Circulating Tumor DNA is Unreliable to Detect Somatic Gene Alterations in Gastrointestinal Peritoneal Carcinomatosis.

INTRODUCTION: Tumor agnostic circulating tumor DNA (ctDNA) is routinely used to guide treatment decisions in gastrointestinal (GI) cancers, especially metastatic cancers. The amount of ctDNA detected in plasma is affected by stage, tumor burden, and tumor vascularization. We hypothesized that peritoneal carcinomatosis (PC) is associated with lower ctDNA levels than other metastatic sites in GI cancers due to the plasma-peritoneal barrier. METHODS: We conducted a retrospective analysis of patients with stage II-IV GI cancers treated at our institution between 2015 and 2020 with available panel-based ctDNA results (Guardant 360TM). ctDNA analysis was performed on early and pretreatment samples. We compared the reported maximum variant allele frequency (mVAF) of somatic mutations across metastatic sites. RESULTS: Of the 279 patients with GI cancers (colorectal, upper GI, pancreaticobiliary), 212 had stage IV disease (PC: n = 61; visceral metastases: n = 138; other metastases: n = 13). Mean mVAF increased with increasing stages of disease (stage II: 3.6 ± 7; stage III: 6.4 ± 10; stage IV: 28.0 ± 51; p < 0.01). Among patients with stage IV disease, PC was associated with lower ctDNA levels independent of primary tumor site (PC only: 12.1%; PC+ visceral metastases: 26.8%; and visceral metastases only: 35.0%; p < 0.01). In a subset of patients (n = 27, matched pair analysis of genomic alterations (GAs) showed fewer GAs were detected in plasma compared with tissue. CONCLUSIONS: PC of GI origin is associated with significantly lower ctDNA levels compared with visceral metastasis. Caution is warranted when interpreting ctDNA results from patients with PC due to lower sensitivity for detecting actionable mutations.

Recurrence and Survival Rates for 1400 Early Breast Tumors Treated with Intraoperative Radiation Therapy (IORT).

INTRODUCTION: Intraoperative radiotherapy (IORT) permits accurate delivery of radiation therapy directly to the tumor bed. We report local, regional, and distant recurrence data along with overall and breast cancer-specific survival for 1400 tumors treated with x-ray IORT. METHODS: A total of 1367 patients with 1400 distinct tumors were enrolled in a registry trial. All received breast conservation surgery and low-energy 50 kV x-ray IORT. To be eligible for excision plus IORT as the only local treatment, histopathology had to confirm tumor size ≤30 mm, margins ≥2 mm, negative lymph nodes, and no extensive lymphovascular invasion. Patients who failed any parameters were referred for additional surgery and/or whole breast radiation therapy (WBRT). RESULTS: There were 64 ipsilateral local recurrences, 60 were in the IORT only group, 7 axillary recurrences, and 7 distant recurrences. Forty-one local recurrences were within the same quadrant as the index cancer. Twenty-three were in different quadrants. With 62 months of median follow-up, the 5-year Kaplan-Meier probability of any event for all 1400 tumors was 5.27%. For 1175 patients who received IORT only, it was 5.98%. For favorable subtypes, it ranged from 2.41 to 4.31%. Multivariate analysis revealed that biologic subtype luminal A and the addition of WBRT significantly reduced the risk of local recurrence. CONCLUSIONS: The local, regional, and distant recurrence rates observed were comparable to those reported in the literature for IORT but higher than those reported for standard forms of WBRT, hypofractionated treatment, or APBI. IORT benefits include convenience, decreased exposure to medical environments, and low complication rates.

Overnight olfactory enrichment using an odorant diffuser improves memory and modifies the uncinate fasciculus in older adults.

