Immune system defects in DiGeorge syndrome and association with clinical course

We evaluated 18 DiGeorge syndrome (DGS) patients and aimed to investigate the immunological changes in this population. DGS patients with low naive CD4⁺T and CD8⁺T cells were defined as high‐risk (HR) patients, whereas patients with normal numbers of naive CD4⁺ and CD8⁺T cells were defined as standard risk (SR) patients. Level of serum IgM, CD3⁺ T cell counts and percentages of class‐switched memory B cells were significantly low in HR group compared to SR ones. Severe infections and persistent hypoparathyroidism were detected significantly higher in HR group. Patients with reduced percentages of class‐switched B cells had earlier onset of infection, lower blood IgM, lower CD4⁺ and CD8⁺T counts than patients with normal class‐switched memory B cells. Decreased levels of IgM were associated with low numbers of naive CD4⁺ and recent thymic emigrants T cells. Monitoring the immune changes of patients with DGS would be useful to predict the severe phenotype of disease.     

Quality of life, symptom experience and distress of lung cancer patients undergoing chemotherapy

The diagnosis of lung cancer in the advanced stage of illness, the poor prognosis associated with the disease, and the side effects of chemotherapy all have an impact on various dimensions of quality of life (QoL).

The purpose of the research

The current study was designed to describe the QoL and symptom distress of lung cancer patients undergoing chemotherapy and to explore the relationships between demographic/treatment-related characteristics and QoL.

Methods and sample

The sample consisted of 154 lung cancer patients undergoing chemotherapy. The symptom experiences and QoL of lung cancer patients undergoing chemotherapy were evaluated using the Memorial Symptom Assessment Scale and Quality of Life Index – Cancer Version.

Results

The lung cancer patients had low QoL scores. The scores on the Health and Functioning subscale were the lowest (20.33 ± 5.59), while those of the Family subscale were the highest (27.66 ± 2.77). The most common physical symptoms experienced by lung cancer patients were lack of energy, coughing, pain, lack of appetite, and nausea, while the psychological symptoms were feeling nervous, difficulty sleeping, feeling sad, and worrying. There was a negative relationship between the symptom distress and quality of life scores (r = −0.45; p < 0.000). Females and those with low income levels and performance status experienced greater symptom distress.

Conclusions

Lung cancer patients receiving chemotherapy suffer many limitations due to the symptoms and disruptions to their QoL, arising from both the disease process and its treatment. Lung cancer patients need to be assessed regularly and supported.     

The quality of life and self-efficacy of Turkish breast cancer patients undergoing chemotherapy

Self-efficacy has a positive effect on health behaviors, symptom control, compliance with cancer treatment, and quality of life. This study aims to describe the quality of life and self-efficacy of Turkish breast cancer patients undergoing chemotherapy. The sample consisted of 141 patients. Data was gathered using a Patient Information Form, the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B), a scale about Strategies Used by Patients to Promote Health and the Rotterdam Symptom Checklist. All quality of life dimensions were negatively affected at a significant level. Following commencement of chemotherapy, there was an increase in the negative effect on physical well-being, emotional well-being and additional concerns subscales and total FACT-B and their self-efficacy was negatively affected to a moderate degree. However, a significant degree of change did not occur in the self-efficacy. During treatment the physical symptoms and psychological distress increased and the activity level was negatively affected. The quality of life and self-efficacy were influenced by personal and medical characteristics, showing consistency with similar studies. Because there are negative effects of cancer and chemotherapy on patients' quality of life and self-efficacy, nurses need to focus on designing psychosocial interventions to improve their self-efficacy and quality of life.     

Meta-analysis of breast cancer outcome and toxicity in adjuvant trials of aromatase inhibitors in postmenopausal women

The present meta-analysis examines randomized trials of third-generation aromatase inhibitors (AIs) as alternatives to tamoxifen in three treatment settings: monotherapy, sequenced therapy and extended therapy. Eleven randomized controlled trials (RCTs) were chosen based on their similarity in terms of study design and included 34,070 post-menopausal women who had undergone surgery for estrogen-sensitive early breast cancer. DFS was significantly improved by AI monotherapy (Hazard Ratio (HR): 0.89, p = 0.001), sequenced therapy (HR: 0.7, p < 0.00001) and extended therapy (HR: 0.62, p < 0.00001). All of the patients benefited significantly from sequenced therapy (HR: 0.81, p = 0.003), and hormone receptor-positive patients benefited from AI monotherapy (HR = 0.92, p = 0.046) with respect to OS. AI monotherapy conferred significantly lower risks for thromboembolic events (OR = 0.61; p < 0.001) and endometrial cancer (OR = 0.26; p < 0.001) compared with tamoxifen monotherapy; however, there was a greater risk of cardiovascular events (OR = 1.20; p = 0.030). Sequenced therapy was also superior in terms of endometrial cancer but was inferior with respect to fractures, thromboembolic and cardiovascular events.     

