When sarcoidosis hits down: a case of prostatic sarcoidosis.

A 69-year-old North African male with established diagnosis of sarcoidosis underwent a stereotactic prostate biopsy with fusion technique. At the histological analysis, non-necrotizing micro-granulomas were highlighted in 2 samples, while the immunohistochemical staining resulted negative for CK903/p63/racemase. To the best of our knowledge, only 16 cases of prostatic sarcoidosis have been reported in literature. With this case report we describe an incidental diagnosis of prostatic involvement of sarcoidotic disease and briefly review and discuss the available literature on the topic.

ERS International Congress 2023: highlights from the Clinical Techniques, Imaging and Endoscopy Assembly.

The Clinical Techniques, Imaging and Endoscopy Assembly is involved in the diagnosis and treatment of several pulmonary diseases, as demonstrated at the 2023 European Respiratory Society (ERS) International Congress in Milan, Italy. From interventional pulmonology, the congress included several exciting results for the use of bronchoscopy in lung cancer, including augmented fluoroscopy, robotic-assisted bronchoscopy and cryobiopsies. In obstructive lung disease, the latest results on bronchoscopic treatment of emphysema with hyperinflation and chronic bronchitis were presented. Research on using cryobiopsies to diagnose interstitial lung disease was further explored, with the aims of elevating diagnostic yield and minimising risk. For imaging, the latest updates in using artificial intelligence to overcome the increased workload of radiologists were of great interest. Novel imaging in sarcoidosis explored the use of magnetic resonance imaging, photon-counting computed tomography and positron emission tomography/computed tomography in the diagnostic work-up. Lung cancer screening is still a hot topic and new results were presented regarding incorporation of biomarkers, identifying knowledge gaps and improving screening programmes. The use of ultrasound in respiratory medicine is an expanding field, which was demonstrated by the large variety in studies presented at the 2023 ERS Congress. Ultrasound of the diaphragm in patients with amyotrophic lateral sclerosis and myasthenia gravis was used to assess movements and predict respiratory fatigue. Furthermore, studies using ultrasound to diagnose or monitor pulmonary disease were presented. The congress also included studies regarding the training and assessment of competencies as an important part of implementing ultrasound in clinical practice.

Physiological effects of lung-protective ventilation in patients with lung fibrosis and usual interstitial pneumonia pattern versus primary ARDS: a matched-control study.

BACKGROUND: Although patients with interstitial pneumonia pattern (ILD-UIP) and acute exacerbation (AE) leading to severe acute respiratory failure may require invasive mechanical ventilation (MV), physiological data on lung mechanics during MV are lacking. We aimed at describing the physiological effect of lung-protective ventilation in patients with AE-ILD-UIP compared with primary ARDS. METHODS: Partitioned lung and chest wall mechanics were assessed in a series of AE-ILD-UIP patients matched 1:1 with primary ARDS as controls (based on BMI and PaO2/FiO2 ratio). Three PEEP levels (zero = ZEEP, 4-8 cmH2O = PEEPLOW, and titrated to achieve positive end-expiratory transpulmonary pressure PL,EE = PEEPTITRATED) were used for measurements. RESULTS: Ten AE-ILD-UIP patients and 10 matched ARDS were included. In AE-ILD-UIP median PL,EE at ZEEP was - 4.3 [- 7.6- - 2.3] cmH2O and lung elastance (EL) 44 [40-51] cmH2O/L. At PEEPLOW, PL,EE remained negative and EL did not change (p = 0.995) versus ZEEP. At PEEPTITRATED, PL,EE increased to 0.8 [0.3-1.5] cmH2O and EL to 49 [43-59] (p = 0.004 and p < 0.001 compared to ZEEP and PEEPLOW, respectively). ΔPL decreased at PEEPLOW (p = 0.018) and increased at PEEPTITRATED (p = 0.003). In matched ARDS control PEEP titration to obtain a positive PL,EE did not result in significant changes in EL and ΔPL. CONCLUSIONS: In mechanically ventilated AE-ILD-UIP patients, differently than in patients with primary ARDS, PEEP titrated to obtain a positive PL,EE significantly worsened lung mechanics.

