Visitation policies at NCI-designated comprehensive cancer centers during the COVID-19 pandemic.

PURPOSE: Family/caregiver visitation provides critical support for patients confronting cancer and is associated with positive outcomes. However, the COVID-19 pandemic brought historic disruptions including widespread visitation restrictions. Here, we characterize in-depth the visitor policies of NCI-designated comprehensive cancer centers (CCCs) and analyze geographic/temporal patterns across CCCs. METHODS: The public-facing CCC websites, including archived webpages, were reviewed to abstract initial visitation policies and revisions, including end-of-life (EoL) exceptions and timing of visitation restrictions relative to regional lockdowns. Chi-squared and Fisher's exact tests were employed to analyze associations between geographic region, timing, and severity of restrictions. RESULTS: Most CCCs (n=43, 86%) enacted visitation restrictions between March 15 and April 15, 2020. About half barred all visitors for COVID-negative inpatients (n=24, 48%) or outpatients (n=26, 52%). Most (n=36, 72%) prohibited visitors for patients with confirmed/suspected COVID-19. Most (n=40, 80%) published EoL exceptions but the specifics were highly variable. The median time from initial restrictions to government-mandated lockdowns was 1 day, with a wide range (25 days before to 26 days after). There was no association between timing of initial restrictions and geographic location (p=0.14) or severity of inpatient policies (p=1.0), even among centers in the same city. Outpatient policies published reactively (after lockdown) were more restrictive than those published proactively (p=0.04). CONCLUSION: CCCs enacted strict but strikingly variable COVID-19 visitation restrictions, with important implications for patients/families seeking cancer care. A unified, evidence-based approach to visitation policies is needed to balance proven infection control measures with the needs of patients and families.

Gender Matters: Characteristics of Hepatocellular Carcinoma in Women From a Large, Multicenter Study in the United States.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide, affecting men to women at a ratio of about 4:1. Risk factors, characteristics, and outcomes for HCC in women in the United States remain poorly understood; therefore, we aim to explore gender differences further. METHODS: Patients diagnosed with HCC between January 2000 and June 2014 at 5 large centers were identified. Clinical information, tumor characteristics, and survival data were extracted manually. The presence of underlying cirrhosis was assessed based on published criteria. RESULTS: Of 5,327 patients with HCC in our cohort, 1,203 (22.6%) were women. There were important differences in the underlying etiology of liver disease between the 2 genders (P < 0.0001): women had a significantly higher frequency of nonalcoholic fatty liver disease (23% vs 12%) and lower frequency of alcoholic liver disease (5% vs 15%). The proportion of noncirrhotic HCC was significantly higher among women (17% vs 10%, P < 0.0001). Women had less-advanced HCC at presentation by tumor, node, metastasis staging (P < 0.0001) and a higher proportion within Milan criteria (39% vs 35%, P = 0.002). Women had a greater overall survival (2.5 ± 2.9 years vs 2.2 ± 2.7 years, P = 0.0031). DISCUSSION: The frequency of underlying nonalcoholic fatty liver disease and noncirrhotic HCC were significantly higher in women than men in this large cohort. Women presented with less-advanced HCC and had a greater overall survival. Further investigation is warranted to explore potential mechanisms and implications for these gender differences, especially with noncirrhotic HCC (see Visual Abstract, Supplementary Digital Content 1, http://links.lww.com/AJG/B535).

GPR56 identifies primary human acute myeloid leukemia cells with high repopulating potential in vivo.

