Local Anesthesia for Endovascular Repair of Abdominal Aortic Aneurysm Allows for Accurate Graft Deployment with Durable Results.

BACKGROUND: Local anesthesia (LA) is sparsely used in endovascular aneurysm repair (EVAR) despite short-term benefit, likely secondary to concerns over patient movement preventing accurate endograft deployment. The objective of this study is to examine the association between anesthesia type and endoleak, sac regression, reintervention, and mortality. METHODS: The Vascular Quality Initiative database was queried for all EVAR cases from 2014 to 2022. Patients were included if they underwent percutaneous elective EVAR with anatomical criteria within instructions for use of commercially approved endografts. Multivariable logistic regression with propensity score weighting was used to determine the association between anesthesia type on the risk of any endoleak noted by intraoperative completion angiogram and sac regression. Multivariable survival analysis with propensity score weighting was used to determine the association between anesthesia type and endoleak at 1 year, long-term reintervention, and mortality. RESULTS: Thirteen thousand nine hundred thirty two EVARs met inclusion criteria: 1,075 (8%) LA and 12,857 (92%) general anesthesia (GA). On completion angiogram, LA was associated with fewer rates of any endoleaks overall (16% vs. 24%, P < 0.001). On multivariable analysis with propensity score weighting, LA was associated with similar adjusted odds of any endoleak on intraoperative completion angiogram (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.47-0.68) as well as combined type 1a and type 1b endoleaks (OR 0.72, 95% CI 0.47-1.09). Follow-up computed tomography imaging at 1 year was available for 4,892 patients, 377 (8%) LA and 4,515 (92%) GA. At 1 year, LA was associated with similar rate of freedom from any endoleaks compared to GA (0.66 [95% CI 0.63-0.69] vs. 0.71 [95% CI 0.70-0.72], P = 0.663) and increased rates of sac regression (50% vs. 45%, P = 0.040). On multivariable analysis with propensity score weighting, LA and GA were associated with similar adjusted odds of sac regression (OR 1.22, 95% CI 0.97-1.55). LA and GA had similar rates of endoleak at 1 year (hazard ratio [HR] 0.14, 95% CI 0.63-1.07); however, LA was associated with decreased hazards of combined type 1a and 1b endoleaks at 1 year (HR 0.87, 95% CI 0.80-0.96). LA and GA had similar adjusted long-term reintervention rate (HR 0.77, 95% CI 0.44-1.38) and long-term mortality (HR 1.100, 95% CI 079-1.25). CONCLUSIONS: LA is not associated with increased adjusted rates of any endoleak on completion angiogram or at 1-year follow-up compared to GA. LA is associated with decreased adjusted rates of type 1a and type 1b endoleak at 1 year, but similar rates of sac regression, long-term reintervention, and mortality. Concerns for accurate graft deployment should not preclude use of LA and LA should be increasingly considered when deciding on anesthetic type for standard elective EVAR.

Effect of vitamin E-enhanced highly cross-linked polyethylene on wear rate and particle debris in anatomic total shoulder arthroplasty: a biomechanical comparison to ultrahigh-molecular-weight polyethylene.

