Thorntonellison5017

RNA methylation throughout mammalian advancement and also cancer.

Splicing factor variations inside hematologic malignancies.

The development of tools, specifically designed to assess capacity of DVSPs to serve LGBTQ survivors, is a unique contribution as no tools existed to do so. The common capacity-building needs and data-informed recommendations identified provide a starting point for agencies expanding into LGBTQ-focused work, who may not have the benefit of grant funding, tools, or evaluators to assist. Our findings, lessons learned, and tools may be used by agencies to evaluate and inform their own practices, thereby creating safer, more affirming agencies that are capable provide effective care to meet unique needs of LGBTQ survivors.

Level V.

Level V.

For better treatment outcome, exploring the knowledge of glaucoma and practices among glaucomatous patients is much more important.

The aimed of this study was to determine the knowledge and self-care practice and their associated factors towards glaucoma and its medications among glaucoma patients.

Cross section design study was conducted between May and July, 2017. The data was collected from glaucoma patients. Descriptive statistics was done to summarize socio demography data and associated factors with good knowledge and good practice were determined using binary logistic regression. Statistically significant variables were generated by considering p-value < 0.05.

A total of 360 glaucoma patients were participated in this survey. The median age of the participant was 65 years. About 177 (49.25%) (95%CI 43.9, 54.4) had good knowledge and a total of 197 or 54.7% (95%CI 49.4, 59.7) had good practice about glaucoma and its medical treatments. The factors such as residence, marital status, educational status and stages of glaucoma of study participants were independently associated with having good knowledge. With respect to practice, educational status, duration of glaucoma, laterality and frequency of follow up were significantly associated with practice status of study participants.

In this study among glaucoma patients in a tertiary hospital, only half of patients have good knowledge about the disease and good practice pattern. Those with urban residence, higher education status and advanced stage of glaucoma were more likely to have good knowledge.

In this study among glaucoma patients in a tertiary hospital, only half of patients have good knowledge about the disease and good practice pattern. Those with urban residence, higher education status and advanced stage of glaucoma were more likely to have good knowledge.

The transradial approach (TRA) for endovascular procedures has become a frequent practice in neurointervention. Advantages of the TRA include less access-site complications, early ambulation, and less postprocedural pain. The Rist 079 radial access guide catheter (Medtronic) is the first device designed specifically for neurointerventions performed through the TRA. In this study, we report our initial experience with the Rist catheter in a variety of neurointerventional procedures, aiming to evaluate the performance of this device and discuss its limitations.

A prospectively maintained database was retrospectively searched to identify patients who underwent procedures using the Rist catheter. Information on demographics, procedural details, and complications was recorded.

Seventy-eight patients were included in the study, with a mean age of 60.3 years (range, 25-92 years); 45 (57.7%) were men. The interventional or diagnostic procedure was successfully completed in 77 patients (98.7%). The radial artery was the primary access-site choice in 71 patients (91%). The most frequent type of procedures performed were coiling or stent-assisted coiling (16.7%) and angioplasty and stenting (16.7%), followed by middle meningeal artery embolization (14.1%). Crossover to femoral artery access while maintaining use of the Rist was done in 5 cases (6.4%). Reasons for access or procedural failure included anatomical anomaly of the target vessel, unfavorable geometry of the great vessels, and proximal tortuosity of the supra-aortic vessels.

We demonstrated a high success rate with use of the Rist catheter system for a variety of procedures.

We demonstrated a high success rate with use of the Rist catheter system for a variety of procedures.Access to real-time glucose data in real time allows users to make informed decisions about their insulin dosages, appropriate carbohydrate intake, exercise, and other health behaviors. Programmable alarms and alerts warn users about current and/or impending acute glycemic events. However, the value and utility of retrospective data analysis for clinical decision-making have gone mostly unrecognized. This article presents a series of patient case examples that illustrate how our use of retrospective data enables us to identify and effectively address patterns of problematic glycemia.The possible role of the naturally occurring deuterium in the regulation of cell division was first described in the 1990s. To investigate the mechanism of influence of deuterium (D) on cell growth, expression of 236 cancer-related and 536 kinase genes were tested in deuterium-depleted (40 and 80 ppm) and deuterium-enriched (300 ppm) media compared to natural D level (150 ppm). Among genes with expression changes exceeding 30% and copy numbers over 30 (124 and 135 genes, respectively) 97.3% of them was upregulated at 300 ppm D-concentration. In mice exposed to chemical carcinogen, one-year survival data showed that deuterium-depleted water (DDW) with 30 ppm D as drinking water prevented tumor development. One quarter of the treated male mice survived 344 days, the females 334 days, while one quarter of the control mice survived only 188 and 156 days, respectively. In our human retrospective study 204 previously treated cancer patients with disease in remission, who consumed DDW, were followed. Cumulative follow-up time was 1024 years, and average follow-up time per patient, 5 years (median 3.6 years). One hundred and fifty-six patients out of 204 (77.9%) did not relapse during their 803 years cumulative follow-up time. Median survival time (MST) was not calculable due to the extremely low death rate (11 cancer-related deaths, 5.4% of the study population). Importantly, 8 out of 11 deaths occurred several years after stopping DDW consumption, confirming that regular consumption of DDW can prevent recurrence of cancer. These findings point to the likely mechanism in which consumption of DDW keeps D-concentration below natural levels, preventing the D/H ratio from increasing to the threshold required for cell division. This in turn can serve as a key to reduce the relapse rate of cancer patients and/or to reduce cancer incidence in healthy populations.

