Is hydrogen electronegativity higher than Pauling's value? New clues from the 13C and 29Si NMR chemical shifts of [CHF3] and [SiHF3] molecules

Abstract We previously demonstrated that the δ NMR chemical shift of central NMR active atoms (A), in simple halido [AXn] (A=C, Si, Ge, Sn, Pb, Pt; Xn = combination of n halides, n = 4 or 6) derivatives, could be directly related to X radii overall sum, Σ(r L ). Further correlation have also been observed for tetrahedral [AX4] (A=C, Si; X4 = combination of four halides) compounds where the X Pauling electronegativities sum, Σ ( χ L Pau ) , $\Sigma (\chi _L^{{\rm{Pau}}}),$ exceeds a specific value (≈12.4). In this work, we focused on these latter systems considering the H vs. X substitution. The analysis of the literature reported δ(13C) and δ(29Si) NMR chemical shift for the mono hydrogenated derivatives and in particular for [CHF3] and [SiHF3], characterized by the lowest Σ(r L ) and the highest Σ ( χ L Pau ) , $\Sigma (\chi _L^{{\rm{Pau}}}),$ suggests a revised value for the H electronegativity ranking with respect to Pauling's

Hair analysis to monitor abuse of analgesic combinations containing butalbital and propyphenazone

Butalbital, a barbiturate, is present in analgesic combinations used by headache sufferers. Overuse/abuse of these combinations may cause dependence, chronic migraine, and medication-overuse headache (MOH). MOH is difficult to manage: it improves interrupting analgesic overuse, but requires monitoring, because relapses are frequent. A gas chromatography-mass spectrometry (GC–MS) method for hair analysis has been developed and validated to document abuse of an analgesic combination containing butalbital and propyphenazone by a patient with MOH. For over ten years the patient managed her headache using eight suppositories/day of an analgesic combination containing butalbital 150 mg, caffeine 75 mg, and propyphenazone 375 mg per suppository. An outpatient detoxification treatment was carried out. After three weeks, the patient reduced the consumption to one suppository/day. At the first control visit, after three months from the beginning of detoxification, the patient increased the use of the combination to four suppositories/day and at the second control visit, after seven months from the beginning of detoxification, she was back to eight suppositories/day. At the two control visits, a hair sample was taken for determination of butalbital and propyphenazone. Moreover blood and urine samples for determination of butalbital were drawn at the beginning of detoxification treatment and at the two control visits. With the segmental analysis of two hair samples the medication history of ten months could be estimated. In the first hair sample, collected at the first control visit, in the distal segment, butalbital and propyphenazone concentrations were, respectively, 17.5 ng/mg and 56.0 ng/mg, confirming the prolonged abuse; in the proximal segment, concurrently with the detoxification treatment, butalbital and propyphenazone concentrations had reduced respectively to 5.45 ng/mg and 11.1 ng/mg. The second hair sample, collected at the second control visit, proved the fair course of the detoxification treatment in the distal segment and signalled relapse in the abuse of the analgesic combination in the proximal segment. In the clinical context, hair analysis can be advantageously used to monitor the abuse of analgesic combinations with butalbital, common among headache patients. The validation data showed that GC–MS method developed for determination of butalbital and propyphenazone was rapid, highly sensitive, specific and selective

Impact of continuing or quitting smoking on episodic cluster headache: a pilot survey

Abstract BACKGROUND: The majority of patients suffering from cluster headache (CH) are smokers and it has been suggested that smoking may trigger the development of CH. The aim of this pilot survey was to describe: 1. the differences between current, former, and never smokers CH patients; 2. if smoking changed during an active cluster period; 3. if CH changed after quitting. METHODS: All outpatients with episodic CH according to the criteria of ICHD-II who were consecutively seen for the first time from October 2010 to April 2012 at a headache centre were interviewed by phone using a specifically prepared questionnaire. Statistical differences between continuous variables were analysed by the Student's t-test or the one-way analysis of variance (ANOVA), followed by Newman-Keuls post-hoc testing. Comparisons between percentages were made using the Chi-square test or Fisher's exact test. All data were expressed as the mean ± standard deviation (SD). RESULTS: Among a total of 200 patients surveyed (172 males, 28 females; mean age ± SD: 48.41 ± 12 years) there were 60%, 21%, and 19% of current, former, and never smokers, respectively. Current smokers reported longer active periods (12.38 ± 10 weeks) and a higher maximum number of attacks per day (3.38 ± 1) compared to never smoker CH patients (5.68 ± 4 weeks, P <0.05 and 2.47 ± 1, P <0.05, respectively). During the active period most of the patients stated to decrease (45.7%) or not to change (45.7%) the number of cigarettes smoked. Among those who decreased smoking, most (83.8%) reported that they had less desire to smoke. After quitting, the majority of former smokers stated that their headache had not changed. CONCLUSIONS: Patients with episodic CH who are also smokers appear to have a more severe form of the disorder. However, it is unlikely that between CH and smoking there is a causal relationship, as CH patients rarely improve quitting smoking

