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The aim of this study was to validate an HPLC-UV method to assess vitamin D status by determining the linearity and precision of the 25-hydroxyvitamin D 3 (25(OH)D 3 ) calibration curve, the limits of detection, quantitation and robustness of the method, and its accuracy. A second stock solution of 25(OH)D 3 was prepared (500 ng/mL), and working dilutions (5, 10, 20, 30, 40, and 50 ng/mL) were prepared for a calibration curve. The HPLC equipment had a UV-Vis diode-array detector and utilized an Acclaim TM 120 C18 column (5 µm, 4.6 × 250 mm) with a flow rate of 1.2 mL/min, a column temperature of 30 °C, and the standards and samples were maintained at 4 °C, with an injection volume of 100 µL. Detection of 25(OH)D 3 was determined at 265 nm, with a retention time of 4.0 min. The validation was conducted according to the FDA Validation of Analytical Procedures: Guidance for Industry. Vitamin D was extracted from plasma samples using acetonitrile (ACN)-0.1% formic acid (2:1 v / v ), and the percentage of recovery was calculated. The proposed method conditions gave excellent linearity (R 2 = 0.9989) and the linearity coefficient was R 2 > 0.99 for 25(OH)D 3 . The detection and quantification limits were 1.1703 ng/mL and 3.5462 ng/mL, respectively. Decreasing or increasing the reading temperature by 1 °C decreased the response units (AU) of vitamin D, 25(OH)D 3 . When the current flow rate decreased by 0.2 mL/min (1.0 mL/min), the retention time increased to 4.913 min, whereas an increase of 0.2 mL/min of the proposed flow rate (1.4 mL/min) decreased the retention time to 3.500 min. The percentage of recovery varied from 92.2% to 97.1%. The proposed method to quantify a vitamin D metabolite (25(OH)D 3 ) in human plasma samples was reliable and validated.

Background: This phase 1 study evaluated PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in two clinical states of prostate cancer (PC), metastatic castration-resistant PC (mCRPC) and biochemical recurrence (BCR)., Methods: For dose escalation, patients with mCRPC received intramuscular PrCa VBIR (adenovirus vector and plasmid DNA expressing prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA), and prostate stem cell antigen (PSCA)) with or without immune checkpoint inhibitors (ICIs, tremelimumab 40 or 80 mg with or without sasanlimab 130 or 300 mg, both subcutaneous). For dose expansion, patients with mCRPC received recommended phase 2 dose (RP2D) of PrCa VBIR plus tremelimumab 80 mg and sasanlimab 300 mg; patients with BCR received PrCa VBIR plus tremelimumab 80 mg (Cohort 1B-BCR) or tremelimumab 80 mg plus sasanlimab 130 mg (Cohort 5B-BCR) without androgen deprivation therapy (ADT). The primary endpoint was safety., Results: Ninety-one patients were treated in dose escalation (mCRPC=38) and expansion (BCR=35, mCRPC=18). Overall, treatment-related and immune-related adverse events occurred in 64 (70.3%) and 39 (42.9%) patients, with fatigue (40.7%), influenza-like illness (30.8%), diarrhea (23.1%), and immune-related thyroid dysfunction (19.8%) and rash (15.4%), as the most common. In patients with mCRPC, the objective response rate (ORR, 95% CI) was 5.6% (1.2% to 15.4%) and the median radiographic progression-free survival (rPFS) was 5.6 (3.5 to not estimable) months for all; the ORR was 16.7% (3.6% to 41.4%) and 6-month rPFS rate was 45.5% (24.9% to 64.1%) for those who received RP2D with measurable disease (n=18). 7.4% of patients with mCRPC achieved a ≥50% decline in baseline PSA (PSA-50), with a median duration of 4.6 (1.2-45.2) months. In patients with BCR, 9 (25.7%) achieved PSA-50; the median duration of PSA response was 3.9 (1.9-4.2) and 10.1 (6.9-28.8) months for Cohorts 5B-BCR and 1B-BCR. Overall, antigen specific T-cell response was 88.0% to PSMA, 84.0% to PSA, and 80.0% to PSCA., Conclusions: PrCa VBIR overall demonstrated safety signals similar to other ICI combination trials; significant side effects were seen in some patients with BCR. It stimulated antigen-specific immunity across all cohorts and resulted in modest antitumor activity in patients with BCR without using ADT., Trial Registration Number: NCT02616185., Competing Interests: Competing interests: This work was sponsored by Pfizer. KAA: PI/research funding to