Median Difference Research Articles

Mevalonate in blood and muscle: Response to atorvastatin treatment and the relationship to statin intolerance in patients with coronary heart disease.

Statin-associated muscle symptoms are frequently reported and often lead to discontinuation of statin therapy with an increased risk of cardiovascular events. Invitro studies suggest that statin-mediated inhibition of the mevalonate pathway leads to muscle cell toxicity. We aimed to determine the relationship between mevalonate, LDL-cholesterol, and atorvastatin metabolites in patients with coronary heart disease and self-perceived muscle side effects. Furthermore, we assessed the correlation between mevalonate in blood and muscle and the relationship to statin intolerance due to muscle symptoms. We used blood plasma from a randomized crossover trial (n = 70) and muscle biopsies and plasma from a subgroup in a subsequent open intervention study (n = 26). Both studies tested atorvastatin 40 mg/day. Seven patients did not tolerate ≥3 statins throughout the follow-up and were classified as statin-intolerant. Mevalonate in blood plasma decreased during atorvastatin treatment (median difference -38%, range -77% to 43%, p < 0.001), whereas mevalonate in muscle tissue was not lowered (0.05%, range -47% to 145%). Mevalonate correlated poorly with LDL-cholesterol and atorvastatin metabolites (Spearman's rho -0.28 to 0.10). The statin-intolerant patients had a smaller reduction in circulating mevalonate compared with the tolerant patients; median difference -8.1 (-22 to 3.5) nmol/L versus -25 (-93 to 12) nmol/L, p = 0.028. A similar observation was made for LDL-cholesterol. Cutoffs based on these biomarkers classified >50% correctly as tolerant. Inhibition of the mevalonate pathway does not appear to be the mechanism underlying statin intolerance in the present study. Further studies of mevalonate as a biomarker for statin tolerance are needed to clarify the potential.

Ultrashort Oncologic Whole-Body [18F]FDG Patlak Imaging Using LAFOV PET.

Methods to shorten [18F]FDG Patlak PET imaging procedures ranging from 65-90 to 20-30 min after injection, using a population-averaged input function (PIF) scaled to patient-specific image-derived input function (IDIF) values, were recently evaluated. The aim of the present study was to explore the feasibility of ultrashort 10-min [18F]FDG Patlak imaging at 55-65 min after injection using a PIF combined with direct Patlak reconstructions to provide reliable quantitative accuracy of lung tumor uptake, compared with a full-duration 65-min acquisition using an IDIF. Methods: Patients underwent a 65-min dynamic PET acquisition on a long-axial-field-of-view (LAFOV) Biograph Vision Quadra PET/CT scanner. Subsequently, direct Patlak reconstructions and image-based (with reconstructed dynamic images) Patlak analyses were performed using both the IDIF (time to relative kinetic equilibrium between blood and tissue concentration (t*) = 30 min) and a scaled PIF at 30-60 min after injection. Next, direct Patlak reconstructions were performed on the system console using only the last 10 min of the acquisition, that is, from 55 to 65 min after injection, and a scaled PIF using maximum crystal ring difference settings of both 85 and 322. Tumor lesion and healthy-tissue uptake was quantified and compared between the differently obtained parametric images to assess quantitative accuracy. Results: Good agreement was obtained between direct- and image-based Patlak analyses using the IDIF (t* = 30 min) and scaled PIF at 30-60 min after injection, performed using the different approaches, with no more than 8.8% deviation in tumor influx rate value (Ki ) (mean difference ranging from -0.0022 to 0.0018 mL/[min × g]). When direct Patlak reconstruction was performed on the system console, excellent agreement was found between the use of a scaled PIF at 30-60 min after injection versus 55-65 min after injection, with 2.4% deviation in tumor Ki (median difference, -0.0018 mL/[min × g]; range, -0.0047 to 0.0036 mL/[min × g]). For different maximum crystal ring difference settings using the scan time interval of 55-65 min after injection, only a 0.5% difference (median difference, 0.0000 mL/[min × g]; range, -0.0004 to 0.0013 mL/[min × g]) in tumor Ki was found. Conclusion: Ultrashort whole-body [18F]FDG Patlak imaging is feasible on an LAFOV Biograph Vision Quadra PET/CT system without loss of quantitative accuracy to assess lung tumor uptake compared with a full-duration 65-min acquisition. The ultrashort 10-min direct Patlak reconstruction with PIF allows for its implementation in clinical practice.

Fast Competitive Swimmers Demonstrate a Diminished Diving Reflex.