An Imaging Overview of COVID-19 ARDS in ICU Patients and Its Complications: A Pictorial Review

A significant proportion of patients with COVID-19 pneumonia could develop acute respiratory distress syndrome (ARDS), thus requiring mechanical ventilation, and resulting in a high rate of intensive care unit (ICU) admission. Several complications can arise during an ICU stay, from both COVID-19 infection and the respiratory supporting system, including barotraumas (pneumothorax and pneumomediastinum), superimposed pneumonia, coagulation disorders (pulmonary embolism, venous thromboembolism, hemorrhages and acute ischemic stroke), abdominal involvement (acute mesenteric ischemia, pancreatitis and acute kidney injury) and sarcopenia. Imaging plays a pivotal role in the detection and monitoring of ICU complications and is expanding even to prognosis prediction. The present pictorial review describes the clinicopathological and radiological findings of COVID-19 ARDS in ICU patients and discusses the imaging features of complications related to invasive ventilation support, as well as those of COVID-19 itself in this particularly fragile population. Radiologists need to be familiar with COVID-19's possible extra-pulmonary complications and, through reliable and constant monitoring, guide therapeutic decisions. Moreover, as more research is pursued and the pathophysiology of COVID-19 is increasingly understood, the role of imaging must evolve accordingly, expanding from the diagnosis and subsequent management of patients to prognosis prediction

The role of MRI in the detection of local recurrence: Added value of multiparametric approach and Signal Intensity/Time Curve analysis

Objective: The aim of the study was to evaluate the accuracy of multiparametric Magnetic Resonance Imaging (mpMRI) in the detection of local recurrence of prostate cancer (PCa) with the evaluation of the added value of signal Intensity/Time (UT) curves.Materials and methods: A retrospective analysis of 22 patients undergoing mpMRI from 2015 to 2020 was carried out, with the following inclusion criteria: performing trans rectal ultrasound guided biopsy within 3 months in the case of positive or doubtful findings and undergoing biopsy and/or clinical follow-up for 24 months in the case of negative results. The images were reviewed, and the lesions were catalogued according to morphological, diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) features.Results: The presence of local recurrence was detected in 11/22 patients (50%). Greater diameter, hyperintensity on DWI, positive contrast enhancement and type 2/3 signal UT curves were more frequently observed in patients with local recurrence (all p &lt; 0.05). Of all the sequences, DCE was the most accurate; however, the combination of DCE and DWI showed the best results, with a sensitivity of 100%, a specificity of 82%, a negative predictive value of 100% and a positive predictive value of 85%.Conclusions: The utility of MRI in the detection of local recurrence is tied to the multiparametric approach, with all sequences providing useful information. A combination of DCE and DWI is particularly effective. Moreover, specificity could be additionally improved using analysis of the signal UT curves

Clinical Application of the New Prostate Imaging for Recurrence Reporting (PI-RR) Score Proposed to Evaluate the Local Recurrence of Prostate Cancer after Radical Prostatectomy

