DNA repair protein DNA-PK protects PC12 cells from oxidative stress-induced apoptosis involving AKT phosphorylation.

BACKGROUND: Emerging evidence suggest that DNA-PK complex plays a role in the cellular response to oxidative stress, in addition to its function of double strand break (DSB) repair. In this study we evaluated whether DNA-PK participates in oxidative stress response and whether this role is independent of its function in DNA repair. METHODS AND RESULTS: We used a model of H2O2-induced DNA damage in PC12 cells (rat pheochromocytoma), a well-known neuronal tumor cell line. We found that H2O2 treatment of PC12 cells induces an increase in DNA-PK protein complex levels, along with an elevation of DNA damage, measured both by the formation of γΗ2ΑX foci, detected by immunofluorescence, and γH2AX levels detected by western blot analysis. After 24 h of cell recovery, γΗ2ΑX foci are repaired both in the absence and presence of DNA-PK kinase inhibitor NU7026, while an increase of apoptotic cells is observed when DNA-PK activity is inhibited, as revealed by counting pycnotic nuclei and confirmed by FACS analysis. Our results suggest a role of DNA-PK as an anti-apoptotic factor in proliferating PC12 cells under oxidative stress conditions. The anti-apoptotic role of DNA-PK is associated with AKT phosphorylation in Ser473. On the contrary, in differentiated PC12 cells, were the main pathway to repair DSBs is DNA-PK-mediated, the inhibition of DNA-PK activity causes an accumulation of DNA damage. CONCLUSIONS: Taken together, our results show that DNA-PK can protect cells from oxidative stress induced-apoptosis independently from its function of DSB repair enzyme.

Detection of Pathological Markers of Neurodegenerative Diseases following Microfluidic Direct Conversion of Patient Fibroblasts into Neurons.

Neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are clinically diagnosed using neuropsychological and cognitive tests, expensive neuroimaging-based approaches (MRI and PET) and invasive and time-consuming lumbar puncture for cerebrospinal fluid (CSF) sample collection to detect biomarkers. Thus, a rapid, simple and cost-effective approach to more easily access fluids and tissues is in great need. Here, we exploit the chemical direct reprogramming of patient skin fibroblasts into neurons (chemically induced neurons, ciNs) as a novel strategy for the rapid detection of different pathological markers of neurodegenerative diseases. We found that FAD fibroblasts have a reduced efficiency of reprogramming, and converted ciNs show a less complex neuronal network. In addition, ciNs from patients show misfolded protein accumulation and mitochondria ultrastructural abnormalities, biomarkers commonly associated with neurodegeneration. Moreover, for the first time, we show that microfluidic technology, in combination with chemical reprogramming, enables on-chip examination of disease pathological processes and may have important applications in diagnosis. In conclusion, ciNs on microfluidic devices represent a small-scale, non-invasive and cost-effective high-throughput tool for protein misfolding disease diagnosis and may be useful for new biomarker discovery, disease mechanism studies and design of personalised therapies.

Post-Acute Sequelae of COVID-19 Pneumonia: Six-month Chest CT Follow-up.

