Sustained metabolic benefits of ΔTRTX-Ac1, a tarantula venom-derived peptide, when administered together with exenatide in high-fat fed mice.

AIM: The aim of the present study was to assess the long-term therapeutic efficacy of a recently discovered 28 amino acid peptide, Δ-theraphotoxin-Ac1 (Δ-TRTX-Ac1), originally isolated from venom of the Aphonopelma chalcodes tarantula. Δ-TRTX-Ac has previously been shown to improve pancreatic beta-cell function and suppress appetite. MATERIALS AND METHODS: Δ-TRTX-Ac1 was administered twice daily in high-fat fed (HFF) mice with streptozotocin (STZ)-induced insulin deficiency, namely HFF/STZ mice, for 28 days both alone and in combination with the venom-derived glucagon-like peptide-1 (GLP-1) mimetic, exenatide. RESULTS: Initial pharmacokinetic profiling of ΔTRTX-Ac1 revealed a plasma half-life of 2 h in mice, with ΔTRTX-Ac1 also evidenced in the pancreas 12 h post-injection. Accordingly, HFF-STZ mice received twice-daily injections of Δ-TRTX-Ac1, exenatide or a combination of both peptides for 28 days. As anticipated, HFF/STZ mice presented with hyperglycaemia, impaired glucose tolerance, decreased plasma and pancreatic insulin and disturbed pancreatic islet morphology. Administration of ΔTRTX-Ac1 reduced body weight, improved glucose tolerance and augmented pancreatic insulin content while decreasing glucagon content. Exenatide had similar benefits on body weight and pancreatic hormone content while also reducing circulating glucose. ΔTRTX-Ac1 decreased energy expenditure on day 28 whereas exenatide had no impact. All treatment regimens restored pancreatic islet and beta-cell area towards lean control levels, which was linked to significantly elevated beta-cell proliferation rates. In terms of benefits of combined ΔTRTX-Ac1 and exenatide treatment over individual agents, there was augmentation of glucose tolerance and ambulatory activity with combination therapy, and these mice presented with increased pancreatic glucagon. CONCLUSION: These data highlight the therapeutic promise of ΔTRTX-Ac1 for diabetes, with suggestion that benefits could be enhanced through combined administration with exenatide.

Replacing the Scalpel With a Computer Mouse: An Evaluation of Time Spent on Electronic Health Record for Plastic Surgery Residents and Its Impact on Resident Training.

BACKGROUND: Following the integration of the electronic health record (EHR) into the healthcare system, concern has grown regarding EHR use on physician well-being. For surgical residents, time spent on the EHR increases the burden of a demanding, hourly restricted schedule and detracts from time spent honing surgical skills. To better characterize these burdens, we sought to describe EHR utilization patterns for plastic surgery residents. METHODS: Integrated plastic surgery resident EHR utilization from March 2019 to March 2020 was extracted via Cerner Analytics at a tertiary academic medical center. Time spent in the EHR on-duty (0600-1759) and off-duty (1800-0559) in the form of chart review, orders, documentation, and patient discovery was analyzed. Statistical analysis was performed in the form of independent t tests and Analysis of Variance (ANOVA). RESULTS: Twelve plastic surgery residents spent a daily average of 94 ± 84 minutes on the EHR, one-third of which was spent off-duty. Juniors (postgraduate years 1-3) spent 123 ± 99 minutes versus seniors (postgraduate years 4-6) who spent 61 ± 49 minutes (P < 0.01). Seniors spent 19% of time on the EHR off-duty, compared with 37% for juniors (P < 0.01). Chart review comprised the majority (42%) of EHR usage, followed by patient discovery (22%), orders (14%), documentation (12%), other (6%), and messaging (1%). Seniors spent more time on patient discovery (25% vs 21%, P < 0.001), while juniors spent more time performing chart review (48% vs 36%, P = 0.19). CONCLUSION: Integrated plastic surgery residents average 1.5 hours on the EHR daily. Junior residents spend 1 hour more per day on the EHR, including more time off-duty and more time performing chart review. These added hours may play a role in duty hour violations and detract from obtaining operative skill sets.

