Intraovarian Platelet-Rich Plasma Administration for Anovulatory Infertility: Preliminary Findings of a Prospective Cohort Study.

Background/Objectives: Infertility constitutes a significant challenge for couples around the world. Ovarian dysfunction, a major cause of infertility, can manifest with anovulatory cycles, elevated follicle-stimulating hormone levels, and diminished ovarian reserve markers such as anti-Müllerian hormone (AMH) levels or the Antral Follicle Count (AFC). Blood-derived therapies including platelet-rich plasma (PRP) have been used in fertility treatments in women with low ovarian reserve or premature ovarian insufficiency. This prospective clinical cohort study aims to assess the effects of intraovarian PRP therapy on ovarian function in women diagnosed with anovulatory cycles. Methods: The preliminary findings of this prospective cohort study are based on the first 32 patients enrolled. In this study, patients over 40 years old with anovulatory infertility were included. Venous blood samples were collected from each participant for the preparation of autologous platelet-rich plasma (PRP). Each participant received two courses of intraovarian PRP injections using a transvaginal ultrasound-guided approach. Serum levels of reproductive hormones before and after PRP intervention were measured. Results: This study's results demonstrate a significant improvement in ovarian physiology following transvaginal ultrasound-guided PRP infusion. A 75% increase in Antral Follicle Count (AFC) was observed, which was statistically significant. Furthermore, statistically significant reductions in follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin levels were observed. Serum Vitamin D 1-25 levels were substantially increased after the injection. Conclusions: These findings highlight the beneficial impact of intraovarian PRP injection in optimizing ovarian function and other metabolic parameters. However, the published literature on this subject is limited and further clinical studies should be conducted to confirm the role of intraovarian PRP in fertility treatments.

Secular Trends in Preterm Birth Rates: Uncovering the Primary Challenge for Perinatal Medicine in Greece.

INTRODUCTION: Preterm labour is a serious pregnancy complication that is the primary cause of infant mortality, with detrimental impacts on the offspring and the mother in the short as well as the long term. This study aims to comprehensively present the time trends of national preterm birth rates (PBRs) in Greece. METHODS: Official national data regarding live births in Greece were acquired from the Hellenic Statistical Authority, and the annual total PBR and rates for gestational age groups were computed per 100 total live births spanning from 1980 to 2022. Time trends were analyzed through joinpoint regression analysis, and annual percent changes (APC) and average annual percent change (AAPC) were calculated with a 95% confidence interval (95% CI). RESULTS: Following a steady decline from 4.66% in 1980 to a historic low of 2.77% in 1991 with an APC of -5.1 (-6.2 to -4.2), the PBR exhibited a dramatic increase during 1991-2011 with an APC of 7.3 (6.9 to 7.8). Subsequently, between 2011 and 2022, the rise in PBR was attenuated, showing a slight statistically non-significant upward trend (APC = 0.5, 95% CI: -0.6 to 1.5). This led to a historical high of 12.07% in 2018, 4.4 times higher than that in 1991, and eventually, the PBR reached 11.90% in 2022. From 1991 to 2022, there were sharper increases in the rates of moderate (32-33 weeks) and late (34-36 weeks) preterm births, with AAPCs of 4.9 (3.5-6.4) and 5.8 (5.3-6.3), respectively. In contrast, the rates of extremely (<28 weeks) and very (28-31 weeks) preterm births saw slower growth, with AAPCs of 2.2 (1.7-2.7) and 0.7 (0.5-1.0), respectively. CONCLUSION: The PBR in Greece more than quadrupled during 1991-2022, mainly due to increases in moderate and late preterm births. Although its rise has markedly decelerated since 2011, amidst the country's economic recession, the PBR is alarmingly higher than those in all other European and developed nations. More than one in nine neonates is born prematurely in the Greek population, posing challenges in implementing evidence-based prevention strategies and perinatal care.

Does exogenous glucocorticoid administration during pregnancy precipitate the timing of labor? A scoping review.

