Early regression index (ERI) on MR images as response predictor in esophageal cancer treated with neoadjuvant chemo-radiotherapy: Interim analysis of the prospective ESCAPE trial.

PURPOSE: The early regression index (ERI) predicts treatment response in rectal cancer patients. Aim of current study was to prospectively assess tumor response to neoadjuvant chemo-radiotherapy (nCRT) of locally advanced esophageal cancer using ERI, based on MRI. MATERIAL AND METHODS: From January 2020 to May 2023, 30 patients with esophageal cancer were enrolled in a prospective study (ESCAPE). PET-MRI was performed: i) before nCRT (tpre); ii) at mid-radiotherapy, tmid; iii) after nCRT, 2-6 weeks before surgery (tpost); nCRT delivered 41.4 Gy/23fr with concurrent carboplatin and paclitaxel. For patients that skipped surgery, complete clinical response (cCR) was assessed if patients showed no local relapse after 18 months; patients with pathological complete response (pCR) or with cCR were considered as complete responders (pCR + cCR). GTV volumes were delineated by two observers (Vpre, Vmid, Vpost) on T2w MRI: ERI and other volume regression parameters at tmid and tpost were tested as predictors of pCR + cCR. RESULTS: Complete data of 25 patients were available at the time of the analysis: 3/25 with complete response at imaging refused surgery and 2/3 were cCR; in total, 10/25 patients showed pCR + cCR (pCR = 8/22). Both ERImid and ERIpost classified pCR + cCR patients, with ERImid showing better performance (AUC:0.78, p = 0.014): A two-variable logistic model combining ERImid and Vpre improved performances (AUC:0.93, p < 0.0001). Inter-observer variability in contouring GTV did not affect the results. CONCLUSIONS: Despite the limited numbers, interim analysis of ESCAPE study suggests ERI as a potential predictor of complete response after nCRT for esophageal cancer. Further validation on larger populations is warranted.

68Ga-DOTATOC PET/MR imaging and radiomic parameters in predicting histopathological prognostic factors in patients with pancreatic neuroendocrine well-differentiated tumours.

PURPOSE: To explore the role of fully hybrid 68Ga-DOTATOC PET/MR imaging and radiomic parameters in predicting histopathological prognostic factors in patients with pancreatic neuroendocrine tumours (PanNETs) undergoing surgery. METHODS: One hundred eighty-seven consecutive 68Ga-DOTATOC PET/MRI scans (March 2018-June 2020) performed for gastroenteropancreatic neuroendocrine tumour were retrospectively evaluated; 16/187 patients met the eligibility criteria (68Ga-DOTATOC PET/MRI for preoperative staging of PanNET and availability of histological data). PET/MR scans were qualitatively and quantitatively interpreted, and the following imaging parameters were derived: PET-derived SUVmax, SUVmean, somatostatin receptor density (SRD), total lesion somatostatin receptor density (TLSRD), and MRI-derived apparent diffusion coefficient (ADC), arterial and late enhancement, necrosis, cystic degeneration, and maximum diameter. Additionally, first-, second-, and higher-order radiomic parameters were extracted from both PET and MRI scans. Correlations with several PanNETs' histopathological prognostic factors were evaluated using Spearman's coefficient, while the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to evaluate parameters' predictive performance. RESULTS: Primary tumour was detected in all 16 patients (15/16 by 68Ga-DOTATOC PET and 16/16 by MRI). SUVmax and SUVmean resulted good predictors of lymphnodal (LN) involvement (AUC of 0.850 and 0.783, respectively). Second-order radiomic parameters GrayLevelVariance and HighGrayLevelZoneEmphasis extracted from T2 MRI demonstrated significant correlations with LN involvement (adjusted p = 0.009), also showing good predictive performance (AUC = 0.992). CONCLUSION: This study demonstrates the role of the fully hybrid PET/MRI tool for the synergic function of imaging parameters extracted by the two modalities and highlights the potentiality of imaging and radiomic parameters in assessing histopathological features of PanNET aggressiveness.

Deep learning radiomic nomogram can predict the number of lymph node metastasis in locally advanced gastric cancer: an international multicenter study.

BACKGROUND: Preoperative evaluation of the number of lymph node metastasis (LNM) is the basis of individual treatment of locally advanced gastric cancer (LAGC). However, the routinely used preoperative determination method is not accurate enough. PATIENTS AND METHODS: We enrolled 730 LAGC patients from five centers in China and one center in Italy, and divided them into one primary cohort, three external validation cohorts, and one international validation cohort. A deep learning radiomic nomogram (DLRN) was built based on the images from multiphase computed tomography (CT) for preoperatively determining the number of LNM in LAGC. We comprehensively tested the DLRN and compared it with three state-of-the-art methods. Moreover, we investigated the value of the DLRN in survival analysis. RESULTS: The DLRN showed good discrimination of the number of LNM on all cohorts [overall C-indexes (95% confidence interval): 0.821 (0.785-0.858) in the primary cohort, 0.797 (0.771-0.823) in the external validation cohorts, and 0.822 (0.756-0.887) in the international validation cohort]. The nomogram performed significantly better than the routinely used clinical N stages, tumor size, and clinical model (P < 0.05). Besides, DLRN was significantly associated with the overall survival of LAGC patients (n = 271). CONCLUSION: A deep learning-based radiomic nomogram had good predictive value for LNM in LAGC. In staging-oriented treatment of gastric cancer, this preoperative nomogram could provide baseline information for individual treatment of LAGC.

Effects of phytoestrogenic isoflavones from red clover (Trifolium pratense L.) on experimental osteoporosis.

