Combined immunodeficiency (CVID and CD4 lymphopenia) is associated with a high risk of malignancy among adults with primary immune deficiency

Primary immunodeficiency disorders (PID) are a group of heterogeneous disorders characterized by recurrent infections, autoimmunity, increased lymphoproliferative disorders and other malignancies. PID is classified into cellular or humoral disorders or a combination of both. We evaluated the clinical differences among adult patients with three variants of PID: common variable immunodeficiency (CVID), idiopathic CD4 lymphopenia (ICL) and combined immunodeficiency (CID). We retrospectively compared demographics, immunological characteristics, clinical presentations and outcomes of CVID, CID and ICL patients followed from 2012 to 2018. In our cohort, we identified 44 adult patients diagnosed with CVID (22), CID (11) and ICL (11). Malignancy was associated with CID, as seven of 11 patients in this group were diagnosed with malignancy compared to CVID (three of 22) or ICL (two of 11) (P = 0·002 and 0·03, respectively). Malignancies were also linked to male gender [odds ratio (OR) = 5, 95% confidence interval (CI) = 1·12-22·18) P = 0·0342] and a low ratio of CD4/CD8 < 0·8 (OR = 5·1, 95% CI = 1·22-21·28, P = 0·025). Among CID and ICL, two of 11 patients died in each group, while no death was documented among CVID group (P = 0·04). Autoimmune manifestations did not differ between groups. Similarly, the rate of infections was similar between groups, although infectious agents vary. CID is associated with a high risk of malignancy compare to CVID or ICL. Among adults with PID, male gender, low CD4 and a CD4/CD8 ratio of < 0·8 may serve as risk factors of concomitant malignancy. Surveillance of lymphocyte subpopulations should be considered for all adults.

Depression and anxiety symptoms in cardiac patients: a cross-sectional hospital-based study in a Palestinian population.

BACKGROUND: Mental health problems have an adverse effect on the course of cardiac disease. The integration of their diagnosis and treatment into cardiology care is generally poor. It is particularly challenging in cultural environments where mental health problems are stigmatized. The objective of the current study was to investigate the proportion of cardiac patients with depression and anxiety as well as factors associated with the presence of these symptoms in a Palestinian population. METHODS: This cross-sectional hospital-based study was conducted on patients consecutively admitted with a new or existing cardiac diagnosis to one of the four main hospitals in Nablus, Palestine over an eight-month period. Data was obtained from hospital medical charts and an in-person interview, using a structured questionnaire with a sequence of validated instruments. All subjects were screened for depression and anxiety using the Cardiac Depression Scale (CDS) and the Depression Anxiety Stress Scale (DASS-42). Multivariate ordered logistic regression analyses were performed to identify factors among four categories (socio-demographic, clinical, psychosocial, lifestyle) independently associated with depression and anxiety. RESULTS: In total, 1053 patients with a confirmed cardiac diagnosis were included in the study with a participation rate of 96%. Based on the CDS and DASS-42, 54% met the criteria for severe depression (CDS > 100) and 19.2% for severe-to-very severe anxiety (DASS-anxiety > 15), respectively. Symptoms of depression and anxiety were more prevalent among females and less educated patients. Factors independently associated with both depressive and anxiety symptoms were post-traumatic stress disorder symptoms, low level of self-esteem, high somatic symptoms, low physical and mental health component scores, active smoking, physical inactivity, and longer disease duration. Patients with depressive and anxiety symptoms also reported poor social support and lower resilience. CONCLUSION: There was a high level of depression and anxiety in this sample of cardiac patients. The results point to characteristics of patients in particular need for mental health screening and suggest possible targets for intervention such as strengthening of social support and of physical activity. The integration of mental health services into cardiac rehabilitation in Palestine and comparable cultural settings is warranted from the time of first diagnosis and onward.

Beta(2)-agonists block tussive responses in guinea pigs via an atypical cAMP-dependent pathway.

beta(2)-Adrenoceptor agonists are the most effective bronchodilators currently available, and are used for symptom management in asthmatics. However, whether beta(2)-agonists are also antitussive is controversial. Identifying an antitussive role for beta(2)-agonists and dissecting the possible mechanism of action may help to explain the inconsistencies in the clinical literature and lead to the development of novel therapeutic agents. The aim of the present study was to determine whether or not beta(2)-agonists attenuate the tussive response in guinea pig and human models, and, if so, to identify the mechanism(s) involved. Depolarisation of vagal sensory nerves (human and guinea pig) was assessed as an indicator of sensory nerve activity. Cough was measured in a conscious guinea pig model. A beta(2)-agonist, terbutaline, dose-dependently inhibited the cough response to tussive agents in conscious guinea pigs. Terbutaline and another beta(2)-agonist, fenoterol, blocked sensory nerve activation in vitro. Using these mechanistic models, it was established that beta(2)-agonists suppress the tussive response via a nonclassical cyclic adenosine monosphosphate-dependent pathway that involves the activation of protein kinase G and, subsequently, the opening of large-conductance calcium-activated potassium channels. In conclusion, beta(2)-adrenoceptor agonists are antitussive, and this property occurs due to a direct inhibition of sensory nerve activation. These findings may help to explain the confusion that exists in the clinical literature, and could be exploited to identify novel therapies for the treatment of cough, which is a significant unmet medical need.

Anti-prothrombin antibodies cause thrombosis in a novel qualitative ex-vivo animal model.

Anti-prothrombin antibodies (aPT) are associated with thrombotic manifestations, and their association with reproductive failure is debatable. The aim of this study was to examine whether aPT could induce thrombosis and other clinical manifestations of the anti-phospholipid syndrome (APS). Mice were immunized with either prothrombin, beta2-glycoprotein-I (beta2GPI), or beta2GPI followed by prothrombin. The presence of clinical manifestation of APS, including thrombocytopenia, lupus anticoagulant and fetal resorption rates, was evaluated in all mice groups compared with nonimmunized mice. Thrombosis was studied in a novel ex-vivo model in which the aorta was sutured for 1 min and the presence or absence of visible thrombus was qualitatively evaluated. Immunized mice developed high autoantibody levels directed towards their immunizing autoantigens. The groups immunized with beta2GPI or beta2GPI/prothrombin, but not with prothrombin alone, developed prolonged aPTT, thrombocytopenia and increased fetal resorption rate. All prothrombin-immunized mice as well as most beta2GPI/prothrombin-immunized mice developed visible thrombus within the aorta. Some beta2GPI immunized mice developed very mild thrombus. None of the CFA/PBS-injected or the nonimmunized mice developed such thrombus. Active immunization with prothrombin or beta2GPI/prothrombin is associated with prothrombotic activity of blood in an ex-vivo model. This is the first direct evidence for thrombus induction by aPT.