Treatment Status Research Articles

Effect of mixed probiotics on pulmonary flora in patients with mechanical ventilation: an exploratory randomized intervention study

ObjectiveThe study objective was to investigate the effect of mixed probiotics on the diversity of the pulmonary flora in critically ill patients requiring mechanical ventilation by analysing the changes in lung microbes.Methods24 adult critically ill patients who needed mechanical ventilation in our hospital were randomly divided into a probiotic group and a control group. Then, the probiotic group was given Live Combined Bifidobacterium, Lactobacillus and Enterococcus Capsules, Oral (Bifico) by nasal feeding within 24 h after mechanical ventilation. Bronchoalveolar lavage fluid (BALF) and venous blood were collected within 24 h after mechanical ventilation and on the 5th day after mechanical ventilation, and the treatment status of patients (mechanical ventilation time, 28-day survival), measured cytokine levels (IL-1 β, IL-6, IL-8, IL-17A) and changes in pulmonary microorganisms were observed.ResultsThe microbial diversity of BALF samples decreased in the control group, and there was no significant difference in the probiotic group. Species difference analysis showed that among the three probiotics (Bifidobacterium, Lactobacillus, Enterococcus) used for intervention, Lactobacillus caused significant differences in BALF in the control group. Clinical factor association analysis displayed significant associations with IL-17A levels in both blood and BALF.ConclusionMechanical ventilation can cause a decline in pulmonary microbial diversity, which can be improved by administering mixed probiotics.

Applying the 2023 ESH Hypertension Guidelines to the Irish Population- findings from the Irish Longitudinal Study on Ageing (TILDA)

Abstract Background Hypertension (HTN) is an important risk factor for cardiovascular disease (CVD), the leading cause of mortality worldwide. The aim of this study was to apply the latest European Society of Hypertension (ESH) Guidelines 2023 to the Irish general population. Methods This study used data from Wave 1 (2009-2010) and Wave 3 (2014-2015) of the Irish Longitudinal Study on Ageing (TILDA). TILDA is a prospective cohort study based on stratified random sampling, which is representative of the community living older population in Ireland (Aged 50 years and over). Using this data, the prevalence of HTN in the general population by grade and stage, as set out in the ESH 2023 guidelines, was calculated. Population awareness of diagnosis, treatment status, control on treatment and adherence to recommended anti-hypertensive medication classes were assessed. Subgroup analyses were explored in alignment with specified groups highlighted in the Guidelines including those over 80 years old with and without frailty, those with chronic kidney disease and those with home blood pressure (BP) measurements. Inverse probability weighting was applied to account for the complex survey design used in TILDA and data analysis was conducted using Stata 15.1. Results Results from Wave 3 (N=5,329): The prevalence of hypertension was 64.0% (95% confidence interval (CI) 62.4-65.6%). Of those with HTN, 55.5% (95% CI 53.3-57.7) were aware of their HTN diagnosis and 70.4% (95% CI 68.3-72.2%) were on antihypertensive treatment. Of those on treatment, 53.2% were controlled (BP < 140/90), and only 20.0% (95% CI 18.3-21.8) were on a recommended dual therapy. 55.2% were on at least one agent recommended by the ESH guidelines. Conclusion This study indicates a high prevalence of HTN in the general population in Ireland aged 50+ years with low levels of awareness, control, and poor adherence to the most recent ESH HTN guidelines.

Immunohistochemical Evaluation of Cathepsin B, L, and S Expression in Breast Cancer Patients.

