Black cancer patients navigating a health-care system of racial discrimination.

BACKGROUND: Exposure to racial discrimination may exacerbate disparities throughout the cancer care continuum. Therefore, we explored how experiences of racial discrimination in the health-care setting manifest for Black cancer patients and how it contributes to racial disparities in cancer care. METHODS: This qualitative analysis used semistructured in-depth interviews with Black cancer survivors not on active treatment from May 2019 to March 2020. All interviews were audio recorded, professionally transcribed, and uploaded into Dedoose software for analysis. We identified major themes and subthemes that highlight exposure to racial discrimination and its consequences for Black cancer patients when receiving cancer care. RESULTS: Participants included 18 Black cancer survivors, aged 29-88 years. Most patients experienced racial discrimination when seeking care. Participants experienced racial discrimination from their interactions with health-care staff, medical assistants, front desk staff, and health insurance administrators. Exposure to overt racial discrimination in the health-care setting was rooted in racial stereotypes and manifested through verbal insults such as physicians using phrases such as "you people." These experiences impacted the ability of the health-care delivery system to demonstrate trustworthiness. Patients noted "walking out" of their visit and not having their health issues addressed. Despite experiences with racial discrimination, patients still sought care out of necessity believing it was an inevitable part of the Black individual experience. CONCLUSION: We identified that exposure to racial discrimination in the health-care setting is pervasive, affects health-seeking behaviors, and degrades the patient-clinician relationship, which may likely contribute to racial disparities in cancer care.

Racial and ethnic disparities in self-reported general and mental health status among colorectal cancer survivors: impact of sociodemographic factors and implications for mortality-a SEER-CAHPS study.

PURPOSE: Patient-reported outcomes are recognized as strong predictors of cancer prognosis. This study examines racial and ethnic differences in self-reported general health status (GHS) and mental health status (MHS) among patients with colorectal cancer (CRC). METHODS: A retrospective analysis of Medicare beneficiaries between 1998 and 2011 with non-distant CRC who underwent curative resection and completed a Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey within 6-36 months of CRC diagnosis. Analysis included a stepwise logistic regression to examine the relationship between race and ethnicity and fair or poor health status, and a proportional hazards model to determine the mortality risk associated with fair or poor health status. RESULTS: Of 1867 patients, Non-Hispanic Black (OR 1.56, 95% CI 1.06-2.28) and Hispanic (OR 1.48, 95% CI 1.04-2.11) patients had higher unadjusted odds for fair or poor GHS compared to Non-Hispanic White patients, also Hispanic patients had higher unadjusted odds for fair or poor MHS (OR 1.92, 95% CI 1.23-3.01). These relationships persisted after adjusting for clinical factors but were attenuated after subsequently adjusting for sociodemographic factors. Compared to those reporting good to excellent health status, patients reporting fair or poor GHS or MHS had an increased mortality risk (OR 1.52, 95% CI 1.31-1.76 and OR 1.63, 95% CI 1.34-1.99, respectively). CONCLUSION: Racial and ethnic differences in GHS and MHS reported after CRC diagnosis are mainly driven by sociodemographic factors and reflect a higher risk of mortality. Identifying unmet biopsychosocial needs is necessary to promote equitable care.

Reflection on the Role of a Hospital Chaplain as a Resource for Ethical Concerns.

As I take a legal approach to religion and spirituality, I reflect on how a chaplain can be beneficial as a resource to ethical concerns with which medical teams and patients/caregivers are confronted. This rather new approach can help medical professionals to understand the scope of a chaplain's work and to distinguish the work of a chaplain from that of clergy in organized religion.

Experience of a single academic institution with the National Accreditation Program for Rectal Cancer and the resulting improvement in care.

