Mini-review on the properties and possible applications of therapeutic oxygen carrier Hemarina-M101.

Therapeutic Oxygen Carriers (TOCs) have been studied in the past for utilization in resuscitation fluid, treatment of organ ischemia, and as an alternative to red blood cell transfusion. One TOC, Hemarina-M101, seems promising in transplantation and oxygenation due its capability as a non-immunogenic, nontoxic, high-oxygen-carrying capacity TOC with little to no side effects. This mini-review focuses on Hemarina-M101 and explores its characteristics and possible utilities through past and recent studies.

CAR T-Cell-Associated Neurotoxicity: Current Management and Emerging Treatment Strategies.

Axicabtagene ciloleucel and tisagenlecleucel are 2 chimeric antigen receptor (CAR) T-cell immunotherapies targeting CD19 for the treatment of B-cell acute lymphoblastic leukemia and non-Hodgkin lymphoma. Two commonly recognized complications associated with CAR T-cell therapies are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). ICANS can occur in isolation or concomitantly with CRS following CAR T-cell therapy and may be due to disruption of the blood-brain barrier and the effects of elevated cytokine levels on the central nervous system. Presently, the optimum management of ICANS remains elusive, as there lacks consensus guidelines. The objective of this review is to provide a comprehensive summary of ICANS and strategies for prompt identification and management of patients presenting to the intensive care unit with this syndrome.

Disparities in Access to Radiotherapy Among Hispanic/Latinx Populations in the United States: How Far Have We Left to Go?

OBJECTIVES: The Hispanic/Latinx population has consistently faced disparities in oncology access and outcomes with cancer being the leading cause of death in this population. We evaluate recent research in radiation therapy disparities among the Hispanic/Latinx population in the United States since our seminal analysis from 2017. METHODS: A PubMed literature search was conducted for articles published from January 2017 through March 2023. Four term combinations were utilized, including: (1) "Hispanic" and "Radiotherapy" and "Disparities", (2) "Latino" and "Radiotherapy" and "Hispanic", (3) "Hispanic" and "Radiation" and "Disparities", and (4) "Latino" and "Radiation" and "Disparities." Included studies were those taking place in the United States, examined radiation oncology care, and examined health disparities. RESULTS: Fifty-eight of 245 articles returned met inclusion criteria and spanned 6 disparity-types: (1) Stage at Presentation, (2) Time to Treatment Initiation & Completion, (3) Receipt of Treatment and Guideline-Concordant Care, (4) Geography, (5) Clinical Trial Access and (6) Insurance Barriers and Treatment Center Type. The most common disparity was receipt of treatment and guideline-concordant care (n=39 studies), demonstrating that the Hispanic/Latinx population was less likely to receive guideline-concordant treatment or treatment at all. In additon, studies identified disparities in time to treatment and completion (n=12), geography (n=5), clinical trial access (n=3), and insurance and treatment center access (n=5). CONCLUSIONS: Disparities in radiotherapy access remain prominent for the Hispanic/Latinx population through a multitude of barriers, despite increasing interest in disparities research. Continued health care disparities research with tangible interventions are needed in radiation oncology to properly understand and address this problem.

Predictors of Financial Toxicity in Patients Receiving Concurrent Radiation Therapy and Chemotherapy.

