miR-21, miR-29a, and miR-106b: serum and tissue biomarkers with diagnostic potential in metastatic testicular cancer.

The imperative need for sensitive and precise tools is underscored in cancer diagnostics, with biomarkers playing a pivotal role in facilitating early detection and tumor diagnosis. Despite their classical pathological classification, testicular tumors lack valuable markers, emphasizing the necessity to identify and apply serum tumor markers in clinical management. Unfortunately, existing biomarkers exhibit limited sensitivities and specificities. Recent years have witnessed the discovery of novel RNA molecules, presenting a potential breakthrough as diagnostic tools and promising biomarkers. This report presents compelling evidence supporting the detection of early testicular cancer by applying a set of nine microRNAs (miRNAs), establishing them as valuable serum biomarkers for diagnosis. We developed a standardized serum-based measurement protocol and conducted comprehensive statistical analyses on the dataset to underscore the diagnostic accuracy of the miRNA pool. Notably, with a sensitivity exceeding 93%, miR-21, miR-29a, and miR-106b surpass classical serum tumor markers in the context of testicular cancer. Specifically, these miRNAs are poised to enhance clinical decision-making in testicular cancer detection and hold the potential for assessing tumor growth in monitoring chemotherapy outcomes.

Snus Use in Adolescents: A Threat to Oral Health.

Background: Snus consumption is increasingly popular, mainly among the youth, due to the promotion of the tobacco industry and the lack of knowledge regarding its adverse effects. Even though some of its systemic complications are common knowledge, the oral consequences are rarely known. Aim: Therefore, the objective of this study is to evaluate the oral health effects of snus consumption among a highly exposed group of adolescent athletes. Design: Participants received an interactive presentation, followed by interviews and dental screenings by young doctors to establish trust. They were categorized into groups based on the frequency of snus usage. The oral hygiene habits and status, snus consumption habits, and awareness about its adverse effects were evaluated. Results: Statistically significantly (p < 0.05), more regular snus users experience gum bleeding while tooth brushing than nonusers (60% and 37%, p = 0.004). Snus consumption and poor oral hygiene have a cumulative effect on oral health. Some young athletes experience ulcerous oral mucosal lesions coinciding with snus placement. Nonusers exhibit greater awareness of the adverse effects of snus than regular users (27% and 49%). Conclusions: Regular snus use negatively affects oral health, especially the gums. Early education is of the utmost importance in preventing snus usage by raising awareness.

Computer-assisted open exposure of palatally impacted canines for orthodontic eruption: A randomized clinical trial.

OBJECTIVE: This randomized clinical trial aimed to assess the feasibility of computer-assisted open exposure of palatally impacted canines. MATERIALS AND METHODS: Patients aged 11-30 years who required orthodontic eruption for the full palatal impaction of their canines were included in this study. Exclusion criteria were psychosocial and dental contraindications of orthodontic treatment, congenital craniofacial disorders, and trauma in the patient's history in the vicinity of the surgical site. Virtual planning software was used to register the intraoral scans and cone-beam computed tomography data and to design a surgical template. In the test group, exposure of the canines was guided by a surgical template, whereas in the control group, the surgeon relied on the surgical plan to localize the impacted canine. The success of the intervention, duration of surgery, and complications, including excessive hemorrhage, damage to the canine or neighboring anatomical landmarks, and postoperative inflammation of the surgical site were assessed. Postoperative pain was reported by the patients using the visual analog pain scale (VAS). RESULTS: Surgery was deemed successful in all patients in both groups. During healing, no complications were observed. The duration of surgery decreased significantly in the test group (4 min 45.1 s ± 1 min 8.4 s) compared to that in the control group (7 min 22.3 s ± 56.02 s). No statistically significant differences were observed between the VAS scores of the two study groups. CONCLUSIONS: The application of virtual planning and static navigation is a viable approach for the open exposure of palatally impacted canines. CLINICAL TRIAL REGISTRATION NUMBER: NCT05909254. CLINICAL SIGNIFICANCE: Computer-assisted surgery is a feasible method for open exposure of palatally impacted canines, which decreases the duration of surgery compared to the freehand method.

