Social Determinants of Health Mediate Racial Disparities in Cardiovascular Disease in Men With Prostate Cancer.

Background: Cardiovascular disease (CVD) is a significant cause of morbidity and mortality in men with prostate cancer; however, data on racial disparities in CVD outcomes are limited. Objectives: We quantified the disparities in CVD according to self-identified race and the role of the structural social determinants of health in mediating disparities in prostate cancer patients. Methods: A retrospective cohort study of 3,543 prostate cancer patients treated with systemic androgen deprivation therapy (ADT) between 2008 and 2021 at a quaternary, multisite health care system was performed. The multivariable adjusted association between self-reported race (Black vs White) and incident major adverse cardiovascular events (MACE) after ADT initiation was evaluated using cause-specific proportional hazards. Mediation analysis determined the role of theme-specific and overall social vulnerability index (SVI) in explaining the racial disparities in CVD outcomes. Results: Black race was associated with an increased hazard of MACE (HR: 1.38; 95% CI: 1.16-1.65; P < 0.001). The association with Black race was strongest for incident heart failure (HR: 1.79; 95% CI: 1.32-2.43), cerebrovascular disease (HR: 1.98; 95% CI: 1.37-2.87), and peripheral artery disease (HR: 1.76; 95% CI: 1.26-2.45) (P < 0.001). SVI, specifically the socioeconomic status theme, mediated 98% of the disparity in MACE risk between Black and White patients. Conclusions: Black patients are significantly more likely to experience adverse CVD outcomes after systemic ADT compared with their White counterparts. These disparities are mediated by socioeconomic status and other structural determinants of health as captured by census tract SVI. Our findings motivate multilevel interventions focused on addressing socioeconomic vulnerability.

Diversity of Ehrlichia spp., Anaplasma spp. and Neorickettsia spp. in vampire bats.

Although bats (Mammalia: Chiroptera) act as natural reservoirs for many zoonotic pathogens around the world, few studies have investigated the occurrence of Anaplasmataceae agents in bats, especially vampire bats. The family Anaplasmataceae (order Rickettsiales) encompasses obligate intracellular bacteria of the genera Anaplasma, Ehrlichia, Neorickettsia, Neoehrlichia, Wolbachia, and Allocryptoplasma. The present study aimed to investigate, using molecular techniques, the presence of species of Anaplasma, Ehrlichia, and Neorickettsia in vampire bats sampled in northern Brazil. Between 2017 and 2019, spleen samples were collected from vampire bats belonging to two species, Desmodus rotundus (n = 228) from the states of Pará (n = 207), Amazonas (n = 1), Roraima (n = 18) and Amapá (n = 3), and Diaemus youngii (n = 1) from Pará. Positivity rates of 5.2% (12/229), 3% (7/229), and 10.9% (25/229) were found in PCR assays for Anaplasma spp. (16S rRNA gene), Ehrlichia spp. (dsb gene) and Neorickettsia spp. (16S rRNA gene), respectively. The present study revealed, for the first time, the occurrence of Anaplasma spp. and different genotypes of Ehrlichia spp. in vampire bats from Brazil. While phylogenetic analyses based on the dsb and ftsZ genes of Ehrlichia and 16S rRNA of Anaplasma spp. revealed phylogenetic proximity of the genotypes detected in vampire bats with Anaplasmataceae agents associated with domestic ruminants, phylogenetic inferences based on the gltA and groEL genes evidenced the occurrence of genotypes apparently exclusive to bats. Neorickettsia sp. phylogenetically associated with N. risticii was also detected in vampire bats sampled in northern Brazil.

Access to Sudden Hearing Loss Care at Urgent Care Centers.