The purpose of this systematic review is to identify whether non-salvage procedures can provide satisfactory and acceptable outcomes in Lichtman stage IV disease.

The MEDLINE, Embase, and Cochrane databases were systematically searched for English publications between 1989 and 2019 that reported stage IV-specific primary treatment outcomes. Revisions and skeletally immature patients were excluded. Data extracted were patient demographics, pain scores, range of motion (ROM), grip strength, and patient-reported outcome measures (PROMs). The results were pooled into 3 categories conservative management, non-salvage, and salvage procedures.

Data from 24 studies (n = 114 patients) were extracted. Compared with conservative management and non-salvage treatment (joint-leveling radial osteotomies, lunate reconstruction), salvage procedures (intercarpal and radiocarpal arthrodesis, proximal row carpectomy, total wrist arthroplasty) showed significantly decreased ROM in flexion-extension arc of motion (89° vs 95° vs 73°, respectively,

= .0001) and no significant differences in grip strength as a percentage of the contralateral side (83% vs 86% vs 79%, respectively,

= .28). All reported treatments provided pain relief, ability to return to previous occupations, and variable PROMs.

In young, active, and labor-intensive patients, motion-preserving, non-salvage options may be worth trialing as they do not preclude future salvage options.

In young, active, and labor-intensive patients, motion-preserving, non-salvage options may be worth trialing as they do not preclude future salvage options.Background The pathophysiological mechanism behind adverse outcomes associated with ischemia-inducing epicardial coronary stenoses and microcirculatory dysfunction remains unclear. Wall shear stress (WSS) plays an important role in atherosclerotic plaque progression and vulnerability. We aimed to evaluate the relationship between WSS, functionally significant epicardial coronary stenoses, and microcirculatory dysfunction. Methods and Results Patients undergoing invasive coronary physiology testing were included. Fractional flow reserve, instantaneous wave-free ratio, and the index of microcirculatory resistance were measured. Quantitative coronary angiography was used to obtain the lesion percentage diameter stenosis. Computational fluid dynamics analysis was performed to calculate WSS parameters. Multiple regression analysis was performed to calculate the standardized regression coefficient (β) for the coronary physiology indices. A total of 107 vessels from 88 patients were included. Fractional flow reserve independently predicted the total area of low WSS (β=-0.44; 95% CI, -0.62 to -0.25; P less then 0.001) and maximum lesion WSS (β=-0.53; 95% CI, -0.70 to -0.36; P less then 0.001) after adjusting for percentage diameter stenosis and index of microcirculatory resistance. Similarly, instantaneous wave-free ratio also independently predicted the total area of low WSS (β=-0.45; 95% CI, -0.62 to -0.28; P less then 0.001) and maximum lesion WSS (β=-0.58; 95% CI, -0.73 to -0.43; P less then 0.001). The index of microcirculatory resistance did not predict either low or high WSS. Conclusions Fractional flow reserve and instantaneous wave-free ratio independently predicted the total burden of low WSS and maximum lesion WSS in coronary arteries. No relationship was found between microcirculatory dysfunction and WSS.Breast cancer is a malignant tumor, which has derived from cells of the breast. Further, a relatively rapid metastasis, and resistance development against all the conventional drug combinations are major clinical issues in breast cancer patients as well as limitations like toxicity, genetic mutation, and metastasis make difficult the use of conventional therapy methods such as chemotherapy, radiotherapy, and local surgery. Therefore, considering the urgent needs, and high death rate in breast cancer cases, the development of new diagnosis and treatment regimens which diagnosed at the early stage and protected normal tissues required for clinical applications. Recently, the combination of tumor diagnosis and treatment within a single platform is a novel perspective, and magnetic nanoparticles are potential candidate owing to their low toxic effect, biocompatibility, biological degradability, superior magnetic properties, and targeting ability to overcome the problems of conventional diagnosis and therapy techn-conjugated magnetic PS-Agsbox nanoparticles were also confirmed.Traumatic heterotopic ossification (THO) is a serious and common clinical post-traumatic complication for which there is no effective and safe drug treatment. Routine administration of nonsteroidal anti-inflammatory drugs (NSAIDs) after injury is extensively used approach for THO. However, serious adverse events can occur in the event of an overdose of NSAIDs. In our study, we have developed a poly(lactic acid-co-glycolic acid) (PLGA) microsphere by emulsifying solvent volatilization for the prolonged slow delivery of celecoxib (CLX). Three groups of celecoxib-poly(lactic acid-co-glycolic acid) microspheres (CLX-PLGA MPs) were prepared with particle sizes of 3.75±1.28 μm, 49.56±17.15 μm, and 94.98±42.53 μm. Meanwhile, related parameters of microspheres in each group were studied drug loading (DL), encapsulation rate (EE), and slow-release behavior. The DL and EE of the 3 CLX-PLGA MPs did not vary significantly, and subsequently, we selected the second drug loading microspheres with a retardation period of about 70 days for subsequent experiments. Moreover, cellular and animal experiments suggest that the microspheres are biocompatible and can be safely applied to localized trauma tissue. Finally, it is demonstrated that CLX-PLGA MPs have an effect on inhibiting the osteogenic differentiation of bone marrow mesenchymal stem cells and have the potential to inhibit ectopic bone formation of the THO model in Sprague-Dawley rat. Therefore, this study suggests that CLX-PLGA MPs are expected to be applied topically in the early post-traumatic period to prevent the development of THO.Osteosarcoma (OS) is the most common primary malignant bone tumor, which usually occurs in children and adolescents. It is generally a high-grade malignancy presenting with extreme metastases to the lungs or other bones. The etiology of the disease is multifaceted and still remains obscure. A combination of surgery and chemotherapy has played a major role in the treatment of OS over the past three decades, and consequently, the overall survival rates for the disease have remained unchanged. Therefore, there is an urgent need to employ new comprehensive analyses and technologies to develop significantly more informative classification systems, with the aim of developing more effective and less toxic therapies for OS patients. This review discusses the existing knowledge of OS therapy and potential methods to develop novel therapeutic agents for the disease.

