Total aortic arch debranching with antegrade Thoracic Endovascular Aortic Repair (TEVAR) in acute non-A non-B aortic dissection.

BACKGROUND: The surgical evaluation and management of non-A non-B aortic dissections, in the absence of ascending aortic involvement, remains a grey area. It is in these scenarios when thorough evaluation of patient/family history, clinical presentation, but also overall lifestyle, is of immense importance when determining an optimal intervention. CASE PRESENTATION: We present a 38-year-old patient with a physically demanding lifestyle as a professional wrestler, uncontrolled hypertension due to history of medical non-adherence, and family history of aortic dissection who presented with acute non-A non-B aortic dissection. He was spared a total arch replacement by undergoing a hybrid approach of complete aortic debranching with antegrade Thoracic Endovascular Aortic Repair (TEVAR). The patient was able to benefit from reduced cardiopulmonary bypass (CPB) time, avoidance of aortic cross clamp, circulatory arrest, and hypothermic circulation. CONCLUSIONS: This patient's unique composition of a physically demanding lifestyle, personal history of medical non-adherence, family history of aortic dissection, and clinical presentation required a holistic approach to understanding an ideal intervention that would be best suited long-term. Due to this contextualization, the patient was able to be spared a total arch replacement, or suboptimal medical management, by instead undergoing a hybrid-approach with total aortic arch debranching with antegrade TEVAR.

Trends in Mohs surgery fellowship directors.

The purpose of this study is to illustrate demographic trends among Mohs Micrographic Surgery (MMS) Fellowship Directors. Our search was constructed from the 2022 to 2023 Mohs Micrographic Surgery Fellowship Directory on the Accreditation Council for Graduate Medical Education (ACGME) website. Datapoints gathered included: age, sex, residency/fellowship training location, time since training completion until FD appointment, length in FD role, and personal research H-index. We identified 77 FDs, of which all 77 were included in this study. The mean age was 55.5 years; 55 (71.4%) were men and 20 (26.0%) were women. Most of the FDs who completed the survey did not self-report ethnicity or race, so these measures were not included. The top residency institutions that produced the most FDs were Cleveland Clinic (n = 4), Mayo Clinic (n = 4), New York University Medical Center (NYU, n = 4), and University of California-Los Angeles (UCLA, n = 4); the top fellowship institutions were NYU (n = 7), UCLA (n = 5), Cleveland Clinic (n = 4), and Geisinger Medical Center (n = 4). The mean H-index was 15.9, the mean number of peer-reviewed publications was 71, and the mean time from training completion until FD appointment was 10 years. Our results indicate that a majority of FDs are men (71.4%) and that FDs are more likely to have graduated from certain residency and fellowship programs.

Gynecologic oncology fellowship leadership trends by gender.

Our objective was to examine the educational, research, and leadership trends among gynecologic oncology (GYO) fellowship program directors (PD) and how these vary by gender. PDs were identified using the Society of Gynecologic Oncology Fellowship Directory. Surveys were sent to PDs' emails to obtain information about demographics, education, and research background. Publicly available data and institutional biographies were used to supplement primary survey data for incomplete responses or survey non-responders. Scopus was used to determine the h-index and number of publications and citations for each PD. Parametric data were compared using unpaired two-tailed t-tests. Chi-square and Fisher's exact tests were performed for categorical data. The significance level was p < 0.05. Approximately one-half of PDs were female (50.8%). Female PDs had a younger mean age than male PDs (46.4 years vs 51.9 years, p = 0.0014). The average overall h-index was 22 (SD = 14.5) and the average number of publications was 71.2 (SD = 63.3). The average h-index was higher in male PDs than females (27.8 vs 16.3, p = 0.0012), as were the number of publications (97.3 vs 45.8, p = 0.0008). Differences exist among GYO PDs by gender. While research productivity may be reflective of age, gender-based equity in research time should be further explored.

Demographics and characteristics of leadership at allergy and immunology fellowships in the U.S. as of 2022.