OBJECTIVES: To compare patient access to urgent care centers (UCCs) with a diagnosis of sudden hearing loss based on insurance. METHODS: One hundred twenty-five random UCCs in states with Medicaid expansion and 125 random UCCs in states without Medicaid expansion were contacted by a research assistant posing as a family member seeking care on behalf of a patient with a one-week history of sudden, unilateral hearing loss. Each clinic was called once as a Medicaid patient and once as a private insurance (PI) patient for 500 total calls. Each phone encounter was evaluated for insurance acceptance and self-pay price. Secondary outcomes included other measures of timely/accessible care. Chi-square/McNemar's tests and independent/paired sample t-tests were performed to determine whether there were statistically significant differences between expansion status and insurance type. Calls ended before answering questions were not included in the analysis. RESULTS: Medicaid acceptance rate was significantly lower than PI (68.1% vs. 98.4%, p < 0.001). UCCs in Medicaid expansion states were significantly more likely to accept Medicaid (76.8% vs. 59.2%, p = 0.003). The mean wage-adjusted self-pay price was significantly greater in states with Medicaid expansion at $169.84 than in states without at $145.34 when called as a Medicaid patient (mean difference: $24.50, 95% Confidence Interval: $0.45-$48.54, p = 0.046). The rates of referral to an emergency department and self-pay price nondisclosure rates were greater for Medicaid calls than for private insurance calls (8.2% vs. 0.4% and 17.4% vs. 5.8%; p < 0.001 for both). CONCLUSION: Medicaid patients with otologic emergencies face reduced access to care at UCCs. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Symptomatology in Unilateral Versus Bilateral Superior Canal Dehiscence Patients Undergoing Unilateral Surgery.

OBJECTIVE: To compare symptomatology in patients with unilateral versus bilateral superior semicircular canal dehiscence who underwent unilateral surgical repair. STUDY DESIGN: Retrospective cohort study. SETTING: Single surgeon series at tertiary academic medical center from 2002 to 2021. METHODS: Patients were administered a standardized questionnaire regarding the presence or absence of 16 symptoms (11 auditory and 8 vestibular) pre- and postoperatively. Symptom rates were compared between patients with unilateral and bilateral dehiscence, and paired statistical testing was used to analyze symptom improvement with surgery. RESULTS: Our final cohort included 125 patients, 93 (74%) with unilateral superior canal dehiscence syndrome (SCDS) and 32 (26%) with bilateral SCDS. Bilateral patients had an increased burden of auditory and vestibular symptoms compared to unilateral patients before surgery (7.6 vs 6.2, P = .03) and after surgery (3.1 vs 1.9, P = .02). Both groups experienced a significant reduction of symptoms following repair (P < .01 for both). CONCLUSION: Our study has 2 key findings: First, patients with bilateral dehiscence seem to be more symptomatic, reporting more auditory and vestibular symptoms both before and after surgery. Second, bilateral patients still seem to benefit from unilateral repair, demonstrating a significant reduction in the number of symptoms with surgery. Our findings may help inform the management of the sizable proportion of SCDS patients with bilateral defects.

First report of unusual case of parasitism by Amblyomma nodosum (Neumann, 1889) in a yellow cururu toad (Rhinella icterica) in the Northeastern Brazilian Caatinga.

The Amblyomma genus (Arachnida: Ixodidae) is widely distributed in South America, with 34 species occurring in Brazil. Amblyomma nodosum Neumann 1889 is a species that predominantly feeds on Passeriformes during immature stages (larvae and nymphs) and anteaters (Myrmecophagidae) during adult stages. The aim of the present study is to report, for the first time, an unusual case of parasitism by adults of A. nodosum on a yellow cururu toad (Rhinella icterica) captured in the city of Nossa Senhora da Glória, Sergipe state (Northeastern Brazil) in the Caatinga biome, and also investigate the presence of DNA of Rickettsia in the collected material. DNA was extracted from all specimens collected (N=8) and subjected to PCR assays based on the tick 16S rRNA endogenous gene and gltA gene for Rickettsia sp. All samples (8/8; 100%) were positive for the 16S rRNA endogenous gene and two amplicons (obtained from one male and one female) were purified and sequenced. The BLASTn analysis of the sequences revealed a high degree of similarity (95-100%) with A. nodosum sequences previously deposited on GenBank, while the phylogenetic analysis clustered the sequences obtained in the same clade as A. nodosum sequences from Brazil.

Design of substituted tetrahydrofuran derivatives for HIV-1 protease inhibitors: synthesis, biological evaluation, and X-ray structural studies.

Substituted tetrahydrofuran derivatives were designed and synthesized to serve as the P2 ligand for a series of potent HIV-1 protease inhibitors. Both enantiomers of the tetrahydrofuran derivatives were synthesized stereoselectivity in optically active forms using lipase-PS catalyzed enzymatic resolution as the key step. These tetrahydrofuran derivatives are designed to promote hydrogen bonding and van der Waals interactions with the backbone atoms in the S2 subsite of the HIV-1 protease active site. Several inhibitors displayed very potent HIV-1 protease inhibitory activity. A high-resolution X-ray crystal structure of an inhibitor-bound HIV-1 protease provided important insight into the ligand binding site interactions in the active site.