The Need for Systems Approaches for Precision Communications in Public Health.

A major challenge in communicating health-related information is the involvement of multiple complex systems from the creation of the information to the sources and channels of dispersion to the information users themselves. To date, public health communications approaches have often not adequately accounted for the complexities of these systems to the degree necessary to have maximum impact. The virality of COVID-19 misinformation and disinformation has brought to light the need to consider these system complexities more extensively. Unaided, it is difficult for humans to see and fully understand complex systems. Luckily, there are a range of systems approaches and methods, such as systems mapping and systems modeling, that can help better elucidate complex systems. Using these methods to better characterize the various systems involved in communicating public health-related information can lead to the development of more tailored, precise, and proactive communications. Proceeding in an iterative manner to help design, implement, and adjust such communications strategies can increase impact and leave less opportunity for misinformation and disinformation to spread.

Mechanism of Injury and Age Predict Operative Intervention in Pediatric Perineal Injury.

OBJECTIVES: Literature characterizing pediatric perineal trauma is sparse and generally limited to females. The purpose of this study was to characterize pediatric perineal injuries with specific focus on patient demographics, mechanisms of injury, and care patterns at a regional level 1 pediatric trauma center. METHODS: Retrospective review of children aged younger than 18 years evaluated at a level 1 pediatric trauma center from 2006 to 2017. Patients were identified by International Classification of Diseases-9 and 10 codes. Extracted data included demographics, injury mechanism, diagnostic studies, hospital course, and structures injured. The χ 2 and t tests were used to examine differences between subgroups. Machine learning was used to predict variable importance in determining the need for operative interventions. RESULTS: One hundred ninety-seven patients met inclusion criteria. Mean age was 8.5 years. A total of 50.8% were girls. Blunt trauma accounted for 83.8% of injuries. Motor vehicle collisions and foreign bodies were more common in patients aged 12 years and older, whereas falls and bicycle-related injuries were more common in those younger than 12 years ( P < 0.01). Patients younger than 12 years were more likely to sustain blunt trauma with isolated external genital injuries ( P < 0.01). Patients aged 12 and older had a higher incidence of pelvic fractures, bladder/urethral injuries, and colorectal injuries, suggesting more severe injury patterns ( P < 0.01). Half of patients required operative intervention. Children aged 3 years or younger and older than 12 years had longer mean hospital stays compared with children aged 4 to 11 years ( P < 0.01). Mechanism of injury and age constituted more than 75% of the variable importance in predicting operative intervention. CONCLUSIONS: Perineal trauma in children varies by age, sex, and mechanism. Blunt mechanisms are the most common, with patients frequently requiring surgical intervention. Mechanism of injury and age may be important in deciding which patients will require operative intervention. This study describes injury patterns in pediatric perineal trauma that can be used to guide future practice and inform injury prevention efforts.

Benefits of Trimodality Therapy Compared with Systemic Therapy Alone in Male Patients with Stage IV Breast Cancer.