INTRODUCTION: To investigate whether synthetic (s) glucocorticoids (GCs) administrated between 24th and 34th gestational weeks in pre-term labor, might precipitate labor, studies upon sGCs administration were reviewed. Physiology of endogenous glucocorticoids-related increase in fetal-maternal circulation and its association with labor, followed by a scoping review with studies on exogenous sGCs administrated for fetal lung maturation and the timing of labor were included. MATERIAL AND METHODS: Methodology of systematic reviews was followed. MEDLINE, Cochrane library and Google Scholar databases were searched till October 2023, for original studies investigating administration of sGCs in pregnancies risking pre-term labor. Duplicates were removed and 1867 abstracts were excluded as irrelevant. Six controlled and four non-controlled studies were included. The index group consisted of 6001 subjects and 7691 controls in the former, while in the latter the index group consisted of 2069 subjects. RESULTS: In three out of the six controlled studies, gestational age at labor was significantly lower in sGCs-treated women than in controls, while in three studies gestational age at labor was lower in sGCs-treated women than in controls with a trend of statistical significance . In one study, gestational age at labor was significantly lower in controls than in sGCs-treated women. In the non-controlled studies, the majority of women delivered less than one week from the day of sGCs administration. CONCLUSIONS: In this scoping review, studies lack homogeneity. However, in the controlled studies, a pattern of earlier labor emerges among sGCs-treated pregnant women. The use of multiple courses of ante-natal sGCs appears to be associated to precipitated labor. Their use should be carefully weighed. Carefully designed trials should examine this still open scientific query.

The transcriptome of CD14 + CD163 - HLA-DR low monocytes predicts mortality in Idiopathic Pulmonary Fibrosis.

Rationale: The association between immune-cell-specific transcriptomic profiles and Idiopathic Pulmonary Fibrosis (IPF) mortality is unknown. Objectives: To determine immune-cell-specific transcriptomic profiles associated with IPF mortality. Methods: We profiled peripheral blood mononuclear cells (PBMC) in 18 participants [University of South Florida: IPF, COVID-19, post-COVID-19 Interstitial Lung Disease (Post-COVID-19 ILD), controls] by single-cell RNA sequencing (scRNA-seq) and identified 16 immune-cell-specific transcriptomic profiles. The Scoring Algorithm of Molecular Subphenotypes (SAMS) was used to calculate Up-scores based on these 16 gene profiles. Their association with outcomes was investigated in peripheral blood, Bronchoalveolar Lavage (BAL) and lung tissue of N=416 IPF patients from six cohorts. Findings were validated in an independent IPF, PBMC scRNA-seq dataset (N=38). Measurements and main results: Cox-regression models demonstrated that 230 genes from CD14 + CD163 - HLA-DR low circulating monocytes predicted IPF mortality [Pittsburgh (p=0.02), Chicago (p=0.003)]. PBMC proportions of CD14 + CD163 - HLA-DR low monocytes were higher in progressive versus stable IPF (Yale, 0.13±0.05 versus 0.09±0.05, p=0.034). Receiving operating characteristic identified a 230 gene, Up-score >41.84 (Pittsburgh) predictive of mortality in Chicago (HR: 6.58, 95%CI: 2.15-20.13, p=0.001) and in pooled analysis of BAL cohorts (HR: 2.20, 95%CI: 1.44-3.37, p=0.0003). High-risk patients had decreased expression of the T-cell co-stimulatory genes CD28 , ICOS , ITK and LCK (Pittsburgh and Chicago, p<0.01). 230 gene-up-scores negatively correlated with Forced Vital Capacity (FVC) in IPF lung tissues (LGRC, rho=-0.2, p=0.02). Results were replicated using a subset of 13 genes from the 230-gene signature (pooled PBMC cohorts - HR: 5.34, 95%CI: 2.83-10.06, p<0.0001). Conclusions: The transcriptome of CD14 + CD163 - HLA-DR low monocytes is associated with increased IPF mortality.

Bridging the Gap between Galectin-3 Expression and Hypertensive Pregnancy Disorders: A Narrative Review.

Galectin-3 belongs to a family of soluble glycan-binding proteins, which are increasingly recognized as modulators of pregnancy-associated processes, including proper placental development. Gestational hypertension and preeclampsia are significant complications of pregnancy, affecting millions of women annually. Despite their prevalence, the underlying pathophysiological mechanisms remain poorly understood. Several theories have been proposed, including inflammation, placental insufficiency, disturbed placental invasion, and angiogenesis. The Scopus and PubMed/MEDLINE databases were utilized until the end of May 2024. In total, 11 articles with 1011 patients, with 558 in the control group and 453 in the preeclampsia group, were included. Seven articles investigated the expression of galectin-3 (Gal-3) in placental tissue samples, eight studies calculated the serum levels of Gal-3 in maternal blood samples, while one study referred to the possible correlation of galectin-3 levels in umbilical cord blood. The results were inconsistent in both the placental tissue and maternal serum; Gal-3 placental expression was found to be statistically increased in five studies compared to that in women without gestational hypertensive disorders, while two studies either mentioned decreased expression or no difference. Similarly, the Gal-3 maternal serum levels, compared to those in women without gestational hypertensive disorders, were found to be statistically increased in five studies, while three studies did not find any statistical difference. Gal-3 can play a crucial role in the pathogenesis of preeclampsia, and its expression is influenced by gestational age and placental insufficiency. A further investigation ought to be conducted to enlighten the correlation of Gal-3 with gestational hypertension and preeclampsia development.

