Peri-operative outcomes following radical prostatectomy in the setting of advanced prostate cancer.

OBJECTIVE: To compare the peri-operative outcomes of radical prostatectomy (RP) for locally advanced, node-positive, and metastatic prostate cancer (PCa), as determined through pathological staging, using the American College of Surgeons National Surgical Quality Improvement Project. METHODS: We identified RP procedures performed between 2019 and 2021. Patients were stratified by pathological staging to compare the effect of locally advanced disease (T3-4), node positivity (N+) and metastasis (M+) vs localised PCa (T1-2 N0 M0). Baseline demographics and 30-day outcomes, including operating time, length of hospital stay (LOS), 30-day mortality, readmissions, reoperations, major complications, minor complications and surgery-specific complications, were compared between groups. RESULTS: Pathological staging data were available for 9276 RPs. Baseline demographics were comparable. There was a slightly higher rate of minor complications in the locally advanced cohort, but no significant difference in major complications, 30-day mortality, readmissions, or rectal injuries. Node positivity was associated with longer operating time, LOS, and some slightly increased rates of 30-day complications. RP in patients with metastatic disease appeared to be similarly safe to RP in patients with M0 disease, although it was associated with a longer LOS and slightly increased rates of certain complications. CONCLUSIONS: For patients with pathologically determined locally advanced, node-positive, and metastatic PCa, RP appears to be safe, and is not associated with significantly higher rates of 30-day mortality or major complications compared to RP for localised PCa. This study adds to the growing body of literature investigating the role of RP for advanced PCa; further studies are needed to better characterise the risks and benefits of surgery in such patients.

Incidence of Pneumonia, Related Hospitalization, and Mortality Among Younger Unvaccinated IBD Patients in a Nationwide Cohort.

BACKGROUND AND GOALS: Community Acquired Pneumonia (CAP) is among the most common infections among Inflammatory Bowel Disease (IBD) patients. Our aim was to determine the absolute and relative risk of CAP, related hospitalization, and death among younger (age < 65) unvaccinated IBD patients exposed and unexposed to immunosuppressive medications. MATERIALS AND METHODS: We conducted a retrospective cohort study among a nationwide cohort of younger IBD unvaccinated patients in the VAHS. Exposure was administration of any immunosuppressive medication. The primary outcome was the first occurrence of pneumonia; secondary outcomes being pneumonia related hospitalization and mortality. We reported event rate per 1000 person-years, hazard ratio, and 95% confidence intervals (CIs) for each outcome. RESULTS: Among a total of 26,707 patients, 513 patients developed pneumonia. Mean age in years (SD) was 51.67 (11.34) for the exposed and 45.91 (12.34) for the unexposed group. The overall crude incidence rate was 3.2 per 1000 patient-years (PYs) [4.04/1000 PYs in the exposed versus 1.45/1000 PYs in the unexposed]. The overall crude incidence rates for pneumonia-related-hospitalization and mortality 1.12 and 0.09 per 1000 PYs, respectively. In Cox regression, the exposed group was associated with an increased risk of pneumonia (AHR 2.85; 95% CI: 2.21 to 3.66, P < 0.001) and pneumonia-related-hospitalization (AHR 3.46; 95% CI: 2.20 to 5.43, P < 0.001). CONCLUSIONS: Overall incidence of CAP among younger unvaccinated IBD patients was 3.2 per 1000 PYs. The overall associated hospitalization rates were low, however, higher amongst those exposed to immunosuppressive medications. This data will help patients and physicians make informed decisions regarding pneumococcal vaccine recommendations.

Groove pancreatitis: From enigma to future directions-A comprehensive review.