Prognostic potential of CUL3 ligase with differential roles in luminal A and basal type breast cancer tumors.

Breast cancer is a prevalent and significant cause of mortality in women, and manifests as six molecular subtypes. Its further histologic classification into non-invasive ductal or lobular carcinoma (DCIS) and invasive carcinoma (ILC or IDC) underscores its heterogeneity. The ubiquitin-proteasome system plays a crucial role in breast cancer, with inhibitors targeting the 26S proteasome showing promise in clinical treatment. The Cullin-RING ubiquitin ligases, including CUL3, have direct links to breast cancer. This study focuses on CUL3 as a potential biomarker, leveraging high-throughput sequencing, gene expression profiling, experimental and data analysis tools. Through comprehensive analysis using databases like GEPIA2 and UALCAN, as well as TCGA datasets, CUL3's expression and its association with prognostic values were assessed. Additionally, the impact of CUL3 overexpression was explored in MCF-7 and MDA-MB-231 breast cancer cell lines, revealing distinct differences in molecular and phenotypic characteristics. We further profiled its expression and localization in breast cancer tissues identifying prominent differences between luminal A and TNBC tumors. Conclusively, CUL3 was found to be associated with cell cycle progression, and DNA damage response, exhibiting diverse roles depending on the tumor's molecular type. It exhibits a tendency to act as an oncogene in triple-negative tumors and as a tumor suppressor in luminal A types, suggesting a potential significance in breast cancer progression and therapeutic directions.

Are Artificial Intelligence-Assisted Three-Dimensional Histological Reconstructions Reliable for the Assessment of Trabecular Microarchitecture?

Objectives: This study aimed to create a three-dimensional histological reconstruction through the AI-assisted classification of tissues and the alignment of serial sections. The secondary aim was to evaluate if the novel technique for histological reconstruction accurately replicated the trabecular microarchitecture of bone. This was performed by conducting micromorphometric measurements on the reconstruction and comparing the results obtained with those of microCT reconstructions. Methods: A bone biopsy sample was harvested upon re-entry following sinus floor augmentation. Following microCT scanning and histological processing, a modified version of the U-Net architecture was trained to categorize tissues on the sections. Detector-free local feature matching with transformers was used to create the histological reconstruction. The micromorphometric parameters were calculated using Bruker's CTAn software (version 1.18.8.0, Bruker, Kontich, Belgium) for both histological and microCT datasets. Results: Correlation coefficients calculated between the micromorphometric parameters measured on the microCT and histological reconstruction suggest a strong linear relationship between the two with p-values of 0.777, 0.717, 0.705, 0.666, and 0.687 for BV/TV, BS/TV, Tb.Pf Tb.Th, and Tb.Sp, respectively. Bland-Altman and mountain plots suggest good agreement between BV/TV measurements on the two reconstruction methods. Conclusions: This novel method for three-dimensional histological reconstruction provides researchers with a tool that enables the assessment of accurate trabecular microarchitecture and histological information simultaneously.

Routine molecular applications and recent advances in breast cancer diagnostics.

Cancer stands as one of the most common and lethal diseases, imposing a substantial burden on global mortality rates. Breast cancer is distinct from other forms of cancer in which it is the primary cause of death for women. Early detection of breast cancer can significantly lower the risk of mortality, improving the prognosis for those who are affected. The death rate of breast cancer has been steadily rising, according to epidemiological data, especially since the COVID-19 pandemic. This emphasizes the necessity of sensitive and precise technologies that can be utilized in early breast cancer diagnosis. In this process, biomarkers play a pivotal role by facilitating the early detection and diagnosis of breast cancer. Currently, a wide variety of cancer biomarkers have been identified, improving the accuracy of cancer diagnosis. These biomarkers can be applied in liquid biopsies as well as on solid tissues. In the context of breast cancer, biomarkers are particularly valuable for determining who is predisposed to the disease, predicting prognosis at the time of diagnosis, and selecting the best course of therapy. This review comprehensively explores the recently developed gene-based biomarkers from biofluids that are used in the context of breast cancer, as well as the conventional and cutting-edge techniques that have been employed for breast cancer diagnosis.