Performance of EUS-FNA and EUS-B-FNA for the diagnosis of left adrenal glands metastases in patients with lung cancer: A systematic review and meta-analysis.

OBJECTIVES: For diagnosing left adrenal gland metastasis in lung cancer, clinical guidelines recommend to perform EUS, but EUS-B (EUS using an EBUS-scope) is increasingly being used. We evaluated the diagnostic performance of both procedures. MATERIALS AND METHODS: We did a systematic review (PROSPERO, CRD42023416205) and searched MEDLINE and EMBASE on 04-July-2023 for studies evaluating EUS and/or EUS-B in diagnosing left adrenal gland metastases in adults with (suspected) lung cancer. Outcomes were: (1) ability to visualize the left adrenal gland, (2) ability to sample (in those with successful visualization and in whom sampling was attempted), (3) ability to obtain adequate material (in those with successful sampling), (4) malignancy detection rate (in those with successful sampling), and (5) remaining risk of malignancy (in those with a negative EUS(-B)-FNA and undergoing a reference standard). We performed random-effects meta-analyses. RESULTS: We included 19 studies (EUS: n = 11, EUS-B: n = 6, both: n = 2), covering 1712 patients. All studies had high (n = 18) or unclear (n = 1) risk of bias (QUADAS-2). Average ability to visualize the left adrenal gland was 0.94 (95 %CI 0.82-0.98; n = 7 studies). Average ability to sample was 1.00 (95 %CI 0.99-1.00; n = 9). Average ability to obtain adequate material was 0.96 (95 %CI 0.93-0.98; n = 18). Average malignancy detection rate was 0.42 (95 %CI 0.34-0.49; n = 18). Remaining risk of malignancy was 0.07 (95 %CI 0.04-0.12; n = 8). Ability to visualize was slightly higher for EUS (0.99; 95 %CI 0.90-1.00) than EUS-B (0.84; 95 %CI 0.70-0.92; p = 0.025), but the other performance characteristics were similar. No major complications were reported. CONCLUSION: Both EUS and EUS-B have good performance and are safe for left adrenal gland analysis in patients with lung cancer, but the number of high-quality studies is limited and further well-constructed prospective studies are needed.

Phylogeny and mycotoxin profiles of pathogenic Alternaria and Curvularia species isolated from date palm in southern Tunisia.

Date palm (Phoenix dactylifera L.), is a widely cultivated crop across North Africa, with about 300 thousand tons of fruits produced per year, in Tunisia. A wide range of fungal pathogens has been associated with leaf spots of date palm, Alternaria species being the most frequently reported. Symptomatic leaves of Deglet Nour variety were randomly collected in six localities in Tunisia. We used a polyphasic approach to identify 45 Alternaria and five Curvularia strains isolated from date palm, confirming their pathogenicity. Sequencing of allergen Alt-a1, glyceraldehyde-3-phosphate dehydrogenase (gpd) and calmodulin genes allowed us to group 35 strains in Alternaria Section, and 10 strains in Ulocladioides section. Based on sequencing analyses of Internal Transcribed Spacer, gpd and elongation factor genomic regions, all Curvularia strains were identified as Curvularia spicifera. All Alternaria and Curvularia species tested on date palm plantlets proved to be pathogenic, fulfilling Koch's postulates. Although no significant differences were observed among the species, the highest mean disease severity index was observed in A. arborescens, while the lowest corresponded to C. spicifera. The capability of these strains to produce mycotoxins in vitro was evaluated. None of the A. consortialis strains produced any known Alternaria mycotoxin, whereas more than 80% of the strains included in Alternaria section Alternaria produced variable amounts of multiple mycotoxins such as alternariol, alternariol monomethyl ether, altenuene, tenuazonic acid and tentoxin. Curvularia spicifera strains produced detectable traces of fumonisins B. This work reports a first comprehensive multidisciplinary study of mycotoxigenic Alternaria species and C. spicifera associated with leaf spot disease on date palm.

