Multiscale drainage dynamics with Haines jumps monitored by stroboscopic 4D X-ray microscopy.

Slow multiphase flow in porous media is intriguing because its underlying dynamics is almost deterministic, yet depends on a hierarchy of spatiotemporal processes. There has been great progress in the experimental study of such multiphase flows, but three-dimensional (3D) microscopy methods probing the pore-scale fluid dynamics with millisecond resolution have been lacking. Yet, it is precisely at these length and time scales that the crucial pore-filling events known as Haines jumps take place. Here, we report four-dimensional (4D) (3D + time) observations of multiphase flow in a consolidated porous medium as captured in situ by stroboscopic X-ray micro-tomography. With a total duration of 6.5 s and 2 kHz frame rate, our experiments provide unprecedented access to the multiscale liquid dynamics. Our tomography strategy relies on the fact that Haines jumps, although irregularly spaced in time, are almost deterministic, and therefore repeatable during imbibition-drainage cycling. We studied the time-dependent flow pattern in a porous medium consisting of sintered glass shards. Exploiting the repeatability, we could combine the radiographic projections recorded under different angles during successive cycles into a 3D movie, allowing us to reconstruct pore-scale events, such as Haines jumps, with a spatiotemporal resolution that is two orders of magnitude higher than was hitherto possible. This high resolution allows us to explore the detailed interfacial dynamics during drainage, including fluid-front displacements and velocities. Our experimental approach opens the way to the study of fast, yet deterministic mesoscopic processes also other than flow in porous media.

Improved Utilization of Serial Testing Without Increased Admissions after Implementation of High-Sensitivity Troponin I: a Controlled Retrospective Cohort Study.

BACKGROUND: Guidelines recommend high-sensitivity cardiac troponin (hs-cTn) for diagnosis of myocardial infarction. Use of hs-cTn is increasing across the U.S., but questions remain regarding clinical and operational impact. Prior studies have had methodologic limitations and yielded conflicting results. OBJECTIVE: To evaluate the impact of transitioning from conventional cardiac troponin (cTn) to hs-cTn on test and resource utilization, operational efficiency, and patient safety. DESIGN: Retrospective cohort study in two New York City hospitals during the months before and after transition from conventional cTn to hs-cTn at Hospital 1. Hospital 2 served as a control. PARTICIPANTS: Consecutive emergency department (ED) patients with at least one cTn test resulted. INTERVENTION: Multifaceted hs-cTn intervention bundle, including a 0/2-h diagnostic algorithm for non-ST-elevation myocardial infarction, an educational bundle, enhancements to the electronic medical record, and nursing interventions to facilitate timed sample collection. MAIN MEASURES: Primary outcomes included serial cTn test utilization, probability of hospital admission, ED length of stay (LOS), and among discharged patients, probability of ED revisit within 72 h resulting in hospital admission. Multivariable regression models adjusted for age, sex, temporal trends, and interhospital differences. KEY RESULTS: The intervention was associated with increased use of serial cTn testing (adjusted risk difference: 48 percentage points, 95% CI: 45-50, P < 0.001) and ED LOS (adjusted geometric mean difference: 50 min, 95% CI: 50-51, P < 0.001). There was no significant association between the intervention and probability of admission (adjusted relative risk [aRR]: 0.99, 95% CI: 0.89-1.1, P = 0.81) or probability of ED revisit within 72 h resulting in admission (aRR: 1.1, 95% CI: 0.44-2.9, P = 0.81). CONCLUSIONS: Implementation of a hs-cTn intervention bundle was associated with an improvement in serial cTn testing, a neutral effect on probability of hospital admission, and a modest increase in ED LOS.

Clinical outcomes of conventional HDR intracavitary brachytherapy combined with complementary applicator-guided intensity modulated radiotherapy boost in patients with bulky cervical tumour.

