Radiological lung sequelae, functional status and symptoms in older patients 3 and 6 months after hospitalization for COVID-19 pneumonia.

The aim of our study was to assess the lung sequelae and clinical consequences 3 and 6 months after hospitalization for COVID-19 pneumonia in older patients. An observational study was conducted on 55 patients aged 65 years and older. Activities of daily living (ADL) and clinical frailty scale (CFS) were assessed at baseline and after 3 months. Both quantitative assessment at chest high-resolution computed tomography (CT) and semi-quantitative severity score (CTSS) were performed at baseline and after 3 and 6 months. Mean age: 82.3 ± 7.1 years. Male prevalence: 56.4%. After 6 months, ground-glass opacities (GGO) were still detectable in 22% of subjects, while consolidations were no longer appreciable. During follow-up, CTSS reached an overall median score of zero after 6 months. Fibrotic-like changes were found in 40% of subjects with an overall median score of 0 (0-5) points, being more prevalent in males. Patients reporting worsening ADL and CFS were 10.9% and 45.5%, respectively. They were associated with the burden of comorbidities, especially history of heart failure and chronic obstructive pulmonary disease at baseline. Amnesic disorders, exertional dyspnea, and fatigue were the most relevant symptoms reported. No association emerged between persistent or new-onset symptoms and evidence of fibrotic-like changes. The typical chest CT abnormalities of the COVID-19 pneumonia acute phase resolved in most of our older patients. Mild fibrotic-like changes persisted in less than half of the patients, especially males, without significantly affecting the functional status and frailty condition, which instead were more likely associated with pre-existing comorbidities.

A magnetic resonance imaging-based nomogram for predicting clinically significant prostate cancer at radical prostatectomy.

PURPOSE: To develop a nomogram incorporating clinical and multiparametric magnetic resonance imaging (mpMRI) parameters for the detection of clinically significant prostate cancer (csCaP) at radical prostatectomy (RP). MATERIALS AND METHODS: We retrospectively analyzed all consecutive patients who underwent robotic RP between 2016 and 2020. All patients underwent a 1.5-T mp-MRI according to the PI-RADS-v2 scoring system. RP specimens were examined with the whole-mount technique. csCaP definition: any tumor with a volume larger than 0.5 cm3 or with a Gleason score ≥7. Univariable logistic regression models explored the association between clinical and imaging data and the risk of csCaP. Significant variables (P < 0.05) were selected into multivariable regression models to identify independent predictors. A nomogram was designed to select the significant relevant predictors. The nomogram was internally validated in terms of discrimination and calibration. Receiver operating characteristics of the area under the curve was used to assess the discrimination ability of the nomogram. To assess the predictive performance of mpMRI, the accuracy of the mpMRI-based nomogram was compared with that excluding either PI-RADS score or mpMRI IL size. RESULTS: The analysis involved 393 patients. The median age was 65(9) years. The median prostate specific antigen was 5.81(3.76) ng/ml. 363 had csCaP. PI-RADS v2 score of 4-5, prostate specific antigen density of 0.15 or more, and mpMRI index lesion (IL) size were significantly associated with csCaP in the multivariable regression analyses. Based on these variables, a diagnostic model was developed. The full model yielded an area under the curve of 0.77 (95%CI:0.75-0.80) which was significantly better than those excluding mpMRI findings (P = 0.02) Decision curve analysis showed a slight but significant net benefit associated with the use of the mp-MRI based nomograms compared with those excluding either PI-RADS score (Delta net benefit 0.0278) or mpMRI maximum IL size (Delta net benefit 0.0111). CONCLUSIONS: The nomogram constructed in this study can assist urologists in assessing an individual's risk of csCaP at RP.

Chest X-ray Score and Frailty as Predictors of In-Hospital Mortality in Older Adults with COVID-19.