Background: The subspecialty of allergy and immunology (AI) has grown tremendously since the first fellowship programs were developed nearly 80 years ago; however, there is little information with regard to the demographic characteristics and trends in training of fellowship directors (FDs). Objective: Our goal was to analyze the demographic characteristics and pathways in training that have led FDs to advance in the field and train the next generation of allergists and immunologists. Methods: We created a list of all current AI fellowship programs and FDs within the United States. Specific biographical, training, and research information was collected via an Internet search and questionnaire responses. The data were recorded and analyzed in a spreadsheet and unpaired t-tests were performed between male versus female groups for H - index comparison to establish if there was a statistically significant difference. Results: There were 84 total AI fellowship programs with 84 FDs. Forty-one FDs (48.8%) were men and 43 FDs (51.2%) were women; mean age was 51.1 years; and the average age at appointment for men was 45.7 years and for women was 41.4 years, with a statistically significant difference (p = 0.02). Self-reported race and ethnicity (77.4% response rate [n = 65]) were as follows: 55.4% white (n = 36), 23.1% Asian (n = 15), 6.2% biracial (n = 4), 7.7% Middle Eastern (n = 5), 4.6% Hispanic (n = 3), and 3.1% Black (n = 2). The average Hirsch-index (h-index) for FDs was 14.2, with an average of 42.1 publications and 1532.2 citations. The difference between the h-index for the men and for the women was statistically significant, being 17.8 and 11.2 respectively, with p = 0.0143. Conclusion: In AI FDs, women were adequately represented, and men and women were hired at similar ages. There was a statistically significant difference in research output (estimated by the h-index) between men and women. This suggests that research output did not limit women in being appointed as FDs.

Trends in Leadership Among Neurosurgical Oncology Fellowships.

OBJECTIVE: To examine current neurosurgical oncology leadership trends and provide a guide for those interested in obtaining fellowship directorship, we investigated fellowship director (FD) demographic, educational, and leadership characteristics. METHODS: The American Association of Neurological Surgeons Academic Fellowship Directory and Committee on Advanced Subspecialty Training websites were reviewed for current U.S. program FDs for which data were collected using online resources and surveys. RESULTS: In total, 23 FDs (20 male and 3 female) were represented whose mean age was 52.4 years (standard deviation = 8.7). Our analysis found 65% of current neurosurgical oncology FDs to be singularly trained in neurosurgical oncology, with 8.7% possessing multiple fellowships and 34.8% possessing additional degrees. Fellowship programs producing the most FDs were University of Texas MD Anderson (4), Memorial Sloan Kettering (3), and University of Miami (2). FDs possessed an average of 148 publications, 6423 citations, and an h-index of 33.9. H-index had a high-positive correlation with age and time from residency graduation but not duration of FD appointment. Among survey respondents, 91.7% reported membership and 75% reported leadership positions among national academic societies, whereas 66.7% reported holding journal-editorial positions. The mean age of FD appointment was 46.8 years, with a mean time from fellowship completion to FD appointment of 10.0 years. CONCLUSIONS: Through the characterization of current leaders in the field, we provide valuable information with regards to training location trends, research productivity goals, career timelines, and target journal/national academic society involvement worth consideration among young trainees when making career decisions and plans.

Leadership Trends at Hand Surgery Fellowships.

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.

The Impact of Targetable Mutations on Clinical Outcomes of Metastatic Epidural Spinal Cord Compression in Patients With Non-Small-Cell Lung Cancer Treated With Hybrid Therapy (Surgery Followed by Stereotactic Body Radiation Therapy).