institution: Amgen, AstraZeneca, CytomX, Eli Lilly and Company, GlaxoSmithKline, Parker Institute for Cancer Immunotherapy, Pfizer, Trishula. CSH: consulting fees: Astellas, AstraZeneca, Bayer, Blue Earth Diagnostics, Carrick Therapeutics, Clovis Oncology, Ferring Pharmaceuticals, Genentech, Hinova, Janssen, Menarini, Merck Sharp & Dohme, Myovant Sciences, Novartis, Pfizer; contracted research support: Aragon Pharmaceuticals, Astellas, AstraZeneca, Bayer, Clovis Oncology, eFFECTOR Therapeutics, Emergent BioSolutions, Ferring Pharmaceuticals, Medivation, Roche; ownership interest: CTI BioPharma; honoraria: Astellas. LN and X-HZ: nothing to disclose. LJA: consulting or advisory role: AADi; research funding (institution as recipient): Amgen, Astellas, Aveo, Bayer, BioNTech, Bristol Myers Squibb, Calithera Biosciences, Eisai, Eli Lilly and Company, Epizyme, Exelixis, Genentech/Roche, Inovio, Merck, Novartis, Peloton Therapeutics, Pfizer, Seattle Genetics, Surface Oncology; other relationship: Pfizer; uncompensated relationships: Exelixis. TZ: PI/research funding: AbbVie/StemCentrx, Acerta, Astellas, AstraZeneca, Eli Lilly and Company, Janssen, Merck, Merrimack, Mirati Therapeutics, Novartis, OmniSeq, Personal Genome Diagnostics, Pfizer, Regeneron; speaker: Genomic Health (end 2020), Sanofi-Aventis (end 2020); advisory board/consultant: Amgen, Aptitude Health, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera Biosciences, Clinical Care Options, Dendreon, Eisai, Eli Lilly and Company, Exelixis, Janssen, Merck, MJH Associates, Peerview, Pfizer, Pharmacyclics, QED Therapeutics, Sanofi-Aventis, Seattle Genetics, Vaniam; employee/stockholder: Archimmune Therapeutics (spouse), Capio Biosciences (spouse), Nanorobotics (spouse). HB: consultancy: Caris, Idera, Myovant, Novocure, Tracon; speaker’s bureau: Guardant360. NJV: PI/research funding: none; advisory boards: Caris, Clovis, Eisai, Fujifilm, Gilead Sciences, Merck, OnQuality Pharmaceuticals, Pfizer-Myovant, Sanofi-Aventis, Seagen; speaker’s bureau: Aveo, Bayer, Caris, Janssen, PER, Pfizer-Myovant, Sanofi, Seagen. SMP: PI funding: Janssen, Merck, Pfizer, UroGen Pharma. MTS: paid consultant and/or received honoraria: AstraZeneca, PharmaIn, Resverlogix, Sanofi; research funding to institution: Ambrx, AstraZeneca, Bristol Myers Squibb, F. Hoffman-La Roche, Immunomedics, Janssen, Madison Vaccines, Merck, Pfizer, SignalOne Bio, Tmunity, Zenith Epigenetics. RAM: research funding: Bayer. SB, NC, OB, RL, MK, I-MW, JZ, S-YT, and KAK: employees of Pfizer with stock and/or stock options. KC, HC, and RH: employees of Pfizer at the time of the study. DPP: stock and other ownership interests: Bellicum Pharmaceuticals, TYME Technologies; consulting or advisory role: Advanced Accelerator Applications, Amgen, Astellas, AstraZeneca, Bayer, Bicycle Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Eli Lilly and Company, Exelixis, Gilead Sciences, Incyte, Ipsen, Janssen, Mirati Therapeutics, Monopteros Therapeutics, Pfizer, Pharmacyclics, Regeneron, Roche, Seattle Genetics, UroGen Pharma; research funding: Advanced Accelerator Applications (Inst), Agensys (Inst), Astellas Medivation (Inst), AstraZeneca (Inst), Bayer (Inst), BioXcel Therapeutics (Inst), Bristol Myers Squibb (Inst), Clovis Oncology (Inst), Eisai (Inst), Endocyte (Inst), Eli Lilly and Company (Inst), Genentech (Inst), Gilead Sciences (Inst), Innocrin Pharma (Inst), MedImmune (Inst), Medivation (Inst), Merck (Inst), Mirati Therapeutics (Inst), Novartis (Inst), Pfizer (Inst), Progenics (Inst), Replimune (Inst), Roche (Inst), Sanofi (Inst), Seattle Genetics (Inst); expert testimony: Celgene, Sanofi., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction COVID-19 is an emerging disease and the neurotologic symptoms are still not well understood. Furthermore, the development of a neurotological profile and its associated factors can help the clinician in the diagnosis and treatment of this disease. The objective is to determine the neurotologic manifestations experienced by COVID-19 positive health care workers and their associated factors. Methods A symptoms survey was administered to health care workers who were positive to COVID-19 from September to October 2020. An informed consent form was digitally signed and Google Forms software was used for the