Objective: Cognitive loss in older adults is a growing issue in our society, and there is a need to develop inexpensive, simple, effective in-home treatments. This study was conducted to explore the use of olfactory enrichment at night to improve cognitive ability in healthy older adults. Methods: Male and female older adults (N = 43), age 60-85, were enrolled in the study and randomly assigned to an Olfactory Enriched or Control group. Individuals in the enriched group were exposed to 7 different odorants a week, one per night, for 2 h, using an odorant diffuser. Individuals in the control group had the same experience with de minimis amounts of odorant. Neuropsychological assessments and fMRI scans were administered at the beginning of the study and after 6 months. Results: A statistically significant 226% improvement was observed in the enriched group compared to the control group on the Rey Auditory Verbal Learning Test and improved functioning was observed in the left uncinate fasciculus, as assessed by mean diffusivity. Conclusion: Minimal olfactory enrichment administered at night produces improvements in both cognitive and neural functioning. Thus, olfactory enrichment may provide an effective and low-effort pathway to improved brain health.

Impact of an automated large vessel occlusion detection tool on clinical workflow and patient outcomes.

Purpose: Automated large vessel occlusion (LVO) tools allow for prompt identification of positive LVO cases, but little is known about their role in acute stroke triage when implemented in a real-world setting. The purpose of this study was to evaluate the automated LVO detection tool's impact on acute stroke workflow and clinical outcomes. Materials and methods: Consecutive patients with a computed tomography angiography (CTA) presenting with suspected acute ischemic stroke were compared before and after the implementation of an AI tool, RAPID LVO (RAPID 4.9, iSchemaView, Menlo Park, CA). Radiology CTA report turnaround times (TAT), door-to-treatment times, and the NIH stroke scale (NIHSS) after treatment were evaluated. Results: A total of 439 cases in the pre-AI group and 321 cases in the post-AI group were included, with 62 (14.12%) and 43 (13.40%) cases, respectively, receiving acute therapies. The AI tool demonstrated a sensitivity of 0.96, a specificity of 0.85, a negative predictive value of 0.99, and a positive predictive value of 0.53. Radiology CTA report TAT significantly improved post-AI (mean 30.58 min for pre-AI vs. 22 min for post-AI, p < 0.0005), notably at the resident level (p < 0.0003) but not at higher levels of expertise. There were no differences in door-to-treatment times, but the NIHSS at discharge was improved for the pre-AI group adjusted for confounders (parameter estimate = 3.97, p < 0.01). Conclusion: Implementation of an automated LVO detection tool improved radiology TAT but did not translate to improved stroke metrics and outcomes in a real-world setting.

Prevalence of Primary Liver Cancer is Affected by Place of Birth in Hispanic People Residing in the United States: All of Us Research Program Report.

BACKGROUND: Hispanic individuals have a disproportionately higher incidence and mortality for stomach, cervix, and liver cancers compared to Non-Hispanic White people. Since disparities in cancer incidence are influenced by multiple factors including immigration, elucidating the effect of birthplace and exposure to risk factors on the prevalence of these cancers is crucial for identifying high-risk populations and target risk reduction interventions. METHODS: The National Institutes of Health All of Us Research Program is a prospective, multidimensional biomedical data resource of underrepresented, minoritized people. The Registered Tier Dataset v5 was utilized to evaluate the prevalence and risk of stomach, cervix, and liver cancers among United States (US) born and non-US born Hispanic participants. RESULTS: Of over 434 000 current participants, 60 540 are Hispanic; 30 803 (50.9%) reported being US born and 29 294 (48.4%) non-US born. Non-US born Hispanic participants had significantly higher prevalence (.39% vs .21%, P < .001) and associated risk (OR 1.84, 95% CI 1.29-2.64, P < .001) of liver cancer, and trend towards higher prevalence of stomach (.14% vs .09%, P = .076) and cervix cancers (.27% vs .20%, P = .083) compared to US born counterparts. US born Hispanic patients with these 3 cancers were significantly younger than non-US born cohort (mean age 56.8 vs 61.7 years, P < .001). DISCUSSION: This is the first report using All of Us data to show that non-US born Hispanic participants have a higher risk of liver cancer compared to US born participants. Further analyses, including genomic studies, are necessary to understand these differences and identify targets for risk reduction interventions.

Misdiagnosis of appendiceal neoplasms as ovarian tumors: Impact of prior gynecologic surgery on definitive cytoreduction and HIPEC.