Acute myeloid leukemia (AML) is a genetically heterogeneous hematologic malignancy, which is initiated and driven by a rare fraction of leukemia stem cells (LSCs). Despite the difficulties of identifying a common LSC phenotype, there is increasing evidence that high expression of stem cell gene signatures is associated with poor clinical outcome. Identification of functionally distinct subpopulations in this disease is therefore crucial to dissecting the molecular machinery underlying LSC self-renewal. Here, we combined next-generation sequencing technology with in vivo assessment of LSC frequencies and identified the adhesion G protein-coupled receptor 56 (GPR56) as a novel and stable marker for human LSCs for the majority of AML samples. High GPR56 expression was significantly associated with high-risk genetic subgroups and poor outcome. Analysis of GPR56 in combination with CD34 expression revealed engraftment potential of GPR56(+)cells in both the CD34(-)and CD34(+)fractions, thus defining a novel LSC compartment independent of the CD34(+)CD38(-)LSC phenotype.

Phase I and Phase II Objective Response Rates are Correlated in Pediatric Cancer Trials: An Argument for Better Clinical Trial Efficiency.

Although many phase I trials report tumor response, formal analysis of efficacy is deferred to phase II. We reviewed paired phase I and II pediatric oncology trials to ascertain the relationship between phase I and II objective response rate (OR%). Single-agent phase I trials were paired with corresponding phase II trials (comparable study drug, dosing schedule, and population). Phase I trials without efficacy data or a matching phase II trial were excluded. OR% was tabulated for all trials, and phase II authors' subjective conclusions regarding efficacy were documented; 35 pairs of trials were analyzed. The correlation between phase I and II OR% was 0.93. Between phase II studies with a "positive" conclusion versus a "negative" one, there was a statistically significant difference in mean phase I OR% (32.0% vs. 4.5%, P<0.001). Thirteen phase II studies were undertaken despite phase I OR% of 0%; only 1 had a "positive" conclusion, and none exceeded OR% of 15%. OR% are highly correlated between phase I and II pediatric oncology trials. Although not a formal measure of drug efficacy, phase I OR% may provide an estimate of phase II response, inform phase II study design, and should be given greater consideration.

Outpatient Training During Hospice and Palliative Medicine Fellowship: A National Survey.

CONTEXT: Outpatient palliative care (PC) has strong evidence demonstrating impact across serious illnesses, resulting in growing demand for skilled outpatient PC clinicians. However, there is limited literature examining the existing state and quality of outpatient PC education during postgraduate training. OBJECTIVES: Characterize the current state of outpatient training in United States (US) Hospice and Palliative Medicine (HPM) physician fellowships and elicit perceptions regarding quality of outpatient PC education. METHODS: A cross-sectional survey of US adult HPM fellowship program directors (PDs) or their designee conducted between March and July, 2023. RESULTS: Of 161 programs, 85 participated (53% response rate) with representation across all US regions. HPM fellows spend a median of 4.8 weeks in outpatient PC compared to 24 weeks inpatient PC and 10.5 weeks in hospice settings. Over half (51%) of fellows saw outpatients from primarily one disease type with limited exposure to patients with other serious illnesses. Across programs, fellows' clinic structure, interdisciplinary team composition, and didactic experiences varied. On a 5-point rating scale, PDs reported significantly lower quality outpatient versus inpatient training (mean rating: 3.58 vs. 4.62, P<0.001) and perceived fellows as less prepared for independent outpatient practice upon graduation (mean: 4.06 vs. 4.73, P<0.001). CONCLUSION: Our survey of US HPM fellowships identified multiple gaps between outpatient and inpatient PC education and training during fellowship and raises concern about the adequacy of outpatient PC training. To prepare the HPM workforce to meet the diverse needs of seriously ill populations and ensure adequate access, outpatient PC training requires reform.

Wnt5a is a cell-extrinsic factor that supports self-renewal of mouse spermatogonial stem cells.