Groove pancreatitis (GP) is a rare and clinically distinct form of chronic pancreatitis affecting the pancreaticoduodenal groove comprising the head of the pancreas, duodenum, and the common bile duct. It is more prevalent in individuals in their 4-5th decade of life and disproportionately affects men compared with women. Excessive alcohol consumption, tobacco smoking, pancreatic ductal stones, pancreatic divisum, annular pancreas, ectopic pancreas, duodenal wall thickening, and peptic ulcers are significant risk factors implicated in the development of GP. The usual presenting symptoms include severe abdominal pain, nausea, vomiting, diarrhea, weight loss, and jaundice. Establishing a diagnosis of GP is often challenging due to significant clinical and radiological overlap with numerous benign and malignant conditions affecting the same anatomical location. This can lead to a delay in initiation of treatment leading to increasing morbidity, mortality, and complication rates. Promising research in artificial intelligence (AI) has garnered immense interest in recent years. Due to its widespread application in diagnostic imaging with a high degree of sensitivity and specificity, AI has the potential of becoming a vital tool in differentiating GP from pancreatic malignancies, thereby preventing a missed or delayed diagnosis. In this article, we provide a comprehensive review of GP, covering the etiology, pathogenesis, clinical presentation, radiological and endoscopic evaluation, management strategies, and future directions. This article also aims to increase awareness about this lesser known and often-misdiagnosed clinical entity amongst clinicians to ultimately improve patient outcomes.

Perioperative risk predictors for gender affirming surgery in the NSQIP database.

INTRODUCTION: Gender affirming surgeries (GAS), such as phalloplasty (PLPs) and vaginoplasty (VGPs), are important aspects of medical care for transgender patients. Here, we aim to better characterize patient demographics and surgical outcomes for PLPs and VGPs using the National Surgical Quality Improvement Program (NSQIP). We hypothesized that frailty indices would be predictive of perioperative PLP and VGP risk and outcomes for PLPs and VGPs. MATERIALS AND METHODS: Primary GAS, specifically PLPs and VGPs performed from 2006-2020 were identified in NSQIP. Baseline frailty was based on NSQIP's modified frailty index (mFI) and preoperative morbidity probability (morbprob) variable. RESULTS: Fifty-eight PLPs and 468 VGPs were identified. The overall 30-day complication rate for PLP was 26%, with 17% of total patients experiencing minor complications and 16% experiencing major complications. The overall, minor, and major complication rates for VGP were 14%, 7%, and 9% respectively. Readmissions and reoperations occurred in 7% PLP and 5% VGP patients. No deaths occurred in either group within 30 days. The mFI scores were not predictive of 30-day complications or LOS. NSQIP morbprob was predictive of 30-day complications for both PLP (OR 4.0, 95% CI 1.08-19.59, p = 0.038) and VGP (OR 2.39, 95% CI 1.46-3.97, p = 0.0005). NSQIP's morbprob was also predictive of extended LOS for PLP patients (6.3 ± 1.3 days, p = 0.03). CONCLUSIONS: This study describes patient characteristics and complication rates of PLPs and VGPs. The NSQIP preoperative morbprob is an effective predictor of surgical complications and is better than the mFI.

A Multi-Aperture Technique for Longitudinal Miniaturization of UWB 3 dB Dual-Layer SIW Coupler.

Microwave couplers are used in large numbers in beamforming networks, and their miniaturization can lead to a significant size reduction in the overall phased array. While the miniaturization of 3 dB couplers in the transverse direction (width) has been given considerable attention in the literature, there is minimal to no information on reducing coupler length. This is because of the trade-off between aperture length, bandwidth and coupling strength. The Bethe-Hole theory requires adding multiple apertures in the longitudinal direction for wide bandwidth, thus increasing the device length. Another factor is the aperture size, which determines the coupling strength and puts additional strain on the compactness of a 3 dB coupler. Contrariwise, this paper proposes to merge two weak (and hence compact) coupling mechanisms to design a wideband 3 dB coupler. This is achieved by using a longitudinal rectangular slot and three cross-slots in the transverse direction. Because of weak coupling, the slot sizes are smaller than a conventional 3 dB coupler, hence yielding a device whose length is less than one guided wavelength (λg) without compromising the bandwidth. The presented coupler is 0.63 λg in length, which is smaller than the state-of-the-art while maintaining a fractional bandwidth of 37% that is comparable to half-mode substrate integrated waveguide (HMSIW) couplers.

