Tag: nevin manimala

Am J Respir Crit Care Med. 2022 Apr 5. doi: 10.1164/rccm.202106-1439OC. Online ahead of print.

ABSTRACT

RATIONALE: Outdoor air pollution is a potential risk factor for lower lung function and chronic obstructive pulmonary disease (COPD). Little is known on how airway abnormalities and lung growth might modify this relationship.

OBJECTIVE: To evaluate the associations of ambient air pollution exposure with lung function and COPD, and to examine possible interactions with dysanapsis.

METHODS: We made use of cross-sectional post-bronchodilator spirometry data from 1452 individuals enrolled in the Canadian Cohort Obstructive Lung Disease (CanCOLD) with linked ambient fine particulate matter (PM2.5) and nitrogen dioxide (NO2) air pollution estimates. Dysanapsis, or the ratio of airway-to-lung volume calculated from thoracic computed tomography images, was used to examine possible interactions.

MEASUREMENTS AND MAIN RESULTS: In adjusted models, 101.7 mL [95% CI: -166.2, -37.2] and 115.0 mL [95% CI: -196.5, -33.4] lower forced expiratory volume in one second (FEV1) were demonstrated per increase of 2.4 ug/m3 PM2.5, and 9.2 ppb NO2, respectively. Interaction between air pollution and dysanapsis was not statistically significant when modelling airway-to-lung ratio as a continuous variable. However, a 109.8 mL [95% CI: -209.0, -10.5] lower FEV1 and an 87% [95% CI: 12%; 213%] higher odds of COPD was observed amongst individuals in the lowest, relative to highest, airway-to-lung ratio, per 2.4 μg/m3 increment of PM2.5.

CONCLUSION: Ambient air pollution exposure was associated with lower lung function, even at relatively low concentrations. Individuals with dysanaptic lung growth might be particularly susceptible to inhaled ambient air pollutants, especially those at the extremes of dysanapsis.

PMID:35380941 | DOI:10.1164/rccm.202106-1439OC

BMJ Open. 2021 Dec 30;11(12):e055013. doi: 10.1136/bmjopen-2021-055013.

ABSTRACT

OBJECTIVES: To examine the associations between self-stigma and diabetes duration in a sample of Japanese people with type 2 diabetes.

DESIGN: A secondary analysis of a cross-sectional study.

SETTING: Two university hospitals, one general hospital and one clinic in Tokyo, Japan.

PARTICIPANTS: Outpatients with type 2 diabetes aged 20-74 years and receiving treatment from diabetes specialist physicians (n=209) completed a self-administered questionnaire.

PRIMARY AND SECONDARY OUTCOME MEASURES: Self-stigma was measured as the primary outcome. Patient Activation Measure, body mass index and haemoglobin A1c were measured as secondary outcomes.

RESULTS: One-way analysis of covariance showed significant differences in self-stigma levels between the five groups of diabetes duration (≤5 years, 6-10 years, 11-15 years, 16-21 years and 22 years or more) after controlling for age, gender, education, marital status, diabetes treatment (insulin use) and diabetes-related complications, F(4,198)=2.83, p=0.026. Multiple comparisons using Bonferroni correction showed statistically significant differences in self-stigma levels between the groups with ≤5 years (95% CI 59.63 to 69.73) and 11-15 years with diabetes (95% CI 71.12 to 80.82; p=0.020). The highest mean level of self-stigma was observed in the group having diabetes for 11-15 years.

CONCLUSIONS: Self-stigma was associated with diabetes duration and was lowest after diagnosis and gradually increased, with its highest levels being observed in those having diabetes for 11-15 years. Self-stigma takes time to develop and gradually increases in individuals as it is learnt through direct experiences of diabetes-related stigma after self-administering treatment in everyday social situations.

PMID:35380981 | DOI:10.1136/bmjopen-2021-055013

Am J Respir Cell Mol Biol. 2022 Apr 5. doi: 10.1165/rcmb.2021-0346OC. Online ahead of print.

