Pulmonary arterial hypertension (PAH) from autopsy study: T-cells, B-cells and mastocytes detection as morphological evidence of immunologically mediated pathogenesis.

Background: Pulmonary arterial hypertension (PAH) is characterized by severe vascular remodelling, resulting in increased pulmonary vascular resistance with cardiac hypertrophy and heart failure. However, the diagnosis of PAH is often inaccurate. Many cases of PAH are incorrectly diagnosed or missed, and they are often associated with death. The aim of this study was to verify the morphological and histological criteria of fatal cases of PAH and evaluate the lymphocytic populations associated to lesions with reactive neo-angiogenesis. Methods: Pulmonary lung sections from 10 cases of sudden unexpected death (SUD) in the absence of previously diagnosed diseases and in an apparent state of well-being, with final histological post autopsy diagnosis of PAH were collected. The pathological findings were compared using ten controls from non-pathological lung from deaths from other causes. The autopsies included 4 males (40%) and 6 females (60%) with an average age of 52.1 ± 10.1 years. Sections stained with hematoxylin and eosin (H&E) were revised for a morphological diagnosis. Subsequently, serial sections were performed and stained with immunohistochemistry for anti-CD20 (B-lymphocytes), anti-CD3 (T-lymphocytes), anti-CD4 (T-helper lumphocytes), anti-CD8 (T-cytotoxic lymphocytes) and anti-CD117/C-Kit (mast cells/MCs) to detect inflammatory infiltrate and different ratios of cell-type. Statistical analysis was conducted using a paired t-test looking at 100 cells in 3 different tissue samples representative of vascular lesion and 3 different random normal lung parenchyma fields without lesion (from 10 normal control lungs), to identify specific lymphocyte subpopulations in inflammatory infiltrates. Results: There was a significant percentage increase of CD20 (p < 0.001), CD8 (p = 0.002), CD4 (p < 0.001), and CD117/C-Kit positive (C-Kit+; p < 0.001) cells mainly detected around wall vessels; while increased MCs positivity and C-Kit+ were observed especially in alveolar septa. In addition, reactive angiomatosis was observed. Conclusions: The inflammatory infiltrate should be included for a correct diagnosis of PAH besides the vascular remodelling. The inflammatory infiltrate seems to be implicated as a main factor in the pathogenesis. This finding is important to rule out secondary pulmonary hypertension, to identify SUDs of unknown causes and to add new elements to the literature that can explain the immunologically related pathogenesis of PAH

First-line erlotinib and fixed dose-rate gemcitabine for advanced pancreatic cancer

AIM: To investigate activity, toxicity, and prognostic factors for survival of erlotinib and fixed dose-rate gemcitabine (FDR-Gem) in advanced pancreatic cancer. METHODS: We designed a single-arm prospective, multicentre, open-label phase II study to evaluate the combination of erlotinib (100 mg/d, orally) and weekly FDR-Gem (1000 mg/m2, infused at 10 mg/m2per minute) in a population of previously untreated patients with locally advanced, inoperable, or metastatic pancreatic cancer. Primary endpoint was the rate of progression-free survival at 6 mo (PFS-6); secondary endpoints were overall response rate (ORR), response duration, tolerability, overall survival (OS), and clinical benefit. Treatment was not considered to be of further interest if the PFS-6 was < 20% (p0 = 20%), while a PFS-6 > 40% would be of considerable interest (p1 = 40%); with a 5% rejection error (α = 5%) and a power of 80%, 35 fully evaluable patients with metastatic disease were required to be enrolled in order to complete the study. Analysis of prognostic factors for survival was also carried out. RESULTS: From May 2007 to September 2009, 46 patients were enrolled (male/female: 25/21; median age: 64 years; median baseline carbohydrate antigen 19-9 (CA 19-9): 897 U/mL; locally advanced/metastatic disease: 5/41). PFS-6 and median PFS were 30.4% and 14 wk (95%CI: 10-19), respectively; 1-year and median OS were 20.2% and 26 wk (95%CI: 8-43). Five patients achieved an objective response (ORR: 10.9%, 95%CI: 1.9-19.9); disease control rate was 56.5% (95%CI: 42.2-70.8); clinical benefit rate was 43.5% (95%CI: 29.1-57.8). CA 19-9 serum levels were decreased by > 25% as compared to baseline in 14/23 evaluable patients (63.6%). Treatment was well-tolerated, with skin rash being the most powerful predictor of both longer PFS (P < 0.0001) and OS (P = 0.01) at multivariate analysis (median OS for patients with or without rash: 42 wk vs 15 wk, respectively, Log-rank P = 0.03). Additional predictors of better outcome were: CA 19-9 reduction, female sex (for PFS), and good performance status (for OS). CONCLUSION: Primary study endpoint was not met. However, skin rash strongly predicted erlotinib efficacy, suggesting that a pharmacodynamic-based strategy for patient selection deserves further investigation

Strategies and Controversies in the Treatment With Carbon Dioxide Laser of Laryngeal Hemangioma: A Case Series and Review of the Literature