BACKGROUND: The purpose of this study was to evaluate the prognostic impact of chest X-ray (CXR) score, frailty, and clinical and laboratory data on in-hospital mortality of hospitalized older patients with COVID-19. METHODS: This retrospective study included 122 patients 65 years or older with positive reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and with availability to CXRs on admission. The primary outcome of the study was in-hospital mortality. Statistical analysis was conducted using Cox regression. The predictive ability of the CXR score was compared with the Clinical Frailty Scale (CFS) and fever data using Area Under the Curve (AUC) and net reclassification improvement (NRI) statistics. RESULTS: Of 122 patients, 67 died during hospital stay (54.9%). The CXR score (HR: 1.16, 95% CI, 1.04-1.28), CFS (HR: 1.27; 95% CI, 1.09-1.47), and presence of fever (HR: 1.75; 95% CI, 1.03-2.97) were significant predictors of in-hospital mortality. The addition of both the CFS and presence of fever to the CXR score significantly improved the prediction of in-hospital mortality (NRI, 0.460; 95% CI, 0.102 to 0.888; AUC difference: 0.117; 95% CI, 0.041 to 0.192, p = 0.003). CONCLUSIONS: CXR score, CFS, and presence of fever were the main predictors of in-hospital mortality in our cohort of hospitalized older patients with COVID-19. Adding frailty and presence of fever to the CXR score statistically improved predictive accuracy compared to single risk factors.

Oncological and functional outcome after partial prostate HIFU ablation with Focal-One®: a prospective single-center study.

BACKGROUND: We aimed to evaluate oncological and functional outcomes of index lesion HIFU ablation with Focal-One®. MATERIALS AND METHODS: We prospectively assessed treatment-naïve men with localized prostate cancer between 2017 and 2019. Inclusion criteria were stage cT ≤ 2, ≥5 years of life expectancy, grade group ≤3. Multiparametric magnetic resonance was performed before ablation. Patients with a prostate volume of ≥80 ml underwent debulking. Treatment failure was defined as a histologically confirmed tumor that required salvage treatment or androgen deprivation therapy. RESULTS: One hundred and eighty nine patients were enrolled. Data are presented as median and Interquartile Range (IQR). Median age was 70(11) years. Median baseline PSA was 5.8(3) ng/ml. Fourteen (7.4%) patients had prostate debulking before ablation. 104 (55%) patients underwent targeted ablation, 45 (23.8%) extended targeted ablation, 31 (16.4%) hemiablation, and 9 (4.8%) extended hemiablation. Median targeted ablated volume was 14(9) ml. Ninety-three complications occurred in 63/189 (33.3%) patients within 90 days. There were 77/93 (82.8%) minor (Clavien grade 1-2) and 16/93 (17.2%) major complications (Clavien grade 3a). Thirty-nine patients suffered from genito-urinary infections (Clavien grade 2). Fifteen patients required transurethral resection of the prostate/urethrotomy for recurrent urinary retention (Clavien grade 3a). One patient developed a recto-urethral fistula (Clavien grade 3a) and two long-lasting urinary incontinence. Median PSA nadir was 2.2(2.9) ng/ml. At a median follow-up of 29(15) months, 21/177 (11.9%) patients were treatment failures, 26 on monitoring, and 26 had a further ablation. Multivariable logistic regression found that failure patients had higher PSA (7.8 vs 5.7 ng/ml,p0.001) and double PSA nadir (4.8 vs 2.0 ng/ml, p < 0.001). Higher PSA nadir correlated with a 74% higher probability of failure (OR 1.74 95% CI 1.40-2.16). Cancer in the anterior stroma increased the odds of failure of three folds (OR 3.36 95% CI 1.18-9.53). Two mixed effect models (one for IPSS and one for IEEF-15) were estimated and they showed that time reaches the statistical significance coefficient only for the IEEF-15, meaning that subsequent evaluations of the indicators were significantly lower at each time point. CONCLUSIONS: Index lesion HIFU ablation demonstrated satisfactory early oncological outcome but anteriorly located tumors had inadequate ablation. Urinary function was well preserved. Sexual function slightly decreased during follow-up.

Combination of Multiparametric Magnetic Resonance Imaging With Elastic-fusion Biopsy Has a High Sensitivity in Detecting Clinically Significant Prostate Cancer in Daily Practice.

