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Evaluation of alpha-defensins as a marker of severity in chronic obstructive pulmonary disease

Lung India. 2024 Jul 1;41(4):259-264. doi: 10.4103/lungindia.lungindia_395_23. Epub 2024 Jun 28.

ABSTRACT

BACKGROUND: Defensins are key effector molecules of innate immunity that can contribute towards the diagnosis and monitoring of chronic obstructive pulmonary disease (COPD). The present study was conducted to investigate the role of alpha-defensins in patients with COPD by quantifying serum and sputum samples.

METHODS: A total of 180 patients were enrolled and divided into four groups, and sputum and serum values of alpha-defensins were assessed. The sensitivity, specificity, and accuracy of sputum alpha-defensin as a diagnostic biomarker were evaluated to assess its utility in diagnosing COPD.

RESULTS: The mean value of sputum alpha-defensins was found to be statistically significant amongst the four groups (P < 0.001). The highest levels were found in subjects with AECOPD (385.76 ± 116.62 ng/mL). Sputum alpha-defensins were found to be negatively correlated with FEV 1 values (rho = -0.31, P < 0.001).

CONCLUSION: Sputum alpha-defensins can be used as a potential marker for predicting acute exacerbation of COPD. In addition, they could serve as an indicator of disease severity in COPD patients.

PMID:38953188 | DOI:10.4103/lungindia.lungindia_395_23

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Multiple forms of perceived job discrimination and hypertension risk among employed women: Findings from the Sister Study

Am J Ind Med. 2024 Jul 2. doi: 10.1002/ajim.23634. Online ahead of print.

ABSTRACT

BACKGROUND: Hypertension has been linked to socially patterned stressors, including discrimination. Few studies have quantified the risk of hypertension associated with exposure to perceived job discrimination.

METHODS: We used prospective cohort data from the Sister Study (enrollment from 2003-2009) to estimate self-reported incident hypertension associated with perceived job discrimination based on race, gender, age, sexual orientation, or health status. Job discrimination in the prior 5 years was assessed in 2008-2012, and incident doctor-diagnosed hypertension was ascertained in previously hypertension-free participants.

RESULTS: Among the 16,770 eligible participants aged 37-78 years at the start of follow-up, 10.5% reported job discrimination in the past 5 years, and 19.2% (n = 3226) reported incident hypertension during a median follow-up of 9.7 years (interquartile range 8.2-11.0 years). Self-reported poor health or inclusion in minoritized groups based on race/ethnicity or sexual orientation were more frequent among those reporting job discrimination. In a Cox proportional hazards model adjusting for covariates, report of at least one type of job discrimination (compared to none) was associated with a 14% (hazard ratio = 1.14 [95% confidence: 1.02-1.27]) higher hypertension risk. Results from sensitivity analyses reinforced the findings.

CONCLUSIONS: Results suggest that interventions addressing job discrimination could have workplace equity and health benefits.

PMID:38953171 | DOI:10.1002/ajim.23634

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Immunomodulatory Effects of Yu-Ping-Feng Formula on Primary Sjögren’s Syndrome: Interrogating the T Cell Response

J Leukoc Biol. 2024 Jul 2:qiae155. doi: 10.1093/jleuko/qiae155. Online ahead of print.

ABSTRACT

Ethnopharmacological treatments have shown beneficial effects in the clinical practice of autoimmune disorders. However, the underlying mechanism of immunomodulatory effects remains challenging, given the complicate composition of herbal medicines. Here, we developed an immunological approach to interrogate the T helper cell response. Through data mining we hypothesized that Chinese medicine formula, Yu-Ping-Feng (YPF) might be a promising candidate for treating primary Sjögren’s syndrome (pSS), a common autoimmune disease manifested by exocrine gland dysfunction. We took advantage of a mouse model of experimental Sjögren’s syndrome (ESS) that we previously established for YPF formula treatment. YPF therapy ameliorated the ESS pathology in mice with active disease, showing improved salivary function and decreased serum levels of autoantibodies. Phenotypic analysis suggested that both effector T and B cells were significantly suppressed. Using co-culture assay and adoptive transfer models, we demonstrated that YPF formula directly restrained effector/memory T cell expansion and differentiation into Th17 and T follicular helper (Tfh) cells, the key subsets in ESS pathogenesis. Importantly, we recruited 20 pSS patients and conducted a pilot study of 8-week therapy of YPF formula. YPF treatment effectively improved fatigue symptoms, exocrine gland functions and reduced serum IgG/IgA levels, while effector T and B cell subsets were significantly decreased. There was a trend of reduction on disease activity, but not statistically significant. Together, our findings suggested a novel approach to assess the immunomodulatory effects of YPF formula, which may be favorable for patients with autoimmune disorders.

