Influence of immunosuppressive drugs on the CD30 molecule in kidney transplanted patients

Background

Soluble CD30 (sCD30) is a suggested marker for kidney transplantation outcomes. We investigated whether sCD30 serum levels are influenced by immunosuppression and whether they correlate with findings in protocol biopsies and with CD30 gene expression in peripheral blood mononuclear cells (PBMC).

Circulating histocompatibility antigen (HLA) gene products may help differentiate benign from malignant indeterminate pulmonary lesions

Background

This study explores the potential diagnostic utility of soluble Human Leukocyte Antigen (sHLA) molecules differentially released by lung adenocarcinoma and benign lung lesions.

Randomized Trial of the Parent And Caregiver Active Participation Toolkit for Child Mental Health Treatment

The purpose of this pilot study was to examine preliminary feasibility, acceptability, and effectiveness of a toolkit (Parent And Caregiver Active Participation Toolkit) to increase parent participation in community-based child mental health services. Study participants included 29 therapists (93% female; M age = 34.1 years; 38% Latino) and 20 parent/child dyads (children 80% female; M age = 8.6 years; parents 40% Latino) in 6 diverse community mental health clinics. Therapists were randomly assigned to standard care or the toolkit with standard care. Therapist and parent survey data and observational coding of treatment sessions were utilized. Mean comparisons and repeated measures analyses were used to test differences between study conditions over 4 months. Results supported preliminary feasibility and acceptability of the toolkit, with therapists assigned to the toolkit participating in ongoing training, adhering to toolkit use, and perceiving the toolkit as feasible and acceptable within their setting. Results preliminarily demonstrated improvement in therapists’ job attitudes, as well as actual use of parent engagement strategies. Results also preliminarily demonstrated increases in parent participation in child therapy sessions and more regular attendance, as well as some indication of support for perceived treatment effectiveness. Overall, results suggest the feasibility, acceptability, and potential effectiveness of the toolkit to enhance therapist job attitudes; practices that support parent engagement, parent engagement itself, and consumer perspectives on treatment outcomes; and the potential promise of future research in the area of parent participation interventions in child mental health services.     

PLAG1 immunohistochemistry is a sensitive marker for pleomorphic adenoma: a comparative study with PLAG1 genetic abnormalities

Aims

Pleomorphic adenoma gene 1 (PLAG1) gene rearrangement is the most common genetic abnormality in pleomorphic adenoma (PA), resulting in overexpression of PLAG1 protein. PA and carcinoma ex pleomorphic adenoma (CA ex‐PA) can mimic various benign and malignant salivary gland tumours. The aims of this study are to evaluate the sensitivity and specificity of PLAG1 immunohistochemistry (IHC) in the differential diagnosis of PA and CA ex‐PA and to compare the PLAG1 immunohistochemical results to PLAG1 gene abnormalities as detected by fluorescence in‐situ hybridisation (FISH).

Methods and results

PLAG1 immunostaining was performed on 83 salivary gland tumours, including 23 PA, 15 CA ex‐PA and 45 other salivary gland tumours. In addition, PLAG1 FISH was performed in 44 cases for the presence of gene rearrangements/amplifications. The results showed high sensitivity of PLAG1 IHC in 96% of PA; however, discordant results between PLAG1 FISH abnormalities and IHC were noted in 15 of 44 cases (34%). Seven PA, four de‐novo myoepithelial carcinomas and one basal cell adenocarcinoma had negative FISH results, but were positive for IHC; while three salivary duct carcinomas (SDC) ex‐PA were positive for FISH but negative for IHC. PLAG1 IHC can differentiate CA ex‐PA from de‐novo SDC (P = 0.02), but not from de‐novo myoepithelial carcinoma. PLAG1 IHC is a sensitive marker for PA. This could be due to PLAG1 gene abnormalities beyond FISH resolution.

Conclusions

A negative PLAG1 IHC might be helpful in excluding a PA diagnosis. Interestingly, in the context of CA ex‐PA, FISH is more sensitive than IHC in detecting PLAG1 abnormalities.     

Audiological manifestations in HIV-positive adults

OBJECTIVE:

To characterize the findings of behavioral hearing assessment in HIV-positive individuals who received and did not receive antiretroviral treatment.

METHODS:

This research was a cross-sectional study. The participants were 45 HIV-positive individuals (18 not exposed and 27 exposed to antiretroviral treatment) and 30 control-group individuals. All subjects completed an audiological evaluation through pure-tone audiometry, speech audiometry, and high-frequency audiometry.

RESULTS:

The hearing thresholds obtained by pure-tone audiometry were different between groups. The group that had received antiretroviral treatment had higher thresholds for the frequencies ranging from 250 to 3000 Hz compared with the control group and the group not exposed to treatment. In the range of frequencies from 4000 through 8000 Hz, the HIV-positive groups presented with higher thresholds than did the control group. The hearing thresholds determined by high-frequency audiometry were different between groups, with higher thresholds in the HIV-positive groups.

CONCLUSION:

HIV-positive individuals presented poorer results in pure-tone and high-frequency audiometry, suggesting impairment of the peripheral auditory pathway. Individuals who received antiretroviral treatment presented poorer results on both tests compared with individuals not exposed to antiretroviral treatment.     