ABSTRACT

Chronic alcohol drinking is associated with increased susceptibility to viral and bacterial respiratory pathogens. In this study, we utilize a rhesus macaque model of voluntary ethanol self-administration to study the effects of long-term alcohol drinking on the immunological landscape of the lung. We report heightened inflammatory state in alveolar macrophages (AM) obtained from ethanol (EtOH) drinking animals that is accompanied by increased chromatin accessibility in intergenic regions that regulate inflammatory genes and contain binding motifs for transcription factors AP-1, IRF8, and NFKB p-65. In line with these transcriptional and epigenetic changes at basal state, AM from EtOH drinking animals generate elevated inflammatory mediator responses to LPS and respiratory syncytial virus (RSV). However, transcriptional analysis revealed an inefficient induction of interferon stimulated genes with EtOH in response to RSV, suggesting disruption of anti-microbial defenses. Correspondingly, AM from EtOH drinking animals exhibited transcriptional shifts indicative of increased oxidative stress and oxidative phosphorylation which was coupled with higher cytosolic reactive oxygen species (ROS) and mitochondrial potential. This heightened oxidative stress state was accompanied by decreased ability to phagocytose bacteria. Bulk RNA and ATAC sequencing data further revealed reduced expression and chromatin accessibility of loci associated with tissue repair and maintenance with chronic EtOH drinking. Similarly, analysis of scRNA-Seq data revealed shifts in cell states from tissue maintenance to inflammatory responses with EtOH. Collectively, these data provide novel insight into mechanisms by which chronic EtOH drinking increases susceptibility to infection in patients with alcohol use disorders.

PMID:35380939 | DOI:10.1165/rcmb.2021-0346OC

Environ Sci Pollut Res Int. 2022 Apr 5. doi: 10.1007/s11356-022-19730-w. Online ahead of print.

ABSTRACT

We researched China’s climate and sustainable development goal with relevant and susceptible instruments capable of inducing and mitigating carbon emissions. Amidst the contributor to the global carbon emissions, China is caught in between mitigating its carbon emission and aiming towards placing its national contribution of emissions to the acceptable levels of 1.5 °C and below 2 °C. Following the intricacies surrounding China’s sustainable development as it contains its economic and environmental performance, we adopt China’s data of 1980 and 2018 with different scientific approaches (nonlinear autoregressive distributed lag (NARDL), dynamic ordinary least square test, and bootstrap Granger causality) with different instruments (such as economic growth, financial development, renewable energy, and innovation policies) to research China’s sustainable development. For clear exposition and insight into our findings with policies attached, we draw a conclusion from the outcomes of the mentioned approaches. From NARDL and dynamic ordinary least squares (DOLS), we find that economic growth through economic activities is statistically significant in determining the trend (increase) of carbon emissions in China in both periods (short run and long run). However, other selected instruments (financial, renewable, and innovation policies) tend towards controlling and moderating the carbon emissions in China. Thus, China has good prospects to mitigate its carbon emissions if considered tailoring its policies towards favorable instruments. From bootstrap Granger causality, we find similar inferential results that support previous findings thereby confirming the positive implication of the selected instruments to China’s sustainable development. Hence, the nexus that is established among the selected instruments clearly show the importance of technological innovation and renewable energy in mitigating carbon emissions.

PMID:35380330 | DOI:10.1007/s11356-022-19730-w

J Neurooncol. 2022 Apr 5. doi: 10.1007/s11060-022-03996-8. Online ahead of print.

ABSTRACT

INTRODUCTION: Glioblastoma (GBM) is the most aggressive central nervous system (CNS) tumor with astrocytic differentiation. The growth pattern of GBM mimics that of the precursor cell migration during the fetal development of the brain. Diaphanous homolog (Diaph3) has been established to play a role in both CNS maturation and cancer progression as it is required both for cell migration and division. Furthermore, Diaph3 has been shown to play a role in malignant disease progression through hyperactivation of the EGFR/MEK/ERK in loss of expression and its overexpression correlating to hyperactivity of the mTOR pathway, both of which are with a well-established role in GBM. Herein, we aimed at establishing the diagnostic role of Diaph3 immunohistochemistry expression patterns in GBM and their possible implications for molecular response to different therapies.

