Molecular Classification Outperforms Histologic Classification in Prognostication of High-grade Endometrial Carcinomas With Undifferentiated and Sarcomatous Components.

Since the establishment of 4 molecular subgroups of endometrial carcinoma (EC), there has been significant interest in understanding molecular classification in the context of histologic features and diagnoses. ECs with undifferentiated, spindle, and/or sarcomatous components represent a diagnostically challenging subset of tumors with overlapping clinical and histologic features. We examined the clinicopathologic, morphologic, immunohistochemical, and molecular features of these tumors identified in our institutions' pathology databases using immunohistochemistry and targeted sequencing. Disease-specific survival (DSS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves and log-rank tests. One hundred sixty-two ECs were included: carcinosarcomas (UCS; n=96), dedifferentiated/undifferentiated EC (DDEC/UDEC; n=49), and grade 3 endometrioid EC with spindled growth (GR3spEEC) (n=17). All molecular subgroups were represented in all histologic subtypes and included 12 (7%) POLE-mutated (POLEmut), 43 (27%) mismatch repair-deficient (MMRd), 77 (48%) p53-abnormal (p53abn), and 30 (19%) no specific molecular profile (NSMP) tumors. However, the molecular classification (irrespective of histologic diagnosis) was a significant predictor for both DSS (P=0.008) and P≤0.0001). POLEmut EC showed an excellent prognosis with no recurrences or deaths from the disease. MMRd tumors also showed better outcomes relative to NSMP and p53abn tumors. In conclusion, molecular classification provides better prognostic information than histologic diagnosis for high-grade EC with undifferentiated and sarcomatous components. Our study strongly supports routine molecular classification of these tumors, with emphasis on molecular group, rather than histologic subtyping, in providing prognostication.

Trichomoniasis and retesting in Durham County, North Carolina, United States, 2021 - 2022.

BACKGROUND: The Centers for Disease Control and Prevention recommends universal retesting within 3 months after treatment of Trichomonas vaginalis infection given high rates of persistent infection or reinfection, or if this is not possible, within 12 months following treatment. Data is lacking on how often this is actually done. METHODS: We analyzed the demographic and clinical characteristics, rate of return for the recommended retesting, concordance between wet prep and nucleic acid amplification testing, and percent positivity for T. vaginalis on repeat vaginal specimens at a local public health department in Durham, North Carolina, United States. RESULTS: Of 193 females treated for trichomoniasis between March 1, 2021 - May 31, 2022, 83% were Black or African American and 44% between the ages of 20 and 29 years. Of these individuals, 32% had retesting performed within 3 months and 50% within 365 days after treatment. Females between the ages of 20 and 29 years were more likely to return for retesting than those between the ages of 30 and 39 years. Of those who returned for retesting, 10% were positive on repeat testing. CONCLUSION: In this study, 50% of females diagnosed with trichomoniasis completed retesting within 365 days. Improved scheduling of clients at the time of trichomoniasis treatment and improved identification in our electronic health record of individuals diagnosed with trichomoniasis within the prior year would likely improve retesting rates. Given the high prevalence of trichomoniasis, expanded screening of asymptomatic females in settings where this is feasible may be warranted.

Uterine injury during diestrus leads to placental and embryonic defects in future pregnancies in mice†.

Uterine injury from procedures such as Cesarean sections (C-sections) often have severe consequences on subsequent pregnancy outcomes, leading to disorders such as placenta previa, placenta accreta, and infertility. With rates of C-section at ~30% of deliveries in the USA and projected to continue to climb, a deeper understanding of the mechanisms by which these pregnancy disorders arise and opportunities for intervention are needed. Here we describe a rodent model of uterine injury on subsequent in utero outcomes. We observed three distinct phenotypes: increased rates of resorption and death, embryo spacing defects, and placenta accreta-like features of reduced decidua and expansion of invasive trophoblasts. We show that the appearance of embryo spacing defects depends entirely on the phase of estrous cycle at the time of injury. Using RNA-seq, we identified perturbations in the expression of components of the COX/prostaglandin pathway after recovery from injury, a pathway that has previously been demonstrated to play an important role in embryo spacing. Therefore, we demonstrate that uterine damage in this mouse model causes morphological and molecular changes that ultimately lead to placental and embryonic developmental defects.

