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Efficacy of Αtezolizumab-Βevacizumab in BCLC-C cirrhotic patients with hepatocellular carcinoma according to the type of disease progression, the type of BCLC-C and liver disease severity

J Cancer Res Clin Oncol. 2023 May 18. doi: 10.1007/s00432-023-04846-4. Online ahead of print.

ABSTRACT

PURPOSE: The aim of our study was to evaluate, under real-life conditions, survival of patients with advanced HCC (BCLC-C), either initially presenting in that stage or migrating from BCLC-A to BCLC-C within 2 years after curative LR/RFA, treated either with Atezolizumab-Bevacizumab or TKIs.

METHODS: Sixty-four cirrhotic patients with advanced HCC, who either initially presented as BCLC-C and were treated with Atezo-Bev (group A, N = 23) or TKIs (group B, N = 15) or who migrated from BCLC-A to BCLC-C stage within 2 years after LR/RFA and were either treated with Atezo-Bev (group C, N = 12) or TKIs (group D, N = 14), were retrospectively evaluated.

RESULTS: The four groups were comparable for all baseline parameters (demographics/platelets/liver disease etiology/diabetes/varices/Child-Pugh stage/ALBI grade) except for CPT score and MELD-Na. Using Cox-regression analysis, we observed that survival of group C after systemic treatment onset was significantly higher compared to group A (HR 3.71, 1.20-11.46, p = 0.02) and presented a trend to statistical significance when compared to group D (HR 3.14, 0.95-10.35, p = 0.06), adjusted for liver disease severity scores. When all BCLC-C patients classified as such due to PS only were excluded from the study, a trend for the same survival benefit in group C was shown, even in the most difficult-to-treat population with extrahepatic disease or macrovascular invasion.

CONCLUSION: Cirrhotic patients with advanced HCC initially diagnosed in BCLC-C, exhibit the worst survival irrespective of treatment schedule, whereas patients progressing to BCLC-C following disease recurrence after LR/RFA, seem to mostly benefit from Atezo-Bev, even patients with extrahepatic disease and/or macrovascular invasion. Liver disease severity seems to drive survival of these patients.

PMID:37199835 | DOI:10.1007/s00432-023-04846-4

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Assessment of clinical outcomes in patients with fibromyalgia: Analysis from the UK Medical Cannabis Registry

Brain Behav. 2023 May 18:e3072. doi: 10.1002/brb3.3072. Online ahead of print.

ABSTRACT

INTRODUCTION: There are limited therapeutic options for individuals with fibromyalgia. The aim of this study is to analyze changes in health-related quality of life and incidence of adverse events of those prescribed cannabis-based medicinal products (CBMPs) for fibromyalgia.

METHODS: Patients treated with CBMPs for a minimum of 1 month were identified from the UK Medical Cannabis Registry. Primary outcomes were changes in validated patient-reported outcome measures (PROMs). A p-value of <.050 was deemed statistically significant.

RESULTS: In total, 306 patients with fibromyalgia were included for analysis. There were improvements in global health-related quality of life at 1, 3, 6, and 12 months (p < .0001). The most frequent adverse events were fatigue (n = 75; 24.51%), dry mouth (n = 69; 22.55%), concentration impairment (n = 66; 21.57%), and lethargy (n = 65; 21.24%).

CONCLUSION: CBMP treatment was associated with improvements in fibromyalgia-specific symptoms, in addition to sleep, anxiety, and health-related quality of life. Those who reported prior cannabis use appeared to have a greater response. CBMPs were generally well-tolerated. These results must be interpreted within the limitations of study design.

PMID:37199833 | DOI:10.1002/brb3.3072

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Comparison of Different Adjuvant Therapies for Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review and Network Meta-Analysis

Indian J Pediatr. 2023 May 18. doi: 10.1007/s12098-023-04563-3. Online ahead of print.

