Biology matters: the clinical impact of single-receptor discordance on breast cancer

n/

Subsidence evolution of the Firenze–Prato–Pistoia plain (Central Italy) combining PSI and GNSS data

Subsidence phenomena, as well as landslides and floods, are one of the main geohazards affecting the Tuscany region (central Italy). The monitoring of related ground deformations plays a key role in their management to avoid problems for buildings and infrastructure. In this scenario, Earth observation offers a better solution in terms of costs and benefits than traditional techniques (e.g., GNSS (Global Navigation Satellite System) or levelling networks), especially for wide area applications. In this work, the subsidence-related ground motions in the Firenze–Prato–Pistoia plain were back-investigated to track the evolution of displacement from 2003 to 2017 by means of multi-interferometric analysis of ENVISAT and Sentinel-1 imagery combined with GNSS data. The resulting vertical deformation velocities are aligned to the European Terrestrial Reference System 89 (ETRS89) datum and can be considered real velocity of displacement. The vertical ground deformation maps derived by ENVISAT and Sentinel-1 data, corrected with the GNSS, show how the area affected by subsidence for the period 2003–2010 and the period 2014–2017 evolved. The differences between the two datasets in terms of the extension and velocity values were analysed and then associated with the geological setting of the basin and external factors, e.g., new greenhouses and nurseries. This analysis allowed for reconstructing the evolution of the subsidence for the area of interest showing an increment of ground deformation in the historic centre of Pistoia Town, a decrement of subsidence in the nursery area between Pistoia and Prato cities, and changes in the industrial sector close to Prato

ALG3-CDG: a patient with novel variants and review of the genetic and ophthalmic findings

BACKGROUND: ALG3-CDG is a rare autosomal recessive disease. It is characterized by deficiency of alpha-1,3-mannosyltransferase caused by pathogenic variants in the ALG3 gene. Patients manifest with severe neurologic, cardiac, musculoskeletal and ophthalmic phenotype in combination with dysmorphic features, and almost half of them die before or during the neonatal period. CASE PRESENTATION: A 23 months-old girl presented with severe developmental delay, epilepsy, cortical atrophy, cerebellar vermis hypoplasia and ocular impairment. Facial dysmorphism, clubfeet and multiple joint contractures were observed already at birth. Transferrin isoelectric focusing revealed a type 1 pattern. Funduscopy showed hypopigmentation and optic disc pallor. Profound retinal ganglion cell loss and inner retinal layer thinning was documented on spectral-domain optical coherence tomography imaging. The presence of optic nerve hypoplasia was also supported by magnetic resonance imaging. A gene panel based next-generation sequencing and subsequent Sanger sequencing identified compound heterozygosity for two novel variants c.116del p.(Pro39Argfs*40) and c.1060 C > T p.(Arg354Cys) in ALG3. CONCLUSIONS: Our study expands the spectrum of pathogenic variants identified in ALG3. Thirty-three variants in 43 subjects with ALG3-CDG have been reported. Literature review shows that visual impairment in ALG3-CDG is most commonly linked to optic nerve hypoplasia

A Retrospective Multicenter Analysis of the Incidence of Bone-Only Disease at PSMA PET/CT in Castration Resistant Prostate Cancer Patients

PSMA PET/CT has unprecedented accuracy for localization of initial or recurrent prostate cancer (PC), which can be applied in a metastasis-directed therapy approach. PSMA PET/CT (PET) also has a role in the selection of patients for metastasis-directed therapy or radioligand therapy and therapy assessment in CRPC patients. The purpose of this multicenter retrospective study was to determine the incidence of bone-only metastasis in CRPC patients who underwent PSMA PET/CT for restaging, as well as identifying potential predictors of bone-only PET positivity. The study analyzed data from 179 patients from two centers in Essen and Bologna. Results showed that 20.1% of the patients had PSMA uptake only in the bone, with the most frequent lesions located in the vertebrae, ribs, and hip bone. Half half of the patients showed oligo disease in bone and may benefit from a bone-metastasis-directed therapy. Initial positive nodal status and solitary ADT were shown to be negative predictors of osseous metastasis. The role of PSMA PET/TC in this patient population needs to be further explored in terms of its role in the evaluation and adoption of bone-specific therapies

Postoperative procalcitonin is a biomarker for excluding the onset of clinically relevant pancreatic fistula after pancreaticoduodenectomy

Background: Early detection and therapy of pancreatic fistula after pancreaticoduodenectomy is crucial to improve outcomes of this surgery. Since it is not clear if procalcitonin (PCT), can predict the onset of clinically relevant pancreatic fistula (CR-POPF), we aimed to investigate this ability.Methods: One-hundred-thirty pancreaticoduodenectomies (PD) were analyzed. Receiver Operating Characteristic curves analysis defined the optimal cut-of fs for PCT and drains amylase levels (DAL). Complications were compared using chi-square for proportions test.Results: DAL >_2,000 U/L in postoperative day (POD) 2 had 71% PPV and 91% NPV for CR-POPF (P<0.001). In POD2, PCT >_0.5 ng/mL showed NPV 91% (P<0.045) and increased DAL PPV for CR-POPF to 81%. In POD3, POD4 and POD5, DAL (cut-offs 780 U/L, 157 U/L and 330 U/L, respectively) showed NPV for CR-POPF >90% (P<0.0001). PCT >_0.5 ng/mL showed NPV for CR-POPF of about 90%. In POD5, combining DAL (cut-off 330 U/L) and PCT (cut-off 0.5 ng/mL), a PPV for CR-POPF of 81% was detected. A progressive increased risk of CR-POPF from POD2 (OR =3.05; P=0.0348) to POD5 (OR =4.589; P=0.0082) was observed. In POD2 and 5, PCT >_0.5 ng/mL, alone and in combination with DAL, may be a reliable marker for identifying patients at highest risk of CR-POPF after PD.Conclusions: This association could be proposed to select high risk patients that could benefit of "intensive" postoperative management