Advances in Gluten Hypersensitivity: Novel Dietary-Based Therapeutics in Research and Development.

Gluten hypersensitivity is characterized by the production of IgE antibodies against specific wheat proteins (allergens) and a myriad of clinical allergic symptoms including life-threatening anaphylaxis. Currently, the only recommended treatment for gluten hypersensitivity is the complete avoidance of gluten. There have been extensive efforts to develop dietary-based novel therapeutics for combating this disorder. There were four objectives for this study: (i) to compile the current understanding of the mechanism of gluten hypersensitivity; (ii) to critically evaluate the outcome from preclinical testing of novel therapeutics in animal models; (iii) to determine the potential of novel dietary-based therapeutic approaches under development in humans; and (iv) to synthesize the outcomes from these studies and identify the gaps in research to inform future translational research. We used Google Scholar and PubMed databases with appropriate keywords to retrieve published papers. All material was thoroughly checked to obtain the relevant data to address the objectives. Our findings collectively demonstrate that there are at least five promising dietary-based therapeutic approaches for mitigating gluten hypersensitivity in development. Of these, two have advanced to a limited human clinical trial, and the others are at the preclinical testing level. Further translational research is expected to offer novel dietary-based therapeutic options for patients with gluten hypersensitivity in the future.

Inherited bone marrow failure with macrothrombocytopenia due to germline tubulin beta class I (TUBB) variant.

Germline mutations in tubulin beta class I (TUBB), which encodes one of the ß-tubulin isoforms, were previously associated with neurological and cutaneous abnormalities. Here, we describe the first case of inherited bone marrow (BM) failure, including marked thrombocytopenia, morphological abnormalities, and cortical dysplasia, associated with a de novo p.D249V variant in TUBB. Mutant TUBB had abnormal cellular localisation in transfected cells. Following interferon/ribavirin therapy administered for transfusion-acquired hepatitis C, severe pancytopenia and BM aplasia ensued, which was unresponsive to immunosuppression. Acquired chromosome arm 6p loss of heterozygosity was identified, leading to somatic loss of the mutant TUBB allele.

Rapid single-photon color imaging of moving objects.

This paper outlines an experimental demonstration of a Bayesian image reconstruction approach to achieve rapid single-photon color imaging of moving objects. The capacity to extract the color of objects is important in a variety of target identification and computer vision applications. Nonetheless, it remains challenging to achieve high-speed color imaging of moving objects in low-photon flux environments. The low-photon regime presents particular challenges for efficient spectral separation and identification, while unsupervised image reconstruction algorithms are often slow and computationally expensive. In this paper, we address both of these difficulties using a combination of hardware and computational solutions. We demonstrate color imaging using a Single-Photon Avalanche Diode (SPAD) detector array for rapid, low-light-level data acquisition, with an integrated color filter array (CFA) for efficient spectral unmixing. High-speed image reconstruction is achieved using a bespoke Bayesian algorithm to produce high-fidelity color videos. The analysis is conducted first on simulated data allowing different pixel formats and photon flux scenarios to be investigated. Experiments are then performed using a plasmonic metasurface-based CFA, integrated with a 64 × 64 pixel format SPAD array. Passive imaging is conducted using white-light illumination of multi-colored, moving targets. Intensity information is recorded in a series of 2D photon-counting SPAD frames, from which accurate color information is extracted using the fast Bayesian method introduced herein. The per-frame reconstruction rate proves to be hundreds of times faster than the previous computational method. Furthermore, this approach yields additional information in the form of uncertainty measures, which can be used to assist with imaging system optimization and decision-making in real-world applications. The techniques demonstrated point the way towards rapid video-rate single-photon color imaging. The developed Bayesian algorithm, along with more advanced SPAD technology and utilization of time-correlated single-photon counting (TCSPC) will permit live 3D, color videography in extremely low-photon flux environments.

Evaluation of Consumer Health Information Available to Patients on Twitter About Bariatric Surgery.