ABSTRACT

OBJECTIVES: Neonatal hypoxic-ischemic encephalopathy is a major cause of perinatal death and neurodevelopmental impairment (NDI). Hypothermia (HT) is the standard of care; however, additional neuroprotective agents are required to improve prognosis. The authors searched for all drugs in combination with HT and compared their effects using a network meta-analysis.

METHODS: The authors searched PubMed, Embase, and Cochrane Library until September 24, 2022 for articles assessing mortality, NDI, seizures, and abnormal brain imaging findings in neonates with hypoxic-ischemic encephalopathy. Direct pairwise comparisons and a network meta-analysis was performed under random effects.

RESULTS: Thirteen randomized clinical trials enroled 902 newborns treated with six combination therapies: erythropoietin magnesium sulfate, melatonin (MT), topiramate, xenon, and darbepoetin alfa. The results of all comparisons were not statistically significant, except for NDI, HT vs. MT+HT: odds ratio = 6.67, 95% confidence interval = 1.14-38.83; however, the overall evidence quality was low for the small sample size.

CONCLUSIONS: Currently, no combination therapy can reduce mortality, seizures, or abnormal brain imaging findings in neonatal hypoxic-ischemic encephalopathy. According to low quality evidence, HT combined with MT may reduce NDI.

PMID:37199820 | DOI:10.1007/s12098-023-04563-3

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Intra- and Peritumoral Based Radiomics for Assessment of Lymphovascular Invasion in Invasive Breast Cancer

J Magn Reson Imaging. 2023 May 18. doi: 10.1002/jmri.28776. Online ahead of print.

ABSTRACT

BACKGROUND: Radiomics has been applied for assessing lymphovascular invasion (LVI) in patients with breast cancer. However, associations between features from peritumoral regions and the LVI status were not investigated.

PURPOSE: To investigate the value of intra- and peritumoral radiomics for assessing LVI, and to develop a nomogram to assist in making treatment decisions.

STUDY TYPE: Retrospective.

POPULATION: Three hundred and sixteen patients were enrolled from two centers and divided into training (N = 165), internal validation (N = 83), and external validation (N = 68) cohorts.

FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T/dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI).

ASSESSMENT: Radiomics features were extracted and selected based on intra- and peritumoral breast regions in two magnetic resonance imaging (MRI) sequences to create the multiparametric MRI combined radiomics signature (RS-DCE plus DWI). The clinical model was built with MRI-axillary lymph nodes (MRI ALN), MRI-reported peritumoral edema (MPE), and apparent diffusion coefficient (ADC). The nomogram was constructed with RS-DCE plus DWI, MRI ALN, MPE, and ADC.

STATISTICAL TESTS: Intra- and interclass correlation coefficient analysis, Mann-Whitney U test, and least absolute shrinkage and selection operator regression were used for feature selection. Receiver operating characteristic and decision curve analyses were applied to compare performance of the RS-DCE plus DWI, clinical model, and nomogram.

RESULTS: A total of 10 features were found to be associated with LVI, 3 from intra- and 7 from peritumoral areas. The nomogram showed good performance in the training (AUCs, nomogram vs. clinical model vs. RS-DCE plus DWI, 0.884 vs. 0.695 vs. 0.870), internal validation (AUCs, nomogram vs. clinical model vs. RS-DCE plus DWI, 0.813 vs. 0.695 vs. 0.794), and external validation (AUCs, nomogram vs. clinical model vs. RS-DCE plus DWI, 0.862 vs. 0.601 vs. 0.849) cohorts.

DATA CONCLUSION: The constructed preoperative nomogram might effectively assess LVI.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

PMID:37199241 | DOI:10.1002/jmri.28776

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Detecting Double Expression Status in Primary Central Nervous System Lymphoma Using Multiparametric MRI Based Machine Learning

J Magn Reson Imaging. 2023 May 18. doi: 10.1002/jmri.28782. Online ahead of print.