Laparoscopic Surgery During Pregnancy: A Meta-Review and Quality Analysis Using the Assessment of Multiple Systematic Reviews (AMSTAR) 2 Instrument.

Accumulation of experience with minimally invasive surgery over the last three decades has rendered laparoscopic surgery the mainstay of management for surgical pathology during pregnancy. In the present meta-review, we compiled the available evidence on the safety of laparoscopic and robotic-assisted surgeries during pregnancy, based on relevant systematic reviews (SR) and meta-analyses (MA). A systematic review was performed for articles published until February 2024 in English using PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online) and Google Scholar based on predefined selection and exclusion criteria. We implemented the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included SRs and MAs examining women of childbearing age (population) who had undergone laparoscopic surgery or robotic-assisted laparoscopic surgery during pregnancy (intervention). The presence of comparison to open surgery was desirable but not mandatory (comparator). The included studies should necessarily report on fetal loss (outcome), and optionally on other metrics of fetal, maternal, or operative performance. We considered SRs/MAs analyzing randomized trials, observational studies, case reports, and case series (study design). The methodological quality of SRs/MAs not exclusively including case reports and case series was assessed with the Assessment of Multiple Systematic Reviews (AMSTAR) 2 instrument. A total of 1229 articles were screened, of which 78 were potentially eligible. Of these, 33 articles met our inclusion criteria, 18 containing SRs only and 15 SRs with MA. The examined disciplines were laparoscopic appendectomy (10 studies, 30.3%), laparoscopic cerclage for cervical insufficiency (eight studies, 24.2%), adnexal-ovarian laparoscopic surgery (five studies, 15.2%), laparoscopic cholecystectomy and biliary tree exploration (three studies, 9.1%), laparoscopic myomectomy (two studies, 6.1%), and one study each for laparoscopic surgery regarding pancreatic indications, adrenal indications, and bariatric complications (3.0%). The odds ratio/relative risk for fetal loss rate ranged from 0-1.9, with variable statistical significance depending on the discipline. Twenty-three out of the 33 studies were submitted to quality evaluation with the AMSTAR 2 instrument, with three being of "low quality" (13.0%) and the remaining 20 of "critically low quality" (87.0%). In conclusion, the widespread acceptance of laparoscopic surgery for treating surgical pathology during pregnancy is substantiated by heterogeneous and low-quality evidence. Literature mainly revolves around laparoscopic appendectomy, whereas other disciplines that may commonly arise during pregnancy, such as cholecystectomy and the acute abdomen following bariatric surgery, are underrepresented in the literature. Factors such as anatomical alterations that may affect surgical access, surgeon's expertise, and the biological course of the underlying pathology should be taken into consideration when selecting the appropriate mode of operating during pregnancy.

Enhancing Ovarian Tumor Diagnosis: Performance of Convolutional Neural Networks in Classifying Ovarian Masses Using Ultrasound Images.

Background/Objectives: This study aims to create a strong binary classifier and evaluate the performance of pre-trained convolutional neural networks (CNNs) to effectively distinguish between benign and malignant ovarian tumors from still ultrasound images. Methods: The dataset consisted of 3510 ultrasound images from 585 women with ovarian tumors, 390 benign and 195 malignant, that were classified by experts and verified by histopathology. A 20% to80% split for training and validation was applied within a k-fold cross-validation framework, ensuring comprehensive utilization of the dataset. The final classifier was an aggregate of three pre-trained CNNs (VGG16, ResNet50, and InceptionNet), with experimentation focusing on the aggregation weights and decision threshold probability for the classification of each mass. Results: The aggregate model outperformed all individual models, achieving an average sensitivity of 96.5% and specificity of 88.1% compared to the subjective assessment's (SA) 95.9% sensitivity and 93.9% specificity. All the above results were calculated at a decision threshold probability of 0.2. Notably, misclassifications made by the model were similar to those made by SA. Conclusions: CNNs and AI-assisted image analysis can enhance the diagnosis and aid ultrasonographers with less experience by minimizing errors. Further research is needed to fine-tune CNNs and validate their performance in diverse clinical settings, potentially leading to even higher sensitivity and overall accuracy.