The maintenance of spermatogonial stem cells (SSCs) provides the foundation for life-long spermatogenesis. Although glial-cell-line-derived neurotrophic factor and fibroblast growth factor 2 are crucial for self-renewal of SSCs, recent studies have suggested that other growth factors have important roles in controlling SSC fate. Because ß-catenin-dependent Wnt signaling promotes self-renewal of various stem cell types, we hypothesized that this pathway contributes to SSC maintenance. Using transgenic reporter mice for ß-catenin-dependent signaling, we found that this signaling was not active in SSCs in vitro and in most spermatogonia in vivo. Nonetheless, a pan-Wnt antagonist significantly reduced SSC activity in vitro, suggesting that some Wnt molecules exist in our serum-free culture system and contribute to SSC maintenance. Here, we report that Wnt5a promotes SSC activity. We found that Wnt5a-expressing fibroblasts supported SSC activity better than those not expressing Wnt5a in culture, and that recombinant Wnt5a stimulated SSC maintenance. Furthermore, Wnt5a promoted SSC survival in the absence of feeder cells, and this effect was abolished by inhibiting the Jun N-terminal kinase cascade. In addition, Wnt5a blocked ß-catenin-dependent signaling. We detected the expression of Wnt5a and potential Wnt5a receptors in Sertoli cells and stem/progenitor spermatogonia, respectively. These results indicate that Wnt5a is a cell-extrinsic factor that supports SSC self-renewal through ß-catenin-independent mechanisms.

Stability of DNA methylation patterns in mouse spermatogonia under conditions of MTHFR deficiency and methionine supplementation.

Little is known about the conditions contributing to the stability of DNA methylation patterns in male germ cells. Altered folate pathway enzyme activity and methyl donor supply are two clinically significant factors that can affect the methylation of DNA. 5,10-Methylenetetrahydrofolate reductase (MTHFR) is a key folate pathway enzyme involved in providing methyl groups from dietary folate for DNA methylation. Mice heterozygous for a targeted mutation in the Mthfr gene (Mthfr(+/-)) are a good model for humans homozygous for the MTHFR 677C>T polymorphism, which is found in 10% of the population and is associated with decreased MTHFR activity and infertility. High-dose folic acid is administered as an empirical treatment for male infertility. Here, we examined MTHFR expression in developing male germ cells and evaluated DNA methylation patterns and effects of a range of methionine concentrations in spermatogonia from Mthfr(+/-) as compared to wild-type, Mthfr(+/+) mice. MTHFR was expressed in prospermatogonia and spermatogonia at times of DNA methylation acquisition in the male germline; its expression was also found in early spermatocytes and Sertoli cells. DNA methylation patterns were similar at imprinted genes and intergenic sites across chromosome 9 in neonatal Mthfr(+/+) and Mthfr(+/-) spermatogonia. Using spermatogonia from Mthfr(+/+) and Mthfr(+/-) mice in the spermatogonial stem cell (SSC) culture system, we examined the stability of DNA methylation patterns and determined effects of low or high methionine concentrations. No differences were detected between early and late passages, suggesting that DNA methylation patterns are generally stable in culture. Twenty-fold normal concentrations of methionine resulted in an overall increase in the levels of DNA methylation across chromosome 9, suggesting that DNA methylation can be perturbed in culture. Mthfr(+/-) cells showed a significantly increased variance of DNA methylation at multiple loci across chromosome 9 compared to Mthfr(+/+) cells when cultured with 0.25- to 2-fold normal methionine concentrations. Taken together, our results indicate that DNA methylation patterns in undifferentiated spermatogonia, including SSCs, are relatively stable in culture over time under conditions of altered methionine and MTHFR levels.

Delivering Palliative Care to Hospitalized Oncology Patients: A Scoping Review.