OBJECTIVE: To investigate the clinical outcomes and toxicity in patients with locally advanced cervical cancer treated with supplementary applicator guided-intensity modulated radiation therapy (IMRT) based on conventional intracavitary brachytherapy (IC/IMRT). DESIGN: A retrospective cohort study. SETTING: Sichuan Cancer Hospital & Institute, Sichuan Cancer Centre, China. POPULATION: Large high-risk clinical target volume (HR-CTV) volume (>40 ml) at the time of brachytherapy cervical cancer patients were recruited. METHODS: This study is a retrospective analysis of 76 patients with locally advanced cervical cancer (FIGO IIB-IVA) treated with concurrent chemoradiotherapy followed by IC/IMRT between June 2010 and October 2016. External radiotherapy (45 Gy in 25 fractions) was adminstered with cisplatin chemotherapy treatment before IC/IMRT. The IMRT plan was optimised using the ICBT plan base dose plan by an inverse dose optimisation tool which allows the use of DVH constraints on the total dose of ICBT. A seven-field gantry angle IMRT plan was devised to avoid hotspots when optimising the boost plan. The prescription dose for HR-CTV and IR-CTV were 6 and 5 Gy per fraction for five fractions, respectively. RESULTS: Mean HR-CTV was 65.8 ± 23.6 ml at the time of brachytherapy. D90 for HR-CTV and IR-CTV were 88.7 ± 3.6 Gy and 78.1 ± 2.5 Gy. D2cc for bladder, rectum, sigmoid and small intestine were 71.8 ± 3.8, 64.6 ± 4.9, 63.9 ± 5.3 and 56.7 ± 8.7 Gy, respectively. Median follow-up was 85 months (47.9-124.2 months). Five-year local recurrence-free survival rate, metastasis recurrence-free survival rate, disease-free survival rate and cancer-special survival rate were 87.6, 82.4, 70.9 and 76.3%, respectively. The grade 1 + 2 gastrointestinal and urinary late toxicities were 15.8 and 21.1%, and grade 3 late toxicities were 3.9 and 5.2%, respectively. Neither acute nor late grade 4 gastrointestinal or urinary toxicities were seen. CONCLUSIONS: The combination of ICBT with an applicator-guided supplementary IMRT boost achieved excellent local control and overall survival with low toxicity for bulky residual cervical tumour.

High-resolution polarization-sensitive Fourier ptychography microscopy using a high numerical aperture dome illuminator.

Polarization-sensitive Fourier-ptychography microscopy (pFPM) allows for high resolution imaging while maintaining a large field of view, and without mechanical movements of optical-setup components. In contrast to ordinary light microscopes, pFPM provides quantitative absorption and phase information, for complex and birefringent specimens, with high resolution across a wide field of view. Using a semi-spherical home-built LED illumination array, a single polarizer, and a 10x /0.28NA objective, we experimentally demonstrate high performance pFPM with a synthesized NA of 1.1. Applying the standard quantitative method, a measured half-pitch resolution of 244 nm is achieved for the 1951 USAF resolution test target. As application examples, the polarimetric properties of a herbaceous flowering plant and the metastatic carcinoma of human liver cells are analyzed and quantitatively imaged.

Work relative value units and perioperative outcomes in patients undergoing brain tumor surgery.

The work relative value unit (wRVU) is a commonly cited surrogate for surgical complexity; however, it is highly susceptible to subjective interpretation and external forces. Our objective was to evaluate whether wRVU is associated with perioperative outcomes, including complications, after brain tumor surgery. The 2006-2014 American College of Surgeons National Surgical Quality Improvement Program database was queried to identify patients ≥ 18 years who underwent brain tumor resection. Patients were categorized into approximate quintiles based on total wRVU. The relationship between wRVU and several perioperative outcomes was assessed with univariate and multivariate analyses. Subgroup analyses were performed using a Current Procedural Terminology code common to all wRVU groups. The 16,884 patients were categorized into wRVU ranges 0-30.83 (4664 patients), 30.84-34.58 (2548 patients), 34.59-38.04 (3147 patients), 38.05-45.38 (3173 patients), and ≥ 45.39 (3352 patients). In multivariate logistic regression analysis, increasing wRVU did not predict more 30-day postoperative complications, except respiratory complications and need for blood transfusion. Linear regression analysis showed that wRVU was poorly correlated with operative duration and length of stay. On multivariate analysis of the craniectomy subgroup, wRVU was not associated with overall or respiratory complications. The highest wRVU group was still associated with greater risk of requiring blood transfusion (OR 3.01, p < 0.001). Increasing wRVU generally did not correlate with 30 days postoperative complications in patients undergoing any surgery for brain tumor resection; however, the highest wRVU groups may be associated with greater risk of respiratory complications and need for transfusion. These finding suggests that wRVU may be a poor surrogate for case complexity.