BACKGROUND: Particle-induced osteolysis resulting from polyethylene wear remains a source of implant failure in anatomic total shoulder designs. Modern polyethylene components are irradiated in an oxygen-free environment to induce cross-linking, but reducing the resulting free radicals with melting or heat annealing can compromise the component's mechanical properties. Vitamin E has been introduced as an adjuvant to thermal treatments. Anatomic shoulder arthroplasty models with a ceramic head component have demonstrated that vitamin E-enhanced polyethylene show improved wear compared with highly cross-linked polyethylene (HXLPE). This study aimed to assess the biomechanical wear properties and particle size characteristics of a novel vitamin E-enhanced highly cross-linked polyethylene (VEXPE) glenoid compared to a conventional ultrahigh-molecular-weight polyethylene (UHMWPE) glenoid against a cobalt chromium molybdenum (CoCrMo) head component. METHODS: Biomechanical wear testing was performed to compare the VEXPE glenoid to UHMWPE glenoid with regard to pristine polyethylene wear and abrasive endurance against a polished CoCrMo alloy humeral head in an anatomic shoulder wear-simulation model. Cumulative mass loss (milligrams) was recorded, and wear rate calculated (milligrams per megacycle [Mc]). Under pristine wear conditions, particle analysis was performed, and functional biologic activity (FBA) was calculated to estimate particle debris osteolytic potential. In addition, 95% confidence intervals for all testing conditions were calculated. RESULTS: The average pristine wear rate was statistically significantly lower for the VEXPE glenoid compared with the HXLPE glenoid (0.81 ± 0.64 mg/Mc vs. 7.00 ± 0.45 mg/Mc) (P < .05). Under abrasive wear conditions, the VEXPE glenoid had a statistically significant lower average wear rate compared with the UHMWPE glenoid comparator device (18.93 ± 5.80 mg/Mc vs. 40.47 ± 2.63 mg/Mc) (P < .05). The VEXPE glenoid demonstrated a statistically significant improvement in FBA compared with the HXLPE glenoid (0.21 ± 0.21 vs. 1.54 ± 0.49 (P < .05). CONCLUSIONS: A new anatomic glenoid component with VEXPE demonstrated significantly improved pristine and abrasive wear properties with lower osteolytic particle debris potential compared with a conventional UHMWPE glenoid component. Vitamin E-enhanced polyethylene shows early promise in shoulder arthroplasty components. Long-term clinical and radiographic investigation needs to be performed to verify if these biomechanical wear properties translate to diminished long-term wear, osteolysis, and loosening.

The effect of photobiomodulation on hearing loss: A systematic review.

OBJECTIVES: To assess outcomes associated with photobiomodulation therapy (PBMT) for hearing loss in human and animal studies. DESIGN: Systematic review and narrative synthesis in accordance with PRISMA guidelines. SETTING: Data bases searched: MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov and Web of Science. No limits were placed on language or year of publication. Review conducted in accordance with the PRISMA 2020 statement. PARTICIPANTS: All human and animal subjects treated with PBMT for hearing loss. MAIN OUTCOME MEASURES: Pre- and post-PBMT audio metric outcomes. RESULTS: Searches identified 122 abstracts and 49 full text articles. Of these, 17 studies met the inclusion criteria, reporting outcomes in 327 animals (11 studies), 30 humans (1 study), and 40 animal specimens (5 studies). PBMT parameters included 6 different wavelengths: 908 nm (1 study), 810 nm (1 study), 532 & 635 nm (1 study), 830 nm (3 studies), 808 nm (11 studies). The duration ranged from 4 to 60 minutes in a session, and the follow-up ranged from 5-28 days. Outcomes improved significantly when wavelengths within the range of 800-830 nm were used, and with greater duration of PBMT exposure. Included studies predominantly consisted of non-randomized controlled trials (10 studies). CONCLUSIONS: Hearing outcomes following PBMT appear to be superior to no PBMT for subjects with hearing loss, although higher level evidence is required to verify this. PBMT enables concentrated, focused delivery of light therapy to the inner ear through a non-invasive manner with minimal side effects. As a result of heterogeneity in reporting PBMT parameters and outcomes across the included studies, direct comparison is challenging.

The effect of photobiomodulation on tinnitus: a systematic review.

OBJECTIVE: To establish outcomes following photobiomodulation therapy for tinnitus in humans and animal studies. METHODS: A systematic review and narrative synthesis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The databases searched were: Medline, Embase, Cochrane Central Register of Controlled Trials ('Central'), ClinicalTrials.gov and Web of Science including the Web of Science Core collection. There were no limits on language or year of publication. RESULTS: The searches identified 194 abstracts and 61 full texts. Twenty-eight studies met the inclusion criteria, reporting outcomes in 1483 humans (26 studies) and 34 animals (2 studies). Photobiomodulation therapy parameters included 10 different wavelengths, and duration ranged from 9 seconds to 30 minutes per session. Follow up ranged from 7 days to 6 months. CONCLUSION: Tinnitus outcomes following photobiomodulation therapy are generally positive and superior to no photobiomodulation therapy; however, evidence of long-term therapeutic benefit is deficient. Photobiomodulation therapy enables concentrated, focused delivery of light therapy to the inner ear through a non-invasive manner, with minimal side effects.

