Notes

Rational style of ASCT2 inhibitors employing an included experimental-computational approach.
Immune checkpoint inhibitor (ICPis) re-challenge could be an attractive therapeutic option considering its good safety profile. However, little data is available regarding anti-PD-1/anti-PD-L1 retreatment. We conducted a meta-analysis focusing on outcomes of solid cancer patients performing this strategy.

Fourteen full papers involving 74 patients were included. Individual data about best response or progression-free survival (PFS) upon the first and second course of anti-PD-1/anti-PD-L1 were collected.

Non-small-cell lung cancer (53%) and melanoma (34%) were the most represented cancers. Higher objective response (46% versus 24%, P=4.10
) and disease control rates (73% versus 52%, P=7.10
) were obtained upon the first ICPi course compared to re-challenge. No association between responses obtained with the two ICPis courses was found (P=3.10
). The PFS upon the first ICPi (PFS1) was longer than after re-challenge (PFSR) (6.6 versus 2.8 months, hazard ratio (HR) 0.57, P=2.10
). A longer PFSR was obtained in patients with a longer PFS1 (P=6.10
), in those who discontinued the first ICPi due to toxicity or per protocol (8.8 versus 2.1 months if disease progression occurs, P=2.10
), and in those not receiving intercalated treatment between the two ICPis (6.6 versus 2.1 months for the treated ones, P=1.10
).

Anti-PD-1/anti-PD-L1 re-challenge showed interesting clinical activity in selected patients, mainly in those achieving a long-term response upon the first ICPi course, that do not discontinue therapy because of disease progression, or that are able to keep a treatment-free period.
Anti-PD-1/anti-PD-L1 re-challenge showed interesting clinical activity in selected patients, mainly in those achieving a long-term response upon the first ICPi course, that do not discontinue therapy because of disease progression, or that are able to keep a treatment-free period.
To evaluate the effect of testosterone treatment on metabolic and inflammation parameters and leukocyte-endothelium interactions in transgender men (TGM).

Prospective observational study.

University hospital.

One hundred fifty-seven TGM.

Administration of testosterone undecanoate (1,000 mg, intramuscular) every 12 weeks.

Endocrine parameters, adhesion molecules (vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, and E-selectin), proinflammatory cytokines interleukin-6, and tumor necrosis factor alpha were evaluated in serum before and after treatment using Luminex's xMAP technology. In addition, interactions between human umbilical vein endothelial cells and polymorphonuclear leukocytes were assessed by flow chamber microscopy.

Testosterone treatment led to an increase in leukocyte-endothelium interactions due to an increase in polymorphonuclear leukocytes rolling and adhesion and decreased rolling velocity. It also boosted levels of vascular cell adhesion molecule-1, E-selectin, interleukin-6, and tumor necrosis factor alpha. As expected, testosterone also produced a significant increase in free androgenic index, androstenedione, total testosterone, and atherogenic index of plasma and a decrease in sex hormone-binding globulin and high-density lipoprotein cholesterol.

Treatment of TGM with testosterone induces an increase in leukocyte-endothelium interactions and adhesion molecules and proinflammatory cytokines. These effects are a reason to monitor cardiovascular risk in these patients.
Treatment of TGM with testosterone induces an increase in leukocyte-endothelium interactions and adhesion molecules and proinflammatory cytokines. These effects are a reason to monitor cardiovascular risk in these patients.
Contradictory results have been reported about hyperintensity of the globus pallidus and/or dentate nucleus on unenhanced T1-weighted magnetic resonance (MR) images after exposure to various gadolinium-based contrast agents. This change in signal intensity varies with different gadolinium-based contrast agents. We aimed to determine whether signal intensity in the dentate nucleus is increased in unenhanced T1-weighted images in patients who have undergone multiple studies with the macrocyclic gadolinium-based contrast agent gadoterate meglumine. We thoroughly reviewed the literature to corroborate our results.

We included patients who had undergone more than 10 MR studies with gadoterate meglumine. We quantitatively analyzed the signal intensity in unenhanced T1-weighted MR images measured in regions of interest placed in the dentate nucleus and the pons, and we calculated the dentate nucleus-to-pons signal intensity ratios and the differences between the ratio in the first MR study and the last MR study.P=0.9064; ρ=-0.0164 [95%]).

Receiving more than 10 doses of gadoterate meglumine was not associated with increased signal intensity in the dentate nucleus.
Receiving more than 10 doses of gadoterate meglumine was not associated with increased signal intensity in the dentate nucleus.Adenoid basal cell carcinoma (ABC) is considered a rare cervical neoplasm which when present in 'pure' form, uniquely amongst apparently malignant cervical tumours, has never been reported to metastasise or lead to fatal patient outcome. We recently encountered a case of ABC that was morphologically reminiscent of prostatic differentiation, more specifically basal cell hyperplasia of the prostate. Immunohistochemistry was strongly positive for the prostate related marker NKX3.1 in the glandular cells, but there was no expression of prostate specific antigen (PSA) or prostatic acid phosphatase (PAP). Cell Cycle inhibitor However, subsequent review of five additional cervical ABCs demonstrated focal PAP expression in two of four tested cases, and all were NKX3.1 positive. NKX3.1 expression was also demonstrated in the glandular epithelium of 10 additional gynaecological lesions considered to show prostatic differentiation including five cases of cervical ectopic prostatic tissue, three ovarian teratomas with prostatic differentiation, and two vaginal tubulosquamous polyps. We suggest that some lesions traditionally classified as ABC may in fact represent a variant of prostatic differentiation within the cervix, possibly analogous to basal cell hyperplasia of the prostate.
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