Induction of a different immune response in non-titanized compared to titanized polypropylene meshes.

It is well known that pelvic organ prolapse (POP) significantly reduces the quality of life of affected women and in many cases requires corrective surgery. Aim of the study was to compare the immune response against titanized versus non-titanized meshes, especially macrophage polarization and immune checkpoint association. For this, we analyzed 644 POP surgeries, which were performed between 2017 and 2022, in our department. Four of them needed revision surgery caused by erosion. We analyzed the influx of CD68 & CD163 positive macrophages and the expression of immune checkpoint molecules PD-L1 and PD1 in these 4 patients. We identified a large number of CD68 and CD163 positive macrophages and additionally a PD-L1 expression of these cells. Based on the in-vivo results, we isolated monocytes and co-cultivated monocytes with different mesh material covered with or without fibroblasts. We identified a significantly enhanced macrophage activation and PD-L1 expression in macrophages surrounding non-titanized polypropylene mesh material. Encapsulation of the material by fibroblasts was crucial for that. Specifically, CD68-positive macrophages are upregulated (p < 0.001), co-expressing PD-L1 (p < 0.001) in monocytes co-cultivated with non-titanized polypropylene meshes. Monocytes co-cultivated with titanized polypropylene meshes showed significantly lower expression of CD163 (p = 0.027) and PD-L1 (p = 0.022). In conclusion, our in vitro data suggest that the titanium coating leads to a decreased polarization of macrophages and to a decreased immune response compared to non-titanized meshes. This could be an indication for the increased incidence of erosion of the non-titanized meshes, which is a severe complication of this procedure and requires revision surgery. STATEMENT OF SIGNIFICANCE: Pelvic organ prolapse is a well-known problem for women and often requires corrective surgery. Polypropylene meshes are often used, which differ in their coating (titanized vs. non-titanized). A severe side effect of these surgeries is mesh erosion, due to onset of inflammation, which requires revision surgery. We examined all erosion cases (4 of 644 patients) with implanted nontitanium-coated meshes by immunohistochemistry and found upregulation of macrophage polarization (as markers CD68 and CD163) and increased expression of the immune checkpoint molecules PD-L1 and PD1. This suggests inflammatory processes and an enhanced immune response. In addition, we set up an in vitro experiment to investigate whether coating plays a role. Here, we demonstrated that the non-titanized meshes elicited a significantly higher immune response in comparison to titanized meshes, which could lead to the higher erosion rate of the non-titanized meshes. Our results highlight the benefit of titanized meshes, which should lead to a lower revision surgery rate and thus improved patient outcome.

High viral loads: what drives fatal cases of COVID-19 in vaccinees? - an autopsy study.

The rate of SARS-CoV-2 infections in vaccinees has become a relevant serious issue. This study aimed to determine the causes of death, histological organ alteration, and viral spread in relation to demographic, clinical-pathological, viral variants, and vaccine types for deceased individuals with proven SARS-CoV-2 infection after vaccination who died between January and November 2021. Twenty-nine consecutively collected cases were analyzed and compared to 141 nonvaccinated control cases. Autopsies were performed on 16 partially and 13 fully vaccinated individuals. Most patients were elderly and suffered from several relevant comorbidities. Real-time RT-PCR (RT-qPCR) identified a significantly increased rate of generalized viral dissemination within organ systems in vaccinated cases versus nonvaccinated cases (45% vs. 16%, respectively; P = 0.008) mainly with Ct-values of higher than 25 in non-respiratory samples. However, vaccinated cases also showed high viral loads, reaching Ct-values below 10, especially in the upper airways and lungs. This was accompanied by high rates of pulmonal bacterial or mycotic superinfections and the occurrence of immunocompromising factors, such as malignancies, immunosuppressive drug intake, or decreased immunoglobulin levels. All these findings were particularly accentuated in partially vaccinated patients compared to fully vaccinated individuals. The virus dissemination observed in our case study may indicate that patients with an impaired immune system have a decreased ability to eliminate the virus. However, the potential role of antibody-dependent enhancement must also be ruled out in future studies. Fatal cases of COVID-19 in vaccinees were rare and often associated with severe comorbidities or other immunosuppressive conditions.

IgG4-related pseudotumours: a series of 12 cases and a review of the literature.

IgG4-related pseudotumours (IgG4-RPT) represent a distinctive manifestation in the broad spectrum of IgG4-related diseases (IgG4-RD). Due to their wide morphology and rarity, IgG4-RPTs represent a diagnostic challenge in the differential between reactive lesions and a fibrous soft tissue tumours. Thus, our aim was to characterise our cases and review the literature, focusing on the macroscopic and microscopic features of the lesions. In this paper, we summarise the possible presentations and histomorphological features of IgG4-RPT based on data collected from the literature and from cases at our institute and provide an overview of the pathogenesis and histological characteristics based on the knowledge accumulated in recent years. We collected surgical cases with a diagnosis of IgG4-RPT over the period 2013-2020 at two centres and analysed their macroscopic, histological, and immunohistochemical profiles. Furthermore, we performed a literature research in the MEDLINE and EBSCO databases regarding case reports and studies with the explicit diagnosis of IgG4-RPT. Our cases consist of nine men and three women, with an average age of 60±14 years, representing about 0.05% of the lesions evaluated at the two departments. The involved sites include the kidney, lung, gallbladder, pterygopalatine fossa, spleen, tongue, mediastinum, and submandibular gland. Grossly, nine lesions showed sharp margins. On histological examination, all the lesions showed an abundant inflammatory infiltrate with lymphocytes and IgG4-positive plasma cells as well as characteristic fibroblastic storiform proliferation. The literature search revealed 266 cases and similar histomorphological features in 23 locations. In 30 of these cases (11%), IgG4-RPTs were multifocal. IgG4-RPT are exceedingly rare lesions, which makes them challenging to diagnose. They can affect different sites, and the histomorphological presentation may differ.

Diagnostic Accuracy and Post-Procedural Complications Associated with Ultrasound-Guided Core Needle Biopsy in the Preoperative Evaluation of Parotid Tumors.

Correct diagnosis of a parotid neoplasm based on histology preoperatively is of utmost importance in order to guide patient management. The aim of this study was to evaluate the diagnostic accuracy of an ultrasound-guided core needle biopsy of a parotid lesion and to describe associated post-procedural complications. A retrospective study was conducted between January 2015 and March 2021 of all patients who were referred to a tertiary care center for evaluation of a parotid lesion and who underwent core needle biopsy due to high-risk features or when malignancy was suspected on clinical examination or ultrasonography. Patient characteristics, histological findings, and post-procedural complications were recorded and evaluated. Among 890 patients referred for evaluation of a parotid lesion, in 138 patients a core needle biopsy was undertaken. On the basis of core needle biopsy findings, 11 lymphomas and 82 non-lymphoma malignancies were diagnosed in the parotid gland. The sensitivity of the core needle biopsy predicting the accurate tumor type was 97.56% (95% CI 91.47-99.70%) and the specificity 94.64% (95% CI 85.13-98.88%). The accuracy for the correct histopathological diagnosis was 93.48% (95% CI 87.98-96.97%). Post-procedural minor complications occurred in 19 patients (13.8%). In conclusion, a core needle biopsy can identify malignancy in the parotid gland with high sensitivity and specificity in a safe manner and therefore guide surgical treatment.