AIM: The American College of Surgeons Committee on Cancer developed the National Accreditation Program for Rectal Cancer (NAPRC) to reduce variations in rectal cancer care, standardize clinical practice and encourage multidisciplinary approaches. The aim of this study was to analyse if accreditation achieved a higher quality of care at one hospital. METHOD: The University of California Davis Medical Center was accredited in 2019. A retrospective review of rectal adenocarcinoma patients was performed between the years 2013 and 2018. Patients presenting from 2013 to 2015 were discussed at a gastrointestinal tumour board while patients in 2018 had an accredited rectal cancer tumour board. Patients from 2016 to 2017 were excluded as the programme was still developing. Compliance to the NAPRC standards was compared between the cohorts. RESULTS: One hundred and thirty patients were evaluated, 88 (68%) in the prerectal tumour board cohort and 42 (32%) in the rectal tumour board cohort. The prerectal tumour board cohort often failed to meet attendance standards. All patients in the rectal tumour board cohort met all criteria. Similarly, clinical service compliance improved in the rectal tumour board cohort for 13 metrics, 10 of which were statistically significant. Although a high proportion of patients in both groups experienced quality surgery, i.e. complete total mesorectal excision and negative margins, the lack of complete pathological reporting in the prerectal tumour board cohort limited analysis. CONCLUSION: Multidisciplinary rectal cancer tumour boards are associated with improved compliance with recommended care by the NAPRC. Patients discussed at a rectal cancer tumour board were more likely to receive appropriate staging, coordinated care and have better clinical documentation.

Legionella monitoring results by water quality characteristics in a large public water system.

Legionella, the causative agent of Legionnaires' disease, is an emerging concern for water utilities. Passaic Valley Water Commission (PVWC) is a public drinking water supplier, which provides treated surface water to approximately 800,000 customers in New Jersey. To evaluate the occurrence of Legionella in the PVWC distribution system, swab, first draw, and flushed cold water samples were collected from total coliform sites (n = 58) during a summer and winter sampling event. Endpoint PCR detection methods were combined with culture for Legionella detection. Among 58 total coliform sites during the summer, 17.2% (10/58) of first draw samples were positive for 16S and mip Legionella DNA markers and 15.5% (9/58) in flushed samples. Across both summer and winter sampling, a total of four out of 58 sites had low-level culture detection of Legionella spp. (0.5-1.6 CFU/mL) among first draw samples. Only one site had both a first and flush draw detection (8.5 CFU/mL and 1.1 CFU/mL) for an estimated culture detection frequency of 0% in the summer and 1.7% in the winter among flushed draw samples. No L. pneumophila was detected by culture. Legionella DNA detection was significantly greater in the summer than in the winter, and detection was greater in samples collected from areas treated with phosphate. No statistical difference was found between first draw and flush sample detection. Total organic carbon, copper, and nitrate were significantly associated with Legionella DNA detection.

Patient and provider perspectives to utilization of telemedicine in surgery.

Objectives: Determine patient and provider perspectives on widespread rapid telemedicine implementation, understand the key components of a surgical telemedicine visit and identify factors that affect future telemedicine use. Summary of background data: Compared to other specialties, the field of surgery heretofore has had limited adoption of telemedicine. During the COVID-19 pandemic Healthcare, including the surgical specialties, saw new widespread use of telemedicine. Methods: We conducted a prospective cohort study during the COVID-19 California stay-at-home and physical distancing executive orders. Utilization data were collected from clinics and compared to usage data during the same time 1 year later. All patients and providers who participated in a telemedicine visit during the study period were asked to complete a survey after each encounter and the surveys were analyzed for trends in opinions on future use by stakeholders. Results: Over the 10-week period, the median percentage of telemedicine visits per clinic was 33% (17%-51%) which peaked 3 weeks into implementation. One hundred and ninety-one patients (48% women) with a median age of 64 years (IQR 53-73) completed the patient survey. Patients were first-time participants in telemedicine in 41% (n = 79) of visits. Fifty-seven percent (n = 45) of first-time users preferred that future visits be in-person versus 31% of prior users (p = 0.007). The median travel time from home to the clinic was 40 min (IQR = 20-90). Patients with longer travel times were not more likely to use telemedicine in the future (61% with longer travel vs. 53% shorter, p = 0.11). From the 148 provider responses, 90% of the visits providers were able to create a definitive plan with the telemedicine visit. A physical exam was determined not to be needed in 45% of the visits. An attempt at any physical exam was not performed in 84% of routine follow-up or new-patient visits, compared to 53% of post-op visits (p = 0.001). Conclusion: Telemedicine is a viable ambulatory visit option for surgical specialists and their patients. During rapid telemedicine deployment, travel distance did not correlate with increased use of telemedicine, and in-person visits are still preferred. However, nearly half of all visits did not need a physical exam, which favors telemedicine use.