Incretin-based drugs as potential therapy for neurodegenerative diseases: current status and perspectives.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most frequent neurodegenerative disorders. Despite their pathophysiological and clinical differences, they share several mechanistic similarities at cellular and sub-cellular levels. The current treatments of AD and PD are only symptomatic, since many clinically-tested drugs failed to prevent or halt their progression. There is now evidence that type 2 diabetes mellitus is among the main risk factors for AD and PD and that the insulin resistance in the brain plays a crucial role in their neuropathological processes. Therefore, insulin nasal administration was suggested for the treatment of AD and PD, both in diabetic and non-diabetic patients. However, the adverse effects of chronic insulin prompted the research of alternative strategies, such as the novel antidiabetic drugs based on the incretin hormones glucagon-like protein-1 (GLP-1) and glucose-dependent insulinotropic Peptide (GIP). The rapid inactivation of these incretins by dipeptidyl-peptidase IV (DPP-IV) suggested the development of DPP-IV-resistant GLP-1 receptor agonists (GLP-1Ras), the recent dual GLP-1/GIP receptor agonists and the DPP-IV inhibitors (DPP-IVis). This review will first describe the experimental, pathophysiological and clinical approach for AD and PD treatment with insulin. Afterwards, the main pharmacologic properties of GLP-1Ras and of DPP-IVis will be discussed, detailing their ability to cross the BBB and get access to the brain for GLP-1Ras, and the novel strategies for BBB crossing as regards DPP-IVis. Emphasis will be placed on the main findings obtained from AD and PD experimental models about the neuroprotective effects of these drugs. For AD, the improvement of learning and memory exerted by incretin-based drugs correlated with reduction of chronic inflammation, brain Aß plaque, tau hyperphosphorylation, protection of mitochondria, enhancement of energy utilisation. For PD, both GLP-1Ras and of DPP-IVis reversed the nigrostriatal dopaminergic cell loss progression, restored dopamine synthesis, exerted anti-inflammatory activity and improved motor functions. Finally, the encouraging results of the first clinical trials on AD and PD patients and the adverse effects of GLP-1Ras and DPP-IVis will be discussed, highlighting how the above-mentioned neuroprotective effects have a great potential to be translated into clinical settings and that the incretin-based approach represents novel promising strategy for the treatment of AD and PD, although more convincing clinical pieces of evidence are required. In perspective, the new approaches that are being developed to allow GLP-1Ras and DPP-IVis rapid entering into the Central Nervous System may substantially contribute to their repurposing for neurodegenerative disease.

Molecular Mechanisms and Physiological Changes behind Benign Tracheal and Subglottic Stenosis in Adults.

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS.

Molecular Mechanisms and Cellular Contribution from Lung Fibrosis to Lung Cancer Development.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease (ILD) of unknown aetiology, with a median survival of 2-4 years from the time of diagnosis. Although IPF has unknown aetiology by definition, there have been identified several risks factors increasing the probability of the onset and progression of the disease in IPF patients such as cigarette smoking and environmental risk factors associated with domestic and occupational exposure. Among them, cigarette smoking together with concomitant emphysema might predispose IPF patients to lung cancer (LC), mostly to non-small cell lung cancer (NSCLC), increasing the risk of lung cancer development. To this purpose, IPF and LC share several cellular and molecular processes driving the progression of both pathologies such as fibroblast transition proliferation and activation, endoplasmic reticulum stress, oxidative stress, and many genetic and epigenetic markers that predispose IPF patients to LC development. Nintedanib, a tyrosine-kinase inhibitor, was firstly developed as an anticancer drug and then recognized as an anti-fibrotic agent based on the common target molecular pathway. In this review our aim is to describe the updated studies on common cellular and molecular mechanisms between IPF and lung cancer, knowledge of which might help to find novel therapeutic targets for this disease combination.

Volatile Organic Compounds Emitted by Aspergillus flavus Strains Producing or Not Aflatoxin B1.