Data of postoperative complications related to fibrinogen-to-albumin ratio in pancreatic resections

Pancreatic surgery is one of the surgeries burdened with the highest mortality and morbidity rate. This is due both to the aggressive biological nature of the pathology affecting the organ and to the technical difficulties associated with surgery. A further aspect on which research is focusing is represented by inflammation related to oncological pathology. Inflammation plays an important role in tumor progression, and growing evidence has confirmed that the fibrinogen-to-albumin ratio (FAR) is an important prognostic factor for overall survival (OS) in malignant tumors. Inflammatory markers had demonstrated also a role in the prediction of postoperative complication after pancreatic surgery. We speculate that FAR, as an easily available, cost-effective, and non-invasive prognostic indicator for pancreatic cancer patients, could help to identify patients at increased risk of postoperative pancreatic fistula (POPF). We therefore retrospectively analyzed the data relating to 117 pancreatic resections relating direct and indirect markers of inflammation with the incidence of post-operative complications. (c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/

Exacerbations and Pseudomonas aeruginosa colonization are associated with altered lung structure and function in primary ciliary dyskinesia

Background: Recurrent bacterial infections of the respiratory tract are one of the major clinical features of the primary ciliary dyskinesia (PCD), a rare genetic disease due to malfunctioning of motile cilia. Chronic infections and persistent inflammation of the respiratory system result in progressive lung disease. Aim of the study was to highlight the main factors associated with clinical, functional and anatomical deterioration in PCD patients. Methods: We retrospectively analyzed data from 58 patients with PCD, 37 adults and 21 children. The demographic and clinical data, forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC), sputum microbiology and imaging results (chest CT scores-modified Bhalla) were recorded. Patients were stratified according to the number of exacerbations (< 2/year vs 65 2/year) and chronic Pseudomonas aeruginosa (PA) colonization. The possible correlations between lung function and chest CT scores were assessed; we also evaluated the correlation between these parameters and the severity scores for bronchiectasis (BSI, FACED and e-FACED). Results: Chest CT scores showed a significant correlation with FEV1 (p = 0.0002), age (p < 0.0001), BMI (p = 0.0002) and number of lung lobes involved (p < 0.0001). PA colonization had an overall prevalence of 32.6%: no significant difference in FEV1 between PA colonized and non-colonized patients was found (p = 0.70), while chest CT score was significantly worse in chronic PA colonized patients (p = 0.009). Patients with a high number of exacerbation ( 65 2/year) were older (p = 0.01), had lower FEV1 (p = 0.03), greater number of lobes involved (p < 0.001) and worse CT score than patients with low number of exacerbations (p = 0.001); they also had higher prevalence of PA chronic bronchial infection (33.3% versus 13.6%, p = 0.10). Multivariable linear regression analyses adjusted for gender, age and BMI showed positive associations between PA colonization and number of exacerbations with severity of disease (number of lobes involved, CT score, BSI, FACED, and e-FACED). Conclusions: In our PCD population the number of exacerbations ( 65 2/year) and PA colonization were the two most relevant factors associated with severity of disease

Endometrioid Cancer Associated With Endometriosis: From the Seed and Soil Theory to Clinical Practice

Endometriosis is a benign condition characterized by the presence of ectopic endometrial tissue. It is still debated whether endometriosis is a disease that can predispose to the pathogenesis of endometrial cancer outside the uterus. Deficiencies in mismatch repair (MMR) genes are a known risk factor for developing endometrioid cancer. Starting from two cases of patients with abnormal MMR endometrioid carcinoma of the uterus and synchronous endometrioid carcinoma in non-ovarian and ovarian endometriosis, we performed a somatic mutation profile and phylogenetic analysis of the lesions in order to identify if they were metastasis or primary de novo tumors. In the first case, we identified de novo activating mutations in PIK3CA and KRAS in endometrioid cancer lesions but not in endometriosis. Although the acquisition of a de novo mutation in ESR1 and a decrease in mutant allele fraction (MAF) from the endometrial tumor to the localizations in the endometriosis lesions, the clonal relationship was confirmed by the limited number of heteroplasmic mutations in D-loop mitochondrial DNA region. In the other case, the clonal behavior was demonstrated by the overlap of MAF at each site. Our data support the hypothesis of a retrograde dissemination of tumor cells, moving from the primary carcinoma in the endometrium to ectopic sites of endometriosis where localizations of tumor arise