BACKGROUND: The index lesion (IL) is the largest cancer focus, usually harbors the highest grade, and might drive the history of prostate cancer (PCA). Multiparametric magnetic resonance imaging (mp-MRI) has a high negative predictive value in ruling out clinically significant (cs)PCA. We aimed evaluating the efficiency of mp-MRI and targeted biopsy in detecting csPCA and the concordance between the MRI index lesion (MRI-IL) and the presence of csPCA inside it. MATERIALS AND METHODS: We retrospectively evaluated 158 men who underwent prostate biopsy after a positive pre-biopsy mp-MRI scan. All mp-MRI lesions were biopsied using a transrectal ultrasound elastic-fusion approach (2-4 targeted plus 10-12 random systematic biopsies). csPCA was defined as grading group ≥ 2 or > 3 cores with cancer or ≥ 50% of core involved by tumor. RESULTS: mp-MRI detected 158 ILs and 46 non-ILs. One hundred were Prostate Imaging-Reporting and Data System version 2 (PI-RADS v2) score 3, 84 score 4, and 20 score 5. csPCA was found in 63.9% of the MRI-ILs. Eighty percent of detected cancer using mp-MRI and targeted biopsy was clinically significant. Eighty-seven percent of the transitional zone lesions were clinically non-significant or negative for cancer. The probability of detecting csPCA increases with increasing size of MRI-IL, and every extra millimeter raises the odds of detecting csPCA of 12.2%. All PI-RADS v2 score lesions showed a strong association with csPCA. The risk of matching between MRI-IL and csPCA inside it increases by 36.2% as the total percentage of cancer in all cores increases. CONCLUSIONS: mp-MRI showed high sensitivity in detecting csPCA in the peripheral zone, with concordance between MRI-IL and csPCA.

Identification of positive and negative regulatory regions controlling expression of the Xenopus laevis betaTrCP gene.

betaTrCP mediates the ubiquitination and subsequent degradation of several key molecules thereby playing a relevant role in different cellular processes during development and in the adult. In Xenopus embryo, betaTrCP acts as a negative regulator of Wnt signaling by interacting with beta-catenin. In this paper, we report results of the study on expression and regulation of the Xenopus betaTrCP gene. We found that xbetaTrCP is expressed in Xenopus oocytes as three transcripts, which very likely correspond to the previously identified localized mRNAs, and four isoforms. The xbetaTrCP promoter functional and structural analysis showed the presence of elements target of positive transcriptional control. Among them, we have identified a beta-catenin/Tcf signaling responsive region and a 45-bp element containing a sequence motif conforming to the SRF binding site, closer to the transcription initiation sites. There are also elements of transcriptional negative control.

The Xenopus laevis beta TrCP gene: genomic organization, alternative splicing, 5' and 3' region characterization and comparison of its structure with that of human beta TrCP genes.

beta TrCP plays a relevant role in the control of stability of several key protein factors. In Xenopus, beta TrCP acts as an inhibitor of Wnt signaling and dorsal axis formation. We determined the primary structure of the frog beta TrCP gene, which consists of 14 exons and 13 introns, spanning over 34 kb. Isoforms of x-beta TrCP have been found, which show differences in the NH(2) and COOH regions. NH(2) isoforms differ for the presence or absence of a 30 aa sequence, coded by exon III. In COOH isoforms, 19 C-terminal amino acids are replaced by three different amino acids. Occurrence of two 5' splice donor sites for splicing of intron XIII provides an explanation for these isoforms, based on alternative splicing. The DNA region of the putative beta TrCP promoter contains several TATA elements, one GCCAAT box, and putative binding sites for Ets, Tcf/Lef and NF-kappa B transcription factors. Two transcription initiation sites have been mapped downstream of TATA boxes proximal to ATG for start of translation. Comparison of the Xenopus and human beta TrCP genes indicates high conservation of exon nucleotide and amino acid sequences, size and organization; differences are limited to exons coding for N- and C-terminal regions.