INTRODUCTION: Patients are increasingly utilizing social media to help them make medical decisions. Previous studies have examined Facebook for the quality of bariatric-related content; however, no research has examined Twitter, a globally favored platform, in this context. The goal of this study is to investigate the quality of bariatric-related content on Twitter that patients use to inform their decisions regarding bariatric surgery. METHODS: Six comprehensive terms were searched on six Twitter accounts for 4 wk. Each keyword generated corresponding tweets that were classified as being either informational or noninformational. The top ten informational posts for each search term were categorized based on content type, tweet posters, and type of evidence used. A DISCERN score was calculated for each tweet to determine its quality of consumer health information. RESULTS: A total of 7531 tweets about bariatric surgery were collected over the course of approximately 1 mo. We found that 58.9% of tweets pertained to surgical interventions, 16.2% were nutrition-related, 11.3% were progress posts, 7.8% were inspirational posts, and 5.9% pertained to lifestyle. Of the tweets pertaining to surgical interventions, 26% were posted by physicians, and 13.7% of those physicians used scientific evidence. The relationship between the average total DISCERN scores and each variable was statistically significant. CONCLUSIONS: Even though physicians posted the highest quality consumer information, that information still correlated with an average DISCERN score of "very poor". Twitter may provide a good way to foster community and get anecdotal information but is not a place to gather high-quality scientific consumer health information.

Life-threatening altered mental status secondary to memantine in an adolescent undergoing cranial radiotherapy for medulloblastoma.

INTRODUCTION: Memantine is used for neurocognitive protection in patients undergoing cranial radiotherapy for central nervous system tumors and is reported to be well-tolerated. CASE REPORT: Presented is a case of memantine-induced altered mental status requiring an intensive care unit admission. An 18-year-old male with relapsed, progressive medulloblastoma presented with severe altered mental status shortly after the first fraction of palliative whole brain radiotherapy. At the time, the patient was on day five of memantine therapy, which had been prescribed to reduce neurocognitive toxicity risk. MANAGEMENT & OUTCOME: Memantine was withheld while dexamethasone, valproate, and morphine were continued for headache. Approximately 50 h after admission, the patient's confusion significantly improved. Evaluation of acute altered mental status was unrevealing, including but not limited to negative urinary toxicology screen and lack of disease progression on imaging. Whole brain radiotherapy was resumed after a two-day cessation and he was discharged home after four days with complete resolution of symptoms. DISCUSSION: Clinicians should be aware of and consider the risk of altered mental status with memantine, given the increased utilization and upcoming clinical trials in pediatric patients.

Adjunctive use of cenobamate for pediatric refractory focal-onset epilepsy: A single-center retrospective study.

OBJECTIVE: We explored the efficacy and safety profile of cenobamate as an adjunctive therapy in patients with refractory focal-onset epilepsy in the pediatric population. METHODS: This was a retrospective, single-center study of cenobamate used as an adjunctive medication in pediatric patients with refractory focal-onset epilepsy . We measured seizure reduction, median reduction in seizure frequency, median dose, responder rate, and treatment-emergent adverse events. RESULTS: We studied the efficacy and safety profile of cenobamate in 21 pediatric patients (mean age 15.9). Cenobamate was up titrated using the prescribed starter pack with final doses ranging from 100 mg to 400 mg daily. The mean and median dose of cenobamate was 209.8 mg (±98.87 mg) and 200 mg (175-275), respectively. For patients weighing less than 50 kg, mean and median dose was 4.0 mg/kg/day (3.20-4.63) and 4.32 mg/kg/day, respectively. Mean and median baseline seizure frequency per month in this cohort was 15.38 and 16, respectively, prior to the introduction of cenobamate. After the adjunctive use of cenobamate, mean and median seizure frequency per month reduced to 7.29 and 1, respectively; median reduction in seizure frequency was 93.7%. Seizure reduction of at least 50% (responder rate) was noted in 13 (62.5%) patients and a seizure reduction of at least 75% noted in 11 (52.4%) patients, similar to that seen in adults. Four patients (19%) achieved seizure freedom. Of the 21 pediatric patients, 9 (42.8%) patients had treatment-emergent adverse events (TEAE) with the most commonly reported symptom being ataxia (5, 23.8%) and sedation (2, 9.5%). Three (14.3%) patients discontinued early due to these side effects. No children developed drug rash with eosinophilia and systemic symptoms (DRESS). CONCLUSION: Cenobamate demonstrates similar efficacy rates and safety profile within the pediatric population when compared to the published adult data, making it an effective, safe, and tolerable adjunctive medication for children with refractory focal-onset epilepsy, even at the maximum daily dose.

