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36 result(s) for "Brooks, Ari D."
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Switching to Tumescent Dissection in Mastectomy
Introduction: Tumescent dissection (TUM) combines the use of crystalloid, local anesthetic, and epinephrine to create a bloodless plane to raise skin flaps. We aim to compare outcomes of TUM versus standard electrocautery dissection in mastectomies with and without reconstruction. Methods: We conducted a retrospective cohort study of patients who underwent mastectomy by a single surgeon between January 2016 and October 2020 utilizing the electronic medical record. The primary outcome was complication rate, and the secondary outcome was operative time. Chi‐squared analysis and two‐sample t ‐tests were used to examine outcomes. Results: Among 242 patients, 141 patients underwent TUM and 101 patients underwent electrocautery. 44.68% of TUM patients experienced one or more complications compared to 59.41% of electrocautery patients ( p = 0.024). There were fewer cases of wound healing complications in the TUM group with reconstruction compared to the electrocautery group with reconstruction (6.1% vs. 21%, p = 0.005). Infection rate was higher in the TUM group with reconstruction compared to the electrocautery group with reconstruction (14.3% vs. 3.2%, p = 0.023). There was no significant difference in rates of hematoma, seroma, skin flap necrosis, nipple areolar complex necrosis, or re‐exploration by dissection technique. The mean operative time was shorter with TUM compared to electrocautery (216.09 min vs. 250.16 min, p = 0.016). Conclusion: TUM yields comparable results with decreased overall complication rates compared to electrocautery dissection. Electrocautery thermal effect may account for skin‐related complications. Additionally, tumescent mastectomies have shorter length of operative time which could reduce the risk of complications associated with increased time under general anesthesia.
Involvement of multiple stressors induced by non-thermal plasma-charged aerosols during inactivation of airborne bacteria
A lab-scale, tunable, single-filament, point-to-point nonthermal dieletric-barrier discharge (DBD) plasma device was built to study the mechanisms of inactivation of aerosolized bacterial pathogens. The system inactivates airborne antibiotic-resistant pathogens efficiently. Nebulization mediated pre-optimized (4 log and 7 log) bacterial loads were challenged to plasma-charged aerosols, and lethal and sublethal doses determined using colony assay, and cell viability assay; and the loss of membrane potential and cellular respiration were determined using cell membrane potential assay and XTT assay. Using the strategies of Escherichia coli wildtype, over-expression mutant, deletion mutants, and peroxide and heat stress scavenging, we analyzed activation of intracellular reactive oxygen species (ROS) and heat shock protein (hsp) chaperons. Superoxide dismutase deletion mutants (ΔsodA, ΔsodB, ΔsodAΔsodB) and catalase mutants ΔkatG and ΔkatEΔkatG did not show significant difference from wildtype strain, and ΔkatE and ΔahpC was found significantly more susceptible to cell death than wildtype. The oxyR regulon was found to mediate plasma-charged aerosol-induced oxidative stress in bacteria. Hsp deficient E. coli (ΔhtpG, ΔgroEL, ΔclpX, ΔgrpE) showed complete inactivation of cells at ambient temperature, and the treatment at cold temperature (4°C) significantly protected hsp deletion mutants and wildtype cells, and indicate a direct involvement of hsp in plasma-charged aerosol mediated E. coli cell death.
Mitochondria-Mediated Anticancer Effects of Non-Thermal Atmospheric Plasma
Non-thermal atmospheric pressure plasma has attracted great interest due to its multiple potential biomedical applications with cancer treatment being among the most urgent. To realize the clinical potential of non-thermal plasma, the exact cellular and molecular mechanisms of plasma effects must be understood. This work aimed at studying the prostate cancer specific mechanisms of non-thermal plasma effects on energy metabolism as a central regulator of cell homeostasis and proliferation. It was found that cancer cells with higher metabolic rate initially are more resistant to plasma treated phosphate-buffered saline (PBS) since the respiratory and calcium sensitive signaling systems were not responsive to plasma exposure. However, dramatic decline of cancer oxidative phosphorylation developed over time resulted in significant progression of cell lethality. The normal prostate cells with low metabolic activity immediately responded to plasma treated PBS by suppression of respiratory functions and sustained elevation of cytosolic calcium. However, over time the normal cells start recovering their mitochondria functions, proliferate and restore the cell population. We found that the non-thermal plasma induced increase in intracellular ROS is of primarily non-mitochondrial origin. The discriminate non-thermal plasma effects hold a promise for clinical cancer intervention.