Contemporary Trends and Outcomes of Intravascular Lithotripsy in Percutaneous Coronary Intervention: Insights From BMC2.

BACKGROUND: With an aging population and an increase in the comorbidity burden of patients undergoing percutaneous coronary intervention (PCI), the management of coronary calcification for optimal PCI is critical in contemporary practice. OBJECTIVES: This study sought to examine the trends and outcomes of coronary intravascular lithotripsy (IVL), rotational/orbital atherectomy, or both among patients who underwent PCI in Michigan. METHODS: We included all PCIs between January 1, 2021, and June 30, 2022, performed at 48 Michigan hospitals. Outcomes included in-hospital major adverse cardiac events (MACEs) and procedural success. RESULTS: IVL was used in 1,090 patients (2.57%), atherectomy was used in 1,743 (4.10%) patients, and both were used in 240 patients (0.57% of all PCIs). IVL use increased from 0.04% of PCI cases in January 2021 to 4.28% of cases in June 2022, ultimately exceeding the rate of atherectomy use. The rate of MACEs (4.3% vs 5.4%; P = 0.23) and procedural success (89.4% vs 89.1%; P = 0.88) were similar among patients treated with IVL compared with atherectomy, respectively. Only 15.6% of patients treated with IVL in contemporary practice were similar to the population enrolled in the pivotal IVL trials. Among such patients (n = 169), the rate of MACEs (0.0%) and procedural success (94.7%) were similar to the outcomes reported in the pivotal IVL trials. CONCLUSIONS: Since its introduction in February 2021, coronary IVL use has steadily increased, exceeding atherectomy use in Michigan by February 2022. Contemporary use of IVL and atherectomy is generally associated with high rates of procedural success and low rates of complications.

Identification of retinal oligomeric, citrullinated, and other tau isoforms in early and advanced AD and relations to disease status.

This study investigates various pathological tau isoforms in the retina of individuals with early and advanced Alzheimer's disease (AD), exploring their connection with disease status. Retinal cross-sections from predefined superior-temporal and inferior-temporal subregions and corresponding brains from neuropathologically confirmed AD patients with a clinical diagnosis of either mild cognitive impairment (MCI) or dementia (n = 45) were compared with retinas from age- and sex-matched individuals with normal cognition (n = 30) and non-AD dementia (n = 4). Retinal tau isoforms, including tau tangles, paired helical filament of tau (PHF-tau), oligomeric-tau (Oligo-tau), hyperphosphorylated-tau (p-tau), and citrullinated-tau (Cit-tau), were stereologically analyzed by immunohistochemistry and Nanostring GeoMx digital spatial profiling, and correlated with clinical and neuropathological outcomes. Our data indicated significant increases in various AD-related pretangle tau isoforms, especially p-tau (AT8, 2.9-fold, pS396-tau, 2.6-fold), Cit-tau at arginine residue 209 (CitR209-tau; 4.1-fold), and Oligo-tau (T22+, 9.2-fold), as well as pretangle and mature tau tangle forms like MC-1-positive (1.8-fold) and PHF-tau (2.3-fold), in AD compared to control retinas. MCI retinas also exhibited substantial increases in Oligo-tau (5.2-fold), CitR209-tau (3.5-fold), and pS396-tau (2.2-fold). Nanostring GeoMx analysis confirmed elevated retinal p-tau at epitopes: Ser214 (2.3-fold), Ser396 (2.6-fold), Ser404 (2.4-fold), and Thr231 (1.8-fold), particularly in MCI patients. Strong associations were found between retinal tau isoforms versus brain pathology and cognitive status: a) retinal Oligo-tau vs. Braak stage, neurofibrillary tangles (NFTs), and CDR cognitive scores (ρ = 0.63-0.71), b) retinal PHF-tau vs. neuropil threads (NTs) and ABC scores (ρ = 0.69-0.71), and c) retinal pS396-tau vs. NTs, NFTs, and ABC scores (ρ = 0.67-0.74). Notably, retinal Oligo-tau strongly correlated with retinal Aß42 and arterial Aß40 forms (r = 0.76-0.86). Overall, this study identifies and quantifies diverse retinal tau isoforms in MCI and AD patients, underscoring their link to brain pathology and cognition. These findings advocate for further exploration of retinal tauopathy biomarkers to facilitate AD detection and monitoring via noninvasive retinal imaging.