Cysteine cathepsins are proteases that play a role in normal cellular physiology and neoplastic transformation. Elevated expression and enzymatic activity of cathepsins in breast cancer (BCa) indicates their potential as a target for tumor imaging. In particular cathepsin B (CTSB), L (CTSL), and S (CTSS) are used as targets for near-infrared (NIR) fluorescence imaging (FI), a technique that allows real-time intraoperative tumor visualization and resection margin assessment. Therefore, this immunohistochemical study explores CTSB, CTSL, and CTSS expression levels in a large breast cancer patient cohort, to investigate in which BCa patients the use of cathepsin-targeted NIR FI may have added value. Protein expression was analyzed in tumor tissue microarrays (TMA) of BCa patients using immunohistochemistry and quantified as a total immunostaining score (TIS), ranging from 0-12. In total, the tissues of 557 BCa patients were included in the TMA. CTSB, CTSL, and CTSS were successfully scored in respectively 340, 373 and 252 tumors. All tumors showed CTSB, CTSL, and/or CTSS expression to some extent (TIS > 0). CTSB, CTSL, and CTSS expression was scored as high (TIS > 6) in respectively 28%, 80%, and 18% of tumors. In 89% of the tumors scored for all three cathepsins, the expression level of one or more of these proteases was scored as high (TIS > 6). Tumors showed significantly higher cathepsin expression levels with advancing Bloom-Richardson grade (p < 0.05). Cathepsin expression was highest in estrogen receptor (ER)-negative, human epidermal growth factor receptor 2(HER2)-positive and triple-negative (TN) tumors. There was no significant difference in cathepsin expression between tumors that were treated with neoadjuvant systemic therapy and tumors that were not. The expression of at least one of the cysteine cathepsins B, L and S in all breast tumor tissues tested suggests that cathepsin-activatable imaging agents with broad reactivity for these three proteases will likely be effective in the vast majority of breast cancer patients, regardless of molecular subtype and treatment status. Patients with high grade ER-negative, HER2-positive, or TN tumors might show higher imaging signals.

Evaluation of Exposure to Bisphenol A, Bisphenol F, and Phthalates in Patients with Phenylketonuria and Its Differences According to Dietary Status.

Phenylketonuria (PKU) is the most common amino acid metabolism disorder. Patients with blood phenylalanine (Phe) levels of ≥6 mg/dL require treatment, and the most definitive treatment is the Phe-restricted diet. Bisphenols and phthalates are widely used endocrine-disrupting chemicals (EDCs) found in personal care products, baby bottles, and food packaging. In this study, we evaluated the possible routes of exposure to these EDCs in patients diagnosed with PKU (n = 105, 2-6 years of age) and determined the relationship between the plasma levels of bisphenol A (BPA), bisphenol F (BPF), di-butyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), mono-(2ethylhexyl) phthalate (MEHP), and dietary regimens. Participant characteristics and exposure routes were evaluated according to their dietary treatment status. Thirty-four of these patients were on a Phe-restricted diet, while the remaining 71 had no dietary restrictions. DBP and DEHP levels were higher in those using plastic tablecloths (p = 0.049 and p = 0.04, respectively). In addition, plasma DBP levels were higher in those who used bottled water (p = 0.01). Being under 4 years of age, using plastic food containers, and using plastic shower curtains were characteristics associated with higher MEHP levels (p = 0.027, p = 0.019, and p = 0.014, respectively). After adjustment for baseline characteristics (Model 1), the odds of having a plasma BPA level in the upper tertile were 3.34 times higher in the free-diet group (95% CI = 1.09-10.25). When we additionally adjusted for plastic exposure (Model 2), the odds ratio was found to be 18.64 (95% CI = 2.09-166.42) for BPA. In the free-diet group, the probability of having plasma DEHP levels in the upper tertile was increased by a relative risk of 3.01 (p = 0.039, 95% CI = 1.06-8.60). Our results indicate that exposure to bisphenols and phthalates varies with dietary treatment. The difference in sources of exposure to EDCs between the diet and non-diet groups indicates that diet plays an important role in EDC exposure.