Background The long-term post-acute pulmonary sequelae of COVID-19 remain unknown. Purpose To evaluate lung injury in patients affected by COVID-19 pneumonia at the 6-month follow-up CT examination compared with the baseline chest CT examination. Materials and Methods From March 19, 2020, to May 24, 2020, patients with moderate to severe COVID-19 pneumonia who had undergone baseline chest CT were prospectively enrolled at their 6-month follow-up. The CT qualitative findings, semiquantitative Lung Severity Score (LSS), and the well-aerated lung volume at quantitative chest CT (QCCT) analysis were analyzed. The performance of the baseline LSS and QCCT findings for predicting fibrosis-like changes (reticular pattern and/or honeycombing) at the 6-month follow-up chest CT examination was tested by using receiver operating characteristic curves. Univariable and multivariable logistic regression analyses were used to test clinical and radiologic features that were predictive of fibrosis-like changes. The multivariable analysis was performed with clinical parameters alone (clinical model), radiologic parameters alone (radiologic model), and the combination of clinical and radiologic parameters (combined model). Results One hundred eighteen patients who had undergone baseline chest CT and agreed to undergo follow-up chest CT at 6 months were included in the study (62 women; mean age, 65 years ± 12 [standard deviation]). At follow-up chest CT, 85 of 118 (72%) patients showed fibrosis-like changes and 49 of 118 (42%) showed ground-glass opacities. The baseline LSS (>14) and QCCT findings (≤3.75 L and ≤80%) showed excellent performance for predicting fibrosis-like changes at follow-up chest CT. In the multivariable analysis, the areas under the curve were 0.89 (95% CI: 0.77, 0.96) for the clinical model, 0.81 (95% CI: 0.68, 0.9) for the radiologic model, and 0.92 (95% CI: 0.81, 0.98) for the combined model. Conclusion At 6-month follow-up chest CT, 72% of patients showed late sequelae, in particular fibrosis-like changes. The baseline Lung Severity Score and the well-aerated lung volume at quantitative chest CT (QCCT) analysis showed excellent performance for predicting fibrosis-like changes at the 6-month chest CT (area under the curve, >0.88). Male sex, cough, lymphocytosis, and the well-aerated lung volume at QCCT analysis were significant predictors of fibrosis-like changes at 6 months, demonstrating an inverse correlation (area under the curve, 0.92). © RSNA, 2021 See also the editorial by Wells and Devaraj in this issue.

Gene signature and immune cell profiling by high-dimensional, single-cell analysis in COVID-19 patients, presenting Low T3 syndrome and coexistent hematological malignancies.

BACKGROUND: Low T3 syndrome is frequent in patients admitted to intensive care units for critical illness and pneumonia. It has been reported also in patients with COVID-19, Hodgkin disease and chronic lymphocytic leukemia. We analyzed the clinical relevance of Low T3 syndrome in COVID-19 patients and, in particular, in those with associated hematological malignancies. METHODS: Sixty-two consecutive patients, hospitalized during the first wave of SARS-CoV-2 outbreak in Sant'Andrea University Hospital in Rome, were subdivided in 38 patients (Group A), showing low levels of FT3, and in 24 patients (Group B), with normal FT3 serum values. During the acute phase of the disease, we measured serum, radiologic and clinical disease severity markers and scores, in search of possible correlations with FT3 serum values. In addition, in 6 COVID-19 patients, 4 with Low T3 syndrome, including 2 with a hematological malignancy, and 2 with normal FT3 values, we performed, high-dimensional single-cell analysis by mass cytometry, multiplex cytokine assay and gene expression profiling in peripheral blood mononuclear cells (PBMC). RESULTS: Low FT3 serum values were correlated with increased Absolute Neutrophil Count, NLR and dNLR ratios and with reduced total count of CD3+, CD4+ and CD8+ T cells. Low FT3 values correlated also with increased levels of inflammation, tissue damage and coagulation serum markers as well as with SOFA, LIPI and TSS scores. The CyTOF analysis demonstrated reduction of the effector memory and terminal effector subtypes of the CD4+ T lymphocytes. Multiplex cytokine assay indicates that mainly IL-6, IP-10 and MCAF changes are associated with FT3 serum levels, particularly in patients with coexistent hematological malignancies. Gene expression analysis using Nanostring identified four genes differently expressed involved in host immune response, namely CD38, CD79B, IFIT3 and NLRP3. CONCLUSIONS: Our study demonstrates that low FT3 serum levels are associated with severe COVID-19. Our multi-omics approach suggests that T3 is involved in the immune response in COVID-19 and coexistent hematological malignancy and new possible T3 target genes in these patients have been identified.

Circulating Vitamin D levels status and clinical prognostic indices in COVID-19 patients.