To explore the current literature for effects of oral nutritional supplement on wound healing rates in humans.

A systematic review of the literature was performed using the Medline and PubMed database following PRISMA guidelines. The PubMed database was searched using terms relating to oral nutritional supplement and wound healing from 1837 to March 2020. Study inclusion criteria were (i) design randomized controlled trials, clinical studies, observational studies, clinical trials; (ii) population adults; and (iii) intervention oral nutritional supplement.

The search yielded 2433 studies, 313 of which were clinical trials or clinical studies. After abstract review, 28 studies qualified to be included in the review evaluating the following supplementation categories on wound healing protein and amino acids (10), mineral, vitamin and antioxidants (9), probiotics (1), and mixed nutrients (8). Arginine and omega-3 supplement were shown to improve wound healing in head and neck cancer patients with surgical wounds by decreasing incidence of postoperative complications and reducing length of hospital stay. EGFR inhibitors list Mineral, vitamins, and antioxidants enriched supplements were more beneficial in increasing wound healing than non-enriched protein supplement for diabetic foot and pressure ulcers.

Supplementation of a variety of nutrients had variable effects on improving wound healing in different types of wounds. However, further research on the impact of nutritional supplements on surgical wound healing is necessary. The impact of multiple nutrient formulations may also need to be further evaluated for efficacy.

Supplementation of a variety of nutrients had variable effects on improving wound healing in different types of wounds. However, further research on the impact of nutritional supplements on surgical wound healing is necessary. The impact of multiple nutrient formulations may also need to be further evaluated for efficacy.Background One-quarter of all strokes are subsequent events. It is not known whether higher levels of blood glucose are associated with an increased risk of subsequent stroke after high-risk transient ischemic attack or minor ischemic stroke. Methods and Results We performed a secondary analysis of the POINT (Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial to evaluate the relationship between serum glucose hyperglycemia (≥180 mg/dL) versus normoglycemia ( less then 180 mg/dL) before enrollment in the trial and outcomes at 90 days. The primary end point was subsequent ischemic stroke modeled by a multivariable Cox model with adjustment for age, sex, race, ethnicity, study treatment assignment, index event, and key comorbidities. Of 4878 patients included in this study, 267 had a recurrent stroke. There was a higher hazard of subsequent stroke in patients with hyperglycemia compared with normoglycemia (adjusted hazard ratio [HR], 1.50 [95% CI, 1.05-2.14]). Treatment with dual antiplatelet therapy was not associated with a reduced hazard of subsequent stroke in patients with hyperglycemia (HR, 1.18 [95% CI, 0.69-2.03]), though the wide confidence interval does not exclude a treatment effect. When modeled as a continuous variable, there was evidence of a nonlinear association between serum glucose and the hazard of subsequent stroke (P less then 0.001). Conclusions Hyperglycemia on presentation is associated with an increased risk of subsequent ischemic stroke after high-risk transient ischemic attack or minor stroke. A rapid, simple assay of serum glucose may be a useful biomarker to identify patients at particularly high risk of subsequent ischemic stroke. Registration URL https//www.clinicaltrials.gov; Unique identifier NCT0099102.

Large-diameter metal-on-metal (MoM) total hip arthroplasty (THA) has demonstrated unexpected high failure rates and pseudotumour formation. The purpose of this prospective cohort study is to report ten-year results in order to establish revision rate, prevalence of pseudotumour formation, and relation with whole blood cobalt levels.

All patients were recalled according to the guidelines of the Dutch Orthopaedic Association. They underwent clinical and radiographical assessments (x-ray and CT scan) of the hip prosthesis and whole blood cobalt ion measurements. Overall, 94 patients (95 hips) fulfilled our requirements for a minimum ten-year follow-up.

