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Complementary and Alternative Medicine in Breast Cancer: Considerations for the Breast Surgical Oncologist
No full textA significant portion of cancer patients will consider or ultimately pursue complementary or alternative medicine (CAM) treatment strategies. Having a working knowledge of these topics is important for a surgical oncologist to participate in informed consent discussions when patients are considering CAM approaches. Psychological, physical, and dietary complementary approaches are discussed, as well as ethical considerations and communication strategies to approach these discussions
Genomic Analysis and Virulence Features of Vibrio cholerae Non-O1/Non-O139 Harbouring CARB-Type β-Lactamases From Freshwater Bodies, Argentina
No full textVibrio cholerae is a globally distributed, free-living bacterium in aquatic ecosystems. While non-O1/non-O139 serogroups typically do not produce cholera toxin, they have the potential to cause diarrhoea. These strains may act as reservoirs of antibiotic resistance in rivers, lakes and oceans. Understanding their genetic resistance and virulence can shed light on their role in spreading antimicrobial resistance and their pathogenicity. In this study, we characterised 60 V. cholerae non-O1/non-O139 strains from 16 freshwater bodies located throughout the Province of Córdoba, Argentina. We found none of the strains carried cholera toxin and identified ampicillin resistance as the most prevalent phenotype. Whole genome sequencing revealed that all ampicillin-resistant strains (n = 10) carried CARB β-lactamases, leading to the identification of new CARB variants (CARB-59 to CARB-62) likely associated with the V. cholerae superintegron. Two strains were notably related and exhibited enhanced virulence due to an unusual genetic arrangement of the VPI-1 pathogenicity island, encoding both the toxin co-regulated pilus and a type VI secretion system cluster subclass i5, commonly found in non-cholera Vibrio species. These findings provide significant insights into the genetic diversity and virulent potential of ampicillin-resistant environmental V. cholerae non-O1/non-O139 and enhance our understanding of the evolution of CARB β-lactamases within the species
Trends and Disparities in Ventricular Tachycardia-Related Mortality According to Cardiomyopathy Type in the United States
No full textBACKGROUND: Recent data show increased ventricular tachycardia (VT) related mortality. We aimed to investigate the trends and disparities of VT-related mortality according to cardiomyopathy subtypes.
METHODS: Mortality and demographic data were obtained from the CDC Wide-ranging Online Data for Epidemiologic Research database between 1999 and 2020. VT-related mortality was defined as the underlying cause of death and ischemic cardiomyopathy (ICM) or nonischemic cardiomyopathy (NICM) as the contributing cause of death. The direct method of standardization was utilized to estimate age-adjusted mortality rates (AAMRs). Temporal trends were evaluated using log-linear regression models.
RESULTS: A total of 15 888 deaths were related to both VT and ICM, and 16 777 were due to both VT and NICM. There was a significant increase in VT and ICM-related mortality between 2006 and 2020 with an APC of +1.38% (p \u3c 0.05). Similarly, VT and NICM-related mortality increased between 2008 and 2020 with an APC of +0.60% (p \u3c 0.05). ICM had a higher AAMR in males [6.23 (6.12-6.34)], Whites [3.49 (3.43-3.54)], Hispanics [2.11 (1.95-2.26)], and the Midwest region [3.73 (3.61-3.85)] compared to NICM. In contrast, NICM had a higher AAMR in females [1.57 (1.52-1.61)], Black or African Americans [5.02 (4.84-5.20)], and the South region [3.10 (3.03-3.18)]. p for all trend \u3c 0.05.
CONCLUSIONS: Real-world data show significant differences in VT-related mortality according to cardiomyopathy subtypes with prominent sex, race, and regional disparities. Clinical and public health strategies are needed to address inequities and improve outcomes
Sex, racial, and ethnic disparities in United States liver transplantation clinical trials
No full textBACKGROUND: Regulatory agencies are increasingly recognizing that minority trial representation is inadequate, contributing to healthcare disparities. The scope of minority population disparities in clinical trial participation remains unclear, as previous studies have compiled enrollment data from published trials, which frequently do not report participant race and ethnicity.
AIM: To evaluate sex, racial and ethnic inequities in liver transplantation (LT) trials participation in the United States.
METHODS: We used data from completed United States liver transplant clinical trials registered and reported on the National Institute of Health (NIH) website (clincaltrials.gov). Demographic data, including race, ethnicity, sex, and age were collected. To make inferences to a larger population, 95%CIs were computed for estimates in each demographic group using the Wilson method for binomial proportions. We also computed the simultaneous 95%CIs by applying a Bonferroni correction to reflect the multinomial distribution of race proportions. The numbers and percentages of racial/ethnic minority and female individuals compared with United States census data from 2010 and 2018. Secondary outcome measures were inclusion by trial funding source and year of completion.