BACKGROUND: In treatment of metastatic epidural spinal cord compression (MESCC), hybrid therapy, consisting of separation surgery, followed by stereotactic body radiation therapy, has become the mainstay of treatment for radioresistant pathologies, such as non-small-cell lung cancer (NSCLC). OBJECTIVE: To evaluate clinical outcomes of MESCC secondary to NSCLC treated with hybrid therapy and to identify clinical and molecular prognostic predictors. METHODS: This is a single-center, retrospective study. Adult patients (≥18 years old) with pathologically confirmed NSCLC and spinal metastasis who were treated with hybrid therapy for high-grade MESCC or nerve root compression from 2012 to 2019 are included. Outcome variables evaluated included overall survival (OS) and progression-free survival, local tumor control in the competing risks setting, surgical and radiation complications, and clinical-genomic correlations. RESULTS: One hundred and three patients met inclusion criteria. The median OS for this cohort was 6.5 months, with progression of disease noted in 5 (5%) patients at the index tumor level requiring reoperation and/or reirradiation at a mean of 802 days after postoperative stereotactic body radiation therapy. The 2-year local control rate was 94.6% (95% CI: 89.8-99.3). Epidermal growth factor receptor (EGFR) treatment-naïve patients who initiated EGFR-targeted therapy after hybrid therapy had significantly longer OS (hazard ratio 0.47, 95% CI 0.23-0.95, P = .04) even after adjusting for smoking status. The presence of EGFR exon 21 mutation was predictive of improved progression-free survival. CONCLUSION: Hybrid therapy in NSCLC resulted in 95% local control at 2 years after surgery. EGFR treatment-naïve patients initiating therapy after hybrid therapy had significantly improved survival advantage. EGFR-targeted therapy initiated before hybrid therapy did not confer survival benefit.

Cross-sectional Evaluation of Neurotology Fellowship Directors: A Present-day Snapshot of Leadership.

Objective: To identify demographic, training, and career trends of neurotology fellowship directors (FDs). Study Design: Cross-sectional study. Setting: United States. Subjects: All 26 neurotology FDs identified using the American Neurotology Society (ANS) ACGME Accredited Neurotology Fellowship Program Directory, accessed November 2021. Main Outcome Measures: Data were collected via CVs, institutional biographies, and emailed questionnaires. Data collected includes age, gender, race and ethnicity, residency and fellowship training institution, time since training completion until FD, length of time as FD, and Hirsch-index (h-index). Results: Twenty-six FDs were identified, and 17/26 (65.4%) FDs responded to the questionnaire. The majority (23/26; 88.5%) were male. The mean age of male and female FDs was 56 versus 47 years, respectively. Of the 17 that responded to the survey, 82.4% (14/17) self-identified as Caucasian. The mean h-index was 25.4. Older age correlated with a higher h-index (r = 0.46, P = 0.019). The duration (mean ± SD, years) from fellowship graduation to FD appointment was 10.7 ± 8.1 and 6.3 ± 4.8 from institutional hire. Six (23.1%) FDs had secondary graduate degrees, and 9 (34.6%) held a leadership position at a national otolaryngology organization. Conclusion: This observational study assesses demographic data on current neurotology FDs in the United States with an analysis of gender disparities. The objective measures identified can provide a baseline for growth in FD leadership.

Combination Nivolumab, CD137 Agonism, and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma.

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 programmed cell death protein 1 (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 TILs. PATIENTS AND METHODS: Patients with stage III/IV metastatic melanoma with unresectable disease who were anti-PD-1 treatment-naïve were enrolled. TILs 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+ TILs 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 nonresponders 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 TILs and nivolumab was safe and feasible for patients with metastatic melanoma and provides important insights for future therapeutic developments in ACT with TILs.

A snapshot of contemporary leadership at pediatric neurosurgery fellowships.

