Experimental and Numerical Analysis of Steel-Polypropylene Hybrid Fibre Reinforced Concrete Deep Beams.

This work experimentally and numerically explored how varied steel-polypropylene fibre mixtures affected simply supported reinforced concrete deep beams. Due to their better mechanical qualities and durability, fibre-reinforced polymer composites are becoming more popular in construction, with hybrid polymer-reinforced concrete (HPRC) promising to increase the strength and ductility of reinforced concrete structures. The study evaluated how different combinations of steel fibres (SF) and polypropylene fibres (PPF) affected beam behaviour experimentally and numerically. The study's focus on deep beams, research of fibre combinations and percentages, and integration of experimental and numerical analysis provide unique insights. The two experimental deep beams were the same size and were composed of hybrid polymer concrete or normal concrete without fibres. Fibres increased deep beam strength and ductility in experiments. The calibrated concrete damage plasticity model in ABAQUS was used to numerically calibrate HPRC deep beams with different fibre combinations at varied percentages. Based on six experimental concrete mixtures, calibrated numerical models of deep beams with different material combinations were investigated. The numerical analysis confirmed that fibres increased deep beam strength and ductility. HPRC deep beams with fibre performed better than those without fibres in numerical analysis. The study also determined the best fibre percentage to improve deep beam behaviour where a combination of 0.75% SF and 0.25% PPF was recommended to enhance load-bearing capacity and crack distribution, while a higher content of PPF was suggested for reducing deflection.

Limited Optimal Plastic Behavior of RC Beams Strengthened by Carbon Fiber Polymers Using Reliability-Based Design.

The plastic behavior of strengthened haunched beams utilizing carbon fiber-reinforced polymers (CFRP) was investigated using a probabilistic design that took into account random concrete properties, CFRP properties, and complementary strain energy values, with the reliability index serving as a limiting index, as the proposed method considers a novel method that deals with probabilistic parameters for models with limited plastic behavior designed based on the reliability index. The data used in this research were gathered and evaluated in a recent study on simply supported haunched beams reinforced with carbon fiber-reinforced polymers. The purpose of this research was to use the reliability limitation index for simulated strengthened haunched beams by taking into account randomness in concrete and CFRP properties and the complementary strain energy value, which is considered a plastic behavior controller that provides an illustration of the damage amount within the reinforcement steel bars. The results indicate how randomness affects the behavior of the presented models, which are chosen to have different numbers of CFRP strips. The variable randomness affects load and deflection values where the reliability index value increases as the corresponding load value decrease, reflecting the increased probability of failure in models subjected to higher loading conditions, while tension concrete damage percentages are reflected in the damage pattern presented in the results, showing that as the produced load increases, so does the damage intensity. It is also obvious that the reliability index served as a limitation index while taking concrete characteristics and complementary strain energy as random variables.

Reliability­based probabilistic numerical plastically limited analysis of reinforced concrete haunched beams.

This research proposes a novel method that considers the optimal reliability-based design of reinforced concrete haunched beams subjected to probabilistic concrete properties and complementary strain energy values. The theory is applied twice, once to evaluate a deterministic solution, where the plastic behaviour is constrained by the complementary strain energy of residual stresses induced within steel bars. Secondly, the same method is considered for a probabilistic solution where the concrete characteristics-compressive strength and modulus of elasticity-and complementary strain energy value vary randomly. The reliability index acts as a bound for the solution. It is important to mention that the model utilised in this publication is derived from recent research after being calibrated using Abaqus. This work represents an extension of that recent research that exclusively considered deterministic work. This research led deterministically to new estimates for the complementary strain energy, which will be interpreted as reflecting the behaviour of plastic thresholds and quantifying the associated loads. Afterwards, uncertainty is studied when probability interferes, showing various load values and damage in concrete and steel when the complementary strain energy and concrete properties are probabilistically evaluated, giving a less reliable solution as the load reduces. These effects are reflected in the varying plastic behaviour of the investigated haunched beams.