The Expression of microRNAs and Their Involvement in Recurrent Pregnancy Loss.

Background: Recurrent pregnancy loss refers to the spontaneous demise of two or more pregnancies before the 24 weeks of gestation. In almost half of the cases of recurrent miscarriages, the causes remain unknown since there is no reliable way of prognosis, early diagnosis, or treatment. Recent research has detected differential expression of certain miRNAs in reproductive system pathologies. Methods: The aim of the present review is to focus on microRNAs and their relationship with idiopathic recurrent miscarriages and to correlate miRNA expression with recurrent miscarriage and examine their potential role as biomarkers. Pubmed/Medline and Scopus databases were searched up to 31st January 2024 with terms related to recurrent pregnancy loss and miRNAs. Results: In total, 21 studies were selected for the review. A total of 75 different miRNAs were identified, showing a statistically significant differential expression. Around 40 miRNAs had increased expression, such as miR-520, miR-184 and miR-100-5p, 21 decreased, such as let-7c, and 14 had either increased or decreased expression depending on the study, such as miR-21. Conclusions: The dysregulation of miRNA expression is strongly associated with recurrent miscarriages. The circulating in the peripheral blood miRNAs, miR-100-5p and let-7c, might be utilized as biomarkers and establish a valuable non-invasive prognostic and diagnostic tool in the future.

Association between cytokine polymorphisms and recurrent pregnancy loss: A review of current evidence.

Cytokines are a type of protein that play an important role in the immune response and can also affect many physiological processes in the body. Cytokine polymorphisms refer to genetic variations or mutations that occur within the genes that code for cytokines, which may affect the level of cytokine production and function. Some cytokine polymorphisms have been associated with an increased risk of developing certain diseases, while others may be protective or have no significant effect on health. In recent years, the role of cytokine polymorphisms in the development of recurrent pregnancy loss (RPL) has been studied. RPL or miscarriage is defined as the occurrence of two or more consecutive pregnancy losses before the 20th week of gestation. There are diverse causes leading to RPL, including genetic, anatomical, hormonal, and immunological factors. With regard to cytokine polymorphisms, a few of them have been found to be associated with an increased risk of RPL, for instance, variations in the genes that code for interleukin-6, tumor necrosis factor-alpha, and interleukin-10. The exact mechanisms by which cytokine polymorphisms affect the risk of recurrent miscarriage are still being studied, and further research is essential to fully understand this complex condition. This brief review aims to summarize the recent literature on the association between cytokine polymorphisms and RPL.

The Contribution of Proteomics in Understanding Endometrial Protein Expression in Women with Recurrent Implantation Failure.

Recurrent implantation failure (RIF) poses a significant challenge in assisted reproductive technology (ART) outcomes. The endometrium plays a crucial role in embryo implantation, and its protein expression profile is integral in determining receptivity. Proteomics has emerged as a valuable tool in unraveling the molecular intricacies underlying endometrial receptivity and RIF. The aim of the present review is to analyze the contribution of proteomics to the understanding of endometrial protein expression in women with RIF, based on the results of significant proteomic studies. Medline/Pubmed databases were searched using keywords pertaining to proteomics combined with terms related to RIF. 15 studies were included in the present review. Several proteins have been found to exbibit differential expression in endometrial biopsies and fluid samples between fertile women and women with RIF during the receptive endometrial phase. The profile of endometrial proteins varied significantly among the studies. Nevertheless, similar changes in the expression levels of annexin-6, progesterone receptor, MMP-2, and MMP-9 in the endometrium of women with RIF, were found in more than one study indicating that certain proteins could potentially be effective biomarkers of endometrial receptivity. Proteomics contributes significantly to the understanding of protein expression in the endometrium of women with RIF and the analysis of proteins in endometrial fluid are promising for improving the clinical management of RIF.

Mast-cell expressed membrane protein-1 is expressed in classical monocytes and alveolar macrophages in idiopathic pulmonary fibrosis and regulates cell chemotaxis, adhesion, and migration in a TGFß-dependent manner.