A comparison of iCare and Goldmann applanation tonometry measurements during the COVID-19 pandemic: a retrospective study.

PURPOSE: To evaluate factors associated with differences in intraocular pressure (IOP) readings between iCare and Goldmann applanation tonometry (GAT) in established glaucoma patients. METHODS: This retrospective comparative study included clinical data of 350 eyes from 350 established glaucoma patients who had iCare and GAT IOP measured by an ophthalmic technician and a glaucoma specialist, respectively. The main outcome measure was the difference in IOP measurements of the right eyes with iCare and GAT. RESULTS: The intraclass correlation coefficient (ICC) between GAT and iCare was 0.90. The mean IOP difference between tonometers was - 0.18 ± 2.89 mmHg. Bland-Altman plots indicated a 95% limit of agreement of - 5.8 to 5.5 mmHg. Central corneal thickness (CCT) and age were significantly correlated with the difference in IOPs of the iCare and GAT. GAT-IOP and age were significantly associated with the absolute difference in measured IOP of the two tonometers. The difference in measurements was not significantly associated with prior glaucoma surgery, average global index of optical coherence tomography, axial length, technician years of experience and certification, and IOP range. CONCLUSION: Although there is good agreement between the iCare and GAT mean values, these devices are not interchangeable in glaucoma patients due to the wide range of the limit of agreement.

Analgesia efficacy of erector spinae plane block in laparoscopic Abdominal surgeries: A systemic review and meta-analysis.

BACKGROUND: Multimodal analgesia is now widely practised to minimise postoperative opioid consumption while optimising pain control. The aim of this meta-analysis was to assess the analgesic efficacy of erector spinae plane block (ESPB) in patients undergoing laparoscopic abdominal surgeries. This will be determined by perioperative opioid consumption, subjective pain scores and incidences of postoperative nausea and vomiting. METHODS: We systemically searched electronic databases for randomised controlled trials (RCTs) published up to February 2023 comparing ESPB with other adjuvant analgesic techniques in laparoscopic abdominal surgeries. Nine randomised controlled trials encompassing 666 subjects were included in our study. RESULTS: ESPB was shown to reduce postoperative opioid consumption [mean difference (MD) of -5.95mg (95% CI: -8.86 to -3.04; P< 0.0001); I2=89%], intraoperative opioid consumption [mean difference (MD) of -102.4mcg (95% CI: -145.58 to -59.21; P< 0.00001); I2=39%] and incidence of nausea [RR 0.38 (95% CI: 0.25 to 0.60; P< 0.0001); I2=0%] and vomiting [RR 0.32 (95% CI: 0.17 to 0.63; P=0.0009); I2=0%] in laparoscopic abdominal surgeries. Subgroup analysis on laparoscopic colorectal surgeries further showed reduction in postoperative pain scores [mean difference (MD) of -0.68 (95% CI: -0.94 to -0.41); P< 0.00001; I2=0%]. CONCLUSIONS: This study concludes that ESPB is a valuable technique with proven efficacy to potentially promote faster postoperative recovery through optimising pain control while minimising opioid requirements.

Facial Implants in Male Rejuvenation.

Many different methods achieve male facial augmentation. Arranged from shorter- to longer-term results, these methods include filler, fat/tissue grafting, fat/tissue transposition, and alloplastic implants. This study solely reviews allografts, which provide the most predictable hard-tissue augmentation. An array of alloplasts will be discussed in this study including chin, cheek, mandibular angle, frontal, and temporal implants. The most common and severe complications will also be explored with preventative and treatment algorithms.

Label-Free Imaging of Inflammation at the Level of Single Cells in the Living Human Eye.