Aspergillus flavus is a phytopathogenic fungus able to produce aflatoxin B1 (AFB1), a carcinogenic mycotoxin that can contaminate several crops and food commodities. In A. flavus, two different kinds of strains can co-exist: toxigenic and non-toxigenic strains. Microbial-derived volatile organic compounds (mVOCs) emitted by toxigenic and non-toxigenic strains of A. flavus were analyzed by solid phase microextraction (SPME) coupled with gas chromatography-mass spectrometry (GC-MS) in a time-lapse experiment after inoculation. Among the 84 mVOCs emitted, 44 were previously listed in the scientific literature as specific to A. flavus, namely alcohols (2-methylbutan-1-ol, 3-methylbutan-1-ol, 2-methylpropan-1-ol), aldehydes (2-methylbutanal, 3-methylbutanal), hydrocarbons (toluene, styrene), furans (2,5-dimethylfuran), esters (ethyl 2-methylpropanoate, ethyl 2-methylbutyrate), and terpenes (epizonaren, trans-caryophyllene, valencene, α-copaene, ß-himachalene, γ-cadinene, γ-muurolene, δ-cadinene). For the first time, other identified volatile compounds such as α-cadinol, cis-muurola-3,5-diene, α-isocomene, and ß-selinene were identified as new mVOCs specific to the toxigenic A. flavus strain. Partial Least Square Analysis (PLSDA) showed a distinct pattern between mVOCs emitted by toxigenic and non-toxigenic A. flavus strains, mostly linked to the diversity of terpenes emitted by the toxigenic strains. In addition, the comparison between mVOCs of the toxigenic strain and its non-AFB1-producing mutant, coupled with a semi-quantification of the mVOCs, revealed a relationship between emitted terpenes (ß-chamigrene, α-corocalene) and AFB1 production. This study provides evidence for the first time of mVOCs being linked to the toxigenic character of A. flavus strains, as well as terpenes being able to be correlated to the production of AFB1 due to the study of the mutant. This study could lead to the development of new techniques for the early detection and identification of toxigenic fungi.

Fibrotic Idiopathic Interstitial Lung Disease: The Molecular and Cellular Key Players.

Interstitial lung diseases (ILDs) that are known as diffuse parenchymal lung diseases (DPLDs) lead to the damage of alveolar epithelium and lung parenchyma, culminating in inflammation and widespread fibrosis. ILDs that account for more than 200 different pathologies can be divided into two groups: ILDs that have a known cause and those where the cause is unknown, classified as idiopathic interstitial pneumonia (IIP). IIPs include idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP) known also as bronchiolitis obliterans organizing pneumonia (BOOP), acute interstitial pneumonia (AIP), desquamative interstitial pneumonia (DIP), respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), and lymphocytic interstitial pneumonia (LIP). In this review, our aim is to describe the pathogenic mechanisms that lead to the onset and progression of the different IIPs, starting from IPF as the most studied, in order to find both the common and standalone molecular and cellular key players among them. Finally, a deeper molecular and cellular characterization of different interstitial lung diseases without a known cause would contribute to giving a more accurate diagnosis to the patients, which would translate to a more effective treatment decision.

Mycotoxin Profile and Phylogeny of Pathogenic Alternaria Species Isolated from Symptomatic Tomato Plants in Lebanon.

The tomato is one of the most consumed agri-food products in Lebanon. Several fungal pathogens, including Alternaria species, can infect tomato plants during the whole growing cycle. Alternaria infections cause severe production and economic losses in field and during storage. In addition, Alternaria species represent a serious toxicological risk since they are able to produce a wide range of mycotoxins, associated with different toxic activities on human and animal health. Several Alternaria species were detected on tomatoes, among which the most important are A. solani, A. alternata, and A. arborescens. A set of 49 Alternaria strains isolated from leaves and stems of diseased tomato plants were characterised by using a polyphasic approach. All strains were included in the recently defined phylogenetic Alternaria section and grouped in three well-separated sub-clades, namely A. alternata (24 out of 49), A. arborescens (12 out of 49), and A. mali morpho-species (12 out of 49). One strain showed high genetic similarity with an A.limoniasperae reference strain. Chemical analyses showed that most of the Alternaria strains, cultured on rice, were able to produce alternariol (AOH), alternariol methyl ether (AME), altenuene (ALT) and tenuazonic acid (TA), with values up to 5634, 16,006, 5156, and 4507 mg kg-1, respectively. In addition, 66% of the strains were able to co-produce simultaneously the four mycotoxins investigated. The pathogenicity test carried out on 10 Alternaria strains, representative of phylogenetic sub-clades, revealed that they were all pathogenic on tomato fruits. No significant difference among strains was observed, although A. alternata and A. arborescens strains were slightly more aggressive than A. mali morpho-species strains. This paper reports new insights on mycotoxin profiles, genetic variability, and pathogenicity of Alternaria species on tomatoes.