Mast-cell expressed membrane protein-1 (MCEMP1) is higher in patients with idiopathic pulmonary fibrosis (IPF) with an increased risk of death. Here we aimed to establish the mechanistic role of MCEMP1 in pulmonary fibrosis. We identified increased MCEMP1 expression in classical monocytes and alveolar macrophages in IPF compared with controls. MCEMP1 is upregulated by transforming growth factor beta (TGFß) at the mRNA and protein levels in monocytic leukemia THP-1 cells. TGFß-mediated MCEMP1 upregulation results from the cooperation of SMAD3 and SP1 via concomitant binding to SMAD3/SP1 cis-regulatory elements within the MCEMP1 promoter. We also found that MCEMP1 regulates TGFß-mediated monocyte chemotaxis, adhesion, and migration. Our results suggest that MCEMP1 may regulate the migration and transition of monocytes to monocyte-derived alveolar macrophages during pulmonary fibrosis development and progression.NEW & NOTEWORTHY MCEMP1 is highly expressed in circulating classical monocytes and alveolar macrophages in IPF, is regulated by TGFß, and participates in the chemotaxis, adhesion, and migration of circulating monocytes by modulating the effect of TGFß in RHO activity.

The Effectiveness of Metabolic Bariatric Surgery in Preventing Gynecologic Cancer - from Pathophysiology to Clinical Outcomes.

Obesity and cancer represent two pandemics of current civilization, the progression of which has followed parallel trajectories. To time, thirteen types of malignancies have been recognized as obesity-related cancers, including breast (in postmenopausal women), endometrial, and ovarian cancer. Pathophysiologic mechanisms that connect the two entities include insulin resistance, adipokine imbalance, increased peripheral aromatization and estrogen levels, tissue hypoxia, and disrupted immunity in the cellular milieu. Beyond the connection of obesity to carcinogenesis at a molecular and cellular level, clinicians should always be cognizant of the fact that obesity might have secondary impacts on the diagnosis and treatment of gynecologic cancer, including limited access to effective screening programs, resistance to chemotherapy and targeted therapies, persisting lymphedema, etc. Metabolic bariatric surgery represents an attractive intervention not only for decreasing the risk of carcinogenesis in high-risk women living with obesity but most importantly as a measure to improve disease-specific and overall survival in patients with diagnosed obesity-related gynecologic malignancies. The present narrative review summarizes current evidence on the underlying pathophysiologic mechanisms, the clinical data, and the potential applications of metabolic bariatric surgery in all types of gynecologic cancer, including breast, endometrial, ovarian, cervical, vulvar, and vaginal.

Spontaneous Coronary Artery Dissection as a Cause of Acute Myocardial Infarction in COVID-19 Patients: A Case Report and Review of the Literature.

Patients with COVID-19 often experience significant cardiovascular complications, including heart failure, myocarditis, and acute coronary syndrome. We present the case of a male patient with severe COVID-19 pneumonia, complicated with inferior ST-segment elevation myocardial infarction (STEMI), which was attributed to spontaneous coronary artery dissection (SCAD). We also make a review of the literature on case reports of patients with COVID-19 and acute myocardial infarction due to SCAD. Through these clinical cases, a potential correlation between SCAD and COVID-19 infection is implied. Endothelial dysfunction, thrombotic complications, and disturbance of the vascular tone are established COVID-19 sequelae, triggered either by direct viral injury or mediated by the cytokines' storm. These abnormalities in the coronary vasculature and the vasa vasorum could result in SCAD. Moreover, disturbances of the vascular tone can cause coronary vasospasm, a reported precipitant of SCAD. Thus, SCAD should be considered in COVID-19 patients with acute coronary syndrome (ACS), and in the case of STEMI, an early angiographic evaluation, if feasible, should be performed rather than thrombolysis to avoid potential adverse events of the latter in the setting of SCAD.

Investigating the Association of Assisted Reproduction Techniques and Adverse Perinatal Outcomes.

