BACKGROUND Fellowship directors (FDs) in sports medicine influence the future of trainees in the field of orthopaedics. Understanding the characteristics these leaders share must be brought into focus. For all current sports medicine FDs, our group analyzed their demographic background, institutional training, and academic experience. AIM To serve as a framework for those aspiring to achieve this position in orthopaedics and also identify opportunities to improve the position. METHODS Fellowship programs were identified using both the American Orthopaedic Society for Sports Medicine and the Arthroscopy Association of North America Sports Medicine Fellowship Directories. The demographic and educational background data for each FD was gathered via author review of current curriculum vitae (CVs). Any information that was unavailable on CV review was gathered from institutional biographies, Scopus Web of Science, and emailed questionnaires. To ensure the collection of as many data points as possible, fellowship program coordinators, orthopaedic department offices and FDs were directly contacted via phone if there was no response via email. Demographic information of interest included: Age, gender, ethnicity, residency/fellowship training, residency/fellowship graduation year, year hired by current institution, time since training completion until FD appointment, length in FD role, status as a team physician and H-index. RESULTS Information was gathered for 82 FDs. Of these, 97.5% ( n = 80) of the leadership were male; 84.15% ( n = 69) were Caucasian, 7.32% ( n = 6) were Asian-American, 2.44% ( n = 2) were Hispanic and 2.44% ( n = 2) were African American, and 3.66% ( n = 3) were of another race or ethnicity. The mean age of current FDs was 56 years old (± 9.00 years), and the mean Scopus H-index was 23.49 (± 16.57). The mean calendar years for completion of residency and fellowship training were 1996 (± 15 years) and 1997 (± 9.51 years), respectively. The time since fellowship training completion until FD appointment was 9.77 years. 17.07% ( n = 14) of FDs currently work at the same institution where they completed residency training; 21.95% ( n = 18) of FDs work at the same institution where they completed fellowship training; and 6.10% ( n = 5) work at the same institution where they completed both residency and fellowship training. Additionally, 69.5% ( n = 57) are also team physicians at the professional and/or collegiate level. Of those that were found to currently serve as team physicians, 56.14% ( n = 32) of them worked with professiona...
Adoptive T cell therapy (ACT) in combination with lymphodepleting chemotherapy is an effective strategy to induce the eradication of tumors, providing long-term regression in cancer patients. Despite that lymphodepleting regimens condition the host for optimal engraftment and expansion of adoptively transferred T cells, lymphodepletion concomitantly promotes immunosuppression during the course of endogenous immune recovery. In this study, we have identified that lymphodepleting chemotherapy initiates the mobilization of hematopoietic progenitor cells that differentiate to immunosuppressive myeloid cells, leading to a dramatic increase of peripheral myeloidderived suppressor cells (MDSCs). In melanoma and lung cancer patients, MDSCs rapidly expanded in the periphery within 1 week after completion of a lymphodepleting regimen and infusion of autologous tumor-infiltrating lymphocytes (TILs). This expansion was associated with disease progression, poor survival, and reduced TIL persistence in melanoma patients. We demonstrated that the interleukin 6 (IL-6)-driven differentiation of mobilized hematopoietic progenitor cells promoted the survival and immunosuppressive capacity of post-lymphodepletion MDSCs. Furthermore, the genetic abrogation or therapeutic inhibition of IL-6 in mouse models enhanced host survival and reduced tumor growth in mice that received ACT. Thus, the expansion of MDSCs in response to lymphodepleting chemotherapy may contribute to ACT failure, and targeting myeloid-mediated immunosuppression may support anti-tumor immune responses.