CONTEXT: Early, longitudinal integration of palliative care (PC) is recommended for patients with advanced cancer, in both inpatient and outpatient settings. Despite the growth of specialty PC teams in the last decade, the majority of PC is still delivered in the inpatient setting using a traditional referral-based consult delivery model. However, traditional consultation can lead to significant variation or delay in inpatient PC utilization. New care delivery models and strategies are emerging to deliver PC to hospitalized oncology patients who would most benefit from their services and to better align with professional society recommendations. OBJECTIVES: To identify different care models to deliver PC to ho`spitalized oncology patients and summarize their impact on patient and health system-related outcomes. METHODS: We conducted a scoping review of peer-reviewed articles from 2006 to 2021 evaluating delivery of PC to oncology patients in acute inpatient care. We abstracted study characteristics, the study's intervention and comparison arms, and outcomes related to specialty PC intervention. RESULTS: We identified four delivery models that have been reported to deliver PC: 1) traditional referral-based consultation, 2) criterion-based or "triggered" consultation, 3) co-rounding with primary inpatient team, and 4) PC clinicians serving as the primary team. We summarize the known outcomes data from each model, and compare the benefits and limitations of each model. CONCLUSION: Our findings provide guidance to health systems about care delivery models to deploy and implement inpatient PC resources to best serve their unique populations.

Palliative Care Education in US Physical Medicine and Rehabilitation Residency Programs: Current Practices, Perceived Needs, and Barriers.

Background: Physical medicine and rehabilitation (PM&R) clinicians commonly care for patients with serious illness/injury and would benefit from primary palliative care (PC) training. Objective: To assess current practices, attitudes, and barriers toward PC education among U.S. PM&R residencies. Design: This is a cross-sectional study utilizing an electronic 23-question survey. Setting/Subjects: Subjects were program leaders from U.S. PM&R residency programs. Results: Twenty-one programs responded (23% response). Only 14 (67%) offered PC education through lectures, elective rotations, or self-directed reading. Pain management, communication, and nonpain symptom management were identified as the most important PC domains for residents. Nineteen respondents (91%) felt residents would benefit from more PC education, but only five (24%) reported undergoing curricular change. Lack of faculty availability/expertise and teaching time were the most endorsed barriers. Conclusion: PC education is heterogeneous across PM&R programs despite its perceived value. PC and PM&R educators can collaborate to build faculty expertise and integrate PC principles into existing curricula.

Development of single retinofugal axon arbors in normal and ß2 knock-out mice.

The maturation of retinal ganglion cell (RGC) axon projections in the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus (SC) relies on both molecular and activity-dependent mechanisms. Despite the increasing popularity of the mouse as a mammalian visual system model, little is known in this species about the normal development of individual RGC axon arbors or the role of activity in this process. We used a novel in vivo single RGC labeling technique to quantitatively characterize the elaboration and refinement of RGC axon arbors in the dLGN and SC in wild-type (WT) and ß2-nicotinic acetylcholine receptors mutant (ß2(-/-)) mice, which have perturbed retinal waves, during the developmental period when eye-specific lamination and retinotopic refinement occurs. Our results suggest that eye-specific segregation and retinotopic refinement in WT mice are not the result of refinement of richly exuberant arbors but rather the elaboration of arbors prepositioned in the proper location combined with the elimination of inappropriately targeted sparse branches. We found that retinocollicular arbors mature ∼1 week earlier than retinogeniculate arbors, although RGC axons reach the dLGN and SC at roughly the same age. We also observed striking differences between contralateral and ipsilateral RGC axon arbors in the SC but not in the LGN. These data suggest a strong influence of target specific cues during arbor maturation. In ß2(-/-) mice, we found that retinofugal single axon arbors are well ramified but enlarged, particularly in the SC, indicating that activity-dependent visual map development occurs through the refinement of individual RGC arbors.

Soluble growth factors stimulate spermatogonial stem cell divisions that maintain a stem cell pool and produce progenitors in vitro.