Simple framework for constructing functional spiking recurrent neural networks.

Cortical microcircuits exhibit complex recurrent architectures that possess dynamically rich properties. The neurons that make up these microcircuits communicate mainly via discrete spikes, and it is not clear how spikes give rise to dynamics that can be used to perform computationally challenging tasks. In contrast, continuous models of rate-coding neurons can be trained to perform complex tasks. Here, we present a simple framework to construct biologically realistic spiking recurrent neural networks (RNNs) capable of learning a wide range of tasks. Our framework involves training a continuous-variable rate RNN with important biophysical constraints and transferring the learned dynamics and constraints to a spiking RNN in a one-to-one manner. The proposed framework introduces only 1 additional parameter to establish the equivalence between rate and spiking RNN models. We also study other model parameters related to the rate and spiking networks to optimize the one-to-one mapping. By establishing a close relationship between rate and spiking models, we demonstrate that spiking RNNs could be constructed to achieve similar performance as their counterpart continuous rate networks.

Nonlinear dynamics underlying sensory processing dysfunction in schizophrenia.

Natural systems, including the brain, often seem chaotic, since they are typically driven by complex nonlinear dynamical processes. Disruption in the fluid coordination of multiple brain regions contributes to impairments in information processing and the constellation of symptoms observed in neuropsychiatric disorders. Schizophrenia (SZ), one of the most debilitating mental illnesses, is thought to arise, in part, from such a network dysfunction, leading to impaired auditory information processing as well as cognitive and psychosocial deficits. Current approaches to neurophysiologic biomarker analyses predominantly rely on linear methods and may, therefore, fail to capture the wealth of information contained in whole EEG signals, including nonlinear dynamics. In this study, delay differential analysis (DDA), a nonlinear method based on embedding theory from theoretical physics, was applied to EEG recordings from 877 SZ patients and 753 nonpsychiatric comparison subjects (NCSs) who underwent mismatch negativity (MMN) testing via their participation in the Consortium on the Genetics of Schizophrenia (COGS-2) study. DDA revealed significant nonlinear dynamical architecture related to auditory information processing in both groups. Importantly, significant DDA changes preceded those observed with traditional linear methods. Marked abnormalities in both linear and nonlinear features were detected in SZ patients. These results illustrate the benefits of nonlinear analysis of brain signals and underscore the need for future studies to investigate the relationship between DDA features and pathophysiology of information processing.

A Pilot Study to Explore a Correlation between Inflammatory Markers and the Wound Healing Rate in Diabetic Patients.

Background and objectives: We examined whether there is a significant correlation between inflammatory markers and the wound healing rate (WHR) in diabetic patients. Materials and Methods: A total of 60 patients were divided into two groups depending on the completion of wound healing (WH) at 5 weeks: the early WH group (period of WH < 5 weeks; n = 27) and the late WH group (period of WH > 5 weeks; n = 33). The baseline characteristics and wound measurements were compared between the two groups. To identify the correlation between inflammatory markers (e.g., white blood cell counts (WBCs), serum C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR)) and WHR, we performed a Pearson correlation analysis. Results: The WHR was 8.06 ± 4.02 mm2/day in the early WH group and 2.71 ± 0.88 mm2/day in the late group. This difference reached statistical significance (p < 0.001). Moreover, WBC counts were significantly higher and serum levels of CRP and ESR were significantly lower in the early WH group than in the late group (p = 0.027, 0.036 and 0.043, respectively). Conclusions: Our results indicate that WBC as well as serum CRP and ESR levels have a significant correlation with WHR in diabetic patients.