BACKGROUND: Infertility affects about 80 million individuals worldwide and 10-15% of couples at reproductive age will seek medical assistance. There is increasing evidence that pregnancies after Assisted Reproduction Techniques (ART) are associated with pre-term birth, low birthweight, congenital defects, and increased mortality rates. The aim of this review is to assess all the published literature and provide an updated review on the effect of assisted conception and perinatal and neonatal outcomes. METHODS: Comprehensive research on Pubmed/Medline, Scopus, and Google scholar electronic databases was conducted from July 2023 up to September 2023, using the terms assisted reproductive techniques, ART, in vitro fertilization, IVF, intracytoplasmic sperm injection, ICSI, preterm birth, PTB, low birth weight, LBW, chromosomal defects, congenital defects, and hypospadias. In total, 87 full text articles were retrieved and after a careful evaluation, 31 studies were selected for data extraction. RESULTS: Our review demonstrated a higher risk of congenital and chromosomal defects, and a higher incidence of male genital tract defects and heart defects in ART pregnancies. Regarding pre-term birth, our results were contradictory. CONCLUSIONS: Although assisted reproduction techniques are associated with increased risks, they are safe regarding perinatal outcomes and couples should not be discouraged from utilizing them. Our results aim to alert clinicians to these specific outcomes and offer more personalized care and counseling to infertile couples and their children.

Bronchoscopy-related outbreaks and pseudo-outbreaks: A systematic review.

OBJECTIVE: To identify and report the pathogens and sources of contamination associated with bronchoscopy-related outbreaks and pseudo-outbreaks. DESIGN: Systematic review. SETTING: Inpatient and outpatient outbreaks and pseudo-outbreaks after bronchoscopy. METHODS: PubMed/Medline databases were searched according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, using the search terms "bronchoscopy," "outbreak," and "pseudo-outbreak" from inception until December 31, 2022. From eligible publications, data were extracted regarding the type of event, pathogen involved, and source of contamination. Pearson correlation was used to identify correlations between variables. RESULTS: In total, 74 studies describing 23 outbreaks and 52 pseudo-outbreaks were included in this review. The major pathogens identified in these studies were Pseudomonas aeruginosa, Mycobacterium tuberculosis, nontuberculous mycobacteria (NTM), Klebsiella pneumoniae, Serratia marcescens, Stenotrophomonas maltophilia, Legionella pneumophila, and fungi. The primary sources of contamination were the use of contaminated water or contaminated topical anesthetics, dysfunction and contamination of bronchoscopes or automatic endoscope reprocessors, and inadequate disinfection of the bronchoscopes following procedures. Correlations were identified between primary bronchoscope defects and the identification of P. aeruginosa (r = 0.351; P = .002) and K. pneumoniae (r = 0.346; P = .002), and between the presence of a contaminated water source and NTM (r = 0.331; P = .004) or L. pneumophila (r = 0.280; P = .015). CONCLUSIONS: Continued vigilance in bronchoscopy disinfection practices remains essential because outbreaks and pseudo-outbreaks continue to pose a significant risk to patient care, emphasizing the importance of stringent disinfection and quality control measures.

Detection of GSTM1-null Genotype in Women Undergoing IVF Treatment.

BACKGROUND: Glutathione S-transferase (GST) M1 belongs to a family of detoxification enzymes and deficiency in enzyme activity is due to a homozygous deletion of the GSTM1 gene. Several studies reveal a possible correlation between female infertility and GSTM1 polymorphisms. The aim of this study is to investigate the effect of the GSTM1-null polymorphism in female infertility as well as in IVF parameters. METHODS: In the study group 125 women were classified as infertile according to WHO and 49 women with at least one successful pregnancy and no miscarriages, as control group. Genomic DNA from blood samples was isolated and PCR amplification was applied to determine the presence of GSTM1-null genotype. RESULTS: Data analysis demonstrated a statistically significant higher presence of GSTM1-null variant in the infertile group compared to the control group. In a subgroup analysis of the infertile group, the estradiol levels, the number of fertilized oocytes as well as the number and the quality of the cumulus-oocyte complex, were statistically significant higher in women detected with the wildtype of GSTM1 gene compared to those who had the GSTM1 null genotype (deletion). CONCLUSIONS: Our study results propose a possible involvement of GMST1 in female infertility and may help elucidate possible interactions between the microenvironment of oocytes and the oxidative stress.

Coexistence of Autoimmune Pulmonary Alveolar Proteinosis With Small Cell Lung Cancer in a Man Presenting With Acute Onset Respiratory Failure.