Levels of Natural Antibodies Before and After Immunoglobulin Replacement Treatment Affect the Clinical Phenotype in Common Variable Immunodeficiency

Natural antibodies (NAbs) occurring in individuals without prior exposure to specific antigens, provide direct first barrier protection against pathogens, and exert immunoregulation thus actively contributing to the maintenance of immune homeostasis, controlling inflammatory processes and preventing autoimmunity. Common variable immunodeficiency (CVID) is a heterogeneous group of disorders characterized by a compromised immune function that brings into focus the role of NAbs. Our aim was to explore whether NAb levels could serve as potential key indicators in CVID for monitoring disease progression and predicting outcomes. In this study, we analyzed a Hellenic cohort of 56 patients with CVID (31 newly diagnosed and 25 under immunoglobulin replacement therapy-IgRT) and 33 healthy controls, for total Ig levels and serum IgM and IgG NAb levels against five informative target-antigens of NAbs, namely, actin, DNA, carbonic anhydrase, F(ab΄)2 fragments of human IgG and TriNitroPhenyl. In addition, follow-up pre- and post- IgRT samples were analyzed in ten (10) patients of our cohort. Results showed that Ig-treated patients exhibited significantly lower IgM NAb levels than untreated patients and healthy controls against all panel antigens. In the follow-up samples, pre-treatment IgM NAb levels negatively correlated with total serum IgM. This imbalance was only partially restored after IgRT, with a significant decrease in IgM NAb levels observed in nine out of ten patients. Moreover, post-treatment patients with recurrent infections presented significantly lower IgM NAb levels, a reduction also observed in patients with bronchiectasis independently of treatment status. On the contrary, post-treatment patients with enteropathy had significantly higher IgM NAb levels against all panel antigens, an increase also noted in patients with autoimmune diseases. Regarding IgG NAbs, replacement therapy restored levels to those of healthy controls. In conclusion, impaired NAb levels are found in CVID patients, particularly related to certain phenotypes. Moreover, the significant decrease in IgM NAb levels after IgRT suggests a potential association with disease course and complications. The results suggest that administration of human IgM NAbs may be an effective combinatorial treatment in selected patients. Further research is needed to understand the functional roles of NAbs in CVID and its complex clinical phenotypes.

Epidemiology and burden of chronic insomnia disorder in Europe: an analysis of the 2020 National Health and Wellness Survey

Introduction Chronic insomnia disorder (CID) is considered a significant worldwide public health concern; however, its exact burden is unknown. We estimate its prevalence across France, Germany, Italy, Spain, and the United Kingdom, and assess the economic and humanistic burden for a broader insomnia population. Methods This retrospective, cross-sectional, observational study used 2020 National Health and Wellness Survey (NHWS) data. Patients reporting insomnia were characterized to define CID. Health-related quality of life (HRQoL), work productivity, and healthcare resource use (HCRU) outcomes were assessed in four cohorts according to insomnia diagnosis and treatment status and examined using multivariable analyses according to Insomnia Severity Index categories. Results Among 62,319 respondents, 9,035 (21.2%) reported experiencing insomnia over the previous 12 months. CID prevalence rates were 5.5% to 6.7% across the five countries and 6.0% overall. HRQoL outcomes were persistently poorer in cohorts of patients diagnosed with insomnia than those with undiagnosed insomnia. Undiagnosed and treated insomnia patients reported the highest work presenteeism and total work productivity impairment and the highest number of emergency room and hospitalization visits than patients with insomnia (either treated or untreated). After adjusting for covariates, patients with severe insomnia reported significantly worse EQ-5D-5L utility scores, higher absenteeism and presenteeism rates, and more healthcare provider visits over the past 6 months than patients without insomnia (all p < 0.01). Conclusions Our prevalence rates for CID align with published literature. A diagnosis of insomnia, use of sleep medications, and severity of insomnia are associated with poor quality of life, loss of work productivity, and higher HCRU, confirming the high unmet need and substantial humanistic and economic burden of CID.

Trends and Disparities in Mental Health Use Among Asian American Sub-groups, 2013-2019.

