Tag: nevin manimala

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

Eur Radiol. 2022 Apr 5. doi: 10.1007/s00330-022-08709-3. Online ahead of print.

ABSTRACT

OBJECTIVES: To analyze the response in the management of both radiological emergencies and continuity of care in oncologic/fragile patients of a radiology department of Sant’Andrea Academic Hospital in Rome supported by a dedicated business analytics software during the COVID-19 pandemic.

METHODS: Imaging volumes and workflows for 2019 and 2020 were analyzed. Information was collected from the hospital data warehouse and evaluated using a business analytics software, aggregated both per week and per quarter, stratified by patient service location (emergency department, inpatients, outpatients) and imaging modality. For emergency radiology subunit, radiologist workload, machine workload, and turnaround times (TATs) were also analyzed.

RESULTS: Total imaging volume in 2020 decreased by 21.5% compared to that in 2019 (p < .001); CT in outpatients increased by 11.7% (p < .005). Median global TAT and median code-blue global TAT were not statistically significantly different between 2019 and 2020 and between the first and the second pandemic waves in 2020 (all p > .09). Radiologist workload decreased by 24.7% (p < .001) during the first pandemic wave in 2020 compared with the same weeks of 2019 and showed no statistically significant difference during the second pandemic wave, compared with the same weeks of 2019 (p = 0.19).

CONCLUSIONS: Despite the reduction of total imaging volume due to the COVID-19 pandemic in 2020 compared to 2019, management decisions supported by a dedicated business analytics software allowed to increase the number of CT in fragile/oncologic outpatients without significantly affecting emergency radiology TATs, and emergency radiologist workload.

KEY POINTS: • During the COVID-19 pandemic, management decisions supported by business analytics software guaranteed efficiency of emergency and preservation of fragile/oncologic patient continuity of care. • Real-time data monitoring using business analytics software is essential for appropriate management decisions in a department of radiology. • Business analytics should be gradually introduced in all healthcare institutions to identify strong and weak points in workflow taking correct decisions.

PMID:35380224 | DOI:10.1007/s00330-022-08709-3

Osteoporos Int. 2022 Apr 5. doi: 10.1007/s00198-022-06376-0. Online ahead of print.

ABSTRACT

Data are contradictory regarding the relationship between osteoarthritis (OA) and osteoporosis (OP) with some studies showing the increased risk of OP in OA. The study was conducted to determine whether OP prevalence is increased in patients with OA, compared to age and sex-matched population. MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library (inception-2019) were searched for studies reporting the frequency, rate, prevalence, incidence, risk, or excess risk of OP in patients with OA compared to age and sex-matched population. Estimates were combined using a random effects model. Consistency was evaluated using the I² statistic. Articles with fewer than 200 participants were excluded. Of 2772 articles, 49 had full article screening, and 8 articles met the inclusion criteria. Other articles reporting mean BMD and not OP were excluded. In women, 998 participants with OA were compared with 1903 controls. The pooled estimate of the odds ratio for prevalence of OP vs general matched population was not statistically different. In men, 136 participants with OA were compared with 682 controls. The results did not show a statistically significant difference in the frequency of OP in OA in men. According to the site of bone mineral density measurement, a higher prevalence of OP at lumbar spine was found in both men and women. The frequency of OP overall in participants with OA was not different, except for a higher prevalence of OP in lumbar spine in both men and women compared to the matched controls.

PMID:35380214 | DOI:10.1007/s00198-022-06376-0