BACKGROUND: Male breast cancer (MBC) represents <1% of all breast cancer (BC) diagnoses. Recent publications in female stage IV BC have shown that surgical intervention has a survival benefit. This study aims to determine the impact of surgical intervention in men with stage IV BC and known estrogen (ER) and progesterone receptor (PR) status. METHODS: The National Cancer Database was used to identify 539 stage IV MBC patients with known ER/PR status from 2004 to 2017. Chi-square tests examined subgroup differences between the treatment modalities received. Overall survival (OS) was assessed using the Kaplan-Meier method. Multivariate Cox proportional hazard models examined factors associated with survival. RESULTS: The Kaplan-Meier estimation showed that ER-positive (ER+) and PR-positive (PR+) patients who received surgery, systemic therapy, and radiation (Trimodality) or systemic therapy and surgery (ST+Surg) had improved survival compared with systemic therapy alone (ST) [ER+, p < 0.003; PR+, p < 0.033]. For ER+ patients, the 5-year OS rates by treatment were: Trimodality, 40%; ST+Surg, 27%; and ST, 20%. For PR+ patients, the 5-year OS rates were: Trimodality, 39%; ST+Surg, 24%; and ST, 20%. The Cox proportional hazard model revealed a survival advantage in patients who received Trimodality compared with ST (hazard ratio 0.622; p < 0.002). The timing of systemic therapy in relation to surgery was not found to be significant. CONCLUSIONS: Trimodality therapy has a survival benefit in stage IV MBC patients with known ER+ status than in male patients who receive systemic therapy alone.

Development of a Standardized Program for the Collaboration of Adult and Children's Surgeons.

BACKGROUND: Children's hospitals within larger hospitals (CH/LH) have the specific clinical advantage of easily facilitated collaboration between adult and children's surgeons. These collaborations, which we have termed hybrid surgical offerings (HSOs) are often required for disease processes requiring interventions that fall outside the customary practice of children's surgeons. Formal models to describe or evaluate these practices are lacking. METHODS: HSOs within a CH/LH were identified. Principles of systems-engineering were used to develop a standardized model (Children's Hybrid Enhanced Surgical Services [CHESS]) to describe and evaluate HSOs. Face validity was established via unstructured interviews of CH leaders and HSO surgeons. Areas for improved system-wide standardization and programmatic development were identified. RESULTS: HSOs were identified in collaboration with adult bariatric, minimally invasive, advanced endoscopic, endocrine, thoracic, and orthopedic trauma surgical services. The CHESS framework encompassed: 1) quality improvement metrics, 2) credentialing and oversight, 3) transitions of care, 4) pediatric family-centered care, 5) maintenance of the cycle of expertise, 6) continuing medical education, 7) scholarship. While HSOs fulfilled the majority of aforementioned programmatic domains across all six HSO-providing services, areas for improvement included maintaining a cycle of expertise (33%), quality improvement metrics (50%), and pediatric family-centered care (66%).  Additional noted advantages included faster translation of adult innovation to pediatric care and facilitation of emergency interdisciplinary care. CONCLUSION: Formal evaluation of HSOs is necessary to standardize and improve the quality of children's surgical care. Development of a structured framework such as CHESS addresses gaps in quality oversight and provides a basis for performance improvement, patient safety, and programmatic development.

Insurance Status and Travel Distance to Single Treatment Facility Predictive of Mastectomy.

BACKGROUND: We evaluated the impact of insurance status and travel distance on the receipt of total mastectomy without reconstruction (TM) compared to breast conserving surgery with radiation (BCT) for early-stage breast cancer (BC) patients who received care at a single facility. We hypothesized that, lack of insurance and increased travel distance would be predictive of TM over BCT and disparities would vary by different races and/or ethnicities. METHODS: Using the National Cancer Database from 2010-2017, we examined surgical patients with stage I or II BC, who received care at one facility. Chi-square tests examined subgroup differences by BCT or TM. Multivariable logistic regressions evaluated patient, facility, and pathologic factors associated with the receipt of TM over BCT for the entire cohort and by races and/or ethnicities. RESULTS: Of the 284,202 patients, 70.1% received BCT while 29.9% received TM. After adjustment travel distance > 60 miles to a treatment facility, and non-insured patients were more likely to receive TM over BCT, when compared to travel distance < 20 miles and private insurance (all P < 0.05). Compared to other races and/or ethnicities, African Americans traveling > 60 miles were 65.4% more likely to receive TM over BCT compared to those traveling < 20 miles (P < .0001). Across all races and/or ethnicities after adjustment, lack of insurance was predictive for receipt of TM over BCT (P < 0.05). CONCLUSIONS: Despite treatment at one facility, increased travel distance and insurance status are independently predictive of the receipt of TM over BCT in patients with early-stage BC. While travel distance is particularly impactful for African Americans, the impact of not having insurance on surgical treatments is universal across all races and/or ethnicities.