Evolution of Care and Outcomes Across Surges in Hospitalized Patients with Coronavirus Disease 2019.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has unfolded in distinct surges. Understanding how surges differ may reveal important insights into the evolution of the pandemic and improve patient care. METHODS: We leveraged the Michigan Medicine COVID-19 Cohort, a prospective observational study at an academic tertiary medical center that systematically enrolled 2309 consecutive patients hospitalized for COVID-19, comprising 5 distinct surges. RESULTS: As the pandemic evolved, patients hospitalized for COVID-19 tended to have a lower burden of comorbidities and a lower inflammatory burden as measured by admission levels of C-reactive protein, ferritin, lactate dehydrogenase, and D-dimer. Use of hydroxychloroquine and azithromycin decreased substantially after Surge 1, while use of corticosteroids and remdesivir markedly increased (P < .001 for all). In-hospital mortality significantly decreased from 18.3% in Surge 1 to 5.3% in Surge 5 (P < .001). The need for mechanical ventilation significantly decreased from 42.5% in Surge 1 to 7.0% in Surge 5 (P < .001), while the need for renal replacement therapy decreased from 14.4% in Surge 1 to 2.3% in Surge 5 (P < .001). Differences in patient characteristics, treatments, and inflammatory markers accounted only partially for the differences in outcomes between surges. CONCLUSIONS: The COVID-19 pandemic has evolved significantly with respect to hospitalized patient populations and therapeutic approaches, and clinical outcomes have substantially improved. Hospitalization after the first surge was independently associated with improved outcomes, even after controlling for relevant clinical covariates.

Quality of Life After Transcatheter Aortic Valve Replacement in Normal-Flow, Low-Gradient Aortic Stenosis.

Background: Prior studies of aortic valve replacement (AVR) in patients with normal-flow, low-gradient aortic stenosis (NF-LG AS) have demonstrated conflicting results regarding the survival benefit of AVR. Changes in quality of life (QoL) after transcatheter AVR (TAVR) have not been reported in this population. Objectives: The purpose of this study was to compare changes in QoL after TAVR for patients with NF-LG AS to patients with high-gradient aortic stenosis (HG-AS). Methods: Patients who underwent TAVR for severe aortic stenosis (AS) were divided into 4 hemodynamic profiles of AS, including NF-LG AS. Changes in Kansas City Cardiomyopathy Questionnaire-12 score from baseline to 1 year were compared between AS groups. The primary composite outcome indicating clinical improvement consisted of survival to 1 year and improved Kansas City Cardiomyopathy Questionnaire overall summary score of ≥5 points while adjusting for relevant baseline factors. Results: Out of 860 patients who underwent TAVR, high gradient AS was present in 368 (42.8%) patients and NF-LG AS in 245 (28.5%). HG-AS and NF-LG AS groups had a similar proportion of patients who met the primary unadjusted outcome of clinical improvement (70.4% vs 63.9%, respectively; P = 0.189). One-year Kaplan-Meier mortality estimates were higher for NF-LG AS patients than HG-AS patients (12.9% vs 5.8%, P < 0.001). In the primary adjusted analysis, there was no significant difference in the composite outcome between HG and NF-LG AS groups (adjusted OR: 0.72, 95% CI: 0.47-1.11). Conclusions: Selected patients with NF-LG AS experienced similar improvement in QoL after TAVR compared with HG-AS. Further investigation of patients with NF-LG AS will help to inform optimal selection for treatment with TAVR.

Relationship Between Preexisting Cardiovascular Disease and Death and Cardiovascular Outcomes in Critically Ill Patients With COVID-19.

BACKGROUND: Preexisting cardiovascular disease (CVD) is perceived as a risk factor for poor outcomes in patients with COVID-19. We sought to determine whether CVD is associated with in-hospital death and cardiovascular events in critically ill patients with COVID-19. METHODS: This study used data from a multicenter cohort of adults with laboratory-confirmed COVID-19 admitted to intensive care units at 68 centers across the United States from March 1 to July 1, 2020. The primary exposure was CVD, defined as preexisting coronary artery disease, congestive heart failure, or atrial fibrillation/flutter. Myocardial injury on intensive care unit admission defined as a troponin I or T level above the 99th percentile upper reference limit of normal was a secondary exposure. The primary outcome was 28-day in-hospital mortality. Secondary outcomes included cardiovascular events (cardiac arrest, new-onset arrhythmias, new-onset heart failure, myocarditis, pericarditis, or stroke) within 14 days. RESULTS: Among 5133 patients (3231 male [62.9%]; mean age 61 years [SD, 15]), 1174 (22.9%) had preexisting CVD. A total of 1178 (34.6%) died, and 920 (17.9%) had a cardiovascular event. After adjusting for age, sex, race, body mass index, history of smoking, and comorbidities, preexisting CVD was associated with a 1.15 (95% CI, 0.98-1.34) higher odds of death. No independent association was observed between preexisting CVD and cardiovascular events. Myocardial injury on intensive care unit admission was associated with higher odds of death (adjusted odds ratio, 1.93 [95% CI, 1.61-2.31]) and cardiovascular events (adjusted odds ratio, 1.82 [95% CI, 1.47-2.24]), regardless of the presence of CVD. CONCLUSIONS: CVD risk factors, rather than CVD itself, were the major contributors to outcomes in critically ill patients with COVID-19. The occurrence of myocardial injury, regardless of CVD, and its association with outcomes suggests it is likely due to multiorgan injury related to acute inflammation rather than exacerbation of preexisting CVD. REGISTRATION: NCT04343898; https://clinicaltrials.gov/ct2/show/NCT04343898.