The objective of this study was to characterize and compare national estimates of mental healthcare use among White and Asian American groups to provide an update using post Affordable Care Act data. We analyzed yearly cross-sectional data from the 2013-2019 Medical Expenditure Panel Survey, including White (n=112,590) and Asian American (n=10,210) individuals, and examined rates of mental healthcare use for Asian (overall), Asian Indian, Chinese, Filipino, and Other Asian individuals relative to White individuals. Using multivariable logistic regression models and predictive margin methods, we estimated overall Asian disparities and Asian subgroup disparities compared to White group rates in mental health care (outpatient, specialty, psychotropic medication) among adults with and without elevated risk for mental illness. Regression models were adjusted for variables related to need for treatment, demographic, and socioeconomic status variables. Asian individuals had lower rates of mental healthcare use than White individuals. Unadjusted results and adjusted regression model predictions are consistent in identifying wide disparities in mental health care treatment across risk for mental illness, Asian subgroups, and types of treatment. Asian Americans have significantly lower rates of mental healthcare use than White Americans, even among those with elevated risk for mental illness. There is small variation by Asian subgroups but disparities persist across subgroups and types of treatment. Our results imply interventions are needed to improve linguistically, culturally, and ethnically tailored outreach and engagement in treatment services, as well as examining treatment and its effectiveness for Asian American individuals living with psychological distress.

Diagnosis of Lung Cancer Through Exhaled Breath: A Comprehensive Study.

Exhaled breath analysis is an attractive lung cancer diagnostic tool. However, various factors that are not related to the disease status, comorbidities, and other diseases must be considered to obtain a reliable diagnostic model. Exhaled breath samples from 646 individuals including 273 patients with lung cancer (LC), 90 patients with cancer of other localizations (OC), 150 patients with noncancer lung diseases (NLD), and 133 healthy controls (HC) were analyzed using gas chromatography-mass spectrometry (GC-MS). The samples were collected in Tedlar bags. Volatile organic compounds (VOCs) were preconcentrated on Tenax TA sorbent tubes with subsequent two-stage thermal desorption followed by GC-MS analysis. The influence of age, gender, smoking status, time since last food consumption, and comorbidities on exhaled breath were evaluated. Also, the effect of histology, TNM, tumor localization, treatment status, and the presence of a tumor on VOC profile of patients with lung cancer were assessed. Intergroup statistics were estimated, diagnostic models were created using artificial neural networks (ANNs) and gradient boosted decision trees (GBDTs). Smoking status and food consumption affect exhaled breath VOC profile: benzene, ethylbenzene, toluene, 1,3-pentadiene 1,4-pentadiene acetonitrile, and some ratios are significantly different in exhaled breath of smokers and nonsmokers; the ratios 2,3-butandione/2-pentanone, 2,3-butandione/dimethylsulfide, and 2-butanone/2-pentanone are affected by time since last food consumption. Exhaled breath of LC is affected by the form of the disease and comorbidities. One-pentanol and 2-butanone were different in exhaled breath of patients with various tumor localization; 2-butanone was different in exhaled breath of patients before and during treatment. Diabetes as a comorbidity affects the pentanal level in exhaled breath; obesity affects the ratios of 2,3-butanedione/dimethylsulfide and 2-butanone/isoprene. Sensitivity and specificity of diagnostic models aimed to discriminate LC and HC, OC, and NLD were 78.7% and 51.0%, 62.2% and 53.4%, and 60.4% and 58.0%, respectively. HC and patients, regardless of the disease, can be classified with sensitivity of 76.6% and specificity of 68.2%. The models created to diagnose lung cancer can also classify OC and NLD as patients with lung cancer. Additionally, the influence of comorbidities and factors not related to the disease status must be considered before the creation of diagnostic models to avoid false results.

Experiences and Comfort of Young Cancer Patients Discussing Cannabis with Their Providers: Insights from a Survey at an NCI-Designated Cancer Center.

