Nevin Manimala

Neurol Ther. 2022 Jul 2. doi: 10.1007/s40120-022-00380-6. Online ahead of print.

ABSTRACT

INTRODUCTION: This randomized, double-blind, placebo-controlled study in healthy volunteers assessed the safety, tolerability, and pharmacokinetics of single ascending doses of intravenously administered NX210-a linear peptide derived from subcommissural organ-spondin-and explored the effects on blood/urine biomarkers and cerebral activity.

METHODS: Participants in five cohorts (n = 8 each) were randomized to receive a single intravenous dose of NX210 (n = 6 each) (0.4, 1.25, 2.5, 5, and 10 mg/kg) or placebo (n = 2 each); in total, 10 and 29 participants received placebo and NX210, respectively. Blood samples were collected for pharmacokinetics within 180 min post dosing. Plasma and urine were collected from participants (cohorts: 2.5, 5, and 10 mg/kg) for biomarker analysis and electroencephalography (EEG) recordings within 48 h post dosing. Safety/tolerability and pharmacokinetic data were assessed before ascending to the next dose.

RESULTS: The study included 39 participants. All dosages were safe and well tolerated. All treatment-emergent adverse events (n = 17) were of mild severity and resolved spontaneously (except one with unknown outcome). Twelve treatment-emergent adverse events (70.6%) were deemed drug related; seven of those (58.3%) concerned nervous system disorders (dizziness, headache, and somnolence). The pharmacokinetic analysis indicated a short half-life in plasma (6-20 min), high apparent volume of distribution (1870-4120 L), and rapid clearance (7440-16,400 L/h). In plasma, tryptophan and homocysteine showed dose-related increase and decrease, respectively. No drug dose effect was found for the glutamate or glutamine plasma biomarkers. Nevertheless, decreased blood glutamate and increased glutamine were observed in participants treated with NX210 versus placebo. EEG showed a statistically significant decrease in beta and gamma bands and a dose-dependent increasing trend in alpha bands. Pharmacodynamics effects were sustained for several hours (plasma) or 48 h (urine and EEG).

CONCLUSION: NX210 is safe and well tolerated and may exert beneficial effects on the central nervous system, particularly in terms of cognitive processing.

PMID:35779189 | DOI:10.1007/s40120-022-00380-6

Appl Biochem Biotechnol. 2022 Jul 2. doi: 10.1007/s12010-022-04053-w. Online ahead of print.

ABSTRACT

Prodigiosin is natural red colourant derived from Serratia marcescens. However, the high cost of prodigiosin restricts its use in food and pharmaceutical industries, which can be addressed with the design of a suitable extraction procedure. Therefore, the present study aims to use Taguchi methodology to optimize various process parameters during ultrasound-assisted extraction (UAE) to get a higher prodigiosin extraction yield. The most significant contribution comes from the solid-to-liquid ratio (36.66%), followed by sonication of duty cycle (34.82%), medium pH (15.7%), and acoustic intensity (12.82%). The Taguchi technique predicts the highest optimal yield using the solid-liquid ratio (0.3 g/mL), duty cycle sonication (75%), acoustic intensity (12.5 w/cm²), and medium pH (3) as parameters. When the extraction conditions were optimized, the yield of prodigiosin increased by 4166.89 mg/L. In the future, the above extraction conditions determined using Taguchi approach will be applied for large-scale extraction of prodigiosin. Finally, a second-order kinetic model is used to suit the batch extraction investigation and the second-order rate constant (k) has a value of 4 × 10^-5 L/mg/min. In the future, the rate constant, which is reported for the first time, will be used to create a batch extractor for commercial extraction of prodigiosin. Prodigiosin has also been shown to have substantial antioxidant and scavenging properties, which increase in a dose-dependent way with prodigiosin concentration. Because of its antioxidant and scavenging properties, prodigiosin can be used as food additives or pharmaceutical ingredients in industries.

PMID:35779175 | DOI:10.1007/s12010-022-04053-w

Int J Biometeorol. 2022 Jul 2. doi: 10.1007/s00484-022-02323-0. Online ahead of print.