Severe Obesity Contributes to Worse Outcomes After Elective Colectomy for Chronic Diverticular Disease.

BACKGROUND: Both obesity and chronic diverticular disease (DD) are on the rise. Understanding surgical outcomes for patients with obesity undergoing colectomy for DD is imperative to improve care and minimize complications. Our objective was to investigate the impact of obesity on outcomes after elective colectomy specifically for chronic DD. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2018, patients who underwent elective colectomy for chronic DD were grouped into four body mass index categories. Baseline characteristics, surgical approach and procedure, and 30-day morbidity and mortality were assessed. RESULTS: Of 24,559 patients, 21.7% were of normal weight, 35.8% were overweight, 35.9% were obese, and 6.6% were severely obese. Patients with severe obesity were younger, more functionally dependent, and had more comorbidities (all P [Formula: see text] 0.0001). Patients with severe obesity were more likely to have unplanned conversion to open surgery from laparoscopic and robotic approaches (AOR 2.15, 95% CI 1.24-3.70). Obesity class did not significantly affect the type of surgical procedure patients underwent (Hartmann's, colectomy with anastomosis and diversion, or colectomy with primary anastomosis). There were increased odds of any perioperative complications (AOR 1.43, 95% CI 1.19-1.71) and non-home discharge (AOR 2.39, 95% CI 1.59-3.57) in patients with severe obesity compared to normal weight patients. CONCLUSIONS: Obesity is associated with poorer outcomes in patients undergoing elective colectomy for chronic DD. Futures studies to examine the impact of preemptive weight loss to improve outcomes after elective colectomy for chronic sequelae of DD are needed.

A meta-analysis of the effect of binge drinking on the oral microbiome and its relation to Alzheimer's disease.

The diversity of bacterial species in the oral cavity makes it a key site for research. The close proximity of the oral cavity to the brain and the blood brain barrier enhances the interest to study this site. Changes in the oral microbiome are linked to multiple systemic diseases. Alcohol is shown to cause a shift in the microbiome composition. This change, particularly in the oral cavity, may lead to neurological diseases. Alzheimer's disease (AD) is a common neurodegenerative disorder that may cause irreversible memory loss. This study uses the meta-analysis method to establish the link between binge drinking, the oral microbiome and AD. The QIAGEN Ingenuity Pathway Analysis (IPA) shows that high levels of ethanol in binge drinkers cause a shift in the microbiome that leads to the development of AD through the activation of eIF2, regulation of eIF4 and p70S6K signaling, and mTOR signaling pathways. The pathways associated with both binge drinkers and AD are also analyzed. This study provides a foundation that shows how binge drinking and the oral microbiome dysbiosis lead to permeability changes in the blood brain barrier (BBB), which may eventually result in the pathogenesis of AD.

CRISPR interference-mediated gene regulation in Pseudomonas putida KT2440.