Cannabis use among cancer patients for managing treatment-related symptoms is increasing, yet little is known about patterns in patient-provider communication. This study examines demographic differences in cannabis use communication at a National Cancer Institute-designated cancer center. The analysis included cancer patients aged ≥ 18years who self-reported current cannabis use (past 30days) and had visited Sylvester Comprehensive Cancer Center within the past 5years (N = 226). Data were collected via an anonymous electronic survey on REDCap. Responses on patients' disclosure of cannabis use to cancer doctor/care team and their comfort in discussing cannabis were analyzed. Chi-squared/Fisher's exact tests and t-tests were applied. Logistic regression estimated the associations between age and stage of cancer treatment with patients' comfort in discussing cannabis use with cancer doctor (oncologist). The sample was 51.8% male and 39.4% Hispanic (mean age, 45.9years (SD = 15.1)); 41.1% were aged 20-39years, 43.8% were undergoing treatment, and 35.4% were in follow-up/had finished treatment. Over half (50.4%) did not disclose cannabis use to their cancer doctor/care team. Non-disclosers were more often younger (20-39years) than disclosers (52.6% vs. 29.5%, p < 0.01). Most patients (72.5%) felt comfortable discussing cannabis use with their oncologist; however, younger patients (20-39years) were more often uncomfortable (40.8%). Logistic regression showed newly diagnosed patients had lower odds (aOR, 0.41; 95% CI, 0.12-0.98) of comfort discussing cannabis compared to those in follow-up/finished treatment. Younger patients (20-39years) also had lower odds (aOR, 0.11; 95% CI, 0.03-0.40) of feeling comfortable discussing cannabis compared to older patients (≥ 60years). Age and treatment stage significantly impact the cannabis use disclosure and comfort in discussing it with cancer doctor/care team. These findings underscore the importance of considering age-related factors and treatment status when addressing cannabis use discussions within oncology setting.

Bibliometric analysis of nutrition in gastric cancer from 2013 to 2023.

Increasing evidence suggests that nutrition plays an important role in the treatment of gastric cancer. However, no bibliometrics analysis has been conducted in this field. Our study aimed to conduct a bibliometric study to explore the latest publishing trends and areas of intense activity within the sphere of nutrition in gastric cancer. Publications were extracted from the Web of Science Core Collection. CiteSpace (Version 6.2.4) and VOSviewer (Version 1.6.18) were used for visual analysis. In total, there were 441 publications authored by 2,941 authors from 809 organizations and 47 countries, published in 182 journals from 2013 to 2023. The most prolific country was China, and the most productive institution was the Chinese Academy of Medical Sciences. The leading core journal was Nutrients. P Daisuke Kobayashi and Yasuhiro Kodera were the most influential authors. The first highly cited document was published in Gastric Cancer by Kamarajah et al. The hotspots in this field were nutrition treatment and nutritional status. Moreover, research on nutritional status and nutrition-related prognosis in gastric cancer might be a potential trend. Nutrition in gastric cancer is a burgeoning research field garnering increasing attention. Further investigation is necessary to better understand the impact of nutritional status on the prognosis of gastric cancer.

Probability of Causation with Sample Selection: A Reanalysis of the Impacts of Jóvenes en Acción on Formality

This article identifies the probability of causation when there is sample selection. We show that the probability of causation is partially identified for individuals who are always observed regardless of treatment status and derive sharp bounds under three increasingly restrictive sets of assumptions. The first set imposes an exogenous treatment and a monotone sample selection mechanism. To tighten these bounds, the second set also imposes the monotone treatment response assumption, while the third set additionally imposes a stochastic dominance assumption. Finally, we use experimental data from the Colombian job training program Jóvenes en Acción to empirically illustrate our approach’s usefulness. We find that, among always-employed women, at least 10.2% and at most 13.4% transitioned to the formal labor market because of the program. However, our 90%-confidence region does not reject the null hypothesis that the lower bound is equal to zero.