Soluble Urokinase Plasminogen Activator Receptor and Venous Thromboembolism in COVID-19.

Background Venous thromboembolism (VTE) contributes significantly to COVID-19 morbidity and mortality. The urokinase receptor system is involved in the regulation of coagulation. Levels of soluble urokinase plasminogen activator receptor (suPAR) reflect hyperinflammation and are strongly predictive of outcomes in COVID-19. Whether suPAR levels identify patients with COVID-19 at risk for VTE is unclear. Methods and Results We leveraged a multinational observational study of patients hospitalized for COVID-19 with suPAR and D-dimer levels measured on admission. In 1960 patients (mean age, 58 years; 57% men; 20% Black race), we assessed the association between suPAR and incident VTE (defined as pulmonary embolism or deep vein thrombosis) using logistic regression and Fine-Gray modeling, accounting for the competing risk of death. VTE occurred in 163 (8%) patients and was associated with higher suPAR and D-dimer levels. There was a positive association between suPAR and D-dimer (ß=7.34; P=0.002). Adjusted for clinical covariables, including D-dimer, the odds of VTE were 168% higher comparing the third with first suPAR tertiles (adjusted odds ratio, 2.68 [95% CI, 1.51-4.75]; P<0.001). Findings were consistent when stratified by D-dimer levels and in survival analysis accounting for death as a competing risk. On the basis of predicted probabilities from random forest, a decision tree found the combined D-dimer <1 mg/L and suPAR <11 ng/mL cutoffs, identifying 41% of patients with only 3.6% VTE probability. Conclusions Higher suPAR was associated with incident VTE independently of D-dimer in patients hospitalized for COVID-19. Combining suPAR and D-dimer identified patients at low VTE risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04818866.

Inflammation, Hyperglycemia, and Adverse Outcomes in Individuals With Diabetes Mellitus Hospitalized for COVID-19.

OBJECTIVE: Diabetes mellitus (DM) is a major risk factor for severe coronavirus disease 2019 (COVID-19) for reasons that are unclear. RESEARCH DESIGN AND METHODS: We leveraged the International Study of Inflammation in COVID-19 (ISIC), a multicenter observational study of 2,044 patients hospitalized with COVID-19, to characterize the impact of DM on in-hospital outcomes and assess the contribution of inflammation and hyperglycemia to the risk attributed to DM. We measured biomarkers of inflammation collected at hospital admission and collected glucose levels and insulin data throughout hospitalization. The primary outcome was the composite of in-hospital death, need for mechanical ventilation, and need for renal replacement therapy. RESULTS: Among participants (mean age 60 years, 58.2% males), those with DM (n = 686, 33.5%) had a significantly higher cumulative incidence of the primary outcome (37.8% vs. 28.6%) and higher levels of inflammatory biomarkers than those without DM. Among biomarkers, DM was only associated with higher soluble urokinase plasminogen activator receptor (suPAR) levels in multivariable analysis. Adjusting for suPAR levels abrogated the association between DM and the primary outcome (adjusted odds ratio 1.23 [95% CI 0.78, 1.37]). In mediation analysis, we estimated the proportion of the effect of DM on the primary outcome mediated by suPAR at 84.2%. Hyperglycemia and higher insulin doses were independent predictors of the primary outcome, with effect sizes unaffected by adjusting for suPAR levels. CONCLUSIONS: Our findings suggest that the association between DM and outcomes in COVID-19 is largely mediated by hyperinflammation as assessed by suPAR levels, while the impact of hyperglycemia is independent of inflammation.

Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Outcomes in Patients Hospitalized for COVID-19.