Targeted gene regulation is indispensable for reprogramming a cellular network to modulate a microbial phenotype. Here, we adopted the type II CRISPR interference (CRISPRi) system for simple and efficient regulation of target genes in Pseudomonas putida KT2440. A single CRISPRi plasmid was generated to express a nuclease-deficient Cas9 gene and a designed single guide RNA, under control of l-rhamnose-inducible Prha BAD and the constitutive Biobrick J23119 promoter respectively. Two target genes were selected to probe the CRISPRi-mediated gene regulation: exogenous green fluorescent protein on the multicopy plasmid and endogenous glpR on the P. putida KT2440 chromosome, encoding GlpR, a transcriptional regulator that represses expression of the glpFKRD gene cluster for glycerol utilization. The CRISPRi system successfully repressed the two target genes, as evidenced by a reduction in the fluorescence intensity and the lag phase of P. putida KT2440 cell growth on glycerol. Furthermore, CRISPRi-mediated repression of glpR improved both the cell growth and glycerol utilization, resulting in the enhanced production of mevalonate in an engineered P. putida KT2440 harbouring heterologous genes for the mevalonate pathway. CRISPRi is expected to become a robust tool to reprogram P. putida KT2440 for the development of microbial cell factories producing industrially valuable products.

Advances in Modeling the Immune Microenvironment of Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related death in the US. CRC frequently metastasizes to the liver and these patients have a particularly poor prognosis. The infiltration of immune cells into CRC tumors and liver metastases accurately predicts disease progression and patient survival. Despite the evident influence of immune cells in the CRC tumor microenvironment (TME), efforts to identify immunotherapies for CRC patients have been limited. Here, we argue that preclinical model systems that recapitulate key features of the tumor microenvironment-including tumor, stromal, and immune cells; the extracellular matrix; and the vasculature-are crucial for studies of immunity in the CRC TME and the utility of immunotherapies for CRC patients. We briefly review the discoveries, advantages, and disadvantages of current in vitro and in vivo model systems, including 2D cell culture models, 3D culture systems, murine models, and organ-on-a-chip technologies.

One-Year Outcomes of an Integrated Multiple Sclerosis Disease Management Program.

BACKGROUND: Multiple sclerosis (MS) is associated with high total health care cost, the majority of which is attributable to medications. Patients with MS are less likely to experience relapses, emergency department (ED) visits, and hospitalizations when they are adherent to disease-modifying treatments. Disease management programs are hypothesized to improve medication adherence thereby improving clinical and economic outcomes. OBJECTIVE: To evaluate the clinical and economic effects of a specialty pharmacy and chronic disease management program for patients with MS from a health plan perspective. METHODS: This study was a retrospective analysis using prescription drug claims, medical claims, and electronic medical record information (2013-2015) 1 year before and after enrollment in the disease management program for members with 24 months of continuous health plan coverage. Medication adherence was calculated using proportion of days covered (PDC). Relapse rate was defined as an MS outpatient visit associated with a corticosteroid dispense within 7 days of the visit or an MS hospitalization. Disease progression was assessed using the Modified Expanded Disability Status Scale (mEDSS). Resource use included outpatient visits, ED visits, and hospitalizations. Cost information was collected as health plan-paid amount and was reported in 2013 U.S. dollars. RESULTS: The analysis included 377 patients (mean age 55 years, 76.4% female). After enrollment in the program, 78.7% of the study group had a PDC of ≥ 0.80 compared with 70.0% before enrollment (P < 0.001). There was no difference in MS relapse rate (0.25 after vs. 0.45 before, P = 0.11) or mEDSS score (3.77 after vs. 3.76 before, P = 0.19). Health care resource utilization was minimal and did not change significantly throughout the study period: mean outpatient visits (13.09 after vs. 13.78 before, P = 0.69); mean ED visits (0.18 after vs. 0.16 before, P = 0.60); and mean hospitalizations (0.12 after vs. 0.12 before, P = 1.00). This nonsignificant finding remained when the analysis was limited to MS-related visits only. Average annual health plan spend per patient on MS medications significantly increased ($55,835 after vs. $40,883 before, P < 0.001). CONCLUSIONS: Specialty pharmacy and chronic disease management for patients with MS can increase the proportion of patients adherent to medication. The increase in health plan spend on MS medications is not offset by savings in health care resource utilization. DISCLOSURES: This study was funded by Kaiser Permanente Washington Health Research Institute and Kaiser Permanente Washington Pharmacy Administration. The authors have no disclosures to report.