Purpose: Financial toxicity (FT) is a significant concern for patients with cancer. We reviewed prospectively collected data to explore associations with FT among patients undergoing concurrent, definitive chemoradiation therapy (CRT) within a diverse, urban, academic radiation oncology department. Methods and Materials: Patients received CRT in 1 of 3 prospective trials. FT was evaluated before CRT (baseline) and then weekly using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Core-30 questionnaire. Patients were classified as experiencing FT if they answered ≥2 on a Likert scale question (1-4 points) asking if they experienced FT. Rate of change of FT was calculated using linear regression; worsening FT was defined as increase ≥1 point per month. χ2, t tests, and logistic regression were used to assess predictors of FT. Results: Among 233 patients, patients attended an average of 9 outpatient and 4 radiology appointments over the 47 days between diagnosis and starting CRT. At baseline, 52% of patients reported experiencing FT. Advanced T stage (odds ratio, 2.47; P = .002) was associated with baseline FT in multivariate analysis. The mean rate of FT change was 0.23 Likert scale points per month. In total, 26% of patients demonstrated worsening FT during CRT. FT at baseline was not associated with worsening FT (P = .98). Hospitalization during treatment was associated with worsening FT (odds ratio, 2.30; P = .019) in multivariate analysis. Conclusions: Most patients reported FT before CRT. These results suggest that FT should be assessed (and, potentially, addressed) before starting definitive treatment because it develops early in a patient's cancer journey. Reducing hospitalizations may mitigate worsening FT. Further research is warranted to design interventions to reduce FT and avoid hospitalizations.

Radiation Oncology Residency Training Program Integration of Diversity, Equity, and Inclusion: An Association of Residents in Radiation Oncology Equity and Inclusion Subcommittee Inaugural Program Director Survey.

PURPOSE: The aim of this study was to investigate United States (US) radiation oncology (RO) program directors' (PDs) attitudes and practices regarding racial/ethnic diversity, equity, and inclusion (DEI) to better understand potential effects on underrepresented in medicine (UIM) residents in RO. METHODS AND MATERIALS: A 28-item survey was developed using the validated Ethnic Harassment Experiences Scale and the Daily Life Experiences subscale, as well as input from DEI leaders in RO. The survey was institutional review board-approved and administered to RO PDs. PDs were provided with the American Association of Medical Colleges definition of UIM, that is, "Underrepresented in medicine means those racial and ethnic populations that are underrepresented in the medical profession relative to their numbers in the general population." Descriptive statistics were used in analysis. RESULTS: The response rate was 71% (64/90). Institutional Culture and Beliefs: 42% responded that they had a department DEI director. A minority (17%, n = 11) agreed "I believe that people from UIM backgrounds have equal access to quality tertiary education in the US." The majority (97%, n = 62) agreed "My program values residents from UIM backgrounds." Support and Resources: The majority (78%, n = 50) agreed "My program has resources in place to assist/provide support for resident physicians from UIM backgrounds." Interview and Recruitment: Most PDs (53%) had not taken part in activities aimed at recruiting UIM residents and 17% had interviewed no UIM applicants in the past 5 years for residency. Resident Experiences of Racism: 17% (n = 11) agreed "UIM residents in my program have reported incidents of racism to me," and 28% (n = 18) agreed "I believe that UIM residents in my program have been treated differently because of their race/ethnicity by faculty, staff, coresidents or patients." CONCLUSIONS: Most PDs reported that they did not believe that UIM residents were treated differently in their department because of their race/ethnicity, and only a minority had received reports of racial discrimination experienced by residents. These data contrast resident experiences and suggest a disconnect between DEI perceptions and resident experiences among US RO PDs that should be addressed through increased programmatic action and evaluation.

Tailored Mentorship for the Underrepresented and Allies in Radiation Oncology: The Association of Residents in Radiation Oncology Equity and Inclusion Subcommittee Mentorship Experience.

