Interferon beta-1b retinopathy during a treatment for multiple sclerosis

Ocular adverse effects of interferon are described during the treatment of malignant diseases and chronic viral hepatitis with interferon alpha. At this time, there is no report of these effects during multiple sclerosis treatment with interferon beta-1b. The authors report a bilateral retinopathy during this treatment. The production of neutralizing antibodies during interferon beta-1b treatment leads to a decrease in diminution of therapeutic efficacy. When treatment failure occurs, neutralizing antibodies are to be tested.     

Birdshot chorioretinopathy associated with tamoxifen retinal toxicity

We report a case of Birdshot retinochoroidopathy associated with ocular toxicity due to tamoxifen. Adverse drug effects were suspected due to the presence of yellow-white dots in the paramacular region and the fovea and by modifications of the retinal epithelial pigments. Ocular toxicity should be suspected as it may be reversible if recognized and stopped early. Other adverse ocular effects are described and the pathogenic mechanism of tamoxifen retinopathy analyzed.     

Clinical study of vertical dimension before and after orthodontic treatment in a Class II population]

The authors tried to highlight orthodontics only or mixed "orthopedics + orthodontics" repercussions about vertical dimensions while comparing the measurements before and after treatment done on teleradiographies of profile of 30 hyperdivergent and hypodivergent patients with skeletal class II. The clinical conclusions have been drawn after discussion of the results.     

Unraveling most abundant mutational signatures in head and neck cancer

Genomic alterations are a driving force in the multistep process of head and neck cancer (HNC) and result from the interaction of exogenous environmental exposures and endogenous cellular processes. Each of these processes leaves a characteristic pattern of mutations on the tumor genome providing the unique opportunity to decipher specific signatures of mutational processes operative during HNC pathogenesis and to address their prognostic value. Computational analysis of whole exome sequencing data of the HIPO‐HNC (Heidelberg Center for Personalized Oncology‐head and neck cancer) (n = 83) and TCGA‐HNSC (The Cancer Genome Atlas‐Head and Neck Squamous Cell Carcinoma) (n = 506) cohorts revealed five common mutational signatures (Catalogue of Somatic Mutations in Cancer [COSMIC] Signatures 1, 2, 3, 13 and 16) and demonstrated their significant association with etiological risk factors (tobacco, alcohol and HPV16). Unsupervised hierarchical clustering identified four clusters (A, B, C1 and C2) of which Subcluster C2 was enriched for cases with a higher frequency of signature 16 mutations. Tumors of Subcluster C2 had significantly lower p16^INK4A expression accompanied by homozygous CDKN2A deletion in almost one half of cases. Survival analysis revealed an unfavorable prognosis for patients with tumors characterized by a higher mutation burden attributed to signature 16 as well as cases in Subcluster C2. Finally, a LASSO‐Cox regression model was applied to prioritize clinically relevant signatures and to establish a prognostic risk score for head and neck squamous cell carcinoma patients. In conclusion, our study provides a proof of concept that computational analysis of somatic mutational signatures is not only a powerful tool to decipher environmental and intrinsic processes in the pathogenesis of HNC, but could also pave the way to establish reliable prognostic patterns.     

Experimental IGF-I receptor deficiency generates a sexually dimorphic pattern of organ-specific growth deficits in mice, affecting fat tissue in particular

Reduced IGF type I receptor levels diminish postnatal growth rate and adult body weight in mice. Here, we studied the impact of experimental IGF receptor deficiency on tissue-specific growth by Cre-lox-mediated dosage of a floxed IGF-IR gene. We generated mice with a wide spectrum of receptor deficiency (5-82%), and separated them into two groups with either strong (> or =50%) IGF-IR deficiency (XS mice) or moderate deficiency (<50%, M mice). The growth of XS mice was significantly retarded from 3 wk after birth onward, with respect to M littermates. This effect was twice as strong in males as in females. Growth deficits persisted throughout adult life, and at 10-12 months, most organs and tissues showed specific weight defects. Skin, bone and connective tissue, muscle, spleen, heart, lung, and brain were the most severely affected organs in the XS males. With the exception of muscle and spleen, the same tissues were also significantly reduced in size in females, although to a lesser extent. The most severe growth defect, however, concerned adipose tissue. Fat pad size in XS males was only 29% (females, 44%) of M mice. The estimated number of adipocytes in XS male fat pads was only 21% that of M males (XS female, 27%). Lipid content per cell was significantly higher in XS adipocytes, whereas plasma glucose and insulin levels were low in XS males. Thus, IGF type I receptor deficiency produced mice with disproportionate postnatal organ growth, and these effects depended strongly on sex. A marked reduction in IGF-IR levels resulted in a major defect in adipose tissue.     

A Specific High-Protein Weight Loss Program Does Not Impair Renal Function in Patients Who Are Overweight/Obese

Although high-protein diets appear to be the most efficient way to lose weight, concerns may arise about their innocuity on renal function. The objective of this study is to assess the impact of a weight loss program on renal function. A multicentric cohort-based study was performed using the RNPC© French national weight loss program. Patients with at least two creatinine measurements at the beginning of the program and at the end of the weight loss phase between 1 January 2016 and 1 July 2021 were included. Renal function was assessed by Modification of Diet in Renal Disease (MDRD) equation-based estimated glomerular filtration rate (eGFR). From 4394 patients with two creatinine measurements included, 1579 (35.9%) had normal eGFR (MDRD 90–120 mL/min/1.73 m²), 210 (4.8%) had hyperfiltration (MDRD > 120 mL/min/1.73 m²), 2383 (54.2%) had chronic kidney disease (CKD) grade 2 (MDRD 60–90 mL/min/1.73 m²), and 221 (5.0%) had CKD grade 3 (MDRD 30–60 mL/min/1.73 m²). Multivariable analyses showed no eGFR change for patients in initial CKD grade 2, normal eGFR and hyperfiltration, and a significant increase in CKD grade 3. The RNPC© program avoids renal function impairment during the two first phases, regardless of the initial eGFR.