Purpose: Putative microglia were recently detected using adaptive optics ophthalmoscopy in healthy eyes. Here we evaluate the use of nonconfocal adaptive optics scanning light ophthalmoscopy (AOSLO) for quantifying the morphology and motility of presumed microglia and other immune cells in eyes with retinal inflammation from uveitis and healthy eyes. Design: Observational exploratory study. Participants: Twelve participants were imaged, including 8 healthy participants and 4 posterior uveitis patients recruited from the clinic of 1 of the authors (M.H.E.). Methods: The Pittsburgh AOSLO imaging system was used with a custom-designed 7-fiber optical fiber bundle for simultaneous confocal and nonconfocal multioffset detection. The inner retina was imaged at several locations at multiple timepoints in healthy participants and uveitis patients to generate time-lapse images. Main Outcome Measures: Microglia and macrophages were manually segmented from nonconfocal AOSLO images, and their morphological characteristics quantified (including soma size, diameter, and circularity). Cell soma motion was quantified across time for periods of up to 30 minutes and their speeds were calculated by measuring their displacement over time. Results: A spectrum of cell morphologies was detected in healthy eyes from circular amoeboid cells to elongated cells with visible processes, resembling activated and ramified microglia, respectively. Average soma diameter was 16.1 ± 0.9 µm. Cell movement was slow in healthy eyes (0.02 µm/sec on average), but macrophage-like cells moved rapidly in some uveitis patients (up to 3 µm/sec). In an eye with infectious uveitis, many macrophage-like cells were detected; during treatment their quantity and motility decreased as vision improved. Conclusions: In vivo adaptive optics ophthalmoscopy offers promise as a potentially powerful tool for detecting and monitoring inflammation and response to treatment at a cellular level in the living eye. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Oncologic control and predictors of urologic reconstruction after Mohs micrographic surgery for low-risk penile malignancy.

PURPOSE: Mohs micrographic surgery (MMS) is a low-risk penile cancer management option. However, contemporary patients' short-term oncologic control and preoperative characteristics predicting reconstruction needs are undefined. This study assesses MMS's oncologic efficacy for low-risk penile cancer and identifies baseline predictors of post-resection reconstruction referral. METHODS: We retrospectively reviewed 73 adult males with 78 penile cutaneous malignancies treated with MMS from 2005 to 2019. Patients underwent MMS with or without surgical reconstruction. Demographic information, MMS operative details, lesion pathology, and short-term outcomes were recorded. Descriptive statistics for all variables were calculated, and logistic regression identified predictive factors for urologic referral for complex reconstruction. RESULTS: Seventy-three men with 78 lesions, all staged ≤ cT1a prior to MMS, were identified. Twenty-one men were found to have invasive SCC. Median follow-up was 2.0 years (IQR 0.8-5.2 years). MMS was able to clear the disease in 90.4% of cases. One patient had disease related death following progression. Dermatology closed primarily in 68% of patients. Twenty percent of patients had a complication, most commonly poor wound healing. On univariate and multivariate linear regression analysis, lesion size > 3 cm and involvement of the glans independently predicted the need for referral to a reconstructive surgeon. CONCLUSIONS: MMS for penile cancer appears to provide sound oncologic control in the properly selected patient. Involvement of a reconstructive surgeon may be needed for glandular and large lesions, necessitating early referral to a comprehensive multidisciplinary care team.

Polymeric Prodrugs using Dynamic Covalent Chemistry for Prolonged Local Anesthesia.

Depot-type drug delivery systems are designed to deliver drugs at an effective rate over an extended period. Minimizing initial "burst" can also be important, especially with drugs causing systemic toxicity. Both goals are challenging with small hydrophilic molecules. The delivery of molecules such as the ultrapotent local anesthetic tetrodotoxin (TTX) exemplifies both challenges. Toxicity can be mitigated by conjugating TTX to polymers with ester bonds, but the slow ester hydrolysis can result in subtherapeutic TTX release. Here, we developed a prodrug strategy, based on dynamic covalent chemistry utilizing a reversible reaction between the diol TTX and phenylboronic acids. These polymeric prodrugs exhibited TTX encapsulation efficiencies exceeding 90 % and the resulting polymeric nanoparticles showed a range of TTX release rates. In vivo injection of the TTX polymeric prodrugs at the sciatic nerve reduced TTX systemic toxicity and produced nerve block lasting 9.7±2.0 h, in comparison to 1.6±0.6 h from free TTX. This approach could also be used to co-deliver the diol dexamethasone, which prolonged nerve block to 21.8±5.1 h. This work emphasized the usefulness of dynamic covalent chemistry for depot-type drug delivery systems with slow and effective drug release kinetics.