Understanding the implementation of health checks in the prevention and early detection of chronic diseases among Aboriginal and Torres Strait Islander people in Australia: a realist review protocol.

INTRODUCTION: Chronic disease remains the leading cause of morbidity and mortality among Aboriginal and Torres Strait Islander peoples in Australia. Regular structured, comprehensive health assessments are available to Aboriginal and Torres Strait Islander people as annual health checks funded through the Medicare Benefits Schedule. This realist review aims to identify context-specific enablers and tensions and contribute to developing an evidence framework to guide the implementation of health checks in the prevention and early detection of chronic diseases for Aboriginal and Torres Strait Islander people. METHODS AND ANALYSIS: The review will involve the following steps: (1) Aboriginal and Torres Strait Islander engagement and research governance; (2) defining the scope of the review; (3) search strategy; (4) screening, study selection and appraisal; (5) data extraction and organisation of evidence; (6) data synthesis and drawing conclusions. This realist review will follow the Realist and MEta-narrative Evidence Syntheses: Evolving Standards guidance and will be reported as set up by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement. The realist programme theory will be developed through a literature review using multiple database searches from 1 November 1999 to 31 June 2022, limited to the English language, and stakeholder consultation, which will be refined throughout the review process. The study findings will be reported by applying the context-mechanism-outcome configuration to gain a deeper understanding of context and underlying mechanisms that influence the implementation of health checks in the prevention and early detection of chronic diseases among Aboriginal and Torres Strait Islander people in Australia. ETHICS AND DISSEMINATION: Ethical approval is not required as this review will be using secondary data. Findings will be published in a peer-reviewed journal and presented at scientific conferences. SYSTEMATIC REVIEW REGISTRATION: The review protocol has been registered on the international prospective register of systematic reviews: CRD42022326697.

Vascular protection afforded by zinc supplementation in human coronary artery smooth muscle cells mediated by NRF2 signaling under hypoxia/reoxygenation.

Zinc (Zn) has antioxidant, anti-inflammatory and anti-proliferative actions, with Zn dysregulation associated with coronary ischemia/reperfusion injury and smooth muscle cell dysfunction. As the majority of studies concerning Zn have been conducted under non-physiological hyperoxic conditions, we compare the effects of Zn chelation or supplementation on total intracellular Zn content, antioxidant NRF2 targeted gene transcription and hypoxia/reoxygenation-induced reactive oxygen species generation in human coronary artery smooth muscle cells (HCASMC) pre-adapted to hyperoxia (18 kPa O2) or normoxia (5 kPa O2). Expression of the smooth muscle marker SM22-α was unaffected by lowering pericellular O2, whereas calponin-1 was significantly upregulated in cells under 5 kPa O2, indicating a more physiological contractile phenotype under 5 kPa O2. Inductively coupled plasma mass spectrometry established that Zn supplementation (10 µM ZnCl2 + 0.5 µM pyrithione) significantly increased total Zn content in HCASMC under 18 but not 5 kPa O2. Zn supplementation increased metallothionein mRNA expression and NRF2 nuclear accumulation in cells under 18 or 5 kPa O2. Notably, NRF2 regulated HO-1 and NQO1 mRNA expression in response to Zn supplementation was only upregulated in cells under 18 but not 5 kPa. Furthermore, whilst hypoxia increased intracellular glutathione (GSH) in cells pre-adapted to 18 but not 5 kPa O2, reoxygenation had negligible effects on GSH or total Zn content. Reoxygenation-induced superoxide generation in cells under 18 kPa O2 was abrogated by PEG-superoxide dismutase but not by PEG-catalase, and Zn supplementation, but not Zn chelation, attenuated reoxygenation-induced superoxide generation in cells under 18 but not 5kPaO2, consistent with a lower redox stress under physiological normoxia. Our findings highlight that culture of HCASMC under physiological normoxia recapitulates an in vivo contractile phenotype and that effects of Zn on NRF2 signaling are altered by oxygen tension.

Low-dose vanadium pentoxide perturbed lung metabolism associated with inflammation and fibrosis signaling in male animal and in vitro models.