Spermatogonial stem cells (SSCs) support life-long spermatogenesis by self-renewing and producing spermatogonia committed to differentiation. In vitro, SSCs form three-dimensional spermatogonial aggregates (clusters) when cultured with glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2); serial passaging of clusters results in long-term SSC maintenance and expansion. However, the role of these growth factors in controlling patterns of SSC division and fate decision has not been understood thoroughly. We report here that in a short-term culture, GDNF and FGF2 increase the number of dividing SSCs, but not the total SSC number, compared to a no-growth-factor condition. Since the total germ cell number increases with growth factors, these results suggest that GDNF and FGF2 promote a SSC division pattern that sustains the size of the stem cell pool while generating committed progenitors. Our data also show that SSC numbers increase when the cluster structure is disintegrated and cell-cell interaction in clusters is disrupted. Collectively, these results suggest that in this culture system, GDNF and FGF2 stimulate SSC divisions that promote self-renewal and differentiation in the SSC population, and imply that the destruction of the cluster structure, a potential in vitro niche, may contribute to SSC expansion.

Different Associations Between Inpatient or Outpatient Palliative Care and End-of-Life Outcomes for Hospitalized Patients With Cancer.

PURPOSE: Palliative care (PC) improves outcomes in advanced cancer, and guidelines recommend early outpatient referral. However, many PC teams see more inpatient than outpatient consults. We conducted a retrospective study of hospitalized patients with cancer to quantify exposure to inpatient and outpatient PC and describe associations between PC and end-of-life (EOL) quality measures. METHODS: We identified all decedents admitted to an inpatient oncology unit in 1 year (October 1, 2017-September 30, 2018) and abstracted hospitalization statistics, inpatient and outpatient PC visits, and EOL outcomes. Descriptive statistics, univariate tests, and multivariate analysis evaluated associations between PC and patient outcomes. RESULTS: In total, 522 decedents were identified. 50% saw PC; only 21% had an outpatient PC visit. Decedents seen by PC were more likely to enroll in hospice (78% v 44%; P < .001), have do-not-resuscitate status (87% v 55%; P < .001), have advance care planning documents (53% v 31%; P < .001), and die at home or inpatient hospice instead of in hospital (67% v 40%; P < .01). Decedents seen by PC had longer hospital length-of-stay (LOS; 8.4 v 7.0 days; P = .03), but this association reversed for decedents seen by outpatient PC (6.3 v 8.3 days; P < .001), who also had longer hospice LOS (46.5 v 27.1 days; P < .01) and less EOL intensive care (6% v 15%; P < .05). CONCLUSION: PC was associated with significantly more hospice utilization and advance care planning. Patients seen specifically by outpatient PC had shorter hospital LOS and longer hospice LOS. These findings suggest different effects of inpatient and outpatient PC, underscoring the importance of robust outpatient PC.

Are Opioid Infusions Used Inappropriately at End of Life? Results From a Quality/Safety Project.

CONTEXT: Opioid continuous infusions are commonly used for end-of-life (EOL) symptoms in hospital settings. However, prescribing practices vary, and even the recent literature contains conflicting protocols and guidelines for best practice. OBJECTIVES: To determine the prevalence of potentially inappropriate opioid infusion use for EOL comfort care at an academic medical center, and determine if inappropriate use is associated with distress. METHODS: Through literature review and iterative interdisciplinary discussion, we defined three criteria for "potentially inappropriate" infusion use. We conducted a retrospective, observational study of inpatients who died over six months, abstracting demographics, opioid use patterns, survival time, palliative care (PC) involvement, and evidence of patient/caregiver/staff distress from the electronic medical record. RESULTS: We identified 193 decedents who received opioid infusions for EOL comfort care. Forty-four percent received opioid infusions that were classified as "potentially inappropriate." Insufficient use of as-needed intravenous opioid boluses and use of opioid infusions in opioid-naïve patients were the most common problems observed. Potentially inappropriate infusions were associated with more frequent patient (24% vs. 2%; P < 0.001) and staff distress (10% vs. 2%; P = 0.02) and were less common when PC provided medication recommendations (20% vs. 50%; P < 0.001). CONCLUSION: Potentially inappropriate opioid infusions are prevalent at our hospital, an academic medical center with an active PC team and existing contracts for in-hospital hospice care. Furthermore, potentially inappropriate opioid infusions are associated with increased patient and staff distress. We are developing an interdisciplinary intervention to address this safety issue.