The significant others' responses to trauma scale (SORTS): applying factor analysis and item response theory to a measure of PTSD symptom accommodation.

Background: Symptom accommodation by family members (FMs) of individuals with posttraumatic stress disorder (PTSD) includes FMs' participation in patients' avoidance/safety behaviours and constraining self-expression to minimise conflict, potentially maintaining patients' symptoms. The Significant Others' Responses to Trauma Scale (SORTS) is the only existing measure of accommodation in PTSD but has not been rigorously psychometrically tested.Objective: We aimed to conduct further psychometric analyses to determine the factor structure and overall performance of the SORTS. Method: We conducted exploratory and confirmatory factor analyses using a sample of N = 715 FMs (85.7% female, 62.1% White, 86.7% romantic partners of individuals with elevated PTSD symptoms).Results: After dropping cross-loading items, results indicated good fit for a higher-order model of accommodation with two factors: an anger-related accommodation factor encompassed items related largely to minimising conflict, and an anxiety-related accommodation factor encompassed items related primarily to changes to the FM's activities. Accommodation was positively related to PTSD severity and negatively related to relationship satisfaction, although the factors showed somewhat distinct associations. Item Response Theory analyses indicated that the scale provided good information and robust coverage of different accommodation levels.Conclusions: SORTS data should be analysed as both a single score as well as two factors to explore the factors' potential differential performance across treatment and relationship outcomes.

We examined the Significant Others' Responses to Trauma Scale (SORTS), a measure of symptom accommodation in PTSD, among a large sample of family members.As measured by the SORTS, accommodation in PTSD could be broken down into two aspects: anger-related accommodation and anxiety-related accommodation.Accommodation was positively related to PTSD severity and negatively related to relationship satisfaction.

Perceptual heterogeneity in developmental prosopagnosia is continuous, not categorical.

Developmental prosopagnosia (DP) is associated with considerable perceptual heterogeneity, though the nature of this heterogeneity and whether there are discrete subgroups versus continuous deficits remains unclear. Bennetts et al. (2022) recently found that holistic versus featural processing deficits distinguished discrete DP subgroups, but their sample was relatively small (N = 37), and subgroups were defined using a single task. To characterize perceptual heterogeneity in DPs more comprehensively, we administered a broad face perception battery to a large sample of 109 DPs and 134 controls, including validated measures of face matching (Cambridge Face Perception Test - CFPT, Computerized Benton Facial Recognition Test, Same/Different Face Matching Task), holistic processing (Part-Whole Task), and feature processing (Georges Task and Part-Whole part trials). When examining face matching measures, DPs exhibited a similar distribution of performance as controls, though shifted towards impairment by an average of 1.4 SD. We next applied Bennetts (2022) hierarchical clustering approach and k-means clustering to the CFPT upright, inverted, and inversion index measures, similarly finding one group of DPs with poorer inverted face performance and another with a decreased face inversion effect (holistic processing). However, these subgroup differences failed to generalize to other measures of feature and holistic processing beyond the CFPT. We finally ran hierarchical and k-means cluster analyses on our larger battery of face matching, feature, and holistic processing measures. Results clearly showed subgroups with generally better versus worse performance across all measures, with the distinction between groups being somewhat arbitrary. Together, these findings support a continuous account of DP perceptual heterogeneity, with performance differing primarily across all aspects of face perception.

Safe Continuation of Glucagon-like Peptide 1 Receptor Agonists at Endoscopy: A Case Series of 57 Adults Undergoing Endoscopic Sleeve Gastroplasty.