Does antithrombotic use enable earlier diagnosis of bladder cancer? A brief institutional assessment.

INTRODUCTION: Wallis et al (JAMA 2017) demonstrated use of antithrombotic medications (ATMs) is associated with increased prevalence of hematuria-related complications and subsequent bladder cancer diagnosis within 6 months. Stage of diagnosis was lacking in this highly publicized study. This study examined the association of ATM use on bladder cancer stage at the time of diagnosis. MATERIALS AND METHODS: We completed a retrospective chart review of patients with a bladder cancer diagnosis at our institution. Patient demographics and bladder cancer work up information were assessed. Patients were stratified based on use of ATMs at time diagnosis. Descriptive statistics were completed to identify association between ATM use and stage of bladder cancer diagnosis, as stratified by non-muscle invasive bladder cancer (NMIBC) versus muscle invasive bladder cancer (MIBC). RESULTS: A total of 1052 patient charts were reviewed. Eight hundred and forty-four were included and 208 excluded due to unavailability of diagnosis history. At diagnosis, 357 (42.3%) patients were taking ATMs. Patients on ATMs presented with NMIBC at similar rates as patients not taking ATMs (81.2% vs. 77.8%, p = 0.23). Subgroup analysis by ATM class similarly demonstrated no statistically significant differences in staging. CONCLUSION: While Wallis et al established that patients on blood thinners who present with hematuria are more likely to be diagnosed with genitourinary pathology, this factor does not appear to enable an earlier diagnosis of bladder cancer. Future study may assess hematuria at presentation (gross, microscopic), type of blood thinners, and low versus high risk NMIBC presentation.

A Novel Device for the Quantification of Synovial Fluid Viscosity Via Magnetic Deflection.

Changes in synovial fluid viscosity may be used to detect joint disease; however, methods to evaluate these changes at the point-of-care are currently rudimentary. Previously, we demonstrated that magnetic particle translation through static synovial fluid could serve as a surrogate marker of synovial fluid mechanics. In this work, we examine the magnetic deflection of a stream of particles flowing through a stream of synovial fluid and relate this deflection to changes in fluid mechanics. First, a flow device was designed, where a stream of magnetic particles flows along with synovial fluid. As the particle stream approaches and passes a fixed permanent magnet, the particle stream deflects. Conceptually, as the synovial fluid viscosity decreases, the deflection of the particle stream should increase due to a decreased drag force opposing the force magnetization. To assess this concept, particle deflection was first measured in Newtonian glycerol solutions of known varying viscosity under different flow conditions. Next, the device was used to test bovine synovial fluid viscosity, which had been progressively degraded using ultrasonication. A strong correlation was observed between the deflection of the magnetic particles and the viscosity of the glycerol solutions (R2 = 0.987) and the amount of ultrasonic degradation of synovial fluid (R2 = 0.7045). In the future, the principle of particle deflection may be used to design point-of-care quantification of synovial fluid mechanics, as the assessment does not require particles to be separated from the fluid for quantification and could be conducted under simple flow conditions.

Surgical timing in neonatal brachial plexus palsy: A PRISMA-IPD systematic review.