BACKGROUND: Several immune mechanisms activate in COVID-19 pathogenesis. Usually, coronavirus infection is characterized by dysregulated host immune responses, interleukine-6 increase, hyper-activation of cytotoxic CD8 T lymphocytes. Interestingly, Vitamin D deficiency has been often associated with altered immune responses and infections. In the present study, we evaluated Vitamin D plasma levels in patients affected with different lung involvement during COVID-19 infection. METHODS: Lymphocyte phenotypes were assessed by flow cytometry. Thoracic CT scan involvement was obtained by an image analysis program. RESULTS: Vitamin D levels were deficient in (80%) of patients, insufficient in (6.5%) and normal in (13.5%). Patients with very low Vitamin D plasma levels had more elevated D-Dimer values, a more elevated B lymphocyte cell count, a reduction of CD8 + T lymphocytes with a low CD4/CD8 ratio, more compromised clinical findings (measured by LIPI and SOFA scores) and thoracic CT scan involvement. CONCLUSIONS: Vitamin D deficiency is associated with compromised inflammatory responses and higher pulmonary involvement in COVID-19 affected patients. Vitamin D assessment, during COVID-19 infection, could be a useful analysis for possible therapeutic interventions. TRIAL REGISTRATION: 'retrospectively registered'.

Quantitative Chest CT analysis in discriminating COVID-19 from non-COVID-19 patients.

INTRODUCTION: COVID-19 pneumonia is characterized by ground-glass opacities (GGOs) and consolidations on Chest CT, although these CT features cannot be considered specific, at least on a qualitative analysis. The aim is to evaluate if Quantitative Chest CT could provide reliable information in discriminating COVID-19 from non-COVID-19 patients. MATERIALS AND METHODS: From March 31, 2020 until April 18, 2020, patients with Chest CT suggestive for interstitial pneumonia were retrospectively enrolled and divided into two groups based on positive/negative COVID-19 RT-PCR results. Patients with pulmonary resection and/or CT motion artifacts were excluded. Quantitative Chest CT analysis was performed with a dedicated software that provides total lung volume, healthy parenchyma, GGOs, consolidations and fibrotic alterations, expressed both in liters and percentage. Two radiologists in consensus revised software analysis and adjusted areas of lung impairment in case of non-adequate segmentation. Data obtained were compared between COVID-19 and non-COVID-19 patients and p < 0.05 were considered statistically significant. Performance of statistically significant parameters was tested by ROC curve analysis. RESULTS: Final population enrolled included 190 patients: 136 COVID-19 patients (87 male, 49 female, mean age 66 ± 16) and 54 non-COVID-19 patients (25 male, 29 female, mean age 63 ± 15). Lung quantification in liters showed significant differences between COVID-19 and non-COVID-19 patients for GGOs (0.55 ± 0.26L vs 0.43 ± 0.23L, p = 0.0005) and fibrotic alterations (0.05 ± 0.03 L vs 0.04 ± 0.03 L, p < 0.0001). ROC analysis of GGOs and fibrotic alterations showed an area under the curve of 0.661 (cutoff 0.39 L, 68% sensitivity and 59% specificity, p < 0.001) and 0.698 (cutoff 0.02 L, 86% sensitivity and 44% specificity, p < 0.001), respectively. CONCLUSIONS: Quantification of GGOs and fibrotic alterations on Chest CT could be able to identify patients with COVID-19.

Chest CT Features of COVID-19 in Rome, Italy.