Predictive Potential of RNA Polymerase B (II) Subunit 1 (RPB1) Cytoplasmic Aggregation for Neoadjuvant Chemotherapy Failure.

We aimed to investigate the contribution of co-translational protein aggregation to the chemotherapy resistance of tumor cells. Increased co-translational protein aggregation reflects altered translation regulation that may have the potential to buffer transcription under genotoxic stress. As an indicator for such an event, we followed the cytoplasmic aggregation of RPB1, the aggregation-prone largest subunit of RNA polymerase II, in biopsy samples taken from patients with invasive carcinoma of no special type. RPB1 frequently aggregates co-translationally in the absence of proper HSP90 chaperone function or in ribosome mutant cells as revealed formerly in yeast. We found that cytoplasmic foci of RPB1 occur in larger sizes in tumors that showed no regression after therapy. Based on these results, we propose that monitoring the cytoplasmic aggregation of RPB1 may be suitable for determining-from biopsy samples taken before treatment-the effectiveness of neoadjuvant chemotherapy.

Evaluation of Retinal Blood Flow in Patients with Monoclonal Gammopathy Using OCT Angiography.

BACKGROUND: Monoclonal gammopathy (MG) is characterized by monoclonal protein overproduction, potentially leading to the development of hyperviscosity syndrome. OBJECTIVE: To assess retinal circulation using optical coherence tomography angiography (OCTA) parameters in patients with monoclonal gammopathy. METHODS: OCTA measurements were performed using the Optovue AngioVue system by examining 44 eyes of 27 patients with MG and 62 eyes of 36 control subjects. Superficial and deep retinal capillary vessel density (VD SVP and DVP) in the whole 3 × 3 mm macular and parafoveal area, foveal avascular zone (FAZ) area, and central retinal thickness (CRT) were measured using the AngioAnalytics software. The OCTA parameters were evaluated in both groups using a multivariate regression model, after controlling for the effect of imaging quality (SQ). RESULTS: There was no significant difference in age between the subjects with monoclonal gammopathy and the controls (63.59 ± 9.33 vs. 58.01 ± 11.46 years; p > 0.05). Taking into account the effect of image quality, the VD SVP was significantly lower in the MG group compared to the control group (44.54 ± 3.22% vs. 46.62 ± 2.84%; p < 0.05). No significant differences were found between the two groups regarding the other OCTA parameters (p > 0.05). CONCLUSIONS: A decreased superficial retinal capillary vessel density measured using OCTA in patients with MG suggests a slow blood flow, reduced capillary circulation, and consequent tissue hypoperfusion. An evaluation of retinal circulation using OCTA in cases of monoclonal gammopathy may be a sensitive method for the non-invasive detection and follow-up of early microcirculatory dysfunction caused by increased viscosity.

Does implant drill design influence the accuracy of dental implant placement using static computer-assisted implant surgery? An in vitro study.

BACKGROUND: The purpose of this in vitro study was to compare the accuracy of implant placement in model surgeries according to the design of the drills (straight drills or step drills) used to finalize the implant bed during pilot-guided static computer-assisted implant surgery (sCAIS). METHODS: Model surgeries were carried out on resin models randomly assigned to three study groups. Virtual planning software (coDiagnostiX 10.6, Dental Wings, Montreal, Canada) was used to plan the implant positions. In Groups 1 and 2, pilot-guided sCAIS was performed. Straight drills were used in Group 1, and step drills were used in Group 2 to finalize the implant beds. In Group 3, fully guided sCAIS was performed using a universal fully guided kit (RealGUIDE Full Surgical Kit 3DIEMME, RealGUIDE, Cantù, Como, Italy). A total of 90 dental implants (Callus Pro, Callus Implant Solutions GmbH, Nuremberg, Germany) were placed (six implants per model, five models per study group). The primary outcome variables (angular deviation, coronal global deviation, and apical global deviation) were calculated for all implants based on the comparison of the preoperative surgical plan with the postoperative scans. RESULTS: Group 2 (coronal global deviation, 0.78 ± 0.29 mm; apical global deviation, 1.02 ± 0.56 mm) showed significantly lower values of both global deviation variables than Group 1 (coronal global deviation, 0.95 ± 0.20 mm; apical global deviation, 1.42 ± 0.49 mm). However, there was no significant difference in angular deviation between Groups 1 and 2 (7.56 ± 2.92° and 6.44 ± 2.84°). Group 3 produced significantly lower values of all three primary outcome variables (angular deviation, 2.36 ± 0.90°; coronal global deviation, 0.59 ± 0.28 mm; apical global deviation, 0.90 ± 0.29 mm) than Group 1 and significantly lower angular deviation and coronal global deviation values than Group 2. CONCLUSIONS: The design of the drills used to finalize implant osteotomies during pilot-guided sCAIS influences dental implant placement accuracy. Using step drills instead of straight drills for final osteotomies decreases deviation from the surgical plan. The fully guided approach performed better than the pilot-guided sCAIS.