Simple Summary The aim of the new Prostate Imaging for Recurrence Reporting (PI-RR) is a standardization in reporting to assess the likelihood of relapse after radical prostatectomy. Our study documented an excellent inter-observer agreement in recurrence reporting when using the PI-RR score, demonstrating a wide reproducibility, thus supporting the wide use of the PI-RR score in the clinical practice. The diagnostic accuracy was 68.4%, with the detection rate influenced by the PSA values. Overall, the PI-RR score globally showed a higher detection rate than PET/CT scans for local recurrence. Background: We investigated the diagnostic accuracy of the new Prostate Imaging for Recurrence Reporting (PI-RR) score and its inter-observer variability. Secondly, we compared the detection rate of PI-RR and PET and analyzed the correlation between Prostate Specific Antigen (PSA) levels and the PI-RR score. Methods: We included in the analysis 134 patients submitted to multiparametric magnetic resonance imaging for suspected local recurrence. The images were independently reviewed by two radiologists, assigning a value from 1 to 5 to the PI-RR score. Inter-observer agreement and diagnostic accuracy of the PI-RR score (compared to histopathological data, available for 19 patients) were calculated. The detection rate was compared to those of choline PET/CT (46 patients) and PSMA PET/CT (22 patients). The distribution of the PSA values in relation to the PI-RR scores was also analyzed. Results: The accuracy of the PI-RR score was 68.4%. The reporting agreement was excellent (K = 0.884, p &lt; 0.001). The PI-RR showed a higher detection rate than choline PET/CT (69.6% versus 19.6%) and PSMA PET-CT (59.1% versus 22.7%). The analysis of the PSA distribution documented an increase in the PI-RR score as the PSA value increased. Conclusion: The excellent reproducibility of the PI-RR score supports its wide use in the clinical practice to standardize recurrence reporting. The detection rate of PI-RR was superior to that of PET, but was linked to the PSA level

Outcome Prediction for SARS-CoV-2 Patients Using Machine Learning Modeling of Clinical, Radiological, and Radiomic Features Derived from Chest CT Images

Featured Application The present study demonstrates that semi-automatic segmentation enables the identification of regions of interest affected by SARS-CoV-2 infection for the extraction of prognostic features from chest CT scans without suffering from the inter-operator variability typical of segmentation, hence offering a valuable and informative second opinion. Machine Learning methods allow identification of the prognostic features potentially reusable for the early detection and management of other similar diseases. (1) Background: Chest Computed Tomography (CT) has been proposed as a non-invasive method for confirming the diagnosis of SARS-CoV-2 patients using radiomic features (RFs) and baseline clinical data. The performance of Machine Learning (ML) methods using RFs derived from semi-automatically segmented lungs in chest CT images was investigated regarding the ability to predict the mortality of SARS-CoV-2 patients. (2) Methods: A total of 179 RFs extracted from 436 chest CT images of SARS-CoV-2 patients, and 8 clinical and 6 radiological variables, were used to train and evaluate three ML methods (Least Absolute Shrinkage and Selection Operator [LASSO] regularized regression, Random Forest Classifier [RFC], and the Fully connected Neural Network [FcNN]) for their ability to predict mortality using the Area Under the Curve (AUC) of Receiver Operator characteristic (ROC) Curves. These three groups of variables were used separately and together as input for constructing and comparing the final performance of ML models. (3) Results: All the ML models using only RFs achieved an informative level regarding predictive ability, outperforming radiological assessment, without however reaching the performance obtained with ML based on clinical variables. The LASSO regularized regression and the FcNN performed equally, both being superior to the RFC. (4) Conclusions: Radiomic features based on semi-automatically segmented CT images and ML approaches can aid in identifying patients with a high risk of mortality, allowing a fast, objective, and generalizable method for improving prognostic assessment by providing a second expert opinion that outperforms human evaluation

Incidental finding of bronchial diverticula in a non-smoker population: evaluation on thin-section CT

Bronchial diverticula have been described as a common radiological finding in smoker patients with COPD, but the specificity of this sign should be further investigated. Thus, the aim of our study was to evaluate the prevalence of diverticula in a cohort of non-smoker subjects. Between February and July 2012, 2438 patients were admitted to our Radiology Unit to undergo a chest CT. Among them, we enrolled 121 non-smoking patients (78/121-64.5% females, 43/121-35.5% males), of different age (57.0±20.7 years-range: 12-88), without any respiratory symptoms, submitted to chest CT for several reasons (oncologic evaluation: 59/121-48.8%; follow up of lung nodules: 27/121-22.3%; screening in connectivitis: 12/121-9.9%; others: 23/121-19.0%). We considered thin-section CT scan on axial, coronal and sagittal plans to evaluate prevalence, numbers and level of bronchial diverticula. Diverticula were found in 41/121-33.9% patients, with a slight major prevalence in males (p=0.048), but no significant difference on age. In 31/41-75.6% the number was <3, whereof 17/31-54.8% with just one diverticulum assessed. Regarding the level, in 30/41-73.2% they were subcarinal, but they were also detected in mainstem (2/41-4.9%) and lobar bronchi (with the right upper lobe bronchus most frequently involved- 12/41-29.3%). Bronchial diverticula can be observed in non-smokers, as well as in smoker patients with COPD. However, their prevalence seems to be lower than in smokers and they tend to be isolated and subcarinal. The age of patients does not influence their finding. More studies should be proposed to better define a cut-off between smokers and healthy subjects