PURPOSE: There are limited opportunities for mentorship for underrepresented in medicine (URM) trainees and physicians in radiation oncology (RO). The purpose of this study was to create and evaluate a formal mentorship program open to URMs and allies with interests in diversity, equity, and inclusion. METHODS AND MATERIALS: A mentorship program incorporating a virtual platform was designed by the Association of Residents in Radiation Oncology Equity and Inclusion Subcommittee. It was structured to include 6 sessions over 6 months with matched mentor-mentee pairs based on responses to a publicized online interest form. A compilation of evidence-based guidelines was provided to optimize the mentorship relationship. Linked pre- and postprogram surveys were administered to collect demographic data, define baseline goals and level of support, and evaluate program satisfaction. RESULTS: Thirty-five mentor-mentee pairs were matched; 31 mentees completed the preprogram survey and 17 completed the postprogram survey. Preprogram, only 3 mentees (9.7%) reported satisfaction with current mentorship and 5 (16%) reported mechanisms or mentorship in place at their program to support URMs. On the postprogram survey, mentees reported high satisfaction with areas of mentorship, mentor attributes, and the program overall. Opportunities for improvement include implementation of mechanisms to enhance communication with mentor-mentee pairs and maintain longitudinal engagement. CONCLUSIONS: In the first tailored mentorship program in RO for URMs and those with diversity, equity, and inclusion interests, our results demonstrate that there is self-reported interest for better mentorship for URMs in RO, and that a nationwide structured mentorship program can address participants' goals with high satisfaction. Program expansion could provide URMs and allies in RO more opportunities for career development and promote a greater sense of community and inclusion within the field.

Radiation Oncology Resident Perspectives on Diversity, Equity, and Inclusion: An Association of Residents in Radiation Oncology Equity and Inclusion Subcommittee Inaugural Resident Survey.

PURPOSE: In this study, radiation oncology residents were surveyed on perceptions of diversity, equity, inclusion, and belonging in their residency training programs. METHODS AND MATERIALS: A 23-item survey was developed by the Association of Residents in Radiation Oncology Equity and Inclusion Subcommittee resident members and faculty advisors. The survey was divided into 4 sections: institutional culture, support and resources, interview and recruitment, and experiences of bias. The survey was sent individually to residents from all Accreditation Council for Graduate Medical Education-accredited radiation oncology programs. RESULTS: The survey was issued to 757 residents. A total of 319 residents completed the survey, for a response rate of 42%. All postgraduate years and geographic regions were represented. Significant racial, ethnic, and gender differences were present in survey response patterns. White residents (94%, 164 of 174) and male residents (96%, 186 of 194) were more likely to strongly agree/agree that they were treated with respect by their colleagues and their coworkers than other racial groups (P < .005) or gender groups (P < .008). Only 3% (5 of 174) of White residents strongly agreed/agreed that they were treated unfairly because of their race/ethnicity, while 31% (5 of 16) of Black residents and 10% (9 of 94) of Asian residents strongly agreed/agreed (P < .0001). Similarly, Hispanic residents were more likely to strongly agree/agree (24%, 5 of 21) than non-Hispanic residents (7%, 20 of 298) (P = .003). Regarding mentorship, there were no differences by gender or ethnicity. There were differences by race in residents reporting that they had a supportive mentor (P = .022), with 89% (154 of 174) of White residents who strongly agreed/agreed, 88% (14 of 16) of Black residents, and 91% of Asian residents (86 of 94). CONCLUSIONS: This survey reveals that experiences of support, mentorship, inclusion, and bias vary significantly among radiation oncology residents based on race, ethnicity, and gender. Radiation oncology has opportunity for growth to ensure an equitable experience for all residents.

Simple headache revealed a rare lymphoma: Waldenstrom macroglobulinemia with unique markers: a case report and review of the literature.

BACKGROUND: Waldenstrom macroglobulinemia (WM) is a rare lymphoma with an incidence rate of 3 per million people per year, with approximately 1000 to 1500 new cases diagnosed each year in the USA. It is primarily seen in Caucasian males with a median age of 70 years old. Patients are most often asymptomatic, but WM can manifest itself with constitutional symptoms such as lethargy, bleeding, organomegaly, and neurological or fundoscopic abnormalities. WM is characterized by immunoglobulin M (IgM) monoclonal gammopathy, lymphocytic infiltration of bone marrow, and normocytic anemia due to bone marrow replacement. CASE PRESENTATION: Our patient is a Hispanic 67-year-old female that presents with one month of intermittent band-like bilateral headache accompanied by dizziness, light-headedness, nausea, and blurred vision. A thorough diagnostic workup was performed, including serum protein electrophoresis (SPEP) with serum immunofixation (SIFE) showing an M spike and IgM kappa. Bone marrow biopsy was significant for lymphoplasmacytic infiltration with nodular B cells (CD19+, CD20+, CD22+). Computerized Tomography (CT) imaging showed splenomegaly in the patient. Treatment was provided for hyperviscosity syndrome with plasmapheresis twice. The patient reported improvement of her symptoms and was then scheduled for chemotherapy. Throughout 7 months, our patient received multiple cycles of bortezomib, dexamethasone, and rituximab. While her symptoms improved her psychiatric status got progressively worse. CONCLUSION: It is important not to neglect symptoms such as a headache, which may seem small, but could serve as a clue in the diagnosis of Waldenstrom's macroglobulinemia.