The five-point Likert scale for dyspnea can properly assess the degree of pulmonary congestion and predict adverse events in heart failure outpatients

OBJECTIVES:

Proper assessment of dyspnea is important in patients with heart failure. Our aim was to evaluate the use of the 5-point Likert scale for dyspnea to assess the degree of pulmonary congestion and to determine the prognostic value of this scale for predicting adverse events in heart failure outpatients.

METHODS:

We undertook a prospective study of outpatients with moderate to severe heart failure. The 5-point Likert scale was applied during regular outpatient visits, along with clinical assessments. Lung ultrasound with ≥15 B-lines and an amino-terminal portion of pro-B-type natriuretic peptide (NT-proBNP) level >1000 pg/mL were used as a reference for pulmonary congestion. The patients were then assessed every 30 days during follow-up to identify adverse clinical outcomes.

RESULTS:

We included 58 patients (65.5% male, age 43.5±11 years) with a mean left ventricular ejection fraction of 27±6%. In total, 29.3% of these patients had heart failure with ischemic etiology. Additionally, pulmonary congestion, as diagnosed by lung ultrasound, was present in 58% of patients. A higher degree of dyspnea (3 or 4 points on the 5-point Likert scale) was significantly correlated with a higher number of B-lines (p = 0.016). Patients stratified into Likert = 3-4 were at increased risk of admission compared with those in class 1-2 after adjusting for age, left ventricular ejection fraction, New York Heart Association functional class and levels of NT-proBNP >1000 pg/mL (HR = 4.9, 95% CI 1.33-18.64, p = 0.017).

CONCLUSION:

In our series, higher baseline scores on the 5-point Likert scale were related to pulmonary congestion and were independently associated with adverse events during follow-up. This simple clinical tool can help to identify patients who are more likely to decompensate and whose treatment should be intensified.     

XLP1 inhibitory effect by 2B4 does not affect DNAM‐1 and NKG2D activating pathways in NK cells

X‐linked lymphoproliferative disease 1 (XLP1) is a rare congenital immunodeficiency caused by SH2D1A (Xq25) mutations resulting in lack or dysfunction of SLAM‐associated protein adaptor molecule. In XLP1 patients, upon ligand (CD48) engagement, 2B4 delivers inhibitory signals that impair the cytolytic activity of NK (and T) cells. This causes the selective inability to control EBV infections and the occurrence of B‐cell lymphomas. Here, we show that in the absence of SLAM‐associated protein, co‐engagement of 2B4 with different activating receptors, either by antibodies or specific ligands on target cells, inhibits different ITAM‐dependent signaling pathways including activating killer Ig‐like receptors. In XLP1 NK cells, 2B4 affected both the cytolytic and IFN‐γ production capabilities, functions that were restored upon disruption of the 2B4/CD48 interactions. Notably, we provide evidence that 2B4 dysfunction does not affect the activity of DNAM‐1 and NKG2D triggering receptors. Thus, while CD48⁺ B‐EBV and lymphoma B cells devoid of NKG2D and DNAM‐1 ligands were resistant to lysis, the preferential usage of these receptors allowed XLP1 NK cells to kill lymphomas that expressed sufficient amounts of the specific ligands. The study sheds new light on the XLP1 immunological defect and on the cross‐talk of inhibitory 2B4 with triggering NK (and T) receptors.     

Clustering of genomic breakpoints at the MLL locus in therapy‐related acute leukemia with t(4;11)(q21;q23)

Genomic characterization of translocation breakpoints is relevant to identify possible mechanisms underlying their origin. The consistent association of anthracylines (e.g., epirubicin and idarubicin) in inducing therapy‐related acute leukemias (t‐AL) with mixed lineage leukemia (MLL) gene rearrangement suggests that MLL translocations are causative events for t‐AL. Using asymmetric multiplex PCR strategy followed by direct DNA sequencing, we characterized the genomic breakpoints of the MLL and AFF1 genes in two patients who developed t‐AL with t(4;11)(q21;q23). Chemotherapeutic treatment of the primary disease in both patients included topoisomerase II (topo II) targeting agents. In one case, the MLL breakpoint was located in intron 9 at nucleotide position chr11:118354284 while the AFF1 breakpoint was in intron 3 at nucleotide position chr4:87992070. The breakpoint junction sequences revealed an insertion of two nucleotides at the MLL‐AFF1 junction. In the other patient, the MLL breakpoint was located in intron 11 at nucleotide position chr11:118359130‐32 and the AFF1 break was in intron 3 at nucleotide position chr4:87996215‐17. The MLL breakpoint found in the latter patient was identical to that of two previously reported cases, strongly suggesting the presence of a preferential site of DNA cleavage in the presence of topo II inhibitor. In addition, microhomologies at the breakpoint junctions were indicative of DNA repair by the non‐homologous end joining (NHEJ) pathway. This study further supports the evidence that MLL breakpoints in therapy‐related acute leukemia with MLL‐AFF1 are clustered in the telomeric half of the breakpoint cluster region that contains topo II recognition sites. © 2013 Wiley Periodicals, Inc.