Fecal microbiota transplantation to improve efficacy of immune checkpoint inhibitors in renal cell carcinoma (TACITO trial)

Background: Renal cell carcinoma (RCC) is the 6° most common cancer in men and the 8° in women in the USA. In Italy RCC incidence was 11,500 new cases in 2017, while mortality was 3,371 cases in 2015. Increasing evidence suggests that response to immune checkpoint inhibitors (ICIs), a novel treatment for advanced RCC (aRCC) and other epithelial tumors, can be influenced by the patient gut microbiota. Fecal microbiota transplantation (FMT) is a novel treatment option aimed to restore healthy gut microbiota, and is the most effective therapy for recurrent C. difficile infection. Preliminary nonrandomized findings show that FMT is able to improve efficacy of ICIs in patients with advanced melanoma. The aim of this study is to evaluate, through a double-blinded placebo-controlled randomized clinical trial, the efficacy of targeted FMT (from donors who are responding to ICIs) in improving response rates to ICIs in subjects with aRCC. Methods: 50 patients who are about to receive, or have started by &lt;8 weeks, pembrolizumab + axitinib as first-line therapy for aRCC will be enrolled. Exclusion criteria include major comorbidities, concomitant GI or autoimmune disorders, or HIV, HBV, HCV infection, continuative corticosteroid therapy, previous treatment with systemic immune-suppressants or immune-modulatory drugs, antibiotic therapy within 4 weeks prior to enrollment. Stool samples and clinical data will be collected at baseline. Then, patients will be randomized to donor FMT or placebo FMT. They will receive the first infusion by colonoscopy and then oral frozen fecal or placebo capsules (8 capsules t.i.d.) 90 and 180 days after the first FMT. Stool donors will be searched among long-term (&gt;12 months) responders to ICIs, and will be selected by following protocols recommended by international guidelines. Patients in the FMT group will always receive feces from the same donor throughout the three fecal transplants. Frozen fecal batches and frozen fecal capsules will be manufactured according to international guidelines. Patients will be followed-up 7, 15, 30, 90, 180, 270, and 360 days after randomization for clinical evaluation and collection of stool samples. Patients will also undergo radiological assessment at 90, 180, 270 and 360 days after randomization. Microbiome analysis will be performed with shotgun metagenomics. The primary endpoint is the progression-free survival (PFS) at 12 months. Secondary endpoints are: objective response rate at 12 months; overall survival at 12 months; adverse events after FMT; microbiome changes after FMT. Sample size calculation was based on the hypothesis that FMT can improve the 1-year PFS rate from 60% (reported 1-year PFS for SOC) to 80% wen associated to SOC. Clinical trial information: NCT04758507

Cabozantinib After a Previous Immune Checkpoint Inhibitor in Metastatic Renal Cell Carcinoma: A Retrospective Multi-Institutional Analysis

Background: Angiogenesis has been recognized as the most important factor for tumor invasion, proliferation, and progression in metastatic renal cell carcinoma (mRCC). However, few clinical data are available regarding the efficacy of cabozantinib following immunotherapy. Objective: To describe the outcome of cabozantinib in patients previously treated with immunotherapy. Patients and methods: Patients with mRCC who received cabozantinib immediately after nivolumab were included. The primary endpoint was to assess the outcome in terms of efficacy and activity. Results: Eighty-four mRCC patients met the criteria to be included in the final analysis. After a median follow-up of 9.4&nbsp;months, median overall survival was 17.3&nbsp;months. According to the IMDC criteria, the rates of patients alive at 12&nbsp;months in the good, intermediate, and poor prognostic groups were 100%, 74%, and 33%, respectively (p &lt; 0.001). The median progression-free survival (PFS) was 11.5&nbsp;months (95% CI 8.3-14.7); no difference was found based on duration of previous first-line therapy or nivolumab PFS. The overall response rate was 52%, stable disease was found as the best response in 25.3% and progressive disease in 22.7% of patients. Among the 35 patients with progressive disease on nivolumab, 26 (74.3%) patients showed complete/partial response or stable disease with cabozantinib as best response after nivolumab. The major limitations of this study are the retrospective nature and the short follow-up. Conclusions: Cabozantinib was shown to be effective and active in patients previously receiving immune checkpoint inhibitors. Therefore, cabozantinib can be considered a valid therapeutic option for previously treated mRCC patients, irrespective of the type and duration of prior therapies