MATERIALS AND METHODS: The study utilized a retrospective nonclinical approach. Results of Diaph3 immunohistochemical expression were compared to healthy controls and reactive gliosis and statistically analyzed for correlation with neuroradiological tumor parameters and patient survival.

RESULTS: Healthy controls showed individual weakly positive cells, while reactive gliosis controls showed a strong expression in astrocytic projections. GBM samples showed a heterogeneous positive reaction to Diaph3, mean number of positive cells 62.66%, median 61.5, range 12-96%. Areas of migrating cells showed a strong diffuse cytoplasmic reaction. Cells located in the tumor core and those in areas of submeningeal aggregation had no antibody expression. Statistical analysis revealed no correlation with tumor size or patient survival.

CONCLUSION: The different expression pattern of Diaph3 in healthy controls, reactive gliosis and GBM shows promise as a clinical differentiating marker. Despite Diaph3 expression not correlating with survival and tumor size in GBM, there is an accumulating body of evidence that Diaph3 correlates with mTOR activity and can thus be used as a predictor for response to rapamycin and taxanes, clinical studies of which have shown promising, if mixed results in GBM.

PMID:35380294 | DOI:10.1007/s11060-022-03996-8

Wien Klin Wochenschr. 2022 Apr 5. doi: 10.1007/s00508-022-02026-x. Online ahead of print.

ABSTRACT

BACKGROUND: There are conflicting results concerning sex-specific differences in the post-cardiac arrest period. We investigated the sex distribution of patients after successful cardiopulmonary resuscitation (CPR), differences in treatment, complications, outcome and sex-specific performance of biomarkers for prognostication of neurological outcome.

METHODS: Prospective observational study including cardiac-arrest (CA) patients treated with mild therapeutic hypothermia (MTH) at 33 °C for 24 h or normothermia. We investigated common complications including pneumonia and acute kidney injury (AKI) and neuron-specific enolase, secretoneurin and tau protein as biomarkers of neurological outcome, which was assessed with the cerebral performance categories score at hospital discharge.

RESULTS: Out of 134 patients 26% were female. Women were significantly older (73 years, interquartile range (IQR) 56-79 years vs. 62 years, IQR 53-70 years; p = 0.038), whereas men showed a significantly higher rate of pneumonia (29% vs. 6%; p = 0.004) and a trend towards higher rates of AKI (62% vs. 45%; p = 0.091). Frequency of MTH treatment was not significantly different (48% vs. 31%; p = 0.081). Female sex was not associated with neurological outcome in multivariable analysis (p = 0.524). There was no significant interaction of sex with prognostication of neurological outcome at 24, 48 and 72 h after CPR. At the respective time intervals p_interaction for neuron-specific enolase was 0.524, 0.221 and 0.519, for secretoneurin 0.893, 0.573 and 0.545 and for tau protein 0.270, 0.635, and 0.110.

CONCLUSION: The proportion of female patients was low. Women presented with higher age but had fewer complications during the post-CA period. Female sex was not associated with better neurological outcome. The performance of biomarkers is not affected by sex.

PMID:35380262 | DOI:10.1007/s00508-022-02026-x

Graefes Arch Clin Exp Ophthalmol. 2022 Apr 5. doi: 10.1007/s00417-022-05641-6. Online ahead of print.

ABSTRACT

PURPOSE: The study aims to evaluate visual outcome, central corneal thickness, and rebubbling rate in a cohort with oversized DMEK grafts after failed penetrating keratoplasty (PK). The unique feature of the study is a descemetorhexis diameter larger than the full-thickness graft, i.e., peripheral to the PK interface.

METHODS: A monocentric, retrospective evaluation of all patients with endothelial graft failure after PK treated with an oversized DMEK graft and descemetorhexis outside of the PK interface (i.e., in host tissue) between January 2015 and July 2019 at the Department of Ophthalmology at the University of Düsseldorf (Germany) was performed.