Microstructural properties within the amygdala and affiliated white matter tracts across adolescence.

The amygdala is a heterogenous set of nuclei with widespread cortical connections that continues to develop postnatally with vital implications for emotional regulation. Using high-resolution anatomical and multi-shell diffusion MRI in conjunction with novel amygdala segmentation, cutting-edge tractography, and Neurite Orientation Dispersion and Density (NODDI) methods, the goal of the current study was to characterize age associations with microstructural properties of amygdala subnuclei and amygdala-related white matter connections across adolescence (N = 61, 26 males; ages of 8-22 years). We found age-related increases in the Neurite Density Index (NDI) in the lateral nucleus (LA), dorsal and intermediate divisions of the basolateral nucleus (BLDI), and ventral division of the basolateral nucleus and paralaminar nucleus (BLVPL). Additionally, there were age-related increases in the NDI of the anterior commissure, ventral amygdalofugal pathway, cingulum, and uncinate fasciculus, with the strongest age associations in the frontal and temporal regions of these white matter tracts. This is the first study to utilize NODDI to show neurite density of basolateral amygdala subnuclei to relate to age across adolescence. Moreover, age-related differences were also notable in white matter microstructural properties along the anterior commissure and ventral amydalofugal tracts, suggesting increased bilateral amygdalae to diencephalon structural connectivity. As these basolateral regions and the ventral amygdalofugal pathways have been involved in associative emotional conditioning, future research is needed to determine if age-related and/or individual differences in the development of these microstructural properties link to socio-emotional functioning and/or risk for psychopathology.

Disruption of Adaptive Immunity Enhances Disease in SARS-CoV-2-Infected Syrian Hamsters.

Animal models recapitulating human COVID-19 disease, especially severe disease, are urgently needed to understand pathogenesis and to evaluate candidate vaccines and therapeutics. Here, we develop novel severe-disease animal models for COVID-19 involving disruption of adaptive immunity in Syrian hamsters. Cyclophosphamide (CyP) immunosuppressed or RAG2 knockout (KO) hamsters were exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the respiratory route. Both the CyP-treated and RAG2 KO hamsters developed clinical signs of disease that were more severe than those in immunocompetent hamsters, notably weight loss, viral loads, and fatality (RAG2 KO only). Disease was prolonged in transiently immunosuppressed hamsters and was uniformly lethal in RAG2 KO hamsters. We evaluated the protective efficacy of a neutralizing monoclonal antibody and found that pretreatment, even in immunosuppressed animals, limited infection. Our results suggest that functional B and/or T cells are not only important for the clearance of SARS-CoV-2 but also play an early role in protection from acute disease.IMPORTANCE Syrian hamsters are in use as a model of disease caused by SARS-CoV-2. Pathology is pronounced in the upper and lower respiratory tract, and disease signs and endpoints include weight loss and viral RNA and/or infectious virus in swabs and organs (e.g., lungs). However, a high dose of virus is needed to produce disease, and the disease resolves rapidly. Here, we demonstrate that immunosuppressed hamsters are susceptible to low doses of virus and develop more severe and prolonged disease. We demonstrate the efficacy of a novel neutralizing monoclonal antibody using the cyclophosphamide transient suppression model. Furthermore, we demonstrate that RAG2 knockout hamsters develop severe/fatal disease when exposed to SARS-CoV-2. These immunosuppressed hamster models provide researchers with new tools for evaluating therapies and vaccines and understanding COVID-19 pathogenesis.

Learning the Synaptic and Intrinsic Membrane Dynamics Underlying Working Memory in Spiking Neural Network Models.

Recurrent neural network (RNN) models trained to perform cognitive tasks are a useful computational tool for understanding how cortical circuits execute complex computations. However, these models are often composed of units that interact with one another using continuous signals and overlook parameters intrinsic to spiking neurons. Here, we developed a method to directly train not only synaptic-related variables but also membrane-related parameters of a spiking RNN model. Training our model on a wide range of cognitive tasks resulted in diverse yet task-specific synaptic and membrane parameters. We also show that fast membrane time constants and slow synaptic decay dynamics naturally emerge from our model when it is trained on tasks associated with working memory (WM). Further dissecting the optimized parameters revealed that fast membrane properties are important for encoding stimuli, and slow synaptic dynamics are needed for WM maintenance. This approach offers a unique window into how connectivity patterns and intrinsic neuronal properties contribute to complex dynamics in neural populations.

