Significance For Clinical Use Research Articles

Administration of Extensive Hydrolysates From Caseins and Lactobacillus rhamnosus GG Probiotic Does Not Prevent Cow's Milk Proteins Allergy in a Mouse Model.

BackgroundEarly nutrition may influence the development of food allergies later in life. In the absence of breastfeeding, hydrolysates from cow’s milk proteins (CMP) were indicated as a prevention strategy in at risk infants, but their proof of effectiveness in clinical and pre-clinical studies is still insufficient. Thanks to a validated mouse model, we then assessed specific and nonspecific preventive effects of administration of extensive hydrolysates from caseins (eHC) on the development of food allergy to CMP. The additional nonspecific effect of the probiotic Lactobacillus GG (LGG), commonly used in infant formula, was also assessed.MethodsGroups of young BALB/cByJ female mice were pretreated by repeated gavage either with PBS (control mice), or with PBS solution containing non-hydrolyzed milk protein isolate (MPI), eHC or eHC+LGG (eq. of 10 mg of protein/gavage). All mice were then experimentally sensitized to CMP by gavage with whole CM mixed with the Th2 mucosal adjuvant Cholera toxin. All mice were further chronically exposed to cow’s milk. A group of mice was kept naïve. Sensitization to both caseins and to the non-related whey protein β-lactoglobulin (BLG) was evaluated by measuring specific antibodies in plasma and specific ex vivo Th2/Th1/Th17 cytokine secretion. Elicitation of the allergic reaction was assessed by measuring mMCP1 in plasma obtained after oral food challenge (OFC) with CMP. Th/Treg cell frequencies in gut-associated lymphoid tissue and spleen were analyzed by flow cytometry at the end of the protocol. Robust statistical procedure combining non-supervised and supervised multivariate analyses and univariate analyses, was conducted to reveal any effect of the pretreatments.ResultsPBS pretreated mice were efficiently sensitized and demonstrated elicitation of allergic reaction after OFC, whereas mice pretreated with MPI were durably protected from allergy to CMP. eHC+/-LGG pretreatments had no protective effect on sensitization to casein (specific) or BLG (non-specific), nor on CMP-induced allergic reactions. Surprisingly, eHC+LGG mice demonstrated significantly enhanced humoral and cellular immune responses after sensitization with CMP. Only some subtle changes were evidenced by flow cytometry.ConclusionNeither specific nor nonspecific preventive effects of administration of casein-derived peptides on the development of CMP food allergy were evidenced in our experimental setup. Further studies should be conducted to delineate the mechanisms involved in the immunostimulatory potential of LGG and to clarify its significance in clinical use.

An update on clinical significance of use of THSD7A in diagnosing idiopathic membranous nephropathy: a systematic review and meta-analysis of THSD7A in IMN

Background: THSD7A is a new target antigen of idiopathic membranous nephropathy (IMN). Moreover, malignancies are also found in patients with THSD7A-positive membranous nephropathy. We aimed to systematically evaluate the prevalence of THSD7A in IMN patients and malignancies in THSD7A-positive patients.Methods: We searched English and Chinese database to 31 December 2017 with the term ‘THSD7A’ or ‘thrombospondin type 1 domain-containing 7A’. Meta-analysis was used to explore the positive rate of THSD7A in the IMN patients. Subgroup analysis was performed according to the race, sample size, and detecting method of THSD7A.Results: Ten studies involving 4121 participants were eventually included. The prevalence of THSD7A was 3% (95% CI, 3%–4%) in all patients and 10% (95% CI, 6%–15%) in PLA2R-negative patients. 77 patients had positive circulating antibodies, and the prevalence of THSD7A was also low at 3% (95% CI, 2%–4%). Overall, 72 patients had positive THSD7A staining on renal biopsy, and the prevalence was 3% (95% CI 2%–4%). Subgroup analysis showed significant differences in the prevalence of THSD7A based on the study sample sizes, however, no significant differences were seen in different ethnic groups. Furthermore, among THSD7A-positive patients, 3/10 studies reported malignancies with the incidence varied from 6% to 25%.Conclusions: The prevalence of THSD7A is more common in the PLA2R-negative patients than the IMN patients. Screening for malignancies in THSD7A-positive MN patients is recommended.

Practice patterns and clinical significance of use of capsule endoscopy in suspected and established Crohn's disease.