Does Diffusely Infiltrating Lobular Carcinoma of the Breast Arise from Epithelial-Mesenchymal Hybrid Cells?

Classic diffusely infiltrating lobular carcinoma has imaging features divergent from the breast cancers originating from the terminal ductal lobular units and from the major lactiferous ducts. Although the term "invasive lobular carcinoma" implies a site of origin within the breast lobular epithelium, we were unable to find evidence supporting this assumption. Exceptional excess of fibrous connective tissue and the unique cell architecture combined with the aberrant features at breast imaging suggest that this breast malignancy has not originated from cells lining the breast ducts and lobules. The only remaining relevant component of the fibroglandular tissue is the mesenchyme. The cells freshly isolated and cultured from diffusely infiltrating lobular carcinoma cases contained epithelial-mesenchymal hybrid cells with both epithelial and mesenchymal properties. The radiologic and histopathologic features of the tumours and expression of the mesenchymal stem cell positive markers CD73, CD90, and CD105 all suggest development in the direction of mesenchymal transition. These hybrid cells have tumour-initiating potential and have been shown to have poor prognosis and resistance to therapy targeted for malignancies of breast epithelial origin. Our work emphasizes the need for new approaches to the diagnosis and therapy of this highly fatal breast cancer subtype.

Teledentistry: A Future Solution in the Diagnosis of Oral Lesions: Diagnostic Meta-Analysis and Systematic Review.

Introduction: Teledentistry (TD) can offer a wide range of possibilities in the field of oral medicine. Oral potentially malignant disorders (OPMDs) are hard to detect, and even harder to diagnose correctly. With the help of TD, OPMDs can be detected and diagnosed by a remote specialist. Our aim was to investigate whether TD could provide a reliable diagnostic method compared with clinical oral examination (COE) in the diagnosis of OPMDs. Methods: A systematic search was conducted in three databases (Medline, EMBASE, CENTRAL) until November 2021. We included studies that compared telediagnosis and COE, both made by experts. Pooled specificity and sensitivity were calculated and visualized on a two-dimensional plot. Risk of bias was assessed using the QUADAS-2 tool, and the level of evidence is shown with the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) tool. Results: Of the 7,608 studies, 13 were included in the qualitative and 9 in the quantitative synthesis. Using TD tools in the detection of oral lesions (OLs) showed high specificity (0.92 confidence interval [95% CI] = 0.59-0.99) and sensitivity (0.93 95% CI = 0.17-1.00). In the differential diagnosis of lesions, we found high sensitivity and specificity (0.942 95% CI = 0.826-0.982 and 0.982 95% CI = 0.913-0.997), respectively. We summarized the available data on time-effectiveness, screening person, referral decision, and technical settings. Conclusion: Detecting OLs with TD tools might lead to earlier diagnosis, treatment, and stricter follow-up of OPMD. TD may offer a great substitution for COE in the diagnosis of OLs, and thus, fewer referrals could be made to special care, resulting in a greater number of treated OPMDs.

Good practice: The experiences with the utilization of residual cancer burden-A single institution study.