Pulmonary Stretch and Lung Mechanotransduction: Implications for Progression in the Fibrotic Lung.

Lung fibrosis results from the synergic interplay between regenerative deficits of the alveolar epithelium and dysregulated mechanisms of repair in response to alveolar and vascular damage, which is followed by progressive fibroblast and myofibroblast proliferation and excessive deposition of the extracellular matrix. The increased parenchymal stiffness of fibrotic lungs significantly affects respiratory mechanics, making the lung more fragile and prone to non-physiological stress during spontaneous breathing and mechanical ventilation. Given their parenchymal inhomogeneity, fibrotic lungs may display an anisotropic response to mechanical stresses with different regional deformations (micro-strain). This behavior is not described by the standard stress-strain curve but follows the mechano-elastic models of "squishy balls", where the elastic limit can be reached due to the excessive deformation of parenchymal areas with normal elasticity that are surrounded by inelastic fibrous tissue or collapsed induration areas, which tend to protrude outside the fibrous ring. Increasing evidence has shown that non-physiological mechanical forces applied to fibrotic lungs with associated abnormal mechanotransduction could favor the progression of pulmonary fibrosis. With this review, we aim to summarize the state of the art on the relation between mechanical forces acting on the lung and biological response in pulmonary fibrosis, with a focus on the progression of damage in the fibrotic lung during spontaneous breathing and assisted ventilatory support.

First report of Leaf Wilt caused by Fusarium proliferatum and F. brachygibbosum on Date Palm (Phoenix dactylifera) in Tunisia.

Since 2017, a new leaf wilt syndrome was observed in plantations of date palm in Tunisia. Its incidence increases sharply from year to year, especially in 'Deglet Nour' trees, aged between 5 and 15 years. In severe cases, the large number of dried leaves per tree can lead to complete cessation of date production. Symptoms appear on one or more leaves in the center of the crown. Whitening and drying start at the top of the leaflets and proceed to their base, while the midrib remains green. Then the whole leaf dies. Small white-creamy leaflet fragments and roots were collected from five different regions in the Djerid Oases. They were disinfected with diluted bleach (0,8 % NaOCl) and ethanol (80%) (each 2 min), rinsed with sterile distilled water, dried and finally plated in Petri dishes containing Potato Dextrose Agar (PDA) amended with 50mg/l neomycin. After incubation for 7 days at 25ºC±2, emerging fungal colonies were single-spored by serial dilution. They were transferred to PDA, Carnation Leaf Agar (CLA) and Spezieller Nahrstoffarmer Agar (SNA) for morphological identification. Based on the colony color on PDA, conidial morphology and phialide structures on CLA and/or SNA, of the 85 Fusarium isolates, around 90% were identified as F. proliferatum and around 10% as F. brachygibbosum (Leslie and Summerell, 2006). Fusarium proliferatum colonies rapidly developed white aerial mycelium that became purple in old cultures. Microconidia were abundant in the aerial mycelium and formed chains of variable length, on monophialides and polyphialids, a characteristic that distinguishes F. proliferatum from F. verticilloides. Less often, they were observed in false heads. Chlamydospores were absent. On CLA, microconidia were mostly 2 × 15 µm in size, a large number of sickle shaped macroconidia (2 × 25 µm) had one septum, some were larger (2 × 50 µm) with 3 septa and tips at both ends. Molecular identification was carried out based on elongation factor (EF-1α) gene sequencing. The region between the EF1 and EF2 primers (O'Donnell et al., 1998) was amplified and the sequences were compared to Fusarium reference sequences (GenBank). The sequences of the isolates Fus 1953 (539 bp), Fus 1962 (618 bp), and Fus 1965 (605 bp) shared respectively 100%, 99.51% and 99.51% homology with that of F. proliferatum JF740713.1 and were deposited in GenBank with the following accession numbers: MT630418, MT630419, and MT630420, respectively. The sequences of isolates 7F, 28F, Fus 1955 and Fus 1956 shared 100 % homology with that of F. brachygibbosum (GQ505418.1) while those of Fus 1955 and Fus 1956 showed 99.02 and 98.91 % identity, respectively, with F. brachygibbosum JX118981.1. The sequences of 7F (535 bp), 28F (535 bp), Fus 1955 (608 bp), and Fus 1956 (647 bp) were deposited in GenBank with the following accession numbers: MT630409, MT630410, MT630411, and MT630412, respectively. Two ml suspension of 106 conidia / ml of each isolate was sprayed separately or in combinations on in vitro cloned 'Deglet Nour' plants, placed in a greenhouse at 28°±2 °C and 70% R.H.. Isolates of F. proliferatum led to dryness and wilting leaflets after 3 weeks. Fusarium brachygibbosum only induced mild leaf yellowing, while in combination they were more virulent. Fungal isolates of both species were re-isolated and their identity confirmed to be the same of those isolated from leaflets infected in the open field, confirming Koch's postulates. Control plants lacked symptoms. Fusarium proliferatum is known as date palm pathogen in many countries (Saleh et al. 2017), however, to our knowledge, this is the first report of F. proliferatum and also F. brachygibbosum causing Leaf Wilt symptoms on P. dactylifera in Tunisia.