Competitive swimmers complete 50-m front crawl swimming without breathing or with a limited number of breaths. Breath holding during exercise can trigger diving reflex including bradycardia and diminished active muscle blood flow, whereas oxygen supply to vital organ such as brain is maintained. We hypothesized that swimmers achieving faster time in 50-m front crawl with limited number of breaths demonstrate a blunted diving reflex of cardiac and active muscle blood flow responses with elevated cerebral perfusion to counteract peripheral and central fatigues. Twenty-eight competitive swimmers (12 females) underwent a 50-m front crawl swimming time trial with minimum respiratory interruptions, following which they were categorized into two groups: Fast (n = 13) and Slow (n = 15). Additionally, they performed knee extension exercises with maximal voluntary breath- holding, wherein leg blood flow (Doppler ultrasound), cardiac output (Modelflow), heart rate (electrocardiogram), and middle cerebral artery mean blood velocity (transcranial Doppler ultrasound) were evaluated. The pattern of leg blood flow response differed between the two groups (p = 0.031) with the Fast group experiencing a delayed onset of reductions in leg blood flow (p = 0.035). The onset of bradycardia was also delayed in the Fast group (p = 0.014), with this group demonstrating a higher value of the lowest heart rate (between-trial difference in average: 15.9 [3.73, 28.2] beats/min) and cardiac output (between-trial difference in median: 2.84 L/min) (both, p ≤ 0.013). Middle cerebral artery mean blood velocity was similar between the groups (all p ≥ 0.112). We show that swimmers with superior performance in 50-m front crawl swim with limited breaths display a diminished diving reflex.

An investigation of scattered light integrating collector technology for rapid blood culture sensitivity testing.

Introduction. Sepsis rates are increasing, with Gram-negative organisms representing a large proportion of bloodstream infections. Rapid antibiotic administration, alongside diagnostic investigations, is required for the effective management of these patients.Gap statement. Current diagnostics take ~48 h for a final report; therefore, rapid diagnostics are required.Aim. This study investigated a novel antibiotic sensitivity method, the scattered light integrating collector (SLIC), combined with a rapid identification method using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) technology to determine if an accurate identification and susceptibility result can be provided within 4 h of a positive blood culture report.Methodology. A total of 47 blood cultures containing Gram-negative bacteria from 46 patients were processed using the MALDI-TOF Biotyper Sepsityper for identification directly from the blood and the SLIC instrument for susceptibility testing. All organisms were also tested using the current standard workflow used in the host laboratory. Categorical agreement (CA), major errors (MaEs) and very major errors (VMEs) were determined.Results. SLIC produced susceptibility results with a 71.9% CA, 30.6% MaE and 17.5% VME. The median difference in time to the final result was 44.14 (43 : 05-45 : 15) h earlier compared to the current method.Conclusion. We conclude that SLIC was unable to consistently provide sufficiently accurate antibiotic susceptibility results compared to the current standard method.

The efficacy of sildenafil therapy in dismal prognosis early-onset intrauterine growth restriction: the STRIDER RCT

Background Severe early-onset intrauterine growth restriction is associated with stillbirth, neonatal death and neurodevelopmental impairment. There is no treatment for intrauterine growth restriction with timely delivery being the only management option. Placentas from intrauterine growth restriction pregnancies often show failure to remodel maternal spiral arteries leading to a persistent vasoactive responsiveness. Sildenafil, a phosphodiesterase type 5 inhibitor, potentiates naturally occurring nitrous oxide, encouraging vasodilation of vasoactive vessels. Previous studies in animal models and humans show recovery of placental function and improvement in fetal growth. The STRIDER trial aimed to address whether treatment with sildenafil is beneficial to fetal growth and perinatal and toddler outcomes. Methods The STRIDER trial was a superiority, randomised double-blind placebo-controlled trial that was carried out in 19 fetal medicine units in the United Kingdom. Women with a singleton pregnancy between 22+0 and 29+6 weeks’ gestation, with severe early-onset intrauterine growth restriction, were asked to participate. Women were randomised (1 : 1) to receive either sildenafil 25-mg three times daily or placebo until 31+6 weeks’ gestation or delivery. Women were stratified by site and their gestational age at randomisation (before 26+0 or at 26+0 weeks or later). Severe intrauterine growth restriction was defined as a combination of estimated fetal weight or abdominal circumference below the 10th percentile and absent or reversed end-diastolic blood flow in the umbilical artery on Doppler velocimetry. The primary outcome was the time from randomisation to delivery, measured in days with a 1-week difference deemed to be clinically significant. The phase 2 study followed up all babies alive at discharge to assess for cardiovascular function and neurodevelopment at 2 years of age. Results Between 21 November 2014 and 6 July 2016, a total number of 135 women were recruited to the study, of these 70 were assigned to sildenafil and 65 to the placebo. No difference was found in the median randomisation to delivery interval between sildenafil [17 days (interquartile range 7–24)] and placebo [18 days (8–28), p = 0.23]. Live births [relative risk 1.06, 95% confidence interval 0.84 to 1.33; p = 0.62], fetal deaths (relative risk 0.89, 95% confidence interval 0.54 to 1.45; p = 0.64), neonatal deaths (relative risk 1.33, 95% confidence interval 0.54 to 3.28; p = 0.53), and birthweight [mean difference −14 g (95% confidence interval −100 to 126); p = 0.81] did not differ between the treatment arms and no differences were found for other maternal or perinatal secondary outcomes. Eight serious adverse events were reported during the study (six in the placebo group and two in the sildenafil group); none of these were attributed to sildenafil. Seventy-five babies were discharged alive from the neonatal unit and of those 61 were available for follow-up with 32 treated with sildenafil and 29 with placebo. Of those that did not have a follow-up 1 baby died (placebo) and 3 declined follow-up and 10 were uncontactable. There was no difference in neurodevelopment, or blood pressure for infants treated with sildenafil versus placebo. Infants who received sildenafil had a greater head circumference compared to those who received placebo (median difference 49.25 cm, interquartile range 46.4–50.26 vs. 47.17 cm, 95% confidence interval 44.71 to 48.95). Conclusion Sildenafil did not prolong pregnancy or improve pregnancy outcomes. There was no effect from sildenafil treatment on infant neurodevelopment. Our data show that sildenafil should not be prescribed for fetal growth restriction. Trial registration This trial is registered as ISRCTN39133303. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/62/109) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 18. See the NIHR Funding and Awards website for further award information.

