 24-hour available multidisciplinary team, in an unlimited time. The first Stein and Test study showed benefits compared to standard treatment, but more recent trials failed in improving hospital use or clinical and social outcomes. Some even show and increased hospitalization rate. This variation can be explained by an improvement of standard care with time, and international heterogeneity. A higher fidelity to the original model could decrease bed use. Fidelity scales have been developed to compare different programs. ACT seems to be useful to improve engagement in care for people with a high level of needs, and to maintain them in housing. Studies also show a dilution of the effectiveness of ACT in routine practice. Those results limit its implementation. The second group of home treatments is crisis intervention and home treatment teams, also called crisis assessment teams. Those teams aim to treat crisis at home for severe mentally ill people. Crisis is defined as a symptomatic exacerbation in severe mental illness. Treatment is provided by a 24 hours available multidisciplinary team which assesses the situation, directs the patient and programs a crisis intervention. The intervention is time limited, about six weeks. It helps people to resolve crisis in the community. It could avoid 50% of psychiatric admissions, without increasing readmission rates. A recent study shows it could reduce the suicide rate. It also improves satisfaction with care and engagement.

Conclusions

Despite the controversy, home treatment services can be useful to improve engagement in care, user's satisfaction, and to avoid psychiatric admissions. Visiting patient at home and associating social interventions with medical treatment improve bed use outcomes. Less intensive but well organized community teams can also bring benefits. In the French context, the lack of visibility of home treatment teams can be explained by several hypotheses. We can cite the lack of systematic evaluation of care programs, the persistence of more inpatient beds than in other countries, the difficulty to implement home treatment in rural areas or the cultural use of hospital.     

AbobotulinumtoxinA (Dysport) dosing in cervical dystonia: an exploratory analysis of two large open-label extension studies

Treatment with botulinum toxin-A is recommended as first-line treatment for cervical dystonia (CD). In clinical practice many factors appear to influence dose adjustment and the retreatment regimen; however, there is little information available in the literature regarding the evolution of dosing over treatment cycles. We report on two similarly designed, long-term, multicenter, open-label extension studies of Dysport for the treatment of CD, which followed 500 U fixed-dose placebo-controlled trials. Both studies specified a fixed 500 U dose for the first open-label treatment cycle, with dose adjustment in subsequent treatment cycles according to the clinical response. These analyses include 218 patients who entered the two studies; doses in the subsequent treatment cycles ranged between 250 and 1,000 U. During open-label treatment, all treatment cycles resulted in improvements in mean Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total scores. However, increasing the dose of Dysport above the initial 500 U dose was not observed to result in an incremental improvement in response as measured by the TWSTRS. No individual patient characteristic was found to reliably predict the use of higher doses at each treatment cycle. Dysport was generally well tolerated with no major differences in the incidence of adverse events (AEs) observed with different doses. Dysphagia was considered an AE of special interest and dysphagia data from the open-label studies were combined with two Phase II studies. Analysis of this enhanced database indicates that unilateral injections of >150 U into the sternocleidomastoid muscle is associated with a higher dysphagia risk. Thus, limiting the dose in the sternocleidomastoid may help reduce the incidence of dysphagia.     

A novel approach to evaluating the benefit of post-urinary tract infection renal ultrasonography,using decision curve analysis

Background

The benefit of post-urinary tract infection (UTI) sonography to detect clinically significant renal abnormalities remains a subject open to debate. Decision curve analysis (DCA) is a novel method for evaluating the clinical usefulness of diagnostic tests. Our objective was to determine, using DCA, the benefit of post-UTI sonography and of post-UTI sonography with biological markers of inflammation to predict the risk of recurrence of febrile UTI in children aged 2 to 24 months without known uropathy.

Methods

We retrospectively analyzed all children aged 2 to 24 months, without known uropathy, who presented with a first episode of febrile UTI between 2009 and 2012 and followed them for 30 months. We then used DCA to estimate the benefit of post-UTI sonography or post-UTI sonography + biological markers of inflammation for detecting the risk of recurrence.

Results

A total of 318 children [144 boys (45.3 %) and 174 girls (54.7 %)], with a mean age of 6.9?±?5.6 months, were identified. Of these, 210 children presented with a significant inflammation [66.2 %; 95 % confidence interval (CI) 61.0–71.4], and 30 (9.4 %; 95 % CI 6.2–12.6) presented with abnormal post-UTI sonographic findings. Eighteen (5.7 %; 95 % CI 3.1–8.2) children presented with recurrent UTI at 30 months.

Conclusions

There were significantly more recurrences in those children who presented with abnormal sonographic findings than in those who did not (relative risk?7.68; 95 % CI 3.03–19.46). However, taking into account the effect of false-positives and false negatives, the DCA revealed that for threshold probabilities of >30 %, at which patients/doctors are concerned about unnecessary interventions (whether tests or treatments), neither post-UTI sonography nor post-UTI sonography + biological markers of inflammation have sufficient value to improve care.

