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Human umbilical cord-derived mesenchymal stem cell transplantation improves the long COVID

J Med Virol. 2024 Jun;96(6):e29757. doi: 10.1002/jmv.29757.

ABSTRACT

No effective treatments can ameliorate symptoms of long COVID patients. Our study assessed the safety and efficacy of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) in the treatment of long COVID patients. Ten long COVID patients were enrolled and received intravenous infusions of UC-MSCs on Days 0, 7, and 14. Adverse events and clinical symptoms were recorded, and chest-high-resolution CT (HRCT) images and laboratory parameters were analyzed. During UC-MSCs treatment and follow-up, we did not observe serious adverse events, the symptoms of long COVID patients were significantly relieved in a short time, especially sleep difficulty, depression or anxiety, memory issues, and so forth, and the lung lesions were also repaired. The routine laboratory parameters did not exhibit any significant abnormalities following UC-MSCs transplantation (UMSCT). The proportion of regulatory T cells gradually increased, but it was not statistically significant until 12 months. The proportion of naive B cells was elevated, while memory B cells, class-switched B-cells, and nonswitched B-cells decreased at 1 month after infusion. Additionally, we observed a transient elevation in circulating interleukin (IL)-6 after UMSCT, while tumor necrosis factor (TNF)-α, IL-17A, and IL-10 showed no significant changes. The levels of circulating immunoglobulin (Ig) M increased significantly at month 2, while IgA increased significantly at month 6. Furthermore, the SARS-CoV-2 IgG levels remained consistently high in all patients at Month 6, and there was no significant decrease during the subsequent 12-month follow-up. UMSCT was safe and tolerable in long COVID patients. It showed potential in alleviating long COVID symptoms and improving interstitial lung lesions.

PMID:38899432 | DOI:10.1002/jmv.29757

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Efgartigimod in refractory autoimmune myasthenia gravis

Muscle Nerve. 2024 Jun 20. doi: 10.1002/mus.28184. Online ahead of print.

ABSTRACT

INTRODUCTION/AIMS: Efgartigimod, a neonatal Fc-receptor inhibitor, has recently been approved as treatment for myasthenia gravis (MG). In this retrospective cohort study, we aimed to systematically assess short- and long-term effectiveness of efgartigimod in patients with refractory MG.

METHODS: Sixteen patients with refractory autoimmune acetylcholine receptor MG were treated with efgartigimod. Data were collected from January 2021 to March 2023 on Myasthenia Gravis Activities of Daily Living (MG-ADL), Quantitative Myasthenia Gravis score (QMG), Myasthenia Gravis Composite score (MGC) and the 15-item revised version of the Myasthenia Gravis Quality of Life questionnaire (MG-QoL15r).

RESULTS: A favorable outcome was seen in 56% of patients at the last measurement. Out of 16 patients, 50% were an MG-ADL responder after the first treatment cycle. After 4 weeks, a clinically meaningful improvement compared to baseline was seen on the MG-ADL, QMG, and MGC. There was a statistically significant improvement on the MGQoL15r from baseline to week 4. The improvement was maintained until the last measurement for the MGC and the MGQoL15r. At the last visit, all patients had discontinued 4-weekly dosages, shifting to administration frequencies of 1, 2, or 3 weeks. Drug doses could be decreased for prednisolone (n = 7), azathioprine (n = 2), and intravenous immunoglobulin (n = 9). Frequency of plasma exchange was decreased in nine patients.

DISCUSSION: In patients with refractory MG, efgartigimod was effective for at least half of all patients. Patients required more frequent dosing compared to the ADAPT phase 3 trial. In 80% of the patients concurrent medication could be reduced or discontinued.

PMID:38899431 | DOI:10.1002/mus.28184

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Robust optimization of the Gross Tumor Volume compared to conventional Planning Target Volume-based planning in photon Stereotactic Body Radiation Therapy of lung tumors

Acta Oncol. 2024 Jun 20;63:448-455. doi: 10.2340/1651-226X.2024.40049.

ABSTRACT

BACKGROUND: Robust optimization has been suggested as an approach to reduce the irradiated volume in lung Stereotactic Body Radiation Therapy (SBRT). We performed a retrospective planning study to investigate the potential benefits over Planning Target Volume (PTV)-based planning.

MATERIAL AND METHODS: Thirty-nine patients had additional plans using robust optimization with 5-mm isocenter shifts of the Gross Tumor Volume (GTV) created in addition to the PTV-based plan used for treatment. The optimization included the mid-position phase and the extreme breathing phases of the 4D-CT planning scan. The plans were compared for tumor coverage, isodose volumes, and doses to Organs At Risk (OAR). Additionally, we evaluated both plans with respect to observed tumor motion using the peak tumor motion seen on the planning scan and cone-beam CTs.

