Orthopedic Surgery Residencies: The Leap to Social Media.

Social media has been previously shown to influence applicants' perception of plastic surgery residencies and increase their likelihood to apply, interview, and rank the program. We wanted to analyze this hypothesized trend in the context of orthopedic surgery residency while also characterizing the content of orthopedic surgery residency program accounts. A current list of US orthopedic residency programs was acquired from the American Orthopaedic Association and cross-referenced with the Accreditation Council for Graduate Medical Education webpage of all orthopedic surgery residencies. Forty-five of 185 (24%) residencies had residency-specific Instagram accounts. We analyzed the number of followers, the number of posts, and the date of the first post for each account. We characterized content by categories including science education, recruitment or hospital promotion, resident highlight, news coverage, events, and community building posts. We analyzed the "social currency" of each post and program, tracking the number of likes, comments, and followers. Twenty-seven of 45 (60%) active residency Instagram pages were created in 2020, with 13 of 45 (29%) pages created in June 2020 alone. Residency programs are increasingly turning to Instagram to showcase the residents at their programs, their lifestyles, and program strengths. Sixty percent of all orthopedic residency Instagram accounts were created in 2020 alone, likely precipitated by travel concerns from COVID-19 forcing programs to conduct online interviews and cancel away rotations this application cycle. Going forward, residency programs will continue using Instagram to recruit potential residents, leaving programs without social media accounts at a relative disadvantage in terms of visibility and their ability to recruit qualified applicants. [Orthopedics. 2023;46(5):e281-e286.].

Prophylactic High-Dose Gabapentin Reduces Opiate Use during Radiation Therapy for Head and Neck Squamous Cell Carcinoma.

BACKGROUND: The role of prophylactic high-dose gabapentin for the management of oral mucositis during radiation therapy for head and neck squamous cell carcinoma (HNSCC) remains controversial. METHODS: A retrospective cohort analysis was performed on primary HNSCC patients treated at our institution. Kruskal-Wallis and Fisher's exact tests were used to compare the patients' baseline characteristics. Multivariate competing risk and logistic regressions were performed to evaluate time to first opioid use and feeding tube placement. RESULTS: In total, 480 consecutive HNSCC patients were included. Within this cohort, 186 patients received 3600 mg gabapentin, 182 received 300 to 3200 mg gabapentin, and 112 received no gabapentin. The time to first opioid use was greater in the 3600 mg group compared with the no gabapentin group (34.3 vs. 23.9 days, p < 0.001) and to the 300 to 3200 mg group (28.0 days, p < 0.001). The proportion of patients requiring opioids at any point during RT was lower in the 3600 mg gabapentin group compared with the no gabapentin group (31.8% vs. 60.1%, p < 0.001) and with the 300 to 3200 mg group (63.8%, p < 0.001). CONCLUSIONS: Prophylactic use of 3600 mg gabapentin was well tolerated, halved overall opioid use, and delayed the time to first opioid use during radiation therapy.

Severe Oral Mucositis After Intensity-Modulated Radiation Therapy for Head and Neck Cancer.