Background The standard for diagnosis of severe acute respiratory syndrome coronavirus 2 is a reverse transcription polymerase chain reaction (RT-PCR) test, but chest CT may play a complimentary role in the early detection of Coronavirus Disease 2019 (COVID-19) pneumonia. Purpose To investigate CT features of patients with COVID-19 in Rome, Italy, and to compare the accuracy of CT with that of RT-PCR. Materials and Methods In this prospective study from March 4, 2020, until March 19, 2020, consecutive patients suspected of having COVID-19 infection and respiratory symptoms were enrolled. Exclusion criteria were contrast material-enhanced chest CT performed for vascular indications, patients who refused chest CT or hospitalization, and severe CT motion artifact. All patients underwent RT-PCR and chest CT. Diagnostic performance of CT was calculated using RT-PCR as the reference standard. Chest CT features were calculated in a subgroup of patients with positive RT-PCR and CT findings. CT features of hospitalized patients and patients in home isolation were compared using the Pearson χ2 test. Results The study population included 158 consecutive participants (83 male, 75 female; mean age, 57 years ± 17 [standard deviation]). Of the 158 participants, fever was observed in 97 (61%), cough was observed in 88 (56%), dyspnea was observed in 52 (33%), lymphocytopenia was observed in 95 (60%), increased C-reactive protein level was observed in 139 (88%), and elevated lactate dehydrogenase level was observed in 128 (81%). Sensitivity, specificity, and accuracy of CT were 97% (95% confidence interval [CI]: 88%, 99%) (60 of 62), 56% (95% CI: 45%, 66%) (54 of 96), and 72% (95% CI: 64%, 78%) (114 of 158), respectively. In the subgroup of 58 participants with positive RT-PCR and CT findings, ground-glass opacities were present in all 58 (100%), both multilobe and posterior involvement were present in 54 (93%), bilateral pneumonia was present in 53 (91%), and subsegmental vessel enlargement (>3 mm) was present in 52 (89%). Conclusion The typical pattern of COVID-19 pneumonia in Rome, Italy, was peripheral ground-glass opacities with multilobe and posterior involvement, bilateral distribution, and subsegmental vessel enlargement (>3 mm). Chest CT had high sensitivity (97%) but lower specificity (56%). © RSNA, 2020.

Mir-370-3p Impairs Glioblastoma Stem-Like Cell Malignancy Regulating a Complex Interplay between HMGA2/HIF1A and the Oncogenic Long Non-Coding RNA (lncRNA) NEAT1.

Glioblastoma (GBM) is the most aggressive and prevalent form of a human brain tumor in adults. Several data have demonstrated the implication of microRNAs (miRNAs) in tumorigenicity of GBM stem-like cells (GSCs). The regulatory functions of miRNAs in GSCs have emerged as potential therapeutic candidates for glioma treatment. The current study aimed at investigating the function of miR-370-3p in glioma progression, as aberrant expression of miR-370-3p, is involved in various human cancers, including glioma. Analyzing our collection of GBM samples and patient-derived GSC lines, we found the expression of miR-370-3p significantly downregulated compared to normal brain tissues and normal neural stem cells. Restoration of miR-370-3p expression in GSCs significantly decreased proliferation, migration, and clonogenic abilities of GSCs, in vitro, and tumor growth in vivo. Gene expression analysis performed on miR-370-3p transduced GSCs, identified several transcripts involved in Epithelial to Mesenchymal Transition (EMT), and Hypoxia signaling pathways. Among the genes downregulated by the restored expression of miR-370-3p, we found the EMT-inducer high-mobility group AT-hook 2 (HMGA2), the master transcriptional regulator of the adaptive response to hypoxia, Hypoxia-inducible factor (HIF)1A, and the long non-coding RNAs (lncRNAs) Nuclear Enriched Abundant Transcript (NEAT)1. NEAT1 acts as an oncogene in a series of human cancers including gliomas, where it is regulated by the Epidermal Growth Factor Receptor (EGFR) pathways, and contributes to tumor growth and invasion. Noteworthy, the expression levels of miR-370-3p and NEAT1 were inversely related in both GBM tumor specimens and GSCs, and a dual-luciferase reporter assay proved the direct binding between miR-370-3p and the lncRNAs NEAT1. Our results identify a critical role of miR-370-3p in the regulation of GBM development, indicating that miR-370-3p acts as a tumor-suppressor factor inhibiting glioma cell growth, migration and invasion by targeting the lncRNAs NEAT1, HMGA2, and HIF1A, thus, providing a potential candidate for GBM patient treatment.

