Xanthogranulomatous oophoritis mimicking a dermoid cyst with ovarian torsion: A case report and review of the literature.

Xanthogranulomatous oophoritis (XO) is a rare pseudotumor representing a destructive chronic inflammatory process often mistaken for malignancy or tubo-ovarian abscess. Xanthogranulomatous inflammation is most commonly seen in the kidneys and gallbladder and very rarely affects the genitourinary system. Definitive treatment is with surgical removal of affected tissue. This report presents the case of a 42-year-old woman with an 8 cm complex right adnexal cyst concerning for a dermoid cyst presenting with intermittent torsion. Final pathology after right salpingo-oophorectomy demonstrated xanthogranulomatous oophoritis. This case is of clinical significance for distinguishing the condition from common benign pathology or cancer since the recommended surgical procedure is different than for a dermoid cyst or malignancy. Correct identification of the condition is crucial for appropriate treatment and to avoid unnecessary morbid procedures if the mass is mistaken for malignancy or future repeat surgery if mistaken for a dermoid cyst or other common benign condition. This case documents the presentation of xanthogranulomatous oophoritis masquerading as a dermoid cyst for a condition with very few reported cases worldwide.

Impact of Hypoxia on Neutrophil Degranulation and Inflammatory Response in Alpha-1 Antitrypsin Deficiency Patients.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is an inflammatory disorder where neutrophils play a key role. Excessive neutrophil activation leads to local hypoxia and tissue damage. Most research on neutrophil function has been conducted under atmospheric conditions (21% O2), which may not represent physiological or pathological conditions. This study aimed to determine the effects of hypoxia on neutrophil degranulation and cytokine production in AATD patients. METHODS: Neutrophils isolated from 54 AATD patients (31 MZ; 8 SZ; 15 ZZ) and 7 controls (MM) were exposed to hypoxia (1% O2) for 4 h. Neutrophil degranulation was assessed by measuring elastase (NE), myeloperoxidase (MPO), lactoferrin, and matrix metalloproteinase-9 (MMP-9) levels using immunoassay-based methods. Pro-inflammatory (IL-8, IL-1 beta, IL-6, and TNF-alpha) and anti-inflammatory (IL-4 and IL-10) cytokine levels were assessed by a Luminex-based method. RESULTS: Our results indicate a significantly increased release of NE (p = 0.015), MPO (p = 0.042), lactoferrin (p = 0.015), and MMP-9 (p = 0.001) compared to controls. Pro-inflammatory cytokines show a significant rise in IL-8 (p = 0.019), a trend towards increased IL-1 beta (p = 0.3196), no change in IL-6 (p = 0.7329), and reduced TNF-alpha (p = 0.006). Anti-inflammatory cytokines show increased IL-4 (p = 0.057) and decreased IL-10 (p = 0.05703). CONCLUSIONS: Increased neutrophil degranulation and inflammatory phenotype are observed in AATD neutrophils under physiological hypoxia.

Hypoxia Enhances Oxidative Stress in Neutrophils from ZZ Alpha-1 Antitrypsin Deficiency Patients.

Alpha-1 antitrypsin deficiency (AATD) is a neutrophilic inflammatory disorder that may result in local hypoxia, reactive oxygen and nitrogen species (ROS/RNS) production, and increased damage in adjacent tissues. This study aims to determine the impact of hypoxia on neutrophil oxidative stress profile in AATD patients. Neutrophils were isolated from AATD patients and control volunteers and exposed to hypoxia (1% O2 for 4 h), ROS/RNS, mitochondrial parameters, and non-enzymatic antioxidant defenses measured by flow cytometry. The expression of enzymatic antioxidant defenses was determined by qRT-PCR. Our results indicate that ZZ-AATD neutrophils produce higher amounts of hydrogen peroxide, peroxynitrite, and nitric oxide and decreased levels of the antioxidant enzymes catalase, superoxide dismutase, and glutathione reductase. Likewise, our results show a decrease in mitochondrial membrane potential, indicating that this organelle could be involved in the production of the reactive species observed. No decrease in glutathione and thiol levels were observed. The accumulation of substances with high oxidative capacity would explain the greater oxidative damage observed in proteins and lipids. In conclusion, our results indicate that, compared to MM control individuals, ZZ-AATD neutrophils show increased ROS/RNS production under hypoxic conditions opening a new rationale for using antioxidant therapies to treat the disease.