Clinical Features of SARS-CoV-2 Infection During Pregnancy and Associated Placental Pathologies.

SUMMARY: We reviewed the clinicopathologic findings of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-exposed placentas at our institution. We identified patients diagnosed with SARS-CoV-2 during pregnancy (March-October 2020). Clinical data included gestational age at diagnosis and delivery and maternal symptoms. Hematoxylin and eosin slides were reviewed for maternal vascular malperfusion, fetal vascular malperfusion, chronic villitis, amniotic fluid infection, intervillous thrombi, fibrin deposition, and infarction. Immunohistochemistry (IHC) for coronavirus spike protein and RNA in situ hybridization (ISH) for SARS-CoV-2 was performed on a subset of blocks. A review of placentas from age-matched patients received March-October 2019 was conducted as a comparison cohort. A total of 151 patients were identified. Placentas in the 2 groups were similar in weight for gestational age and had similar rates of maternal vascular malperfusion, fetal vascular malperfusion, amniotic fluid infection, intervillous thrombi, fibrin deposition, and infarction. Chronic villitis was the only significantly different pathologic finding between cases and controls (29% of cases showed chronic villitis vs. 8% of controls, P <0.001). Overall, 146/151 (96.7%) cases were negative for IHC and 129/133 (97%) cases were negative for RNA ISH. There were 4 cases that stained positively for IHC/ISH, 2 of which showed massive perivillous fibrin deposition, inflammation, and decidual arteriopathy. Coronavirus disease 2019 (COVID-19)-positive patients were more likely to self-identify as Hispanic and more likely to have public health insurance. Our data suggests SARS-CoV-2 exposed placentas that stain positively for SARS-CoV-2 show abnormal fibrin deposition, inflammatory changes, and decidual arteriopathy. The group of patients with clinical COVID-19 are more likely to show chronic villitis. IHC and ISH evidence of viral infection is rare.

The Evolving Spectrum of Endometrial Glandular Proliferations With Corded and Hyalinized Features.

We present the clinicopathologic and immunohistochemical features of 14 endometrial glandular proliferations with conspicuous corded and hyalinized (CH) features comprised entirely or predominantly of endometrial hyperplasia. Endometrial glandular lesions ranged in severity from endometrial hyperplasia with and without cytologic atypia (5/14 [36%]) to hyperplasia with architectural complexity bordering on well-differentiated endometrioid adenocarcinoma (3/14 [21%]) to frank corded and hyalinized endometrial carcinoma ("CHEC") (6/14 [43%]). In addition to sex cord-like growth and hyalinized stroma, other common histologic features included prominent spindle cells (11/14 [79%]), keratinizing and/or morular squamous differentiation (10/14 [71%]), and osseous metaplasia (6/14 [43%]). Immunohistochemical characterization revealed aberrant nuclear beta-catenin in all cases (14/14 [100%]); additionally, all cases demonstrated positive estrogen receptors, intact PTEN, PMS2 and MSH6, and wild-type p53 expression. Patients ranged in age from 24 to 58 (mean 38) years. Of 5 patients with hyperplasia with CH features, 2 experienced complete resolution after progestin therapy and none progressed to adenocarcinoma (mean follow-up 15.6 mo, range 2 to 64). By contrast, of 2 patients with hyperplasia bordering on CHEC and with available follow-up, both subsequently developed adenocarcinoma, suggesting that even focal increased architectural complexity may predict an elevated risk of malignancy. We conclude that CH morphology is not limited to endometrioid carcinoma and may occur across a spectrum of neoplastic proliferations, including those without sufficient architectural complexity or cytologic atypia to warrant classification as adenocarcinoma. We propose the term "corded and hyalinized endometrial hyperplasia" to describe this precursor lesion and report favorable outcomes with conservative treatment.