Changes in out-of-hospital cardiac arrest resuscitation quality during and after the COVID-19 pandemic

AimThe impact of personal protective equipment (PPE) on resuscitation quality is largely unknown. We sought to examine the effect of PPE requirements on CPR quality and resuscitation interventions during the COVID-19 pandemic in Victoria, Australia. MethodsWe performed a retrospective cohort study of adult OHCA patients of medical aetiology who received attempted resuscitation. The study consisted of three periods; a pre-COVID-19 period (1st March 2019 to 15th March 2020), the COVID-19 period (16th March 2020 to 12th October 2022) and a post-COVID-19 period (13th October 2022 to 30th June 2023). Multivariable quantile and logistic regression were used to examine changes in CPR metrics and time to resuscitation interventions across the three periods ResultsWe included 8,956 patients (2,389 pre-COVID-19, 4,935 during COVID-19 and 1,632 post-COVID-19). A number of CPR quality metrics deteriorated during the COVID-19 period compared to the pre-COVID-19 period, including: chest compression fraction (median difference [MD] −0.81 percentage points; 95% CI −1.07,-0.56), release velocity (MD −5.26 mm per second; 95% CI −9.79, −0.72) and resuscitation duration (MD −2.2 min; 95% CI −3.39, −1.05). The COVID-19 period was also associated with longer post-shock pauses (MD 0.22 s; 95% CI 0.05, 0.38), and a reduction in the risk-adjusted odds of receiving adrenaline administration within 5 mins (AOR 0.72, 95% CI 0.63 – 0.82) and laryngeal mask insertion within 10 mins of arrival (AOR 0.83, 95% CI 0.74 – 0.94). These factors, with the exception of resuscitation duration and time to larygeal mask insertion, remained significantly different from baseline for the post-COVID-19 period. ConclusionSeveral CPR quality metrics declined during the COVID-19 period and some remain below pre-pandemic levels. Further research is needed to understand these impacts on OHCA outcomes.

Diaphragm-sparing efficacy of subparaneural upper trunk block for arthroscopic shoulder surgery: A randomised controlled trial.

