Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 study): an open-label, nonrandomized, multicenter, phase II trial.

BACKGROUND: Pembrolizumab demonstrated clinically meaningful and durable antitumor activity with a manageable safety profile in recurrent/metastatic (R/M) cutaneous squamous cell carcinoma (cSCC). PATIENTS AND METHODS: KEYNOTE-629 was a global, open-label, nonrandomized, phase II trial of patients with locally advanced (LA) or R/M cSCC conducted at 59 centers. Eligible patients received intravenous pembrolizumab 200 mg every 3 weeks for up to 35 cycles. Primary endpoint was objective response rate (ORR), defined as the percentage of patients with a complete (CR) or partial response (PR), by blinded independent central review as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints included duration of response (DOR), disease control rate, progression-free survival, overall survival, and safety and tolerability. Efficacy and safety were analyzed in patients who were treated with at least one dose of pembrolizumab. RESULTS: Between 29 November 2017 and 25 September 2019, 159 patients were enrolled and treated with pembrolizumab (LA cohort, n = 54; R/M cohort, n = 105). The median time from the first dose to data cut-off date (29 July 2020) was 14.9 [interquartile range (IQR), 12.6-17.2] months for the LA cohort and 27.2 (IQR, 25.6-29.2) months for the R/M cohort. In the LA cohort, ORR was 50.0% [95% confidence interval (CI), 36.1% to 63.9%], including 16.7% of patients with a CR and 33.3% with a PR. In the R/M cohort, ORR was 35.2% (95% CI, 26.2% to 45.2%), including 10.5% of patients with a CR and 24.8% with a PR. Median DOR was not reached in either cohort. Grade 3-5 treatment-related adverse events occurred in 11.9% of patients. CONCLUSIONS: The robust antitumor activity of pembrolizumab in both LA and R/M cSCC was confirmed and demonstrated to be durable without unexpected safety signals. Our findings establish pembrolizumab as a promising treatment option for cSCC.

Glutathione S-transferase Mu-1 gene polymorphism in Egyptian patients with idiopathic male infertility.

The aim of this study was to examine whether an association exists between glutathione S-transferase Mu-1 (GSTM1) gene polymorphism and idiopathic male infertility. Sixty men with primary idiopathic infertility and 60 fertile men, serving as controls, were recruited for the study. The polymorphism was analysed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The frequency of GSTM1 null genotype was observed to be higher in infertile men 40% in comparison with 33.3% in the fertile men, but this difference was not statistically significant. There was statistically significant difference between cases and controls as regards GSTM1 genotype distribution ((MC) P = 0.006*) in GSTM1-positive men. Patients with the GSTM1 null genotype had significantly lower sperm concentrations and total sperm count when compared with patients with GSTM1-positive genotype. In the control group, men with GSTM1 null genotype had significantly lower sperm concentrations but not total sperm count when compared with men with GSTM1-positive genotype. The results of this study suggest a possible negative effect of GSTM1 null genotype on the spermatogenic potential of the testis.

Stromal vascular fraction improves the durability of autologous fat temple augmentation-A split-face randomized study using ultrasound biomicroscopy.

BACKGROUND: Autologous lipotransfer aims to restore aging-associated volume loss, but with low predictability owing to 20-90% first-year loss of transferred fat. Enrichment by adipose-derived stem cells within the stromal vascular fraction (SVF) aims to improve volume retention through their differentiation potential and paracrine actions exerted by secreted trophic and angiogenic factors. Assessing studies lacked split-face designs, and used multitudes of enrichment ratios, preparation techniques and evaluation methods ending in contradictory reports regarding enrichment advantage. AIM: To test whether enriching the autologous fat graft with SVF will increase its residual volume as compared to non-enriched graft. A standardized enrichment protocol and ratio and objective assessment were employed. PATIENTS AND METHODS: In a split-face design, and after random assignment, bilateral temple augmentation using non-enriched versus SVF-enriched autologous lipotransfer were compared in middle-aged females otherwise healthy non-pregnant or breast-feeding females abstaining from esthetic or weight-controlling procedures. Temple volume scale (TVS), skin layers' thickness measured by ultrasound biomicroscopy (UBM), visual analog scale for patients' satisfaction, and side effects were blindly assessed at 1 week, 3 months, and 6 months. RESULTS: In the included 15 females, TVS was significantly lower (0.5 ± 0.5 versus 1.1 ± 0.7, P = 0.0001), and% hypodermal augmentation was significantly higher (70.92 ± 58.09 versus 18.93 ± 19.33, P = 0.001) on the SVF-enriched side at 6 months. Patient satisfaction was similar bilaterally (P = 1), as were sequelae frequencies as lumping, edema, and ecchymosis. CONCLUSION: SVF enrichment of transferred fat significantly improved its residual volume at 6 months; a conclusion that needs further validation. UBM was an informative objective tool for the following temple skin thickness changes. Trial registration clinical trials.gov (NCT03965936).

