Systemic inflammatory markers might have prognostic utility for patients with metastatic GCT. The planned IGCCCG update could be an opportunity to test these markers in a larger data set.

Background Recruitment and activation of brown adipose tissue (BAT) results in increased energy expenditure (EE) via thermogenesis and represents an intriguing therapeutic approach to combat obesity and treat associated diseases. Thermogenesis requires an increased and efficient supply of energy substrates and oxygen to the BAT. The hemoprotein myoglobin (MB) is primarily expressed in heart and skeletal muscle fibres, where it facilitates oxygen storage and flux to the mitochondria during exercise. In the last years, further contributions of MB have been assigned to the scavenging of reactive oxygen species (ROS), the regulation of cellular nitric oxide (NO) levels and also lipid binding. There is a substantial expression of MB in BAT, which is induced during brown adipocyte differentiation and BAT activation. This suggests MB as a previously unrecognized player in BAT contributing to thermogenesis. Methods and Results This study analyzed the consequences of MB expression in BAT on mitochondrial function and thermogenesis in vitro and in vivo. Using MB overexpressing, knockdown or knockout adipocytes, we show that expression levels of MB control brown adipocyte mitochondrial respiratory capacity and acute response to adrenergic stimulation, signalling and lipolysis. Overexpression in white adipocytes also increases their metabolic activity. Mutation of lipid interacting residues in MB abolished these beneficial effects of MB. In vivo, whole‐body MB knockout resulted in impaired thermoregulation and cold‐ as well as drug‐induced BAT activation in mice. In humans, MB is differentially expressed in subcutaneous (SC) and visceral (VIS) adipose tissue (AT) depots, differentially regulated by the state of obesity and higher expressed in AT samples that exhibit higher thermogenic potential. Conclusions These data demonstrate for the first time a functional relevance of MBs lipid binding properties and establish MB as an important regulatory element of thermogenic capacity in brown and likely beige adipocytes.

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Introduction: Allo-HSCT is a potentially curative option for patients (pts) with classical Hodgkin lymphoma (cHL) who relapse after autologous (auto)-HSCT. Nivolumab (nivo) is approved in the US for treatment of relapsed or progressive cHL after auto-HSCT and post-transplant brentuximab vedotin. Nivo was studied in pts with relapsed cHL in ph 1 (CheckMate 039, NCT01592370) and multicohort ph 2 (CheckMate 205, NCT02181738) studies. Response rate in 95 heavily pretreated cHL pts across those studies was 65%, with an estimated median duration of response of 8.7 mo. Decision to proceed to allo-HSCT after nivo was not restricted within the studies and was at the discretion of treating clinicians; some pts were referred and elected to undergo subsequent allo-HSCT. Allo-HSCT-related immune complications, including graft vs host disease (GVHD) after prior exposure to PD-1 blockade have been reported (Nivolumab US PI; 2016). Here we report safety outcomes in HL pts from these 2 studies who received nivo and subsequent allo-HSCT. Methods: Pts from the CheckMate 039 cHL monotherapy cohort (n=23) and all CheckMate 205 cohorts (n=243) who underwent allo-HSCT after study treatment are included in this post hoc analysis. Basic post-allo-HSCT outcomes (transplant date, GVHD, disease status) were prospectively collected in CheckMate 205. Further details from CheckMate 205 (stem cell source, preparative regimen, additional post-allo-HSCT safety data) and all post-allo-HSCT data from CheckMate 039 were collected retrospectively. Non-relapse mortality (NRM) was defined as death without disease relapse. Steroid-responsive febrile syndrome (SRFS) was defined as steroid-responsive, non-infectious fever that could be accompanied by skin, joint, or liver symptoms. Results: This analysis includes pts from CheckMate 039 (n=5) and 205 (n=12) who underwent allo-HSCT. Median age at time of allo-HSCT was 33 y (range 18-56). Pts had received a median of 9 nivo doses (range 4-16); 16 underwent allo-HSCT without disease progression or intervening therapy between nivo and allo-HSCT; the remaining pt had disease progression on nivo and received combination chemotherapy before allo-HSCT. Median interval between last nivo dose and allo-HSCT was 29 d (range 11-94). Stem cell source was peripheral blood (n=14) or bone marrow (n=3). Donors were HLA-matched sibling (n=3), single-antigen mismatched related (n=1), haploidentical (n=5), matched unrelated (n=7), and mismatched unrelated (n=1). Reduced-intensity conditioning (RIC) was used in 15 pts and myeloablative conditioning (MAC) in 2. Acute GVHD occurred in 14 pts (82%): grade (g)2-4 in 10 pts (59%) and g3-4 in 5 (29%). Among those 14 pts, organs involved were skin (3 g1, 4 g2, 4 g4, 1 g unknown), gut (1 g2, 1 g3, 4 g4), liver (4 g4), and lung (1 g unknown). Median time to onset of g3-4 acute GVHD was 22 d (range 13-139). Two pts had hyperacute GVHD (onset ≤14 d post-transplant). One pt with hepatic veno-occlusive disease died due to multiorgan GVHD. Five pts had SRFS (onset 0-53 d post-allo-HSCT). Two pts experienced g3 encephalitis: 1 lymphocytic encephalitis case without an identified infectious cause resolved on corticosteroids, and 1 suspected viral encephalitis case resolved on antiviral therapy. There were 6 deaths among 17 pts; all 6 were NRM-related: 5 due to GVHD in pts who had received RIC allo, and 1 due to pulmonary injury in a pt who had received MAC. Median time from allo-HSCT to death was 119 d (range 39-440). There were no deaths due to disease progression. Follow-up is ongoing and additional results will be presented. Conclusions: Results of this small cohort indicate that severe GVHD with rapid onset and unique complications such as SRFS, and NRM may occur in pts with prior exposure to PD-1 blockade. Although the data set is small and follow-up is limited, results support a hypothesis that prior anti-PD-1 exposure could potentially magnify the risk of immune-related complications after transplantation. While these data should not be interpreted as showing that allo-HSCT is contraindicated, they highlight a need for caution when considering allo-HSCT after PD-1 blockade. Studies of larger cohorts with longer follow-up and immunologic analyses should be pursued to confirm and understand these results. Funding: BMS. Writing support F. Beebe, Caudex. Disclosures Armand: Infinity Pharmaceuticals: Consultancy; Sequenta Inc: Research Funding; Roche: Research Funding; Merck: Consultancy, Research Funding; Pfizer: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding. Zinzani:Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sandoz: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Infinity: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Collins:Takeda: Consultancy, Honoraria, Speakers Bureau. Cohen:Bristol-Myers Squibb: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Halwani:Abbvie: Consultancy, Research Funding; Genentech: Research Funding; Bristol-Myers Squibb: Research Funding; Pharmacyclics: Consultancy, Research Funding; Immune Design: Research Funding; Seattle Genetics: Research Funding; Kyowa Hakko Kirin: Research Funding; Amgen: Research Funding; Takeda: Research Funding. Carlo-Stella:Boehringer Ingelheim: Consultancy; Rhizen Pharmaceuticals: Research Funding. Millenson:Janssen: Other: Spouse's employment/salary. Kato:Bristol-Myers Squibb: Employment. Popa McKiver:Bristol-Myers Squibb: Employment, Equity Ownership. Sumbul:Bristol-Myers Squibb: Employment. Zhu:Bristol-Myers Squibb: Employment. Santoro:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; ArQule: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees.