INTRODUCTION: The use of neoadjuvant therapy (NAT) has been showing an incraesing tendency in the treatment of locally advanced breast cancer. The evaluation of residual cancer could be performed by Residual Cancer Burden (RCB) calculator. The prognostic system takes the two largest diameters of the tumor, the cellularity, the amount of in situ carcinoma, the number of metastatic lymph nodes, and the size of the largest metastatic deposit into account. The aim of our study was to examine the reproducibility of RCB in NAT treated patients. METHODS: Patients who were treated with NAT and had resection specimens between 2018 and 2021 were selected. Histological examination was performed by five pathologists. After assessment of the examined variables, RCB points and RCB classes were defined. For statistical analysis, interclass correlation was used (SPSS Statistics V.22.0 software). RESULTS: Altogether 100 patients were included in our retrospective, cohort study (average age: 57 years). In two-thirds of the cases, third generation chemotherapy was used, and mastectomy was performed. Significant concordance was found in the two largest diameters of the tumor (coefficients, 0.984 and 0.973), the cellularity (coefficient, 0.970), and the largest metastatic deposit (coefficient, 0.998). Although the amount of in situ carcinoma proved to be the least reproducible factor, it resulted in almost 90% of agreement (coefficient, 0.873). Regarding RCB points and classes, similar results were observed (coefficients, 0.989 and 0.960). CONCLUSIONS: Significant agreement was observed between examiners based on almost all RCB parameters, points, and classes, reflecting the optimal reproducibility of RCB. Therefore, we recommend the use of the calculator in routine histopathological reports in NAT cases.

ONEST (Observers Needed to Evaluate Subjective Tests) Analysis of Stromal Tumour-Infiltrating Lymphocytes (sTILs) in Breast Cancer and Its Limitations.

Tumour-infiltrating lymphocytes (TILs) reflect antitumour immunity. Their evaluation of histopathology specimens is influenced by several factors and is subject to issues of reproducibility. ONEST (Observers Needed to Evaluate Subjective Tests) helps in determining the number of observers that would be sufficient for the reliable estimation of inter-observer agreement of TIL categorisation. This has not been explored previously in relation to TILs. ONEST analyses, using an open-source software developed by the first author, were performed on TIL quantification in breast cancers taken from two previous studies. These were one reproducibility study involving 49 breast cancers, 23 in the first circulation and 14 pathologists in the second circulation, and one study involving 100 cases and 9 pathologists. In addition to the estimates of the number of observers required, other factors influencing the results of ONEST were examined. The analyses reveal that between six and nine observers (range 2-11) are most commonly needed to give a robust estimate of reproducibility. In addition, the number and experience of observers, the distribution of values around or away from the extremes, and outliers in the classification also influence the results. Due to the simplicity and the potentially relevant information it may give, we propose ONEST to be a part of new reproducibility analyses.

A custom-made removable appliance for the decompression of odontogenic cysts fabricated using a digital workflow.

OBJECTIVES: This case series aimed to assess the feasibility of a custom-made decompression appliance fabricated using a digital workflow to decompress odontogenic cysts. Additionally, the treated cysts were assessed for volumetric changes. METHODS: A three-dimensional (3D) reconstruction software (CoDiagnostiX version 10.4) was used to obtain the master cast STL (Standard Tessellation Language) file by placing a customized virtual implant to create a recess for the tube of the decompression device. The decompression appliance was planned using Dental Wings Open Software (DWOS). Following rapid prototyping, the tube of the appliance was perforated using round burs. In cases where the appliances were designed to replace teeth, denture teeth were added using the conventional workflow. The appliances were delivered on the day of the cystostomy. Following decompression, cyst enucleation was performed. Cyst volume was assessed by manual segmentation of pre- and post-operative cone-beam computed tomography (CBCT) reconstructions using slice-by-slice boundary drawing with a scissors tool in the 3DSlicer 4.10.2 software. Percentage of volume reduction was calculated as follows: volume reduction/pre-operative volume × 100. RESULTS: Six odontogenic cysts in six patients (5 male, 1 female; age 40 years, range: 15-49 years) with a pre- and post-operative cyst volume of 5597 ± 3983 mm3 and 2330 ± 1860 mm3 respectively (p < 0.05) were treated. Percentage of volume reduction was 58.84 ± 13.22 % following a 6-month-long decompression period. CONCLUSIONS: The digital workflow described in this case series enables the delivery of decompression appliances at the time of cystostomy, thus effectively reducing the volume of odontogenic cysts. The resulting bone formation established a safe zone around the anatomical landmarks; therefore, during enucleation surgery, complications to these landmarks can be avoided.