Surface-Localized Chemically Modified Reduced Graphene Oxide Nanocomposites as Flexible Conductive Surfaces for Space Applications.

Thermoplastic polymers are a compelling class of materials for emerging space exploration applications due to their wide range of mechanical properties and compatibility with a variety of processing methods, including additive manufacturing. However, despite these benefits, the use of thermoplastic polymers in a set of critical space applications is limited by their low electrical conductivity, which makes them susceptible to static charging and limits their ability to be used as active and passive components in electronic devices, including materials for static charge dissipation, resistive heaters, and electrodynamic dust shielding devices. Herein, we explore the microstructural evolution of electrically conductive, surface-localized nanocomposites (SLNCs) of chemically modified reduced graphene oxide and a set of thermoplastic polymers as a function of critical thermal properties of the substrate (melting temperature for semi-crystalline materials or glass transition temperature for amorphous materials). Selected offsets from critical substrate temperatures were used to produce SLNCs with conductivities between 0.6-3 S/cm and surface structures, which ranged from particle-rich, porous surfaces to polymer-rich, non-porous surfaces. We then demonstrate the physical durability of these electrically conductive SLNCs to expected stress conditions for flexible conductive materials in lunar applications including tension, flexion, and abrasion with lunar simulant. Small changes in resistance (R/R0 < 2) were measured under uniaxial tension up to 20% strain in high density polyethylene and up to 500 abrasion cycles in polysulfone, demonstrating the applicability of these materials as active and passive flexible conductors in exterior lunar applications. The tough, electrically conductive SLNCs developed here could greatly expand the use of polymeric materials in space applications, including lunar exploration, micro- and nano-satellites, and other orbital structures.

Detection of viral RNAs at ambient temperature via reporter proteins produced through the target-splinted ligation of DNA probes.

Nucleic acid assays are not typically deployable in point-of-care settings because they require costly and sophisticated equipment for the control of the reaction temperature and for the detection of the signal. Here we report an instrument-free assay for the accurate and multiplexed detection of nucleic acids at ambient temperature. The assay, which we named INSPECTR (for internal splint-pairing expression-cassette translation reaction), leverages the target-specific splinted ligation of DNA probes to generate expression cassettes that can be flexibly designed for the cell-free synthesis of reporter proteins, with enzymatic reporters allowing for a linear detection range spanning four orders of magnitude and peptide reporters (which can be mapped to unique targets) enabling highly multiplexed visual detection. We used INSPECTR to detect a panel of five respiratory viral targets in a single reaction via a lateral-flow readout and ~4,000 copies of viral RNA via additional ambient-temperature rolling circle amplification of the expression cassette. Leveraging synthetic biology to simplify workflows for nucleic acid diagnostics may facilitate their broader applicability at the point of care.

High-speed reflectance confocal microscopy of human skin at 1251-1342 nm.

OBJECTIVES: Reflectance confocal microscopy (RCM) is an imaging method that can noninvasively visualize microscopic features of the human skin. The utility of RCM can be further improved by increasing imaging speed. In this paper, we report high-speed RCM imaging of human skin with a frame rate that is over 10 times faster and an area imaging rate that is 6-9 times faster than those of commercially available RCM devices. METHODS: The higher imaging speed was achieved using a high-speed RCM technique, termed spectrally encoded confocal microscopy (SECM). SECM uses a diffraction grating and a high-speed, wavelength-swept source to conduct confocal imaging at a very high rate. We developed a handheld SECM probe using a scanned-grating approach. The SECM probe was used in conjunction with a wavelength-swept source with a spectral band of 1251-1342 nm. RESULTS: The SECM probe achieved high lateral resolution of 1.3-1.6 µm and an axial resolution of 3.5 µm. SECM images of the human skin (image size = 439 × 439 µm2 ) obtained at 100 frames/s clearly show previously reported RCM features of the human skin in vivo with adequate image quality. The fast imaging speed allowed for the rapid acquisiton of volumetric SECM image data (200 frames covering a depth range of 200 µm) within 2 s. The use of 1251-1342 nm provided sufficient signal level and contrast required to visualize key cellular morphologic features. CONCLUSIONS: These preliminary results demonstrate that high-speed SECM imaging of the human skin at 1251-1342 nm is feasible.