Benefits of Surgical Treatment of Stage IV Breast Cancer for Patients With Known Hormone Receptor and HER2 Status.

BACKGROUND: For the 6% of breast cancer patients with a diagnosis of stage IV disease, systemic therapy is the cornerstone of treatment, with an unclear role for surgery. Limited evidence exists to delineate treatment methods with regard to hormone receptor and human epidermal growth factor receptor 2 (HER2) status. METHODS: The National Cancer Database was used to identify 12,838 stage IV breast cancer patients with known hormone receptor and HER2 status from 2010 to 2015. Chi square tests examined subgroup differences between the treatment methods received. Using the Kaplan-Meier method, 5-year overall survival (OS) was assessed. Multivariate Cox proportional hazard models examined factors associated with survival. RESULTS: A survival advantage was noted for patients who received either systemic therapy and surgery (ST + Surg: hazard ratio [HR] 0.723; 95% confidence interval [CI] 0.671-0.779) or systemic therapy, surgery, and radiation (Trimodality: HR 0.640; 95% CI 0.591-0.694) (both p < 0.0001) compared with systemic therapy alone (ST). The HER2+ patients who received Trimodality or ST + Surg had a better 5-year OS rate than those who received ST (Trimodality [48%], ST + Surg [41%], ST [29%]; p < 0.0001). The sequence of chemotherapy in relation to surgery is significant, with the greatest survival advantage noted for recipients of neoadjuvant chemotherapy (NAC) compared with patients who had adjuvant chemotherapy when they had positive hormone receptor and HER2 status (HER2 + NAC: HR 0.477; estrogen receptor-positive [ER+] NAC: HR 0.453; progesterone receptor-positive [PR+] NAC: HR 0.448; all p < 0.0001). CONCLUSIONS: Surgery in addition to ST has a survival benefit for stage IV breast cancer patients with known hormone receptor and HER2 status and should be considered after NAC for patients with ER+, PR+, or HER2+ disease.

Established Primary Care Provider Improves Odds of Survival to Discharge for Injured Patients.

INTRODUCTION: The average age and number of comorbidities is increasing among trauma patients. Primary care providers (PCPs) provide pre-injury diagnosis and management of comorbidities that may affect outcomes for injured patients. The role of primary care in trauma systems is currently unknown. METHODS: Observational retrospective review of an institutional trauma databank from 2013 - 2019. PCP was extracted from the electronic medical record and combined with trauma data. Case-control matching was performed to compare outcomes between patients with and without primary care based on age, injury severity score, sex, and injury mechanism. Mann-Whitney U test, chi-square test, and multivariate regression described differences between subgroups. Primary outcome was difference in mortality rate for injured patients with and without PCPs. RESULTS: Within the study period, 19,096 patients were included. 6,626 (34.7%) had a PCP recorded. Of these, 2,158 were matched in a case-control design. Patients with PCPs had a lower mortality rate (1.6%) compared to patients without PCPs (3.6%, P < 0.01). PCP retention was associated with longer length of stay overall, equivalent rates of complications (5.4% vs. 5.7%, P = 0.63), and similar numbers of ICU and ventilator days. Multivariate logistic regression controlling for case-control factors, insurance, and comorbidities conferred an odds ratio of 2.58 (95% Confidence Interval: 1.59 - 4.19, P < 0.001) for survival to discharge. CONCLUSION: Pre-injury primary care significantly improves the odds of survival to discharge for injured patients. Prospective study of this relationship may identify strategies to promote primary care within health systems.

Applying the thresholds for clinical importance for fourteen key domains of the EORTC QLQ-C30: a latent class analysis of cancer survivors.