Nicotine Changes Airway Epithelial Phenotype and May Increase the SARS-COV-2 Infection Severity.

(1) Background: Nicotine is implicated in the SARS-COV-2 infection through activation of the α7-nAChR and over-expression of ACE2. Our objective was to clarify the role of nicotine in SARS-CoV-2 infection exploring its molecular and cellular activity. (2) Methods: HBEpC or si-mRNA-α7-HBEpC were treated for 1 h, 48 h or continuously with 10-7 M nicotine, a concentration mimicking human exposure to a cigarette. Cell viability and proliferation were evaluated by trypan blue dye exclusion and cell counting, migration by cell migration assay, senescence by SA-ß-Gal activity, and anchorage-independent growth by cloning in soft agar. Expression of Ki67, p53/phospho-p53, VEGF, EGFR/pEGFR, phospho-p38, intracellular Ca2+, ATP and EMT were evaluated by ELISA and/or Western blotting. (3) Results: nicotine induced through α7-nAChR (i) increase in cell viability, (ii) cell proliferation, (iii) Ki67 over-expression, (iv) phospho-p38 up-regulation, (v) EGFR/pEGFR over-expression, (vi) increase in basal Ca2+ concentration, (vii) reduction of ATP production, (viii) decreased level of p53/phospho-p53, (ix) delayed senescence, (x) VEGF increase, (xi) EMT and consequent (xii) enhanced migration, and (xiii) ability to grow independently of the substrate. (4) Conclusions: Based on our results and on evidence showing that nicotine potentiates viral infection, it is likely that nicotine is involved in SARS-CoV-2 infection and severity.

The Clinical and Radiological Examination of Acute Intimate Partner Violence Injuries: A Retrospective Analysis of an Italian Cohort of Women.

BACKGROUND: Intimate partner violence (IPV) is the most frequent type of violence against women. We compared clinical and radiological IPV characteristics to stranger assault (SA). METHODS: We retrospectively identified 123 women with IPV from court reports and matched them to 124 SA. Clinical and radiological characteristics were evaluated by testing their sensitivity, specificity, positive and negative predictive value for IPV, and the strength of their association with IPV. RESULTS: IPV women referred with more delay to the emergency department (ED), had more ED accesses, and showed more mismatch between reports to the triage and disclosures to the ED physician. They also displayed more head, neck, and face injuries, and new-plus-old fractures. CONCLUSION: The identification of specific features may help ED physicians to suspect IPV.

Histologic Analysis of Idiopathic Pulmonary Fibrosis by Morphometric and Fractal Analysis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disorder, ultimately leading to respiratory failure and death. Despite great research advances in understanding the mechanisms underlying the disease, its diagnosis, and its treatment, IPF still remains idiopathic without known biological or histological markers able to predict disease progression or response to treatment. The histologic hallmark of IPF is usual interstitial pneumonia (UIP), with its intricate architectural distortion and temporal inhomogeneity. We hypothesize that normal lung alveolar architecture can be compared to fractals, such as the Pythagoras tree with its fractal dimension (Df), and every pathological insult, distorting the normal lung structure, could result in Df variations. In this study, we aimed to assess the UIP histologic fractal dimension in relationship to other morphometric parameters in newly diagnosed IPF patients and its possible role in the prognostic stratification of the disease. Clinical data and lung tissue specimens were obtained from twelve patients with IPF, twelve patients with non-specific interstitial pneumonia (NSIP), and age-matched "healthy" control lung tissue from patients undergoing lung surgery for other causes. Histology and histomorphometry were performed to evaluate Df and lacunarity measures, using the box counting method on the FracLac ImageJ plugin. The results showed that Df was significantly higher in IPF patients compared to controls and fibrotic NSIP patients, indicating greater architectural distortion in IPF. Additionally, high Df values were associated with higher fibroblastic foci density and worse prognostic outcomes in IPF, suggesting that Df may serve as a potential novel prognostic marker for IPF. The scalability of Df measurements was demonstrated through repeated measurements on smaller portions from the same surgical biopsies, which were selected to mimic a cryobiopsy. Our study provides further evidence to support the use of fractal morphometry as a tool for quantifying and determining lung tissue remodeling in IPF, and we demonstrated a significant correlation between histological and radiological Df in UIP pattern, as well as a significant association between Df and FF density. Furthermore, our study demonstrates the scalability and self-similarity of Df measurements across different biopsy types, including surgical and smaller specimens.