Rapid Deployment of Whole Slide Imaging for Primary Diagnosis in Surgical Pathology at Stanford Medicine: Responding to Challenges of the COVID-19 Pandemic.

CONTEXT.­: Stanford Pathology began stepwise subspecialty implementation of whole slide imaging (WSI) in 2018 soon after the first US Food and Drug Administration approval. In 2020, during the COVID-19 pandemic, the Centers for Medicare & Medicaid Services waived the requirement for pathologists to perform diagnostic tests in Clinical Laboratory Improvement Amendments (CLIA)-licensed facilities. This encouraged rapid implementation of WSI across all surgical pathology subspecialties. OBJECTIVE.­: To present our experience with validation and implementation of WSI at a large academic medical center encompassing a caseload of more than 50 000 cases per year. DESIGN.­: Validation was performed independently for 3 subspecialty services with a diagnostic concordance threshold above 95%. Analysis of user experience, staffing, infrastructure, and information technology was performed after department-wide expansion. RESULTS.­: Diagnostic concordance was achieved in 96% of neuropathology cases, 100% of gynecologic pathology cases, and 98% of immunohistochemistry cases. After full implementation, 8 high-capacity scanners were operational, with whole slide images generated on greater than 2000 slides per weekday, accounting for approximately 80% of histologic slides at Stanford Medicine. Multiple modifications in workflow and information technology were needed to improve performance. Within months of full implementation, most attending pathologists and trainees had adopted WSI for primary diagnosis. CONCLUSIONS.­: WSI across all surgical subspecialities is achievable at scale at an academic medical center; however, adoption required flexibility to adjust workflows and develop tailored solutions. WSI at scale supported the health and safety of medical staff while facilitating high-quality patient care and education during COVID-19 restrictions.

A survey of local diagnostic reference levels for the head, thorax, abdomen and pelvis computed tomography in Norway and Canada.

Background: Computed tomography (CT) contributes to 60% of the collective dose in medical imaging. Literature has demonstrated that patient dose varies across regions and countries. Establishing diagnostic reference levels (DRLs) contributes to the optimization of clinical practices and radiation protection. Purpose: To survey the dose indices (CTDIvol and dose-length product) for frequently performed CT examinations from the chosen hospitals in Norway and Canada and to determine local DRLs (LDRLs) based on the collected data. Material and Methods: The survey included eight scanners from two Norwegian hospitals and four scanners from four Canadian hospitals. Dosimetry data were collected for the following routine CT examinations: head, contrast-enhanced thorax, and abdomen and pelvis. Overall 480 adult average-sized patients from Norway and 360 from Canada were included in the survey. The LDRLs were determined as the 75th percentile of distributions of median values of dose indicators from different CT scanners. The differences in dose between scanners were determined using single-factor ANOVA. Results: The LDRLs determined in Norway were higher overall than in Canada. The obtained values were compared to the national DRLs. The dose from several scanners in Norway exceeded national Norwegian DRLs, while Canadian LDRLs were below the Canadian reference levels. The differences between the means of the dose distributions from each scanner were statistically significant (p < 0.05) for all examinations with exception of identical scanners located in the same hospital and using the same protocols. Conclusion: Observed dose variations even in the same hospital, or from the same scanner model confirmed the need for CT protocol optimization.

The menstrual cycle phase impacts the detection of plasma cells and the diagnosis of chronic endometritis in endometrial biopsy specimens.

