Baseline 18F-FDG PET/CT radiomics for prognosis prediction in diffuse large B cell lymphoma with extranodal involvement.

PURPOSE: The objective of this investigation is to explore the capability of baseline 18F-FDG PET/CT radiomics to predict the prognosis of diffuse large B-cell lymphoma (DLBCL) with extranodal involvement (ENI). METHODS: 126 patients diagnosed with DLBCL with ENI were included in the cohort. The least absolute shrinkage and selection operator (LASSO) Cox regression was utilized to refine the optimum subset from the 1328 features. Cox regression analyses were employed to discern significant clinical variables and conventional PET parameters, which were then employed with radiomics score to develop combined model for predicting both progression-free survival (PFS) and overall survival (OS). The fitness and the predictive capability of the models were assessed via the Akaike information criterion (AIC) and concordance index (C-index). RESULTS: 62 patients experienced disease recurrence or progression and 28 patients ultimately died. The combined model exhibited a lower AIC value compared to the radiomics model and SDmax/clinical variables for both PFS (507.101 vs. 510.658 vs. 525.506) and OS (215.667 vs. 230.556 vs. 219.313), respectively. The C-indices of the combined model, radiomics model, and SDmax/clinical variables were 0.724, 0.704, and 0.615 for PFS, and 0.842, 0.744, and 0.792 for OS, respectively. Kaplan--Meier curves showed significantly higher rates of relapse and mortality among patients classified as high-risk compared to those classified as low-risk (all P < 0.05). CONCLUSIONS: The combined model of clinical variables, conventional PET parameters, and baseline PET/CT radiomics features demonstrates a higher accuracy in predicting the prognosis of DLBCL with ENI.

MET overexpression correlated with prognosis of EGFR-mutant treatment­naïve advanced lung adenocarcinoma: a real­world retrospective study.

BACKGROUND: About 50-60% treatment-naïve advanced non-small-cell lung cancers were coexistence of epidermal growth factor receptor (EGFR) and mesenchymal epithelial transition (MET) overexpression. However, few studies demonstrated the prognostic value of MET protein expression in untreated EGFR-mutant lung adenocarcinoma (LUAD). METHODS: A total of 235 EGFR-mutant untreated advanced LUAD patients were retrospectively enrolled. MET expression was determined using immunohistochemistry, and MET positivity was defined as 2 + or 3 + using the METmab scoring algorithm. Progression-free survival (PFS) and overall survival (OS) were analysed according to MET expression status. Independent factors predicting prognosis were identified using multivariate Cox regression analyses. RESULTS: Of the 235 patients, 113 (48.1%) harboured exon 19 deletion (19_del), 103 (43.8%) had exon 21 L858R mutations, and 19 (8.1%) had other mutation types, including exon 21 L861Q, exon 18 G719A/C, exon 20 S768I, and L858R/19_del double mutations. MET-positive expression was observed in 192 (81.7%) cases. There was no significant difference in baseline clinicopathological characteristics between MET positivity and MET negativity groups. Patients were stratified by different EGFR mutation subtypes. MET-positive patients in the L858R mutation subgroup had markedly shorter PFS and OS than MET-negative patients (median PFS: 13 versus 27.5 months, p < 0.001; median OS: 29 versus not reached, p = 0.008), but no significant difference was observed in the 19_del subgroup. Multivariate Cox regression analyses indicated that MET positivity was an independent predictor for poor PFS and OS in L858R subgroup (PFS: HR = 3.059, 95% CI 1.552-6.029, p = 0.001; OS: HR = 3.511, 95% CI 1.346-9.160, p = 0.010). Additionally, an inferior survival outcome of MET positivity was observed in the L858R mutation subgroup when treated with EGFR-tyrosine kinase inhibitor (TKI) monotherapy as the first-line regimen (median PFS: 13 versus 36.5 months, p < 0.001; median OS: 29 versus not reached, p = 0.012) but not with EGFR-TKI plus platinum doublet chemotherapy. CONCLUSIONS: MET positive expression was an independent predictor of poor outcomes in untreated EGFR L858R mutation advanced LUAD patients treated with first-line EGFR-TKI monotherapy.

Patient navigation to address sociolegal barriers for patients with cancer: A comparative-effectiveness study.