Incidence and mortality trends and geographic patterns of follicular lymphoma in Canada.

Background: Follicular lymphoma (fl) is the most common indolent lymphoma and the 2nd most common non-Hodgkin lymphoma, accounting for 10%-20% of all lymphomas in the Western world. Epidemiologic and geographic trends of fl in Canada have not been investigated. Our study's objective was to analyze incidence and mortality rates and the geographic distribution of fl patients in Canada for 1992-2010. Methods: Demographic and geographic patient data for fl cases were obtained using the Canadian Cancer Registry, the Registre québécois du cancer, and the Canadian Vital Statistics database. Incidence and mortality rates and 95% confidence intervals were calculated per year and per geographic area. Rates were plotted using linear regression models to assess trends over time. Overall data were mapped using Microsoft Excel mapping software (Redmond, WA, U.S.A.) to identify case clusters across Canada. Results: Approximately 22,625 patients were diagnosed with fl during 1992-2010. The age-standardized incidence rate of this malignancy in Canada was 38.3 cases per million individuals per year. Geographic analysis demonstrated that a number of Maritime provinces and Manitoba had the highest incidence rates, and that the provinces of Nova Scotia and Quebec had the highest mortality rates in the nation. Regional data demonstrated clustering of fl within cities or regions with high herbicide use, primary mining, and a strong manufacturing presence. Conclusions: Our study provides a comprehensive overview of the fl burden and its geographic distribution in Canada. Regional clustering of this disease in concentrated industrial zones strongly suggests that multiple environmental factors might play a crucial role in the development of this lymphoma.

Role of mast cells and T-lymphocytes in pemphigus vulgaris: significance of CD44 and the c-kit gene product (CD117).

Molecular mechanisms underlying the pathophysiology of pemphigus vulgaris are still not clear. We aimed to determine the significance of detecting expression of some antigens that might be pivotal to the process, namely CD44 and CD117, in patients with active pemphigus vulgaris. Seventeen patients with active pemphigus vulgaris and 19 normal healthy controls were included in the study. The immunohistochemical results showed prominent expression of CD44 in 13 of the patients and CD117 in 9 of the patients with new blister formation. CD44 percentage values in peripheral T-lymphocytes were significantly higher in patients than controls, as detected by flow cytometry. In addition, there was a significant increase in a soluble form of c-kit in sera of patients with active pemphigus vulgaris compared to controls.

Risk profiles for sexually transmitted diseases among patients attending the venereal disease clinic at Alexandria Main University Hospital.

Risk factors for sexually transmitted diseases (STDs) were assessed among 54 male and 36 female patients attending a venereal disease clinic. Sociodemographic data and information on sexual behaviour/STD history were collected. Patients were examined and specimens taken for laboratory diagnosis. Multivariate logistic regression analysis revealed that the significant predictors of genital infections among the male patients were: being unmarried, having multiple sexual partners, exposure to a symptomatic sexual partner, high frequency of intercourse per week, having repeated episode(s) of STDs and practising coitus interfemoris. In the female patients, exposure to a symptomatic sexual partner and high frequency of intercourse per week were the only significant predictors.

Role of mast cells and T-lymphocytes in pemphigus vulgaris: significance of CD44 and the c-kit gene product [CD117]

Molecular mechanisms underlying the pathophysiology of pemphigus vulgaris are still not clear. We aimed to determine the significance of detecting expression of some antigens that might be pivotal to the process, namely CD44 and CD117, in patients with active pemphigus vulgaris. Seventeen patients with active pemphigus vulgaris and 19 normal healthy controls were included in the study. The immunohistochemical results showed prominent expression of CD44 in 13 of the patients and CD117 in 9 of the patients with new blister formation. CD44 percentage values in peripheral T-lymphocytes were significantly higher in patients than controls, as detected by flow cytometry. In addition, there was a significant increase in a soluble form of c-kit in sera of patients with active pemphigus vulgaris compared to controls

Risk profiles for sexually transmitted diseases among patients attending the venereal disease clinic at Alexandria Main University Hospital

Risk factors for sexually transmitted diseases [STDs] were assessed among 54 male and 36 female patients attending a venereal disease clinic. Sociodemographic data and information on sexual behaviour/STD history were collected. Patients were examined and specimens taken for laboratory diagnosis. Multivariate logistic regression analysis revealed that the significant predictors of genital infections among the male patients were: being unmarried, having multiple sexual partners, exposure to a symptomatic sexual partner, high frequency of intercourse per week, having repeated episode[s] of STDs and practising coitus interfemoris. In the female patients, exposure to a symptomatic sexual partner and high frequency of intercourse per week were the only significant predictors