PURPOSE: Glucagon-like receptor agonists (GLP1-RAs) have raised peri-procedural concerns due to their potential to delay gastric emptying. The American Association of Anesthesiologists has advised pausing a single dose before elective endoscopy. However, a subsequent directive from multiple gastroenterology societies underscored the need for further assessment to substantiate this practice. We aimed to evaluate the frequency of serious adverse events and retained gastric products during endoscopic sleeve gastroplasty (ESG) with uninterrupted GLP1-RA use. MATERIALS AND METHODS: We conducted a retrospective evaluation of all patients undergoing ESG while on GLP1-RAs at three centers from August 2022 to February 2024. Per standard protocol, all patients had refrained from solid foods for at least 24 h and maintained nil per os for 12 h preceding their ESG. Records were reviewed for patient characteristics and medication type and doses. Primary outcomes included serious adverse events and retained gastric products based on patient records, procedure reports, and procedural videos. RESULTS: Fifty-seven consecutive adults (89.5% women, mean age of 44 ± 9 years, mean BMI of 40.1 ± 8.1 kg/m2, 35.1% with T2DM, and 26.3% with pre-T2DM) underwent ESG without stopping GLP1-RAs, which included semaglutide (45.6%), liraglutide (19.3%), dulaglutide (22.8%), and tirzepatide (12.3%). During intubation, endoscopy, and recovery, there were no instances of retained gastric solids, pulmonary aspiration, gastroesophageal regurgitation, or hypoxia. CONCLUSION: A ≥ 24-h pre-endoscopy liquid-only diet with ≥ 12-h pre-endoscopy fast may negate the need for GLP1-RA interruption for routine upper endoscopy in adults with native gastric anatomy.

Review of valiltramiprosate (ALZ-801) for the treatment of Alzheimer's disease: a novel small molecule with disease modifying potential.

INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive deterioration, functional impairments, and neuropsychiatric symptoms. Valiltramiprosate is a tramiprosate prodrug being investigated as a novel treatment for AD. AREAS COVERED: The online databases PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched using the terms 'ALZ-801' or 'valiltramiprosate.' Alzheon press releases were reviewed for emerging clinical information. Valiltramiprosate is an oral, well-tolerated synthetic valine-conjugate prodrug of tramiprosate. Valiltramiprosate's active metabolite include tramiprosate and 3-sulfopropanoic acid. Proposed mechanism of action is multiligand binding to Aß42 which stabilizes amyloid monomers to prevent peptide aggregation and oligomerization. Pharmacokinetic studies show 52% oral bioavailability, rapid absorption, approximately 40% brain-drug exposure, and near complete renal clearance. Compared to tramiprosate, valiltramiprosate extends plasma tramiprosate half-life and improves interindividual pharmacokinetic variability. Interim analyses from valiltramiprosate's phase II biomarker trial show: (1) significant reductions in plasma p-tau181 and related AD fluid biomarkers; (2) brain structure preservation and reduced hippocampal atrophy by MRI; and (3) improvements on cognitive assessments at multiple timepoints. Its phase III clinical trial in ApoE ε4 homozygotes is near completion. EXPERT OPINION: Valiltramiprosate's clinical trial data show early indications of efficacy with potential disease modifying effect in AD.

The Association of Psychotherapy With Burnout, Depression, and Measures of Well-Being in Residents and Fellows: A Pilot Study.

PURPOSE: Resident physicians experience high rates of burnout and depression but rarely prioritize their well-being or seek mental health care. The Accreditation Council for Graduate Medical Education mandated that training programs prioritize resident wellness and emotional and mental health to ensure readily available and accessible mental health care. To help meet that requirement and circumvent barriers to accessing care, the University of California San Diego Healer Education Assessment & Referral (HEAR) Program offers residents and fellows short-term therapy for coping with challenges that threaten their well-being. This report describes the results of a pilot study designed to evaluate the feasibility and effectiveness of the HEAR Program's resident therapy program. METHOD: The cohort included residents and fellows who completed at least 1 postbaseline assessment from January to May 2022. Measures of fulfillment, burnout, self-compassion, quality of life, depression, and suicidal ideation were assessed and compared before and up to 12 weeks after enrollment. RESULTS: Of the 39 residents who consented to participation, 30 completed at least 1 postbaseline assessment. Most outcomes improved after therapy, with significant increases in fulfillment (mean [SE] coefficient, 0.24 [0.08]; z score, 2.86; P = .004), self-compassion (mean [SE] coefficient, 0.37 [0.07]; z score, 5.72; P < .001), and quality of life ( P < .001) and significant reductions in burnout (Stanford burnout scale: mean [SE] coefficient, -0.27 [0.07]; z score, -4.01; P < .001; single-item burnout scale: mean [SE] coefficient, -0.34 [0.08]; z score, -4.37; P < .001) and depression severity (mean [SE] coefficient, -1.08 [0.25]; z score, -4.36; P < .001). CONCLUSIONS: This pilot study noted improvements in fulfillment, compassion, quality of life, and function, as well as reductions in burnout and depression severity, among resident physicians. Future studies in larger cohorts are needed to validate these findings and inform further optimization of this program.