Healthcare Disparities and the COVID-19 Pandemic: Analysis of Primary Language and Translations of Visitor Policies at NCI-Designated Comprehensive Cancer Centers.

CONTEXT: Coronavirus Disease 2019 (COVID-19) has caused unprecedented disruptions to cancer care, including through strict hospital visitation policies. Since a substantial proportion of the U.S. population report a non-English language as their primary language, it is critical that information is disseminated in multiple languages. OBJECTIVES: To examine the availability of language translations of visitation restrictions on adult National Cancer Institute-designated comprehensive cancer centers (CCCs) Web sites. METHODS: Cross-sectional analysis of visitation policies abstracted from public-facing Web sites of CCCs in June 2020. Using U.S. Census data, CCC's city and state proportions of self-identifying Hispanic/Latinx population were categorized into three cohorts: low (<10%), moderate (10%-20%), and high (>20%). RESULTS: As of June 2020, all 50 CCCs published a COVID-19 visitation policy on their Web site. Of these, 33 (66%) posted policies only in English, whereas 17 (34%) included one or more non-English translations. A minority of CCCs published Spanish language resources, which did not differ based on state or city demographics: for example, only 42% (8 of 19), 10% (1 of 10), and 38% (8 of 21) of CCCs published Spanish language resources in cities with low, moderate, and high Hispanic/Latinx populations, respectively. CONCLUSION: `Most CCC's did not publish non-English language translations of their visitor policies. Even in cities and states with larger Hispanic/Latinx populations, most CCCs did not publish resources in Spanish. This study highlights a key opportunity to mitigate communication barriers and deliver culturally competent, patient-centered care.

Expanding Canonical Spider Silk Properties through a DNA Combinatorial Approach.

The properties of native spider silk vary within and across species due to the presence of different genes containing conserved repetitive core domains encoding a variety of silk proteins. Previous studies seeking to understand the function and material properties of these domains focused primarily on the analysis of dragline silk proteins, MaSp1 and MaSp2. Our work seeks to broaden the mechanical properties of silk-based biomaterials by establishing two libraries containing genes from the repetitive core region of the native Latrodectus hesperus silk genome (Library A: genes masp1, masp2, tusp1, acsp1; Library B: genes acsp1, pysp1, misp1, flag). The expressed and purified proteins were analyzed through Fourier Transform Infrared Spectrometry (FTIR). Some of these new proteins revealed a higher portion of ß-sheet content in recombinant proteins produced from gene constructs containing a combination of masp1/masp2 and acsp1/tusp1 genes than recombinant proteins which consisted solely of dragline silk genes (Library A). A higher portion of ß-turn and random coil content was identified in recombinant proteins from pysp1 and flag genes (Library B). Mechanical characterization of selected proteins purified from Library A and Library B formed into films was assessed by Atomic Force Microscopy (AFM) and suggested Library A recombinant proteins had higher elastic moduli when compared to Library B recombinant proteins. Both libraries had higher elastic moduli when compared to native spider silk proteins. The preliminary approach demonstrated here suggests that repetitive core regions of the aforementioned genes can be used as building blocks for new silk-based biomaterials with varying mechanical properties.

Hepatocellular Carcinoma in Hispanic Patients: Trends and Outcomes in a Large United States Cohort.