Importance: Oral mucositis (OM) is a common and debilitating adverse effect observed in patients with head and neck cancer (HNC) receiving radiation therapy (RT). Previous studies examining associations between OM and clinical outcomes were performed in the era of 3-dimensional conformal RT planning with low rates of concurrent chemotherapy, and thus may not reflect current practice. Objective: To prospectively assess patient-reported OM and identify its associations with clinical outcomes and quality of life. Design, Setting, and Participants: This cohort study performed at a single institution included 702 consecutive patients who underwent definitive or adjuvant intensity-modulated RT (IMRT) for primary HNC from February 9, 2015, to May 27, 2022. Data were analyzed from November 28, 2022, to August 18, 2023. Main Outcomes and Measures: Severity of OM was assessed based on highest reported mouth and throat soreness (MTS) score during radiotherapy according to the Oral Mucositis Weekly Questionnaire-Head and Neck Cancer survey, which was administered weekly during IMRT. Linear mixed models were used to compare mean MTS scores grouped by disease site and chemotherapy regimen. Fisher exact tests and 1-way analysis of variance tests were performed to identify associations between severity of OM and clinical outcomes. Results: Among 576 eligible patients, the median age was 62.5 (IQR, 56.3-69.1) years, and 451 patients (78.3%) were men. In terms of race and ethnicity, 6 patients (1.0%) were American Indian or Alaska Native; 2 (0.3%), Asian; 31 (5.4%), Black; 8 (1.4%), Hispanic or Latino; 509 (88.4%), White; and 28 (4.9%), unknown. The most common treatment site was oropharynx (268 [46.5%]), and most patients received concurrent chemotherapy (464 [80.6%]). By the end of treatment, 360 patients (62.5%) developed severe OM and 568 (98.6%) developed some degree of OM. Linear mixed models found no significant differences in OM between HNC disease sites. Groups with greater highest severity of OM reported had higher rates of measured outcomes (listed respectively by MTS score 0, 1, 2, 3, and 4): feeding tube placement (0%, 3.6% [2 of 56], 6.6% [10 of 152], 14.7% [40 of 272], and 21.6% [19 of 88]; P = .001), hospitalization (12.5% [1 of 8], 10.7% [6 of 56], 15.1% [23 of 152], 23.9% [65 of 272], and 28.4% [25 of 88]; P = .02), opiate use (0%, 19.6% [11 of 56], 42.8%[65 of 152], 61.4% [167 of 272], and 64.8% [57 of 88]; P < .001) and experienced greater weight loss (median, -0.7 [IQR, -1.7 to -0.4] kg; median, 3.9 [IQR, 1.1 to 6.1] kg; median, 5.0 [IQR, 2.2 to 7.7] kg; median, 4.7 [IQR, 2.1 to 7.7] kg; and median, 7.7 [IQR, 2.8 to 10.6] kg; P < .001). Conclusions and Relevance: In this cohort study of patients with HNC, 62.5% developed severe OM. Higher severity of OM was associated with feeding tube placement, hospitalization, opiate use, and weight loss. Improvements in OM prevention and management are needed.

Gene Expression and Survival of Acute Lymphoblastic Leukemia Cells After Allogeneic Transplant.

BACKGROUND/AIM: This study explored the mechanisms of the allogeneic graft versus leukemia effect in acute lymphoblastic leukemia (ALL) cells by examining whether they change gene expression in the post-transplant environment containing cytokines and the immunosuppressant cyclosporine, and if such changes affect ALL cell survival. MATERIALS AND METHODS: RNASeq was used to assess leukemia global gene expression and flow cytometry to measure ALL survival in the presence of T cells, NK cells, cytokines, and cyclosporine. RESULTS: A total of 4,805 genes were differentially expressed. Gene set enrichment analysis demonstrated up-regulation of biological processes related to cytokine responses, control of viral infection, and regulation of leukocyte function including proliferation. Down-regulated genes were related to mesenchymal tissue morphogenesis. ALL cells exposed to cytokines and cyclosporine retained susceptibility to T and NK cell killing, and also exhibited increased cell death without exposure to killer cells. CONCLUSION: A significant portion of the graft versus leukemia effect may be mediated by cytokines and cyclosporine.

Serine protease inhibitor 6 protects alloreactive T cells from Granzyme B-mediated mitochondrial damage without affecting graft-versus-tumor effect.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for hematologic malignancies. Donor T cells are able to eliminate residual tumor cells after allo-HCT, producing the beneficial graft-versus-tumor (GVT) effect, but can also cause graft-versus-host disease (GVHD) when attacking host normal tissues. We previously reported that granzyme B (GzmB) is involved in activation-induced cell death (AICD) of donor T cells and exerts differential impacts on GVHD and GVT effect. Serine protease inhibitor 6 (Spi6) is the sole endogenous inhibitor of GzmB that can protect immune and tissue cells against GzmB-mediated damage. This study is aimed to delineate the mechanism by which the GzmB-Spi6 axis regulates allogeneic T cell response. Using multiple clinically relevant murine allo-HCT models, we have found that Spi6 is concentrated in mitochondria during allogeneic T cell activation, while Spi6-/- T cells exhibit abnormal mitochondrial membrane potential, mass, reactive oxygen species (ROS) production and increased GzmB-dependent AICD mainly in the form of fratricide. Compared with WT T cells, Spi6-/- T cells exhibit decreased expansion in the host and cause significantly reduced GVHD. Notably, however, Spi6-/- T cells demonstrate the same level of GVT activity as WT T cells, which were confirmed by two independent tumor models. In summary, our findings demonstrate that Spi6 plays a novel and critical role in maintaining the integrity of T cell mitochondrial function during allogeneic response, and suggest that disabling Spi6 in donor T cells may represent a novel strategy that can alleviate GVHD without sacrificing the beneficial GVT effect.