Vanadium is available as a dietary supplement and also is known to be toxic if inhaled, yet little information is available concerning the effects of vanadium on mammalian metabolism when concentrations found in food and water. Vanadium pentoxide (V+5) is representative of the most common dietary and environmental exposures, and prior research shows that low-dose V+5 exposure causes oxidative stress measured by glutathione oxidation and protein S-glutathionylation. We examined the metabolic impact of V+5 at relevant dietary and environmental doses (0.01, 0.1, and 1 ppm for 24 h) in human lung fibroblasts (HLFs) and male C57BL/6J mice (0.02, 0.2, and 2 ppm in drinking water for 7 mo). Untargeted metabolomics using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) showed that V+5 induced significant metabolic perturbations in both HLF cells and mouse lungs. We noted 30% of the significantly altered pathways in HLF cells, including pyrimidines and aminosugars, fatty acids, mitochondrial and redox pathways, showed similar dose-dependent patterns in mouse lung tissues. Alterations in lipid metabolism included leukotrienes and prostaglandins involved in inflammatory signaling, which have been associated with the pathogenesis of idiopathic pulmonary fibrosis (IPF) and other disease processes. Elevated hydroxyproline levels and excessive collagen deposition were also present in lungs from V+5-treated mice. Taken together, these results show that oxidative stress from environmental V+5, ingested at low levels, could alter metabolism to contribute to common human lung diseases.NEW & NOTEWORTHY We used relevant dietary and environmental doses of Vanadium pentoxide (V+5) to examine its metabolic impact in vitro and in vivo. Using liquid chromatography-high-resolution mass spectrometry (LC-HRMS), we found significant metabolic perturbations, with similar dose-dependent patterns observed in human lung fibroblasts and male mouse lungs. Alterations in lipid metabolism included inflammatory signaling, elevated hydroxyproline levels, and excessive collagen deposition were present in V+5-treated lungs. Our findings suggest that low levels of V+5 could trigger pulmonary fibrotic signaling.

Low-Cost, High-Pressure-Synthesized Oxygen-Entrapping Materials to Improve Treatment of Solid Tumors.

Tumor hypoxia drives resistance to many cancer therapies, including radiotherapy and chemotherapy. Methods that increase tumor oxygen pressures, such as hyperbaric oxygen therapy and microbubble infusion, are utilized to improve the responses to current standard-of-care therapies. However, key obstacles remain, in particular delivery of oxygen at the appropriate dose and with optimal pharmacokinetics. Toward overcoming these hurdles, gas-entrapping materials (GeMs) that are capable of tunable oxygen release are formulated. It is shown that injection or implantation of these materials into tumors can mitigate tumor hypoxia by delivering oxygen locally and that these GeMs enhance responsiveness to radiation and chemotherapy in multiple tumor types. This paper also demonstrates, by comparing an oxygen (O2 )-GeM to a sham GeM, that the former generates an antitumorigenic and immunogenic tumor microenvironment in malignant peripheral nerve sheath tumors. Collectively the results indicate that the use of O2 -GeMs is promising as an adjunctive strategy for the treatment of solid tumors.

Root-associated fungal communities are influenced more by soils than by plant-host root traits in a Chinese tropical forest.

Forest fungal communities are shaped by the interactions between host tree root systems and the associated soil conditions. We investigated how the soil environment, root morphological traits, and root chemistry influence root-inhabiting fungal communities in three tropical forest sites of varying successional status in Xishuangbanna, China. For 150 trees of 66 species, we measured root morphology and tissue chemistry. Tree species identity was confirmed by sequencing rbcL, and root-associated fungal (RAF) communities were determined using high-throughput ITS2 sequencing. Using distance-based redundancy analysis and hierarchical variation partitioning, we quantified the relative importance of two soil variables (site average total phosphorus and available phosphorus), four root traits (dry matter content, tissue density, specific tip abundance, and forks), and three root tissue elemental concentrations (nitrogen, calcium, and manganese) on RAF community dissimilarity. The root and soil environment collectively explained 23% of RAF compositional variation. Soil phosphorus explained 76% of that variation. Twenty fungal taxa differentiated RAF communities among the three sites. Soil phosphorus most strongly affects RAF assemblages in this tropical forest. Variation in root calcium and manganese concentrations and root morphology among tree hosts, principally an architectural trade-off between dense, highly branched vs less-dense, herringbone-type root systems, are important secondary determinants.

