Intercellular Interactions of an Adipogenic CXCL12-Expressing Stromal Cell Subset in Murine Bone Marrow

Bone marrow houses a multifunctional stromal cell population expressing C-X-C motif chemokine ligand 12 (CXCL12), termed CXCL12-abundant reticular (CAR) cells, that regulates osteogenesis and adipogenesis. The quiescent pre-adipocyte-like subset of CXCL12⁺ stromal cells (“Adipo-CAR” cells) is localized to sinusoidal surfaces and particularly enriched for hematopoiesis-supporting cytokines. However, detailed characteristics of these CXCL12⁺ pre-adipocyte-like stromal cells and how they contribute to marrow adipogenesis remain largely unknown. Here we highlight CXCL12-dependent physical coupling with hematopoietic cells as a potential mechanism regulating the adipogenic potential of CXCL12⁺ stromal cells. Single-cell computational analyses of RNA velocity and cell signaling reveal that Adipo-CAR cells exuberantly communicate with hematopoietic cells through CXCL12-CXCR4 ligand-receptor interactions but do not interconvert with Osteo-CAR cells. Consistent with this computational prediction, a substantial fraction of Cxcl12-creER⁺ pre-adipocyte-like cells intertwines with hematopoietic cells in vivo and in single-cell preparation in a protease-sensitive manner. Deletion of CXCL12 in these cells using Col2a1-cre leads to a reduction of stromal-hematopoietic coupling and extensive marrow adipogenesis in adult bone marrow, which appears to involve direct conversion of CXCL12⁺ cells to lipid-laden marrow adipocytes without altering mesenchymal progenitor cell fates. Therefore, these findings suggest that CXCL12⁺ pre-adipocyte-like marrow stromal cells prevent their premature differentiation by maintaining physical coupling with hematopoietic cells in a CXCL12-dependent manner, highlighting a possible cell-non-autonomous mechanism that regulates marrow adipogenesis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Meditative and mind-body practice among patients with genitourinary malignancy

Introduction and objectiveResearch on the utility of meditative and mind-body (MB) practices has increased dramatically in the last two decades and both have been suggested as useful adjuncts in coping with stressors associated with cancer survivorship. There exists little data on use among genitourinary (GU) cancer survivors. This study seeks to describe meditative and MB utilization among GU cancer survivors.MethodsAnalysis of data from the 2012 and 2017 National Health Interview Survey was conducted. Patients aged 40 and older reporting a history of any cancer diagnosis (including 3 GU cancers) were included in the analysis. We explored questions about meditative and MB practices in the past 12 months. Complex Samples Logistic regression was performed to compare the relationship between cancer status and use of these practices.ResultsSelf-reported meditative practices were more prevalent in 2017 (17%) than in 2012 (5%). Patients who self-reported a cancer diagnosis of any kind were significantly more likely to utilize meditative practices. Patients with kidney cancer were significantly more likely to meditate and trended towards higher MB utilization. In contrast, bladder cancer patients were less likely to meditate and use MB practices. Increases in meditation were greater than those seen for MB in all groups.ConclusionsMeditative and MB practices increased in prevalence between 2012 and 2017 with notable heterogeneity between cancer types. Given the potential benefit, more broad incorporation into survivorship programs may be warranted. Future work should explore the significance of this heterogeneity and the utility of these practices to patients with urologic malignancy.     

Characterization of perioperative androgen profiles in men with bladder cancer undergoing radical cystectomy

BackgroundPrior studies have demonstrated declines in androgen levels in men with cancer and patients undergoing anesthesia and surgery. In this study, we hypothesized that decreased serum androgen levels are prevalent in male patients undergoing radical cystectomy (RC) for bladder cancer and that it persists in the postoperative period. We characterized perioperative androgen hormonal profiles and examined for associated changes indicative of sarcopenia on computed tomography scans in men undergoing RC.MethodsWe implemented a prospective observational trial in men with newly diagnosed non-metastatic bladder cancer undergoing RC. Baseline pre-operative total testosterone (TT), free testosterone (FT), and luteinizing hormone (LH) were obtained on morning lab draws with 30 days of surgery. TT and FT were then repeated on postoperative days (POD) 2, 3, 30, and 90. The threshold for normal TT was defined as >300 ng/dl, consistent with the AUA Guidelines for Evaluation and Management of Testosterone Deficiency. We evaluated postoperative changes in weight and psoas muscle cross-sectional area using computed tomography scans to assess for sarcopenic changes.ResultsUnivariable statistical analysis was performed. 25 patients were enrolled. The mean patient age was 68.9 years. The mean pre-operative TT was 308 ng/dl, and 12/23 (52.5%) patients had low testosterone. Mean TT onPOD 2 and 3 were 166 ng/dl and 161 ng/dl, respectively (range 24–345). 19/20 (95%) of men who had morning lab draws had decreased TT. The mean TT at 30 days was 253 ng/dl with 37.5% of men having low TT. Mean TT at 90 days was 306 ng/dl. The mean FT levels were 43 ng/dl, 29.25 ng/dl, 28.2 ng/dl, 40.89 ng/dl, and 42.62 ng/dl at baseline, POD 2, POD 3, POD 30, and POD 90, respectively. Mean LH at baseline was 9.9 IU/L. Average weight loss at 30- and 90- days postop was -4.29 and -4.38 kilograms, respectively. Weight loss was persistent with only 3/23 (13%) returning to their presurgery weight by 90 days. Despite significant declines in weight and perioperative TT, no significant differences in psoas muscle cross-sectional area were observed (net change -92 mm², P= 0.13)ConclusionsPerioperative disruption of androgen levels is prevalent in men undergoing RC. Our trial demonstrates a pre-op, immediate postop, 30- and 90-day postoperative prevalence of low TT of 52%, 95%, 63%, and 37.5%, respectively. Significant changes in baseline weight were noted, although no significant changes in psoas muscle cross-sectional area were observed, limiting conclusions regarding a link between changes in androgens and sarcopenia in this setting.     

