Providing a post-vasectomy semen analysis cup at the time of vasectomy rather than post-operatively improves compliance.

Background: Post-vasectomy semen analysis (PVSA) completion rates after vasectomy are poor, and minimizing the need for an additional in-person visit may improve compliance. We hypothesized that providing PVSA specimen cup at time of vasectomy instead of at a postoperative appointment might be associated with higher PVSA completion rates. Methods: We performed a retrospective cohort study with historical control using medical records of all patients seen by a single provider for vasectomy consultation between October 2016 and June 2022. All patients who underwent vasectomy were included. Patients who underwent vasectomy prior to 05/01/2020 had PVSA specimen cup given at postoperative appointment two weeks following vasectomy, and those who underwent vasectomy after 05/01/2020 were given PVSA specimen cup at time of vasectomy. PVSA completion, demographic, and clinical outcomes data were collected. Logistic regressions were used to investigate associations between PVSA completion rates and timing of PVSA specimen cup provision. Results: There were no significant differences among study cohorts across all patient demographics analyzed, including age, body mass index (BMI), age of primary partner, presence of children, and history of prior genitourinary infection. A total of 491 patients were seen for vasectomy consultation between October 2016 and June 2022; among these patients, 370 underwent vasectomy. Of these, 173 (46.8%) patients underwent vasectomy prior to 05/01/2020 and were given PVSA specimen cup at postoperative visit; 197 (53.2%) patients underwent vasectomy after 05/01/2020 and were given PVSA specimen cup at vasectomy. Providing PVSA specimen cup at time of vasectomy was associated with higher odds of PVSA completion than providing PVSA specimen cup at postoperative visit [62.4% vs. 49.7%; odds ratio (OR) =1.68; 95% confidence interval (CI): 1.11, 2.55]. Adjusting for all identified confounders excludes 35 (9.5%) patients without a primary partner and shows no statistically significant association in cup timing [adjusted OR (aOR) =1.53; 95% CI: 0.98, 2.39]. Adjusting for all identified confounders except age of primary partner revealed timing of specimen cup provision at time of vasectomy was associated with higher odds of PVSA completion (aOR =1.64; 95% CI: 1.08, 2.52). Conclusions: PVSA specimen cup provision at time of vasectomy versus at postoperative appointment is associated with higher rates of PVSA completion in this retrospective cohort study.

Sphingosine 1-phosphate receptor 1 inhibition induces a pro-apoptotic signaling cascade in T cells.

Effective immunity requires a large, diverse naïve T cell repertoire circulating among lymphoid organs in search of antigen. Sphingosine 1-phosphate (S1P) and its receptor S1PR1 contribute by both directing T cell migration and supporting T cell survival. Here, we address how S1P enables T cell survival, and the implications for patients treated with S1PR1 antagonists. Contrary to expectations, we found that S1PR1 limits apoptosis by maintaining the appropriate balance of BCL2 family members via restraint of JNK activity. Interestingly, the same residues of S1PR1 that enable receptor internalization are required to prevent this pro-apoptotic cascade. Findings in mice were recapitulated in ulcerative colitis patients treated with the S1PR1 antagonist ozanimod, and the loss of naïve T cells limited B cell responses. Our findings highlight an unexpected effect of S1PR1 antagonists on the ability to mount immune responses within lymph nodes, beyond their effect on lymph node egress, and suggest both limitations and novel uses of this important class of drugs.

Inhibition of Nuclear Pore Complex Formation Selectively Induces Cancer Cell Death.

Nuclear pore complexes (NPC) are the central mediators of nucleocytoplasmic transport. Increasing evidence shows that many cancer cells have increased numbers of NPCs and become addicted to the nuclear transport machinery. How reducing NPC numbers affects the physiology of normal and cancer cells and whether it could be exploited for cancer therapies has not been investigated. We report that inhibition of NPC formation, a process mostly restricted to proliferating cells, causes selective cancer cell death, prevents tumor growth, and induces tumor regression. Although cancer cells die in response to NPC assembly inhibition, normal cells undergo a reversible cell-cycle arrest that allows them to survive. Mechanistically, reducing NPC numbers results in multiple alterations contributing to cancer cell death, including abnormalities in nuclear transport, catastrophic alterations in gene expression, and the selective accumulation of DNA damage. Our findings uncover the NPC formation process as a novel targetable pathway in cancer cells. SIGNIFICANCE: Reducing NPC numbers in cancer cells induces death, prevents tumor growth, and results in tumor regression. Conversely, normal cells undergo a reversible cell-cycle arrest in response to inhibition of NPC assembly. These findings expose the potential of targeting NPC formation in cancer.This article is highlighted in the In This Issue feature, p. 1.