BACKGROUND: Female patients with pelvic/adnexal masses often undergo gynecologic operations due to presumed ovarian origin. The diagnosis of an appendiceal tumor is often only made postoperatively after suboptimal cytoreduction has been performed. We hypothesized that an index gynecological procedure increases the morbidity of definitive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in patients with appendiceal mucinous tumors. METHODS: A single-center retrospective review was performed to identify female patients undergoing CRS/HIPEC for appendiceal tumors from 2012 to 2020. RESULTS: During the 8-year period, CRS/HIPEC was performed in 36 female patients with appendiceal mucinous tumors. Eighteen patients (50.0%) had received a prior pelvic operation by gynecologists (PPO Group) for presumed ovarian origin before referral for definitive CRS/HIPEC. The median peritoneal cancer index (PCI) was higher in the PPO group (21 vs. 9, p = 0.04). The median number of days from gynecologic procedure to definitive CRS/HIPEC was 169 days. Compared to patients who did not undergo a prior gynecologic operation, those in the PPO group had higher intraoperative blood loss (650 vs 100 mL, p < 0.01) during CRS/HIPEC as well as longer length of stay (12 vs 8 days, p = 0.02) and higher overall morbidity (72.3% vs 33.3%, p = 0.02). After controlling for PCI, prior gynecologic operation increased risk of 30-day morbidity after definitive CRS/HIPEC (OR 11.6, p < 0.01). CONCLUSION: A multi-disciplinary approach is needed for the primary evaluation of patients with pelvic masses of undetermined origin. A gynecological resection is associated with increased morbidity during definitive cytoreduction and HIPEC for appendiceal mucinous tumors.

Assessment of Medical Industry Compensation to US Physicians by Gender.

Importance: It has been well established that female physicians earn less than their male counterparts in all specialties and ranks despite controlling for confounding variables. Objective: To investigate payments made from highest-grossing medical industry companies to female and male physicians and to assess compensation and engagement disparities based on gender. Design, Setting, and Participants: This retrospective, population-based cross-sectional study used data from the Open Payments database for the 5 female and 5 male physicians who received the most financial compensation from each of the 15 highest-grossing medical supply companies in the US from January 2013 to January 2019. Main Outcomes and Measures: The primary outcome was total general payments received by female and male physicians from medical industry over time and across industries. The secondary outcome was trends in industry payment to female and male physicians from 2013 to 2019. Results: Among the 1050 payments sampled, 1017 (96.9%) of the 5 highest earners were men and 33 (3.1%) were women. Female physicians were paid a mean (SD) of $41 320 ($88 695), and male physicians were paid a mean (SD) of $1 226 377 ($3 377 957) (P < .001). On multivariate analysis, male gender was significantly associated with higher payment after adjusting for rank, h-index, and specialty (mean [SD], $1 025 413 [$162 578]; P < .001). From 2013 to 2019, the payment gap between female and male physicians increased from $54 343 to $166 778 (P < .001). Conclusions and Relevance: This study found that male physicians received significantly higher payments from the highest-grossing medical industry companies compared with female physicians. This disparity persisted across all medical specialties and academic ranks. The health care industry gender payment gap continued to increase from 2013 to 2019, with a wider compensation gap in 2019.

Methodology for measuring the in vitro seating and unseating forces of prefabricated attachment systems used to retain implant overdentures.