RESULTS: A total of 69 United States based clinical trials involving 6990 participants were included in the analysis. Of these, 35 trials (51%) were randomized, and 26 (38%) were conducted across multiple United States regions. All trials reported sex, while 42 (61%) reported race and 27 (39%) reported ethnicity. Compared to United States census data, Asian individuals were overrepresented (9.3%; 95%CI: 8.1%-10.5%), whereas African American (7.8%; 95%CI: 6.7%-8.9%) and American Indian or Alaska Native individuals (0.4%; 95%CI: 0.1%-0.6%) were underrepresented. The proportion of White participants (75.9%; 95%CI: 74.1%-77.7%) was consistent with census estimates. Hispanic participants were underrepresented (13.3%; 95%CI: 12.2%-14.5%) regardless of the census year referenced. In industry-sponsored trials, Asian representation was three times higher than in the general population (15%). NIH funded trials showed overrepresentation of White participants (83.8%) and underrepresentation of Black participants (4.1%) relative to census data. Women comprised 31.1% of all participants (95%CI: 30.0%-32.2%), indicating underrepresentation. Among trials that reported racial data, 62 (90%) did not include participants of American Indian or Alaska Native, Native Hawaiian, or Pacific Islander descent.
CONCLUSION: Our analysis indicates that women, African Americans, and Hispanic individuals are underrepresented in LT clinical trials compared to the general United States population. These results highlight the need for regulatory initiatives aimed at enhancing the inclusion of historically marginalized racial and ethnic groups in clinical research
Safety of Esophageal Dilation Procedures in Patients on Antithrombotic Therapy: A Propensity-Matched Cohort Study
No full textINTRODUCTION: Esophageal dilation procedures are frequently performed on patients who are taking antithrombotic medications. The aim of this study was to evaluate whether patients on antithrombotic therapies have an increased risk of bleeding from esophageal dilation.
METHODS: A retrospective propensity-matched cohort study was conducted to evaluate patients in the TriNetX US Collaborative Network database who underwent esophageal dilation procedures. The primary outcome was to assess the effect of anticoagulants and dual-antiplatelet therapies (DAPTs) on the rate of postprocedural gastrointestinal bleeding within 30 days.
RESULTS: Patients on anticoagulants were found to be at higher risk of postprocedural gastrointestinal bleeding compared with patients not on anticoagulants (relative risk [RR], 1.43; 95% confidence interval [CI], 1.06-1.92; P = 0.017). The anticoagulant group had higher rates of blood transfusion and intensive care unit admission. The DAPT group had a higher rate of gastrointestinal bleeding compared with no antiplatelet therapy, though this did not reach statistical significance (RR, 1.64; 95% CI, 0.97-2.75; P = 0.06). When compared with aspirin monotherapy, the difference in bleeding rates was also not statistically significant (RR, 1.36; 95% CI, 0.84-2.19; P = 0.2). There was no difference in the rates of blood transfusion or intensive care unit admission when DAPT was compared separately with aspirin and with no antiplatelet groups. In addition, early resumption of anticoagulation or antiplatelet therapy was not associated with increased postprocedural bleeding.
DISCUSSION: Patients on anticoagulants at the time of esophageal dilation were at higher risk of postprocedural bleeding. DAPT was numerically associated with a higher risk of bleeding, but this did not reach statistical significance. These findings aim to inform the clinical decision making in preprocedure and postprocedure management of esophageal dilation procedures
Nrf2 drives activation-driven expansion of CD4(+)T cells by modulating glucose and glutamine metabolism
No full textUpon antigenic stimulation, CD4(+)T cells undergo clonal expansion elevating their bioenergetic demands and utilization of nutrients like glucose and glutamine. The nuclear factor erythroid-2-related factor 2 (Nrf2) is a well-known regulator of oxidative stress, but its involvement in modulating the metabolism of CD4(+)T cells remains unexplored. We report that Nrf2 protein levels are temporally regulated in activated CD4(+)T cells, with elevated expression during early activation followed by a decline. T cell-specific constitutive activation of Nrf2, by deletion of its negative regulator Keap1, enhances early activation and interleukin-2 (IL-2) expression, upregulates T cell receptor (TCR) signaling, and increases activation-driven expansion of CD4(+)T cells. Mechanistically, elevated Nrf2 activity in activated CD4(+)T cells increases chromatin accessibility and proliferation-associated gene expression. Metabolically, high Nrf2 alters glucose metabolism and promotes glutamine metabolism via glutaminolysis to support CD4(+)T cell hyperproliferation. In summary, we elucidate the role of Nrf2 beyond traditional antioxidation in modulating the activation-driven expansion of CD4(+)T cells by influencing their nutrient metabolism and gene expression
A review of diffuse hemispheric glioma, H3 G34-mutant disease development, DNA repair, microenvironment, and treatments on the horizon
No full textDiffuse hemispheric glioma H3 G34-mutant is primarily diagnosed in adolescents/young adults. While molecular diagnostics have improved, cellular mechanisms that drive tumor progression and therapy resistance are poorly understood. Combining previous published studies with findings from the 2024 NIH G34-mutant symposium aid in summarizing translational and clinical updates on disease development, cellular repair processes, and the immune microenvironment. This collective work is meant to outline opportunities for treatment and prolonged survival
Patient-Specific Cost and Quality Value Comparison of Endoscopic Carpal Tunnel Release in Two Surgical Settings
No full textPURPOSE: Prior studies have demonstrated that transitioning surgeries from a hospital outpatient department (HOPD) to an ambulatory surgical center (ASC) lowers costs. With 500,000 carpal tunnel release (CTR) surgeries annually, CTR offers an opportunity to determine the value of one of the most performed upper-extremity surgeries. We aim to quantify the value of an endoscopic CTR in a HOPD compared to an ASC by analyzing differences in costs and patient outcomes. We hypothesize the ASC will provide greater value by lowering costs while maintaining patient outcomes.