OBJECTIVE: Many pathways to positions of leadership exist within pediatric neurological surgery. The authors sought to investigate common trends in leadership among pediatric neurosurgery fellowship directors (FDs) and describe how formalized pediatric neurosurgical training arrived at its current state. METHODS: Fellowship programs were identified using the Accreditation Council for Pediatric Neurosurgery Fellowships website. Demographic, training, membership, and research information was collected via email, telephone, curricula vitae, and online searches. RESULTS: The authors' survey was sent to all 35 identified FDs, and 21 responses were received. Response data were supplemented with curricula vitae and online data prior to analysis. FDs were predominantly male, self-identified predominantly as Caucasian, and had a mean age of 53 years. The mean duration from residency graduation until FD appointment was 13.4 years. The top training programs to produce future FDs were New York University and Washington University in St. Louis (residency) and Washington University in St. Louis (fellowship). CONCLUSIONS: This study characterizes the current state of pediatric neurosurgery fellowship program leadership. The data serve as an important point of reference to compare with future leadership as well as contrast with neurosurgery and other surgical disciplines in general.

Demographics and Academic Productivity of Cardiothoracic Imaging Fellowship Program Directors in the United States: A Cross-Sectional Review.

Background In this study, we aimed to assess current demographics, measures of academic productivity, and other objective leadership characteristics among United States cardiothoracic imaging fellowship directors (FDs). Methodology A survey was sent to active members listed in the Society of Thoracic Radiology Cardiothoracic Imaging Fellowship Directory. Demographic, post-graduate training, and scholarly activity data were collected, including, but not limited to, age, sex, residency and fellowship training institutions, time since training completion until FD, length of time as FD, and Hirsch-index (h-index) to measure research activity. Results We identified 53 FDs from 50 cardiothoracic imaging fellowship programs. Of these, 31 (58.5%) were male and 22 (41.5%) were female with an average age of 48.5 years (standard deviation (SD) = 8.4, range = 35-67). There was no statistically significant difference between the mean age of male and female FDs (47.5 vs 50.2 years, p = 0.2811). The mean age of appointment to the FD role was 41.8 years. On average, FDs graduated from residency in 2005 and 2007 for fellowships. Most attended allopathic medical schools (52/53, 98.1%). The average Scopus h-index was 15.7 (SD = 17.4). Gender-wise comparison of mean h-indices revealed 16.2 for males and 15 for females, with no statistically significant difference between the two groups (p = 0.81). Ten (18.9%) FDs and 20 (37.7%) FDs were at the same location they completed residency and fellowship training, respectively. Conclusions This cross-sectional study shows the present demographics within the cardiothoracic radiology FD position. This field of radiology is observed to have FDs with research productivity that is comparable with other medical specialties. Some radiology residency and fellowship programs were shown to produce more FDs than others; however, we were not able to identify causality. Program directors appear to be selected from a familiar pool of applicants, and ultimately FDs are being replaced by individuals with similar distinctions. Overall, this research into cardiothoracic radiology FDs demographics and research productivity can add to the current body of literature on FDs in various medical specialties. It is important to continue to reflect on medical leadership as the field continues to advance.

Trends in leadership at breast surgical oncology fellowships.

Introduction: Breast surgical oncology is a defined sub-specialty of general surgery that focuses on the surgical management of breast disease and malignancy within a multidisciplinary context. The fellowship directors (FD) that lead these programs have been selected for their abilities. As programs do research to ensure proper training for the next generation of breast surgical oncologists, we wanted to look into the FDs responsible for their training. Methods: The Breast Surgical Oncology care program list was compiled via the Society of Surgical Oncology and American Society of Breast Surgeons Accredited programs (n = 60). The demographic information that was of interest included, but was not limited to, gender, age, ethnicity/background, past residency training, past fellowship training, year graduated from residency and fellowship, year since graduation to FD appointment, time at institution till FD appointment, and Hirsch index (h-index). Results: Data were collected on all 60 FDs. The average age of FDs was 52 years old, 27% of FDs are men and 73% of FDs are women. The average H-index, number of publications, and number of citations were 19, 67, and 2648, respectively. The mean graduation year from residency was 2003, and from fellowship was 2006; with a mean of 9 years post fellowship graduation until becoming an FD. The most frequently attended residency was Rush (n = 4), and the most common fellowships were Memorial Sloan Kettering (n = 8), MD Anderson Cancer Center (n = 7), and John Wayne Cancer Institute (n = 4). Nine of the FDs stayed at the same institution after doing both residency and fellowship there (15%). Conclusion: This is the first study to examine the demographics of those in FD positions in Surgical Breast Oncology, which is a relatively young fellowship. We found that FDs in Breast Surgical Oncology are defined by their high output of research. This qualification may be why the average age, and the number of years to FD are higher compared to other specialties where this research has been undertaken. Initial evaluation of FDs suggest more diversity in this field is needed. Further insight into the leaders training our next generation of surgeons is warranted.