OBJECTIVE: To assess the impact of menstrual cycle phase on the detection of plasma cells. DESIGN: A retrospective cohort study. SETTING: Fertility clinic. PATIENT(S): Biopsies from 157 patients met criteria for inclusion, 91 in the follicular phase and 60 in the luteal phase. Patient groups were similar in body mass index and number of previous live births; however, differed in terms of age, infertility history, and biopsy indication. INTERVENTIONS: Endometrial biopsies from patients at a fertility clinic from 2018-2020 were retrospectively reviewed. Biopsies were excluded if patients had a previous chronic endometritis diagnosis, abnormal uterine cavity or were on hormone therapy. Each case was reviewed by a gynecologic pathologist for plasma cells by hematoxylin and eosin and CD138 staining. Demographic and clinical data were collected. Continuous variables were compared using Welch t test and Wilcoxon's rank sum test, and categorical variables using Pearson's χ2 test. Logistic regression was used to calculate odds ratio and 95% confidence intervals for the association between the presence of plasma cells and cycle phase. Multinomial logistic regression was used to estimate the odds ratios for nominal outcomes. Pathology reports were reviewed. Plasma cell enumeration using hematoxylin and eosin-stained sections and CD138 immunohistochemical stains (performed at the time of biopsy by a gynecologic pathologist) was recorded. MAIN OUTCOME MEASURE(S): Presence and density of plasma cells. RESULT(S): We found a higher likelihood of finding plasma cells in the follicular than in luteal phase (59.3% vs. 19.7%). There was a higher likelihood of finding plasma cells in the early (cycle days 5-8, 29 cases or 76.3% of cases with plasma cells) than in the late follicular phase (cycle days 9-14, 25 cases or 47.2%). There was a higher density of plasma cells in the follicular phase group than in the luteal phase group (25.3% vs. 1.5% scattered and 13.2% vs. 0 clusters). CONCLUSION(S): Plasma cells are more likely to be present during the follicular phase compared with the luteal phase and in the early compared with the late follicular phase. Further studies are needed to identify the optimal timing of biopsy to standardize the diagnosis.

Test-of-Cure After Treatment of Pharyngeal Gonorrhea in Durham, North Carolina, 2021-2022.

BACKGROUND: In December 2020, the Centers for Disease Control and Prevention updated its treatment guidelines for gonococcal infection and, for the first time, recommended universal test-of-cure for all individuals treated for pharyngeal gonorrhea. After the release of these guidelines, data are lacking on rates of return for the test-of-cure, particularly in populations other than men who have sex with men. METHODS: We analyzed the demographic characteristics, clinical characteristics, rate of return for the recommended test-of-cure, and percent positivity for Neisseria gonorrhoeae on repeat pharyngeal specimens at a local public health department in Durham, NC. RESULTS: Of 101 individuals treated for pharyngeal gonorrhea between March 2021 and April 2022, 54.5% were men, 71.2% Black or African American, and 58.4% between the ages of 20 and 29 years. Most identified as either women who have sex with men (38.6%), men who have sex with men (24.8%), or men who have sex with women (22.8%). Of these individuals, 41 (40.6%) returned for a test-of-cure, with LGBTQ+ individuals more likely to return than men who have sex with women and women who have sex with men. Of those who returned for the test-of-cure, 4.9% of pharyngeal samples were equivocal and 2.4% positive for N. gonorrhoeae by nucleic acid amplification testing, likely reflecting false-positive tests. CONCLUSION: Despite recommendations to perform a test-of-cure 7 to 14 days after treatment of pharyngeal gonorrhea, rates of return continue to be low. Alternative strategies should be investigated to increase test-of-cure rates.

Passively scanned, single-fiber optical coherence tomography probes for gastrointestinal devices.