For inconclusive testicular tumors with negative tumor markers, frozen section examination (FSE) during inguinal exploration is recommended. However, FSE is time-consuming and therefore often not requested. Furthermore, the exact diagnostic benefit remains poorly defined. We performed a systematic review and meta-analysis summarizing 12 published studies and our own series of FSE in patients with inconclusive testicular tumors, resulting in a cohort of 1052 FSEs. FSE showed sensitivity of 99% and specificity of 96% with a positive predictive value of 98% and a negative predictive value of 97%. Most importantly, one-third of all testicular tumors investigated were correctly identified as being suitable for testis-sparing surgery and orchiectomy could be avoided. For patients with inconclusive testicular tumors, FSE is useful for deciding whether testis-sparing surgery is an option or whether radical orchiectomy should be performed. Thus, these patients should be optimally treated in institutions where FSE is available. Patient summary: We found that intraoperative examination of a frozen section is useful in deciding on whether the entire or only parts of the testicle can be removed. We conclude that frozen section examination should be offered to men with small testicular lesions and negative tumor markers.

PURPOSE To investigate whether the use of pre-orchiectomy instead of pre-chemotherapy tumor marker (TM) levels has an impact on the International Germ Cell Consensus Classification (IGC-CCG) risk group assignment in patients with metastatic germ cell tumors (GCT). METHODS Demographic and clinical information of all patients treated for primary metastatic testicular non-seminomatous GCT in our tertiary care academic center were extracted from medical charts. IGCCCG risk group assignment was correctly performed with pre-chemotherapy marker levels and additionally with pre-orchiectomy marker levels. Agreement between pre-chemotherapy and pre-orchiectomy risk group assignments was assessed using Cohen's kappa. RESULTS Our cohort consisted of 83 patients. The use of pre-orchiectomy TMs resulted in an IGCCCG risk group upstaging in 12 patients (16%, 8 patients from good to intermediate risk and 4 patients from intermediate to poor risk) and a downstaging in 1 patient (1.2%, from intermediate-to good-risk). The agreement between pre-orchiectomy and pre-chemotherapy IGCCCG risk groups resulted in a Cohen's kappa of 0.888 (p < 0.001). CONCLUSIONS Using pre-orchiectomy TMs can result in incorrect IGCCCG risk group assignment, which in turn can impact on the clinical management and follow-up of patients with metastatic GCT. Thus, adherence to the IGCCCG standard using pre-chemotherapy TMs levels is recommended.

The parents and children of homeless families are highly vulnerable to illness and the failure to receive timely and continuous health care. Data on health status and health care utilization were collected from 70 homeless families selected for an intensive case management program and compared to data for low-income families. The data suggest that homeless children do not utilize primary care or preventive care on a regular basis in comparison to low income children generally. These results have implications for the delivery of health care services to homeless families in shelters.