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Introduction: The impact of peripheral cytokine levels on the prognosis and treatment of immune checkpoint inhibitor (ICI) myocarditis has not been well studied. Objectives: This study aimed to identify cytokines that can prognosticate and direct the treatment of ICI myocarditis. Methods: This was a single-center, retrospective cohort study of patients with ICI myocarditis who had available peripheral cytokine levels between January 2011 and May 2022. Major adverse cardiovascular events (MACEs) were defined as a composite of heart failure with/without cardiogenic shock, arterial thrombosis, life-threatening arrhythmias, pulmonary embolism, and sudden cardiac death. Results: In total, 65 patients with ICI myocarditis had cytokine data available. Patients were mostly males (70%), with a mean age of 67.8 ± 12.7 years. Interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) were the most common cytokines to be elevated with 48/65 (74%) of patients having a peak IL-6 above normal limits (>5 pg/mL) and 44/65 (68%) of patients with peak TNF-α above normal limits (>22 pg/mL). Patients with elevated peak IL-6 had similar 90-day mortality and MACE outcomes compared to those without (10.4% vs. 11.8%, p = 0.878 and 8.8% vs. 17.7%, p = 0.366, respectively). Similarly, those with elevated peak TNF-α had similar 90-day mortality and MACEs compared to those without (29.6% vs. 14.3%, p = 0.182 and 13.6% vs. 4.8%, p = 0.413, respectively). Kaplan–Meier survival analysis also showed that there was not a significant difference between MACE-free survival when comparing elevated and normal IL-6 and TNF-α levels (p = 0.182 and p = 0.118, respectively). MACEs and overall survival outcomes were similar between those who received infliximab and those who did not among all patients and those with elevated TNF-α (p-value 0.70 and 0.83, respectively). Conclusion: Peripheral blood levels of IL-6 and TNF-α are the most commonly elevated cytokines in patients with ICI myocarditis. However, their role in the prognostication and guidance of immunomodulatory treatment is currently limited. [ABSTRACT FROM AUTHOR]

The addition of surgery to chemoradiation for esophageal cancer has not shown a survival benefit in randomized trials. Patients with more comorbidities or advanced age are more likely to be given definitive chemoradiation due to surgical risk. We aimed to identify subsets of patients in whom the addition of surgery to chemoradiation does not provide an overall survival (OS) benefit. The National Cancer Database was queried for patients with locally advanced esophageal cancer who received either definitive chemoradiation or neoadjuvant chemoradiation followed by surgery. Bivariate analysis was used to assess the association between patient characteristics and treatment groups. Log-rank tests and Cox proportional hazards models were performed to assess for differences in survival. A total of 15,090 with adenocarcinoma and 5,356 with squamous cell carcinoma met the inclusion criteria. Patients treated with neoadjuvant chemoradiation and surgery had significantly improved survival by Cox proportional hazards model regardless of histology if <50, 50–60, 61–70, or 71–80 years old. There was no significant benefit or detriment in patients 81–90 years old. Survival advantage was also significant with a Charlson/Deyo comorbidity condition score of 0, 1, 2, and ≥3 in adenocarcinoma squamous cell carcinoma with scores of 2 or ≥3 had no significant benefit or detriment. Patients 81–90 years old or with squamous cell carcinoma and a Charlson/Deyo comorbidity score ≥ 2 lacked an OS benefit from neoadjuvant chemoradiation followed by surgery compared with definitive chemoradiation. Careful consideration of esophagectomy-specific surgical risks should be used when recommending treatment for these patients. [ABSTRACT FROM AUTHOR]

Purpose: American Brachytherapy Society (ABS) guidelines recommend using a 3-5 cm active length (AL) when treating vaginal cuff (VC) in adjuvant setting of endometrial cancer (EC). The purpose of this study was to evaluate local control and toxicity, using an AL of 1 or 2 cm and immobilization with a traditional table-mounted (stand) or patient-mounted (suspenders) device. Material and methods: Between 2005 and 2019, 247 patients with EC were treated with adjuvant high-dose-rate vaginal cuff (HDR-VC) brachytherapy with or without external beam radiation (EBRT). Treatment was prescribed to a 0.5 cm depth, with an AL of 1 or 2 cm, using stand or suspenders. VC boost after EBRT was typically administered with 2 fractions of 5.5 Gy, while VC brachytherapy alone was typically applied with 3 fractions of 7 Gy or 5 fractions of 5.5 Gy. Results: The combination of suspender immobilization and an AL of 2 cm (n = 126, 51%) resulted in 5-year local control of 100%. An AL of 2 cm compared to 1 cm correlated with better local control (99.1% vs. 88.5%, p = 0.0479). Regarding immobilization, suspenders correlated with improved local control compared to stand (100% vs. 86.7%, p = 0.0038). Immobilization technique was significantly correlated with AL (p < 0.0001). Only 5 (2.0%) patients experienced grade ≥ 3 toxicity, all of whom received EBRT. Conclusions: In the present series, an AL of 2 cm provided excellent local control, while 1 cm was inadequate. Suspender immobilization was a practical alternative to stand immobilization in HDR brachytherapy of the vaginal cuff. [ABSTRACT FROM AUTHOR]