BACKGROUND: Sociolegal barriers to cancer care are defined as health-related social needs like affordable healthy housing, stable utility service, and food security that may be remedied by public policy, law, regulation, or programming. Legal support has not been studied in cancer care. METHODS: The authors conducted a randomized controlled trial of patients who had newly diagnosed cancer at a safety-net medical center in Boston from 2014 through 2017, comparing standard patient navigation versus enhanced navigation partnered with legal advocates to identify and address sociolegal barriers. English-speaking, Spanish-speaking, or Haitian Creole-speaking patients with breast and lung cancer were eligible within 30 days of diagnosis. The primary outcome was timely treatment within 90 days of diagnosis. Secondary outcomes included patient-reported outcomes (distress, cancer-related needs, and satisfaction with navigation) at baseline and at 6 months. RESULTS: In total, 201 patients with breast cancer and 19 with lung cancer enrolled (response rate, 78%). The mean patient age was 55 years, 51% of patients were Black and 22% were Hispanic, 20% spoke Spanish and 8% spoke Haitian Creole, 73% had public health insurance, 77% reported 1 or more perceived sociolegal barrier, and the most common were barriers to housing and employment. Ninety-six percent of participants with breast cancer and 73% of those with lung cancer initiated treatment within 90 days. No significant effect of enhanced navigation was observed on the receipt of timely treatment among participants with breast cancer (odds ratio, 0.88; 95% CI, 0.17-4.52) or among those with lung cancer (odds ratio, 4.00; 95% CI, 0.35-45.4). No differences in patient-reported outcomes were observed between treatment groups. CONCLUSIONS: Navigation enhanced by access to legal consultation and support had no impact on timely treatment, patient distress, or patient needs. Although most patients reported sociolegal barriers, few required intensive legal services that could not be addressed by navigators. LAY SUMMARY: In patients with cancer, the experience of sociolegal barriers to care, such as unstable housing, utility services, or food insecurity, is discussed. Addressing these barriers through legal information and assistance may improve care. This study compares standard patient navigation versus enhanced navigation partnered with legal advocates for patients with breast and lung cancers. Almost all patients in both navigation groups received timely care and also reported the same levels of distress, needs, and satisfaction with navigation. Although 75% of patients in the study had at least 1 sociolegal barrier identified, few required legal advocacy beyond what a navigator who received legal information and coaching could provide.

Association of raised serum progesterone level with ovulation trigger and histology of endometrium in stimulated cycles

Abstract This was a forthcoming study of those patients, who undergo in-vitro fertilization (IVF) and freeze-all embryo, who acquiesce for the study. The number of participated patients (n=350) in this study, underwent for IVF. The blood sample was collected from patients to evaluate the level of serum progesterone in vacuum vials on the day of ovulation trigger. After 36 hrs of ovulation trigger, ovum picked up was done. Quantitative methods were used to estimate the level of serum progesterone through the electrochemiluminescence immunoassay and correlation of serum progesterone with embryo transfer (ET) outcomes. Main outcome of this current study was to evaluate the value of mean serum progesterone level i.e.0.868± 0.712 ng/ml and 0.88±0.723 ng/ml was found in case of pregnancy positive and negative respectively, at p=0.216 value. In antagonist (n=40) and agonist (n=310) cases, it was 8(20%) and 37(11.94%) PL occurrence was noted at p=0.143 respectively. An overall value of the premature lutenization (PL) occurrences was 13.63% and 15.25% observed in both positive and negative cases of pregnancy at p=0.216 respectively. This study concluded that 12.66% of PL occurrences were recorded in the case of IVF. Study results proved, there were no significant effect of PL on pregnancy outcomes.

Health Literacy, Language, and Cancer-Related Needs in the First 6 Months After a Breast Cancer Diagnosis.