Nasal Tip Rotation by Exclusive Superficial Musculoaponeurotic System Deep Medial Ligament Management: An Objective Evaluation.

The nasal tip constitutes the mobile portion of the nose, in direct contraposition to the pyramid that is a fixed structure. Its configuration, position, and shape are derived mainly from the outline and from the thickness of the wing cartilages, important elements of the nasal tip, that together with skin and subcutaneous tissue can deeply influence the configuration and dynamics of this section of the nose as well. In reshaping the nasal tip, 2 fundamental concepts must be considered: projection and rotation; these may be modified, acting on the nasal cartilaginous framework and/or on the superficial nasal fibromuscular structure (SMAS). The aims of this study are to evaluate the nasal tip changes in terms of rotation and projection obtained just acting on superficial muscle aponeurotic deep medial layer without performing any dissection or modification of the nasal tip framework, and to try to explain these possible changes according to the SMAS structure rearrangements only. Twenty-one patients (18 female and 3 male) were subjected to closed rhinoplasty, without tip cartilage dissection/modification. Preoperative and postoperative tip rotation angle, nasolabial angle, and tip projection were measured. The only tip procedure performed was the resection of the SMAS deep medial layer. Our results show significant rotation of the nasal tip and no statistically significant tip deprojection.

Strategies to minimize soft tissues and septic complications in staged management of high-energy proximal tibia fractures.

BACKGROUND: Soft tissues (wound dehiscence, skin necrosis) and septic (wound infection, osteomyelitis) complications have been historically recognized as the most frequent complications in surgical treatment of high-energy proximal tibia fractures (PTFs). Staged management with a temporary external fixator is a commonly accepted strategy to prevent these complications. Nonetheless, there is a lack of evidence about when and how definitive external or internal definitive fixation should be chosen, and which variables are more relevant in determining soft tissues and septic complications risk. The aim of the present study is to retrospectively evaluate at midterm follow-up the results of a staged management protocol applied in a single trauma center for selective PTFs. METHODS: The study population included 24 cases of high-energy PTFs treated with spanning external fixation followed by delayed internal fixation. Severity of soft tissues damage and fracture type, timing of definitive treatment, clinical (ROM, knee stability, WOMAC and IOWA scores) and radiographic results as well as complications were recorded. RESULTS AND CONCLUSION: Complex fracture patterns were prevalent (AO C3 58.3%, Schatzker V-VI 79.1%), with severe soft tissues damage in 50% of cases. Mean time to definitive internal fixation was 6 days, with double-plate fixation mostly chosen. Clinical results were highly satisfying, with mean WOMAC and IOWA scores as 21.3 and 82.5, respectively. Soft tissue complication incidence was very low, with a single case of wound superficial infection (4.3%) and no cases (0%) of deep infection, skin necrosis or osteomyelitis. Staged management of high-energy PTFs leads to satisfying clinical and radiographic results with few complications in selected patients.