A person's quality of life is impacted from the beginning of their oncology experience. One of the most common tools to measure quality of life is the EORTC QLQ-C30. The absolute scores it produces can be difficult to interpret in the clinical setting, and thresholds to help identify those who require intervention have recently been introduced. The aim of this research was to identify heterogeneity of these thresholds for clinical importance using latent class analysis in cancer survivors (those undergoing and those who have completed treatment) attending a hospital in the northwest of Ireland. We identified 3 distinct classes of cancer survivors, using Mplus 6.11: high clinical impact (13.9%), compromised physical function (40.3%) and low clinical impact (45.9%). The compromised physical function group were slightly more likely to be older (OR = 1.042, p < .05, CI = 1.000-1.086), not employed (OR = 8.347, p < .01, CI = 2.092-33.305), have lower PG-SGA scores (OR = .826, p < .001, CI = .755-.904), and not have been diagnosed in the last 2 years (OR = .325, p < .05, CI = .114-.923) compared to the high clinical impact group. The low clinical impact group were more likely to be female (OR = 3.288, p < .05, CI = 1.281-1.073), not employed (OR = 10.129, p < .01, CI = 2.572-39.882), have a lower BMI (OR = .921, p < .05, CI = .853-.994), and lower PG-SGA scores (OR = .656, p < .001, CI = .573-.750) than the high clinical impact group. Functional and symptom issues impact on quality of life, and therefore, identifying those of clinical importance is crucial for developing supportive care strategies.

Oculomotor corollary discharge signaling is related to repetitive behavior in children with autism spectrum disorder.

Corollary discharge (CD) signals are "copies" of motor signals sent to sensory regions that allow animals to adjust sensory consequences of self-generated actions. Autism spectrum disorder (ASD) is characterized by sensory and motor deficits, which may be underpinned by altered CD signaling. We evaluated oculomotor CD using the blanking task, which measures the influence of saccades on visual perception, in 30 children with ASD and 35 typically developing (TD) children. Participants were instructed to make a saccade to a visual target. Upon saccade initiation, the presaccadic target disappeared and reappeared to the left or right of the original position. Participants indicated the direction of the jump. With intact CD, participants can make accurate perceptual judgements. Otherwise, participants may use saccade landing site as a proxy of the presaccadic target and use it to inform perception. We used multilevel modeling to examine the influence of saccade landing site on trans-saccadic perceptual judgements. We found that, compared with TD participants, children with ASD were more sensitive to target displacement and less reliant on saccade landing site when spatial uncertainty of the post-saccadic target was high. This pattern was driven by ASD participants with less severe restricted and repetitive behaviors. These results suggest a relationship between altered CD signaling and core ASD symptoms.

Lymphatic malformations: a 20-year single institution experience.

PURPOSE: Lymphatic malformations (LMs) are congenital abnormalities which result from disturbances in the embryologic development of the lymphatic system. We sought to determine the characteristics and treatment patterns for LMs in a rural setting, and the effect of a specialized vascular malformations clinic on triage and follow-up. METHODS: This is a retrospective cohort study at a single tertiary care institution. Sixty-two patients were identified; chart review was completed to obtain demographic, surgery/sclerotherapy session and follow-up information. RESULTS: The head/neck region was the most predominant LM location (N = 26, 41.9%), followed by trunk (N = 16, 25.8%), extremity (N = 11, 17.7%), and intraabdominal/retroperitoneal (N = 7, 11.3%). Twenty-eight patients were managed non-surgically, while 21, 7 and 6 patients required surgery, sclerotherapy, or both. Head/neck LMs were the most likely to recur (73%, p = 0.028). Patients seen in specialty clinic had similar duration of follow-up and time to intervention, but were more often below 1 year of age (p = 0.030). Average LM volume among patients with available imaging was much larger in those referred to specialty clinic (73.2 cm3 versus 14.8 cm3, p = 0.022). CONCLUSION: Our experience reiterates not only the wide variety of clinical presentations of lymphatic malformations, but also demonstrates the necessity of multiple subspecialties and their collaboration to achieve prompt and efficacious treatment.