Purpose: We present our institutional experience in treating brain metastases with GK-SRS and a headframe fixed to the skull with only 3 pins to avoid collisions between the headframe and the Gamma Knife (GK) machine. Methods and materials: Among 3500 consecutive patients who received GK-SRS in 2011-2017, 50 had 1 of the 2 anterior pins removed immediately before treatment of ≥1 brain lesion. Endpoints were local control, dosimetric parameters, and toxicity. Results: Median follow-up time for the 49 patients with follow-up was 7.0 months (range 0.2- 57.0). Median number of lesions treated per session was 6 (range 1-18); a median 1 lesion was treated with 3-pin fixation (range 1-2) and a median 5 lesions treated with 4-pin fixation (range 0-17) during the same session. Lesions treated with 3-pin fixation were in the occipital lobe (n=41), cerebellum (n=9), or temporal lobe (n=1). No local failures were noted. The sole grade 2 toxicity (partial seizure) was attributed to treatment of a 4-pin-fixed lesion. Except for gradient index, dosimetry did not vary for lesions treated with 3-pin versus 4-pin fixation. Conclusions: Treating brain metastases with 3-pin fixation did not compromise treatment outcome and is a good option for posterior brain metastases that cannot otherwise be treated with 4-pin GK-SRS. [ABSTRACT FROM AUTHOR]

Purpose: We sought to validate the Prognostic Index for Spinal Metastases (PRISM), a scoring system that stratifies patients into subgroups by overall survival. Methods and materials: The PRISM was previously created from multivariate Cox regression with patients enrolled in prospective single institution trials of stereotactic spine radiosurgery (SSRS) for spinal metastasis. We assess model calibration and discrimination within a validation cohort of patients treated off-trial with SSRS for metastatic disease at the same institution. Results: The training and validation cohorts consisted of 205 and 249 patients respectively. Similar survival trends were shown in the 4 PRISM. Survival was significantly different between PRISM subgroups (P<0.0001). C-index for the validation cohort was 0.68 after stratification into subgroups. Conclusions: We internally validated the PRISM with patients treated off-protocol, demonstrating that it can distinguish subgroups by survival, which will be useful for individualizing treatment of spinal metastases and stratifying patients for clinical trials. [ABSTRACT FROM AUTHOR]

Background The Bacillus genus of Firmicutes bacteria is ubiquitous in nature and includes one of the best characterized model organisms, B. subtilis, as well as medically significant human pathogens, the most notorious being B. anthracis and B. cereus. As the most abundant living entities on the planet, bacteriophages are known to heavily influence the ecology and evolution of their hosts, including providing virulence factors. Thus, the identification and analysis of Bacillus phages is critical to understanding the evolution of Bacillus species, including pathogenic strains. Results Whole genome nucleotide and proteome comparison of the 83 extant, fully sequenced Bacillus phages revealed 10 distinct clusters, 24 subclusters and 15 singleton phages. Host analysis of these clusters supports host boundaries at the subcluster level and suggests phages as vectors for genetic transfer within the Bacillus cereus group, with B. anthracis as a distant member. Analysis of the proteins conserved among these phages reveals enormous diversity and the uncharacterized nature of these phages, with a total of 4,442 protein families (phams) of which only 894 (20%) had a predicted function. In addition, 2,583 (58%) of phams were orphams (phams containing a single member). The most populated phams were those encoding proteins involved in DNA metabolism, virion structure and assembly, cell lysis, or host function. These included several genes that may contribute to the pathogenicity of Bacillus strains. Conclusions This analysis provides a basis for understanding and characterizing Bacillus and other related phages as well as their contributions to the evolution and pathogenicity of Bacillus cereus group bacteria. The presence of sparsely populated clusters, the high ratio of singletons to clusters, and the large number of uncharacterized, conserved proteins confirms the need for more Bacillus phage isolation in order to understand the full extent of their diversity as well as their impact on host evolution. [ABSTRACT FROM AUTHOR]