PURPOSE: The purpose of this in vitro investigation was to measure the forces generated during the continuous seating and unseating of prefabricated attachment systems used to retain implant overdentures. MATERIALS AND METHODS: An experimental design consisting of interchangeable fixture mounts, a radially indexable fixture holder, and a materials testing systems (MTS) machine was used to measure forces generated during the insertion and removal of spherical stud attachments (Straumann, Inc, Waltham, WA). Three separate experiments were conducted measuring the seating and unseating forces of a vertically aligned patrix/matrix assembly, a 20 degrees angled patrix opposing a vertically positioned matrix, and a vertically positioned patrix opposing a 20 degrees angled matrix. For each patrix/matrix combination, three specimens were tested. Measurements were continuously recorded under reproducible conditions in the presence of artificial saliva. All specimens were subjected to 10,000 seating/unseating cycles. Statistical analysis was performed with rank analysis of variance (ANOVA) for a group comparison (alpha= 0.05). RESULTS: Results showed variability in the initial insertion and removal forces among experimental groups and among specimens within each experiment. A marked increase in the seating and unseating forces was recorded for all specimens during the first 300 cycles, followed by a gradual decrease in these forces. The exact p-values for the Kruskal-Wallis test showed no significant difference between the initial and final seating/unseating forces (p > 0.1) nor in the maximum seating/unseating forces (p > 0.6) among the three experimental groups. CONCLUSIONS: Spherical stud attachments exhibited consistent seating and unseating forces over 10,000 cycles. A 20 degrees angle between the patrix and matrix had no effect on the overall seating and unseating force values.

Preferences of Type 1 Diabetic Patients on Devices for Islet Transplantation.

Transplantation of pancreatic islets within a biomaterial device is currently under investigation in clinical trials for the treatment of patients with type 1 diabetes (T1D). Patients' preferences on such implants could guide the designs of next-generation implantable devices; however, such information is not currently available. We surveyed the preferences of 482 patients with T1D on the size, shape, visibility, and transplantation site of islet containing implants. More than 83% of participants were willing to receive autologous stem cells, and there was no significant association between implant fabricated by one's own stem cell with gender (χ2 (1, n = 468) = 0.28; P = 0.6) or with age (χ2 (4, n = 468) = 2.92; P = 0.6). Preferred location for islet transplantation within devices was under the skin (52.7%). 48.3% preferred microscopic disks, and 32.3% preferred a thin device (like a credit card). Moreover, 58.4% preferred the implant to be as small as possible, 25.4% did not care about visibility, and 16.2% preferred their implants not to be visible. Among female participants, 81% cared about the implant visibility, whereas this number was 64% for male respondents (χ2 test (1, n = 468) = 16.34; P < 0.0001). 22% of those younger than 50 years of age and 30% of those older than 50 did not care about the visibility of implant (χ2 test (4, n = 468) = 23.69; P < 0.0001). These results suggest that subcutaneous sites and micron-sized devices are preferred choices among patients with T1D who participated in our survey.

Targeted antimicrobial activity of a specific IgG-SMAP28 conjugate against Porphyromonas gingivalis in a mixed culture.

Antimicrobial peptides coupled to a ligand, receptor or antibody for a specific pathogenic bacteria could be used to develop narrow-spectrum pharmaceuticals with 'targeted' antimicrobial activity void of adverse reactions often associated with the use of broad-spectrum antibiotics. To assess the feasibility of this approach, in this study sheep myeloid antimicrobial peptide (SMAP) 28 was linked to affinity- and protein G-purified rabbit immunoglobulin G (IgG) antibodies specific to the outer surface of Porphyromonas gingivalis strain 381. The selective activity of the P. gingivalis IgG-SMAP28 conjugate was then assessed by adding it to an artificially generated microbial community containing P. gingivalis, Aggregatibacter actinomycetemcomitans and Peptostreptococcus micros. The specificity of the P. gingivalis IgG-SMAP28 conjugate in this mixed culture was concentration-dependent. The conjugate at 50 microg protein/mL lacked specificity and killed P. gingivalis, A. actinomycetemcomitans and P. micros. The conjugate at 20 microg protein/mL was more specific and killed P. gingivalis. This is an initial step to develop a selective antimicrobial agent that can eliminate a specific periodontal pathogen, such as P. gingivalis, from patients with periodontal disease without harming the normal commensal flora.

Factors associated with dental caries experience in 1-year-old children.