Prehospital administration of broad-spectrum antibiotics for sepsis patients: A systematic review and meta-analysis.

Background and Aims: Some studies have suggested that earlier initiation of antibiotics has shown positive outcomes in sepsis patients. We aimed to do a systematic review and meta-analysis to evaluate the effect of prehospital administration of antibiotics on 28 days mortality and length of stay in hospital and intensive care unit for sepsis patients. Methods: We formulated a search strategy and used it on search databases PubMed, Scopus, Web of Science, and Embase. We then screened the records for eligibility and included controlled studies, either clinical trials or cohort studies reporting prehospital antibiotic administration for sepsis patients. We excluded duplicates, books, conferences' abstracts, case reports, editorials, letters, author responses, not English studies, and studies with nonavailable full text. Animal and lab studies were also excluded. Results: The total number of studies identified is 1811, 19 were eligible for systematic review and 4 for meta-analysis (three cohort and one clinical trial). The total number of sepsis patients in the four included studies in the 28 days mortality outcome was 3523 (1779 took prehospital antibiotics and 1744 did not take prehospital antibiotics). Of 1779 who took the antibiotics, 190 died, and of 1744 who did not take antibiotics, 292 died (95% confidence interval 0.68-0.97, p = 0.02). Conclusion: This meta-analysis reveals that receiving prehospital antibiotics can significantly lower mortality in sepsis patients compared to patients who do not receive prehospital antibiotics. However, more clinical trials and multicenter prospective studies with high sample sizes are needed to get strong evidence supporting our findings.

COVID-19 and arrhythmia: An overview.

Arrhythmias in COVID-19 patients are associated with hypoxia, myocardial ischemia, cytokines, inflammation, electrolyte abnormalities, pro-arrhythmic or QT-prolonging medications, and underlying heart conditions such as severe congestive heart failure, inherited arrhythmia syndromes, or congenital heart conditions. In the pediatric population, multisystem inflammatory syndrome can lead to cardiac injury and arrhythmias. In addition, arrhythmias and cardiac arrests are most prevalent in the critically ill intensive care unit COVID-19 patient population. This review presents an overview of the association between COVID-19 and arrhythmias by detailing possible pathophysiological mechanisms, existing knowledge of pro-arrhythmic factors, and results from studies in adult and pediatric COVID-19 populations, and the clinical implications.

Evidence-based practice of stereotactic radiosurgery: Outcomes from an educational course for neurosurgery and radiation oncology residents.

BACKGROUND: As the field of brain and spine stereotactic radiosurgery (SRS) continues to grow, so will the need for a comprehensive evidence base. However, it is unclear to what degree trainees feel properly equipped to use SRS. We assess the perceptions and comfort level reported by neurosurgery and radiation oncology residents concerning the evidence-based practice of SRS. METHODS: A continuing medical education (CME) course provided peer-reviewed updates regarding treatment with intracranial and spinal SRS. Presentations were given by neurosurgery and radiation oncology residents with mentorship by senior faculty. To gauge perceptions regarding SRS, attendees were surveyed. Responses before and after the course were analyzed using the Fisher's exact test in R statistical software. RESULTS: Participants reported the greatest knowledge improvements concerning data registries (P < 0.001) and clinical trials (P = 0.026). About 82% of all (n = 17) radiation oncology and neurosurgery residents either agreed or strongly agreed that a brain and spine SRS rotation would be beneficial in their training. However, only 47% agreed or strongly agreed that one was currently part of their training. In addition, knowledge gains in SRS indications (P = 0.084) and ability to seek collaboration with colleagues (P = 0.084) showed notable trends. CONCLUSION: There are clear knowledge gaps shared by potential future practitioners of SRS. Specifically, knowledge regarding SRS data registries, indications, and clinical trials offer potential areas for increased educational focus. Furthermore, the gap between enthusiasm for increased SRS training and the current availability of such training at medical institutions must be addressed.