Primary antibody deficiencies in Turkey: molecular and clinical aspects

Primary antibody deficiencies (PAD) are the most common subtype of primary immunodeficiencies, characterized by increased susceptibility to infections and autoimmunity, allergy, or malignancy predisposition. PAD syndromes comprise of immune system genes highlighted the key role of B cell activation, proliferation, migration, somatic hypermutation, or isotype switching have a wide spectrum from agammaglobulinemia to selective Ig deficiency. In this study, we describe the molecular and the clinical aspects of fifty-two PAD patients. The most common symptoms of our cohort were upper and lower respiratory infections, bronchiectasis, diarrhea, and recurrent fever. Almost all patients (98%) had at least one of the symptoms like autoimmunity, lymphoproliferation, allergy, or gastrointestinal disease. A custom-made next-generation sequencing (NGS) panel, which contains 24 genes, was designed to identify well-known disease-causing variants in our cohort. We identified eight variants (15.4%) among 52 PAD patients. The variants mapped to BTK (n?=?4), CD40L (n?=?1), ICOS (n?=?1), IGHM (n?=?1), and TCF3 (n?=?1) genes. Three novel variants were described in the BTK (p.G414W), ICOS (p.G60*), and IGHM (p.S19*) genes. We performed Sanger sequencing to validate pathogenic variants and check for allelic segregation in the family. Targeted NGS panel sequencing can be beneficial as a suitable diagnostic modality for diagnosing well-known monogenic PAD diseases (only 2–10% of PADs); however, screening only the coding regions of the genome may not be adequately powered to solve the pathogenesis of PAD in all cases. Deciphering the regulatory regions of the genome and better understanding the epigenetic modifications will elucidate the molecular basis of complex PADs.

     

Correction to: Primary antibody deficiencies in Turkey: molecular and clinical aspects

Immunologic Research -     

Clinical Heterogeneity of Immunodysregulation,Polyendocrinopathy, Enteropathy,X-linked: Pulmonary Involvement as a Non-Classical Disease Manifestation

Purpose

IPEX (Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked) is a rare X-linked recessive life-threatening disorder characterized by autoimmunity and early death. Pulmonary complication related with IPEX has not been elucidated exactly. Here, we report 4 IPEX patients, 3 of which died from severe pulmonary disease.

Methods

Clinical data and laboratory findings including autoantibodies, immunoglobulin levels as well as number of T, B and NK cells were evaluated. FOXP3 expression and T reg activity were analyzed. The FOXP3 gene was sequenced and RNA analysis was performed.

Results

Patient I (PI) presented with nephrotic syndrome at 3 years of age and then developed autoimmune hepatitis without eczema, enteropathy or high IgE and died at 9 years of age due to acute respiratory distress syndrome (ARDS). Two cousins of PI had the same hypomorphic splice site mutation leading to a deletion of 27 amino acids, but normal FOXP3 protein expression and normal suppressive capacity of T reg in a proliferation inhibition assay. However, they exhibited typical symptoms such as eczema, diabetes and enteropathy with eosinophilia at early age (PII, PIII) and were transplanted in infancy. One of them had severe respiratory distress right after birth (PIII). Patient IV from another family presented with chronic diarrhea without autoimmune manifestations and died due to ARDS.

Conclusion

Lung disease related to IPEX syndrome has not been reported before and this entity could be a critical factor in disease outcome.     

Results of using Ilizarov distraction osteogenesis technique for the treatment of cubitus varus deformities in adults

Introduction  

Five adult patients, with posttraumatic cubitus varus deformity underwent corrective surgery by the Ilizarov method of distraction osteogenesis.     

Induction chemotherapy with triweekly docetaxel and cisplatin followed by concomitant chemoradiotherapy with or without surgery in stage III non-small-cell lung cancer: a phase II study

Background

The main goal of this study was to evaluate the feasibility and effectivity of triweekly docetaxel/cisplatin followed by weekly docetaxel/cisplatin concomitantly with radiotherapy with or without surgery in locally advanced non–small-cell lung cancer (NSCLC) patients.

Materials and Methods

Thirty five patients with locally advanced NSCLC were enrolled. Combination chemotherapy with triweekly docetaxel/cisplatin (75 mg/m²) was administered as induction regimen. After induction chemotherapy, patients were evaluated for surgery if their disease subsequently downstaged. Six cycles of weekly docetaxel/cisplatin (20 mg/m²) concurrently with radiotherapy up to a 60 Gy were administered after induction chemotherapy with or without surgery. Response, toxicity, time-to-progression and overall survival were evaluated.

Results

Twelve patients with stage IIIA-N2 and 23 patients with stage IIIB-T4N0-2 were evaluated (median age, 54 years). After 94 cycles of induction chemotherapy, partial response was achieved in 20 patients, 9 patients had stable disease and six had progressive disease. After overall treatment, 6 patients achieved complete response, 19 patients had partial response, 8 patients had progressive disease, and 2 patients had stable disease. Two patients experienced grade 3-4 pulmonary toxicity and 1 patient experienced grade 3 esophageal toxicity. Six patients underwent surgery. Median overall survival for all patients was 15 months and time-to-progression was 13 months with a median follow-up of 22 months.

Conclusion

Triweekly docetaxel plus cisplatin followed by weekly docetaxel plus cisplatin concomitantly with radiotherapy is effective and feasible and seems to be an alternative option for patients who have locally advanced NSCLC. Surgery may provide additional benefit for patients whose disease adequately downstaged after induction chemotherapy.