BACKGROUND: Neonatal brachial plexus palsy (NBPP) is a serious complication of high-risk deliveries with controversy surrounding timing of corrective nerve surgery. This review systematically examines the existing literature and investigates correlations between age at time of upper trunk brachial plexus microsurgery and surgical outcomes. METHODS: A systematic screening of PubMed, Cochrane, Web of Science, and CINAHL databases using PRISMA-IPD guidelines was conducted in January 2020 to include full-text English papers with microsurgery in upper trunk palsy, pediatric patients. Spearman rank correlation analysis and two-tailed t-tests were performed using individual patient data to determine the relationship between mean age at time of surgery and outcome as determined by the Mallet, Medical Research Council (MRC), or Active Movement Scale (AMS) subscores. RESULTS: Two thousand nine hundred thirty six papers were screened to finalize 25 papers containing individual patient data (n = 256) with low to moderate risk of bias, as assessed by the ROBINS-I assessment tool. Mallet subscore for hand-to-mouth and shoulder abduction, AMS subscore for elbow flexion and external rotation, and MRC subscore for elbow flexion were analyzed alongside the respective age of patients at surgery. Spearman rank correlation analysis revealed a significant negative correlation (ρ = -0.30, p < .01, n = 89) between increasing age (5.50 ± 2.09 months) and Mallet subscore for hand-to-mouth (3.43 ± 0.83). T-tests revealed a significant decrease in Mallet hand-to-mouth subscores after 6 months (p < .05) and 9 months (p < .05) of age. No significant effects were observed for Mallet shoulder abduction, MRC elbow flexion, or AMS elbow flexion and external rotation. CONCLUSION: The cumulative evidence suggests a significant negative correlation between age at microsurgery and Mallet subscores for hand-to-mouth. However, a similar correlation with age at surgery was not observed for Mallet shoulder abduction, MRC elbow flexion, AMS external rotation, and AMS elbow flexion subscores.

Length of stay linked to neurodiagnostic workup for seizures presenting to the pediatric emergency department.

INTRODUCTION: Patients presenting to the pediatric emergency department (ED) often undergo unnecessary testing that leads to prolonged ED visits. Lower ED length of stay has been linked to improved patient experience and may reduce ED overcrowding, a costly burden on a health system. METHODS: This is a retrospective cohort study involving patient records over the period of 6 months at an urban tertiary children's hospital who presented with seizures. Febrile seizures, seizures associated with trauma, and charts of patients who did not present initially through our ED were excluded. RESULTS: 328 charts were obtained through this search criteria. Head imaging was performed in 52 (16%) patients and consisted of 81% CT (n = 42) and 19% (n = 10) magnetic resonance imaging (MRI). Obtaining an MRI was associated with a 3.5 h longer ED visit (p = 0.07); obtaining a CT was associated with a 1.5 h longer ED visit (p = 0.005). An Electroencephalogram (EEG) was obtained for 67 (20%) visits and was associated with a 3.0 h longer ED length of stay (p < 0.001). Ten % of the CT scans showed new or progressive findings and 40% of the MRIs done provided useful information for management. Thirty-seven % of EEGs performed in new onset seizure patients revealed epileptiform findings and 5% of EEGs in established seizure patients provided meaningful findings important to management. CONCLUSION: Obtaining neurodiagnostic studies significantly prolongs duration of stay in the ED. Electroencephalograms appear to have the greatest yield in new onset seizure patients and can help make a diagnosis of an epilepsy syndrome in children.

Overlap Between Medicare's Comprehensive Care for Joint Replacement Program and Accountable Care Organizations.