     

Bariatric Surgery in Obese Patients with Type 1 Diabetes: Effects on Weight Loss and Metabolic Control

Background

Type 1 diabetes patients, although typically lean, experience an increased prevalence of obesity, and bariatric surgery is considered in severe cases. Bariatric surgery in such patients leads to significant weight loss and decreased insulin requirements; however, effects on glycemic control remain discussed. We assessed, in obese patients with type 1 diabetes, the effects of bariatric surgery upon body weight, body composition, and glycemic control, including the occurrence of hypoglycemic events.

Methods

Thirteen obese patients with type 1 diabetes who underwent bariatric surgery (Roux-en-Y gastric bypass n?=?6, sleeve gastrectomy n?=?7) were matched with obese patients without diabetes and with type 2 diabetes patients during 12 months of follow-up. Outcomes included body weight, DXA-assessed body composition, HbA1c, and incidence of hypoglycemia.

Results

At 12 months, median surgery-induced weight loss was 27.9 % (21.1–33.3), 26.1 % (24.8–29.7), and 27.5 % (21.8–32.1) in patients with type 1 diabetes, type 2 diabetes, and without diabetes, respectively, with no significant differences across the groups. Similar findings were observed for body fat changes. At 12 months, median HbA1c decreased from 8.3 to 7.6 % in type 1 diabetes patients versus 8.0 to 5.9 % in type 2 diabetes patients (P?=?0.04 between the groups). In type 1 diabetes patients, the number of reported minor hypoglycemia increased transiently only at 6 months. Two patients reported severe hypoglycemia (one episode each).

Conclusions

Type 1 diabetes patients benefit from bariatric surgery in terms of weight loss and glycemic control. Close monitoring of insulin therapy appears warranted to prevent minor hypoglycemia in the first months post-surgery.

     

A CFSE based assay for measuring CD4+CD25+ regulatory T cell mediated suppression of auto-antigen specific and polyclonal T cell responses

CD4(+)CD25(+) regulatory T cells (Tregs) are considered to play a key role as suppressors of immune mediated reactions. The analysis of Treg function in patients with autoimmune, allergic or oncogenic diseases has emerged over the past years. In the present study we describe a CFSE based protocol to measure Treg mediated suppression of CD4(+) T cells. Measuring Treg suppressive capacity towards proliferation of anti-CD3 Ab stimulated CD4(+)CD25(-) T cells in coculture experiments by means of a CFSE based and a classical [(3)H]thymidine incorporation assay gave similar results, provided that CD4(+)CD25(+) T cells were anergic. However, when CD4(+)CD25(+) T cells proliferated upon mitogenic stimulation, data obtained by the CFSE assay allowed the detection of a significant Treg suppression whereas this was clearly underestimated using the [(3)H]thymidine assay. In addition, an indirect CFSE based method was developed to analyze antigen specific responses of total CD4(+) T cells and Treg depleted CD4(+) T cells (i.e. CD4(+)CD25(-) T cells). Our results indicate that, in healthy individuals, CD4(+) T cell responses against the multiple sclerosis (MS) auto-antigens, myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG), were increased in Treg depleted CD4(+) T cells as compared to total CD4(+) T cells. Our initial data suggest that Tregs in MS patients show an impaired suppression of myelin reactive T cells when compared to healthy controls. Moreover, this experimental setup permits the measurement of cytokine production of the antigen proliferated CFSE(low) T cells by additional flow cytometric analyses. In conclusion, the described CFSE based Treg suppression assay is a valuable tool to study suppressor T cells in (auto)immune disorders.     

Dolosigranulum pigrum causing nosocomial pneumonia and septicemia

We report a case of non-ventilator-associated nosocomial pneumonia and septicemia due to Dolosigranulum pigrum, a rare gram-positive opportunistic pathogen. The organism was isolated from bronchoalveolar lavage fluid and blood of a debilitated patient. D. pigrum was identified after 16S rRNA gene sequencing.     

Early development of the lower deciduous dentition and oral vestibule in human embryos

The aim of this work was to investigate the early development of the deciduous dentition and oral vestibule in the human embryonic lower jaw. Histological sections and three-dimensional reconstructions from prenatal weeks 6-9 were used. A continuous anlage for the oral vestibule did not exist in the mandible. In contrast to the upper jaw, where we previously observed that the dental and vestibular epithelia developed separately, two dento-vestibular bulges differentiated in the incisor region of the mandible. The lingual parts of each bulge were found to give rise to the respective central and lateral incisors, whereas the labial parts differentiated into the vestibular epithelium. In the canine and molar areas, the dental and vestibular epithelia originated separately. Later, the segments of the vestibular epithelium fused into the labial vestibular ridge, giving rise to the lower oral vestibule in the lip region. In the cheek region, the oral vestibule was found to originate in the mucosal inflection between the developing jaw and the cheek. A similar heterogeneous developmental base for the oral vestibule was also observed in the upper jaw. There is thus no general scheme for the early development of the dental and vestibular epithelia that applies to both the upper and lower jaws, and to both their anterior and posterior regions.