Atypical language organization in a Spanish-speaking adolescent with drug-resistant epilepsy: a multicultural case report

Objective: Epilepsy disproportionally affects children from Hispanic/Latino backgrounds, particularly among those born outside the U.S. Longstanding health-related disparities associated with ethnicity (e.g. language use) further contribute to gaps in care. Neuropsychologists are beginning to outline best practices when working with non-English speakers; however, the lack of appropriately normed/validated measures for pre-surgical language evaluation is a limiting factor. This report informs practices among neuropsychologists by discussing atypical language organization in a non-English speaker using a multicultural framework and collaborative therapeutic assessment process. Method: The current study presents a 16-year-old, right-handed, monolingual Spanish-speaking, Latina designated female with drug-resistant focal seizures with impaired awareness. Comprehensive presurgical epilepsy workup included: CBC, video EEG, brain MRI, functional MRI, PET, MEG, baseline neuropsychological evaluation by bilingual Spanish-English providers, and Wada testing. Results: Neuropsychological testing revealed the most pronounced deficits in language, working memory, and processing speed domains. Functional MRI showed bilateral language activation, which Wada testing confirmed along with bilateral memory representation. Conclusion: Diagnosis, treatment, surgical intervention, and post-operative status are discussed. The clinical course is examined through a multicultural lens, highlighting limitations in international health services, barriers accessing health care in the U.S., and patient-specific factors that were considered as a part of the clinical decision-making process. Targeted recommendations related to culturally-informed care are offered.

A triple hormone receptor ER, AR, and VDR signature is a robust prognosis predictor in breast cancer

BackgroundDespite evidence indicating the dominance of cell-of-origin signatures in molecular tumor patterns, translating these genome-wide patterns into actionable insights has been challenging. This study introduces breast cancer cell-of-origin signatures that offer significant prognostic value across all breast cancer subtypes and various clinical cohorts, compared to previously developed genomic signatures.MethodsWe previously reported that triple hormone receptor (THR) co-expression patterns of androgen (AR), estrogen (ER), and vitamin D (VDR) receptors are maintained at the protein level in human breast cancers. Here, we developed corresponding mRNA signatures (THR-50 and THR-70) based on these patterns to categorize breast tumors by their THR expression levels. The THR mRNA signatures were evaluated across 56 breast cancer datasets (5040 patients) using Kaplan–Meier survival analysis, Cox proportional hazard regression, and unsupervised clustering.ResultsThe THR signatures effectively predict both overall and progression-free survival across all evaluated datasets, independent of subtype, grade, or treatment status, suggesting improvement over existing prognostic signatures. Furthermore, they delineate three distinct ER-positive breast cancer subtypes with significant survival in differences—expanding on the conventional two subtypes. Additionally, coupling THR-70 with an immune signature identifies a predominantly ER-negative breast cancer subgroup with a highly favorable prognosis, comparable to ER-positive cases, as well as an ER-negative subgroup with notably poor outcome, characterized by a 15-fold shorter survival.ConclusionsThe THR cell-of-origin signature introduces a novel dimension to breast cancer biology, potentially serving as a robust foundation for integrating additional prognostic biomarkers. These signatures offer utility as a prognostic index for stratifying existing breast cancer subtypes and for de novo classification of breast cancer cases. Moreover, THR signatures may also hold promise in predicting hormone treatment responses targeting AR and/or VDR.

Reinforcement learning processes as forecasters of depression remission

BackgroundAspects of reinforcement learning have been associated with specific depression symptoms and may inform the course of depressive illness. MethodsWe applied support vector machines to investigate whether blood‑oxygen-level dependent (BOLD) responses linked with neural prediction error (nPE) and neural expected value (nEV) from a probabilistic learning task could forecast depression remission. We investigated whether predictions were moderated by treatment use or symptoms. Participants included 55 individuals (n = 39 female) with a depression diagnosis at baseline; 36 of these individuals completed standard cognitive behavioral therapy and 19 were followed during naturalistic course of illness. All participants were assessed for depression diagnosis at a follow-up visit. ResultsBoth nPE and nEV classifiers forecasted remission significantly better than null classifiers. The nEV classifier performed significantly better than the nPE classifier. We found no main or interaction effects of treatment status on nPE or nEV accuracy. We found a significant interaction between nPE-forecasted remission status and anhedonia, but not for negative affect or anxious arousal, when controlling for nEV-forecasted remission status. LimitationsOur sample size, while comparable to that of other studies, limits options for maximizing and evaluating model performance. We addressed this with two standard methods for optimizing model performance (90:10 train and test scheme and bootstrapped sampling). ConclusionsResults support nEV and nPE as relevant biobehavioral signals for understanding depression outcome independent of treatment status, with nEV being stronger than nPE as a predictor of remission. Reinforcement learning variables may be useful components of an individualized medicine framework for depression healthcare.