Leucine zipper-mediated targeting of multi-enzyme cascade reactions to inclusion bodies in Escherichia coli for enhanced production of 1-butanol.

Metabolons in nature have evolved to facilitate more efficient catalysis of multistep reactions through the co-localization of functionally related enzymes to cellular organelles or membrane structures. To mimic the natural metabolon architecture, we present a novel artificial metabolon that was created by targeting multi-enzyme cascade reactions onto inclusion body (IB) in Escherichia coli. The utility of this system was examined by co-localizing four heterologous enzymes of the 1-butanol pathway onto an IB that was formed in E. coli through overexpression of the cellulose binding domain (CBD) of Cellulomonas fimi exoglucanase. To target the 1-butanol pathway enzymes to the CBD IB, we utilized a peptide-peptide interaction between leucine zipper (LZ) peptides. We genetically fused the LZ peptide to the N-termini of four heterologous genes involved in the synthetic 1-butanol pathway, whereas an antiparallel LZ peptide was fused to the CBD gene. The in vivo activity of the CBD IB-based metabolon was examined through the determination of 1-butanol synthesis using E. coli transformed with two plasmids containing the LZ-fused CBD and LZ-fused 1-butanol pathway genes, respectively. In vivo synthesis of 1-butanol using the engineered E. coli yielded 1.98g/L of 1-butanol from glucose, representing a 1.5-fold increase over that obtained from E. coli expressing the LZ-fused 1-butanol pathway genes alone. In an attempt to examine the in vitro 1-butanol productivity, we reconstituted CBD IB-based metabolon using CBD IB and individual enzymes of 1-butanol pathway. The 1-butanol productivity of in vitro reconstituted CBD IB-based metabolon using acetoacetyl-CoA as the starting material was 2.29mg/L/h, 7.9-fold higher than that obtained from metabolon-free enzymes of 1-butanol pathway. Therefore, this novel CBD-based artificial metabolon may prove useful in metabolic engineering both in vivo and in vitro for the efficient production of desired products.

Fermentative production and direct extraction of (-)-α-bisabolol in metabolically engineered Escherichia coli.

BACKGROUND: (-)-α-Bisabolol, also known as levomenol, is an unsaturated sesquiterpene alcohol that has mainly been used in pharmaceutical and cosmetic products due to its anti-inflammatory and skin-soothing properties. (-)-α-Bisabolol is currently manufactured mainly by steam-distillation of the essential oils extracted from the Brazilian candeia tree that is under threat because its natural habitat is constantly shrinking. Therefore, microbial production of (-)-α-bisabolol plays a key role in the development of its sustainable production from renewable feedstock. RESULTS: Here, we created an Escherichia coli strain producing (-)-α-bisabolol at high titer and developed an in situ extraction method of (-)-α-bisabolol, using natural vegetable oils. We expressed a recently identified (-)-α-bisabolol synthase isolated from German chamomile (Matricaria recutita) (titer: 3 mg/L), converted the acetyl-CoA to mevalonate, using the biosynthetic mevalonate pathway (12.8 mg/L), and overexpressed farnesyl diphosphate synthase to efficiently supply the (-)-α-bisabolol precursor farnesyl diphosphate. Combinatorial expression of the exogenous mevalonate pathway and farnesyl diphosphate synthase enabled a dramatic increase in (-)-α-bisabolol production in the shake flask culture (80 mg/L) and 5 L bioreactor culture (342 mg/L) of engineered E. coli harboring (-)-α-bisabolol synthase. Fed-batch fermentation using a 50 L fermenter was conducted after optimizing culture conditions, resulting in efficient (-)-α-bisabolol production with a titer of 9.1 g/L. Moreover, a green, downstream extraction process using vegetable oils was developed for in situ extraction of (-)-α-bisabolol during fermentation and showed high yield recovery (>98%). CONCLUSIONS: The engineered E. coli strains and economically viable extraction process developed in this study will serve as promising platforms for further development of microbial production of (-)-α-bisabolol at large scale.

