CVID-Associated Tumors: Czech Nationwide Study Focused on Epidemiology, Immunology, and Genetic Background in a Cohort of Patients With CVID

Background: Common variable immunodeficiency disorder (CVID) is one of the most frequent inborn errors of immunity, increased occurrence of malignancies, particularly lymphomas, and gastric cancers, has long been noted among CVID patients. Multifactorial etiology, including immune dysregulation, infections, chronic inflammation, or genetic background, is suggested to contribute to tumor development. Here, we present the results of the first Czech nationwide study focused on epidemiology, immunology and genetic background in a cohort of CVID patients who also developed tumorsMethods: The cohort consisted of 295 CVID patients followed for 3,070 patient/years. Standardized incidence ratio (SIR) was calculated to determine the risk of cancer, and Risk ratio (RR) was established to evaluate the significance of comorbidities. Moreover, immunophenotyping, including immunoglobulin levels and lymphocyte populations, was assessed. Finally, Whole exome sequencing (WES) was performed in all patients with lymphoma to investigate the genetic background.Results: Twenty-five malignancies were diagnosed in 22 patients in a cohort of 295 CVID patients. SIR was more than 6 times greater in comparison to the general population. The most common neoplasias were gastric cancers and lymphomas. History of Immune thrombocytopenic purpura (ITP) was established as a potential risk factor, with over 3 times higher risk of cancer development. The B cell count at diagnosis of lymphoma was reduced in the lymphoma group; moreover, post-treatment B and T cell lymphopenia, associated with poorer outcome, was found in a majority of the patients. Intriguingly, no NK cell depression was observed after the chemotherapy. WES revealed heterogeneous genetic background among CVID patients with tumors, identifying gene variants associated with primary immunodeficiencies (such as CTLA4, PIK3CD, PMS2) and/or increased cancer susceptibility (including BRCA1, RABEP1, EP300, KDM5A).Conclusions: The incidence of malignancy in our CVID cohort was found to be more than 6 times greater compared to the general population. Gastric cancers and lymphomas were the most frequently diagnosed tumors. ITP was identified as a risk factor for malignancy in CVID patients. WES analysis confirmed a wide genetic heterogeneity among CVID patients. The identified causative or modifying gene variants pointed to errors in mechanisms contributing to both immunodeficiency and malignancy

Effect of expectation on short- and long-term treatment response to Acupuncture in migraine patients

Introduction: There are relatively few studies addressing the relationship between the patient's expectation and the short and long-term response to treatment with acupuncture. The aim of this study was to assess the association between pre- and post-treatment expectation of acupuncture and post-treatment and post-follow-up patient outcomes. Methods: This was an open-label, randomized controlled clinical trial conducted at the Czech-Chinese Centre for Traditional Chinese Medicine at the University Hospital Hradec Kralove between October 2015 and April 2017. Non-specific factors were examined in the intervention arm using regression analysis. Results: Post-treatment positive expectation concerning the success of the treatment, as well as the affective status of the patient, is one of the most significant nonspecific factors contributing to an increased post-treatment effectiveness of acupuncture; however, this positive expectation decreased with time. On the other hand, the post-follow-up effect of acupuncture was significantly improved by the patients’ positive perception of the TCM practitioner. Conclusions: Correct calibration of a patient's expectation, good mental status, and patients' perceptions of an acupuncturist's skills reduced the number of migraine days in patients treated with acupuncture. Understanding non-specific treatment effects can potentially help clinicians to integrate them in to practice and thus optimise treatment effectiveness. Future research is needed to clarify whether interventions targeting modifiable non-specific factors prior to and during acupuncture treatment can result in better patient outcomes and future cost-savings.</p