RESULTS: Statistically significant reductions in irradiated isodose volumes and doses to OAR were achieved with robust optimization, while preserving tumor dose. The reductions were largest for the low-dose volumes and reductions up to 188 ccm was observed. The robust evaluation based on observed peak tumor motion showed comparable target doses between the two planning methods. Accumulated mean GTV-dose was increased by a median of 4.46 Gy and a non-significant increase of 100 Monitor Units (MU) was seen in the robust optimized plans.

INTERPRETATION: The robust plans required more time to prepare, and while it might not be a feasible planning strategy for all lung SBRT patients, we suggest it might be useful for selected patients.

PMID:38899392 | DOI:10.2340/1651-226X.2024.40049

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Disparities and Biases in Food Insecurity Screening Among Admitted Children

Hosp Pediatr. 2024 Jun 20:e2023007602. doi: 10.1542/hpeds.2023-007602. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Food insecurity (FI) has increasingly become a focus for hospitalized patients. The best methods for screening practices, particularly in hospitalized children, are unknown. The purpose of the study was to evaluate results of an electronic medical record (EMR) embedded, brief screening tool for FI among inpatients.

METHODS: This was a cross-sectional study from August 2020 to September 2022 for all children admitted to a quaternary children’s hospital. Primary outcomes were proportion of those screened for FI and those identified to have a positive screen. FI was evaluated by The Hunger Vital Sign, a validated 2-question screen verbally obtained in the nursing intake form in the EMR. Covariates include demographic variables of age, sex, race, ethnicity, primary language, and insurance. Statistical analyses including all univariate outcome and bivariate comparisons were performed with SAS 9.4.

RESULTS: There were 31 553 patient encounters with 81.7% screened for FI. Patients had a median age of 6.3 years, were mostly male (54.2%), White (60.6%), non-Hispanic (92.7%), English-speaking (94.3%), and had government insurance (79.8%). Younger (0-2 years), non-White, and noninsured patients were all screened significantly less often for FI (all P < .001). A total of 3.4% were identified as having FI. Patients who were older, non-White, Hispanic, non-English speaking, and had nonprivate insurance had higher FI (all P < .001).

CONCLUSIONS: Despite the use of an EMR screening tool intended to be universal, we found variation in how we screen for FI. At times, we missed those who would benefit the most from intervention, and thus it may be subject to implementation bias.

PMID:38899389 | DOI:10.1542/hpeds.2023-007602

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Establishment and evaluation of a new fluorescent probe method based on loop-mediated isothermal amplification for the detection of Mycobacterium tuberculosis complex

Luminescence. 2024 Jun;39(6):e4795. doi: 10.1002/bio.4795.

ABSTRACT

We aimed to develop a novel diagnostic method called multiplex fluorescence of loop primer upon self-dequenching loop-mediated isothermal amplification (mFLOS-LAMP) for the rapid detection of Mycobacterium tuberculosis complex (MTBC). A set of specific primers was designed to target the detection of IS1081 and IS6110 genes, which are insertion sequences within the MTBC. The 110 sputum specimens collected were assessed using the established mFLOS-LAMP method, multiplex polymerase chain reaction, Xpert MTB/RIF, and smear microscopy. The optimal reaction temperature and duration for mFLOS-LAMP were determined to be 65°C and 30 min, respectively, by optimizing the entire system. The detection sensitivity of mFLOS-LAMP was 6.0 × 101 CFU/mL, by Bacillus Calmette-Guerin, and the mFLOS-LAMP sensitivity of M. tuberculosis H37Rv genomic DNA was 500 fg, and the specificity was 100%. The sensitivity of mFLOS-LAMP was 94.2% and the specificity was 96.6%, when Xpert MTB/RIF was used as the reference method. There was no statistically significant difference in their detection rate (χ2 = 0, P = 1.000), and the consistency was good (kappa = 0.909, P < 0.001). The receiver operating characteristic analysis yielded the maximum area under the curve of 0.954. The mFLOS-LAMP method demonstrated high sensitivity and specificity, allowing for swift and accurate detection of MTBC.

PMID:38899381 | DOI:10.1002/bio.4795

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A statistical primer on classical period-finding techniques in astronomy

Rep Prog Phys. 2024 Jun 20;87(7). doi: 10.1088/1361-6633/ad4586.