PURPOSE: Low health literacy (HL) and language negatively affect cancer screening and prevention behaviors; less is known about how they affect the patient's experience during cancer treatment. This study explores associations among HL, spoken language, and dimensions of cancer-related needs within 6 months of receiving a breast cancer diagnosis. METHODS: Women speaking English, Spanish, or Haitian Creole, enrolled in a patient navigation study at diagnosis, completed a survey in their primary spoken language at baseline and 6 months to characterize their cancer-related needs. HL was measured using the Brief Health Literacy Screening Tool. Outcomes included the Cancer Needs Distress Inventory (CaNDI; n = 38 items) and the Communication and Attitudinal Self-Efficacy scale (CASE-Cancer) for cancer (n = 12 items). Linear regressions measured the impact of HL and language on total CaNDI and CASE-Cancer scale for cancer scores and subscales, adjusted for demographics. RESULTS: At baseline, 262 women participated and 228 (87%) followed up at 6 months. Of these, 38% had adequate HL, 33% had marginal HL, and 29% had inadequate HL. Women with inadequate or marginal HL had higher median baseline CaNDI scores (P = .02) and lower self-efficacy scores (P = .008), relative to those with adequate HL. Haitian-Creole speakers had significantly lower CANDI scores at baseline (P = .03). Adjusting for demographics, differences in CaNDI scores at baseline remained significant for those with lower HL and Haitian-Creole speakers. At 6 months, differences in self-efficacy persisted for Haitian-Creole speakers. CONCLUSION: Findings suggest that interventions oriented to mitigating HL and language barriers might reduce distress at the time of diagnosis and improve self-efficacy over the course of treatment.

Application value of magnetic resonance hydrography of the inner ear in cochlear implantation.

OBJECTIVE: This study aims to investigate the application value of magnetic resonance (MR) hydrography of the inner ear in cochlear implantation. METHODS: 146 patients were enrolled. MR hydrography and spiral CT examinations for the intracranial auditory canal were performed before surgery, and all imaging results were statistically analyzed in order to explore the application value of MR hydrography of the inner ear in cochlear implantation. RESULTS: 146 patients (292 ears) were examined. Among these patients, 13 were diagnosed with abnormal vestibular aqueducts (20 ears) by MR hydrography, while five were diagnosed with this disease by CT; 15 patients were diagnosed with inner ear malformation (19 ears) by MR hydrography, while 11 were diagnosed by CT (four were misdiagnosed); five patients were diagnosed with internal acoustic canal stenosis (eight ears) by MR hydrography, while two were diagnosed by CT (three were misdiagnosed); and four patients were diagnosed with cochlear fibrosis (five ears) by MR hydrography, while four were diagnosed by CT (four ears). The correct rate of diagnosis was 77.40% (113/146) based on CT, while the rate was 93.84% (137/146) based on MR hydrography. CONCLUSIONS: MR hydrography imaging technique can be applied to the preoperative evaluation of cochlear implantation, providing accurate and reliable anatomic information on the inner membranous labyrinth and nerves in the internal acoustic canal and an accurate basis for the diagnosis of cochlear fibrosis and nerve development. This has a guiding significance for the selection of treatment schemes.

Application value of magnetic resonance hydrography of the inner ear in cochlear implantation

SUMMARY OBJECTIVE This study aims to investigate the application value of magnetic resonance (MR) hydrography of the inner ear in cochlear implantation. METHODS 146 patients were enrolled. MR hydrography and spiral CT examinations for the intracranial auditory canal were performed before surgery, and all imaging results were statistically analyzed in order to explore the application value of MR hydrography of the inner ear in cochlear implantation. RESULTS 146 patients (292 ears) were examined. Among these patients, 13 were diagnosed with abnormal vestibular aqueducts (20 ears) by MR hydrography, while five were diagnosed with this disease by CT; 15 patients were diagnosed with inner ear malformation (19 ears) by MR hydrography, while 11 were diagnosed by CT (four were misdiagnosed); five patients were diagnosed with internal acoustic canal stenosis (eight ears) by MR hydrography, while two were diagnosed by CT (three were misdiagnosed); and four patients were diagnosed with cochlear fibrosis (five ears) by MR hydrography, while four were diagnosed by CT (four ears). The correct rate of diagnosis was 77.40% (113/146) based on CT, while the rate was 93.84% (137/146) based on MR hydrography. CONCLUSIONS MR hydrography imaging technique can be applied to the preoperative evaluation of cochlear implantation, providing accurate and reliable anatomic information on the inner membranous labyrinth and nerves in the internal acoustic canal and an accurate basis for the diagnosis of cochlear fibrosis and nerve development. This has a guiding significance for the selection of treatment schemes.