How can we be more “deliberate” in training surgeons?
Ever since a study by Cox demonstrated there was no correlation between intelligence quotient (IQ) and the degree of success among 300 eminent historical figures that she analyzed, countless studies have supported this finding.1 Children with higher IQs or scores on standardized exams were not necessarily more successful in their careers. [...]students who were told they excelled due to hard-work continued to improve, even beyond their “talented” classmates. [...]instead of talent, the social psychology literature now supports a different term in education: “Grit,” defined by Duckworth et al. at the University of Pennsylvania as “perseverance and passion for long-term goals”.2 If talent is what you are given at birth, grit is the sweat and tears you produce. A training rhetoric based on “Grit,” on the other hand, would encourage trainees to partake in “deliberate practice,” a concept developed by Ericsson et al., which requires setting goals that zero-in on specific weaknesses and devoting undivided attention towards reaching it.6 Athletic superstars such as Lebron James or Lionel Messi may appear flawless in their elements today, but the final product does not convey the greater than “10,000 h” that they spent running specific drills to overcome their weak points.7 In this paradigm, “perfection” is merely the sum of ordinary increments.
Chemical Changes in Nonthermal Plasma-Treated N-Acetylcysteine (NAC) Solution and Their Contribution to Bacterial Inactivation
In continuation of our previous reports on the broad-spectrum antimicrobial activity of atmospheric non-thermal dielectric barrier discharge (DBD) plasma treated N-Acetylcysteine (NAC) solution against planktonic and biofilm forms of different multidrug resistant microorganisms, we present here the chemical changes that mediate inactivation of Escherichia coli. In this study, the mechanism and products of the chemical reactions in plasma-treated NAC solution are shown. UV-visible spectrometry, FT-IR, NMR, and colorimetric assays were utilized for chemical characterization of plasma treated NAC solution. The characterization results were correlated with the antimicrobial assays using determined chemical species in solution in order to confirm the major species that are responsible for antimicrobial inactivation. Our results have revealed that plasma treatment of NAC solution creates predominantly reactive nitrogen species versus reactive oxygen species, and the generated peroxynitrite is responsible for significant bacterial inactivation.
Inadequate T follicular cell help impairs B cell immunity during HIV infection
B cell responses are impaired in HIV-infected individuals. Elias Haddad and colleagues now report that follicular helper T (T FH ) cells, which are crucial for the maturation of B cell memory and development of high-affinity antibodies, are functionally impaired upon interaction with lymph node germinal center B cells from HIV-infected individuals. The interaction of the inhibitory molecule PD-1 on T FH cells with its ligand PD-L1, which is elevated on germinal center B cells in HIV-infected lymph nodes, impairs T FH cell proliferation and antibody production by B cells, thus providing insight into humoral dysfunction in HIV infection. The majority of HIV-infected individuals fail to produce protective antibodies and have diminished responses to new immunizations 1 , 2 , 3 . We report here that even though there is an expansion of follicular helper T (T FH ) cells in HIV-infected individuals, the cells are unable to provide adequate B cell help. We found a higher frequency of programmed cell death ligand 1 (PD-L1) + germinal center B cells from lymph nodes of HIV-infected individuals suggesting a potential role for PD-1–PD-L1 interaction in regulating T FH cell function. In fact, we show that engagement of PD-1 on T FH cells leads to a reduction in cell proliferation, activation, inducible T-cell co-stimulator (ICOS) expression and interleukin-21 (IL-21) cytokine secretion. Blocking PD-1 signaling enhances HIV-specific immunoglobulin production in vitro . We further show that at least part of this defect involves IL-21, as addition of this cytokine rescues antibody responses and plasma cell generation in vitro . Our results suggest that deregulation of T FH cell–mediated B cell help diminishes B cell responses during HIV infection and may be related to PD-1 triggering on T FH cells. These results demonstrate a role for T FH cell impairment in HIV pathogenesis and suggest that enhancing their function could have a major impact on the outcome and control of HIV infection, preventing future infections and improving immune responses to vaccinations.
