Gram-negative septic thrombosis in critically ill patients: A retrospective case-control study

Background: Data on septic thrombosis caused by Gram-negative bacilli (GN-ST) in intensive care unit (ICU) patients are currently limited. Methods: The aim of this retrospective case–control study (matched 1:3) performed over a 15-month period on ICU patients with bacteraemia, associated (cases) or not (controls) with GN-ST, was to assess 30-day mortality and clinical/microbiological features of GN-ST. Results: During the study period, 16 patients with GN-ST and 48 controls were analyzed. Polytrauma was the cause of ICU admission in 12 (75%) cases and 22 (46%) controls (p = 0.019). In no case of septic thrombosis was surgical debridement performed. The site of venous thrombosis was more frequently in the lower limbs, associated with bone fracture in nine out of 12 (75%) cases. The median duration of bacteraemia (22 days vs 1 day; p 72 h was significantly associated with GN-ST (area under the curve (AUC) 0.95, sensitivity 0.996 and specificity 0.810; p < 0.001). Finally, 30-day mortality was 20% in cases and 67% in controls (p < 0.001). Conclusions: Critically ill patients with GN-ST showed specific clinical features. Despite delayed bacteraemia clearance, targeted antibiotic therapy plus anticoagulation usually provided clinical improvement and a low 30-day mortality rate

Transforming growth factor β 869C/T and interleukin 6 -174G/C polymorphisms relate to the severity and progression of bone-erosive damage detected by ultrasound in rheumatoid arthritis

Introduction: Single nucleotide polymorphisms (SNPs) of transforming growth factor β (TGF-β) and IL-6 genes (respectively, 869C/T and -174G/C) have been associated with radiographic severity of bone-erosive damage in patients with rheumatoid arthritis (RA). Musculoskeletal ultrasound (US) is more sensitive than radiography in detecting bone erosion. We analyzed the association between TGF-β 869C/T and IL-6 -174G/C SNPs and bone-erosive damage, evaluated by US, in a cohort of patients with severely active RA.Methods: Seventy-seven patients were enrolled before beginning anti-TNF treatment. Disease activity was measured using the disease activity score in 28 joints, and the clinical response was evaluated according to the European League Against Rheumatism response criteria. Rheumatoid factor (RF) and anticitrullinated protein/peptide antibodies (ACPAs) were detected. The 869C/T TGF-β and -174G/C IL-6 SNPs were analyzed by PCR amplification. US was performed to assess the bone surfaces of metacarpophalengeal (MCP), proximal interphalangeal (PIP) and metatarsophalangeal (MTP) joints by obtaining multiplanar scans. According to the number of erosions per joint, a semiquantitative score ranging from 0 to 3 was calculated in each anatomical site to obtain a MCP total erosion score (TES), a PIP TES and a MTP TES, all ranging from 0 to 30, and a global patient TES calculated as the sum of these scores (range, 0 to 90).Results: Patients carrying the TGF-β 869TT genotype showed a statistically significant lower MTP TES than those with the CC or CT genotype (mean MTP TES ± standard deviation for 869TT 6.3 ± 5.7 vs. 869CC/CT 11.7 ± 7.8; P = 0.011). Interestingly, patients with the TT genotype showed dichotomous behavior that was dependent on autoantibody status. In the presence of ACPAs and/or RF, the TT genotype was associated with lower erosion scores at all anatomical sites compared with the CC and CT genotypes. Conversely, the same 869TT patients showed higher erosion scores in the absence of ACPAs or RF.Conclusions: In RA patients, TGF-β 869C/T SNPs could influence the bone-erosive damage as evaluated by US. The serological autoantibody status (ACPAs and RF) can modulate this interaction. © 2011 Ceccarelli et al.; licensee BioMed Central Ltd

Postembryonic development and aging of the appendicular skeleton in Ambystoma mexicanum