Inter-scalene block (ISB) is associated with an inevitable risk of hemi-diaphragmatic paresis (HDP). To reduce the risk of HDP, an upper trunk block (UTB) has been proposed at the brachial plexus division level. We hypothesised that UTB would be associated with a lower incidence of HDP than ISB while providing sufficient analgesia following arthroscopic shoulder surgery. Randomised controlled trial. A tertiary teaching hospital. Seventy patients aged 20 to 80 years undergoing arthroscopic rotator cuff repair. Ultrasound-guided ISB or UTB was performed with 5 ml 0.75% ropivacaine. The primary outcome was the incidence of complete HDP, assessed by diaphragm excursion using ultrasound, defined as a decrease to 25% or less of baseline or occurrence of paradoxical movement. Postoperative pulmonary function change, pain scores, opioid consumption and pain-related outcomes were the secondary outcomes. The UTB group had a significantly lower incidence of complete HDP than the ISB group [5.9% (2/34) vs. 41.7% (15/36); absolute difference, 35.8%; 95% confidence interval (CI), 17.8 to 53.7%; P < 0.001]. The postblockade decline in pulmonary function was more pronounced in the ISB group than that in the UTB group. The pain score at 1 h postoperatively was not significantly different between the groups (ISB vs. UTB group: median 0 vs. 1; median difference, -1; 95% CI, -2 to 0.5). No significant difference was observed in any other secondary outcomes. UTB was associated with a lower incidence of HDP compared with ISB while providing excellent analgesia in arthroscopic shoulder surgery. Clinical Trial Registry of Korea ( https://cris.nih.go.kr ) identifier: KCT0007002. Chungnam National University Hospital Institutional Review Board No. 2021-12-069.

Kilometer‐Scale Assessment of the Adriatic Dense Water Multi‐Decadal Dynamics

AbstractThe North Adriatic Dense Water (NAddW)—the densest Mediterranean water generated by extreme cooling during wintertime hurricane‐strength winds—drives the thermohaline circulation, ventilates the deep layers, and changes the biogeochemical properties of the Adriatic Sea. However, modeling the dynamical properties of such dense water at the climate scale has been a challenge for decades due to the complex coastal geomorphology of the Adriatic basin not properly reproduced by existing climate models. To overcome these deficiencies, a 31‐year‐long simulation (1987–2017) of the Adriatic Sea and Coast (AdriSC) kilometer‐scale atmosphere‐ocean model is used to analyze the main NAddW dynamical phases (i.e., generation, spreading and accumulation). The study highlights four key results. First, during winter, the NAddW densities are higher in the shallow northern Adriatic shelf than in the deeper Kvarner Bay—where 25%–35% of the overall NAddW are found to be generated—due to a median bottom temperature difference of 2°C between the two generation sites. Second, the NAddW mass transported across most of the Adriatic peaks between February and May, except along the western side of the Otranto Strait. Third, for the accumulation sites, the bottom layer of the Kvarner Bay is found to be renewed annually while the renewal occurs every 1–3 years in the Jabuka Pit and every 5–10 years in the deep Southern Adriatic Pit. Fourth, the NAddW cascading and accumulation is more pronounced during basin‐wide high‐salinity conditions driven by circulation changes in the northern Ionian Sea.

A "one-step" approach to heart rate correction and statistical analysis applied to conscious dog QTc studies.

A "one-step" method which combined the heart rate correction and statistical analysis for conscious nonhuman primate (NHP) QTc assessment was recently published. The principles of this method are applicable to other species. In the current analysis, we demonstrate the utility of the technique in conscious dog QTc studies. Two studies in male dogs (n = 8 and n = 7) implanted with telemetry devices were used. In both studies, treatments were randomized and all animals received all treatments. In the primary study, the effect on QTc of moxifloxacin was compared with vehicle. Each treatment (vehicle and moxifloxacin) was given on two separate occasions. In the second study, dogs were given vehicle or dofetilide. Conventional QTc analysis was compared with the "one-step" method. The effect on QTc relative to vehicle was determined along with the median minimal detectable difference. As expected, both moxifloxacin and dofetilide gave QTc increases with a maximum of ~ 20 ms. There was a significant increase in the sensitivity to detect a QTc effect when using the "one-step" method. The minimal detectable difference was 1.6 ms for the "one-step" method compared with 6.2 ms for the conventional method. These analyses are consistent with the increased sensitivity described for the "one-step" method applied to studies in NHP. The increased sensitivity should enhance the ability to support an integrated assessment of the QTc prolongation liability for new drugs.

Tailoring the Nutritional Composition of Italian Foods to the US Nutrition5k Dataset for Food Image Recognition: Challenges and a Comparative Analysis

Background: Training of machine learning algorithms on dish images collected in other countries requires possible sources of systematic discrepancies, including country-specific food composition databases (FCDBs), to be tackled. The US Nutrition5k project provides for ~5000 dish images and related dish- and ingredient-level information on mass, energy, and macronutrients from the US FCDB. The aim of this study is to (1) identify challenges/solutions in linking the nutritional composition of Italian foods with food images from Nutrition5k and (2) assess potential differences in nutrient content estimated across the Italian and US FCDBs and their determinants. Methods: After food matching, expert data curation, and handling of missing values, dish-level ingredients from Nutrition5k were integrated with the Italian-FCDB-specific nutritional composition (86 components); dish-specific nutrient content was calculated by summing the corresponding ingredient-specific nutritional values. Measures of agreement/difference were calculated between Italian- and US-FCDB-specific content of energy and macronutrients. Potential determinants of identified differences were investigated with multiple robust regression models. Results: Dishes showed a median mass of 145 g and included three ingredients in median. Energy, proteins, fats, and carbohydrates showed moderate-to-strong agreement between Italian- and US-FCDB-specific content; carbohydrates showed the worst performance, with the Italian FCDB providing smaller median values (median raw difference between the Italian and US FCDBs: −2.10 g). Regression models on dishes suggested a role for mass, number of ingredients, and presence of recreated recipes, alone or jointly with differential use of raw/cooked ingredients across the two FCDBs. Conclusions: In the era of machine learning approaches for food image recognition, manual data curation in the alignment of FCDBs is worth the effort.

