Arginase activity mediates reversible T cell hyporesponsiveness in human pregnancy

Complex regulation of T cell functions during pregnancy is required to ensure materno-fetal tolerance. Here we reveal a novel pathway for the temporary suppression of maternal T cell responses in uncomplicated human pregnancies. Our results show that arginase activity is significantly increased in the peripheral blood of pregnant women and remarkably high arginase activities are expressed in term placentae. High enzymatic activity results in high turnover of its substrate L-arginine and concomitant reduction of this amino acid in the microenvironment. Amino acid deprivation is emerging as a regulatory pathway of lymphocyte responses and we assessed the consequences of this enhanced arginase activity on T cell responses. Arginase-mediated L-arginine depletion induces down-regulation of CD3 zeta, the main signalling chain of the TCR, and functional T cell hyporesponsiveness. Importantly, this arginase-mediated T cell suppression was reversible, as inhibition of arginase activity or addition of exogenous L-arginine restored CD3 zeta chain expression and T cell proliferation. Thus, L-arginine metabolism constitutes a novel physiological mechanism contributing to the temporary suppression of the maternal immune response during human pregnancy.     

MRI-Based Shoulder Osteoarthritis Severity score (SOAS) is predictive of functional improvement following total shoulder arthroplasty

BackgroundTotal shoulder arthroplasty (TSA) is an increasingly common treatment for end-stage glenohumeral osteoarthritis. Current established radiographic measures and classification systems do not predict patient-reported outcomes from TSA. We hypothesized that the MRI-based Shoulder Osteoarthritis Severity (SOAS) Score would correlate with subjective improvement following TSA.MethodsPatients undergoing TSA with preoperative shoulder MRIs and pre- and postoperative ASES scores with minimum 2-year follow-up were included from a prospectively collected institutional shoulder arthroplasty database. SOAS scores, which is measured from 0 to 100 with an increasing score reflecting greater global degenerative changes, were assessed by two independent reviewers, and Samilson-Prieto grade and Walch classification were scored by one reviewer. Average SOAS scores were correlated with demographic factors and pre-, post-, and change (Δ) in ASES scores. Statistical analysis was performed with STATA with Pearson's correlation, one-way ANOVA, and ROC analysis, with significance defined by p <.05.Results30 patients (age 63 ± 10 years, 14 females, 16 males) who underwent primary anatomic TSA were included. The intraclass correlation coefficient (ICC) for total SOAS scores calculated by reviewers was 0.91. SOAS score correlated significantly with ΔASES (r = 0.61, p = .0003) and preoperative ASES (r = -0.37, p = .042), with greater MRI-based degenerative change associated with greater improvement after TSA and lower preoperative ASES score. No significant relationship was found between either Samilson-Prieto or Walch classification and SOAS or ASES scores. No significant relationship was found between SOAS scores and age, sex, or BMI. Using an MCID of 21 as previously reported, an ROC curve was generated and found to have an AUC of 0.96. A SOAS score cut-point of 36.25 was found to maximize sensitivity and specificity in predicting reaching MCID.ConclusionWe observed a significant positive correlation between the MRI-based SOAS score and functional improvement following TSA measured using change in ASES scores, indicating that patients with more advanced degenerative changes on MRI had greater improvement after shoulder replacement surgery. We found that the correlation strength was highest when comparing total SOAS score to ΔASES as opposed to any individual sub-component of the SOAS score. The MRI-based SOAS score for shoulder osteoarthritis may be a valuable tool for predicting patient outcomes following TSA.Level of evidenceLevel III; Retrospective Cohort Comparison; Prognosis Study     

Prenatal Care for Adolescents and attributes of Primary Health Care

Objective

evaluate prenatal care for adolescents in health units, in accordance with the attributes of Primary Health Care (PHC) guidelines.

Method

quantitative study conducted with health professionals, using the Primary Care Assessment Tool-Brazil to assess the presence and extent of PHC attributes.

Results

for all the participating units, the attribute Access scored ≤6.6; the attributes Longitudinality, Coordination (integration of care), Coordination (information systems) and Integrality scored ≥6.6, and the Essential Score ≤6.6. Comparing basic units with family health units, the attribute scores were equally distributed; Accessibility scored ≤6.6, the others attributes scored ≥6.6; however, in the basic units, the Essential Score was ≤6.6 and, in the family health units, ≥6.6.

Conclusion

expanding the coverage of family health units and the training of professionals can be considered strategies to qualify health care.     

Long term follow up of through-the-scope balloon dilation as compared to strictureplasty and bowel resection of intestinal strictures in crohn’s disease

Background & aims: Ileo-colonic strictures are common complication of Crohn’s disease (CD), and may result in repeated endoscopic or surgical therapy with a risk of further complications, such as perforation or short bowel syndrome. Strictures develop as a consequence of tissue remodelling and fibrosis due to chronic inflammation. This study compares the outcome of CD patients undergoing primarily endoscopic treatment with those undergoing surgery at an university hospital. Methods: In this study we retrospectively included 88 CD patients with intestinal strictures (37 males, 51 females, mean age 40 years, range 19-65 years) of both our medical and our surgical department, who underwent either surgical or endoscopic therapy between January 2002 and January 2006 with prospective, controlled follow-up, extended till January 2010 (mean follow-up period: 5 years; range 4-8 years). The primary end-point was operation- and symptom-free time. Patients were primarily divided into four groups: only surgical therapy, only endoscopic therapy, endoscopy with subsequent surgery, and initial surgical therapy followed by endoscopic dilations. Results: 53% of all patients remained surgery-free with mean follow-up of 49 months; a single endoscopic dilation was sufficient enough in 9 patients to achieve a surgery-free time of 51 months, other patients required up to 5 dilations. The average interval between first and second dilation was 6.5 months, between second and third 10.5 months. In the group of patients with only endoscopic therapy, surgery- and symptom-free time was shorter, as compared to the group of only surgical therapy. We found that stenoses in the surgical group with an average length of 6.5 cm were as expected longer, as compared to the endoscopic group (3 cm, ranging from 2-4 cm). The surgery-free time was 49 months (42-71 months, P = 0.723) with a symptom-free time of 12 months (4.5-46 months, P = 0.921). In the group of only surgically treated patients, 68.4% of the patients had only one stenosis, 18.4% had 2-3 stenoses and 13.2% more than 3 stenoses. In all patients the surgery- and symptoms- free time was 69 months (57-83 months, P = 0.850 and 0.908). The other two groups showed similar results. We found no significant effect of characteristic of stenosis (length, inflammation, the number of stenoses), injection of prednisolone, disease activity at the time of dilation and medication at the time of dilation on the long-term outcome. Importantly, the success of symptom free time correlated with the diameter of the balloon. Conclusions: Endoscopic dilation should be considered as a first-line therapy for short, accessible, fibrotic strictures. Careful patient selection and proper diagnostic imaging pre-procedure are essential requirements for safe and successful treatment. The balloon diameter seems to correlate positively with the long term outcome of dilation. However, at ever shorter intervals between endoscopic interventions, surgery should be discussed as an option for further treatment.