Difficult Questions With Many Gray Areas: Nuanced Abortion Attitudes Among Physicians.

INTRODUCTION: Abortion is a polarizing social and medical issue, even among physicians. Though the public may expect physicians to hold purely scientific attitudes about abortion, their attitudes and behaviors are just as strongly informed by social and political factors as the public's. In a recent survey study of physicians at an academic medical center about their abortion attitudes, most reported strong support for abortion access. However, more were unwilling to consult in abortion-related cases, and many perceived little or no professional connection to abortion and were reticent to publicly advocate for their position. METHODS: In order to investigate the nuances in physicians' abortion attitudes, we analyzed the open-ended, qualitative responses provided by physicians at the end of a quantitative survey using modified concept mapping procedures and theme generation. RESULTS: Two hundred twenty-two open-ended responses resulted in 487 data units. We categorized respondents' comments into 2 main groups: attempts to depersonalize, or distance oneself, from abortion and expressions of nuance or ambivalence about abortion. Ambivalence and nuance in abortion attitudes centered around multiple factors that varied from individual to structural. CONCLUSIONS: Our findings support previous literature suggesting that physicians' abortion attitudes are not binary and add that nuanced attitudes may be perceived as unwelcome. Acknowledging ambivalence and addressing physicians' tendency to depersonalize abortion could result in more honest, open, and nuanced discourse and contribute to addressing structural issues that result in poor health outcomes, achieving broader reproductive justice goals, and greater access to abortion services.

Correction: Magallon et al. Oxidative Stress and Endoplasmic Reticulum Stress in Rare Respiratory Diseases. J. Clin. Med. 2021, 10, 1268.

Sara Pastor was not included as an author in the original publication [...].

Oxidative Stress and Endoplasmic Reticulum Stress in Rare Respiratory Diseases.

Several studies have shown that some rare respiratory diseases, such as alpha-1 antitrypsin deficiency (AATD), idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF), and primary ciliary dyskinesia (PCD) present oxidative stress (OS) and endoplasmic reticulum (ER) stress. Their involvement in these pathologies and the use of antioxidants as therapeutic agents to minimize the effects of OS are discussed in this review.

New Laboratory Protocol to Determine the Oxidative Stress Profile of Human Nasal Epithelial Cells Using Flow Cytometry.

Several studies have shown the importance of oxidative stress (OS) in respiratory disease pathogenesis. It has been reported that the nasal epithelium may act as a surrogate for the bronchial epithelium in several respiratory diseases involving OS. However, the sample yields obtained from nasal biopsies are modest, limiting the number of parameters that can be determined. Flow cytometry has been widely used to evaluate cellular OS profiles. It has the advantage that analyses can be performed using a small amount of sample. Therefore, we aimed to set up a new method based on flow cytometry to assess the oxidative profile of human nasal epithelial cells which could be used in research on respiratory diseases. Levels of total nitric oxide, superoxide anion, peroxynitrite, and intracellular peroxides were measured. Reduced thiol levels, such as antioxidant-reduced glutathione and oxidative damaged lipids and proteins, were also analysed. The intracellular calcium levels, plasma membrane potential, apoptosis, and percentage of live cells were also studied. Finally, a strategy to evaluate the mitochondrial function, including mitochondrial hydrogen peroxide, superoxide anion, mitochondrial mass, and membrane potential, was set up. Using small amounts of sample and a non-invasive sampling technique, the described method enables the measurement of a comprehensive set of OS parameters in nasal epithelial cells, which could be useful in research on respiratory diseases.

Gene Therapy in Rare Respiratory Diseases: What Have We Learned So Far?