Neighborhood social vulnerability as a mediator of racial disparities in insomnia severity

Study objectivesRecent data has indicated that Black Americans experience more severe insomnia compared to their White counterparts. Although previous studies have identified psychosocial mechanisms driving this disparity, little is known about the structural determinants of insomnia disparities. This study tested neighborhood social vulnerability as a mechanism driving Black-White disparities in insomnia severity in the United States. MethodsParticipants with a previous diagnosis of insomnia (N = 196) reported their race and insomnia severity (Insomnia Severity Index). As a measure of the neighborhood environment Social Vulnerability Index was calculated by geocoding home address at the time of participation to the respective census tract from the 2020 US Census. A mediation analysis tested the indirect effect of the Social Vulnerability Index between race and insomnia severity. ResultsBlack participants reported worse insomnia severity compared to White participants. Black participants also had 3.3 times the odds of living in neighborhoods with higher social vulnerability compared to White participants, with a group median difference of 0.26 percentile points (scale 0 to 1). As hypothesized, results revealed a significant indirect effect of the Social Vulnerability Index, which accounted for 31.1% of the variance between race and insomnia severity. ConclusionLiving in a socially vulnerable neighborhood environment may be a mechanism driving racial disparities in insomnia severity. Interventions that consider structural determinants of health, including community-based and policy-level interventions could have an enhanced impact on addressing insomnia and its public health consequences.

LoVoCCS. II. Weak Lensing Mass Distributions, Red-sequence Galaxy Distributions, and Their Alignment with the Brightest Cluster Galaxy in 58 Nearby X-Ray-luminous Galaxy Clusters

The Local Volume Complete Cluster Survey is an ongoing program to observe nearly a hundred low-redshift X-ray-luminous galaxy clusters (redshifts 0.03 < z < 0.12 and X-ray luminosities in the 0.1–2.4 keV band L X500c > 1044 erg s−1) with the Dark Energy Camera, capturing data in the u, g, r, i, z bands with a 5σ point source depth of approximately 25th–26th AB magnitudes. Here, we map the aperture masses in 58 galaxy cluster fields using weak gravitational lensing. These clusters span a variety of dynamical states, from nearly relaxed to merging systems, and approximately half of them have not been subject to detailed weak lensing analysis before. In each cluster field, we analyze the alignment between the 2D mass distribution described by the aperture mass map, the 2D red-sequence (RS) galaxy distribution, and the brightest cluster galaxy (BCG). We find that the orientations of the BCG and the RS distribution are strongly aligned throughout the interiors of the clusters: the median misalignment angle is 19° within 2 Mpc. We also observe the alignment between the orientations of the RS distribution and the overall cluster mass distribution (by a median difference of 32° within 1 Mpc), although this is constrained by galaxy shape noise and the limitations of our cluster sample size. These types of alignment suggest long-term dynamical evolution within the clusters over cosmic timescales.

Comparison of effects of dexmedetomidine with ketofol and ketofol alone on quality of sedation in pediatric patients undergoing magnetic resonance imaging: A prospective randomized controlled double-blind trial

Background and Aim: Patient movement during magnetic resonance imaging (MRI) is the most frequent cause of artifacts and poor scan quality. Children cannot lie still. Thus, anesthesia is required to keep the child calm and immobile. This randomized double-blinded clinical trial compares the clinical effects of the addition of dexmedetomidine as premedication with ketofol on the quality of sedation. We hypothesized that the addition of dexmedetomidine would improve the quality of sedation. Methods: A total of 132 children aged 6 months to 10 years were randomized into groups DK (dexmedetomidine–ketofol) and K (ketofol). DK received an intravenous bolus of dexmedetomidine (0.5 mcg/kg) as premedication 10 minutes prior. Both the groups were induced with ketofol (0.5 mg/kg), and sedation was maintained with propfol infusion (100 mcg/kg/min). The primary objective was the quality of sedation as assessed by the University of Michigan Sedation Scale. Image quality, requirement of rescue propofol dose, recovery, and adverse events were also studied. Data are given as median [interquartile range (IQR)] or frequency. Results: All 132 children completed MRI scans. The DK group showed significantly better quality of sedation, 71% versus 47% of children, a median difference of 1 (-0.569 to -0.0969), P &lt; .005, a better quality of scan, a reduced number of additional doses of propofol, and a decreased total dose of propofol. Hemodynamic parameters and recovery times for the two groups were similar. There were no significant side effects in both groups. Conclusion: The quality of sedation and the quality of the MRI scan are greatly improved by administering dexmedetomidine (0.5 mcg/kg) 10 minutes before to induction. Additionally, this technique decreases the need of propofol and gives better hemodynamic stability without delaying the recovery time.