X-Ray Psoralen Activated Cancer Therapy (X-PACT).

This work investigates X-PACT (X-ray Psoralen Activated Cancer Therapy): a new approach for the treatment of solid cancer. X-PACT utilizes psoralen, a potent anti-cancer therapeutic with current application to proliferative disease and extracorporeal photopheresis (ECP) of cutaneous T Cell Lymphoma. An immunogenic role for light-activated psoralen has been reported, contributing to long-term clinical responses. Psoralen therapies have to-date been limited to superficial or extracorporeal scenarios due to the requirement for psoralen activation by UVA light, which has limited penetration in tissue. X-PACT solves this challenge by activating psoralen with UV light emitted from novel non-tethered phosphors (co-incubated with psoralen) that absorb x-rays and re-radiate (phosphoresce) at UV wavelengths. The efficacy of X-PACT was evaluated in both in-vitro and in-vivo settings. In-vitro studies utilized breast (4T1), glioma (CT2A) and sarcoma (KP-B) cell lines. Cells were exposed to X-PACT treatments where the concentrations of drug (psoralen and phosphor) and radiation parameters (energy, dose, and dose rate) were varied. Efficacy was evaluated primarily using flow cell cytometry in combination with complimentary assays, and the in-vivo mouse study. In an in-vitro study, we show that X-PACT induces significant tumor cell apoptosis and cytotoxicity, unlike psoralen or phosphor alone (p<0.0001). We also show that apoptosis increases as doses of phosphor, psoralen, or radiation increase. Finally, in an in-vivo pilot study of BALBc mice with syngeneic 4T1 tumors, we show that the rate of tumor growth is slower with X-PACT than with saline or AMT + X-ray (p<0.0001). Overall these studies demonstrate a potential therapeutic effect for X-PACT, and provide a foundation and rationale for future studies. In summary, X-PACT represents a novel treatment approach in which well-tolerated low doses of x-ray radiation are delivered to a specific tumor site to generate UVA light which in-turn unleashes both short- and potentially long-term antitumor activity of photo-active therapeutics like psoralen.

A magnetometer-free indoor human localization based on loosely coupled IMU/UWB fusion.

The magnetic distortions in indoor environment affects the accuracy of yaw angle estimation using magnetometer. Thus, the accuracy of indoor localization based on inertial-magnetic sensors will be affected as well. To address this issue, this paper proposes a magnetometer-free solution for indoor human localization and yaw angle estimation. The proposed algorithm fuses a wearable inertial sensor consisting of MEMS-based accelerometer and gyroscope with a portable ultra-wideband (UWB) localization system in a cascaded two-step filter consisting of a tilt Kalman filter and a localization Kalman filter. By benchmarking against an optical motion capture system, the experimental results show that the proposed algorithm can accurately track position and velocity as well as the yaw angle without using magnetometer.

Adaptive Kalman filter for indoor localization using Bluetooth Low Energy and inertial measurement unit.

This paper proposes a novel indoor localization method using the Bluetooth Low Energy (BLE) and an inertial measurement unit (IMU). The multipath and non-line-of-sight errors from low-power wireless localization systems commonly result in outliers, affecting the positioning accuracy. We address this problem by adaptively weighting the estimates from the IMU and BLE in our proposed cascaded Kalman filter (KF). The positioning accuracy is further improved with the Rauch-Tung-Striebel smoother. The performance of the proposed algorithm is compared against that of the standard KF experimentally. The results show that the proposed algorithm can maintain high accuracy for position tracking the sensor in the presence of the outliers.