Oral Toxicities Associated with Immune Checkpoint Inhibitors: Meta-Analyses of Clinical Trials.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, their oral toxicity profile is not well elucidated. This review aimed to investigate the prevalence of oral toxicities including xerostomia, mucositis/stomatitis, dysgeusia, dysphagia, oral/oropharyngeal pain, oral infections, angular cheilitis, osteonecrosis, osteomyelitis, and oral mucosal reactions with ICIs. A review protocol was registered with PROSPERO (ID: CRD42023391674). A systematic search of ClinicalTrials.gov was conducted as of April 10, 2022. Studies were selected, assessed, and data extracted using PRISMA guidelines. Oral toxicity data were extracted from study arms using a single immunotherapy drug. Meta-analyses were conducted to summarize prevalence of oral toxicities using random-effects models. Of 750 screened records, 95 trials were included in the meta-analysis with published results. Time between study completion and first publication on ClinicalTrials.gov was 1 to 146 months (mean = 20.3, SD = 18.4). Weighted pooled prevalence was 5% (95% CI: 4-6%) for xerostomia, 3% (95% CI: 3-4%) for mucositis/stomatitis, 3% (95% CI: 2-3%) for dysgeusia, 2% (95% CI: 1-2%) for dysphagia, 3% (95% CI: 2-4%) for oropharyngeal/oral pain, 2% (95% CI: 1-3%) for oral candidiasis, and 2% (95% CI: 0-4%) for angular cheilitis. Subgroup differences based on ICI drugs were minimal. No trials reported lichenoid or pemphigoid mucosal reactions. Meta-analysis results revealed low prevalence of oral toxicities with ICIs; however, data reporting was limited and inconsistent. Limitations of study dataset reveal a significant need for systematic collection of oral morbidity data as well as improved consistency and compliance of reporting results on ClinicalTrials.gov.

A fine tuning of embryo loading technique by eliminating the air bubble in the outer sheath of embryo catheter among women undergoing IVF treatment.

OBJECTIVES: The role of air bubbles in bracketing the embryo-containing medium in inner catheter during embryo transfer (ET) has already been established. However, the role of air bubbles in outer catheter (OC) during implantation is yet to be determined. This study aimed to compare the implantation rates between women who have undergone ET with or without ASP (Vitrolife®; Sweden), a medium use for oocyte retrieval and rinsing in OC embryo catheter. The purpose of introducing the ASP medium to the OC was to eliminate air bubbles in that space during implantation. METHODS: A total of 312 women were randomly divided into two groups with 156 participants each group. In Group A, ASP medium was used during ET, whereas in Group B, no ASP medium was utilized. Positive implantation was defined as serum beta-hCG level >5 mIU/mL taken on the 7th day following ET. RESULTS: The average age of the majority of the participants was 30-39 years and had at least 4-5 years of subfertility. The unexplained subfertility was the prominent cause of ET failure in both groups. In most of the participants in both groups, ET was done using fresh embryo cycles with good to excellent embryo grades. After the ASP medium was manipulated in the OC in both groups, the positive implantation rate was not different in both groups (p>0.05). CONCLUSIONS: The elimination of air bubbles in OC by using the ASP medium during ET did not confer an additional benefit nor exert a negative impact on implantation rate.

Oocyte or embryo number needed to optimize live birth and cumulative live birth rates in mild stimulation IVF cycles.

RESEARCH QUESTION: How many oocytes or embryos are needed to optimize the live birth rate (LBR) per cycle and cumulative LBR (CLBR) following mild stimulation IVF (MS-IVF) in women with uncompromised ovarian reserve? DESIGN: Retrospective analysis of a 4-year database of five fertility centres. The study population included women with normal/high ovarian reserve, who underwent autologous MS-IVF (daily ≤150 IU gonadotrophin) with fresh and subsequent frozen embryo transfer(s) (FET) from surplus embryos. Only the first cycle of each patient was included. Cycles with >150 IU daily average of gonadotrophin were excluded. 'Freeze-all embryo' (FAE) cycles were analysed separately. RESULTS: A total of 862 consecutive cycles fulfilled the inclusion criteria; 592 were eligible for fresh embryo transfer, 239 had non-elective 'freeze-all' cycles. Median age (25-75th percentile) of women who had fresh embryo transfer was 35 (32-37) years, median antral follicle count 19 (14-28) and anti-Müllerian hormone 19.2 (13-28.9) pmol/l. LBR/fresh cycle and CLBR inclusive of FAE cycles in the <35, 35-37, 38-39 and 40-42 year age groups were 37.8% and 45.1%, 36.0% and 41.6%, 18.4% and 29.1%, and 8.9% and 18.1%, respectively. The LBR following fresh embryo transfer plateaued after nine oocytes (40.3%) or four embryos (40.8%). The CLBR optimized when 12 oocytes (42.9%) or nine embryos (53.8%) were obtained. The LBR per oocyte peaked in women under 35 years when <5 oocytes were retrieved (11.4%), then declined with age and with higher oocyte yield. There were no cases of severe ovarian hyperstimulation syndrome (OHSS). CONCLUSION: Nine oocytes, or four embryos, can optimize fresh transfer cycle LBR in MS-IVF. The CLBR are optimized with 12 oocytes, or nine embryos in predicted normal responders, while safeguarding against OHSS.

Effect of Plyometric Training on Speed and Change of Direction Ability in Elite Field Hockey Players.

This study investigated the effects of two plyometric training protocols on sprint and change of direction (COD) performance in elite hockey players. A parallel-group randomized controlled trial design was used and seventeen elite male and female field hockey players were randomly allocated into either low-to-high (L-H, n = 8) or high-to-low (H-L, n = 9) training groups. Each group performed separate variations of the drop jump exercise twice weekly for six weeks, with an emphasis on either jump height (L-H) or drop height (H-L). Performance variables assessed included sprint times over 10 m and 20 m, as well as 505 time. A two-way repeated measures analysis of variance was performed and Cohen's d effect sizes (ESs) were calculated. The H-L group displayed a significant small ES improvement from baseline to post-training in the 10 m sprint (1.893 ± 0.08 s pre vs. 1.851 ± 0.06 s post) (ES = -0.44) (p < 0.05). Differences between groups for 10 m and 20 m sprint performance failed to reach statistical significance, and no significant differences were observed within or between groups for 505 time. These findings highlight the difficulty in substantially enhancing speed and COD ability in highly trained athletic populations through the addition of a low volume, short duration plyometric training protocol.