IMPACT OF ANTIHYPERTENSIVE DRUGS ON C REACTIVE PROTEIN (HS-CRP) AND NEUTROPHIL LYMPHOCYTE RATIO (NLR)

Many studies showed the association between inflammation and Hypertension. Inflammatory markers may highlight the state of inflammation in hypertensive patients. This study aimed to investigate impact of antihypertensive drugs on high sensitive C-reactive protein (hsCRP) and neutrophil lymphocyte ratio (NLR). A comparative cross sectional study was conducted on 86 hypertensive patients attending cardiology outpatient clinic in Al-Gamhuoria Modern General Hospital, Aden, in the period from October to December 2023. Participants were divided into three groups: patients treated with mono-therapy from inhibitors of renin angiotensin aldosterone system (RAASI), patients treated with mono-therapy antihypertensive not acting on RAAS (NRAASI) and patients treed with combination of them (drug combination). Data on Age, Sex, BP level, BMI, duration of hypertension (HTN), family history of HTN, and medications used were collected. Blood samples for measuring HsCRP, neutrophils, lymphocytes were drawn. Descriptive statics and chi-square tests were used for data analysis. Almost equivalent distribution for males and females between groups, with a large proportion of the patients within each group laid in the age group 35-55 years. The median values of hypertension duration were 36, 48, and 54 months for RAASIs, NRAASIs and drug combination group, respectively. The target BP was obtained by 46.9% 45.5% and 50% of patients treated with RAASIs, NRAASIs and drug combination respectively. There was a statistically significant difference between SBP and DBP in patients with controlled BP and those with uncontrolled SBP levels and treated by different drug regimens (P=0.000 for each Bp level). There were significant differences between values of hs-CRP of patients with controlled (P=0.000) or uncontrolled (P=0.046) BP and treated with different modalities. The median differences in NLR between the groups were statistically significant; including groups of all patients P=.032, of patients having controlled BP P=0.014 as well as uncontrolled BP P=0.038. Comparing the uncontrolled of BP of the three groups we found the highest prevalence (9.3%)of patients with uncontrolled BP and had the lower level hsCRP (≤3mg /l) was in RAASIs group, while those with higher prevalence (11.6%) of uncontrolled BP and higher level of hs-CRP ( &gt;3mg/l) was in drug combination group. In conclusion, hypertensive patients treated with RAASI, NRAASI and drug combination and reached BP target showed significant reduction in hsCRP and NLR. Patients with uncontrolled BP treated with RAASIs revealed slightly lower hs-CRP than other groups. Careful selection of antihypertensive drugs may affect risks of CVD. This study recommends further prospective studies exploring the anti-inflammatory effect of antihypertensive drugs to ameliorate possible risks of cardiovascular disease.

Uranium and Radium in Groundwater and Incidence of Colorectal Cancer in Georgia Counties, USA: An Ecologic Study.

Colorectal cancer (CRC) is the third most commonly occurring cancer in the United States, with higher incidence rates among Black populations. Groundwater concentrations of natural radionuclides uranium and radium have seldom been investigated in relation to CRC despite their known carcinogenicity. We investigate spatial patterns of CRC by race, and in relation to groundwater concentrations of uranium and radium, testing the hypothesis that uranium and radium in groundwater might differentially contribute to incident CRC in Black and White populations in counties of Georgia, USA. Black populations showed a higher incidence of CRC than White populations; the median incident rate difference was 9.23 cases per 100,000 (95% CI: 2.14, 19.40). Spatial cluster analysis showed high incidence clusters of CRC in similar regions for Black and White populations. Linear regression indicated there are, on average, 1-2 additional cases of colorectal cancer in counties with higher levels of radium in their groundwater, irrespective of race. Uranium was not associated with CRC. This ecologic study suggests that radium in groundwater may be linked with increased incidence of CRC, although it did not explain higher CRC incidence rates in Black populations. Further studies are needed to verify this association given the inherent limitations in the ecologic study design and the crude exposure assessment.