OBJECTIVES: Dental caries in early childhood is an important public health problem. Previous studies have examined risk factors, but they have focused on children during the later stages of the disease process. The purpose of this study was to assess the factors associated with caries in children aged 6 to 24 months as part of a cross-sectional analysis. METHODS: Two hundred twelve mothers with children 6 to 24 months of age were recruited from Special Supplemental Nutrition Program for Women, Infants, and Children clinic sites in southeastern Iowa for participation in a longitudinal study of dental caries. Baseline assessments included detailed questions regarding the children's beverage consumption, oral hygiene, and family socioeconomic status. Dental caries examinations using the d(1)d(2-3)f criteria and semiquantitative assessments of salivary mutans streptococci (MS) levels of mother and child were also conducted. Counts of the number of teeth with visible plaque were recorded for maxillary and mandibular molars and incisors. RESULTS: Of the 212 child/mother pairs, 187 children had teeth. Among these children, the mean age was 14 months, and 23 of the children exhibited either d(1), d(2-3), or filled lesions. Presence of caries was significantly associated with older age, presence of MS in children, family income <$25,000 per year, and proportion of teeth with visible plaque. CONCLUSIONS: Results suggest that not only microbial measures, including MS and plaque levels, are closely associated with caries in very young children, but that other age-related factors may also be associated with caries. Continued study is necessary to more fully assess the risk factors for caries prevalence and incidence in preschool children.

A longitudinal study of dental caries risk among very young low SES children.

OBJECTIVES: Early childhood caries (ECC) is a challenging public health problem in the United States and elsewhere; however, there is limited information concerning risk factors in very young children. The purpose of this study was to assess baseline risk factors for 18-month caries prevalence as part of a longitudinal study of high-risk children. METHODS: About 212 children, 6-24 months of age were recruited from a rural community in Iowa. Subjects were enrolled in the WIC program, which provides nutritional support for low-income families with children. Dental examinations using d1, d2-3 criteria were conducted at baseline and after 18 months. Caries prevalence was determined at the frank decay level (d2-3 or filled surfaces), as well as at the noncavitated level (d1), and combined (d1, d2-3 or f surfaces). Risk factor data were collected at baseline and after 9- and 18- months. These data included beverage consumption data, presence of visible plaque, and use of fluoride toothpaste for children as well as mutans streptococci (MS) levels of mothers and children and family sociodemographic factors. RESULTS: About 128 children (60%) remained in the study after 18 months. Among these children, prevalence of d1,d2-3/f level caries increased from 9% to 77%, while d2-3/f level caries increased from 2% to 20%. Logistic regression models for baseline predictors of d2-3f caries at the 18-month follow-up found the presence of MS in children (OR=4.4; 95% CI: 1.4, 13.9) and sugar-sweetened beverages (OR=3.0; 95% CI: 1.1, 8.6) to be the only significant risk factors. Sociodemographic factors and the use of fluoride toothpaste were not significant in these models. CONCLUSIONS: Results suggest that early colonization by MS and consumption of sugar-sweetened beverages are significant predictors of ECC in high-risk populations.

Video-Assisted Clinical Instruction in Dentistry (VACID) enhances real-time visualisation of clinical procedures.

AIM: The use of Video-Assisted Clinical Instruction in Dentistry (VACID) in the training of dental students represents an innovative teaching medium. Despite the many advantages that this teaching medium promises to offer, little objective research has been published to substantiate its purported benefits. This article examines the students' response to the application of VACID to enhance real-time visualisation of clinical procedures while observing live clinical procedures in periodontics. METHOD: Forty third-year dental students, observing surgical procedures during their rotation in the Department of Periodontics, were invited to participate in a survey designed to examine perceptions relating to their learning experience to using conventional and video-assisted real-time visualisation of clinical procedures. Students' responses were obtained using a questionnaire administered immediately after the completion of the observational period. The survey employed attitude questions addressing both enabling and outcome criteria. Wilcoxon signed-rank test was used to compare the student's responses. An open-ended question was also included in the survey to give students the opportunity to provide additional feedback regarding their experience and suggestions to improve on it. RESULTS: Results suggest that the implementation of VACID in the clinical setting improves the student's learning experience, interest and satisfaction. Ninety per cent of students strongly agreed to have VACID implemented for their next clinical observation. Responses to the open-ended question indicated that improved visualisation was extremely helpful in understanding the progress of clinical procedures. CONCLUSION: The implementation of VACID in the clinical setting enhances real-time visualisation of surgical procedures beyond what is offered by the conventional observational format.