BACKGROUND/OBJECTIVES: Optical coherence tomography (OCT) uses low coherence interferometry to obtain depth-resolved tissue reflectivity profiles (M-mode) and transverse beam scanning to create images of two-dimensional tissue morphology (B-mode). Endoscopic OCT imaging probes typically employ proximal or distal mechanical beam scanning mechanisms that increase cost, complexity, and size. Here, we demonstrate in the gastrointestinal (GI) tracts of unsedated human patients, that a passive, single-fiber probe can be used to guide device placement, conduct device-tissue physical contact sensing, and obtain two-dimensional OCT images via M-to-B-mode conversion. MATERIALS AND METHODS: We designed and developed ultrasmall, manually scannable, side- and forward-viewing single fiber-optic probes that can capture M-mode OCT data. Side-viewing M-mode OCT probes were incorporated into brush biopsy devices designed to harvest the microbiome and forward-viewing M-mode OCT probes were integrated into devices that measure intestinal potential difference (IPD). The M-mode OCT probe-coupled devices were utilized in the GI tract in six unsedated patients in vivo. M-mode data were converted into B-mode images using an M-to-B-mode conversion algorithm. The effectiveness of physical contact sensing by the M-mode OCT probes was assessed by comparing the variances of the IPD values when the probe was in physical contact with the tissue versus when it was not. The capacity of forward- and side-viewing M-mode OCT probes to produce high-quality B-mode images was compared by computing the percentages of the M-to-B-mode images that showed close contact between the probe and the luminal surface. Passively scanned M-to-B-mode images were qualitatively compared to B-mode images obtained by mechanical scanning OCT tethered capsule endomicroscopy (TCE) imaging devices. RESULTS: The incorporation of M-mode OCT probes in these nonendoscopic GI devices safely and effectively enabled M-mode OCT imaging, facilitating real-time device placement guidance and contact sensing in vivo. Results showed that M-mode OCT contact sensing improved the variance of IPD measurements threefold and side-viewing probes increased M-to-B-mode image visibility by 10%. Images of the esophagus, stomach, and duodenum generated by the passively scanned probes and M-to-B-mode conversion were qualitatively superior to B-mode images obtained by mechanically scanning OCT TCE devices. CONCLUSION: These results show that passive, single optical fiber OCT probes can be effectively utilized for nonendoscopic device placement guidance, device contact sensing, and two-dimensional morphologic imaging in the human GI tract in vivo. Due to their small size, lower cost, and reduced complexity, these M-mode OCT probes may provide an easier avenue for the incorporation of OCT functionality into endoscopic/nonendoscopic devices.

Retinal artery and vein occlusion in calciphylaxis.

Purpose: To report a case of branch retinal artery occlusion (BRAO) followed by branch retinal vein occlusion (BRVO) and paracentral acute middle maculopathy (PAMM) in a patient with confirmed calciphylaxis. Observations: A 52-year-old female with a history of BRAO in the right eye one-year prior presented with decreased vision and a new inferotemporal scotoma. Computed tomography angiography of the head and neck demonstrated vascular calcifications at the origin of both ophthalmic arteries, which were otherwise poorly visualized. Ophthalmic examination demonstrated retinal whitening superiorly with intraretinal hemorrhages inferiorly. Optical coherence tomography (OCT) demonstrated middle retinal hyperreflectivity and a mild epiretinal membrane. Fluorescein angiography (FFA) demonstrated delayed perfusion of superior retinal arcade. On further questioning, patient was found to have a history of IgA nephropathy with end-stage renal disease, secondary hyperparathyroidism and calciphylaxis. Calciphylaxis is a systemic disease, characterized by high levels of calcium and progressive calcification of the vascular medial layer leading to ischemia. Anterior ischemic optic neuropathy (AION) and crystalline retinopathy have been reported as ocular manifestations of calciphylaxis, however, there are very few reports on ophthalmic manifestations of calciphylaxis. Conclusion and importance: Clinical manifestations of calciphylaxis are variable and a detailed clinical history is important to suspect calciphylaxis. Calciphylaxis should be considered in the differential diagnosis of BRAO, BRVO, PAMM or any ophthalmic vascular manifestation in patients with end-stage renal disease.

Interfacial studies on the effects of patterned anodes for guided lithium deposition in lithium metal batteries.