ABSTRACT

We evaluated the quantity and quality of scientific publications linked with water treatments using the Web of Science (WoS) database. The WoS was searching by using the following terms “hydrotherapy,” “balneotherapy,” “spa therapy,” “spa treatment,” “creno-balneotherapy,” “water treatments,” and “aqua therapy,” on February 10th, 2022. The recorded data were the total number of articles, year of articles, country of articles, journal, document type, index data, and citation data. Also, the studies performed with natural source mineral water were marked to make a further subgroup analysis through quality and quantity. We obtained 816 articles; 667 (81.74%) were original research articles, and 149 (18.26%) were review articles. A statistically significant and increasing trend was shown in the publication about water treatments (p < 0.01). About three-quarters of the trials were sourced from high-income countries. Italy (n = 98; 12.01%); Turkey (n = 75; 9.19%); Australia (n = 65; 7.97%); Brazil (n = 46; 5.64%); and France (n = 38; 4.66%) were the most productive countries. Calculating the number of articles per million population, Hungary (3.38), Australia (2.53), and Italy (1.64) ranked in the top three. According to 100 billion dollars GDP, the top three countries were Brazil (24.41), Hungary (21.15), and Turkey (10.41). In the average citation calculation, the Netherlands (60.84), Israel (29.86), and Australia (29.06) were in the top three. The International Journal of Biometeorology was the leading journal for publication trials about water treatments. In the subgroup analysis, we found the total number of studies performed with natural source mineral water and non-specified source water trials as 430 and 386, respectively. We also presented that the natural source and non-specified water trials had a statistically significant and increasing trend between 2000 and 2021 (p < 0.01 and p < 0.01, respectively). The trials performed with natural source water mainly were sourced from Italy (n = 79; 18.37%), Turkey (n = 61; 14.19%), France (n = 38; 8.84%), Poland (n = 30; 6.98%), and Hungary (n = 29; 6.74%), the trials performed with non-specified water were sourced from Australia (n = 61; 15.80%), Brazil (n = 46; 11.92%), USA (n = 27; 6.99%), Italy (n = 19; 4.92%), and England (n = 18; 4.66%). The top journal of the natural source water trials was the International Journal of Biometeorology (n = 65; 15.12%), and for the non-specified water trials, it was the International Journal of Sports Physiology (n = 12; 3.11%).Our study presented an increasing trend in trial publications regarding water treatments between 2000 and 2021. Most of the trials were from high and upper-middle-income countries. We suggest that by demonstrating global productivity worldwide, our results can create more scientific attention on this topic and may promote the quantity and quality of the trials.

PMID:35779167 | DOI:10.1007/s00484-022-02323-0

Sleep Breath. 2022 Jul 2. doi: 10.1007/s11325-022-02663-6. Online ahead of print.

ABSTRACT

PURPOSE: Hypoglossal nerve stimulation (HNS) has been shown to treat obstructive sleep apnea (OSA) effectively. The aim of this study was to compare HNS with positive airway pressure (PAP) treatment regarding outcome parameters: (1) sleepiness, (2) apnea-hypopnea index (AHI), and (3) effectiveness.

METHODS: Propensity score matching with nearest neighbor algorithm was used to compare outcomes of HNS and PAP therapy in a real-world setting. Data were collected at baseline and 12 months after initiating OSA treatment including demographics, Epworth Sleepiness Scale (ESS), AHI, and objective adherence data. To account for overall treatment efficacy, the mean disease alleviation (MDA) was calculated.

RESULTS: Of 227 patients who received treatment consecutively, 126 could be matched 1:1 with regard to age, body mass index, and AHI. After matching, no statistically significant differences between the groups were found. A clinically important symptom improvement was seen at 12 months in both cohorts, though there was a greater difference in ESS improvement in patients treated with HNS (8.0 ± 5.1 points vs. 3.9 ± 6.8 points; p = 0.042). In both groups, mean posttreatment AHI was significantly reduced (HNS: 8.1 ± 6.3/h; PAP: 6.6 ± 8.0/h; p < 0.001). Adherence after 12 months among patients treated with HNS was higher than in those receiving PAP therapy (5.0 ± 2.6 h/night; 4.0 ± 2.1 h/night) but not with statistical significance. Overall effectiveness calculated with the MDA was 59% in patients treated with HNS compared to 51% receiving PAP.