Psycho-cognitive assessment and quality of life in older adults with chronic obstructive pulmonary disease-carrying the rs4713916 gene polymorphism (G/A) of gene FKBP5 and response to pulmonary rehabilitation: a proof of concept study.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary and extra-pulmonary multi-morbidity including depression, anxiety and cognitive disorders. Several studies investigated the association of the FKBP5 gene polymorphisms with susceptibility to anxiety, depression, and behavioral disorders. The FKBP5 gene codifies the FKBP51 protein which modulates the glucocorticoid receptor in the adaptive stress response. Genetic variants of the FKBP5 gene have been associated to a higher risk of developing mental disorders. We analyzed the association of genetic variants and stress exposure investigating the susceptibility to psychological distress and the impact on cognitive balance and quality of life (QoL) of COPD patients carrying the rs4713916 polymorphism (G/A) and we examined its association, with COPD rehabilitative outcomes. MATERIALS AND METHODS: A pilot study evaluated cognitive, psychological, clinical alterations/disorders, QoL, and coping strategies in 70 older adults with COPD, undergoing pulmonary rehabilitation, stratified according to the FKBP5 rs4713916 genotype (GG or GA). RESULTS: Carriers of rs4713916 polymorphisms (G/A) show better cognitive performances, a higher degree of independence in the daily living activities, better QoL, no presence of depressive mood and anxiety symptoms, no family history of psychiatric disorders, more ability to cope with stressors by avoiding emotions but demanding emotional support, and lesser use of anti-anxiety, anti-depressant, anti-psychotic, hypnotic-sedative drugs. No difference was found in the number of comorbidities. CONCLUSION: These results offer valuable insights into the role of FKBP5 in the complex network of mechanisms associated to clinical, psychological and behavioral features of COPD patients.

Challenges in Diagnosis and Clinical Management of COVID-19 in Patient with B-Cell Chronic Lymphocytic Leukemia (CLL): Report of One Case.

We report here a case of a patient affected by B-cell chronic lymphocytic leukemia (CLL) that developed COVID-19 during the actual SARS-CoV-2 outbreak. The coexistence of CLL and COVID-19 raises many questions regarding the possible increased risk of developing COVID-19 among patients with CLL, the problems in managing therapies for both diseases and, above all, the difficulties in diagnosing COVID-19 in patients affected by CLL. In our patient, an 84-year-old man, the recognition of COVID-19 was delayed because of its atypical clinical presentation and technical problems related to the methods used for the diagnosis. Based on the symptoms and the radiological aspect of the lung, the occurrence of COVID-19 was suspected. Repeated tests on oro/nasopharyngeal swabs gave negative results, causing a delay in the diagnosis. Moreover, different methods used to identify the SARS-CoV-2 antibodies in serum gave conflicting results, and only two tests were able to identify SARS-CoV-2 Abs of the IgG type. During the clinical course of unrecognized COVID-19, our patient developed severe complications and did not receive any specific treatment for the two diseases. Recognition of COVID-19 in patients with CLL is a challenging task and the most accurate methods are necessary to overcome the diagnostic difficulties encountered.

Exogenous lipoid pneumonia induced by nasal decongestant.