BC-miR: Monitoring Breast Cancer-Related miRNA Profile in Blood Sera-A Prosperous Approach for Tumor Detection.

Breast cancer is the most frequent cancer with a high fatality rate amongst women worldwide. Diagnosing at an early stage is challenging, and due to the limitations of the currently used techniques, including mammography and imaging diagnostics, it still remains unascertained. Serum biomarkers can be a solution for this as they can be isolated in a less painful, more cost-effective, and minimally invasive manner. In this study, we shed light on the relevant role of multiple microRNAs (miRNAs) as potential biomarkers in breast cancer diagnosis. We monitored the expressional changes of 15 pre-selected miRNAs in a large cohort, including 65 patients with breast cancer and 42 healthy individuals. We performed thorough statistical analyses on the cohort sample set and determined the diagnostic accuracy of individual and multiple miRNAs. Our study reveals a potential improvement in diagnostics by implicating the monitoring of miR-15a+miR-16+miR-221 expression in breast cancer management.

Accuracy of dental implant placement using augmented reality-based navigation, static computer assisted implant surgery, and the free-hand method: An in vitro study.

OBJECTIVES: This in vitro study aimed to compare the accuracy of implant placement in model surgeries carried out by implementation of three different methods. METHODS: An in vitro study was conducted on 3D printed study models randomly assigned to three study groups. In Group 1, model surgeries were assisted by augmented reality (AR)based dynamic navigation (Innooral System, Innoimplant Ltd, Budapest, Hungary). In Group 2, implants were placed with a free-hand method, and in Group 3, static Computer Assisted Implant Surgery (CAIS) was used (coDiagnostiX software, version 10.4 Dental Wings, Montreal, CA, USA). A total of 48 dental implants (Callus Pro, Callus Implant Solutions GmbH, Hamburg, Germany) were placed (16 implants in four models per study group). The primary outcome variables were angular deviation, coronal, and apical global deviation. These were calculated for all implants based on preoperative registration of the surgical plan and postoperative cone beam computed tomography (CBCT) reconstruction. RESULTS: The accuracy of implant placement using AR-based dynamic navigation showed no significant difference compared to static CAIS (angular deviation, 4.09 ± 2.79° and 3.21 ± 1.52°; coronal deviation, 1.27 ± 0.40 mm and 1.31 ± 0.42 mm; and apical global deviation 1.34 ± 0.41 mm and 1.38 ± 0.41 mm). Global deviation results were significantly lower with AR-based dynamic navigation than with the free-hand approach (coronal and apical global deviation of 1.93 ± 0.79 mm and 2.28 ± 0.74 mm, respectively). CONCLUSIONS: Implant positioning accuracy of AR-based dynamic navigation was comparable to that of static CAIS and superior to that obtained by the free-hand approach. CLINICAL SIGNIFICANCE: Implementing Augmented Reality based dynamic Computer Assisted Implant Surgery (CAIS) in model surgeries may allow to obtain an implant positioning accuracy comparable to that provided by static CAIS, and superior to that obtained through the free-hand approach. Further clinical studies are necessary to determine the feasibility of AR-based dynamic navigation.

ONEST (Observers Needed to Evaluate Subjective Tests) suggests four or more observers for a reliable assessment of the consistency of histological grading of invasive breast carcinoma: A reproducibility study with a retrospective view on previous studies.