No evidence for a difference in 2D:4D ratio between youth with elevated prenatal androgen exposure due to congenital adrenal hyperplasia and controls.

The second-to-fourth digit ratio (2D:4D) has been associated with sexual dimorphism, with a lower 2D:4D in males. A large body of research has relied on the 2D:4D as a proxy for prenatal androgen exposure, and includes reports of relationships between 2D:4D and a wide range of human traits. Here, we examine the validity of the 2D:4D proxy by studying the association between 2D:4D and classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency, a condition characterized by excessive prenatal exposure to androgens during most of the gestational period. To this end, we retrospectively examine 513 serial radiographs of the left hand obtained clinically in 90 youth with classical CAH (45 female) and 70 control youth (31 female). Replicating previous reports, we observe associations of the 2D:4D with sex (lower 2D:4D in males) and age (increase of 2D:4D through development). However, we find no evidence for differences in 2D:4D between CAH and controls (full sample: ß = -0.001 (-0.008, 0.006); females: ß = -0.004 [-0.015, 0.007]; males: ß = 0.001, [-0.008, 0.011]). Although our findings do not rule out a small association between the 2D:4D and CAH, they cast doubt on the usefulness of the 2D:4D as a biomarker for prenatal androgen exposure in behavioral research.

A Preliminary Retrospective Study to Assess the Short-Term Safety of Traditional Smooth or Microtextured Silicone Gel-Filled Breast Implants in Korea.

Background and objectives: We conducted this preliminary retrospective study to assess the short-term safety of silicone gel-filled breast implants (SGBIs) that are commercially available in Korean women. Materials and methods :The current retrospective, observational study was conducted in a total of 2612 patients (n = 2612) who underwent augmentation mammaplasty using breast implants at our hospitals between 1 January 2017 and 31 August 2021. Results: Overall, there were a total of 248 cases (9.49%) of postoperative complications; these include 112 cases of early seroma, 52 cases of shape deformation, 32 cases of CC, 12 cases of early hematoma, 12 cases of rupture, 12 cases of infection, 12 cases of stretch deformities with skin excess and 4 cases of rippling. Overall complication-free survival of the breast implant was estimated at 1564.32 ± 75.52 days (95% CI 1416.39-1712.32). Then, the Motiva Ergonomix™ SilkSurface showed the longest survival (1528.00 ± 157.92 days [95% CI 1218.48-1837.56]), followed by the BellaGel® SmoothFine (1458.4 ± 65.76 days [95% CI 1329.56-1587.28]), the Sebbin® Sublimity (1322.00 ± 51.20 days [95% CI 1221.64-1422.32]), the BellaGel® Smooth (1138.72 ± 161.28 days [95% CI 822.6-1454.84), the Mentor® MemoryGel™ Xtra (698.4 ± 52.64 days [95% CI 595.28-801.52]) and the Natrelle® INSPIRA™ (380.00 ± 170.88 days [95% CI 45.04-714.96]) in the decreasing order. On subgroup analysis, both the Motiva ErgonomixTM and Mentor® MemoryGel™ Xtra showed no postoperative complications. However, the BellaGel® SmoothFine, Sebbin® Sublimity and BellaGel® Smooth showed incidences of 8.87%, 4.84% and 1.61%, respectively. A subgroup analysis also showed differences in incidences of postoperative complications between microtextured and smooth breast implants (15.18% vs. 16.67%). Conclusions: In conclusion, our results indicate that diverse types of an SGBI are commercially available and their safety profile varies according to the manufacturer. Plastic surgeons should consider the safety profile of each device in selecting the optimal types of the device for Korean women who are in need of an implant-based augmentation mammaplasty. However, this warrants a single-surgeon, single-center study with long periods of follow-up.

Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Randomized Phase 2 Trial.

PURPOSE: Geographic atrophy (GA), a late stage of age-related macular degeneration (AMD), is a major cause of blindness. Even while central visual acuity remains relatively well preserved, GA often causes considerable compromise of visual function and quality of life. No treatment currently exists. We evaluated the safety and efficacy of pegcetacoplan, a complement C3 inhibitor, for treatment of GA. DESIGN: Prospective, multicenter, randomized, sham-controlled phase 2 study. PARTICIPANTS: Two hundred forty-six patients with GA. METHODS: Patients with GA were assigned randomly in a 2:2:1:1 ratio to receive intravitreal injections of 15 mg pegcetacoplan monthly or every other month (EOM) or sham intravitreal injections monthly or EOM for 12 months with follow-up at months 15 and 18. Area and growth of GA were measured using fundus autofluorescence imaging. MAIN OUTCOME MEASURES: The primary efficacy end point was mean change in square root GA lesion area from baseline to month 12. Secondary outcome measures included mean change from baseline in GA lesion area without the square root transformation, distance of GA lesion from the fovea, best-corrected visual acuity (BCVA), low-luminance BCVA, and low-luminance visual acuity deficit. The primary safety end point was the number and severity of treatment-emergent adverse events. RESULTS: In patients receiving pegcetacoplan monthly or EOM, the GA growth rate was reduced by 29% (95% confidence interval [CI], 9-49; P = 0.008) and 20% (95% CI, 0-40; P = 0.067) compared with the sham treatment group. Post hoc analysis showed that the effect was greater in the second 6 months of treatment, with observed reductions of 45% (P = 0.0004) and 33% (P = 0.009) for pegcetacoplan monthly and EOM, respectively. Two cases of culture-positive endophthalmitis and 1 case of culture-negative endophthalmitis occurred in the pegcetacoplan monthly group. New-onset investigator-determined exudative AMD was reported more frequently in pegcetacoplan-treated eyes (18/86 eyes [20.9%] and 7/79 eyes [8.9%] in monthly and EOM groups, respectively) than in sham-treated eyes (1/81 eyes [1.2%]). CONCLUSIONS: Local C3 inhibition with pegcetacoplan resulted in statistically significant reductions in the growth of GA compared with sham treatment. Phase 3 studies will define the efficacy and safety profile further.

Systematic Review for the 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

BACKGROUND: Although large randomized clinical trials have found that primary prevention use of an implantable cardioverter-defibrillator (ICD) improves survival in patients with cardiomyopathy and heart failure symptoms, patients who receive ICDs in practice are often older and have more comorbidities than patients who were enrolled in the clinical trials. In addition, there is a debate among clinicians on the usefulness of electrophysiological study for risk stratification of asymptomatic patients with Brugada syndrome. AIM: Our analysis has 2 objectives. First, to evaluate whether ventricular arrhythmias (VAs) induced with programmed electrostimulation in asymptomatic patients with Brugada syndrome identify a higher risk group that may require additional testing or therapies. Second, to evaluate whether implantation of an ICD is associated with a clinical benefit in older patients and patients with comorbidities who would otherwise benefit on the basis of left ventricular ejection fraction and heart failure symptoms. METHODS: Traditional statistical approaches were used to address 1) whether programmed ventricular stimulation identifies a higher-risk group in asymptomatic patients with Brugada syndrome and 2) whether ICD implantation for primary prevention is associated with improved outcomes in older patients (>75 years of age) and patients with significant comorbidities who would otherwise meet criteria for ICD implantation on the basis of symptoms or left ventricular function. RESULTS: Evidence from 6 studies of 1138 asymptomatic patients were identified. Brugada syndrome with inducible VA on electrophysiological study was identified in 390 (34.3%) patients. To minimize patient overlap, the primary analysis used 5 of the 6 studies and found an odds ratio of 2.3 (95% CI: 0.63-8.66; P=0.2) for major arrhythmic events (sustained VAs, sudden cardiac death, or appropriate ICD therapy) in asymptomatic patients with Brugada syndrome and inducible VA on electrophysiological study versus those without inducible VA. Ten studies were reviewed that evaluated ICD use in older patients and 4 studies that evaluated unique patient populations were identified. In our analysis, ICD implantation was associated with improved survival (overall hazard ratio: 0.75; 95% confidence interval: 0.67-0.83; P<0.001). Ten studies were identified that evaluated ICD use in patients with various comorbidities including renal disease, chronic obstructive pulmonary disease, atrial fibrillation, heart disease, and others. A random effects model demonstrated that ICD use was associated with reduced all-cause mortality (overall hazard ratio: 0.72; 95% confidence interval: 0.65-0.79; P<0.0001), and a second "minimal overlap" analysis also found that ICD use was associated with reduced all-cause mortality (overall hazard ratio: 0.71; 95% confidence interval: 0.61-0.82; P<0.0001). In 5 studies that included data on renal dysfunction, ICD implantation was associated with reduced all-cause mortality (overall hazard ratio: 0.71; 95% confidence interval: 0.60-0.85; P<0.001).

Efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation and chronic kidney disease.

BACKGROUND: Direct oral anticoagulants (DOACs) are effective alternatives to warfarin for stroke prevention in patients with atrial fibrillation (AF) including patients with CKD III. However, data on patient outcomes with DOACs for advanced CKD are limited, while warfarin use is controversial. METHODS: A retrospective study of patients with AF using DOACs and CKD stages III-V was conducted. The primary outcomes were stroke or systemic embolism and major bleeding while on DOAC therapy among CKD IV and V patients. Rates of outcomes from the DOAC trials and from previous studies of warfarin in CKD were referenced. RESULTS: Of 316 patients reviewed, 152 were included with mean CrCl of 38.8 mL/min. Stroke and systemic embolism occurred at a rate of 1.17 per 100 person-years, with no significant difference between CKD IV/V and CKD III (P = .567). Rates were comparable to DOAC use from the DOAC trials, and lower than rates in studies of warfarin in CKD IV/V patients. There was a nonstatistically significant trend toward increased major bleeding in CKD IV/V patients. Rates of major bleeding in CKD III to V subjects were comparable to published rates for warfarin users with similar levels of renal impairment. CONCLUSIONS: In our study, DOACs appeared to be as efficacious and safe in CKD IV and V as in CKD III. In addition, DOACs appeared to be more effective than, and as safe as warfarin when compared with reference studies of patients with advanced CKD. Our findings support the use of DOACs for thromboembolism prevention in patients with advanced CKD and AF.

Incidence of mesorectal node metastasis in locally advanced cervical cancer: its therapeutic implications.

OBJECTIVE: To evaluate the incidence and risk factors for mesorectal node metastasis (MRNM) in locally advanced cervical cancer. METHODS/MATERIALS: We performed an observational retrospective cohort study of 122 patients with cervical cancer who received definitive chemo-radiation treatment between December 2013 and June 2017 to evaluate the incidence of MRNM. Three diagnostic radiologists assessed all available pre-treatment images. In this study, the pelvic node metastasis was defined as ≥ 1.0 cm and MRNM as ≥ 0.5 cm for CT and MRI scans and as a maximum standardized uptake value of > 2.5 for PET/CT. The relationship of MRNM with FIGO stage, pelvic node metastasis, and mesorectal fascia involvement was evaluated. RESULTS: The incidence of MRNM in all 122 patients was 8 (6.6%). However, in advanced stage (III- IV) patients, MRNM occurred in 4 of 39 (10.3%) compared with 4 of 83 (4.8%) in early stage (IB1-IIB) patients (p = 0.27). In patients with a positive pelvic node, MRNM occurred in 7 of 55 (12.7%) and 1 of 67 (1.5%) in those with negative pelvic node (p = 0.02). In addition, the incidence of MRNM was 3 of 9 (33.3%) in the presence of mesorectal fascia involvement and 5 of 113 (4.4%) among those without mesorectal fascia involvement (p = 0.013). CONCLUSION: This study indicates that pelvic node metastasis and mesorectal fascia involvement are high-risk factors for MRNM. Therefore, vigilance of reviewing images in the mesorectum for MRNM is necessary for high-risk patients.