The follow up of complex infants in an aerodigestive clinic.

The current available literature evaluating pediatric multidisciplinary aerodigestive programs for the management of aerodigestive disorders in infants was reviewed. Multidisciplinary aerodigestive programs have emerged to provide coordinated and comprehensive care for the growing population of children with aerodigestive conditions, including complex airway, pulmonary, gastrointestinal, and feeding disorders, which are prevalent among infants discharged from the neonatal intensive care unit (NICU). The team approach central to aerodigestive clinics offers a comprehensive diagnostic workup and unified management plan through consolidated interdisciplinary clinics, combined endoscopic procedures, and regular team discussions, leading to improved resource utilization and health care outcomes. We review common conditions presenting in the NICU that benefit from the aerodigestive model of care, including esophageal atresia, prematurity, bronchopulmonary dysplasia with or without tracheostomy or ventilator dependence, and dysphagia.

Stimulation of the Tibial nerve Repetitively to Improve Incontinence in Parkinson's Electronically (STRIPE trial): a randomised control trial of tibial nerve stimulation for bladder symptoms in Parkinson's disease using a self-contained wearable device.

BACKGROUND: Bladder symptoms are common in Parkinson's disease (PD), affecting half of all individuals. These have significant impact on quality of life as well as implications for morbidity, contributing to falls and hospital admission. The treatment of bladder symptoms can be complicated by the tendency to side-effects in people with PD including cognitive impairment and gait instability with anti-muscarinics. The development of new, better treatments is therefore warranted. Tibial nerve stimulation is a form of neuromodulation demonstrated to improve overactive bladder symptoms in non-neurogenic cohorts. Previously requiring hospital attendance, we aim to explore the use of this intervention using a simple device that can be used by patients at home. METHODS: STRIPE is a phase II randomised control trial of tibial nerve stimulation delivered by the Geko™ device, a small, self-adhesive neuromuscular stimulation device currently used for thromboembolism prophylaxis post-surgery. Active tibial nerve stimulation will be compared to sham stimulation, with participants blinded to treatment allocation and undertaking outcome assessment whilst still blinded. Participants will be asked to self-administer stimulation at home twice per week, for 30 min per session, over the course of 3 months. Primary outcome measure will be the International Consultation on Incontinence Overactive Bladder Questionnaire (OAB) at week 12. Secondary outcomes will include pre- and post-intervention bladder diary (frequency, urgency episodes, nocturia), patient perception of global change, bowel function and bladder-related quality of life. Participants will be recruited from the Proactive Integrated Management and Empowerment (PRIME) cross-sectional trial in which participants have been screened for bladder symptoms and invited to take part, as well as clinician referral from around the region. DISCUSSION: This trial will involve a randomised control trial of a novel and easy to use method of delivering tibial nerve stimulation for PD in the patient's own home. This may potentially have huge benefit, avoiding the problems with side effects that can be seen with anti-muscarinics and providing a new potential modality of treatment. TRIAL REGISTRATION: ISRCTN11484954. Registered on 22 June 2021.

Vanadium pentoxide induced oxidative stress and cellular senescence in human lung fibroblasts.