Histological grade is one of the most important prognosticators of breast cancer which is available for nearly all cases. It also makes part of several multivariable analysis derived combined prognostic profiles despite concerns about its reproducibility. The aims included a reproducibility study of grading in the light of a recently described statistical approach, ONEST (Observers Needed to Evaluate Subjective Tests) and review earlier reproducibility studies in the light of the ONEST analysis. Nine pathologists reviewed 50 core needle biopsies and 50 slides from different excision specimens and recorded the scores for gland (tubule) formation, nuclear pleomorphism and mitotic activity as well as histological grade. Overall percent agreement, Fleiss kappa and the intraclass correlation coefficient (ICC) were used for the analysis of reproducibility. ONEST data and curves were generated from 100 random permutations of the participants. ONEST suggested a minimum of 4 observers for the reliable evaluation of reproducibility for both the scored components and grade in either type of specimen. Our results suggested moderate or moderate to good reproducibility of grading (kappa values of 0.51 for excisions, and 0.54 for biopsies and ICCs of 0.70 and 0.69, respectively) with gland formation being the most and nuclear pleomorphism the worst consistently evaluated feature. In studies with sufficient participants (at least 4) and non-pairwise comparisons in the analysis, the reproducibility of histological grading is fair to moderate, whereas studies with fewer participants or pairwise kappa analysis suggest moderate to almost prefect agreement of the results. ONEST is a valuable complementation of reproducibility analyses.

Ocular signs and comorbidities in monoclonal gammopathy: Analysis of 84 eyes of 42 subjects / A monoklonális gammopathia szemészeti jelei és szövodményei: 42 beteg 84 szemének vizsgálata

Összefoglaló. Célkituzés: A monoklonális gammopathia szemészeti jeleinek és szövodményeinek vizsgálata. Betegek és módszerek: Két nagy budapesti hematológiai ellátóhely 1999 és 2020 között diagnosztizált és/vagy kezelt, monoklonális gammopathiát mutató betegeit vizsgáltuk (42 beteg 84 szeme, 42,86% férfi; átlagéletkor 63,83 ± 10,76 év). A hematológiai diagnózis 3 esetben bizonytalan jelentoségu monoklonális gammopathia, 34 esetben myeloma multiplex, 3 esetben parázsló myeloma, 1-1 esetben Waldenström-macroglobulinaemia és amyloidosis voltak. Kontrollcsoportként véletlenszeruen kiválasztott, hasonló korcsoportú, hematológiai betegség nélküli egyéneket vizsgáltunk (43 beteg 86 szeme, 32,56% férfi; átlagéletkor 62,44 ± 11,89 év). A szemészeti vizsgálat elott minden személy kitöltötte a Szemfelszíni Betegség Index (OSDI-) kérdoívet. A szemészeti vizsgálat során a látóélesség vizsgálata mellett pupillatágítást követoen réslámpás vizsgálatot végeztünk. Eredmények: Monoklonális gammopathiában az OSDI-érték szignifikánsan magasabb volt, mint a kontrollokban (p = 0,002). Gammopathiában 3 beteg 5 szeménél (5,95%) találtunk potenciális szaruhártya-immunglobulinlerakódást. Gammopathiában szárazszem-betegség 66,67%-ban, szürke hályog 55,95%-ban, Meibom-mirigy-diszfunkció 20,24%-ban, hátsó kérgi szürke hályog 19,05%-ban, egyéb szaruhártyahegek és -homályok 17,86%-ban, krónikus szemhéjgyulladás 14,29%-ban, szemészeti eltérés hiánya 11,90%-ban, macula- és/vagy retinadrusen 9,52%-ban, szaruhártya-immunglobulinlerakódás 5,95%-ban, epiretinalis membrán 5,95%-ban, korábbi szürkehályog-mutét 5,95%-ban, glaucoma 4,76%-ban, Fuchs-dystrophia 2,38%-ban, perifériás retinadegeneráció 2,38%-ban, chorioidea naevus 2,38%-ban, diabeteses retinopathia 1,19%-ban, arteria centralis retinae elzáródás 1,19%-ban, vena centralis retinae ágelzáródás 1,19%-ban, amblyopia 1,19%-ban volt kimutatható. A szárazszem-betegség (p = 0,002), a hátsó kérgi szürke hályog (p = 0,001), a szürke hályog (p<0,00001) és az egyéb szaruhártyahegek és -homályok (p = 0,01) szignifikánsan magasabb arányban fordultak elo a monoklonális gammopathiát mutató betegekben, mint a kontrollokban. Következtetés : Monoklonális gammopathiában a szárazszem-betegség és a szürke hályog a leggyakoribb szemészeti eltérés. A monoklonális gammopathia potenciális szemészeti jelei és szövodményei miatt javasoljuk a betegek évenkénti szemészeti ellenorzését, életminoségük javítása érdekében. Orv Hetil. 2021; 162(38): 1533-1540. OBJECTIVE: To examine ocular signs and ocular comorbidities in monoclonal gammopathy. PATIENTS AND METHODS: We analyzed patients from two large referral hematology centers in Budapest, who were diagnosed and/or treated with monoclonal gammopathy between 1997 and 2020 (84 eyes of 42 patients, 42.86% male, mean age 63.83 ± 10.76 years). Before the ophthalmic examination, the subjects filled in the Ocular Surface Disease Index (OSDI) questionnaire. Ophthalmic examination included visual acuity test and slit-lamp examination following dilation of the pupil. RESULTS: OSDI scores were significantly higher in subjects with monoclonal gammopathy than in controls (p = 0.002). Among gammopathy subjects, we observed potential corneal immunoglobulin deposition in 5 eyes of 3 patients (5.95%). In gammopathy subjects, there was dry eye disease (66.67%), cataract (55.95%), Meibomian gland dysfunction (20.24%), posterior cortical cataract (19.05%), corneal scars and degenerations (17.86%), chronic blepharitis (14.29%), absence of ocular complaint (11.90%), macular or retinal drusen (9.52%), corneal immunoglobulin deposition (5.95%), epiretinal membrane (5.95%), previous cataract surgery (5.95%), glaucoma (4.76%), Fuchs dystrophy (2.38%), peripheral retinal degeneration (2.38%), chorioideal naevus (2.38%), diabetic retinopathy (1.19%), central retinal artery occlusion (1.19%), central retinal vein branch occlusion (1.19%) and amblyopia (1.19%). The proportion of dry eye disease (p = 0.002), posterior cortical cataract (p = 0.001), cataract (p<0.00001), and corneal scars and degenerations (p = 0.01) were significantly higher in gammopathy subjects than in controls. CONCLUSION: Dry eye disease and cataracts are the most common ocular comorbidities in patients with monoclonal gammopathy. Therefore, due to the potential ocular signs and comorbidities of monoclonal gammopathy, we suggest a regular, yearly ophthalmic checkup of these patients to improve their quality of life. Orv Hetil. 2021; 162(38): 1533-1540.