The lifetime and health of lithium metal batteries are greatly hindered by nonuniform deposition and growth of lithium at the anode-electrolyte interface, which leads to dendrite formation, efficiency loss, and short circuiting. Lithium deposition is influenced by several factors including local current densities, overpotentials, surface heterogeneity, and lithium-ion concentrations. However, due to the embedded, dynamic nature of this interface, it is difficult to observe the complex physics operando. Here, we present a detailed model of the interface that implements Butler-Volmer kinetics to investigate the effects of overpotential and surface heterogeneities on dendrite growth. A high overpotential has been proposed as a contributing factor in increased nucleation and growth of dendrites. Using computational methods, we can isolate the aspects of the complex physics at the interface to gain better insight into how each component affects the overall system. In addition, studies have shown that mechanical modifications to the anode surface, such as micropatterning, are a potential way of controlling deposition and increasing Coulombic efficiency. Micropatterns on the anode surface are explored along with deformations in the solid-electrolyte interface layer to understand their effects on the dendritic growth rates and morphology. The study results show that at higher overpotentials, more dendritic growth and a more branched morphology are present in comparison to low overpotentials, where more uniform and denser growth is observed. In addition, the results suggest that there is a relationship between surface chemistries and anode geometries.

Feasibility and Safety of Tethered Capsule Endomicroscopy in Patients With Barrett's Esophagus in a Multi-Center Study.

BACKGROUND & AIMS: Tethered capsule endomicroscopy (TCE) involves swallowing a small tethered pill that implements optical coherence tomography (OCT) imaging, procuring high resolution images of the whole esophagus. Here, we demonstrate and evaluate the feasibility and safety of TCE and a portable OCT imaging system in patients with Barrett's esophagus (BE) in a multi-center (5-site) clinical study. METHODS: Untreated patients with BE as per endoscopic biopsy diagnosis were eligible to participate in the study. TCE procedures were performed in unsedated patients by either doctors or nurses. After the capsule was swallowed, the device continuously obtained 10-µm-resolution cross-sectional images as it traversed the esophagus. Following imaging, the device was withdrawn through mouth, and disinfected for subsequent reuse. BE lengths were compared to endoscopy findings when available. OCT-TCE images were compared to volumetric laser endomicroscopy (VLE) images from a patient who had undergone VLE on the same day as TCE. RESULTS: 147 patients with BE were enrolled across all sites. 116 swallowed the capsule (79%), 95/114 (83.3%) men and 21/33 (63.6%) women (P = .01). High-quality OCT images were obtained in 104/111 swallowers (93.7%) who completed the procedure. The average imaging duration was 5.55 ± 1.92 minutes. The mean length of esophagus imaged per patient was 21.69 ± 5.90 cm. A blinded comparison of maximum extent of BE measured by OCT-TCE and EGD showed a strong correlation (r = 0.77-0.79). OCT-TCE images were of similar quality to those obtained by OCT-VLE. CONCLUSIONS: The capabilities of TCE to be used across multiple sites, be administered to unsedated patients by either physicians or nurses who are not expert in OCT-TCE, and to rapidly and safely evaluate the microscopic structure of the esophagus make it an emerging tool for screening and surveillance of BE patients. Clinical trial registry website and trial number: NCT02994693 and NCT03459339.

Effects of Low Dose Caffeine on Post-Exercise Heart Rate Variability: A Double-Blind Placebo-Controlled Trial.