CONCLUSION: Patients treated with HNS therapy had significantly greater improvements in daytime sleepiness compared to PAP therapy, while the mean reduction of AHI and overall effectiveness were comparable for both treatments.

TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT03756805.

PMID:35779166 | DOI:10.1007/s11325-022-02663-6

Eur J Orthop Surg Traumatol. 2022 Jul 2. doi: 10.1007/s00590-022-03320-0. Online ahead of print.

ABSTRACT

PURPOSE: We assessed acetabular erosion, hip function, quality of life (QoL), pain, deep infection, mortality, re-operation and dislocation rates in patients with displaced femoral neck fractures (dFNFs) treated with unipolar versus bipolar hemiarthroplasty at different postoperative time points.

METHODS: Relevant Randomized Controlled Trials (RCTs) were identified, following comprehensive literature research in Medline, Cochrane Central and Scopus databases, from conception until August 31th, 2021 and analyzed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

RESULTS: Database research retrieved 120 studies; sixteen met eligibility criteria, providing 1813 (1814 hips) evaluable patients. Acetabular erosion was significantly higher for unipolar group at 6 and 12 months (p = 0.02 and p = 0.01 respectively). Patients in the bipolar group presented significantly better hip function at 12 and 24 months (p = 0.02 and p = 0.04 respectively). Postoperative pain was significantly less in the bipolar group at 12, 24 and 48 months (p = 0.01). No statistically significant differences were found regarding the postoperative rates of deep infection, mortality, re-operation and dislocation.

CONCLUSION: This study showed that patients with dFNFs treated with bipolar hemiarthroplasty have lower acetabular erosion rates at 6 and 12 months postoperatively, better hip function at 12 and 24 months, better QoL and less pain, when compared with unipolar. No statistically significant difference could be established regarding deep infection, mortality, re-operation and dislocation rates.

PMID:35779144 | DOI:10.1007/s00590-022-03320-0

J Biol Phys. 2022 Jul 2. doi: 10.1007/s10867-022-09609-9. Online ahead of print.

ABSTRACT

Modeling and analysis of biological growth curves are an age-old study area in which much effort has been dedicated to developing new growth equations. Recent efforts focus on identifying the correct model from a large number of equations. The relative growth rate (RGR), developed by Fisher (1921), has largely been used in the statistical inference of biological growth curve models. It is convenient to express growth equations using RGR, where RGR can be expressed as functions of size or time. Even though RGR is model invariant, it has limitations when it comes to identifying actual growth patterns. By proposing interval-specific rate parameters (ISRPs), Pal et al. (2018) appeared to solve this problem. The ISRP is based on the mathematical structure of the growth equations. Therefore, it is not model invariant. The current effort is to develop a measure of growth that is model invariant like RGR and shares the advantages of ISRP. We propose a new measure of growth, which we call instantaneous maturity rate (IMR). IMR is model invariant, which allows it to distinguish growth patterns more clearly than RGR. IMR is also scale-invariant and can take several forms including increasing, decreasing, constant, sigmoidal, bell-shaped, and bathtub. A wide range of possible IMR shapes makes it possible to identify different growth curves. The estimation procedure of IMR under a stochastic setup has been developed. Statistical properties of empirical IMR estimators have also been investigated in detail. In addition to extensive simulation studies, real data sets have been analyzed to prove the utility of IMR.

PMID:35779141 | DOI:10.1007/s10867-022-09609-9

Arch Orthop Trauma Surg. 2022 Jul 2. doi: 10.1007/s00402-022-04530-1. Online ahead of print.

ABSTRACT

INTRODUCTION: High body mass index (BMI) and wound drainage following total joint arthroplasty (TJA) can lead to wound healing complications and periprosthetic joint infection. Silver-embedded occlusive dressings and negative pressure wound therapy (NPWT) have been shown to reduce these complications. The purpose of this prospective trial was to compare the effect of silver-embedded dressings and NPWT on wound complications in patients with BMI ≥ 35 m/kg2 undergoing TJA.