Mean follow-up was 10.9 years (10 to 12), with a cumulative survival rate of 82.4%. Reason for revision was predominantly pseudotumour formation (68%), apart from loosening, pain, infection, and osteolysis. The prevalence of pseudotumour formation around the prostheses was 41%, while our previous report of this cohort (with a mean follow-up of 3.6 years) revvision rates are high, with the main reason being the sequelae of pseudotumour formation, which were rarely observed after five years of implantation. Blood ion measurements show limited discriminatory capacity in diagnosing pseudotumour formation. Our results evidence that an early comprehensive follow-up strategy is essential for MoM THA to promptly identify and manage early complications and revise on time. After ten years follow-up, we do not recommend continuing routine CT scanning or whole cobalt blood measurements, but instead enrolling these patients in routine follow-up protocols for THA. Cite this article Bone Jt Open 2022;3(1)61-67.Background Patients resuscitated from out-of-hospital circulatory arrest (OHCA) frequently have cardiopulmonary resuscitation injuries identifiable by computed tomography, although the prevalence, types of injury, and effects on clinical outcomes are poorly characterized. Methods and Results We assessed the prevalence of resuscitation-associated injuries in a prospective, observational study of a head-to-pelvis sudden-death computed tomography scan within 6 hours of successful OHCA resuscitation. Primary outcomes included total injuries and time-critical injuries (such as organ laceration). Exploratory outcomes were injury associations with mechanical cardiopulmonary resuscitation and survival to discharge. Among 104 patients with OHCA (age 56±15 years, 30% women), 58% had bystander cardiopulmonary resuscitation, and total cardiopulmonary resuscitation time was 15±11 minutes. The prevalence of resuscitation-associated injury was high (81%), including 15 patients (14%) with time-critical findings. Patients with resuscitation injury were older (58±15 versus 46±13 years; P less then 0.001), but had otherwise similar baseline characteristics and survival compared with those without. Mechanical chest compression systems (27%) had more frequent sternal fractures (36% versus 12%; P=0.009), including displaced fractures (18% versus 1%; P=0.005), but no difference in survival (46% versus 41%; P=0.66). Conclusions In patients resuscitated from OHCA, head-to-pelvis sudden-death computed tomography identified resuscitation injuries in most patients, with nearly 1 in 7 with time-critical complications, and one-half with extensive rib-cage injuries. These data suggest that sudden-death computed tomography may have additional diagnostic utility and treatment implications beyond evaluating causes of OHCA. These important findings need to also be taken in context of the certain fatal outcome without resuscitation efforts. Registration URL https//www.clinicaltrials.gov; Unique identifier NCT03111043.Background The 2018 European Society of Cardiology/European Society of Hypertension arterial hypertension guidelines do not recommend routine carotid ultrasound as a tool to identify hypertension-mediated organ damage, unless clinically indicated. However, carotid plaque (CP) is a strong correlate of increased arterial stiffness, which influences blood pressure (BP) control over time. Thus, we assessed whether evidence of CP at first visit could predict BP control during follow-up. Methods and Results From the CSN (Campania Salute Network) Registry, 6684 patients with hypertension had complete carotid ultrasound examination and were categorized by the presence of CP at baseline. Optimal BP control was defined as average BP less then 140/90 mm Hg and less then 135/85 during follow-up for office and home BP, respectively. At baseline, participants with CP (n=3061) were more likely to be men, to be older, to have diabetes, and to exhibit higher systolic BP, lower diastolic BP, worse lipid profile, and higher prevalence of left ventricular hypertrophy (all P less then 0.0001) than patients without CP. Optimal office BP control was adjudicated in 54% with and 62% without CP (P less then 0.0001), and optimal home BP in 51% with and 58% without CP (P less then 0.01). Presence of CP was significantly associated with the reduced probability of controlled office BP during follow-up (both P less then 0.0001), independently of significant effect of older age, male sex, higher baseline BP values, classes of medication, and presence of left ventricular hypertrophy, and only attenuated by duration of hypertension. EGFR inhibitors list Conclusions Presence of CP in treated patients with hypertension is associated with suboptimal BP control during follow-up, independently of worse metabolic profile and presence of left ventricular hypertrophy.Aim To assess homologous recombination repair mutation (HRRm) testing patterns in metastatic castration-resistant prostate cancer. Methods A point-in-time, international survey conducted January-August 2020. Results Three-quarters of physicians (oncologists, urologists, specialist surgeons) globally reported access to genetic/genomic testing and just over half were HRRm testers. Surveyed physicians reported HRRm testing and positivity rates for 1913 patients, which were 18.1% and 33.7%, respectively. Of patients tested (n = 347), the most common HRR genes tested were BRCA (91.6%) and ATM (47.3%). Conclusion Overall testing rates were low, with physicians mostly testing patients they considered higher risk. Increased awareness and education are needed to encourage broader testing, to understand familial risk and to identify patients with worse outcomes or those eligible for life-prolonging treatments.Despite the improved understanding of the molecular and genetic heterogeneity of glioblastoma, there is still an unmet need for better therapeutics, as treatment approaches have remained unchanged in recent years. Research into the role of the immune microenvironment has generated enthusiasm for testing immunotherapy (specifically, immune checkpoint inhibitors). However, to date, trials of immunotherapy in glioblastoma have not demonstrated a survival advantage. Combination approaches aimed at optimally inducing response to immune checkpoint inhibitors with radiotherapy are currently being investigated. Herein, the authors describe their experience of the potential benefit and clinical outcomes of using combination pembrolizumab (an immune checkpoint inhibitor) and laser interstitial thermal therapy in a case series of patients with recurrent IDH-wild-type glioblastoma.Hereditary pulmonary alveolar proteinosis (hPAP) is a rare disorder caused by recessive mutations in GM-CSF receptor subunit α/β genes (CSF2RA/CSF2RB, respectively) characterized by impaired GM-CSF-dependent surfactant clearance by alveolar macrophages (AMs) resulting in alveolar surfactant accumulation and hypoxemic respiratory failure. Because hPAP is caused by CSF2RA mutations in most patients, we created an animal model of hPAP caused by Csf2ra gene disruption (Csf2ra-/- mice) and evaluated the effects on AMs and lungs. Macrophages from