ABSTRACT

The aim of our paper is to investigate the properties of the classical phase-dispersion minimization (PDM), analysis of variance (AOV), string-length (SL), and Lomb-Scargle (LS) power statistics from a statistician’s perspective. We confirm that when the data are perturbations of a constant function, i.e. under the null hypothesis of no period in the data, a scaled version of the PDM statistic follows a beta distribution, the AOV statistic follows an F distribution, and the LS power follows a chi-squared distribution with two degrees of freedom. However, the SL statistic does not have a closed-form distribution. We further verify these theoretical distributions through simulations and demonstrate that the extreme values of these statistics (over a range of trial periods), often used for period estimation and determination of the false alarm probability (FAP), follow different distributions than those derived for a single period. We emphasize that multiple-testing considerations are needed to correctly derive FAP bounds. Though, in fact, multiple-testing controls are built into the FAP bound for these extreme-value statistics, e.g. the FAP bound derived specifically for the maximum LS power statistic over a range of trial periods. Additionally, we find that all of these methods are robust to heteroscedastic noise aimed to mimic the degradation or miscalibration of an instrument over time. Finally, we examine the ability of these statistics to detect a non-constant periodic function via simulating data that mimics a well-detached binary system, and we find that the AOV statistic has the most power to detect the correct period, which agrees with what has been observed in practice.

PMID:38899367 | DOI:10.1088/1361-6633/ad4586

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Clinical impact of clonal hematopoiesis in hematopoietic cell transplantation: a review, metaanalysis, and call to action

Haematologica. 2024 Jun 20. doi: 10.3324/haematol.2024.285392. Online ahead of print.

ABSTRACT

Hematopoietic cell transplantation (HCT) is the only potentially curative treatment option for many patients with hematologic malignancies. While HCT outcomes have improved drastically over the years, patients and clinicians continue to face numerous survivorship challenges, such as relapse, graft-versushost disease, and secondary malignancies. Recent literature suggests that clonal hematopoiesis (CH), the presence of a recurrent somatic mutation in hematopoietic cells, in HCT patients or donors may be associated with outcomes in autologous and allogeneic HCT. Herein, we perform a review of the literature and summarize reported associations between CH and clinical outcomes in HCT. For commonly reported outcomes, we used meta-analysis methods to provide estimates of effect sizes when combining results. A total of 32 articles with relevant and independent contributions were included, covering both autologous (n = 19) and allogeneic (n = 13) HCT. The articles report variable risk for developing outcomes according to CH characteristics, patient disease status, and method of HCT. Using meta-analysis of available results, HCT outcomes with statistically significant effects by CH status include therapy-related myeloid neoplasms (OR 3.65, 95%CI 2.18-6.10) and overall survival (HR 1.38, 95%CI 1.20-1.58) in autologous HCT and relapse (HR 0.80, 95%CI 0.68-0.94) in allogeneic HCT. However, heterogeneity, biases, and limitations in the literature provide challenges for informing the translation of CH to clinical decision-making. We conclude with a call to action and discussion of next steps to build upon the current literature and provide granularity to the true clinical impact of CH in the setting of HCT.

PMID:38899345 | DOI:10.3324/haematol.2024.285392

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Prevalence and social determinants of smoking among men in Mauritius: a cross-sectional study

Glob Health Action. 2024 Dec 31;17(1):2367415. doi: 10.1080/16549716.2024.2367415. Epub 2024 Jun 20.

ABSTRACT

BACKGROUND: Mauritius has implemented a range of stringent policies to control smoking and promote public health. Regular monitoring focuses on the prevalence of tobacco use, yet there is a gap in understanding its socio-economic patterns.

OBJECTIVE: The aim of this study was to estimate the prevalence of tobacco smoking and to identify the social determinants associated with smoking among men in Mauritius in 2021.

METHODS: This is a cross-sectional population-based study conducted by the Ministry of Health and Wellness during 2021. In total, 3622 individuals participated (response rate of 84.1%), of which 1663 were men (45.9%). The study mainly focused on men given the low prevalence of smoking among women. Daily smoking was the outcome and a series of sociodemographic and socioeconomic factors were included as independent variables. Prevalence ratios (PR) and their 95% confidence intervals (95% CI) were estimated to fulfill the study objective.

RESULTS: The prevalence of smoking among men was 30.4%. People in the 25-34 age group (PR = 1.65; 95% CI: 1.12-2.41), those separated, divorced or widowed (PR = 1.57; 95% CI: 1.16-2.11), the ethnic groups Muslim-Mauritians (PR = 1.70; 95% CI: 1.00-2.89) and Creoles (PR = 1.97; 95% CI: 1.16-3.35), and those with secondary (PR = 1.29; 95% CI: 1.00-1.67) and primary education (PR = 1.47; 95% CI: 1.10-1.98) were statistically significantly associated with daily smoking.