survey. Frequencies and percentages were used for categorical variables, and associated clinical features were reported with odds ratios. Results We included 209 COVID-19 positive health care workers, 55.5% (n = 116) were women, and 44.5% (n = 93) were men. Fifty-three percent of patients were 20 to 30 years old and 56.4% had at least one comorbidity. The prevalence of neurotological manifestations was 18.6% (n = 39/209), the most frequent symptoms were vertigo (61.5%, n = 24/39), tinnitus (43.5%, n = 17/39), imbalance (43.5%, n = 17/39), and one case of facial paralysis (2.5%, n = 1/39). Neurotological manifestations were associated predominantly with asthenia ( p = 0.021), loss of smell ( p = 0.002) and taste dysfunction ( p = 0.002). Conclusion The most common neurotological manifestations were vertigo, tinnitus and imbalance. Clinical features associated with a neurotologic profile were asthenia, hyposmia and dysgeusia., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Espinoza-Valdez et al.)

Ibrutinib is highly active in treating mantle cell lymphoma (MCL), an aggressive B-cell lymphoma. We pooled data from three ibrutinib studies to explore the impact of baseline patient characteristics on treatment response. Patients with relapsed/refractory MCL (n = 370) treated with ibrutinib had an objective response rate (ORR) of 66% (20% complete response; 46% partial response); median duration of response (DOR), progression-free survival (PFS) and overall survival (OS) were 18·6, 12·8 and 25·0 months, respectively. Univariate analyses showed patients with one versus >one prior line of therapy had longer OS. Multivariate analyses identified that one prior line of therapy affected PFS; Eastern Cooperative Oncology Group (ECOG) performance status, simplified MCL international prognostic index (sMIPI) score, bulky disease, and blastoid histology affected OS and PFS. Patients with blastoid versus non-blastoid histology had similar time to best response, but lower ORR, DOR, PFS and OS. OS and PFS were longer in patients with better sMIPI, patients with ECOG performance status 0-1, non-bulky disease and non-blastoid histology. Additionally, the proportion of patients with poor prognostic factors increased with increasing lines of therapy. Together, results suggest that patient outcomes following treatment failure with ibrutinib are related to the natural biological evolution of the disease., (© 2017 John Wiley & Sons Ltd.)

Background: An inverse relationship between serum prostate specific antigen (PSA) levels and body mass index (BMI) has been reported in men but not in any animal model., Methods: Serum PSA in a colony of cynomolgus monkeys was assayed and correlated to body weight, prostate weight, and age. In addition, 15 animals were selected and fed a high sugar high fat (HSHF) diet for 49 weeks to increase their BMI and correlate it to PSA RESULTS: Serum PSA levels were positively correlated to prostate weight (r = 0.515, P = 0.025) and age (r = 0.548, P = 0.00072) but was not significantly correlated to body weight (r = -0.032, P = 0.419). For the animals on the HSHF diet, body weight, lean mass, fat mass, and BMI were significantly higher at 49 weeks than at baseline (P < 0.01). PSA was not significantly correlated to body weight and insulin at both baseline and 49 weeks. PSA was negatively correlated to BMI and insulin resistance (HOMA-IR) at 49 weeks but not at baseline. In addition, we observed hepatic steatosis and increases in serum liver enzymes., Conclusions: Increases in BMI in cynomolgus monkeys as a result of consuming a HSHF diet resulted in PSA changes similar to those in humans with increased BMI. Cynomolgus monkeys are a useful model for investigating the relationship between obesity, diabetes, and PSA changes resulting from prostate gland pathology., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: Androgen receptor [CAG](n) microsatellite has been linked to human diseases., Methods: Six non-human primates were genotyped for the [CAG](n) microsatellite., Results: Marmosets and macaques are monomorphic, while mangabeys, baboons, and chimpanzees are polymorphic., Conclusions: Non-human primates that are polymorphic for the microsatellite are candidate animal models for CAG-related diseases., (© 2011 John Wiley & Sons A/S.)