Csf2ra-/- mice were unable to bind and clear GM-CSF, did not exhibit GM-CSF signaling, and had functional defects in phagocytosis, cholesterol clearance, and surfactant clearance. Csf2ra-/- mice developed a time-dependent, progressive lung disease similar to hPAP in children caused by CSF2RA mutations with respect to the clinical, physiological, histopathological, biochemical abnormalities, biomarkers of PAP lung disease, and clinical course. In contrast, Csf2ra+/- mice had functionally normal AMs and no lung disease. Pulmonary macrophage transplantation (PMT) without myeloablation resulted in long-term engraftment, restoration of GM-CSF responsiveness to AMs, and a safe and durable treatment effect that lasted for the duration of the experiment (6 mo). Results demonstrate that homozygous (but not heterozygous) Csf2ra gene ablation caused hPAP identical to hPAP in children with CSF2RA mutations, identified AMs as the cellular site of hPAP pathogenesis in Csf2ra-/- mice, and have implications for preclinical studies supporting the translation of PMT as therapy of hPAP in humans.Background In multisystem inflammatory syndrome in children, there is paucity of longitudinal data on cardiac outcomes. We analyzed cardiac outcomes 3 to 4 months after initial presentation using echocardiography and cardiac magnetic resonance imaging. Methods and Results We included 60 controls and 60 cases of multisystem inflammatory syndrome in children. Conventional echocardiograms and deformation parameters were analyzed at 4 time points (1) acute phase (n=60), (2) subacute phase (n=50; median, 3 days after initial echocardiography), (3) 1-month follow-up (n=39; median, 22 days), and (4) 3- to 4-month follow-up (n=25; median, 91 days). Fourteen consecutive cardiac magnetic resonance imaging studies were reviewed for myocardial edema or fibrosis during subacute (n=5) and follow-up (n=9) stages. In acute phase, myocardial injury was defined as troponin-I level ≥0.09 ng/mL (>3 times normal) or brain-type natriuretic peptide >800 pg/mL. All deformation parameters, including left ventricular global longitudinal strain, peak left atrial strain, longitudinal early diastolic strain rate, and right ventricular free wall strain, recovered quickly within the first week, followed by continued improvement and complete normalization by 3 months. Median time to normalization of both global longitudinal strain and left atrial strain was 6 days (95% CI, 3-9 days). Myocardial injury at presentation (70% of multisystem inflammatory syndrome in children cases) did not affect short-term outcomes. Four patients (7%) had small coronary aneurysms at presentation, all of which resolved. Only 1 of 9 patients had residual edema but no fibrosis by cardiac magnetic resonance imaging. Conclusions Our short-term study suggests that functional recovery and coronary outcomes are good in multisystem inflammatory syndrome in children. Use of sensitive deformation parameters provides further reassurance that there is no persistent subclinical dysfunction after 3 months.After Roux-en-Y gastric bypass (RYGB), rats consume less high-energy foods and fluids, though whether this reflects a concomitant change in palatability remains unclear. By measuring behavior during intraorally delivered liquid meals across days (1 water, 8 sucrose sessions), we showed that RYGB rats (RYGB, n = 8/sex) consumed less 1.0 M sucrose than their sham surgery counterparts (SHAM, n = 8 males, n = 11 females) but displayed similarly high levels of ingestive taste reactivity responses at the start of infusions. Relative to water, both groups increased intake of sucrose, and ingestive responses were dominated by tongue protrusions rather than mouth movements. Thus, RYGB animals still found sucrose palatable despite consuming less than the SHAM group. As the intraoral infusion progressed but before meal termination, aversive behavior remained low and both RYGB and SHAM animals showed fewer ingestive responses, predominantly mouth movements as opposed to tongue protrusions. This shift in responsiveness unrelated to surgical manipulation suggests negative alliesthesia, or a decreased palatability, as rats approach satiation. link2 Notably, only in RYGB rats, across sessions, there was a striking emergence of aversive behavior immediately after the sucrose meal. Thus, although lower intake in RYGB rats seems independent of the hedonic taste properties of sucrose, taste reactivity behavior in these animals immediately after termination of a liquid meal appears to be influenced by postoral events and reflects a state of nimiety or excessive consumption. Measurement of taste reactivity behaviors during an intraorally delivered meal represents a promising way to make inferences about internal state in nonverbal preclinical models.The PROMETCO study is collecting real-world data on metastatic colorectal cancer (mCRC) patients with two progressions. This international, prospective, longitudinal, observational cohort study is collecting data on mCRC patients with two disease progressions since diagnosis and receiving subsequent treatment. Objectives include overall survival, treatment patterns, effectiveness and safety and patient-reported outcomes using the EuroQol 5-level, 5-dimensional questionnaire, the Brief Fatigue Inventory and a modified version of the ACCEPTance by the Patients of their Treatment (ACCEPT©) questionnaire. Data are collected retrospectively and prospectively up to 18 months. As of 13 October 2021, 544 patients from 18 countries had been enrolled. To the authors' knowledge, PROMETCO is the first international, real-world study of the continuum of care of mCRC patients in this setting. Trial registration number NCT03935763 (ClinicalTrials.gov).Anorexia nervosa (AN) is a debilitating eating disorder characterized by severely restricted eating and significant body weight loss. In addition, many individuals also report engaging in excessive exercise. Previous research using the activity-based anorexia (ABA) model has implicated the hypothalamic proopiomelanocortin (POMC) system. Using the ABA model, Pomc mRNA has been shown to be transiently elevated in both male and female rodents undergoing ABA. In addition, the POMC peptide β-endorphin appears to contribute to food anticipatory activity (FAA), a characteristic of ABA, as both deletion and antagonism of the µ opioid receptor (MOR) that β-endorphin targets, results in decreased FAA. The role of β-endorphin in reduced food intake in ABA is unknown and POMC neurons release multiple transmitters in addition to β-endorphin. In the current study, we set out to determine whether targeted inhibition of POMC neurons themselves rather than their peptide products would lessen the severity of ABA. Inhibition of POMC neurons during ABA via chemogenetic Designer Receptors Exclusively Activated by Designer Drugs (DREADD) technology resulted in reduced FAA in both male and female mice with no significant changes in body weight or food intake. The selective reduction in FAA persisted even in the face of concurrent chemogenetic inhibition of additional cell types in the hypothalamic arcuate nucleus. The results suggest that POMC neurons could be