Association Between Mycobacterium tuberculosis Sensitization and Insulin Resistance Among US Adults Screened for Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) may be a long-term sequela of infection with Mycobacterium tuberculosis (Mtb) by mechanisms that remain to be fully explained. We evaluated the association between Mtb sensitization and T2DM and, via mediation analysis, the extent to which it is mediated by insulin resistance and/or β-cell failure. Adults were assessed for T2DM by fasting plasma glucose, 2-hour oral glucose tolerance testing, and hemoglobin A1c; β-cell dysfunction and insulin resistance by homoeostasis model assessment 2; and Mtb sensitization by tuberculin skin testing. Associations between Mtb sensitization and T2DM were modeled with probit regression and decomposed into indirect effects of β-cell dysfunction and insulin resistance. Analyses were adjusted for sociodemographic, behavioral, and clinical characteristics. We included 1843 adults. Individuals with Mtb sensitization were older than those without Mtb (median [IQR], 54 [39-64] vs 47 [33-62] years). As compared with being uninfected, Mtb sensitization was associated with T2DM (adjusted absolute risk difference, 9.34% [95% CI, 2.38%-15.0%]; P < .001) and increased insulin resistance (adjusted median difference, 0.16 [95% CI, .03-.29]; P = .014) but not β-cell dysfunction (adjusted median difference, -3.1 [95% CI, -10.4 to 4.3]; P = .42). In mediation analyses, insulin resistance mediated 18.3% (95% CI, 3.29%-36.0%; P = .020) of the total effect of the association between Mtb sensitization and T2DM. Definitive prospective studies examining incident T2DM following tuberculosis are warranted. Notwithstanding, our findings suggest that exposure to Mtb may be a novel risk factor for T2DM, likely driven by an increase in insulin resistance.

Continuous Glucose Monitoring With Geriatric Principles in Older Adults With Type 1 Diabetes and Hypoglycemia: A Randomized Controlled Trial.

Continuous glucose monitoring (CGM) use in older adults with type 1 diabetes (T1D) has shown benefits. However, the impact of CGM use, coupled with simplified treatment regimens and personalized glycemic goals that are better suited for older patients with multiple comorbidities and hypoglycemia, is not known. Older adults (≥65 years) with T1D with hypoglycemia (two or more episodes of hypoglycemia [blood glucose <70 mg/dL for ≥20 min over 2 weeks]) who were CGM naïve or CGM users were randomized to intervention and control groups. The intervention consisted of the combined use of CGM with geriatric principles (i.e., adjusting goals based on overall health, and simplification of regimens based on CGM patterns and clinical characteristics) over 6 months. The control group received usual care by their endocrinologist. The primary end point was change in time when blood glucose was <70 mg/dL from baseline to 6 months. Cost-effectiveness was calculated using a health care sector perspective. We randomized 131 participants (aged 71 ± 5 years; 21% ≥75 years old) to the intervention (n = 68; CGM users = 33) or the control (n = 63; CGM users = 40) group. The median change in hypoglycemia from baseline to 6 months was -2·6% in the intervention group and -0.3% in the control group (median difference, -2.3% [95% CI -3.7%, -1.3%]; P < 0.001). This improvement was seen in both CGM naïve (-2.8%; 95% CI -5.6%, -0.8%) and CGM users (-1.2%; 95% CI -2.7%, -0.1%). The HbA1c did not differ between the groups (7.5% vs 7.3%). The intervention was cost-effective (incremental cost-effectiveness ratio $71,623 per quality adjusted life-year). In older adults with T1D and high risk of hypoglycemia, CGM use enhanced by geriatric principles can lower hypoglycemia without worsening glycemic control in a cost-effective fashion.

Short-to-Mid-Term Outcomes of Ipsilateral Femoral Head Autograft Combined with Uncemented Total Hip Replacement for Partial Periacetabular Defects Following Tumor Resection.