Background: The axolotl is a key model to study appendicular regeneration. The limb complexity resembles that of humans in structure and tissue components; however, axolotl limbs develop postembryonically. In this work, we evaluated the postembryonic development of the appendicular skeleton and its changes with aging. Results: The juvenile limb skeleton is formed mostly by Sox9/Col1a2 cartilage cells. Ossification of the appendicular skeleton starts when animals reach a length of 10 cm, and cartilage cells are replaced by a primary ossification center, consisting of cortical bone and an adipocyte-filled marrow cavity. Vascularization is associated with the ossification center and the marrow cavity formation. We identified the contribution of Col1a2-descendants to bone and adipocytes. Moreover, ossification progresses with age toward the epiphyses of long bones. Axolotls are neotenic salamanders, and still ossification remains responsive to l-thyroxine, increasing the rate of bone formation. Conclusions: In axolotls, bone maturation is a continuous process that extends throughout their life. Ossification of the appendicular bones is slow and continues until the complete element is ossified. The cellular components of the appendicular skeleton change accordingly during ossification, creating a heterogenous landscape in each element. The continuous maturation of the bone is accompanied by a continuous body growth.Fil: Riquelme Guzmán, Camilo. Technische Universität Dresden; AlemaniaFil: Schuez, Maritta. Technische Universität Dresden; AlemaniaFil: Böhm, Alexander. Technische Universität Dresden; AlemaniaFil: Knapp, Dunja. Technische Universität Dresden; AlemaniaFil: Edwards Jorquera, Sandra. Technische Universität Dresden; AlemaniaFil: Ceccarelli, Alberto Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; ArgentinaFil: Chara, Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Argentina de la Empresa; Argentina. Technische Universität Dresden; AlemaniaFil: Rauner, Martina. Universitätsklinikum Carl Gustav Carus; AlemaniaFil: Sandoval Guzmán, Tatiana. Universitätsklinikum Carl Gustav Carus; Alemania. Technische Universität Dresden; Alemani

Multicenter Evaluation of the C6 Lyme ELISA Kit for the Diagnosis of Lyme Disease

Lyme disease (LD), caused by infection with Borrelia burgdorferi, is the most common tick-borne infection in many regions of Eurasia. Antibody detection is the most frequently used laboratory test, favoring a two-step serodiagnostic algorithm; immunoenzymatic detection of antibodies to C6 has been shown to perform similarly to a standard two-step workflow. The aim of this study was the performance evaluation of the C6 Lyme ELISA kit compared to a standard two-step algorithm in three laboratories located in the northeastern region of Italy which cater to areas with different LD epidemiology. A total of 804 samples were tested, of which 695 gave concordant results between C6 testing and routine workflow (564 negative, 131 positive). Wherever available, clinical presentation and additional laboratory tests were analyzed to solve discrepancies. The C6 based method showed a good concordance with the standard two-step algorithm (Cohen's κ = 0.619), however, the distribution of discrepancies seems to point towards a slightly lower specificity of C6 testing, which is supported by literature and could impact on patient management. The C6 ELISA, therefore, is not an ideal stand-alone test; however, if integrated into a two-step algorithm, it might play a part in achieving a sensitive, specific laboratory diagnosis of LD

Study of the effects of different biomaterials on osteogenic differentiation of oral-periosteal cells

Bone regeneration is currently one of the most important challenges for regenerative medicine and it is considered an ideal clinical strategy in the maxillo-facial area [1]. Bone resorption of alveolar crest occurring after tooth extraction leads to several risks for future treatments, including dental implants. For this reason, alveolar ridge preservation (ARP) has become a key component of contemporary clinical dentistry. Several clinical techniques and bone substitute materials can be used to fill the socket after tooth extraction. For all of them, the principle aim is to keep the shape and the size of the bone socket of the extracted tooth allowing inserting the dental implants [2]. The goal of our study was to compare different biocompatible scaffolds based on PLGA (Fisiograft®), Bioglass (Activioss®) and collagen (Sombrero®) in an in vitro model of tissue engineering for dental applications. The cells used in our study derived from Periosteum obtained from four different patients that underwent socket preservation selected by the School of Dentistry of the University of Pavia, previous informed consent. We created bio-complexes constituted by mesenchymal-periosteal cells seeded on different types of biomaterials and we performed adhesion, morphological, proliferative and bone differentiation analyses at different time points (7, 14 and 28 days of culture) in proliferative and osteogenic conditions. Bone differentiation was evaluated by qRT-PCR on genes involved in osteoblast development, like BMP-2, Osteocalcin and Periostin. Our results demonstrated that Sombrero® enhanced adhesion and proliferation of periosteal cells, as highlighted by Haematoxylin-Eosin staining and XTT test (3 and 7 days). Long-term studies (14 and 28 days) demonstrated that periosteal differentiation is about the same among the different materials tested. From these preliminary studies we can conclude that it could be advantageous the clinical use of both collagenic and PLGA scaffolds in order to ameliorate initial colonization and subsequent mechanical support in maxillo-bone regeneration. This work was supported by grant from NATO 2016 (“RAWINTS” (G-984961): RApid Skin Wound healing by INtegrated Tissue engineering and Sensing)

vaccination campaign strategies in recently arrived migrants experience of an italian reception centre