Background Use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEi/ARB) is thought to affect COVID-19 through modulating levels of angiotensin-converting enzyme 2, the cell entry receptor for SARS-CoV2. We sought to assess the association between ACEi/ARB, biomarkers of inflammation, and outcomes in patients hospitalized for COVID-19. Methods and Results We leveraged the ISIC (International Study of Inflammation in COVID-19), identified patients admitted for symptomatic COVID-19 between February 1, 2020 and June 1, 2021 for COVID-19, and examined the association between in-hospital ACEi/ARB use and all-cause death, need for ventilation, and need for dialysis. We estimated the causal effect of ACEi/ARB on the composite outcomes using marginal structural models accounting for serial blood pressure and serum creatinine measures. Of 2044 patients in ISIC, 1686 patients met inclusion criteria, of whom 398 (23.6%) patients who were previously on ACEi/ARB received at least 1 dose during their hospitalization for COVID-19. There were 215 deaths, 407 patients requiring mechanical ventilation, and 124 patients who required dialysis during their hospitalization. Prior ACEi/ARB use was associated with lower levels of soluble urokinase plasminogen activator receptor and C-reactive protein. In multivariable analysis, in-hospital ACEi/ARB use was associated with a lower risk of the composite outcome of in-hospital death, mechanical ventilation, or dialysis (adjusted hazard ratio 0.49, 95% CI [0.36-0.65]). Conclusions In patients hospitalized for COVID-19, ACEi/ARB use was associated with lower levels of inflammation and lower risk of in-hospital outcomes. Clinical trials will define the role of ACEi/ARB in the treatment of COVID-19. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04818866.

Hibiscus sabdariffa, a Treatment for Uncontrolled Hypertension. Pilot Comparative Intervention.

In Iraq, in 2019, there were about 1.4 million Internally Displaced Persons (IDP); medical treatments were often interrupted. The feasibility of using Hibiscus sabdariffa (HS) decoction to curb hypertension was evaluated. A multicentric comparative pilot intervention for 121 participants with high blood pressure (BP) (≥140/90 mmHg) was conducted. Participants of the intervention group (with or without conventional medication) received HS decoction on a dose regimen starting from 10 grams per day. BP was measured five times over six weeks. The major active substances were chemically quantified. Results: After 6 weeks, 61.8% of participants from the intervention group (n = 76) reached the target BP < 140/90 mmHg, compared to 6.7% in the control group (n = 45). In the intervention group, a mean (±SD) reduction of 23.1 (±11.8) mmHg and 12.0 (±11.2) for systolic and diastolic BP, respectively, was observed, while in the control group the reduction was 4.4 (±10.2)/3.6 (±8.7). The chemical analysis of the starting dose indicated a content of 36 mg of total anthocyanins and 2.13 g of hibiscus acid. The study shows the feasibility of using HS decoction in IDP's problematic framework, as hibiscus is a safe, local, affordable, and culturally accepted food product.

Evaluation of dosimetric impact of inter-application and intra-application variations in fractionated high-dose-rate intra-cavitary brachytherapy of cervical cancer.

PURPOSE: To evaluate feasibility and safety of execution of optimized intra-cavitary brachytherapy (ICBT) plan of first fraction in subsequent fractions in high-volume, low-resource centers. MATERIAL AND METHODS: This non-randomized prospective study included 30 cervical cancer patients, who underwent 4 fractions of high-dose-rate (HDR)-ICBT in 2 applications, one week apart, 2 fractions per application delivered on two consecutive days. Computed tomography (CT) simulation was done before each fraction, organs at risk (OARs) were contoured on all sets of CT images. Optimized plans were generated for each set of CT images and executed for the treatment. Test treatment plans were retrospectively generated by applying first treatment fraction's dwell times adjusted for decay, and dwell positions of the applicator for subsequent treatment fractions paired t-test was performed to analyze D2cc dose variations of OARs among the paired sets of plans. RESULTS: Comparison between the plans showed daily plans provided lower D2cc to OARs than test plans. In intra-application plan comparison, there was a significant dose reduction to 2 cc sigmoid (p = 0.021) and bladder (p = 0.007) in daily plan. Mean D2cc of optimized and unoptimized plans were 361.35 ±114.01 and 411.70 ±152.73 for sigmoid, and 511.23 ±85.47 cGy and 553.57 ±111.23 cGy for bladder, respectively. In inter-application, D2cc rectum and sigmoid demonstrated a statistically significant dose variation (p = 0.002) and (p = 0.007), with mean D2cc rectum of optimized and unoptimized plans being 401.06 ±83.53 cGy and 452.46 ±123.97 cGy, and of 2 cc sigmoid 340.84 ±117.90 cGy and 387.79 ±141.36 cGy, respectively. CONCLUSIONS: Fractionated HDR brachytherapy amounts to significant variation in OAR doses if re-simulation and re-plan is not performed for every fraction and ICBT application. Therefore, plan of the day with optimization of the doses to target and OARs must be followed for each fraction.