ABSTRACT

BACKGROUND: Double expression lymphoma (DEL) is a subtype of primary central nervous system lymphoma (PCNSL) that often has a poor prognosis. Currently, there are limited noninvasive ways to detect protein expression.

PURPOSE: To detect DEL in PCNSL using multiparametric MRI-based machine learning.

STUDY TYPE: Retrospective.

POPULATION: Forty PCNSL patients were enrolled in the study among whom 17 were DEL (9 males and 8 females, 61.29 ± 14.14 years) and 23 were non-DEL (14 males and 9 females, 55.57 ± 14.16 years) with 59 lesions (28 DEL and 31 non-DEL).

FIELD STRENGTH/SEQUENCE: ADC map derived from DWI (b = 0/1000 s/mm2 ), fast spin echo T2WI, T2FLAIR, and contrast-enhanced T1 weighted imaging (T1CE) were collected at 3.0 T.

ASSESSMENT: Two raters manually segmented lesions by ITK-SNAP on ADC, T2WI, T2FLAIR and T1CE. A total of 2234 radiomics features from the tumor segmentation area were extracted. The t-test was conducted to filter the features, and elastic net regression algorithm combined with recursive feature elimination was used to calculate the essential features. Finally, 12 groups with combinations of different sequences were fitted to 6 classifiers, and the optimal models were selected.

STATISTICAL TESTS: Continuous variables were assessed by the t-test, while categorical variables were assessed by the non-parametric test. Interclass correlation coefficient tested variables’ consistency. Sensitivity, specificity, accuracy F1-score, and area under the curve (AUC) were used to evaluate model performance.

RESULTS: DEL status could be identified to varying degrees with 72 models based on radiomics, and model performance could be improved by combining different sequences and classifiers. Both SVMlinear and logistic regression (LR) combined with four sequence group had similar largest AUCmean (0.92 ± 0.09 vs. 0.92 ± 0.05), and SVMlinear was considered as the optimal model in this study since the F1-score of SVMlinear (0.88) was higher than that of LR (0.83).

DATA CONCLUSION: Multiparametric MRI-based machine learning is promising in DEL detection.

EVIDENCE LEVEL: 4 TECHNICAL EFFICACY STAGE: 2.

PMID:37199225 | DOI:10.1002/jmri.28782

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Effect of electroacupuncture at Baihui (GV 20) and Sishencong (EX-HN 1) on presurgical anxiety in patients with gynecological laparoscopic surgery

Zhongguo Zhen Jiu. 2022 Oct 12;42(10):1115-9. doi: 10.13703/j.0255-2930.20211124-k0009.

ABSTRACT

OBJECTIVE: To observe the anti-anxiety effect of electroacupuncture at Baihui (GV 20) and Sishencong (EX-HN 1) in patients with gynecological laparoscopic surgery, and to explore its effect on the anesthetic dosage during anesthesia induction.

METHODS: A total of 270 patients with gynecological laparoscopic surgery were randomized into an electroacupuncture group, a medication group and a control group, 90 cases in each group. At 24 h and 2 h before anesthesia induction, electroacupuncture was applied at Baihui (GV 20) and Sishencong (EX-HN 1) in the electroacupuncture group, with continuous wave, 100 Hz in frequency. At 30 min before anesthesia induction, midazolam of 0.02 mg/kg was given by intravenous drip in the medication group, while 0.9% sodium chloride solution was given by intravenous drip in the control group. At 10 min before anesthesia induction and 6 h after surgery, the scores of 6 item short form of state-trait anxiety inventory (STAI-S6) and visual analogue scale-anxiety (VAS-A) were observed; at 10 min before anesthesia induction (T1) and observer’s assessment of alertness/sedation scale (OAA/S) grade 4 (T2), mean artery pressure (MAP), heart rate (HR) and value of bispectral index (BIS) were recorded; the dosage of propofol at T2 was recorded and the surgery related adverse reactions were compared among the 3 groups.