Introduction: The hemangioma is the most common vascular tumor, involving the head and neck in 60% of cases. It is rare in the larynx. In children, hemangiomas are more frequent on the subglottis, whereas in adults the most common site is the supraglottis. Laryngeal hemangioma with cavernous features isolated to the free edge of the vocal fold is a very rare clinical finding. We present 2 cases of glottic hemangioma. Both patients reported severe hoarseness. Cases: In the first patient, an extensive blue-purple mass was seen on the right vocal cord. The patient was posted for microlaryngeal surgery with carbon dioxide (CO2) laser. Second patient had a large, smooth, flesh-colored polypoid mass emanating from the left vocal cord. The patient was posted for microlaryngeal surgery. After 2 months, both patients showed a considerable voice improvement. Discussion: Vocal cord hemangiomas are very rare, and they usually cause problem in the voice of the patient. A vascular lesion that may mimic a hemangioma may sometimes result from an organizing hematoma following a hemorrhage on the vocal cords due to voice abuse. Laryngeal hemangiomas also need to be distinguished pathologically from polypoidal vascular granulation tissue that may be produced by laryngeal biopsy, intubation, or trauma. Indirect endoscopy is enough to diagnosis. No active treatment is advised for adult laryngeal hemangiomas unless the lesions are symptomatic or show a tendency to involve other parts. There is no uniformly accepted treatment of head and neck hemangiomas. Surgical excision with laser CO2 microlaryngoscopic techniques gives satisfactory results

Fear of missing out (FoMO) and internet use: A comprehensive systematic review and meta-analysis.

FoMO has been considered a predisposing factor toward excessive internet use, and a great deal of literature has investigated the link between FoMO and internet use. However, there is still a lack of cohesion in the literature. The current study have been conducted and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). In the current systematic review and meta-analysis of 86 effect-sizes, representative of 55,134 participants (Mean age = 22.07, SD = 6.15, females = 58.37%), we found that the strength of the trait FoMO- internet use association significantly varies from r = 0.11 to r = 0.63. In some populations, FoMO appears to increase with age and it is reverse in other populations. Facebook use was unrelated to FoMO in some populations, and higher FoMO was linked with stopping Instagram use for some individuals. The FoMO- internet use association was independent of their severity, as the interaction was not significant, and this association was neither linear nor curvilinear. The FoMO-internet use association does not appear to be associated with depressive, anxiety, and stress symptoms or level of life satisfaction. The COVID-19 pandemic was the only significant moderator of the FoMO-internet use association, strengthening this relationship. FoMO demonstrates a considerable role in internet use; however, there is no evidence of interaction or bi-directional association between the mentioned. Overall, we still don't know what factors contribute to individuals exhibiting distinct patterns in the FoMO-internet use association

The Metacognitions about Binge Eating Questionnaire (MBEQ): investigation of the association between specific metacognitions and Binge Eating Disorder

Literature suggested that metacognitions are involved in eating problems and may be relevant to the understanding of Binge Eating Disorder (BED). The goal of the current studies was to develop the first self-report instrument on metacognitions about binge eating. In Study 1, a community sample completed the Metacognitions about Binge Eating Questionnaire (MBEQ); an Exploratory Factor Analysis (EFA) was performed. In study 2, a community sample completed the MBEQ and measures assessing severity of binge eating, irrational food beliefs, anxiety, depression, impulsiveness. A Confirmatory Factor Analysis (CFA) was performed. Concurrent and incremental validity were assessed. In study 3, a clinical sample of participants with a diagnosis of BED completed the MBEQ and other measures. Bivariate correlational analysis and hierarchical linear regression were performed. Participants from the general population and participants with a diagnosis of BED were compared. EFA and CFA supported a two-factor solution consisting of positive and negative metacognitions about binge eating. Concurrent and incremental validity were acceptable. The metacognitions factors correlated positively with anxiety, depression, irrational food beliefs, impulsiveness in the community sample, and anxiety, irrational food beliefs, impulsiveness in clinical sample. The metacognitions factors contributed to the prediction of binge eating disorders symptoms, in community and clinical samples, over and above age, gender, impulsiveness, anxiety, depression, irrational food beliefs. The MBEQ possesses good psychometric properties and appears a reliable and valid measure of positive and negative metacognitions about binge eating. Metacognitions about binge eating could be a therapeutic target to reduce the severity of binge eating episodes

Radiological features of knee joint synovial chondromatosis

Synovial chondromatosis (SC) is a rare condition with a very variable clinical presentation, thus making the diagnosis not immediate. We report a case of massive primary SC of the knee, properly evaluated with X-rays, ultrasonography and magnetic resonance imaging and successfully treated with an arthroscopic approach

Circulating levels of adipose products and differences in fat distribution in the ovulatory and anovulatory phenotypes of polycystic ovary syndrome.

Central fat distribution is increased in anovulatory women with polycystic ovary syndrome (PCOS) compared with ovulatory PCOS and matched controls. Among secreted adipocytokines, this is reflected mainly in lower levels of adiponectin