MicroRNA Expression Profiles in External Cervical Resorption.

INTRODUCTION: External cervical resorption (ECR) has been challenging for its diagnosis, prevention, and treatment. Its etiology and pathogenesis are largely unknown. This study characterized microRNA (miRNA) expression patterns of human tissues from ECR lesions and identified potential messenger RNA targets and pathways. METHODS: Granulomatous tissues from ECR (n = 5) and their adjacent nonaffected asymptomatic gingival connective tissues (n = 5) were collected. Similarly, chronic periodontitis (CP) and control samples were collected (n = 3). Quantitative reverse transcription polymerase chain reaction array analysis compared the expression profiles of 88 miRNAs between diseases. Differentially expressed miRNAs were identified using the Student t test. Bioinformatics for messenger RNA (miRWalk) and KEGG pathway analyses were performed to identify predicted target genes and biological/cellular functions and signaling pathways. RESULTS: Three miRNAs (miR-20a-5p, miR-210-3p, and miR-99a-4p) were significantly down-regulated and 1 miRNA (miR-122-5p) was significantly up-regulated in ECR (P < .05). One up-regulated and 1 down-regulated miRNA reached the significance threshold in CP. A comparison of miRNA expression in ECR and CP identified 3 differentially expressed miRNAs, indicating differences in disease pathobiology. Inflammation-associated Wnt, PI3K-Akt, mitogen-activated protein kinases signaling, and bone formation-associated transforming growth factor beta pathways were identified and predicted to be modulated by differentially expressed miRNAs in both ECR and CP. Biological processes unique to each disease entity were identified, such as T- and B-cell receptor signaling pathways, osteoclast differentiation, and extracellular matrix-receptor interaction for CP. Glycosaminoglycan biosynthesis, mineral absorption, and insulin signaling pathways for ECR were identified. CONCLUSIONS: This proof-of-principle in vivo study indicated that ECR has both common and unique miRNA expression profiles in comparison with CP, which are predicted to target genes regulating inflammation, immunity, and metabolism of mineralized tissues.

Comparing the diagnostic efficacy of intraoral radiography and cone beam computed tomography volume registration in the detection of mandibular alveolar bone defects.

OBJECTIVES: The aim of this study was to (1) compare bone loss detection accuracy with intraoral radiography and registered cone beam computed tomography (CBCT); (2) assess repeatability with both modalities; (3) determine factors affecting defect detection; and (4) determine the effect of buccolingual bone thickness on defect detection. STUDY DESIGN: Six observers viewed intraoral radiographs and CBCT scans before and after the defect to determine defect presence and extent. Receiver operating characteristic (ROC), sensitivity, specificity, logistic regression, odds ratio, intraclass correlation coefficient, and weighted kappa were used. RESULTS: CBCT and intraoral radiography mean ROC area under the curve values were not statistically different (0.90 vs 0.81; P = .06). CBCT had higher sensitivity compared with intraoral radiography (0.85 vs 0.63; P = .01) but similar specificity (0.91 vs 0.84; P = .45). Bone thickness, imaging modality, and observer had significant effects on defect detection (P < .001). Odds ratios for CBCT vs intraoral radiography were 2.29 for diagnostic accuracy and 1.52 for buccolingual bone thickness. There was moderate interobserver agreement for detection of defects and substantial intraobserver agreement for measurement of extent. CONCLUSIONS: CBCT showed equivalent diagnostic efficacy and specificity for defect detection and higher sensitivity compared with intraoral radiography. CBCT increases the odds of accurate defect assessment more than 2-fold compared with intraoral radiography. The odds of bone loss detection increase by approximately 50% per millimeter of buccolingual alveolar bone loss.

Penicillium gravinicasei, a new species isolated from cave cheese in Apulia, Italy.