BACKGROUND: Overlap between Medicare's Comprehensive Care for Joint Replacement (CJR) model and accountable care organizations (ACOs) may result in positive or negative synergies. In this study, we describe the overlap between the programs at the beneficiary and hospital levels. METHODS: We conducted a retrospective study of patient and hospital characteristics using data from 2016 Medicare claims, the US Census Bureau, the American Hospital Association annual survey, Hospital Compare, and the Centers for Medicare & Medicaid Services Improving Medicare Post-Acute Care Transformation file. On the beneficiary level, we conducted 2 comparisons: (1) among patients who received joint replacement at CJR hospitals, ACO patients (overlap) vs not (CJR-only) and 2) among patients who received joint replacement elsewhere, ACO patients (ACO-only) vs not (neither). On the hospital level, we compared hospitals in the top quartile of overlap rate (high overlap) vs those in the bottom 3 (low overlap). RESULTS: We studied 14,519 overlap, 38,972 CJR-only, 26,872 ACO-only, and 68,945 neither beneficiaries. Compared with CJR-only patients, the overlap group was less likely to be older than 85, of black race, of low socioeconomic status, and burdened with clinical complications. Similar results were observed when the ACO-only group was compared with the neither group. Compared with low overlap hospitals, high overlap ones were more likely to be of nonprofit and less likely to be of safety net. CONCLUSION: CJR-ACO overlap is associated with differences in beneficiary and hospital characteristics, which raises key issues for providers and policymakers.

The effects of age on the severity of joint damage and intra-articular inflammation following a simulated medial meniscus injury in 3, 6, and 9 month old male rats.

Purpose: Aging is a known risk factor for osteoarthritis (OA). Several transgenic rodent models have been used to investigate the effects of accelerated or delayed aging in articular joints. However, age-effects on the progression of post-traumatic OA are less frequently evaluated. The objective of this study is to evaluate how animal age affects the severity of intra-articular inflammation and joint damage in the rat medial collateral ligament plus medial meniscus transection (MCLT+MMT) model of knee OA.Methods: Forty-eight, male Lewis rats were aged to 3, 6, or 9 months old. At each age, eight rats received either an MCLT+MMT surgery or a skin-incision. At 2 months post-surgery, intra-articular evidence of CTXII, IL1ß, IL6, TNFα, and IFNγ was evaluated using a multiplex magnetic capture technique, and histological evidence of OA was assessed via a quantitative histological scoring technique.Results: Elevated levels of CTXII and IL6 were found in MCLT+MMT knees relative to skin-incision and contralateral controls; however, animal age did not affect the severity of joint inflammation. Conversely, histological investigation of cartilage damage showed larger cartilage lesion areas, greater width of affected cartilage, and more evidence of hypertrophic cartilage damage in MCLT+MMT knees with age.Conclusions: These data indicate the severity of cartilage damage subsequent to MCLT+MMT surgery is related to the rat's age at the time of injury. However, despite greater levels of cartilage damage, the level of intra-articular inflammation was not necessarily affected in 3, 6, and 9 month old male rats.

Use of magnetic capture to identify elevated levels of CCL2 following intra-articular injection of monoiodoacetate in rats.

PURPOSE: Synovial fluid biomarkers help evaluate osteoarthritis (OA) development. Magnetic capture, our new magnetic nanoparticle-based technology, has proven to be effective for determining extracellular matrix fragment levels in two rat OA models. Here, the feasibility of magnetic capture for detecting monocyte chemoattractant protein-1 (MCP-1 or CCL2) is demonstrated after intra-articular injection of monoiodoacetate (MIA) in the rat knee. METHODS: Forty-eight male Lewis rats received a right hind limb, intra-articular injection of MIA (1 mg in 25 µl of saline) or 25 µl of saline. Magnetic capture and lavage were performed at 7 days after injection (n = 6 per treatment per procedure), with magnetic capture additionally performed at 14 and 28 days post-injection (n = 6 per treatment per time point). CCL2 was also assessed in serum. RESULTS: Serum CCL2 levels revealed no difference between MIA and saline animals (p = 0.0851). In contrast, magnetic capture and lavage detected a significant increase of CCL2 in the MIA-injected knee, with the MIA-injected knee having elevated CCL2 compared to contralateral and saline-injected knees (p = 0.00016 (contralateral) and p = 0.00016 (saline) for magnetic capture; p = 0.00023 (contralateral) and p = 0.00049 (saline) for lavage). CONCLUSIONS: Magnetic capture of CCL2 was successfully developed and applied to determine levels of CCL2 in a rat knee. Magnetic capture detected a statistically significant increase of CCL2 in MIA-injected knees compared to controls, and CCL2 levels stayed relatively stable from week 1 through week 4 post-MIA injection.