METHODS: Total costs were comprised of time-driven activity-based labor costs (TDABC), activity-based supply costs, and claims-based facility costs. Differences in preoperative Patient-Reported Outcome Measure (PROM) Information System Upper Extremity (UE) and Pain Interference (PI) scores and 3-month postoperative PROM Information System UE and PI scores were calculated to determine PROM Information System Quality-Adjusted Life Years (QALY(UE/PI)). Total costs were divided by QALYs for each PROM to calculate the Value(UE/PI) of each cohort. The magnitude of the difference in value between cohorts was elucidated by calculating incremental cost-effectiveness ratios.
RESULTS:A total of 25 patients comprised each cohort. The ASC generated 28% lower costs compared to the HOPD (128.80 vs 140.19). Average QALY(UE) and QALY(PI) gain was not significantly greater for patients at the ASC compared to the HOPD (QALY(UE) 1.06 vs 0.89; QALY(PI) 1.22 vs 0.92). The ASC demonstrated 40% to 45% greater value, represented by a lower cost/QALYs, compared to the HOPD (Value(UE) 5,242.78/QALY, Value(PI) 5,038.04/QALY).
CONCLUSIONS: We observed between 40% to 45% greater value by performing CTRs in the ASC. Although ASCs lowered costs by 28%, costs alone do not fully explain the value differential. Patient-reported outcomes serve a valuable role in providing a holistic picture of the value being delivered to patients. Providers can use this information to guide patient decision-making regarding operative treatment options for carpal tunnel syndrome.
TYPE OF STUDY/LEVEL OF EVIDENCE: Economic/Decision Analysis II
Comparison of clinical and radiological outcomes using solely particles versus particles with coils in middle meningeal artery embolization for chronic subdural hematoma: a longitudinal comparative cohort study
No full textOBJECTIVE: Chronic subdural hematoma (cSDH) recurrence is a significant cause of morbidity in neurosurgical patients. Middle meningeal artery embolization (MMAe) effectively reduces cSDH recurrence by targeting its associated inflammatory cascade. Delayed recanalization can occur from proximal branches of the middle meningeal artery (MMA) after use of particle embolic agents. Surgeons may utilize coil embolization in addition to particle embolic agents to achieve proximal vessel control. This study compares reaccumulation rates for cSDH patients undergoing particle embolization of the MMA with and without coil embolization.
METHODS: A retrospective review of prospectively collected data was performed on the records of patients who underwent particle MMAe with or without coils for cSDH at the authors\u27 institution from 2021 to 2023 The primary outcome was cSDH recurrence at CT follow-up at least 1 month after MMAe.
RESULTS: Sixty-two patients underwent 81 embolization procedures with particles alone (n = 32) or particles and coils (n = 49). There was no significant difference in recurrence between particles versus particles and coils (6.3% vs 10.2%, p = 0.698). There was a statistical difference in procedure length (54.8 ± 28.7 vs 85.9 ± 26.5 minutes, p \u3c 0.001) and fluoroscopy time (34.9 ± 20.8 vs 48.8 ± 24.7 minutes, p = 0.01) between patients who underwent particle embolization versus those who underwent embolization with particles and coils. A noninferiority analysis demonstrated no significant difference between groups in treatment failure, hematoma expansion, and follow-up size \u3e 1 cm.
CONCLUSIONS: In the setting of cSDH, MMAe using particles only versus particles with coils shows similar rates of hematoma reaccumulation and resolution. Procedural time and fluoroscopy time were significantly reduced within the particle embolization-alone cohort. When comparing hematoma resolution and expansion, follow-up hematoma size \u3e 1 cm, and decrease in hematoma size \u3e 1 cm between groups, embolization using particles alone was not inferior to embolization using particles supplemented with coils