RESUMO OBJETIVO Este estudo visa investigar o valor da aplicação da hidrografia por ressonância magnética (RM) do ouvido interno no implante coclear. MÉTODOS Cento e quarenta e seis pacientes foram inscritos. Os exames da hidrografia por RM e do CT espiral para o canal auditivo intracraniano foram executados antes da cirurgia, e todos os resultados da imagem foram analisados estatisticamente, a fim de explorar o valor da aplicação da hidrografia por RM do ouvido interno no implante coclear. RESULTADOS Centro e quarenta e seis pacientes (292 ouvidos) foram examinados. Dentre esses pacientes, 13 foram diagnosticados com aquedutos vestibulares anormais (20 ouvidos) pela hidrografia por RM, enquanto cinco pacientes foram diagnosticados com esta doença pelo CT; 15 pacientes foram diagnosticados com malformação do ouvido interno (19 ouvidos) pela hidrografia por RM, enquanto 11 pacientes foram diagnosticados por CT (quatro foram diagnosticados erroneamente); cinco pacientes foram diagnosticados com estenose de canal acústico interno (oito ouvidos) pela hidrografia por RM, enquanto dois pacientes foram diagnosticados por CT (três foram diagnosticados erroneamente); e quatro pacientes foram diagnosticados com fibrose coclear (cinco ouvidos) pela hidrografia por RM, enquanto quatro foram diagnosticados por CT (quatro ouvidos). A taxa correta de diagnóstico foi de 77,40% (113/146) com base no CT, enquanto a taxa foi de 93,84% (137/146) com base na hidrografia por RM. CONCLUSÕES A técnica de imagem da hidrografia por RM pode ser aplicada à avaliação pré-operatória do implante coclear, que pode fornecer informações anatômicas precisas e confiáveis sobre o labirinto membranoso interno e os nervos no canal acústico interno, além de uma base exata para o diagnóstico da fibrose coclear e do desenvolvimento do nervo. Isso tem um significado orientador para a seleção de esquemas de tratamento.

Cryptic speciation in Protoceratium reticulatum (Dinophyceae): Evidence from morphological, molecular and ecophysiological data.

The cosmopolitan, potentially toxic dinoflagellate Protoceratium reticulatum possesses a fossilizable cyst stage which is an important paleoenvironmental indicator. Slight differences in the internal transcribed spacer ribosomal DNA (ITS rDNA) sequences of P. reticulatum have been reported, and both the motile stage and cyst morphology of P. reticulatum display phenotypic plasticity, but how these morpho-molecular variations are related with ecophysiological preferences is unknown. Here, 55 single cysts or cells were isolated from localities in the Northern (Arctic to subtropics) and Southern Hemispheres (Chile and New Zealand), and in total 34 strains were established. Cysts and/or cells were examined with light microscopy and/or scanning electron microscopy. Large subunit ribosomal DNA (LSU rDNA) and/or ITS rDNA sequences were obtained for all strains/isolates. All strains/isolates of P. reticulatum shared identical LSU sequences except for one strain from the Mediterranean Sea that differs in one position, however ITS rDNA sequences displayed differences at eight positions. Molecular phylogeny was inferred using maximum likelihood and Bayesian inference based on ITS rDNA sequences. The results showed that P. reticulatum comprises at least three ribotypes (designated as A, B, and C). Ribotype A included strains from the Arctic and temperate areas, ribotype B included strains from temperate regions only, and ribotype C included strains from the subtropical and temperate areas. The average ratios of process length to cyst diameter of P. reticulatum ranged from 15% in ribotype A, 22% in ribotype B and 17% in ribotype C but cyst size could overlap. Theca morphology was indistinguishable among ribotypes. The ITS-2 secondary structures of ribotype A displayed one CBC (compensatory change on two sides of a helix pairing) compared to ribotypes B and C. Growth response of one strain from each ribotype to various temperatures was examined. The strains of ribotypes A, B and C exhibited optimum growth at 15 °C, 20 °C and 20-25 °C, respectively, thus corresponding to cold, moderate and warm ecotypes. The profiles of yessotoxins (YTXs) were examined for 25 strains using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The parent compound yessotoxin (YTX) was produced by strains of ribotypes A and B, but not by ribotype C strains, which only produced the structural variant homoyessotoxin (homoYTX). Our results support the notion that there is significant intra-specific variability in Protoceratium reticulatum and the biogeography of the different ribotypes is consistent with specific ecological preferences.

Celastrol Attenuates Intrahepatic Cholestasis of Pregnancy by Inhibiting Matrix Metalloproteinases-2 and 9.