Trends in leadership at orthopaedic surgery sports medicine fellowships.

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 professional sports teams, 29.82% (n = 17) with collegiate sports teams, and 14.04% (n = 8) with both professional and collegiate sports teams. Seven residency programs produced the greatest number of future FDs, included programs produced at least three future FDs. Seven fellowship programs produced the greatest number of future FDs, included programs produced at least four future FDs. Eight FDs (9.75%) completed two fellowships and three FDs (3.66%) finished three fellowships. Three FDs (3.66%) did not graduate from any fellowship training program. The Scopus H-indices for FDs are displayed as ranges that include 1 to 15 (31.71%, n = 26), 15 to 30 (34.15%, n = 28), 30 to 45 (20.73%, n = 17), 45 to 60 (6.10%, n = 5) and 60 to 80 (3.66%, n = 3). Specifically, the most impactful FD in research currently has a Scopus H-index value of 79. By comparison, the tenth most impactful FD in research had a Scopus H-index value of 43 (accessed December 1, 2019). CONCLUSION: This study provides an overview of current sports medicine FDs within the United States and functions as a guide to direct initiatives to achieve diversity equality.

Development of a Phantom Limb Pain Model in Rats: Behavioral and Histochemical Evaluation.

Therapeutic strategies targeting phantom limb pain (PLP) provide inadequate pain relief; therefore, a robust and clinically relevant animal model is necessary. Animal models of PLP are based on a deafferentation injury followed by autotomy behavior. Clinical studies have shown that the presence of pre-amputation pain increases the risk of developing PLP. In the current study, we used Sprague-Dawley male rats with formalin injections or constriction nerve injury at different sites or time points prior to axotomy to mimic clinical scenarios of pre-amputation inflammatory and neuropathic pain. Animals were scored daily for PLP autotomy behaviors, and several pain-related biomarkers were evaluated to discover possible underlying pathological changes. Majority displayed some degree of autotomy behavior following axotomy. Injury prior to axotomy led to more severe PLP behavior compared to animals without preceding injury. Autotomy behaviors were more directed toward the pretreatment insult origin, suggestive of pain memory. Increased levels of IL-1ß in cerebrospinal fluid and enhanced microglial responses and the expression of NaV1.7 were observed in animals displaying more severe PLP outcomes. Decreased expression of GAD65/67 was consistent with greater PLP behavior. This study provides a preclinical basis for future understanding and treatment development in the management of PLP.

Intensive Locomotor Training Provides Sustained Alleviation of Chronic Spinal Cord Injury-Associated Neuropathic Pain: A Two-Year Pre-Clinical Study.

Neuropathic pain often accompanies the functional deficits associated with spinal cord injury (SCI) and further reduces a patient's quality of life. Clinical and pre-clinical research is beginning to highlight the beneficial role that rehabilitative therapies such as locomotor training can have not only on functional recovery but also on chronic pain management. Our group has previously developed an intensive locomotor training (ILT) treadmill protocol on rats that reduced SCI neuropathic pain symptoms for at least 3 months. We have extended these findings in the current study to evaluate the ability of regular ILT regimen over a 2 year period post-SCI to maintain neuropathic pain reduction. To assess this, the rat clip compression SCI model (T7/8) was used and treadmill training was initiated starting 4 weeks after SCI and continuing through the duration of the study. Results showed continued suppression of SCI neuropathic pain responses (reduced mechanical, heat, and cold hypersensitivity throughout the entire time course of the study). In contrast, non-exercised rats showed consistent and sustained neuropathic pain responses during this period. In addition, prolonged survival and improved locomotor outcomes were observed in rats undergoing ILT as the study longevity progressed. Potential contributory mechanisms underlying beneficial effects of ILT include reduced inflammation and restoration of anti-nociceptive inhibitory processes as indicated by neurochemical assays in spinal tissue of remaining rats at 2 years post-SCI. The benefits of chronic ILT suggest that long-term physical exercise therapy can produce powerful and prolonged management of neuropathic pain, partly through sustained reduction of spinal pathological processes.