Both environmental exposure to vanadium pentoxide (V2O5, V+5 for its ionic counterparts) and fibroblast senescence are associated with pulmonary fibrosis, but whether V+5 causes fibroblast senescence remains unknown. We found in a dose-response study that 2-40 µM V+5 caused human lung fibroblasts (HLF) senescence with increased senescence-associated ß-galactosidase activity and p16 expression, while cell death occurred at higher concentration (LC50, 82 µM V+5). Notably, measures of reactive oxygen species (ROS) production with fluorescence probes showed no association of ROS with V+5-dependent senescence. Preloading catalase (polyethylene-conjugated), a H2O2 scavenger, did not alleviate the cellular senescence induced by V+5. Analyses of the cellular glutathione (GSH) system showed that V+5 oxidized GSH, increased GSH biosynthesis, stimulated cellular GSH efflux and increased protein S-glutathionylation, and addition of N-acetyl cysteine inhibited V+5-elevated p16 expression, suggesting that thiol oxidation mediates V+5-caused senescence. Moreover, strong correlations between GSSG/GSH redox potential (Eh), protein S-glutathionylation, and cellular senescence (R2 > 0.99, p < 0.05) were present in V+5-treated cells. Studies with cell-free and enzyme-free solutions showed that V+5 directly oxidized GSH with formation of V+4 and GSSG in the absence of O2. Analyses of V+5 and V+4 in HLF and culture media showed that V+5 was reduced to V+4 in cells and that a stable V+4/V+5 ratio was rapidly achieved in extracellular media, indicating ongoing release of V+4 and reoxidation to V+5. Together, the results show that V+5-dependent fibroblast senescence is associated with a cellular/extracellular redox cycling mechanism involving the GSH system and occurring under conditions that do not cause cell death. These results establish a mechanism by which environmental vanadium from food, dietary supplements or drinking water, can cause or contribute to lung fibrosis in the absence of high-level occupational exposures and cytotoxic cell death.

Exploring connections between pollinator health and human health.

Despite recent advances in understanding the role of biodiversity in ecosystem-service provision, the links between the health of ecosystem-service providers and human health remain more uncertain. During the past decade, an increasing number of studies have argued for the positive impacts of healthy pollinator communities (defined as functionally and genetically diverse species assemblages that are sustained over time) on human health. Here, we begin with a systematic review of these impacts, finding only two studies that concomitantly quantified aspects of pollinator health and human health. Next, we identify relevant research relating to four pathways linking pollinator health and human health: nutrition, medicine provisioning, mental health and environmental quality. These benefits are obtained through improved pollination of nutritious crops and an estimated approximately 28 000 animal-pollinated medicinal plants; the provisioning of pollinator-derived products such as honey; the maintenance of green spaces and biocultural landscapes that improve mental health; and cleaner air, water and food resulting from pollinator-centred initiatives to reduce agrochemical use. We suggest that pollinator diversity could be a proxy for the benefits that landscapes provide to human health. This article is part of the theme issue 'Natural processes influencing pollinator health: from chemistry to landscapes'.

Nitric oxide biosensor uncovers diminished ferrous iron-dependency of cultured cells adapted to physiological oxygen levels.

Iron is an essential metal for cellular metabolism and signaling, but it has adverse effects in excess. The physiological consequences of iron deficiency are well established, yet the relationship between iron supplementation and pericellular oxygen levels in cultured cells and their downstream effects on metalloproteins has been less explored. This study exploits the metalloprotein geNOps in cultured HEK293T epithelial and EA.hy926 endothelial cells to test the iron-dependency in cells adapted to standard room air (18 kPa O2) or physiological normoxia (5 kPa O2). We show that cells in culture require iron supplementation to activate the metalloprotein geNOps and demonstrate for the first time that cells adapted to physiological normoxia require significantly lower iron compared to cells adapted to hyperoxia. This study establishes an essential role for recapitulating oxygen levels in vivo and uncovers a previously unrecognized requirement for ferrous iron supplementation under standard cell culture conditions to achieve geNOps functionality.

Neuromodulation for Storage Lower Urinary Tract Symptoms in Parkinson Disease: A Systematic Review.