Hybrid tandem and ovoids brachytherapy in locally advanced cervical cancer: impact of dose and tumor volume metrics on outcomes.

PURPOSE: To report the impact of dose and tumor volume metrics at brachytherapy on outcomes for locally advanced cervical cancer treated with tandem and ovoids intracavitary/interstitial brachytherapy. MATERIAL AND METHODS: FIGO stage IB1-IIIB locally advanced cervical cancer treated with intracavitary/interstitial brachytherapy via a tandem and ovoids hybrid applicator were analyzed. Median high-risk clinical target volume (HR-CTV), rate of tumor volume reduction, EQD2 D90, organ at risk doses, and outcomes were recorded. Univariable and multivariable Cox regression was applied for survival analysis, and logistic regression was used for toxicity analysis. RESULTS: Seventy-one patients were identified. Median follow-up was 24.9 months, with a 2-year local control of 83.6%, loco-regional control of 72.0%, and overall survival of 88.6%. Median HR-CTV D90 was 87.4 Gy (IQR = 85.7-90.2). Median HR-CTV D90 > 90 Gy10 showed a trend toward improved local control (LC) (p = 0.19). Median HR-CTV was 37.9 cm3, and median V100 was 86.5%. A median HR-CTV of ≥ 40 cm3 demonstrated worse loco-regional control (LRC) (p = 0.018) and progression-free survival (p = 0.021). Two-year LC and LRC for stage IIB patients with a median HR-CTV < 40 cm3 were significantly improved as compared to ≥ 40 cm3 at 100% and 71.8%, respectively (p = 0.019) and 100% and 56.5%, respectively (p = 0.001). However, this trend was not statistically significant for stage IIIB patients. Higher percent per day reduction in HR-CTV during brachytherapy showed improved LRC (p = 0.045). Four percent of patients experienced acute grade 3 genitourinary toxicity, 1% late grade 3 genitourinary and 1% late grade 3 gastrointestinal toxicity. CONCLUSIONS: Tandem and ovoids intracavitary/interstitial brachytherapy provides satisfactory outcomes with modest toxicity. Higher HR-CTV D90 coverage demonstrated a trend toward improved tumor control. Tumor volume based on median HR-CTV ≥ 40 cm3 at brachytherapy was prognostic for poor outcomes, even within initial FIGO stage groups warranting caution.

Solvent-free, Noncontact Electrostatic Sampling for Rapid Analysis with Mass Spectrometry: Application to Drugs and Explosives.

A hand-held Van de Graaf generator is used to apply a high voltage, negligible current electrostatic potential to a wire mesh positioned in close proximity to a particle-laden surface in order to collect those particles for analysis. The electrostatic field effects transfer particles to the mesh without a requirement for mechanical contact between mesh and surface. Analysis of chemicals present in the sampled particles is completed by thermal desorption electrospray ionization. The utility of the method for noncontact sampling is demonstrated using solid drug powder samples, and inorganic explosives dispersed either on solid surfaces or in sand/soil in order to simulate common interfering matrices that might be encountered in the forensic environment. A metal mesh sampling substrate is utilized instead of traditional polymer-based swabs in order to permit thermal desorption at higher temperatures. The method leaves no visible trace of sampling leaving details such as a fingerprint image unperturbed, as demonstrated using fluorescence photography. Direct sampling of trace particles from hard surfaces and skin documents flexibility in the choice of sampling substrates, desorption temperatures, and sampling times. The potential of the device for use in forensic analyses is detailed.