Gene therapy is an alternative therapy in many respiratory diseases with genetic origin and currently without curative treatment. After five decades of progress, many different vectors and gene editing tools for genetic engineering are now available. However, we are still a long way from achieving a safe and efficient approach to gene therapy application in clinical practice. Here, we review three of the most common rare respiratory conditions-cystic fibrosis (CF), alpha-1 antitrypsin deficiency (AATD), and primary ciliary dyskinesia (PCD)-alongside attempts to develop genetic treatment for these diseases. Since the 1990s, gene augmentation therapy has been applied in multiple clinical trials targeting CF and AATD, especially using adeno-associated viral vectors, resulting in a good safety profile but with low efficacy in protein expression. Other strategies, such as non-viral vectors and more recently gene editing tools, have also been used to address these diseases in pre-clinical studies. The first gene therapy approach in PCD was in 2009 when a lentiviral transduction was performed to restore gene expression in vitro; since then, transcription activator-like effector nucleases (TALEN) technology has also been applied in primary cell culture. Gene therapy is an encouraging alternative treatment for these respiratory diseases; however, more research is needed to ensure treatment safety and efficacy.

Alpha-1 antitrypsin deficiency: outstanding questions and future directions.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition that leads to decreased circulating alpha-1 antitrypsin (AAT) levels, significantly increasing the risk of serious lung and/or liver disease in children and adults, in which some aspects remain unresolved. METHODS: In this review, we summarise and update current knowledge on alpha-1 antitrypsin deficiency in order to identify and discuss areas of controversy and formulate questions that need further research. RESULTS: 1) AATD is a highly underdiagnosed condition. Over 120,000 European individuals are estimated to have severe AATD and more than 90% of them are underdiagnosed. CONCLUSIONS: 2) Several clinical and etiological aspects of the disease are yet to be resolved. New strategies for early detection and biomarkers for patient outcome prediction are needed to reduce morbidity and mortality in these patients; 3) Augmentation therapy is the only specific approved therapy that has shown clinical efficacy in delaying the progression of emphysema. Regrettably, some countries reject registration and reimbursement for this treatment because of the lack of larger randomised, placebo-controlled trials. 4) Alternative strategies are currently being investigated, including the use of gene therapy or induced pluripotent stem cells, and non-augmentation strategies to prevent AAT polymerisation inside hepatocytes.

Proceedings of the 2nd BEAT-PCD conference and 3rd PCD training school: part 1.

Primary ciliary dyskinesia (PCD) is a rare heterogenous condition that causes progressive suppurative lung disease, chronic rhinosinusitis, chronic otitis media, infertility and abnormal situs. 'Better Experimental Approaches to Treat Primary Ciliary Dyskinesia' (BEAT-PCD) is a network of scientists and clinicians coordinating research from basic science through to clinical care with the intention of developing treatments and diagnostics that lead to improved long-term outcomes for patients. BEAT-PCD activities are supported by EU funded COST Action (BM1407). The second BEAT-PCD conference, and third PCD training school were held jointly in April 2017 in Valencia, Spain. Presentations and workshops focussed on advancing the knowledge and skills relating to PCD in: basic science, epidemiology, diagnostic testing, clinical management and clinical trials. The multidisciplinary conference provided an interactive platform for exchanging ideas through a program of lectures, poster presentations, breakout sessions and workshops. Three working groups met to plan consensus statements. Progress with BEAT-PCD projects was shared and new collaborations were fostered. In this report, we summarize the meeting, highlighting developments made during the meeting.

Una visión inmunológica del déficit de alfa 1 antitripsina / No disponible

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Atypical squamous metaplasia in a benign cystic thyroid nodule mimicking high-grade carcinoma.

Squamous metaplasia (SM) occurs in a variety of thyroid conditions, both neoplastic and non-neoplastic. In a small subset of benign thyroid lesions, SM can create a diagnostic pitfall by mimicking a malignant process. Here, we describe the case of a 52-year-old male with a 1.5 cm right thyroid nodule. Ultrasound-guided fine-needle aspiration biopsy showed markedly atypical, mitotically active epithelial cells which were suspicious for high-grade carcinoma. Resection of the nodule demonstrated a follicular adenoma with cystic changes and atypical SM of the cyst-lining component. As illustrated here, SM of the thyroid represents an important diagnostic pitfall for the cytopathologist, and should be included in the differential diagnosis of thyroid nodules, particularly those with potentially benign cystic changes.