Modern Breast Cancer Detection: A Technological Review
Breast cancer is a serious threat worldwide and is the number two killer of women in the United States. The key to successful management is screening and early detection. What follows is a description of the state of the art in screening and detection for breast cancer as well as a discussion of new and emerging technologies. This paper aims to serve as a starting point for those who are not acquainted with this growing field.
Preoperative MRI and Its Impact on Surgical Outcomes in Patients with Triple Negative Breast Cancer Treated with Primary Surgery: Did New Margin Guidelines or Cavity Shave Margins Practice Diminish the Role of Preoperative MRI?
BackgroundResults of an earlier retrospective study from our institution suggested that patients with triple negative breast cancer (TNBC) who had preoperative MRI may have had an improved local recurrence rate (LRR) after breast conserving surgery (BCS). We aimed to clarify the impact of preoperative MRI on surgical outcomes in an expanded TNBC cohort treated by BCS in a contemporary era.MethodsOur study cohort comprised 648 patients with TNBC who underwent BCS between 2009 and 2018. Demographic and clinical characteristics were compared between those with (n = 292, 45.1%) and without (n = 356, 54.9%) preoperative MRI. Multivariable logistic regression was performed to assess the association of preoperative MRI with surgical outcomes.ResultsThe crude LRR of 3.5% was lower than previously reported. Univariable analyses demonstrated that the LRR and re-excision rates in the MRI and no-MRI groups were 3.4 and 3.7%, 21.6% and 27.2%, p = 0.876 and p = 0.10, respectively. Multivariable logistic regression analyses demonstrated that preoperative MRI was not associated with a lower LRR: odds ratio (OR) = 1.42 (p = 0.5). During our study period, new margin guidelines and shave margins practice were adopted in 2014 and 2015. To account for their effects, the year of diagnosis/surgery and other clinical variables were adjusted in multivariable logistic regression and inverse probability weighting models to demonstrate that preoperative MRI remained associated with a lower re-excision risk, OR 0.56, p = 0.04l; and a lower re-excision rate, 23.15% versus 36.0%, p < 0.01, respectively.ConclusionsOur findings suggested that patients with TNBC anticipating BCS may benefit from preoperative MRI.
Non-thermal Plasma Induces Apoptosis in Melanoma Cells via Production of Intracellular Reactive Oxygen Species
Non-thermal atmospheric pressure dielectric barrier discharge (DBD) plasma may provide a novel approach to treat malignancies via induction of apoptosis. The purpose of this study was to evaluate the potential of DBD plasma to induce apoptosis in melanoma cells. Melanoma cells were exposed to plasma at doses that did not induce necrosis, and cell viability and apoptotic activity were evaluated by Trypan blue exclusion test, Annexin-V/PI staining, caspase-3 cleavage, and TUNEL® analysis. Trypan blue staining revealed that non-thermal plasma treatment significantly decreased the viability of cells in a dose-dependent manner 3 and 24 h after plasma treatment. Annexin-V/PI staining revealed a significant increase in apoptosis in plasma-treated cells at 24, 48, and 72 h post-treatment (p < 0.001). Caspase-3 cleavage was observed 48 h post-plasma treatment at a dose of 15 J/cm². TUNEL® analysis of plasma-treated cells demonstrated an increase in apoptosis at 48 and 72 h post-treatment (p < 0.001) at a dose of 15 J/cm². Pre-treatment with N-acetyl-l-cysteine (NAC), an intracellular reactive oxygen species (ROS) scavenger, significantly decreased apoptosis in plasma-treated cells at 5 and 15 J/cm². Plasma treatment induces apoptosis in melanoma cells through a pathway that appears to be dependent on production of intracellular ROS. DBD plasma production of intracellular ROS leads to dose-dependent DNA damage in melanoma cells, detected by γ-H2AX, which was completely abrogated by pre-treating cells with ROS scavenger, NAC. Plasma-induced DNA damage in turn may lead to the observed plasma-induced apoptosis. Since plasma is non-thermal, it may be used to selectively treat malignancies.