Multifocal motor neuropathy in Japan: A nationwide survey on prevalence, clinical profiles, and treatment.

Multifocal motor neuropathy (MMN) is a rare disease for which epidemiological and clinical data are limited. We conducted a nationwide survey to determine disease prevalence, incidence, clinical profile, and current treatment status in Japan. A nationwide survey was conducted in 2021 using an established epidemiological method. Questionnaires were sent to all neurology and pediatric neurology departments in Japan. An initial questionnaire was administered to determine the number of patients with and incidence of MMN. A second questionnaire was administered to collect detailed clinical information. The European Federation of Neurological Societies/Peripheral Nerve Society 2010 guidelines were used as diagnostic criteria. The estimated number of patients with MMN was 507. The estimated prevalence was 0.40 per 100,000 individuals. Detailed clinical profiles were available for 120 patients. The male-to-female ratio was 2.3:1 and the median onset age was 42 years. The median disease duration at diagnosis was 25 months. Most patients presented with upper limb-dominant muscle weakness. Motor nerve conduction blocks were found in 62% of patients and positive anti-GM1 IgM antibody results in 54%. A total of 117 (98%) patients received immunoglobulin therapy, and 91% of them showed improvement. At the time of the last visit (median, 82 months from treatment initiation), 89 (74%) patients were receiving maintenance immunoglobulin therapy. A slight progression of neurological deficits was observed during follow-up. Most patients with MMN in Japan received induction and maintenance immunoglobulin therapies, which appear to suppress long-term disease progression.

Association between methylphenidate use and long-term cardiovascular risk in paediatric patients with attention deficit and hyperactivity disorder

BackgroundThere have been concerns about the potential cardiovascular (CV) adverse effects associated with methylphenidate (MTH) use. However, only limited evidence exists on the long-term safety of MTH.ObjectiveTo evaluate whether MTH...

Real-world safety of nivolumab in patients with malignant pleural mesothelioma in Japan: post-marketing surveillance study.

This post-marketing surveillance (PMS) was conducted to evaluate the incidence of adverse events with nivolumab in patients with unresectable, advanced or recurrent malignant pleural mesothelioma (MPM) that had progressed after first-line chemotherapy and to identify factors that potentially affected its safety in real-world clinical practice. Patients who had not received nivolumab previously were registered between November 2018 and February 2021. Nivolumab was given intravenously 240mg every 2weeks or 480mg every 4weeks. Patients were followed up for 6months after treatment initiation. Information on patient characteristics, treatment status, and adverse events was collected. This PMS enrolled 124 patients, involving 48 sites across Japan. At 6months, nivolumab therapy was ongoing in 35.5% of patients (44/124) and had been discontinued in 64.5% (80/124). The overall incidence of treatment-related adverse events (TRAEs) was 40.3%; the incidence of Grade 3 or higher TRAEs was 12.9%. The pattern of TRAEs based on System Organ Class categories was generally consistent with those seen in the Japanese phase II MERIT study. The most common Grade 3 or higher TRAEs were interstitial lung disease (2.4%), lung disorder, and diarrhea (each 1.6%). The incidence of TRAEs was significantly higher in inpatients or patients who had good PS, high bodyweight, high body mass index, or autoimmune diseases than in those without these characteristics. The post-marketing incidence of TRAEs with nivolumab in patients with MPM has been evaluated, and no new safety signals were identified compared to the phase II clinical trial in Japan.

Recruitment of CXCR4+ type 1 innate lymphoid cells distinguishes sarcoidosis from other skin granulomatous diseases.