INTRODUCTION AND AIM: Matrix metalloproteinase (MMP)-2 and MMP-9 are reported to participate in several pregnancy-related diseases, including intrahepatic cholestasis of pregnancy (ICP), which is a severe liver disorder in pregnant women. Meanwhile, ample evidences have demonstrated that celastrol inhibits the activity and expression of MMPs. The present study aims to examine the effect of celastrol to alleviate symptoms of ICP in rat model. MATERIAL AND METHODS: By inducing ICP with 17 - ethinylestradiol in pregnant female rats, we assessed the impact of celastrol administration on symptoms of ICP, such as the rate of bile flow, the level of total bile acids (TBA), and the activities of MMP-2 and -9. Furthermore, the correlations between the levels of MMPs with the examined ICP symptoms were investigated. RESULTS: In rats with ICP, both MMP-2 and -9 exhibited significantly elevated activities, which were inhibited by the administration of celastrol. Furthermore, ICP symptoms such as bile flow rate and total TBA were restored by celastrol. Lastly, there were strong correlations between levels of the two MMPs and TBA. CONCLUSION: Our findings described for the first time the effects of celastrol to attenuate ICP symptoms through an inhibition of both MMP-2 and -9, providing evidence for a potential role of celastrol as a new drug for the treatment of ICP.

Relations of Metabolically Healthy and Unhealthy Obesity to Digital Vascular Function in Three Community-Based Cohorts: A Meta-Analysis.

BACKGROUND: Microvascular dysfunction is a marker of early vascular disease that predicts cardiovascular events. Whether metabolically healthy obese individuals have impaired microvascular function remains unclear. The aim of this study was to evaluate the relation of obesity phenotypes stratified by metabolic status to microvascular function. METHODS AND RESULTS: We meta-analyzed aggregate data from 3 large cohorts (Brazilian Longitudinal Study of Adult Health, the Framingham Heart Study, and the Gutenberg Heart Study; n=16 830 participants, age range 19-90, 51.3% men). Regression slopes between cardiovascular risk factors and microvascular function, measured by peripheral arterial tonometry (PAT), were calculated. Individuals were classified as normal-weight, overweight, or obese by body mass index (BMI) and stratified by healthy or unhealthy metabolic status based on metabolic syndrome using the ATP-III criteria. Male sex, BMI, and metabolic risk factors were associated with higher baseline pulse amplitude and lower PAT ratio. There was stepwise impairment of vascular measures from normal weight to obesity in both metabolic status strata. Metabolically healthy obese individuals had more impaired vascular function than metabolically healthy normal-weight individuals (baseline pulse amplitude 6.12±0.02 versus 5.61±0.01; PAT ratio 0.58±0.01 versus 0.76±0.01, all P<0.0001). Metabolically unhealthy obese individuals had more impaired vascular function than metabolically healthy obese individuals (baseline pulse amplitude 6.28±0.01 versus 6.12±0.02; PAT ratio 0.49±0.01 versus 0.58±0.01, all P<0.0001). CONCLUSIONS: Metabolically healthy obese individuals have impaired microvascular function, though the degree of impairment is less marked than in metabolically unhealthy obese individuals. Our findings suggest that obesity is detrimental to vascular health irrespective of metabolic status.

Preparation and characterization of Nano-graphite/TiO2 composite photoelectrode for photoelectrocatalytic degradation of hazardous pollutant.

Nano-graphite(Nano-G)/TiO2 composite photoelectrode was fabricated via sol-gel reaction, followed by the hot-press approach. The morphology, structure and light absorption capability of composite was characterized by various characterizations. The photoelectrochemical property and photoelectrocatalytic(PEC) activity of photoelectrode were also investigated. Results revealed that anatase TiO2 nanoparticles with an average diameter of 10nm were dispersed uniformly on the thickness of 2-3nm Nano-G, and TiOC bond was formed. The absorption edge of Nano-G/TiO2 photoelectrode was red-shifted towards low energy region and the enhanced visible light absorption was obtained. The charge transfer resistance of Nano-G/TiO2 photoelectrode was significantly decreased after the addition of Nano-G. And its transient photoinduced current was 10.5 times the value achieved using TiO2 electrode. Nano-G/TiO2 photoelectrode displayed greatly enhanced PEC activity of 99.2% towards the degradation of phenol, which was much higher than the 29.1% and 58.3% degradation seen on TiO2 and Nano-G electrode, respectively. The highly efficient and stable PEC activity of Nano-G/TiO2 photoelectrode was attributed to the synergy effect between photocatalysis and electrocatalysis, as well as enhanced light absorption ability and higher separation efficiency of photogenerated charge carriers. Moreover, contribution of series of reactive species to the PEC degradation of Nano-G/TiO2 photoelectrode was determined.