Background/AimsAlthough the role of capsule endoscopy (CE) in Crohn's disease (CD) has expanded, CE is not used routinely for diagnosing and evaluating CD in Korea. We aimed to investigate current patterns of practice and evaluate the clinical significance of the use of CE in CD in Korean patients.MethodsAmong 651 CE procedures performed for various indications, we retrospectively analyzed the medical records of patients who underwent CE in 57 cases of suspected CD (sCD) and 14 cases of established CD (eCD).ResultsIn the sCD group, CE was most commonly used for the initial diagnosis of CD (54.4%). Capsule retention was found in only 1 patient in the eCD group (1/71, 1.4%). In the sCD group, 28.1% of patients were diagnosed with CD on the basis of CE findings; other diseases diagnosed included tuberculous enteritis (7.0%), non-steroidal anti-inflammatory drug-induced enteropathy (5.3%), and other enteritis (17.5%). Only 11.5% of patients with eCD (14/122) underwent CE. The indication for CE in the 14 patients with eCD was to assess disease extent and activity. The overall diagnostic yield of CE was 59.7%. Therapeutic strategies were changed in 70.2% of patients in the sCD group and 50% of those in the eCD group based on CE findings.ConclusionsIn clinical practice, CE was most commonly indicated for the initial diagnosis of CD and was not generally performed in patients with eCD. CE appears to be an effective diagnostic modality for evaluating sCD and is useful for determining therapeutic strategies for patients with sCD and those with eCD.

Abstract P6-19-03: Overexpression of FOXM1 is a potential prognostic marker in male breast cancer

Abstract Background The Forkhead box M1 (FOXM1) transcription factor is known to play an important role in the development and progression of many cancer types including breast cancer. The important role of FOXM1 in cancer affirms its significance for clinical use and therapeutic intervention. Elevated expression of FOXM1 in female breast cancer correlates with undifferentiated tumor phenotype and negative clinical outcome. However, whether FOXM1 has any indication for prognosis in male breast cancer (MBC) patients is still unknown. The purpose of this study was to examine the expression levels of FOXM1 in MBC and to identify the relationship between FOXM1 expression and patient survival. Methodsl Immunohistochemical analysis for FOXM1 was performed in a total of 80 male breast cancer specimens, all with linked clinical outcome data. Kaplan-Meier method and Cox proportional hazards analysis were used to relate FOXM1 expression to clinicopathological variables and overall survival (OS). Results We observed high expression of the FOXM1 protein in 39 % of MBC samples (31/80). FOXM1 overexpression was significantly associated with higher histological grade (p=0.05), lymph node metastasis (p=0.04), tumor size (p=0.05), and estrogen receptor expression (p=0.04). Patients with FOXM1 expression had a significantly poorer overall survival than those without FOXM1 expression (p=0.02). Multivariate analyses indicated that FOXM1 positivity was an independent prognostic factor for OS (p=0.03). Conclusion These results show that FOXM1 may represent a novel MBC marker with prognostic significance that could be included into the limited marker panels for MBC. Citation Format: Rahal K, Abdeljaoued S, Bettaieb I, Bouzaiene H, Adouni O, Miladi S, Goucha A, Bouaziz H, Makhlouf R, Hechiche M, Benna F, Boussen H, El May A, Gamoudi A. Overexpression of FOXM1 is a potential prognostic marker in male breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-19-03.

Fractional allelic loss in non-end-stage cirrhosis: correlations with hepatocellular carcinoma development during follow-up.

Hepatocellular carcinoma (HCC) is usually preceded by cirrhosis whose genetic background is still poorly understood. The aim of this study was to evaluate, in non-end-stage cirrhosis, the fractional allelic loss (FAL) at loci mostly reported to be altered in HCC and the microsatellite instability (MSI). Twenty cases of cirrhosis were retrospectively selected. Eleven had developed an HCC during the follow-up (HCC-prone group), while 9 remained HCC-free (HCC-free group). Microdissected hepatocellular cirrhotic nodules from basal liver biopsies, were studied at 20 loci (on the chromosomal arms 1p and 1q, 3p, 4q, 6q, 7q, 8p, 13q, and 18q) and with the mononucleotide repeats BAT26 and TGFbIIR. Genetic changes were detected in both groups. Overall, the FAL index was statistically increased in the HCC-prone group (0.213) as compared to the HCC-free group (0.094; P =.044). Allelic loss at chromosomal arms 1p, 4q, 13q, 18q, and concurrent losses at more than 3 loci were confined to the HCC-prone group. In both groups, MSI was never ascertained using BAT26 and TGFbIIR. In conclusion, an increased FAL index and the lack of MSI characterize the non-end-stage cirrhosis of patients undergoing HCC during follow-up. These data emphasize the role of early clonal changes in chronic liver disease, and their potential predictive significance for clinical use.

Lasers in endoscopic surgery.

Lasers provide the endoscopic surgeon with a sophisticated tool for high precision cutting, destruction of tissue and coagulation. The laser allows efficient and time-saving operating techniques. Various laser systems emitting at different wavelengths are available. The absorption of the laser is determined by the tissue properties, such as water content or pigmentation, and varies strongly with the wavelength. Each laser offers advantages for the treatment of specific disorders. Further data from clinical studies are required to evaluate whether the advantages found in experimental studies are of significance in clinical use.