Caffeine may impact post-exercise heart rate variability (HRV); although, studies have yielded inconsistent findings. We examined the effects of low dose caffeine on post-exercise HRV. Healthy, college-aged adults [n = 18; age: 22.1 ± 2.6 years; BMI: 26.9 ± 4.3 kg/m2; estimated maximal oxygen consumption (VO2max): 45.1 ± 8.3 ml·kg-1·min-1] participated in a repeated-measures, double-blind, placebo-controlled trial. During the experimental trials, participants were fitted with a heart rate monitor and a mouthpiece with a one-way nonrebreathing valve and then rested for 10 min during baseline HRV and expired gas assessments. Participants chewed either caffeine (~170mg) or placebo gum for 5 min. Following expectoration and a 5 min warmup, participants walked on a treadmill for 20 min at 60% of estimated VO2max and then rested for 30 min. HRV indices were calculated from 10 min measurements during baseline and post-exercise (post 1, 2, and 3). A main effect of treatment was found for standard deviation of RR intervals (SDNN), absolute power of low frequency band (LF), absolute power of high frequency band (HF), and the standard deviation perpendicular to the line-of-identity in Poincaré plot (SD1) (p < 0.05). Further, a trend for higher root mean square of successive RR interval differences (RMSSD) with caffeine was observed (p = 0.066). Post hoc t-tests revealed that post-exercise SDNN, LF, HF, and SD1 were higher with caffeine compared to placebo (p ≤ 0.012). Results demonstrated that low dose caffeine did not delay the recovery of HRV indices reflective of parasympathetic nervous system activity following an acute bout of moderate exercise.

Implementation of a Multifactorial Strategy Including Direct Bedding Is Associated With a Rapid and Sustained Reduction in Left Without Being Seen.

Objective Improve left without being seen (LWBS) in our high volume, tertiary care trauma center. Prior to intervention, our LWBS rate was 4.4%. Including a direct bedding strategy, we successfully reduced our LWBS to <1%. Design and method We utilized a retrospective before and after model. We hired a clinical documentation specialist and tracked several metrics. These included daily census, admission rates, and door to provider, door to room, average boarding, and door to disposition times. Data were collected and disseminated daily. Reports were shared at organization quality meetings. Simultaneously, we implemented the direct bedding initiative in conjunction with quick registration. To accommodate higher numbers of patients and expediate movement to care spaces, all patient spaces were clearly designated and labeled. Results Direct bedding began in September 2015 and our LWBS was 4.4%. One-year post-intervention, our LWBS was <2%. Within four years, it was <0.5%. The LWBS rate for each year, 2016 to 2019, was significantly lower than the control period (p < 0.01) (2015 up to September). Improvement was also seen in door-to-provider time and with patient experience scores. Conclusion Our multifactorial approach was associated with a profound and sustained reduction in LWBS over a short time period.

Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART.

Clinical outcomes are inferior for individuals with HIV having suboptimal CD4 T-cell recovery during antiretroviral therapy (ART). We investigated if the levels of infection and the response to homeostatic cytokines of CD4 T-cell subsets contributed to divergent CD4 T-cell recovery and HIV reservoir during ART by studying virologically-suppressed immunologic responders (IR, achieving a CD4 cell count >500 cells/µL on or before two years after ART initiation), and virologically-suppressed suboptimal responders (ISR, did not achieve a CD4 cell count >500 cells/µL in the first two years after ART initiation). Compared to IR, ISR demonstrated higher levels of HIV-DNA in naïve, central (CM), transitional (TM), and effector (EM) memory CD4 T-cells in blood, both pre- and on-ART, and specifically in CM CD4 T-cells in LN on-ART. Furthermore, ISR had higher pre-ART plasma levels of IL-7 and IL-15, cytokines regulating T-cell homeostasis. Notably, pre-ART PD-1 and TIGIT expression levels were higher in blood CM and TM CD4 T-cells for ISR; this was associated with a significantly lower fold-changes in HIV-DNA levels between pre- and on-ART time points exclusively on CM and TM T-cell subsets, but not naïve or EM T-cells. Finally, the frequency of CM CD4 T-cells expressing PD-1 or TIGIT pre-ART as well as plasma levels of IL-7 and IL-15 predicted HIV-DNA content on-ART. Our results establish the association between infection, T-cell homeostasis, and expression of PD-1 and TIGIT in long-lived CD4 T-cell subsets prior to ART with CD4 T-cell recovery and HIV persistence on-ART.