PMID:38953166 | DOI:10.1093/jleuko/qiae155

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Associations between COVID-19 therapies and outcomes in rural and urban America: A multisite, temporal analysis from the Alpha to Omicron SARS-CoV-2 variants

J Rural Health. 2024 Jul 2. doi: 10.1111/jrh.12857. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the enduring disparities in adverse COVID-19 events between urban and rural communities in the United States, focusing on the effects of SARS-CoV-2 vaccination and therapeutic advances on patient outcomes.

METHODS: Using National COVID Cohort Collaborative (N3C) data from 2021 to 2023, this retrospective cohort study examined COVID-19 hospitalization, inpatient death, and other adverse events. Populations were categorized into urban, urban-adjacent rural (UAR), and nonurban-adjacent rural (NAR). Adjustments included demographics, variant-dominant waves, comorbidities, region, and SARS-CoV-2 treatment and vaccination. Statistical methods included Kaplan-Meier survival estimates, multivariable logistic, and Cox regression.

FINDINGS: The study included 3,018,646 patients, with rural residents constituting 506,204. These rural dwellers were older, had more comorbidities, and were less vaccinated than their urban counterparts. Adjusted analyses revealed higher hospitalization odds in UAR and NAR (aOR 1.07 [1.05-1.08] and 1.06 [1.03-1.08]), greater inpatient death hazard (aHR 1.30 [1.26-1.35] UAR and 1.37 [1.30-1.45] NAR), and greater risk of other adverse events compared to urban dwellers. Delta increased, while Omicron decreased, inpatient adverse events relative to pre-Delta, with rural disparities persisting throughout. Treatment effectiveness and vaccination were similarly protective across all cohorts, but dexamethasone post-ventilation was effective only in urban areas. Nirmatrelvir/ritonavir and molnupiravir better protected rural residents against hospitalization.

CONCLUSIONS: Despite advancements in treatment and vaccinations, disparities in adverse COVID-19 outcomes persist between urban and rural communities. The effectiveness of some therapeutic agents appears to vary based on rurality, suggesting a nuanced relationship between treatment and geographic location while highlighting the need for targeted rural health care strategies.

PMID:38953158 | DOI:10.1111/jrh.12857

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Dose to organs at risk for total body irradiation: Single-institution data using the modulated arc total body irradiation technique

Pediatr Blood Cancer. 2024 Jul 2:e31164. doi: 10.1002/pbc.31164. Online ahead of print.

ABSTRACT

BACKGROUND: Organs at risk (OAR) dose reporting for total body irradiation (TBI) patients is limited, and standardly reported only as mean doses to the lungs and kidneys. Consequently, dose received and effects on other OAR remain unexplored. To remedy this gap, this study reports dose data on an extensive list of OAR for patients treated at a single institution using the modulated arc total body irradiation (MATBI) technique.

METHOD: An audit was undertaken of all patients treated with MATBI between January 2015 and March 2021 who had completed their course of treatment. OAR were contoured on MATBI patient treatment plans, with 12 Gy in six fraction prescription. OAR dose statistics and dose volume histogram data are reported for the whole body, lungs, kidneys, bones, brain, lens, heart, liver and bowel bag.

RESULTS: The OAR dose data for 29 patients are reported. Mean dose results are body 11.77 Gy, lungs 9.86 Gy, kidneys 11.84 Gy, bones 12.03 Gy, brain 12.12 Gy, right lens 12.31 Gy, left lens 12.64 Gy, heart 11.07 Gy, liver 11.81 Gy and bowel bag 12.06 Gy. Dose statistics at 1-Gy intervals of V6-V13 for lungs and V10-V13 for kidneys are also included.