Hepatocellular carcinoma (HCC) has a strong racial and ethnic association, with Hispanic patients having a higher incidence and mortality. However, there are limited data regarding clinical features and outcomes. This study includes Hispanic and non-Hispanic White patients with HCC diagnosed between January 2000 and June 2014 from five United States academic medical centers. The chi-square test for categorical variables and analysis of variance for continuous variables were used for statistical analysis, with two-tailed P < 0.05 considered statistically significant. Of 5,327 patients, 4,217 met inclusion criteria, of whom 12.3% were Hispanic patients. Compared to their non-Hispanic White counterparts, Hispanic patients were older at age of diagnosis (mean ± SD, 64.2 ± 10.9 vs. 61.9 ± 10.5 years; P < 0.0001), with higher body mass index (29.6 ± 6.5 vs. 28.8 ± 5.9 kg/m2; P = 0.01), and were more likely to have diabetes and hypertension. Hispanic patients had significantly more nonalcoholic fatty liver disease and alcohol-related liver disease (both P < 0.0001). Hispanic patients presented with larger tumors, more advanced stage disease, and increased rates of macrovascular invasion and extrahepatic spread. HCCs in Hispanic patients were less likely to be within Milan criteria (26% vs. 38%; P < 0.0001) and were less likely to be treated with resection (9% vs. 13%; P = 0.03) or transplantation (8% vs. 19%; P < 0.0001). Hispanic patients had a median overall survival of 1.4 years (95% confidence interval [CI], 1.22-1.56), which was similar to that of non-Hispanic White patients (1.3 years; 95% CI, 1.26-1.41; P = 0.07). Conclusion: Hispanic patients with HCC were more likely to have metabolic risk factors for chronic liver disease, including obesity. Despite diagnosis at more advanced stages with less curative intervention than non-Hispanic White patients, median overall survival was similar between groups.

Has There Been a Shift in Use of Subacute Rehabilitation Instead of Hospice Referral Since Immunotherapy Has Become Available?

PURPOSE: Immunotherapy has rapidly become the mainstream treatment of multiple cancer types. Since the first drug approval in 2011, we have noted a decline in referrals from inpatient oncology to hospice and an increase in referrals to subacute rehabilitation (SAR) facilities, possibly with the aim of getting strong enough for immunotherapy and other promising drugs. This study explores outcomes after discharge to SAR, including rates of cancer-directed therapy after SAR, overall survival, and hospice use. METHODS: We performed an electronic chart review of patients discharged from our inpatient oncology units to SAR facilities from 2009 to 2017. Demographics, admission statistics, and post-discharge outcomes were gathered from discharge summaries and targeted chart searches. RESULTS: Three hundred fifty-eight patients were referred to SAR 413 times. One hundred seventy-four patients (49%) returned to the oncology clinic before readmission or death, and only 117 (33%) ever received additional cancer-directed treatment (chemotherapy, radiation, or immunotherapy). Among all discharges, 28% led to readmissions within 30 days. Seventy-four patients (21%) were deceased within 30 days, only 31% of whom were referred to hospice. Palliative care involvement resulted in more frequent do not resuscitate code status, documented goals of care discussions, and electronic advance directives. CONCLUSION: A growing number of oncology inpatients are being discharged to SAR, but two thirds do not receive additional cancer therapy at any point, including a substantial fraction who are readmitted or deceased within 1 month. These data can help guide decision making and hospital discharge planning that aligns with patients' goals of care. More clinical data are needed to predict who is most likely to benefit from SAR and proceed to further cancer therapy.

The application of biomarkers of spermatogonial stem cells for restoring male fertility.

Spermatogonial stem cells (SSCs) are defined by their ability to both self-renew and produce differentiated germ cells that will develop into functional spermatozoa. Because of this ability, SSCs can reestablish spermatogenesis after testicular damage caused by cytotoxic agents or after transplantation into an infertile recipient. Therefore, SSCs are an important target cell for restoring male fertility, particularly for cancer patients who have to undergo sterilizing cancer therapies. In the mouse, the identification of SSC markers allows for the isolation of a highly enriched population of stem cells. This enriched stem cell population can be expanded in culture for an indefinite period of time, cryopreserved, and transplanted into infertile recipients to restore fertility. Thus, the identification of markers and the establishment of a long-term culture system for human SSCs will be crucial for realizing the potential of these cells in a clinical setting. In this article, we focus on the markers that have been identified for mouse SSCs and discuss how human SSC markers may be used in the restoration of fertility.