Preexisting Right Ventricular Dysfunction Is Associated With Higher Postoperative Cardiac Complications and Longer Hospital Stay in High-Risk Patients Undergoing Nonemergent Major Vascular Surgery.

OBJECTIVES: To evaluate whether the presence of preexisting right ventricular (RV) dysfunction in high-risk patients undergoing nonemergent major vascular surgery is associated independently with higher incidents of postoperative cardiac complications and a longer length of hospital stay. DESIGN: Retrospective chart review. SETTING: Single-center university hospital setting. PARTICIPANTS: The patient population consisted of those identified as American Society of Anesthesiologists classification III and above who had a preoperative echocardiogram within 1 year of undergoing nonemergent major vascular surgery between January 2010 and May 2017. MEASUREMENTS AND MAIN RESULTS: After multivariate analyses, RV dysfunction (RVD) is associated independently with a higher incidence of postoperative major cardiac complications with an odds ratio = 6.3 (95% confidence interval [CI], 1.0-38.5; p = 0.046). In addition, patients with RVD had a 50% longer length of stay than those without RVD (incident rate ratio [95% CI], 1.5 [1.2-1.8]; p < 0.001). CONCLUSION: In this retrospective study of high-risk patients undergoing major vascular surgery, RV dysfunction was associated independently with a higher incidence of postoperative major cardiovascular events and longer length of hospital stays. Based on current findings, the prognostic value of RVD extends beyond the cardiac surgical cohort. Knowledge in management of patients with RVD in the perioperative setting should be understood by all anesthesiologists. Of note, a future study with a larger sample size is needed to validate the current findings given the small sample size of this study.

Failed Maximal Defibrillation Threshold Testing in the Subcutaneous Implantable Cardioverter Defibrillator.

The subcutaneous implantable cardioverter defibrillator (S-ICD) registry included very few patients with a body mass index (BMI) greater than 40. We present a case of a 40-year-old male with a BMI of 44 and ejection fraction of 25% who underwent S-ICD implantation for primary prevention of sudden cardiac death in the setting of a nonischemic cardiomyopathy. Defibrillation threshold (DFT) testing failed at high output. A posterior to anterior radiograph demonstrated migration of the components despite positioning under fluoroscopy. After repositioning, repeat DFT testing showed an inconsistent efficacy. We discuss the probabilistic nature of DFT testing, clinical factors affecting the S-ICD implant in the obese population and offer a novel insight from this specific experience.

Intestinal brush-border Na+/H+ exchanger-3 drives H+-coupled iron absorption in the mouse.

Divalent metal-ion transporter-1 (DMT1), the principal mechanism by which nonheme iron is taken up at the intestinal brush border, is energized by the H(+)-electrochemical potential gradient. The provenance of the H(+) gradient in vivo is unknown, so we have explored a role for brush-border Na(+)/H(+) exchanger (NHE) isoforms by examining iron homeostasis and intestinal iron handling in mice lacking NHE2 or NHE3. We observed modestly depleted liver iron stores in NHE2-null (NHE2(-/-)) mice stressed on a low-iron diet but no change in hematological or blood iron variables or the expression of genes associated with iron metabolism compared with wild-type mice. Ablation of NHE3 strongly depleted liver iron stores, regardless of diet. We observed decreases in blood iron variables but no overt anemia in NHE3-null (NHE3(-/-)) mice on a low-iron diet. Intestinal expression of DMT1, the apical surface ferrireductase cytochrome b reductase-1, and the basolateral iron exporter ferroportin was upregulated in NHE3(-/-) mice, and expression of liver Hamp1 (hepcidin) was suppressed compared with wild-type mice. Absorption of (59)Fe from an oral dose was substantially impaired in NHE3(-/-) compared with wild-type mice. Our data point to an important role for NHE3 in generating the H(+) gradient that drives DMT1-mediated iron uptake at the intestinal brush border.