BACKGROUND: Bladder symptoms are common in Parkinson disease (PD), affecting quality of life. Medications commonly used such as antimuscarinics can cause frequently intolerable side effects, and therefore, new, better tolerated approaches are needed. Neuromodulation techniques have an established role in urologic disorders; these techniques include tibial nerve stimulation (TNS) and sacral neuromodulation (SNM), which are localized therapies lacking the side effects associated with medication. OBJECTIVES: This study aimed to undertake a systematic review of the literature reporting the use of neuromodulation techniques for the treatment of bladder symptoms in PD and related conditions. MATERIALS AND METHODS: A systematic search of data bases was conducted including MEDLINE, CENTRAL, and Web of Science. Studies were required to present specific outcomes for individuals with PD for neuromodulation interventions. RESULTS: Ten primary studies were identified concerning detailed outcomes of neuromodulation on bladder symptoms in PD, including seven for TNS, one for SNM, and one using transcranial magnetic stimulation (TMS). Two further mixed cohort studies documented minimal data on individuals with PD. All studies demonstrated benefit in a range of outcome measures following neuromodulation. Two randomized sham-controlled studies were carried out using TNS, with one clearly demonstrating superiority over sham, although difficulties with achieving believable yet ineffective sham treatment are highlighted. Further studies reported limited, uncontrolled outcomes of SNM in patients with PD, demonstrating benefit. CONCLUSIONS: Evidence from case series suggests benefit from TNS in PD, with limited literature on SNM or TMS. Placebo effect from neuromodulation is a concern, and only limited controlled data exist. Future well-designed and sham-controlled studies need to be completed to provide definitive data on the benefit of neuromodulation in PD. Definitively proving the utility of a neuromodulation modality will allow better treatment of bladder symptoms without the need for pharmacologic measures that cause side effects.

NCCN Risk Reclassification in Black Men with Low and Intermediate Risk Prostate Cancer After Genomic Testing.

OBJECTIVES: To assess the utility of genomic testing in risk-stratifying Black patients with low and intermediate risk prostate cancer. METHODS: We retrospectively identified 63 Black men deemed eligible for active surveillance based on National Comprehensive Cancer Network (NCCN) guidelines, who underwent OncotypeDx Genomic Prostate Score testing between April 2016 and July 2020. Nonparametric statistical testing was used to compare relevant features between patients reclassified to a higher NCCN risk after genomic testing and those who were not reclassified. RESULTS: The median age was 66 years and median pre-biopsy PSA was 7.3. Initial risk classifications were: very low risk: 7 (11.1%), low risk: 24(38.1%), favorable intermediate risk: 31(49.2%), and unfavorable intermediate risk: 1 (1.6%). Overall, NCCN risk classifications after Genomic Prostate Score testing were significantly higher than initial classifications (P=.003, Wilcoxon signed-rank). Among patients with discordant risk designations, 28(28/40, 70%) were reclassified to a higher NCCN risk after genomic testing. A pre-biopsy prostate specific antigen of greater than 10 did not have significantly higher odds of HBR (OR:2.16 [95% CI: 0.64,7.59, P=.2). Of favorable intermediate risk patients, 20(64.5%) were reclassified to a higher NCCN risk. Ultimately, 18 patients underwent definitive treatment. CONCLUSIONS: Incorporation of genomic testing in risk stratifying Black men with low and intermediate-risk prostate cancer resulted in overall higher NCCN risk classifications. Our findings suggest a role for increased utilization of genomic testing in refining risk-stratification within this patient population. These tests may better inform treatment decisions on an individualized basis.

Associations of practical, emotional, and physical problems with psychosocial distress among cancer patients.

OBJECTIVE: To better understand the relationship between cancer patient distress and psychosocial variables, including problem types, to improve ability to predict and address psychosocial need. METHODS: A variation of National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT) was administered and collected at four sites from an Integrated Network Cancer Program (INCP). The presence of moderate/severe distress was examined relative to patient demographics, disease characteristics, and psychosocial problems. RESULTS: Distress scores were positively correlated with all problem counts. For every count increase of practical, emotional, and physical problems, and for every cancer stage increase the odds of reporting a moderate/severe distress score was significantly higher. Relative to patients with one cancer treatment type, patients with three cancer treatment types were significantly less likely to report moderate/severe distress. CONCLUSION: Problem count could be a useful indicator for clinical intervention. Stage and number of treatment types may also be considered clinically relevant distress predictors.

Implications for Psychosocial ResearchThis study found that NCCN Distress Thermometer distress levels and problem counts are highly correlated in most cancer patients.In addition to distress level, problem count on NCCN Distress Thermometer should be considered a potential trigger for psychosocial intervention.NCCN Distress Thermometer problem count may be a more durable indicator of need for psychosocial intervention then distress level alone. Psychosocial problems are rarely transient, while distress level can fluctuate day-to-day.Future research should examine the role of psychosocial problems on continuous distress scores and the relative contribution of each set of problem types on distress.

An audit of routine practice: a prospective study on the use of mouth props in oral surgery.