Construct Validity and Dimensionality of the Rosenberg Self-Esteem Scale and Its Association with Spiritual Values Within Irish Population.

Until this research, correlation of Rosenberg's (1965) self-esteem scale (RSES), with religious and spiritual values, was never investigated using the measure as a twofold construct instead of the monolithic form. This research paper explores the prediction of RSES by spiritual values using a twofold structure of: self-esteem-positive (SEP) and self-esteem-negative (SEN), to specify individual and fragmented correlations with spirituality, which until now was unobtainable. Confirmatory factor analysis and structural equation modelling were applied to analyse the data. The survey was conducted among two-hundred and sixty-eight participants from the Republic of Ireland. The research finds that spirituality influences peoples' self-esteem, but clear and linear correlation between spirituality and self-esteem is difficult to be concluded. People respond oppositely and differently to positive and to negative items in the RSES which indicates that the measure is a combination of two statistically consistent constructs: SEP and SEN. The results of the study confirm that there are many spiritual areas that affect self-esteem.

Leveraging Colloidal Aggregation for Drug-Rich Nanoparticle Formulations.

While limited drug loading continues to be problematic for chemotherapeutics formulated in nanoparticles, we found that we could take advantage of colloidal drug aggregation to achieve high loading when combined with polymeric excipients. We demonstrate this approach with two drugs, fulvestrant and pentyl-PABC doxazolidine (PPD; a prodrug of doxazolidine, which is a DNA cross-linking anthracycline), and two polymers, polysorbate 80 (UP80) and poly(d,l-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-graft-poly(ethylene glycol) (PLAC-PEG; a custom-synthesized, self-assembling amphiphilic polymer). In both systems, drug-loaded nanoparticles had diameters < 200 nm and were stable for up to two days in buffered saline solution and for up to 24 h in serum-containing media at 37 °C. While colloidal drug aggregates alone are typically unstable in saline and serum-containing media, we attribute the colloid stability observed herein to the polymeric excipients and consequent decreased protein adsorption. We expect this strategy of polymer-stabilized colloidal drug aggregates to be broadly applicable in delivery formulations.

Purification, Conformational Analysis, and Properties of a Family of Tigerinin Peptides from Skin Secretions of the Crowned Bullfrog Hoplobatrachus occipitalis.

Four host-defense peptides belonging to the tigerinin family (tigerinin-1O: RICTPIPFPMCY; tigerinin-2O: RTCIPIPLVMC; tigerinin-3O: RICTAIPLPMCL; and tigerinin-4O: RTCIPIPPVCF) were isolated from skin secretions of the African crowned bullfrog Hoplobatrachus occipitalis. In aqueous solution at pH 4.8, the cyclic domain of tigerinin-2O adopts a rigid amphipathic conformation that incorporates a flexible N-terminal tail. The tigerinins lacked antimicrobial (MIC > 100 µM) and hemolytic (LC50 > 500 µM) activities but, at a concentration of 20 µg/mL, significantly (P < 0.05) inhibited production of interferon-γ (IFN-γ) by peritoneal cells from C57BL/6 mice without affecting production of IL-10 and IL-17. Tigerinin-2O and -4O inhibited IFN-γ production at concentrations as low as 1 µg/mL. The tigerinins significantly (P ≤ 0.05) stimulated the rate of insulin release from BRIN-BD11 clonal ß-cells without compromising the integrity of the plasma membrane. Tigerinin-1O was the most potent (threshold concentration 1 nM) and the most effective (395% increase over basal rate at a concentration of 1 µM). Tigerinin-4O was the most potent and effective peptide in stimulating the rate of glucagon-like peptide-1 release from GLUTag enteroendocrine cells (threshold concentration 10 nM; 289% increase over basal rate at 1 µM). Tigerinin peptides have potential for development into agents for the treatment of patients with type 2 diabetes.