Nationwide Analysis of Resource Utilization and In-Hospital Outcomes in the Obese Patients With Lower Gastrointestinal Hemorrhage.

GOALS: The goal of this study was to evaluate the impact of obesity on the outcomes of patients with lower gastrointestinal hemorrhage (LGIH). BACKGROUND: Obesity is considered as an independent risk factor for LGIH. We sought to analyze in-hospital outcomes and characteristics of nonobese and obese patients who presented with LGIH, and further, identify resource utilization during their hospital stay. MATERIALS AND METHODS: With the use of National Inpatient Sample from January 2005 through December 2014, LGIH-related hospitalizations (age≥18 y) were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnostic codes. Patients were stratified into the nonobese and obese groups depending on their body mass index (>30 kg/m). The statistical analyses were performed using SAS 9.4. RESULTS: Of the total 482,711 patients with LGIH-related hospitalizations, 38,592 patients were found to be obese. In a propensity-matched analysis, the in-hospital mortality was higher in the nonobese patients (4.2% vs. 3.8%, P=0.004), however, the mean length of hospital stay and mean cost was higher in the obese group which could be due to a higher number of comorbidities in the obese group. Secondary outcomes such as the need for mechanical ventilation vasopressor use and colonoscopy was significantly higher in the obese group. CONCLUSIONS: The study results demonstrate that 'obesity paradox' do exist for LGIH-related hospitalizations for mortality. LGIH hospitalizations in the obese patients are associated with higher resource utilization as evidenced by the longer length of stay and higher cost of hospitalizations as compared with the nonobese patients.

Overall and Comparative Risk of Herpes Zoster With Pharmacotherapy for Inflammatory Bowel Diseases: A Nationwide Cohort Study.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) might be at increased risk for herpes zoster infection. We sought to quantify the risk of herpes zoster in patients with IBD and evaluate the effects of IBD and IBD medications on the risk of herpes zoster. METHODS: We conducted 2 retrospective studies of populations of Veterans, from January 2000 through June 2016. In study 1, we compared the incidence of herpes zoster among patients with IBD receiving 5-ASA alone vs matched patients without IBD. In study 2, we compared the incidence of herpes zoster among patients with IBD treated with only 5-ASA, with thiopurines, with antagonists of tumor necrosis factor (TNF), with a combination of thiopurines and TNF antagonists, and with vedolizumab. We used multivariable Cox regression to estimate the hazard ratios and 95% CIs for herpes zoster associated with IBD in study 1 and with different treatments in study 2. We also estimated the incidence rate of herpes zoster based on age and IBD medication subgroups. RESULTS: Compared to no IBD, ulcerative colitis (UC) and Crohn's disease (CD) were each associated with significantly increased risk of herpes zoster infection. In multivariable Cox regression (compared to no IBD), UC, CD, or IBD treated with 5-ASA treatment alone was associated with significantly increased risk of herpes zoster, with adjusted HRs (AHR) of 1.81 for UC (95% CI, 1.56-2.11), 1.56 for CD (95% CI, 1.28-1.91), and 1.72 for treated IBD (95% CI, 1.51-1.96). In multivariable Cox regression analysis, compared to exposure to 5-ASA alone, exposure to thiopurines (AHR, 1.47; 95% CI, 1.31-1.65) or a combination of thiopurines and TNF antagonists (AHR, 1.65; 95% CI, 1.22-2.23) was associated with increased risk of herpes zoster. However, exposure to TNF antagonists alone (AHR, 1.15; 95% CI, 0.96-1.38) was not associated with increased risk of herpes zoster. The incidence rates of herpes zoster in all age groups and all IBD medication subgroups were substantially higher than that in the oldest group of patients without IBD (older than 60 years). CONCLUSIONS: In 2 retrospective studies of Veteran populations, we associated IBD and treatment with thiopurines, alone or in combination with TNF antagonists, with increased risk of herpes zoster. With the approval of a new and potentially safer vaccine for herpes zoster, the effects of immunization of patients with IBD should be investigated.