contributing preferentially to excessive exercise habits in patients with AN. Furthermore, the results also suggest that metabolic control during ABA appears to take place via a POMC neuron-independent mechanism.Background Obesity is an established cardiovascular risk factor in patients with hypertrophic cardiomyopathy. Postoperative atrial fibrillation (POAF) is one of the most common complications after surgery in patients with obstructive hypertrophic cardiomyopathy (OHCM). We aimed to determine the impact of body mass index (BMI) on the occurrence of POAF in patients with OHCM who underwent septal myectomy. Methods and Results In all, 712 OHCM patients without previous atrial fibrillation who underwent septal myectomy were identified. Patients were stratified into 3 groups based on BMI. Of these, 224 (31.5%) had normal weight (BMI less then 24 kg/m2), 339 (47.6%) were overweight (BMI, 24 to less then 28 kg/m2), and 149 (20.9%) were obese (BMI≥28 kg/m2). Overweight and obese patients had increased levels of left atrial diameter (P less then 0.001) and left ventricular end-diastolic diameter (P less then 0.001), compared with patients with normal weight. Among 184 patients (25.8%) developing POAF, 32 cases (14.3%) occurred in the normal weight group, 100 cases (29.5%) occurred in the overweight group, and 52 cases (34.9%) occurred in the obese group (P less then 0.001). Logistic regression analysis indicated that overweight (odds ratio [OR] 2.161, 95% CI, 1.333-3.503; P=0.002) or obesity (OR, 2.803; 95% CI, 1.589-4.944; P less then 0.001), age (OR, 1.037; 95% CI, 1.018-1.057; P less then 0.001), and left atrial diameter (OR, 1.060; 95% CI, 1.027-1.095; P less then 0.001) were independently associated with the occurrence of POAF in patients with OHCM. Conclusions Overweight and obesity are strong predictors of POAF in patients with OHCM. Strategies aimed at lowering BMI may be a potential way to prevent POAF.Gastrointestinal complaints are often reported during ascents to high altitude (>2,500 m), though their etiology is not known. One potential explanation is injury to the intestinal barrier which has been implicated in the pathophysiology of several diseases. High-altitude exposures can reduce splanchnic perfusion and blood oxygen levels causing hypoxic and oxidative stress. These stressors might injure the intestinal barrier leading to consequences such as bacterial translocation and local/systemic inflammatory responses. The purpose of this mini-review is to 1) discuss the impact of high-altitude exposures on intestinal barrier dysfunction and 2) present medications and dietary supplements which may have relevant impacts on the intestinal barrier during high-altitude exposures. There is a small but growing body of evidence which shows that acute exposures to high altitudes can damage the intestinal barrier. Initial data also suggest that prolonged hypoxic exposures can compromise the intestinal barrier through alterations in immunological function, microbiota, or mucosal layers. Exertion may worsen high-altitude-related intestinal injury via additional reductions in splanchnic circulation and greater hypoxemia. Collectively these responses can result in increased intestinal permeability and bacterial translocation causing local and systemic inflammation. More research is needed to determine the impact of various medications and dietary supplements on the intestinal barrier during high-altitude exposures.Exposure to maternal diabetes is increasingly recognized as a risk factor for chronic respiratory disease in children. It is currently unclear; however, whether maternal diabetes affects the lung health of male and female offspring equally. This study characterizes the sex-specific impact of a murine model of diet-induced gestational diabetes (GDM) on offspring lung function and airway inflammation. Female adult mice are fed a high-fat (45% kcal) diet for 6 wk prior to mating. Control offspring are from mothers fed a low-fat (10% kcal) diet. Offspring were weaned and fed a chow diet until 10 wk of age, at which point lung function was measured and lung lavage was collected. Male, but not female, offspring exposed to GDM had increased lung compliance and reduced lung resistance at baseline. link= EGFR inhibitors list Female offspring exposed to GDM displayed increased methacholine reactivity and elevated levels of proinflammatory cytokines [e.g., interleukin (IL)-1β, IL-5, and CXCL1] in lung lavage. Female GDM offspring also displayed elevated abundance of matrix metalloproteinases (MMP) within their airways, namely, MMP-3 and MMP-8. These results indicate disparate effects of maternal diabetes on lung health and airway inflammation of male and female offspring exposed to GDM. Female mice may be at greater risk of inflammatory lung conditions, such as asthma, whereas male offspring display changes that more closely align with models of chronic obstructive pulmonary disease. In conclusion, there are important sex-based differences in the impact of maternal diabetes on offspring lung health that could signal differences in future disease risk.Background This study was conducted to compare frequencies of chronic brain infarctions (CBIs) and white matter hyperintensities (WMHs) as well as their associations with established early recurrence risk scores in patients with transient ischemic attack (TIA) and stroke mimics compared with ischemic stroke. Methods and Results Single-center cohort study including consecutive patients with TIA, stroke mimics, and acute ischemic stroke, with available magnetic resonance imaging from January 2015 to December 2017. Blinded raters adjudicated WMH (age-related white matter changes score) and CBI according to established definitions. A total of 2112 patients (median [Q1-Q3] age 71 [59-80] years, 43% women, National Institutes of Health Stroke Scale score of 2 [1-7], 80% ischemic stroke, 18% TIA, 2% stroke mimics) were included. While CBIs were present in only 10% of patients with stroke mimic, they were detected in 28% of TIAs and 38% of ischemic strokes (P less then 0.001). WMHs were less pronounced (0, 0-1) in paBackground Despite optimized medical management and techniques of primary percutaneous coronary intervention, a substantial proportion of patients with ST-segment-elevation myocardial infarction (STEMI) display significant microvascular damage. Thrombotic microvascular obstruction (MVO) has been implicated in the pathogenesis of microvascular and subsequent myocardial damage attributed to distal embolization and microvascular platelet plugging. However, there are only scarce data regarding the effect of platelet reactivity on MVO. Methods and Results We prospectively evaluated 105 patients in 2 distinct periods (2012-2013 and 2016-2018) who presented with first ST-segment-elevation myocardial infarction and underwent primary percutaneous coronary intervention. All patients were treated with dual antiplatelet therapy (DAPT). Blood samples were analyzed for platelet reactivity, and cardiac magnetic resonance imaging scans were evaluated for late gadolinium enhancement and MVO. DAPT suboptimal response was definoth myocardial and microvascular damage.