CONCLUSION: This is the first time an extensive list of OAR data has been reported for any TBI technique. Due to the paucity of reporting, this information could be used by centres implementing the MATBI technique, in addition to aiding comparison between TBI techniques, with the potential for greater understanding of the relationship between dose volume data and toxicity.

PMID:38953144 | DOI:10.1002/pbc.31164

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Commentary: Clinico-demographic profile of orbital exenteration in a tertiary eye care center – A 20 years’ experience

Indian J Ophthalmol. 2024 Jul 1;72(Suppl 4):S615-S616. doi: 10.4103/IJO.IJO_9_24. Epub 2024 Jul 1.

NO ABSTRACT

PMID:38953132 | DOI:10.4103/IJO.IJO_9_24

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Pediatric Device Clinical Trials Activity: 1999-2022

Pediatrics. 2024 Jul 2:e2023063466. doi: 10.1542/peds.2023-063466. Online ahead of print.

ABSTRACT

OBJECTIVES: This study assessed the state of pediatric medical device (PMD) development by comparing PMD clinical trials to pediatric trials evaluating drugs and biologics, from 1999 to 2022.

METHODS: The site https://www.clinicaltrials.gov was used to identify and quantify both PMD clinical trials and pediatric trials for drugs and biologics. Clinical specialty was also assessed. The institutions included were the 7 children’s hospitals primarily affiliated with the Food and Drug Administration (FDA) Pediatric Device Consortia (PDC) grant program between 2018 and 2023. For a national comparison, an additional search assessed PMD trials across all US medical institutions.

RESULTS: A total of 243 PMD clinical trials were identified at the FDA-PDC institutions on the basis of the year of initiation; the average number of PMD trials initiated per year per institution was 1.5 from 1999 to 2022. However, PMD trials significantly increased during the period 2014 to 2022 compared with 1999 to 2013 (P < .001); the rate of initiation of drug and biologic pediatric trials demonstrated no significant differences between these time periods. A national survey of all institutions initiating PMD trials, and drugs and biologics trials, identified 1885 PMD trials out of a total 12 943. A comparable trend was noted in the national survey with initiation of PMD trials increasing significantly from 2014 to 2022 (P < .001), compared with 1999 to 2013, whereas the rate of initiation of drug and biologic trials during these periods did not demonstrate a significant change.

CONCLUSIONS: Although pediatric clinical trial initiation for drugs and biologics remained stable from 1999 to 2022, the rate of new PMD trials significantly increased during the period 2014 to 2022 at FDA-PDC institutions and nationally.

PMID:38953121 | DOI:10.1542/peds.2023-063466

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Treatment of hypertension during pregnancy: a cohort of pregnancy episodes from the SIDIAP database, Catalonia, Spain

Front Pharmacol. 2024 Jun 17;15:1346357. doi: 10.3389/fphar.2024.1346357. eCollection 2024.

ABSTRACT

INTRODUCTION: Hypertension during pregnancy is one of the most frequent causes of maternal and fetal morbimortality. Perinatal and maternal death and disability rates have decreased by 30%, but hypertension during pregnancy has increased by approximately 10% in the last 30 years. This research aimed to describe the pharmacological treatment and pregnancy outcomes of pregnancies with hypertension.

METHODS: We carried out an observational cohort study from the Information System for the Development of Research in Primary Care (SIDIAP) database. Pregnancy episodes with hypertension (ICD-10 codes for hypertension, I10-I15 and O10-O16) were identified. Antihypertensives were classified according to the ATC WHO classification: β-blocking agents (BBs), calcium channel blockers (CCBs), agents acting on the renin-angiotensin system (RAS agents), diuretics, and antiadrenergic agents. Exposure was defined for hypertension in pregnancies with ≥2 prescriptions during the pregnancy episode. Descriptive statistics for diagnoses and treatments were calculated.

RESULTS: In total, 4,839 pregnancies with hypertension diagnosis formed the study cohort. There were 1,944 (40.2%) pregnancies exposed to an antihypertensive medication. There were differences in mother’s age, BMI, and alcohol intake between pregnancies exposed to antihypertensive medications and those not exposed. BBs were the most used (n = 1,160 pregnancy episodes; 59.7%), followed by RAS agents (n = 825, 42.4%), and CCBs were the least used (n = 347, 17.8%).