Model assessment of individual tumor control rate and adverse effects in comparing locally advanced cervical cancer treatment using intracavitary with and without interstitial brachytherapy.

PURPOSE: This study assessed the modeled probability of tumor control and organ at risk toxicities in locally advanced cervical cancer in patients treated by external beam radiation plus brachytherapy using intracavitary combined with interstitial brachytherapy (IC/IS) vs. intracavitary brachytherapy (IC) alone. MATERIAL AND METHODS: Twenty cervical cancer patients with a mean HR-CTV volume of 47.4 cm3 and a mean width of 54 mm were planned with both IC/IS and IC brachytherapy alone. A probit model was utilized to model 3-year (3-yr) local control rate (LC), 3-yr cancer specific survival rate (CSS), and the adverse effect (AE) of the organ at risk by using a modeled data set from multiple institutions. Modeling results were used to estimate the LC, CSS, and AE of the treatments in this study. RESULTS: Using the IC/IS technique, an EQD2 increase of 12.3 Gy to D90 (from 76.1 Gy to 88.3 Gy) of HR-CTV is expected to increase 3-yr LC and 3-yr CSS by 12.5%, and 11.0%, respectively. Comparing IC/IS to IC alone, the expected G2+ AE were 7.7% vs. 7.9% for the bladder, and 5.9% vs. 6.8% for the rectum. CONCLUSIONS: The IC/IS technique improved dose coverage to the HR-CTV without significantly increasing dose to 2 cm3 of the organ at risk (OAR) surrounding it. With different regimens of EBRT combined with BT, IC/IS can be used to increase the probability of LC and CSS, or decrease the risk of AE.

Tumor volume threshold for achieving improved conformity in VMAT and Gamma Knife stereotactic radiosurgery for vestibular schwannoma.

BACKGROUND AND PURPOSE: Recent advances in multileaf collimator field shaping technology and inverse planning software have resulted in highly conformal LINAC based stereotactic radiosurgery (SRS) plans with minimal dose to critical structures. This modeling study compares Gamma Knife (GK) and LINAC SRS for vestibular schwannoma (VS). MATERIALS AND METHODS: 76 treatment plans from nineteen patients with VS were planned using GK forward planning and volumetric arc therapy (VMAT) inverse planning software. VMAT plans were generated with 1 coplanar, 3 and 5 non-coplanar arcs. Dose to normal structures and beam-on time (dose rate 600MU/min) were compared using Kruskal-Wallis and Dunn's post hoc test. RESULTS: Median tumor volume was 1.2cm(3) (range 0.1-4.8cm(3)). A peripheral tumor dose of 12Gy was prescribed. Tumor coverage was >99.8%. VMAT plans had lower target D2% and mean dose, as well as decreased beam-on time, compared to GK plans (p<0.0001). Paddick conformity index in VMAT 5 arc plans was superior to that of GK plans for targets >0.5cm(3) (p=0.002). Similar dose to cochlea, normal brain tissue and brainstem was observed. CONCLUSION: VMAT should be considered as a safe, alternative modality to GK for VS SRS treatment, especially for tumors larger than 0.5cm(3).

Integral valorization of Leucaena diversifolia by hydrothermal and pulp processing.

Wood from the leguminous tree, Leucaena diversifolia, was subjected to hydrothermal treatment (autohydrolysis) at 160-180 °C for 0-30 min followed by ethanol-soda-anthraquinone delignification. The liquid phase contained 18.65 g of sugars per liter, and the solid phase had a gross heating value of 19.083 MJ/kg, but could also be used as a source of cellulose pulp for the production of paper with tear, burst, and tensile indexes of 2.4 N m2/kg, 2.6 MPa m2/kg and 40.7 kN m/kg, respectively. L. diversifolia lends itself readily to valorization for energy production, and also to integral, fractional exploitation by autohydrolysis and ethanol-soda-anthraquinone delignification, which can additionally bring environmental benefits to cropping zones.