Sarcoidosis is a multiorgan granulomatous disease that lacks diagnostic biomarkers and targeted treatments. Using blood and skin from patients with sarcoid and non-sarcoid skin granulomas, we discovered that skin granulomas from different diseases exhibit unique immune cell recruitment and molecular signatures. Sarcoid skin granulomas were specifically enriched for type 1 innate lymphoid cells (ILC1s) and B cells and exhibited molecular programs associated with formation of mature tertiary lymphoid structures (TLSs), including increased CXCL12/CXCR4 signaling. Lung sarcoidosis granulomas also displayed similar immune cell recruitment. Thus, granuloma formation was not a generic molecular response. In addition to tissue-specific effects, patients with sarcoidosis exhibited an 8-fold increase in circulating ILC1s, which correlated with treatment status. Multiple immune cell types induced CXCL12/CXCR4 signaling in sarcoidosis, including Th1 T cells, macrophages, and ILCs. Mechanistically, CXCR4 inhibition reduced sarcoidosis-activated immune cell migration, and targeting CXCR4 or total ILCs attenuated granuloma formation in a noninfectious mouse model. Taken together, our results show that ILC1s are a tissue and circulating biomarker that distinguishes sarcoidosis from other skin granulomatous diseases. Repurposing existing CXCR4 inhibitors may offer a new targeted treatment for this devastating disease.

Study on the Mechanism of Algae Bacteria Symbiotic System in Treating Fracturing Flowback Fluid

Fracturing operations in oil and gas wells are one of the main measures to increase production. Fracturing flowback fluid has the characteristics of high viscosity, high COD value, and containing multiple chemical reagents, making it difficult to treat. It has become one of the main pollutants in oil fields. Directly discharging untreated fracturing fluid can cause serious pollution to the environment and soil. Therefore, in-depth research on the treatment methods of fracturing flowback fluid is of great significance for environmental protection and cost reduction in oil and gas fields. This article systematically analyzes the sources, components, pollution characteristics, and treatment status of fracturing flowback fluid. The efficient treatment of fracturing flowback fluid using a microalgae aerobic bacteria mixed culture system was conducted, and the mechanism of algae bacteria symbiotic treatment of oily wastewater and the mechanism of microalgae aerobic bacteria mixed culture purification of fracturing flowback fluid were analyzed in depth.

Clinical and economic impact of first-line or drug-naïve catheter ablation and delayed second-line catheter ablation for atrial fibrillation using a patient-level simulation model

Aims To determine the clinical and economic implications of first-line or drug-naïve catheter ablation compared to antiarrhythmic drugs (AADs), or shorter AADs-to-Ablation time (AAT) in atrial fibrillation (AF) patients in France and Italy, using a patient level-simulation model. Materials and methods A patient-level simulation model was used to simulate clinical pathways for AF patients using published data and expert opinion. The probabilities of adverse events (AEs) were dependent on treatment and/or disease status. Analysis 1 compared scenarios of treating 0%, 25%, 50%, 75% or 100% of patients with first-line ablation and the remainder with AADs. In Analysis 2, scenarios compared the impact of delaying transition to second-line ablation by 1 or 2 years. Results Over 10 years, increasing first-line ablation from 0% to 100% (versus AAD treatment) decreased stroke by 12%, HF hospitalization by 29%, and cardioversions by 45% in both countries. As the rate of first-line ablation increased from 0% to 100%, the overall 10-year per-patient costs increased from €13,034 to €14,450 in Italy and from €11,944 to €16,942 in France. For both countries, the scenario with no delay in second-line ablation had fewer AEs compared to the scenarios where ablation was delayed after AAD failure. Increasing rates of first-line or drug-naïve catheter ablation, and shorter AAT, resulted in higher cumulative controlled patient years on rhythm control therapy. Limitations The model includes assumptions based on the best available clinical data, which may differ from real-world results, however, sensitivity analyses were included to combat parameter ambiguity. Additionally, the model represents a payer perspective and does not include societal costs, providing a conservative approach. Conclusion Increased first-line or drug-naïve catheter ablation, and shorter AAT, could increase the proportion of patients with controlled AF and reduce AEs, offsetting the small investment required in total AF costs over 10 years in Italy and France.