METHODS: We conducted a randomized control trial of patients who had a BMI > 35 m/kg² and were undergoing primary TJA between October 2017 and February 2020. Patients who underwent revision surgery, or those with an active infection, previous scar, history of wound healing complications, post-traumatic degenerative joint disease with hardware, or inflammatory arthritis were excluded. Patients were randomized to receive either a silver-embedded occlusive dressing (control) or NPWT. Frequency distributions, means, and standard deviations were used to describe patient demographics, postoperative complications, 90-day readmissions, and reoperations. T-test and chi-squared tests were used to test for significant differences between continuous and categorical variables, respectively.

RESULTS: Two hundred-thirty patients with 3-month follow-up were included. One-hundred-fifteen patients received the control and 115 patients received NPWT. There were six patients (5.2%) in the control group with wound complications (drainage: n = 5, non-healing wound: n = 1) and two patients (1.7%) in the NPWT with complications (drainage: n = 2). There were no 90-day readmissions in the control group versus two (1.8%) 90-day readmissions in the NPWT group. Finally, three patients (2.6%) in the control group underwent reoperations (irrigation and debridement [I&D], I&D with modular implant exchange, and implant revision), while none in the NPWT group had undergone reoperation. The two groups showed insignificant differences in wound complications (p = 0.28), 90-day readmissions (p = 0.50), and reoperations (p = 0.25).

CONCLUSION: Patients with BMI ≥ 35 m/kg2 undergoing TJA have no statistical difference in early wound complications, readmissions, or reoperations when treated with either silver-embedded dressings or NPWT.

PMID:35779102 | DOI:10.1007/s00402-022-04530-1

Eur Radiol. 2022 Jul 2. doi: 10.1007/s00330-022-08934-w. Online ahead of print.

ABSTRACT

OBJECTIVES: To provide a standard for total abdominal muscle mass (TAM) quantification on computed tomography (CT) and investigate its association with cardiovascular risk in a primary prevention setting.

METHODS: We included 3016 Framingham Heart Study participants free of cardiovascular disease (CVD) who underwent abdominal CT between 2002 and 2005. On a single CT slice at the level of L3/L4, we segmented (1) TAM-Area, (2) TAM-Index (= TAM-Area/height) and, (3) TAM-Fraction (= TAM-Area/total cross-sectional CT-area). We tested the association of these muscle mass measures with prevalent and incident cardiometabolic risk factors and incident CVD events during a follow-up of 11.0 ± 2.7 years.

RESULTS: In this community-based sample (49% women, mean age: 50.0 ± 10.0 years), all muscle quantity measures were significantly associated with prevalent and incident cardiometabolic risk factors and CVD events. However, only TAM-Fraction remained significantly associated with key outcomes (e.g., adj. OR 0.68 [0.55, 0.84] and HR 0.73 [0.57, 0.92] for incident hypertension and CVD events, respectively) after adjustment for age, sex, body mass index, and waist circumference. Moreover, only higher TAM-Fraction was associated with a lower risk (e.g., adj. OR: 0.56 [0.36-0.89] for incident diabetes versus TAM-Area: adj. OR 1.26 [0.79-2.01] and TAM-Index: 1.09 [0.75-1.58]).

CONCLUSION: TAM-Fraction on a single CT slice at L3/L4 is a novel body composition marker of cardiometabolic risk in a primary prevention setting that has the potential to improve risk stratification beyond traditional measures of obesity.

KEY POINTS: • In this analysis of the Framingham Heart Study (n = 3016), TAM-F on a single slice CT was more closely associated with prevalent and incident cardiometabolic risk factors as compared to TAM alone or TAM indexed to body surface area. • TAM-F on a single abdominal CT slice at the level of L3/L4 could serve as a standard measure of muscle mass and improve risk prediction.

PMID:35779090 | DOI:10.1007/s00330-022-08934-w

Eur Radiol. 2022 Jul 2. doi: 10.1007/s00330-022-08969-z. Online ahead of print.

ABSTRACT

OBJECTIVES: While chest radiograph (CXR) is the first-line imaging investigation in patients with respiratory symptoms, differentiating COVID-19 from other respiratory infections on CXR remains challenging. We developed and validated an AI system for COVID-19 detection on presenting CXR.