Several species of the genus Penicillium were isolated during a survey of the mycobiota of Apulian cave cheeses ripened in a cave in Gravina di Puglia, Italy. A novel species, Penicillium gravinicasei, is described in Penicillium section Cinnamopurpurea. Its taxonomic novelty was determined using a polyphasic approach, combining phenotypic, molecular (ß-tubulin, calmodulin, ITS and DNA dependent RNA polymerase) DNA sequences and mycotoxin production data. Phylogenetic analyses of the RPB2 data showed that isolates of the novel species form a clade most closely related to Penicillium cinnamopurpureum and P. parvulum with high bootstrap support. The fungus did not produce ochratoxin A, citrinin, patulin, sterigmatocystin or aflatoxin B1 on standard agar media. The novel species had a high growth rate on agar media supplemented with 5% NaCl, and could be distinguished from other Penicillium section Cinnamopurpurea species by phenotypic and molecular characteristics.

Predictors of cut-out after cephalomedullary nail fixation of pertrochanteric fractures: a retrospective study of 813 patients.

BACKGROUND: Cut-out is the most common mechanical complication of the osteosynthesis of pertrochanteric fractures. This complication determines a significant increase in morbidity in elderly patient. Cut-out is defined as the varus collapse of the femoral head-neck fragment with the extrusion of the cephalic screw. Surgical treatment of cut-out might lead to further complications, longer rehabilitation, increased social burden and healthcare system costs. The aim of the study is to identify the predictors of cut-out to prevent its occurrence. MATERIALS AND METHODS: Study population included all patients affected by extracapsular fracture of the proximal femur who were admitted and treated with short cephalomedullary nailing at the Cattinara Hospital-ASUITS of Trieste between 2009 and 2014. A retrospective analysis of clinical and radiographic data was carried out and cut-out cases recorded. The data collected on the study population were analyzed to find an eventual correlation with the occurrence of cut-out. The independent variables were age, gender, side of the fracture, ASA class, Evans classification, nailing system, quality of reduction, TAD, CalTAD, and Parker ratio. RESULTS: The study population counted 813 cases, with an F:M ratio of 4:1 and a mean age of 84.7 years. The cut-out was recorded in 18 cases (2.2%). There was no statistically significant association between cut-out and age, sex, side of fracture, ASA class, and nailing system. The Evans classification, the quality of reduction, the TAD, the CalTAD, and the Parker's ratio demonstrated a significant correlation at univariate analysis with cut-out. The results of multivariate analysis confirmed that TAD, Parker AP, and quality of reduction were independently significantly correlated to cut-out. CONCLUSION: The results of the present study demonstrate that good quality of reduction and correct position of the lag screw are likely to decrease the risk of cut-out complication. A nomogram for cut-out prediction is proposed for clinical validation.

A polyphasic approach for characterization of a collection of cereal isolates of the Fusarium incarnatum-equiseti species complex.

DNA-based phylogenetic analyses have resolved the fungal genus Fusarium into multiple species complexes. The F. incarnatum-equiseti species complex (FIESC) includes fusaria associated with several diseases of agriculturally important crops, including cereals. Although members of FIESC are considered to be only moderately aggressive, they are able to produce a diversity of mycotoxins, including trichothecenes, which can accumulate to harmful levels in cereals. High levels of cryptic speciation have been detected within the FIESC. As a result, it is often necessary to use approaches other than morphological characterization to distinguish species. In the current study, we used a polyphasic approach to characterize a collection of 69 FIESC isolates recovered from cereals in Europe, Turkey, and North America. In a species phylogeny inferred from nucleotide sequences from four housekeeping genes, 65 of the isolates were resolved within the Equiseti clade of the FIESC, and four isolates were resolved within the Incarnatum clade. Seven isolates were resolved as a genealogically exclusive lineage, designated here as FIESC 31. Phylogenies based on nucleotide sequences of trichothecene biosynthetic genes and MALDI-TOF MS (Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry) were largely concordant with phylogeny inferred from the housekeeping gene. Finally, Liquid Chromatography (Time-Of-Flight) Mass Spectrometry [LC-(TOF-)MS(/MS)] revealed variability in mycotoxin production profiles among the different phylogenetic species investigated in this study.