RESULTS: At 10 min before anesthesia induction and 6 h after surgery, the STAI-S6 and VAS-A scores in the electroacupuncture group and the medication group were lower than those in the control group (P<0.05). Values of BIS at T1 and dosage of propofol at T2 in the electroacupuncture group and the medication group were lower than those in the control group (P<0.05). There were no statistical differences in MAP, HR and surgery related adverse reactions among the 3 groups (P>0.05).

CONCLUSION: Electroacupuncture at Baihui (GV 20) and Sishencong (EX-HN 1) can effectively relieve the presurgical anxiety in patients with gynecological laparoscopic surgery, and reduce the dosage of propofol, its effect is similar to traditional anti-anxiety drug.

PMID:37199201 | DOI:10.13703/j.0255-2930.20211124-k0009

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Comparative binding analysis of WGX50 and Alpha-M with APP family proteins APLP1 and APLP2 using structural-dynamics and free energy calculation approaches

Phys Chem Chem Phys. 2023 May 18. doi: 10.1039/d2cp06083c. Online ahead of print.

ABSTRACT

A.D. is a common disease among other neurodegenerative disorders primarily developing due to amyloid-β (Aβ) neurotoxicity derived from the amyloid-β protein precursor (AβPP). The amyloid precursor-like proteins 1 and 2 (APP1 and APLP2) biochemically behave similarly in many aspects to AβPP. We, therefore, proposed to test WGX-50 and Alpha-M for their interaction mechanism with APLP1 and APLP2 because both these drug candidate compounds previously showed inhibition of Aβ aggregation. We employed a comparative atomic investigation on Alpha-M and WGX-50 in complex with novel targets, i.e., APLP1 and APLP2, using biophysical and molecular simulation methods. The docking score was -6.83 kcal mol-1 for Alpha-M-APLP1, -8.41 kcal mol-1 for WGX-50-APLP1, -7.02 kcal mol-1 for Alpha-M-APLP2 and -8.25 kcal mol-1 for the WGX-50-APLP2 complex. Our results also elaborate that in the case of their interaction with both APLP1 and APLP2, the WGX-50 complex exhibits better stability than the APLP1/2-Alpha-M complexes during simulation. Furthermore, WGX50 in both APLP1 and APLP2 stabilized the internal flexibility upon binding in contrast to the Alpha-M complexes. The data showed that the BFE for Alpha-M-APLP1 was calculated to be -27.38 ± 0.93 kcal mol-1, for WGX-50-APLP1 -39.65 ± 0.95 kcal mol-1, for Alpha-M-APLP2 -24.80 ± 0.63 kcal mol-1 while for WGX-50-APLP2 the BFE was -57.16 ± 1.03 kcal mol-1 respectively. These results highlight that APLP2-WGX50 has greater binding energies in all four systems. PCA and FEL analysis further revealed variations in the dynamic behavior of these complexes. Overall, our findings demonstrate that WGX50 potentially acts as a more potent inhibitor for APLP1 and APLP2 than Alpha-M and thus shows the diverse pharmacological potential of WGX50. Due to its stable binding interaction, WGX50 might be a suitable candidate drug compound for targeting these precursors under pathological conditions.

PMID:37199163 | DOI:10.1039/d2cp06083c

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Presence of Peripheral Artery Disease Is Associated With Increased Risk of Heart Failure Events: Insights From EMPEROR-Pooled

Arterioscler Thromb Vasc Biol. 2023 May 18. doi: 10.1161/ATVBAHA.123.319156. Online ahead of print.

NO ABSTRACT

PMID:37199158 | DOI:10.1161/ATVBAHA.123.319156

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Shorter Door-to-Needle Times Are Associated With Better Outcomes After Intravenous Thrombolytic Therapy and Endovascular Thrombectomy for Acute Ischemic Stroke

Circulation. 2023 May 18. doi: 10.1161/CIRCULATIONAHA.123.064053. Online ahead of print.