The most common type of osteoporosis is bone loss associated with ovarian hormone deficiency at menopause. There is evidence that diets which contain high levels of phytoestrogenic isoflavones are associated with a low incidence of osteoporosis and menopausal symptoms. Plant extracts, which contain high levels of isoflavones, such as Red clover (Trifolium pratense L.), have been used to reduce menopausal symptoms. The objective of this study was to evaluate the preventive effects of Red clover total isoflavones on the progression of bone loss induced by estrogens deficiency (ovariectomy) in rats. Bilateral ovariectomy was performed on female Wistar rats. One week after the operation the rats were treated with an oral dose of 20 and 40 mg of total isoflavones daily for 14 weeks. The results from this study showed that the ovariectomy reduced bone mineral content, femoral weight, femoral density, mechanical strength of the tibia and increased the levels of bone specific alkaline phosphatase in the serum and the number of osteoclasts in the femur sections compared with sham operated controls. Treatment with isoflavones significantly increased bone mineral content, mechanical strength of the tibia, femoral weight, femoral density and prevented the rise of serum alkaline phosphatase levels. In addition, the treatment with isoflavones significantly reduced the number of osteoclasts compared with the ovariectomized control rats. These findings suggest that Red clover isoflavones are effective in reducing bone loss induced by ovariectomy, probably by reducing of the bone turnover via inhibition of bone resorption.

Cloning and expression of two plant proteins: similar antimicrobial activity of native and recombinant form.

Antimicrobial peptides and proteins are being studied with increasing interest because of their broad range antimicrobial activity. Among plant antimicrobial proteins, the wheat seed polypeptides, puroindoline a and puroindoline b, are particularly interesting because of their established antibacterial activity. In this paper we describe different strategies used to clone His tagged and GST tagged puroindolines obtaining 1.5 mg recombinant protein from 1 l culture. The antimicrobial activity of recombinant and native puroindolines was comparable.

Conscious analgosedation for radiofrequency ablation of lung neoplasm.

AIM: Radiofrequency ablation (RFA) is a minimally invasive therapy for pulmonary malignant cancers in patients with medical co-morbidities or refusal of surgery. The aim of this study was to evaluate a conscious analgosedation protocol for RFA of lung neoplasm. METHODS: Ten RFAs were performed. Following analgesic premedication patients underwent local anesthesia (lidocaine 2%) and propofol infusion. RESULTS: The procedures were always uneventful. Postoperative severe pain was not reported; a deep sedation was required to allow the quick and safe management of RFA. CONCLUSIONS: Spontaneous breathing sedation is safe in monitored and well-oxygenated patients and may limit the incidence of tension pneumothorax. Postoperative period needs a proper pain control for the first 24 h. Data on the long-term efficacy of lung tumor RFA are not yet available.

Evaluation of HIV RNA and markers of immune activation as predictors of HIV-associated dementia.

OBJECTIVE: To evaluate whether baseline levels of plasma and CSF HIV RNA, tumor necrosis factor alpha (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-2 (MMP-2), or macrophage colony stimulating factor (M-CSF) are predictors of incident HIV-associated dementia (HIVD) in a cohort with advanced HIV infection. METHODS: A total of 203 nondemented subjects with CD4 lymphocyte counts less than 200/muL, or <300/microL but with cognitive impairment, underwent semiannual neurologic, cognitive, functional, and laboratory assessments. HIVD and minor cognitive motor disorder (MCMD) were defined using American Academy of Neurology criteria. The cumulative incidence of HIVD was estimated using Kaplan-Meier curves. Cox proportional hazards regression models were used to examine the associations between biologic variables and time to HIVD, adjusting for age, sex, years of education, duration of HIV infection, type of antiretroviral use, premorbid IQ score, and presence of MCMD. RESULTS: After a median follow-up time of 20.7 months, 74 (36%) subjects reached the HIVD endpoint. The dementia was mild in 70% of cases. The cumulative incidence of HIVD was 20% at 1 year and 33% at 2 years. Highly active antiretroviral therapy (HAART) was used by 73% of subjects at baseline. A plasma HIV RNA level was undetectable in 23% of subjects and a CSF HIV RNA level was undetectable in 48% of subjects. In adjusted analyses, neither plasma nor CSF HIV RNA levels (log10) were associated with time to HIVD; log10 levels of plasma TNFalpha (HR 3.07, p = 0.03) and CSF MCP-1 (HR = 3.36, p = 0.06) tended to be associated with time to HIVD. CONCLUSION: The lack of association between baseline plasma and CSF HIV RNA levels and incident dementia suggests highly active antiretroviral therapy may be affecting CNS viral dynamics, leading to lower HIV RNA levels, and therefore weakening the utility of baseline HIV RNA levels as predictors of HIV-associated dementia.

Estrogen receptor in uteri of mice of different H-2 genotypes.

A relationship between the amount of available estradiol receptors in uteri of inbred mice and their H-2 genotype is suggested by study in congenic animals.

Antibodies to native DNA: detection by immunoperoxidase assay and determination of their immunoglobulin classes.

Antinuclear antibodies are almost always found in sera of patients with systemic lupus erythematosus. To differentiate antinuclear antibodies from antibodies to DNA in the recently described Crithidia luciliae assay, we developed an immunoperoxidase technique for detecting antibodies to native, double-stranded DNA and compared results by it with those by the Farr assay. Smears of cultured Crithidia luciliae were incubated with human sera, peroxidase-labeled anti-human IgG serum, and diaminobenzidine. The peroxidase stain was examined by conventional light microscopy, which facilitated differentiation between the kinetoplast and the nuclear staining. The Crithidia assay appeared to be specific for double-stranded DNA antibodies, seemed to be more sensitive than the Farr assay, and allowed us to determine the immunoglobulin classes of antibodies to native DNA. Some patients with systemic lupus erythematosus had only IgM or IgA antibodies to DNA.