Introduction Mouth props are routinely used for patients treated under general but not local anaesthesia (LA). Patient discomfort and excess operator time is an often cited argument against the routine use of mouth props.Aim and methods We surveyed patients, surgeons and assistants following the use of mouth props during minor oral surgical procedures under LA in order to assess their acceptability and utility in clinical practice.Results Forty-seven patients were included, with 24 patients treated using mouth props and 23 without. Thirty-three patients had dental extractions, three had intraoral biopsies and one underwent a tube removal following cyst marsupialisation.Discussion Patients reported less difficulty in mouth opening where a mouth prop was used. Patients reported similarly low levels of discomfort with or without a mouth prop. Ninety-five percent of patients who used a mouth prop reported they would recommend their use. The surgeon and assistant reported mouth opening as less problematic and assisting as easier where a mouth prop was used.Conclusion The results of this study demonstrate the benefits and broad acceptability of mouth prop use in the awake patient. We question current practice in that mouth props are not routinely offered to patients during oral surgical and dental procedures.

Using community-engaged methods to adapt virtual reality job-interview training for transition-age youth on the autism spectrum.

BACKGROUND: Virtual Reality Job-Interview Training (VR-JIT) is an efficacious Internet-based intervention for adults with severe mental illness (SMI). Evaluations of VR-JIT have shown improved interview skill and access to employment in several cohorts of adults with SMI and with autism spectrum disorders (ASD). VR-JIT trains participants how to fill out job applications and handle job interviews through e-learning content and applied practice. Trainees receive feedback through in-the-moment nonverbal cues, critiques, and recommendations for improving performance. Our study sought to adapt VR-JIT for transition-age youth with ASD (TAY-ASD). METHODS: We recruited TAY-ASD and adult stakeholders from public and charter schools, transition programs, and community service providers. Participants provided feedback on VR-JIT to enhance its applicability to TAY-ASD. We used community-engaged methods to process and analyze data from TAY-ASD and stakeholders, presented their quantitative and qualitative responses to community and scientific advisory boards for review and recommendations, and adapted the intervention design and content. RESULTS: Our adaptations included adding diversity (gender; race/ethnicity) to the virtual hiring manager; shortening the interview by reducing response options; increasing social storytelling to enhance engagement with VR-JIT core components; adding employment opportunities more relevant to younger workers; reducing the reading level; and making the e-learning content more accessible by adding bullet points, voiceover, and imagery/video; and adding new learning goals. CONCLUSIONS: This study presents a rigorous and innovative community-engaged methodology for adapting VR-JIT to meet the needs of TAY-ASD. We review our engagement with TAY-ASD and stakeholders, and discuss the standardized coding scheme we used to adapt VR-JIT and the usefulness and limitations of employing this methodology in adapting other behavioral interventions.

A precision medicine approach to defining the impact of doxorubicin on the bioenergetic-metabolite interactome in human platelets.

Non-invasive measures of the response of individual patients to cancer therapeutics is an emerging strategy in precision medicine. Platelets offer a potential dynamic marker for metabolism and bioenergetic responses in individual patients since they have active glycolysis and mitochondrial oxidative phosphorylation and can be easily isolated from a small blood sample. We have recently shown how the bioenergetic-metabolite interactome can be defined in platelets isolated from human subjects by measuring metabolites and bioenergetics in the same sample. In the present study, we used a model system to assess test the hypothesis that this interactome is modified by xenobiotics using exposure to the anti-cancer drug doxorubicin (Dox) in individual donors. We found that unsupervised analysis of the metabolome showed clear differentiation between the control and Dox treated group. Dox treatment resulted in a concentration-dependent decrease in bioenergetic parameters with maximal respiration being most sensitive and this was associated with significant changes in over 166 features. A metabolome-wide association study of Dox was also conducted, and Dox was found to have associations with metabolites in the glycolytic and TCA cycle pathways. Lastly, network analysis showed the impact of Dox on the bioenergetic-metabolite interactome and revealed profound changes in the regulation of reserve capacity. Taken together, these data support the conclusion that platelets are a suitable platform to predict and monitor therapeutic efficacy as well as anticipate susceptibility to toxicity in the context of precision medicine.