CONCLUSIONS: Although a gradual decline in smoking prevalence was observed compared with the previous 2015 survey, the Ministry of Health and Wellness should persist in fortifying its anti-smoking measures and concentrate on crafting tailored interventions aimed at the vulnerable groups identified in this study.

PMID:38899339 | DOI:10.1080/16549716.2024.2367415

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Measuring and shaping the nutritional environment via food sales logs: case studies of campus-wide food choice and a call to action

Front Nutr. 2024 Jun 4;11:1231070. doi: 10.3389/fnut.2024.1231070. eCollection 2024.

ABSTRACT

Although diets influence health and the environment, measuring and changing nutrition is challenging. Traditional measurement methods face challenges, and designing and conducting behavior-changing interventions is conceptually and logistically complicated. Situated local communities such as university campuses offer unique opportunities to shape the nutritional environment and promote health and sustainability. The present study investigates how passively sensed food purchase logs typically collected as part of regular business operations can be used to monitor and measure on-campus food consumption and understand food choice determinants. First, based on 38 million sales logs collected on a large university campus over eight years, we perform statistical analyses to quantify spatio-temporal determinants of food choice and characterize harmful patterns in dietary behaviors, in a case study of food purchasing at EPFL campus. We identify spatial proximity, food item pairing, and academic schedules (yearly and daily) as important determinants driving the on-campus food choice. The case studies demonstrate the potential of food sales logs for measuring nutrition and highlight the breadth and depth of future possibilities to study individual food-choice determinants. We describe how these insights provide an opportunity for stakeholders, such as campus offices responsible for managing food services, to shape the nutritional environment and improve health and sustainability by designing policies and behavioral interventions. Finally, based on the insights derived through the case study of food purchases at EPFL campus, we identify five future opportunities and offer a call to action for the nutrition research community to contribute to ensuring the health and sustainability of on-campus populations-the very communities to which many researchers belong.

PMID:38899323 | PMC:PMC11186467 | DOI:10.3389/fnut.2024.1231070

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Effect of acupuncture intervention time on the therapeutic effect in patients with sudden hearing loss

Zhen Ci Yan Jiu. 2024 Jun 25;49(6):618-624. doi: 10.13702/j.1000-0607.20230299.

ABSTRACT

OBJECTIVES: To observe the clinical efficacy of acupuncture intervention at different time for patients with sudden hearing loss.

METHODS: According to the timing of acupuncture intervention, 86 patients were divided into early exposure group (n=43) and late exposure group (n=43) . The early exposure group was given acupuncture treatment within 14 days of onset, and the late exposure group was given acupuncture treatment after 14 days of onset. After propensity score matching (PSM, a statistical matching technique for observational data) processing by using SPSS26.0 software, outcomes of 30 cases in the early exposure group and 30 cases in the late exposure group were analyzed. In addition to receiving basic treatment with drugs for vascular dilatation, thrombolysis, nourishing nerve, etc., all patients of the two groups were treated with neck acupuncture (“Neck Seven Meridian Lines” acupuncture), once every other day except Sundays, for a total of 12 time. Before, after the treatment and 3 months after the treatment, the total score of the Tinnitus Handicap Inventory (THI, 0, 2 and 4 points for each of the 25 items, total scores = 100 points) scale was used to evaluate the improvement of tinnitus symptoms caused by hearing loss. The clinical therapeutic effect was evaluated according to the efficacy grading criteria in the Guidelines for Diagnosis and Treatment of Sudden Deafness (2015) and the changes of pure tone audiometry curve. Multivariate Logistic regression was used to analyze the effect of factors that might influence efficacy before propensity score matching.

RESULTS: The THI scores of patients in both groups decreased strikingly after the treatment and 3 months’ follow-up (P<0.05). Compared with the same time-points of the late exposure group, the total THI scores of post-treatment and 3 months’ follow-up were evidently lower in the early exposure group (P<0.05). The effective rate of the early exposure group (22/30, 80.00%) was significantly higher (P<0.05) than that of the late exposure group (16/30, 53.33%). The classification of sudden deafness and the application of traditional Chinese medicine in this study were not independent factors affecting the total effective rate.

CONCLUSIONS: The time point of acupuncture intervention is an important factor affecting the effect on hearing and tinnitus disability of patients with sudden deafness. The earlier acupuncture treatment is accepted, the better the therapeutic effect is.

PMID:38897806 | DOI:10.13702/j.1000-0607.20230299