The aim of this study is to define a core outcome set (COS) to allow consistency in outcome reporting amongst studies investigating the management of orthopaedic treatment in children with spinal dysraphism (SD).

Relevant outcomes will be identified in a four-stage process from both the literature and key stakeholders (patients, their families, and clinical professionals). Previous outcomes used in clinical studies will be identified through a systematic review of the literature, and each outcome will be assigned to one of the five core areas, defined by the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT). Additional possible outcomes will be identified through consultation with patients affected by SD and their families.

Outcomes identified in these stages will be included in a two-round Delphi process that will involve key stakeholders in the management of SD. A final list including the identified outcomes will then be summarized in a consensus meeting attended by representatives ofcal trials, thereby assisting complex decision-making in the clinical management of these children. Cite this article Bone Jt Open 2022;3(1)54-60.Treatment with mineralocorticoid receptor (MR) antagonists beginning at the outset of disease, or early thereafter, prevents pulmonary vascular remodeling in preclinical models of pulmonary arterial hypertension (PAH). However, the efficacy of MR blockade in established disease, a more clinically relevant condition, remains unknown. link3 Therefore, we investigated the effectiveness of two MR antagonists, eplerenone (EPL) and spironolactone (SPL), after the development of severe right ventricular (RV) dysfunction in the rat SU5416-hypoxia (SuHx) PAH model. Cardiac magnetic resonance imaging (MRI) in SuHx rats at the end of week 5, before study treatment, confirmed features of established disease including reduced RV ejection fraction and RV hypertrophy, pronounced septal flattening with impaired left ventricular filling and reduced cardiac index. Five weeks of treatment with either EPL or SPL improved left ventricular filling and prevented the further decline in cardiac index compared with placebo. Interventricular septal displacement was reduced by EPL whereas SPL effects were similar, but not significant. Although MR antagonists did not significantly reduce pulmonary artery pressure or vessel remodeling in SuHx rats with established disease, animals with higher drug levels had lower pulmonary pressures. Consistent with effects on cardiac function, EPL treatment tended to suppress MR and proinflammatory gene induction in the RV. In conclusion, MR antagonist treatment led to modest, but consistent beneficial effects on interventricular dependence after the onset of significant RV dysfunction in the SuHx PAH model. These results suggest that measures of RV structure and/or function may be useful endpoints in clinical trials of MR antagonists in patients with PAH.Lymphatic anomalies comprise a spectrum of disorders ranging from common localized microcystic and macrocystic lymphatic malformations (LMs) to rare complex lymphatic anomalies, including generalized lymphatic anomaly, Kaposiform lymph-angiomatosis, central conducting lymphatic anomaly, and Gorham-Stout disease. Imaging diagnosis of cystic LMs is generally straightforward, but complex lymphatic anomalies, particularly those with multiorgan involvement or diffuse disease, may be more challenging to diagnose. Complex lymphatic anomalies are rare but associated with high morbidity. Imaging plays an important role in their diagnosis, and radiologists may be the first clinicians to suggest the diagnosis. Furthermore, radiologists are regularly involved in management given the frequent need for image-guided interventions. For these reasons, it is crucial for radiologists to be familiar with the spectrum of entities comprising complex lymphatic anomalies and their typical imaging findings. In this article, we review the imaging findings of lymphatic anomalies, including LMs and complex lymphatic anomalies. We discuss characteristic imaging findings, multimodality imaging techniques used for evaluation, pearls and pitfalls in diagnosis, and potential complications. We also review recently discovered genetic changes underlying lymphatic anomaly development and the advent of new molecularly targeted therapies.BACKGROUND. The 2019 WHO classification of digestive system tumors separates neuroendocrine neoplasms (NENs) into neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs), which are considered to represent pathologically distinct entities warranting different management approaches. Dual-layer spectral-detector CT (DLCT) may aid their differentiation through specific material decomposition. OBJECTIVE. The purpose of this study was to assess the utility of quantitative metrics derived from DLCT for the differentiation of pancreatic NET and NEC. METHODS. This retrospective study included 104 patients (mean age, 51 ± 13 [SD] years; 52 women, 52 men) with pathologically confirmed NEN (89 NET, including 22 grade 1, 48 grade 2, and 19 grade 3; 15 NEC) who underwent multiphase DLCT within 15 days before biopsy or resection. Two radiologists independently placed ROIs to record tumor attenuation, iodine concentration (IC), and effective atomic number (Zeff) across phases and assessed qualitative features (compon of IC and Zeff, and 0.855 for attenuation. Predicted probability based on a combination of IC and Zeff achieved sensitivity of 93.33% and specificity of 80.90% for predicting NEC. Significant independent predictors (p less then .05) for differentiating grade 3 NET and NEC were IC (median, 2.0 vs 1.3 mg/mL; AUC = 0.789) and attenuation (mean, 90.3 vs 78.2 HU; AUC = 0.647), both measured in the portal venous phase. CONCLUSION. Incorporation of DLCT metrics improves differentiation of NET and NEC compared with conventional CT attenuation and qualitative features. CLINICAL IMPACT. DLCT may help select patients with pancreatic NENs for platinum-based chemotherapies.BACKGROUND. Despite increasing use of brain MRI to evaluate patients with suspected infective endocarditis, the clinical impact of brain MRI in this setting has not yet been systematically reviewed. OBJECTIVE. The purpose of this study was to evaluate the frequency of brain MRI findings in patients with suspected or confirmed infective endocarditis and to determine the impact of such findings on clinical decisions. EVIDENCE ACQUISITION. A systematic search of the PubMed, Embase, and Cochrane databases was performed from January 1, 1990, to December 31, 2020, to identify original research investigations of brain MRI in patients with suspected or confirmed infective endocarditis. Study quality was assessed with QUADAS-2. Study endpoints included the frequency of brain MRI findings and the frequency of diagnostic modifications, modification of therapeutic plan, and modification of valve surgery plan resulting from MRI findings. Frequencies were pooled by means of the inverse variance method. Subgroup analysis war confirmed infective endocarditis, brain MRI examinations commonly show relevant abnormalities that affect diagnostic and therapeutic clinical decisions. CLINICAL IMPACT. The findings support a potential role for screening brain MRI in the evaluation of patients with suspected or confirmed infective endocarditis, regardless of the presence or absence of neurologic symptoms.BACKGROUND. After rotator cuff tear, properties of the torn muscle predict failed surgical repair. link2 OBJECTIVE. The purpose of our study was to explore the utility of preoperative shear-wave elastography (SWE) measurements of the supraspinatus muscle to predict successful rotator cuff repair, including comparison with MRI-based measures. METHODS. This prospective study included 74 patients (37 men, 37 women; mean age, 63.9 ± 10.0 [SD] years) who underwent rotator cuff repair between May 2019 and January 2021. Patients underwent preoperative clinical shoulder MRI and investigational shoulder ultrasound including SWE using shear modulus. The mean elasticity values of the supraspinatus and trapezius muscles were measured, and the elasticity ratio (i.e., ratio of mean elasticity of supraspinatus muscle to mean elasticity of trapezius muscle) was calculated. The muscular fatty infiltration score (1-3 scale) was recorded on gray-scale ultrasound. On MRI, muscular fatty infiltration was assessed by Goutallier grade (000 for muscle atrophy grade, 0.874 for mean elasticity, 0.971 for elasticity ratio, and 0.912 for gray-scale fatty infiltration grade. Elasticity ratio (cutoff ≥ 2.51) achieved sensitivity of 100.0% and specificity of 90.0% for insufficient repair. At multivariable analysis including tear size, the three MRI measures, elasticity ratio, and gray-scale fatty infiltration grade, the only independent predictors of insufficient repair were muscle atrophy grade of 2-3 (odds ratio [OR] = 9.3) and elasticity ratio (OR = 15.7). CONCLUSION. SWE-derived elasticity is higher in patients with insufficient rotator cuff repair; the elasticity ratio predicts insufficient repair independent of tear size and muscle characteristics. CLINICAL IMPACT. Preoperative SWE may serve as a prognostic marker in patients with rotator cuff tear.As of January 2021, among other transparency requirements, the Centers for Medicare & Medicaid Services require that hospitals publish consumer-friendly displays of charges for shoppable health care services, including four musculoskeletal imaging examinations. Of 250 selected U.S. hospitals, all published charges for these four examinations, although 21% did not provide charges within consumer-friendly displays. link3 Bed count was larger for compliant hospitals than for noncompliant hospitals (500 vs 384 beds). All four examinations had widely variable charges (representing a 73.8-fold difference).