The reproductive biology of only a small fraction of Neotropical freshwater fishes has been described, and detailed comparative studies of reproductive life-history variation in the Neotropical ichthyofauna are lacking. Here we describe interspecific variation in reproductive life history for a multi-species assemblage of the electric knifefish genus Brachyhypopomus (Hypopomidae: Gymnotiformes: Ostariophysi) from Amazonian floodplain and terra firme stream systems. During a year-round quantitative sampling program, we collected and measured key life-history traits from 3,410 individuals. Based on oocyte size distributions, and on circannual variation in gonadosomatic indices, hepatosomatic indices, and capture-per-unit-effort abundance of reproductive adults, we concluded that all species exhibit a single protracted annual breeding season during which females spawn fractionally. We found small clusters of post-larval individuals in one floodplain species and one terra firme stream species, but no signs of parental care. From analyses of body size-frequency distributions and otolith growth increments, we concluded that five species in our study area have approximately one-year (annual) semelparous life history with a single reproductive period followed by death, while two species have a two-year iteroparous life history, with breeding in both year-groups. Despite predictions from life-history theory we found no salient correlations between life history strategy (semelparity or iteroparity) and habitat occupancy (floodplain or terra firme stream). In the iteroparous species B. beebei, we documented evidence for reproductive restraint in the first breeding season relative to the second breeding season and argue that this is consistent with age-regulated terminal investment.
Background: Fellowship directors (FDs) influence the future of trainees in the field of hand surgery. Currently, there are no studies that analyze the demographic background, institutional training, and academic experience of hand surgery FDs. This study aims to serve as a framework to understand the landscape of current leadership positions in hand surgery education and to identify opportunities to improve FD diversity. Methods: The American Society for Surgery of the Hand Fellowship Directory was reviewed to include all hand surgery fellowships in the United States. Collected demographic information regarding FDs included age, sex, ethnicity, residency/fellowship training, residency/fellowship graduation year, year hired by current institution, time since training completion until FD appointment, length in FD role, and H-index. Results: Of the 90 FDs included, 86.7% were men and 71.4% self-reported as Caucasian. The average H-index was 13.98 and significantly correlated with age and duration as FD; 71.1% of FDs were trained in orthopedic surgery. The most attended residency program was the University of Pennsylvania; Mayo Clinic and Harvard University were the most represented fellowship programs. Conclusion: This review reveals specific trends in demographic backgrounds, institutional training, and academic experiences among current FDs in hand surgery. Our observations, such as racial/ethnic and sex disparities, may offer opportunities to improve the representation of the communities these physicians serve. In addition, the trends described in this study provide objective data among current hand surgery FDs and could serve as a guide for individuals who desire academic leadership roles.
Purpose: Metastatic melanoma is a tumor amenable to immunotherapy in part due to the presence of antigen-specific tumor-infiltrating lymphocytes (TIL). These T cells can be activated and expanded for adoptive cell transfer (ACT), which has resulted in relatively high rates of clinical responses. Similarly, immune checkpoint inhibitors, specifically PD-1 blocking antibodies, augment antitumor immunity and increase the influx of T cells into tumors. Thus, we hypothesized that addition of PD-1 inhibition may improve the outcomes for patients undergoing ACT with TIL. Patients and Methods: Stage III/IV metastatic melanoma patients with unresectable disease who were anti-PD-1 treatment-naïve were enrolled. TIL were generated in the presence of anti-4-1BB antibody in vitro and expanded for ACT. Patients in Cohort 1 received TIL infusion followed by nivolumab. Patients in Cohort 2 also received nivolumab prior to surgical harvest and during TIL production. Results: A total of 11 patients were enrolled, all of whom were evaluated for response, and nine completed ACT. Predominantly CD8+ TIL were successfully expanded from all ACT-treated patients and were tumor-reactive in vitro. The trial met its safety endpoint, as there were no protocol-defined dose-limiting toxicity events. The objective response rate was 36% and median progression-free survival was 5 months. Two non-responders who developed new metastatic lesions were analyzed to determine potential mechanisms of therapeutic resistance, which included clonal divergence and intrinsic TIL dysfunction. Conclusions: Combination therapy with TIL and nivolumab was safe and feasible for metastatic melanoma patients and provides important insights for future therapeutic developments in ACT with TIL.
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