A rare case of melorheostosis of the hand in a pediatric patient.

Melorheostosis, a rare mesenchymal dysplasia of bone, generally affects about 0.001% of people globally with about 400 cases total being reported. Melorheostosis of the hand, especially in the pediatric population, has been seldom reported. Previous studies have investigated potential genetic mutations associated with melorheostosis however, questions still remain regarding effective treatment options for this disease. This case report describes a unique case of pediatric melorheostosis of the hand and further clarifies current theories on melorheostosis with regards to pathogenesis, best treatment practices, and future research.

Cell-free circulating tumor DNA in patients with high-grade glioma as diagnostic biomarker - A guide to future directive.

BACKGROUND: Owing to the aggressive nature of high-grade gliomas (HGGs), its early diagnosis holds the key to a favorable prognosis. Currently, tissue biopsy is the gold standard to verify HGG's initial diagnosis and can be challenging due to its invasive nature. In this study, our objective was a noninvasive panel for timely detection of HGG and its progression using cell-free circulating tumor DNA (cfTDNA). MATERIALS AND METHODS: Twenty-seven patients with HGG were tested with a 50-gene tumor panel. cfTDNA isolated from serum was checked for single-nucleotide variations (SNVs) or copy number alterations using targeted next-generation sequencing, with further validation of results by checking respective formalin-fixed paraffin-embedded tumor tissues for the same genetic alterations. RESULTS: About 88.8% of the patients were detected with HGG-associated cfTDNA. Around 25% patients were detected with one, 25% patients had three, 25% patients had four, and 12.5% patients each had five and six genetic alterations. About 12 of 50 genes were detected in the serum samples. The SNVs detected included TP53 in 87.5% of patients; PIK3CA and EGFR in 50% of patients; PTEN in 37.5%; KIT and VHL in each 25% of patients; and RB1, NF2, MET, ATRX, CDK2A, and CTNNB1 each in 8.3%-16.6%. On combining EGFR, KIT, PTEN, PIK3CA, TP53, and VHL genes (Govardhan Diagnostic Genetic Module for high-grade glioma), at least one of the genetic alterations was found in 100% of patients. CONCLUSION: These findings illustrate that cfTDNA is easily demonstrable and can be used as a surrogate to tissue biopsy in brain tumor.

Transjugular closure of a two-hole atrial septal defect in a child with iliac vein thrombosis.

The internal jugular vein is not a typical vascular access line during the percutaneous closure of an atrial septal defect. We report the closure of a double atrial septal defect with a single device, using a transjugular venous approach, in a child with an inferior vena cava obstructed by a thrombosis due to previous cardiac catheterization. That the transjugular venous approach can be used as a possible alternative during the transcatheter closure of an atrial septal defect in children, when the inferior vena cava access is not possible.

Cost-effectiveness of nidotherapy for comorbid personality disorder and severe mental illness: randomized controlled trial.

AIMS: Nidotherapy is the systematic modification of the environment to create a better fit for people. This is the first randomized controlled trial of its efficacy in an assertive community team. METHODS: Patients in an assertive outreach team with continued management problems together with comorbid personality disturbance and severe mental illness were randomized to nidotherapy enhanced assertive treatment (up to 12 sessions) or to continued assertive outreach care. Use of psychiatric beds over one years (primary outcome) and change from base-line in other health service resources, psychiatric symptoms, social functioning and engagement with services were measured at 6 and 12 months (secondary outcomes). RESULTS: 52 patients were recruited over 13 months, with 49 and 37 assessed at 6 and 12 months. Patients referred to nidotherapy had a 63% reduction in hospital bed use after one year compared with control assertive care (P = 0.13) and showed non-significant improvement in psychiatric symptoms, social functioning and engagement than the control group. The mean cost savings for each patient allocated to nidotherapy was 4,112 pounds sterling per year, mainly as a consequence of reduced psychiatric bed use. CONCLUSION: Nidotherapy may be a cost-effective option in the management of comorbid serious mental illness and personality disorder, but larger confirmatory trials are necessary.