INTRODUCTION: Lipoid pneumonia is a clinical condition that may be initially asymptomatic or confused with an infectious or malignant lung disease. OBJECTIVES: We report four cases of this pathological condition. METHODS: The first case concerned an 85-year old woman with bilateral confluent pulmonary opacities, ground-glass type. Diagnosis was based on the cytology of the bronchoalveolar lavage (BAL) fluid followed by its ultrastructural examination. The second case was a 47-year-old man with an isolated pulmonary nodule, which was surgically removed; the diagnosis of lipoid pneumonia was formulated on the basis of the histological and electron microscopy examination. The third case concerned a 73-year-old woman, with bilateral hypodense areas at the bases of the lungs where FDG PET/CT scan showed an increased uptake. Diagnosis was formulated by BAL cytology and electron microscopy examination. The fourth case was a 69-year-old man, who performed a virtual colonoscopy for diverticulosis putting in evidence a round mass (3 cm in diameter) with two small peripheral nodules, located in the pulmonary left lower lobe. The histopathological examination of transthoracic biopsy confirmed a lipoid pneumonia. RESULTS AND CONCLUSION: In all four cases, it was put in evidence a prolonged use of a nasal decongestant containing mineral oils. In literature, the most cases described are characterized by a subclinical evolution and were presented as ground glass opacities which evolve, in the later phases, in an interstitial involvement or in a peripheral mass, simulating a lung tumour.

Immunopathogenesis of ocular allergy: a schematic approach to different clinical entities.

PURPOSE OF REVIEW: The immunopathogenesis of ocular allergic disorders is generally related to the specific immunoglobulin E-mediated mast cell activation and the following cascade of inflammatory mediators. Seasonal and perennial allergic conjunctivitis, however, are the only ocular diseases to involve solely type I hypersensitivity. The other main forms, vernal and atopic keratoconjunctivitis, have a more complex immunological basis and a chronic inflammatory component. Involvement of inflammatory cells, particularly eosinophils and T cells, cytokines and proteases can lead to more serious corneal damage with vision-threatening potential. RECENT FINDINGS: Experimental allergic conjunctival models and clinical research studies have shown that T helper type 2-related mechanisms are definitely involved in the sensitization phase of ocular allergy, however, both T helper type 1 and type 2 cytokines are overexpressed in the active disease, contributing to the development of ocular inflammation. SUMMARY: A review of the recent literature allows us to better understand the mechanisms involved in the development of ocular allergy and to guide us toward a more schematic approach, which could possibly be useful in forming a new classification, standardizing clinical phases and individuating new treatment targets.

The appropriate management of an appendiceal mucocele.

Appendicectomy is one of the most commonly performed surgical procedures. Appendiceal mucocele is a relative rare disease, but appropriate management is critical. Indeed, the intact removal of a mucocele represents a curative treatment; conversely, a rupture may result in the spread of epithelial cells throughout the peritoneal cavity (pseudomyxoma peritonei). We report a case of a 61-year-old woman, admitted to our department, who underwent resection of an appendiceal mucocele, focusing, in the discussion, on the clinical and surgical management of this disease.

True thymic hyperplasia associated with thymic hemorrhage in an adult patient.

A case of true thymic hyperplasia (TTH) associated with thymic hemorrhage (TH) was observed in a 22-year-old male patient who presented with persistent cough and thoracic pain due to an anterior mediastinal mass. The diagnosis of TTH was supported by the observation that the mediastinal mass was essentially composed of histologically normal thymic lobules with preserved cortico-medullary differentiation. The TTH tissue presented multiple areas of hemorrhage associated with the presence of large, tortuous, abnormal vessels in the thymic stroma. Foci of spindle cell proliferations resembling an epitheliod hemangioma were also seen. This finding raises the possibility that vascular malformations, perhaps due to an abnormal growth of the thymus, may be responsible for some cases of TH associated with TTH.