Introduction: Control of vaccine preventable diseases, while constituting a priority of European health policies, is challenged by migrations from countries with suboptimal levels of immunization coverage. We report here two different types of vaccination campaign strategy in one of the bigger Italian asylum seekers' centres. The vaccination service staff of the local national health institute came monthly during the first three years of observation, while in the last year, the vaccinations were offered directly upon arrival of migrants in the asylum seekers' centre. Methodology: we performed a descriptive cross-sectional study that analysed data collected from the database of the internal healthcare facility and ARVA Target tool, regarding vaccinations performed from 2013 to 2017 in the asylum seekers' centre. Results: In the four years of observation period the asylum seekers centre hosted 3941 migrants. Among them, 85% were vaccinated during their stay, for a total of 4252 vaccinations administered, covering 95% of minors and 85% of adults. During the study period, there was an important increase from an average of 10.5% of migrants vaccinated in the first three years to 66% in the last year, when vaccines were delivered directly upon arrival in the centre. Conclusions: To improve the rate of immunization in migrants, the first requirement is a strong collaboration with the local vaccine services and the second,vaccinations must be carried out when migrants arrive at the asylum seekers' centre, avoiding any delay

Early stability and late random tumor progression of a HER2-positive primary breast cancer patient-derived xenograft

We established patient-derived xenografts (PDX) from human primary breast cancers and studied whether stability or progressive events occurred during long-term in vivo passages (up to 4&nbsp;years) in severely immunodeficient mice. While most PDX showed stable biomarker expression and growth phenotype, a HER2-positive PDX (PDX-BRB4) originated a subline (out of 6 studied in parallel) that progressively acquired a significantly increased tumor growth rate, resistance to cell senescence of in vitro cultures, increased stem cell marker expression and high lung metastatic ability, along with a strong decrease of BCL2 expression. RNAseq analysis of the progressed subline showed that BCL2 was connected to three main hub genes also down-regulated (CDKN2A, STAT5A and WT1). Gene expression of progressed subline suggested a partial epithelial-to-mesenchymal transition. PDX-BRB4 with its progressed subline is a preclinical model mirroring the clinical paradox of high level-BCL2 as a good prognostic factor in breast cancer. Sequential in vivo passages of PDX-BRB4 chronically treated with trastuzumab developed progressive loss of sensitivity to trastuzumab while HER2 expression and sensitivity to the pan-HER tyrosine kinase inhibitor neratinib were maintained. Long-term PDX studies, even though demanding, can originate new preclinical models, suitable to investigate the mechanisms of breast cancer progression and new therapeutic approaches

Integrated clinicopathologic and molecular analysis of endometrial carcinoma: Prognostic impact of the new ESGO-ESTRO-ESP endometrial cancer risk classification and proposal of histopathologic algorithm for its implementation in clinical practice

IntroductionThe European Society of Gynecologic Oncology/European Society of Radiation Therapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) committee recently proposed a new risk stratification system for endometrial carcinoma (EC) patients that incorporates clinicopathologic and molecular features. The aim of the study is to compare the new ESGO/ESTRO/ESP risk classification system with the previous 2016 recommendations, evaluating the impact of molecular classification and defining a new algorithm for selecting cases for molecular analysis to assign the appropriate risk class.MethodsThe cohort included 211 consecutive EC patients. Immunohistochemistry and next-generation sequencing were used to assign molecular subgroups of EC: POLE mutant (POLE), mismatch repair deficient (MMRd), p53 mutant (p53abn), and no specific molecular profile (NSMP).ResultsImmuno-molecular analysis was successful in all cases, identifying the four molecular subgroups: 7.6% POLE, 32.2% MMRd, 20.9% p53abn, and 39.3% NSMP. The recent 2020 guidelines showed a 32.7% risk group change compared with the previous 2016 classification system: the reassignment is due to POLE mutations, abnormal p53 expression, and a better definition of lymphovascular space invasion. The 2020 system assigns more patients to lower-risk groups (42.2%) than the 2016 recommendation (25.6%). Considering the 2020 risk classification system that includes the difference between “unknown molecular classification” and “known,” the integration of molecular subgroups allowed 6.6% of patients to be recategorized into a different risk class. In addition, the use of the proposed algorithm based on histopathologic parameters would have resulted in a 62.6% reduction in molecular analysis, compared to applying molecular classification to all patients.ConclusionApplication of the new 2020 risk classification integrating clinicopathologic and molecular parameters provided more accurate identification of low-and high-risk patients, potentially allowing a more specific selection of patients for post-operative adjuvant therapy. The proposed histopathologic algorithm significantly decreases the number of tests needed and could be a promising tool for cost reduction without compromising prognostic stratification