Obliteration with cauterization of the internal opening of pyriform sinus fistulas, with or without marsupialization, has been a mainstay for preventing recurrence. However, this procedure predisposes patients to recurrence caused by the reopening of the cauterized orifice. We applied suture ligation to secure the closure of the internal orifice following cauterization and evaluated treatment.

A total of 42 patients were diagnosed with third or fourth branchial cleft anomaly with internal pyriform sinus fistula and treated either with cauterization or with cauterization and suture ligation, between January 2008 and December 2020. The medical records were reviewed to assess demographic characteristics, clinical presentations, diagnoses, surgical treatment, and outcomes. Treatment flow characteristics for intractable patients were analyzed.

The median age of onset was 9 years (range, 0-57 years). Neck swelling (n = 32, 76.2%) was commonly encountered symptom, and a history of neck infection was found in 27 patients (64.3%). After initial treatment, 11 cases (56.2%) recurred. Younger age (≤9 years) and thyroid involvement were associated with recurrence (

 = .034 and

 = .046, respectively). Cauterization with suture ligation presented lower recurrence rate (19.2%) than cauterization only (37.5%,

 = .037). Cauterization with suture ligation for recurrent cases (n = 11) showed 81.8% (9/11) of cure rate. Intractable fistulas (n = 2) from both groups were also salvaged by suture ligation.

Suture ligation with cauterization for an internal orifice of branchial anomaly showed lower recurrence rate than cauterization only. This method was beneficial for refractory cases.

Suture ligation with cauterization for an internal orifice of branchial anomaly showed lower recurrence rate than cauterization only. This method was beneficial for refractory cases.