DISCUSSION: Pregnancies involving hypertension were exposed to antihypertensive medications, mostly BBs. We conduct a study focused on RAS agent use during pregnancy and its outcomes in the offspring.

PMID:38953107 | PMC:PMC11215181 | DOI:10.3389/fphar.2024.1346357

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Epidemiological and Molecular Characteristics of Hypermucoviscous and Hypervirulent Klebsiella pneumoniae Isolates in Community Patients in Shanghai, China

Infect Drug Resist. 2024 Jun 27;17:2685-2699. doi: 10.2147/IDR.S468482. eCollection 2024.

ABSTRACT

BACKGROUND: The occurrence and dissemination of hypermucoviscous and hypervirulent Klebsiella pneumoniae (hm-hvKp) isolates in clinical settings are a critical public health problem in the world. However, the data on these isolates in community populations are limited. This study aims to understand the prevalence and molecular characteristics of hm-hvKp isolates in community patients in Shanghai, China.

METHODS: In 2018, an active surveillance system focused on hm-hvKp in community diarrhoeal cases was implemented in Pudong New Area, Shanghai, China, involving 12 sentinel hospitals. The antimicrobial susceptibility of hm-hvKp isolates from fecal samples was tested, and whole-genome sequencing (WGS) was performed to predict the serotypes and sequence types and to identify antimicrobial resistance determinants, virulence determinants, and phylogenetic clusters.

RESULTS: The overall prevalence of hm K. pneumoniae isolates was 2.48% (31/1252), with the proportions of 1.76% (22/1252) for hm-hvKp and 0.72% (9/1252) for hm not hv K. pneumoniae. The prevalence of hm-hvKp isolates among different age groups and different months was statistically significant. All the 22 hm-hvKp isolates were susceptible to 20 antimicrobial agents and only carried bla SHV gene, and KL1 and KL2 accounted for eight (36.36%) cases and seven (31.82%) cases, respectively. The eight ST23/KL1 isolates belonged to the predominant CG23-I clade, which typically possessed the virulence determinants profile of rmpA/rmpA2-iro-iuc-ybt-irp-clb. The five ST86/KL2 isolates were assigned to the global clusters ST86/KL2-1 (n=2), ST86/KL2-2 (n=2), ST86/KL2-3 (n=1), all lack of the clb gene. Shanghai ST23/KL1 and ST86/KL2 isolates were closely related to the global isolates from liver abscesses, blood, and urine.

CONCLUSION: Hm-hvKp is carried by the community population of Shanghai, with ST23/KL1 and ST86/KL2 isolates predominant. Hm-hvKp isolates of different continents, different sources, and different virulence levels were closely related. Ongoing surveillance of hm-hvKp isolates in the community population is warranted.

PMID:38953096 | PMC:PMC11216552 | DOI:10.2147/IDR.S468482

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Statistical Assessment of the Effectiveness of Multiple COVID-19 Vaccinations on Daily Confirmed Cases in Seoul City

Cureus. 2024 May 31;16(5):e61457. doi: 10.7759/cureus.61457. eCollection 2024 May.

ABSTRACT

This study investigates the effectiveness of multiple COVID-19 vaccinations on daily confirmed cases in Seoul City. Utilizing comprehensive data on vaccinated individuals and confirmed cases sourced from the official website of the Korean Ministry of the Interior and Safety, we conducted detailed statistical analyses to assess the impact of each vaccination dose. The study covers data from April 21, 2021, to September 29, 2022. Statistical multiple linear regression was employed to analyze the relationship between daily confirmed cases (positive outcomes from PCR tests) and multiple vaccine doses, using p-values as the criteria for determining the effectiveness of each dose. The analysis included data from four vaccination doses. The analysis reveals that the first, second, and third doses of the COVID-19 vaccines have a statistically significant positive effect associated with the daily confirmed cases. However, the study finds that the fourth dose does not show a statistically significant impact on the reduction of daily confirmed cases. This suggests that while the initial three doses are crucial for establishing and maintaining high levels of immunity, the incremental benefit of subsequent doses may diminish.

PMID:38953092 | PMC:PMC11216110 | DOI:10.7759/cureus.61457