A 60-year-old man was referred to our Respiratory Department with progressive dyspnea on exertion and productive cough over the past two months. High-resolution computed tomography showed diffuse ground glass opacities with superimposed interlobular and intralobular septal thickening mainly in the middle and lower lobes, compatible with crazy paving pattern. Serology tests revealed positive antibody transcriptional intermediary factor-γ1 (TIF-1γ) in myositis panel and bronchoalveolar lavage revealed milky appearance and positive periodic acid-Schiff (PAS) stain. Pulmonary function tests showed moderate reduction in diffusing capacity for carbon monoxide. The working diagnosis of autoimmune pulmonary alveolar proteinosis was established by high detectable levels of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies. Despite clinical and radiological improvement following treatment with whole lung lavage and inhaled sargramostim, patient's follow-up chest computed tomography revealed an enlargement of lower left paratracheal lymph node 4L. Endobronchial ultrasound bronchoscopy (EBUS) biopsy was compatible with small cell lung cancer (SCLC). Chemotherapeutic agents were promptly administrated, with no adverse events up until now.

Association between COVID-19 Infection and Miscarriages, What We Really Know?

BACKGROUND: COVID-19 is a modern worldwide pandemic that affected and continues to affect millions of people around the world. Since the discovery that angiotensin-converting enzyme 2 (ACE2) is the binding site for COVID-19 to achieve cell entry, there has been a continuous debate about the effect of COVID-19 infection in first and second trimester abortions. The aim of this review is to investigate the impact of COVID-19 infection on the incidence of miscarriage. Furthermore, we seek to identify potential pathophysiological mechanisms of early pregnancy loss present in infected women. METHODS: A literature review was conducted on different databases, including PubMed, Google Scholar, Ovid, Science Direct, Scopus, and Cochrane library, between 1 January 2020 and 31 August 2023. A total of 364 articles were identified and 32 articles were ultimately included in the review. RESULTS: There are several case studies that provide evidence that early pregnancy loss is associated with COVID-19 infection. These findings are not further confirmed by the majority of systematic reviews and meta-analyses, which demonstrate that the total number of miscarriages do not differ significantly between infected and non-infected groups. Furthermore, there are also case reports that associate COVID-19 infection with late second trimester abortions. CONCLUSIONS: Given that the virus persists globally, it is important to gain a better understanding of its associated risks in the reproductive process, and larger, more homogeneous, and controlled studies are required to obtain more robust data that can be meta-analyzed to obtain an overview of this potential relationship.

Expression of PD-1/PD-L1 axis in mediastinal lymph nodes and lung tissue of human and experimental lung fibrosis indicates a potential therapeutic target for idiopathic pulmonary fibrosis.

BACKGROUND: Mediastinal lymph node enlargement is prevalent in patients with idiopathic pulmonary fibrosis (IPF). Studies investigating whether this phenomenon reflects specific immunologic activation are lacking. METHODS: Programmed cell death-1 (PD-1)/ programmed cell death ligand-1 (PD-L1) expression in mediastinal lymph nodes and lung tissues was analyzed. PD-1, PD-L1 mRNA expression was measured in tracheobronchial lymph nodes of mice following bleomycin-induced injury on day 14. Finally, the effect of the PD-1 inhibitor, pembrolizumab, in bleomycin-induced pulmonary fibrosis was investigated. RESULTS: We analyzed mediastinal lymph nodes of thirty-three patients (n = 33, IPF: n = 14, lung cancer: n = 10, concomitant IPF and lung cancer: n = 9) and lung tissues of two hundred nineteen patients (n = 219, IPF: 123, controls: 96). PD-1 expression was increased, while PD-L1 expression was decreased, in mediastinal lymph nodes of patients with IPF compared to lung cancer and in IPF lungs compared to control lungs. Tracheobronchial lymph nodes isolated on day 14 from bleomycin-treated mice exhibited increased size and higher PD-1, PD-L1 mRNA levels compared to saline-treated animals. Pembrolizumab blunted bleomycin-induced lung fibrosis, as indicated by reduction in Ashcroft score and improvement in respiratory mechanics. CONCLUSIONS: Mediastinal lymph nodes of patients with IPF exhibit differential expression profiles than those of patients with lung cancer indicating distinct immune-mediated pathways regulating fibrogenesis and carcinogenesis. PD-1 expression in mediastinal lymph nodes is in line with lung tissue expression. Lower doses of pembrolizumab might exert antifibrotic effects. Clinical trials aiming to endotype patients based on mediastinal lymph node profiling and accordingly implement targeted therapies such as PD-1 inhibitors are greatly anticipated.