The additional value of ONEST (Observers Needed to Evaluate Subjective Tests) in assessing reproducibility of oestrogen receptor, progesterone receptor, and Ki67 classification in breast cancer.

The reproducibility of assessing potential biomarkers is crucial for their implementation. ONEST (Observers Needed to Evaluate Subjective Tests) has been recently introduced as a new additive evaluation method for the assessment of reliability, by demonstrating how the number of observers impact on interobserver agreement. Oestrogen receptor (ER), progesterone receptor (PR), and Ki67 proliferation marker immunohistochemical stainings were assessed on 50 core needle biopsy and 50 excision samples from breast cancers by 9 pathologists according to daily practice. ER and PR statuses based on the percentages of stained nuclei were the most consistently assessed parameters (intraclass correlation coefficients, ICC 0.918-0.996), whereas Ki67 with 5 different theoretical or St Gallen Consensus Conference-proposed cut-off values demonstrated moderate to good reproducibility (ICC: 0.625-0.760). ONEST highlighted that consistent tests like ER and PR assessment needed only 2 or 3 observers for optimal evaluation of reproducibility, and the width between plots of the best and worst overall percent agreement values for 100 randomly selected permutations of observers was narrow. In contrast, with less consistently evaluated tests of Ki67 categorization, ONEST suggested at least 5 observers required for more trustful assessment of reliability, and the bandwidth of the best and worst plots was wider (up to 34% difference between two observers). ONEST has additional value to traditional calculations of the interobserver agreement by not only highlighting the number of observers needed to trustfully evaluate reproducibility but also by highlighting the rate of agreement with an increasing number of observers and disagreement between the better and worse ratings.