Development and characterization of gene silencing DNA cages.

RNA interference (RNAi) is a powerful therapeutic strategy that induces gene silencing by targeting disease-causing mRNA and can lead to their removal through degradation pathways. The potential of RNAi is especially relevant in cancer therapy, as it can be designed to regulate the expression of genes involved in all stages of tumor development (initiation, growth, and metastasis). We have generated gene silencing 3D DNA prisms that integrate antisense oligonucleotide therapeutics at 1, 2, 4, and 6 positions. Synthesis of these structures is readily achieved and leads to the assembly of highly monodisperse and well-characterized structures. We have shown that antisense strands scaffolded on DNA cages can readily induce gene silencing in mammalian cells and maintain gene knockdown levels more effectively than single and double stranded controls through increased stability of bound antisense units.

Impact of outside referral and dental extractions on package time with post-operative radiation therapy for head and neck cancer.

INTRODUCTION: Patients with squamous cell carcinoma of the head and neck (HNSCC) often receive post-operative radiotherapy (RT). A package time between surgery and completion of RT of ≤100 days is associated with lower recurrence and longer survival. In this study, we investigate the impact of outside referral and dental extractions on package time, with secondary detriment to relapse-free survival (RFS) and overall survival (OS). METHODS: We conducted a retrospective chart review on patients with HNSCC who received primary surgical resection at an academic medical centre. RESULTS: Ninety-four patients met eligibility criteria, 35% experienced recurrence, and 21% died. Median package time was 89.5 days, with 76% of patients achieving a package time ≤100 days. Receiving RT in-house was associated with a shorter package time (P = 0.0004) and higher completion rate within 100 days (P = 0.01). Dental extractions did not affect package time. A Kaplan-Meier analysis was performed to study survival, and a package time ≤100 days was not associated with a change in RFS or OS. A Cox proportional hazard model was used to investigate other factors hypothesized to impact patient survival; none had an effect on RFS, but cancer stage had an effect on OS (P = 0.01). CONCLUSIONS: We identified that outside referrals, but not dental extractions, prolong treatment package times. We also saw no effect of package time on RFS or OS. These results suggest that patients requesting outside facility referrals for RT may benefit from a streamlined program that expedites the referral process.

A randomized trial evaluating a novel hydrogel packing system compared to standard packing during image-guided high-dose rate brachytherapy boost for cervical cancer.

INTRODUCTION: The purpose of this prospective randomized trial was to compare the use of a novel vaginal hydrogel packing system (BrachyGel) to standard vaginal packing (VP) during high dose rate (HDR) brachytherapy (BT) for locally advanced cervical cancer (LACC). METHODS: This cross-over study included LACC patients receiving HDR BT boost (intracavitary +/- interstitial). All patients received alternating gauze or BrachyGel VP on Arms A and B. Patients, physicians, and physicists evaluated BT characteristics via a 4-point Likert scale. Adverse events (AEs) were prospectively collected and scored per CTCAE. RESULTS: The 20 patients enrolled. The mean bladder D2cc difference between gauze and BrachyGel in Arm A was 0.117 Gray (Gy) and in Arm B 0.013 Gy. The mean difference in rectum D2cc in Arm A and Arm B was -0.189 Gy and -0.191 Gy, respectively. The mean dose to 90% of the high-risk clinical target volume (HR-CTV) for gauze compared to BrachyGel was -0.032 Gy (95% CI: 0.472, 0.409). Patient-reported discomfort was similar with BrachyGel and gauze ("mild/moderate" 70.0% vs 74.0%, respectively). The clarity of VP was similar between BrachyGel and gauze (86.8% vs 89.7%, respectively). The completeness of VP was more frequently "excellent/good" with BrachyGel (79.0%) compared to gauze (56.4%). The ease of packing was more frequently "extremely easy" with BrachyGel (21.2% vs 0%). No serious AEs were reported. CONCLUSION: This randomized trial found no clinically significant difference in OAR or HR-CTV dosimetry between BrachyGel and standard VP. BrachyGel performed well compared to gauze for the patient and physician use experience.