RESULTS: Eleven eyes of 10 patients were identified. Mean age was 69 years. On average (arithmetic mean ± standard deviation), 1.7 ± 1.0 previous PKs have been performed per eye in this cohort. The mean time between last PK and DMEK was 10.1 ± 7.3 years (range 2 to 23 years). In all cases, the graft diameter exceeded the diameter of the previous PK and descemetorhexis was performed in host tissue, that is, peripheral to the graft-host interface. Rebubbling was performed in 18.2% of the patients (n = 2 eyes) because of central graft detachment. Mean central corneal thickness showed a statistically significant improvement at 5.3 ± 3.5 months after surgery from 688.23 ± 151.01 to 527.75 ± 88 µm (p = 0.002). Visual acuity increased significantly by 5 lines from 1.24 ± 0.5 logMAR (range from 0.5 to 2) to 0.73 ± 0.76 logMAR (range from 0.1 to 2) within 3 months (p = 0.006). Excluding patients without visual potential and transplant failure, visual acuity improved significantly by 8 lines (p < 0.001), and stayed stable until the last follow-up at 15.1 ± 11.4 months (range 6 to 39 months, p < 0.001, n = 8) after surgery.

CONCLUSION: DMEK can be successfully used to treat endothelial cell failure after PK, and can provide good postoperative results with regards to visual acuity. This study shows that stripping of Descemet’s membrane (DM) peripheral to the PK interface is surgically feasible. Overlapping, larger DMEK grafts with more endothelial cells can be used without increasing rebubbling rates and may potentially improve long-term graft survival.

PMID:35380270 | DOI:10.1007/s00417-022-05641-6

Abdom Radiol (NY). 2022 Apr 5. doi: 10.1007/s00261-022-03497-2. Online ahead of print.

ABSTRACT

PURPOSE: To explore the utility of CTE in the evaluation of bowel invasion in patients with primary ovarian, fallopian tube, and peritoneal cancer.

METHODS: This observational study included 73 patients who received CTE before operation between September 2019 and December 2021. Two radiologists reviewed CTE images, focusing on the sites and depth of bowel involvement. Based on the findings during surgical exploration, we evaluated the diagnostic power, like sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+ LR), and negative likelihood ratio (- LR) of CTE. Additionally, the characteristic images of bowel involvement on CTE corresponding to surgical findings were shown in the study.

RESULTS: The rate of macroscopic bowel invasion in this cohort was 49.31% (36/73), of which eight patients had small bowel involvement, 17 patients had colon involvement and 27 patients had sigmoid-rectum involvement. CTE detected bowel invasion in the small intestine with a sensitivity, specificity, PPV, NPV, and accuracy of 87.50%, 92.31%, 58.33%, 98.36%, 91.78%; for colon, the statistics were 58.82%, 96.43%, 83.33%, 88.52%, 87.67% and for sigmoid-rectum 62.96%, 82.61%, 68.00%, 79.17%, 75.34%, respectively.

CONCLUSION: CTE appeared a preferable diagnostic power on the small bowel and colon invasion in patients with primary ovarian, fallopian tube, and peritoneal cancer.

PMID:35380247 | DOI:10.1007/s00261-022-03497-2

Abdom Radiol (NY). 2022 Apr 5. doi: 10.1007/s00261-022-03502-8. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate if trans-arterial embolization (TAE) of the primary tumor in patients with renal cell carcinoma (RCC) improves symptomatology such as pain and hematuria or oncologic outcomes such as progression-free survival (PFS) and overall survival (OS).

MATERIALS AND METHODS: The systematic review search included PubMed, Ovid/MEDLINE, and Embase for full-text English articles including randomized and non-randomized prospective trials as well as prospective and retrospective case series. To be included, prospective trials needed ≥ 25 patients in each arm while case series and retrospective chart reviews required at least two patients. Evaluated outcomes included PFS, OS, change in tumor size, improvements in pain, improvements in hematuria, and adverse events (AEs).