Reactive Myelopoiesis Triggered by Lymphodepleting Chemotherapy Limits the Efficacy of Adoptive T Cell Therapy.

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 myeloid-derived 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.

Trends in Leadership at Orthopedic Surgery Adult Reconstruction Fellowships.

BACKGROUND: Fellowship directors (FDs) in adult reconstruction have a profound impact on current and future trainees within orthopedics. Our group sought to evaluate the shared characteristics among current adult reconstruction FDs to provide a framework for those aspiring to achieve this position and identify possible areas of improvement. METHODS: Fellowship programs were identified using the American Association of Hip and Knee Surgeons Directory. Data for each FD were gathered via electronic mail, telephone, curriculum vitae, and online searches. Demographic information collected 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, and Scopus H-index. RESULTS: Information was gathered for 94 FDs. Of these, 100% were males; 80.6% were Caucasian, 12.90% were Asian American, 5.38% were Hispanic, and 1.08% were African American. The average age (52.6 years old), H-index (16.54), year of residency (2000) and fellowship (2001) graduation, and time since training until FD appointment (9.55 years) were analyzed. The top training programs to produce future FDs were Mayo Clinic (residency) and Harvard University (fellowship). CONCLUSION: Adult reconstruction FDs are frequently distinguished by their level of research productivity and experience, but certainly more demographic diversity is needed within this cohort. Specific training programs may inherently have a vital role in the development of individuals for future leadership positions. These developments could be a result of unique features inherent to the training programs or because of a subset of applicants who pursue specific programs with aspirations of subsequent leadership opportunities.

Reproductive life-history strategies in a species-rich assemblage of Amazonian electric fishes.

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.

Oxytocin in the tumor microenvironment is associated with lower inflammation and longer survival in advanced epithelial ovarian cancer patients.

BACKGROUND: Prior research demonstrates a protective role for oxytocin in ovarian cancer based on its anti-proliferative, anti-migratory, and anti-invasive effects in vitro and in vivo. However, the role of endogenous oxytocin has not been examined in ovarian cancer patients. Oxytocin also has anti-inflammatory properties that have not been examined in cancer. The purpose of this investigation was to examine relationships between endogenous oxytocin, tumor-associated inflammation (interleukin-6), and survival in advanced epithelial ovarian cancer patients. METHODS: Tumor microenvironment (ascites) and plasma oxytocin levels were analyzed via ELISA on extracted samples obtained from 79 patients. In vitro models were used to characterize oxytocin and oxytocin receptor expression in four ovarian cancer cell lines and to investigate direct anti-inflammatory effects of oxytocin on tumor cell secretion of interleukin-6. High and variable levels of oxytocin were observed in ascites, up to 200 times greater than in plasma. Higher levels of ascites oxytocin were associated with lower levels of systemic and tumor-associated interleukin-6, an inflammatory cytokine implicated in ovarian tumor progression. Oxytocin also attenuated interleukin-6 secretion from multiple ovarian tumor cell lines in vitro. Higher levels of ascites oxytocin were associated with a significant survival advantage and statistical mediation analyses suggested this effect was partially mediated by interleukin-6. CONCLUSIONS: These data identify a previously unacknowledged hormone in the ovarian tumor microenvironment and provide initial evidence that oxytocin has protective effects in ovarian cancer via anti-inflammatory mechanisms. Future studies should examine the therapeutic utility of oxytocin.