Long-term kidney transplant graft survival—Making progress when most needed

Current short-term kidney post–transplant survival rates are excellent, but longer-term outcomes have historically been unchanged. This study used data from the national Scientific Registry of Transplant Recipients (SRTR) and evaluated 1-year and 5-year graft survival and half-lives for kidney transplant recipients in the US. All adult (≥18 years) solitary kidney transplants (n = 331,216) from 1995 to 2017 were included in the analysis. Mean age was 49.4 years (SD +/-13.7), 60% male, and 25% Black. The overall (deceased and living donor) adjusted hazard of graft failure steadily decreased from 0.89 (95%CI: 0.88, 0.91) in era 2000–2004 to 0.46 (95%CI: 0.45, 0.47) for era 2014–2017 (1995–1999 as reference). Improvements in adjusted hazards of graft failure were more favorable for Blacks, diabetics and older recipients. Median survival for deceased donor transplants increased from 8.2 years in era 1995–1999 to an estimated 11.7 years in the most recent era. Living kidney donor transplant median survival increased from 12.1 years in 1995–1999 to an estimated 19.2 years for transplants in 2014–2017. In conclusion, these data show continuous improvement in long-term outcomes with more notable improvement among higher-risk subgroups, suggesting a narrowing in the gap for those disadvantaged after transplantation.     

Remote intervention engagement and outcomes in the Clinical Trials in Organ Transplantation in Children consortium multisite trial

Remote interventions are increasingly used in transplant medicine but have rarely been rigorously evaluated. We investigated a remote intervention targeting immunosuppressant management in pediatric lung transplant recipients. Patients were recruited from a larger multisite trial if they had a Medication Level Variability Index (MLVI) ≥2.0, indicating worrisome tacrolimus level fluctuation. The manualized intervention included three weekly phone calls and regular follow-up calls. A comparison group included patients who met enrollment criteria after the subprotocol ended. Outcomes were defined before the intent-to-treat analysis. Feasibility was defined as ≥50% of participants completing the weekly calls. MLVI was compared pre- and 180 days postenrollment and between intervention and comparison groups. Of 18 eligible patients, 15 enrolled. Seven additional patients served as the comparison. Seventy-five percent of participants completed ≥3 weekly calls; average time on protocol was 257.7 days. Average intervention group MLVI was significantly lower (indicating improved blood level stability) at 180 days postenrollment (2.9 ± 1.29) compared with pre-enrollment (4.6 ± 2.10), p = .02. At 180 days, MLVI decreased by 1.6 points in the intervention group but increased by 0.6 in the comparison group (p = .054). Participants successfully engaged in a long-term remote intervention, and their medication blood levels stabilized. NCT02266888.     

Porndemic? A Longitudinal Study of Pornography Use Before and During the COVID-19 Pandemic in a Nationally Representative Sample of Americans

Of the many changes in daily life brought about by the COVID-19 pandemic, social distancing efforts and governmentally mandated lockdowns were among the most drastic. Coinciding with these changes, popular pornography websites made some previously premium content available for free, spurring dramatic increases in traffic to these websites. This increase in time spent at home and reported increases in traffic to specific pornographic websites led to some speculation that pornography use might generally increase over the course of the pandemic and that problematic use might also increase. To test these speculations and quantify the effects of the pandemic and its associated restrictions on social behaviors on pornography use, we analyzed data from a longitudinal sample of American adults. Baseline, nationally representative data were collected in August 2019 via YouGov (N?=?2518). Subsequent data were collected in February 2020 (n?=?1677), May 2020 (n?=?1533), August 2020 (n?=?1470), and October 2020 (n?=?1269). Results indicated that, in May 2020, immediately following the height of the first wave of pandemic-related lockdowns, more people reported past-month pornography use than at other follow-up time points, but less did so than at baseline. Among those who reported use in May 2020, only 14% reported increases in use since the start of the pandemic, and their use returned to levels similar to all other users by August 2020. In general, pornography use trended downward over the pandemic, for both men and women. Problematic pornography use trended downward for men and remained low and unchanged in women. Collectively, these results suggest that many fears about pornography use during pandemic-related lockdowns were largely not supported by available data.