Periacetabular tumors, especially in young to middle-aged patients with invasive benign tumors or low-grade malignant tumors involving type II or II + III, present significant challenges due to their rarity and the complexity of the anatomical and biomechanical structures involved. The primary difficulty lies in balancing the need to avoid unfavorable oncological outcomes while maintaining postoperative hip joint function during surgical resection. This study aimed to evaluate the effectiveness and reliability of a surgical method involving partial weight-bearing acetabular preservation combined with the use of an uncontaminated femoral head autograft to reconstruct the segmental bone defect after intra-articular resection of the tumorous joint, providing a solution that ensures both oncological safety and functional preservation of the hip joint in these patients. We conducted a retrospective study with a follow-up period of at least 36 months. From January 2010 to October 2020, we reviewed 20 cases of patients under 60 year of age with periacetabular invasive benign tumors or primary low-grade malignant tumors. All patients underwent reconstruction of the tumorous joint using autologous femoral head grafts. Data collected included patient age, gender, tumor type, preoperative and postoperative visual analog scale (VAS) scores, Musculoskeletal Tumor Society (MSTS) scores, Harris Hip Scores (HHS), patient survival rates, postoperative tumor recurrence, and surgical complications. To analyze the data, we utilized various statistical methods, including descriptive statistics to summarize patient demographics and clinical characteristics, and paired sample t-tests to compare preoperative and postoperative scores. The study included 20 patients, and a total median follow-up was 83 months. Their pathologic diagnoses comprised 13 giant cell tumors (GCTs), 5 chondrosarcomas, one chondroblastoma, and 1 leiomyosarcoma. Postoperatively, the median differences in vertical and horizontal center of rotation (COR) were 3.8 and 4.0 mm. Median limb length discrepancy (LLD) postoperatively was 5.7 mm (range, 2.3-17.8 mm). Two patients (10%) experienced delayed wound healing, resolved with antibiotics and early surgical debridement. One patient experienced dislocation 3 months postoperatively, which was promptly addressed under general anesthesia without further dislocation. Through multiplanar osteotomy with limited margins, femoral head autograft, and uncemented total hip replacement for pelvic segmental bone defects in selected patients in type II or II + III appears to be an encouraging limb-sparing surgery worthy of consideration for carefully selected patients.

Classifying Learning Speed Using Brain Networks and Psychological States: Unraveling the Interdependence Between Learning Performance, Psychological States, and Brain Functions.

Introduction The progression of performance learning (PL) may have complex relationships beyond mere concurrent occurrences and may influence each other. This study aimed to classify the speed of PL using a random forest based on brain network and stress state information and to identify the factors necessary for PL. In addition, this study also aimed to clarify the complex interdependent relationships between PL, psychological state, and brain function through these factors, using covariance structure analysis. Methods A total of 20 healthy individuals participated in a choice reaction time task, and brain function was measured using near-infrared spectroscopy (NIRS). Participants were divided into high-PL and low-PL groups based on the median difference in correct responses. Results Random forest analysis identified the left orbitofrontal area, right premotor cortex, right frontal pole, left frontal pole, left dorsolateral prefrontal cortex, and depression and anxiety as key factors. Covariance structure analysis revealed that depression and anxiety affected PL through the frontal pole and prefrontal cortex, suggesting a complex interplay between psychological state, brain function, and learning. Conclusions These findings suggest that psychological states influence brain networks, thereby affecting learning performance. Tailoring rehabilitation programs to address psychological states and providing targeted feedback may improve learning outcomes. The study provides insights into the theoretical and practical applications of understanding the brain's role in PL, as well as the importance of addressing psychological factors to optimize learning and rehabilitation strategies.

Performance of MR learned pulse sequences for 3D bi-exponential, stretched-exponential, and mono-exponential T2 and T1ρ mapping of knee cartilage.

To compare the performance of a learned magnetization-prepared gradient echo (L-MPGRE) sequence against a commonly used sequence for 3D T2 and T1ρ mapping of the knee joint, the magnetization-prepared angle-modulated partitioned k-space spoiled gradient echo snapshots (MAPSS), on bi-exponential (BE), stretched-exponential (SE), and mono-exponential (ME) relaxation models. We used a combined differentiable and non-differentiable optimization to learn pulse sequence structure and its parameters for 3D T2 and T1ρ mapping of the knee joint using ME, SE, and BE models. The learned pulse sequence framework was used to improve quantitative accuracy and SNR and to reduce filtering effects. We compare the measured multi-compartment values between the two sequences (n = 8), and their repeatability (n = 4) in healthy volunteers (n = 12 total). The voxel-wise median absolute percentage difference (MAPD) between the T2 and T1ρ maps obtained with each sequence was 18.6% and 19.9%, respectively. The T2 and T1ρ repeatability tests showed a MAPD of 18.5% and 19.1% for MAPSS, and 16.8% and 15.5% for L-MPGRE. Bland-Altman region of interest (ROI)-wise analysis shows that bias is small, close to -1.5%, and the coefficient of variation is around 5.5% when comparing ROIs from both sequences. The L-MPGRE sequences can be used as a replacement for MAPSS for T2 and T1ρ mapping in the knee cartilage with advantages, achieving similar accuracy and 15% better repeatability in only half of its scan time.