METHODS: A deep learning model (RadGenX), trained on 168,850 CXRs, was validated on a large international test set of presenting CXRs of symptomatic patients from 9 study sites (US, Italy, and Hong Kong SAR) and 2 public datasets from the US and Europe. Performance was measured by area under the receiver operator characteristic curve (AUC). Bootstrapped simulations were performed to assess performance across a range of potential COVID-19 disease prevalence values (3.33 to 33.3%). Comparison against international radiologists was performed on an independent test set of 852 cases.

RESULTS: RadGenX achieved an AUC of 0.89 on 4-fold cross-validation and an AUC of 0.79 (95%CI 0.78-0.80) on an independent test cohort of 5,894 patients. Delong’s test showed statistical differences in model performance across patients from different regions (p < 0.01), disease severity (p < 0.001), gender (p < 0.001), and age (p = 0.03). Prevalence simulations showed the negative predictive value increases from 86.1% at 33.3% prevalence, to greater than 98.5% at any prevalence below 4.5%. Compared with radiologists, McNemar’s test showed the model has higher sensitivity (p < 0.001) but lower specificity (p < 0.001).

CONCLUSION: An AI model that predicts COVID-19 infection on CXR in symptomatic patients was validated on a large international cohort providing valuable context on testing and performance expectations for AI systems that perform COVID-19 prediction on CXR.

KEY POINTS: • An AI model developed using CXRs to detect COVID-19 was validated in a large multi-center cohort of 5,894 patients from 9 prospectively recruited sites and 2 public datasets. • Differences in AI model performance were seen across region, disease severity, gender, and age. • Prevalence simulations on the international test set demonstrate the model’s NPV is greater than 98.5% at any prevalence below 4.5%.

PMID:35779089 | DOI:10.1007/s00330-022-08969-z

Rheumatol Int. 2022 Jul 2. doi: 10.1007/s00296-022-05164-7. Online ahead of print.

ABSTRACT

There are limited data about humoral response to vaccine in Behçet’s syndrome (BS). We compared SARS-CoV-2 antibody response after two doses of inactivated (Sinovac/CoronaVac) or mRNA (Pfizer/BioNTech) vaccines in patients with BS and healthy controls (HCs). We studied 166 (92M/74F) patients with BS (mean age: 42.9 ± 9.6 years) and 165 (75M/90F) healthy controls (mean age: 42.4 ± 10.4 years), in a single-center cross-sectional design between April 2021 and October 2021. A total of 80 patients with BS and 89 HCs received two doses of CoronaVac, while 86 patients with BS and 76 HCs were vaccinated with BioNTech. All study subjects had a negative history for COVID-19. Serum samples were collected at least 21 days after the second dose of the vaccine. Anti-spike IgG antibody titers were measured quantitatively using a commercially available immunoassay method. We found that the great majority in both patient and HC groups had detectable antibodies after either CoronaVac (96.3% vs 100%) or BioNTech (98.8% vs 100%). Among those vaccinated with CoronaVac, BS patients had significantly lower median (IQR) titers compared to HCs [36.5 (12.5-128.5) vs 102 (59-180), p < 0.001]. On the other hand, antibody titers did not differ among patients with BS and HCs who were vaccinated with BioNTech [1648.5 (527.0-3693.8) vs 1516.0 (836.3-2599.5), p = 0.512). Among different treatment regimen subgroups in both vaccine groups, those who were using anti-TNF-based treatment had the lowest antibody titers. However, the difference was statistically significant only among those vaccinated with CoronaVac. Among patients vaccinated with BioNTech, there was no statistically significant difference between different treatment regimen groups. Compared to inactivated COVID-19 vaccine, mRNA-based vaccine elicited higher antibody titers among BS patients. Only in the CoronaVac group, patients especially those using anti-TNF agents were found to have low titers compared to healthy subjects. BS patients vaccinated with BioNTech were found to have similar seroconversion rates and antibody levels compared to healthy controls. Further studies should assess whether the low antibody titers are associated with diminished protection against COVID-19 in both vaccine groups.

PMID:35779083 | DOI:10.1007/s00296-022-05164-7