ABSTRACT

BACKGROUND: Existing data and clinical trials could not determine whether faster intravenous thrombolytic therapy (IVT) translates into better long-term functional outcomes after acute ischemic stroke among those treated with endovascular thrombectomy (EVT). Patient-level national data can provide the required large population to study the associations between earlier IVT, versus later, with longitudinal functional outcomes and mortality in patients receiving IVT+EVT combined treatment.

METHODS: This cohort study included older US patients (age ≥65 years) who received IVT within 4.5 hours or EVT within 7 hours after acute ischemic stroke using the linked 2015 to 2018 Get With The Guidelines-Stroke and Medicare database (38 913 treated with IVT only and 3946 with IVT+EVT). Primary outcome was home time, a patient-prioritized functional outcome. Secondary outcomes included all-cause mortality in 1 year. Multivariate logistic regression and Cox proportional hazards models were used to evaluate the associations between door-to-needle (DTN) times and outcomes.

RESULTS: Among patients treated with IVT+EVT, after adjusting for patient and hospital factors, including onset-to-EVT times, each 15-minute increase in DTN times for IVT was associated with significantly higher odds of zero home time in a year (never discharged to home) (adjusted odds ratio, 1.12 [95% CI, 1.06-1.19]), less home time among those discharged to home (adjusted odds ratio, 0.93 per 1% of 365 days [95% CI, 0.89-0.98]), and higher all-cause mortality (adjusted hazard ratio, 1.07 [95% CI, 1.02-1.11]). These associations were also statistically significant among patients treated with IVT but at a modest degree (adjusted odds ratio, 1.04 for zero home time, 0.96 per 1% home time for those discharged to home, and adjusted hazard ratio 1.03 for mortality). In the secondary analysis where the IVT+EVT group was compared with 3704 patients treated with EVT only, shorter DTN times (≤60, 45, and 30 minutes) achieved incrementally more home time in a year, and more modified Rankin Scale 0 to 2 at discharge (22.3%, 23.4%, and 25.0%, respectively) versus EVT only (16.4%, P<0.001 for each). The benefit dissipated with DTN>60 minutes.

CONCLUSIONS: Among older patients with stroke treated with either IVT only or IVT+EVT, shorter DTN times are associated with better long-term functional outcomes and lower mortality. These findings support further efforts to accelerate thrombolytic administration in all eligible patients, including EVT candidates.

PMID:37199147 | DOI:10.1161/CIRCULATIONAHA.123.064053

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Comparison of likelihood penalization and variance decomposition approaches for clinical prediction models: A simulation study

Biom J. 2023 May 18:e2200108. doi: 10.1002/bimj.202200108. Online ahead of print.

ABSTRACT

Logistic regression is one of the most commonly used approaches to develop clinical risk prediction models. Developers of such models often rely on approaches that aim to minimize the risk of overfitting and improve predictive performance of the logistic model, such as through likelihood penalization and variance decomposition techniques. We present an extensive simulation study that compares the out-of-sample predictive performance of risk prediction models derived using the elastic net, with Lasso and ridge as special cases, and variance decomposition techniques, namely, incomplete principal component regression and incomplete partial least squares regression. We varied the expected events per variable, event fraction, number of candidate predictors, presence of noise predictors, and the presence of sparse predictors in a full-factorial design. Predictive performance was compared on measures of discrimination, calibration, and prediction error. Simulation metamodels were derived to explain the performance differences within model derivation approaches. Our results indicate that, on average, prediction models developed using penalization and variance decomposition approaches outperform models developed using ordinary maximum likelihood estimation, with penalization approaches being consistently superior over the variance decomposition approaches. Differences in performance were most pronounced on the calibration of the model. Performance differences regarding prediction error and concordance statistic outcomes were often small between approaches. The use of likelihood penalization and variance decomposition techniques methods was illustrated in the context of peripheral arterial disease.

PMID:37199142 | DOI:10.1002/bimj.202200108