RESULTS: 1327 articles were retrieved and screened. Nine studies met inclusion criteria (retrospective case series, n = 8; non-randomized prospective trial, n = 1) which included 237 patients (M = 156 (65.8%); F = 56 (23.6%); gender unreported = 25 (10.5%); mean age: 69.4 (range: 38-87)) with a mean tumor diameter of 9.3 cm (5.2-10.5). When reported, the TNM stages were stage I (n = 10), II (n = 18), III (n = 36), and IV (n = 121). 60 patients were treated for pain and hematuria. After TAE, pain improved in 59 patients (98.3%) and hematuria improved in 57 patients (95%). A meta-analysis for improvements in pain and hematuria demonstrated an event rate of pain improvement of 0.952 (0.788-0.990; p < 0.001) and an event rate for hematuria improvement of 0.923 (0.809-0.971; p < 0.001). Median OS ranged from 1 to 39 months but only one study reported PFS (10.5 months). Only one study demonstrated a statistically significant improvement in OS with TAE when compared with patients that did not undergo TAE (p = 0.02). A reduction in tumor size was only achieved in 17 patients (17/49; 34.7%) limiting evaluation. AEs included fever (n = 115/237; 48.5%), flank pain (n = 72/237; 30.4%), nausea (n = 58/237; 24.5%), hematuria (n = 12/237; 5.1%), hypertension (n = 12/237; 5.1%), reduced GFR (n = 6/237; 2.5%), hematoma (n = 6/237,2.5%), and ileus (n = 3/237; 1.3%).

CONCLUSION: TAE monotherapy of the primary tumor in patients with RCC improves symptomatology such as pain and hematuria with an acceptable safety profile.

PMID:35380246 | DOI:10.1007/s00261-022-03502-8

Eur Radiol. 2022 Apr 5. doi: 10.1007/s00330-022-08732-4. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Transarterial ⁹⁰Y radioembolization (TARE) is increasingly being used for hepatocellular carcinoma (HCC) treatment. However, tumor response assessment after TARE may be challenging. We aimed to assess the diagnostic performance of gadoxetate disodium MRI for predicting complete pathologic necrosis (CPN) of HCC treated with TARE, using histopathology as the reference standard.

METHODS: This retrospective study included 48 patients (M/F: 36/12, mean age: 62 years) with HCC treated by TARE followed by surgery with gadoxetate disodium MRI within 90 days of surgery. Two radiologists evaluated tumor response using RECIST1.1, mRECIST, EASL, and LI-RADS-TR criteria and evaluated the percentage of necrosis on subtraction during late arterial, portal venous, and hepatobiliary phases (AP/PVP/HBP). Statistical analysis included inter-reader agreement, correlation between radiologic and pathologic percentage of necrosis, and prediction of CPN using logistic regression and ROC analyses.

RESULTS: Histopathology demonstrated 71 HCCs (2.8 ± 1.7 cm, range: 0.5-7.5 cm) including 42 with CPN, 22 with partial necrosis, and 7 without necrosis. EASL and percentage of tumor necrosis on subtraction at the AP/PVP were independent predictors of CPN (p = 0.02-0.03). Percentage of necrosis, mRECIST, EASL, and LI-RADS-TR had fair to good performance for diagnosing CPN (AUCs: 0.78 – 0.83), with a significant difference between subtraction and LI-RADS-TR for reader 2, and in specificity between subtraction and other criteria for both readers (p-range: 0.01-0.04). Radiologic percentage of necrosis was significantly correlated to histopathologic degree of tumor necrosis (r = 0.66 – 0.8, p < 0.001).

CONCLUSIONS: Percentage of tumor necrosis on subtraction and EASL criteria were significant independent predictors of CPN in HCC treated with TARE. Image subtraction should be considered for assessing HCC response to TARE when using MRI.

KEY POINTS: • Percentage of tumor necrosis on image subtraction and EASL criteria are significant independent predictors of complete pathologic necrosis in hepatocellular carcinoma treated with⁹⁰Y radioembolization. • Subtraction, mRECIST, EASL, and LI-RADS-TR have fair to good performance for diagnosing complete pathologic necrosis in hepatocellular carcinoma treated with⁹⁰Y radioembolization.

PMID:35380226 | DOI:10.1007/s00330-022-08732-4