The impact of post-operative enteral nutrition on duodenal injury outcomes: A post hoc analysis of an EAST multicenter trial.

BACKGROUND: Leak following surgical repair of traumatic duodenal injuries results in prolonged hospitalization and oftentimes nil per os(NPO) treatment. Parenteral nutrition(PN) has known morbidity; however, duodenal leak(DL) patients often have complex injuries and hospital courses resulting in barriers to enteral nutrition(EN). We hypothesized EN alone would be associated with 1)shorter duration until leak closure and 2)less infectious complications and shorter hospital length of stay(HLOS) compared to PN. METHODS: This was a post-hoc analysis of a retrospective, multicenter study from 35 Level-1 trauma centers, including patients >14 years-old who underwent surgery for duodenal injuries(1/2010-12/2020) and endured post-operative DL. The study compared nutrition strategies: EN vs PN vs EN + PN using Chi-Square and Kruskal-Wallis tests; if significance was found pairwise comparison or Dunn's test were performed. RESULTS: There were 113 patients with DL: 43 EN, 22 PN, and 48 EN + PN. Patients were young(median age 28 years-old) males(83.2%) with penetrating injuries(81.4%). There was no difference in injury severity or critical illness among the groups, however there were more pancreatic injuries among PN groups. EN patients had less days NPO compared to both PN groups(12 days[IQR23] vs 40[54] vs 33[32],p = <0.001). Time until leak closure was less in EN patients when comparing the three groups(7 days[IQR14.5] vs 15[20.5] vs 25.5[55.8],p = 0.008). EN patients had less intra-abdominal abscesses, bacteremia, and days with drains than the PN groups(all p < 0.05). HLOS was shorter among EN patients vs both PN groups(27 days[24] vs 44[62] vs 45[31],p = 0.001). When controlling for predictors of leak, regression analysis demonstrated EN was associated with shorter HLOS(ß -24.9, 95%CI -39.0 to -10.7,p < 0.001). CONCLUSION: EN was associated with a shorter duration until leak closure, less infectious complications, and shorter length of stay. Contrary to some conventional thought, PN was not associated with decreased time until leak closure. We therefore suggest EN should be the preferred choice of nutrition in patients with duodenal leaks whenever feasible. LEVEL OF EVIDENCE: IV.

Novel HPV Associated Oropharyngeal Squamous Cell Carcinoma Surveillance DNA Assay Cost Analysis.

OBJECTIVES: We aim to propose a modified surveillance strategy using a novel blood assay that detects plasma circulating tumor-specific HPV DNA with reported 100% NPV and 94% PPV as the main method of detection to understand the cost implications of potentially avoiding routine imaging and surveillance visits at our institution. METHODS: We performed a retrospective chart review focusing on recurrences in p16+ patients with OPSCC and defined two surveillance strategies: "Strategy A", follow-up visits with flexible laryngoscopy (FL) plus regular imaging studies; "Strategy B", follow-up visits with FL plus regular NavDx assays and imaging used at the discretion of the physician(s) in cases of high clinical suspicion. RESULTS: Of the p16+ OPSCC patients (n = 214), 23 had confirmed recurrence (11%). Standard work-flow model determined 72 imaging studies and 2198 physical examinations with FL were needed to detect one recurrence. Potential individual patient cost reduction during surveillance was 42%. CONCLUSION: Implementing NavDx for HPV + OPSCC surveillance would benefit patients by reducing costs and unnecessary diagnostic testing. LEVEL OF EVIDENCE: Step/Level 3 Laryngoscope, 133:3006-3012, 2023.