The Diagnostic Accuracy of Claudin-4 Immunochemistry in Differentiating Metastatic Carcinomas From Mesothelial Processes in Serous Effusion Cytology: A Systematic Review and Meta-analysis.

CONTEXT.­: Distinguishing metastatic carcinomas from mesotheliomas or reactive mesothelial cells in pleural, peritoneal, and pericardial effusions is a common diagnostic problem cytopathologists encounter. OBJECTIVE.­: To perform the first meta-analysis on the pooled diagnostic accuracy of claudin-4 immunochemistry in serous effusion cytopathology. DESIGN.­: This report followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for diagnostic test accuracy studies. Three databases (PubMed, Scopus, and the Cochrane Library) were searched until October 9, 2023, followed by study selection using specific inclusion and exclusion criteria and data extraction. The study quality assessment was performed by using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Statistical analysis was performed by using R to calculate the pooled sensitivity and specificity of claudin-4 immunochemistry. In addition, the diagnostic odds ratio was measured, representing the odds ratio of a positive result indicating a carcinoma rather than a mesothelial process in serous effusion cytology. RESULTS.­: Fourteen observational studies, published between 2011 and 2023, fulfilled the selection criteria and were included. All 14 studies used the 3E2C1 clone. Claudin-4 immunochemistry showed a high diagnostic accuracy in serous effusion cytology. The pooled sensitivity and specificity were 98.02% (95% CI, 93.96%-99.37%) and 99.72% (95% CI, 97.36%-99.97%), respectively. Lastly, the pooled diagnostic odds ratio was 1660.5 (95% CI, 760.0-3627.8) and no evidence of statistical heterogeneity between the included studies was found (I2 = 0%, τ2 = 0). CONCLUSIONS.­: Claudin-4 may be used as a single pan-carcinoma immunochemical biomarker in the differential diagnosis between metastatic carcinomas and mesotheliomas or reactive mesothelial cells in serous effusion cytology.

Very old age impacts masticatory performance: a study among sexagenarians to centenarians.

OBJECTIVE: This cross-sectional pilot study evaluated the impact of age on masticatory performance among individuals aged 65 to 106 years, as part of the Heidelberg Dental Centenarian Study (HD-100Z) conducted in South-Western Germany. MATERIALS AND METHODS: A total of 31 centenarians were recruited, alongside 31 individuals each from the age groups 75-99 and 65-74, matched based on sex, prosthetic status, and number of teeth. Masticatory performance was assessed using a two-colored chewing gum test and digital image processing. Multiple linear regression analysis was performed to assess the effect of age, sex, number of teeth, type of prosthesis on the masticatory performance. RESULTS: Masticatory performance, as measured by the standard deviation of hue in the chewing gum test, decreased significantly in centenarians compared to individuals aged 75-99 years (-0.112, p = 0.037) and those aged 65-74 years (-0.274, p < 0.001). The effects of sex, number of teeth, and type of prosthesis on masticatory performance were not significant associations (p ≥ 0.135). CONCLUSION: The findings suggest that age may have a significant influence on masticatory performance in the studied age groups, challenging previous notions that aging itself has little impact on masticatory ability. The inclusion of centenarians in the study highlights the need for further investigation into masticatory function in age groups reaching up to 100 years or more. CLINICAL RELEVANCE: This study contributes to the understanding of how ageing affects oral function, which may guide dental treatment approaches for older individuals, and set the stage for more in-depth investigations in this field in the future.

Impact of acquisition volume on cone beam computed tomography imaging of marginal bone: an ex vivo study.

OBJECTIVE: The current study explores whether there is a clinically relevant distinction in the measurement of marginal bone loss when comparing high-dose (HD) versus low-dose (LD) cone beam computed tomography (CBCT) protocols in small and large acquisition volumes.  Material and Methods: CBCTs of four human cadaveric preparates were taken in HD and LD mode in two different fields of view 8 × 8 cm2 (LV) and 5 × 5 cm2 (SV). In total, 43 sites of 15 teeth were randomly chosen, and marginal bone loss was measured twice in all protocols at 43 sites of 15 teeth by one calibrated investigator. Bland-Altman plots and Lin's concordance correlation coefficient (CCC) were calculated to assess the extent of agreement of the measurements. Additionally, the rater scored the certainty in each of the measurements. RESULTS: For HD-CBCT CCC of measurements obtained using SV versus LV was 0.991. CCC of measurements obtained using SV versus LV of LD-CBCT was 0.963. Both CCC values indicated excellent agreement between the two volumes in both protocols.  CCC also indicated high intramodality correlation between HD-CBCT and LD-CBCT independent of the acquisition volume (0.963 - 0.992). Bland-Altman plots also indicated no substantial differences. Results of certainty scoring showed significant differences (p = 0.004 (LV), p < 0.001(SV)) between the LD and HD-CBCT. CONCLUSIONS: Accuracy of measurements of bone loss shows no clinical noticeable effects depending on the CBCT volume in this ex vivo study. There appears to be no relevant advantage of SV over LV, neither in HD-CBCT nor in LD-CBCT and additionally no relevant advantage of HD versus LD in visualizing marginal bone loss.

Distinct profiles of proliferating CD8+/TCF1+ T cells and CD163+/PD-L1+ macrophages predict risk of relapse differently among treatment-naïve breast cancer subtypes.

Immunophenotypic analysis of breast cancer microenvironment is gaining attraction as a clinical tool improving breast cancer patient stratification. The aim of this study is to evaluate proliferating CD8 + including CD8 + TCF1 + Τ cells along with PD-L1 expressing tissue-associated macrophages among different breast cancer subtypes. A well-characterized cohort of 791 treatment-naïve breast cancer patients was included. The analysis demonstrated a distinct expression pattern among breast cancer subtypes characterized by increased CD8 + , CD163 + and CD163 + PD-L1 + cells along with high PD-L1 status and decreased fraction of CD8 + Ki67 + T cells in triple negative (TNBC) and HER2 + compared to luminal tumors. Kaplan-Meier and Cox univariate survival analysis revealed that breast cancer patients with high CD8 + , CD8 + Ki67 + , CD8 + TCF1 + cells, PD-L1 score and CD163 + PD-L1 + cells are likely to have a prolonged relapse free survival, while patients with high CD163 + cells have a worse prognosis. A differential impact of high CD8 + , CD8 + Ki67 + , CD8 + TCF1 + T cells, CD163 + PD-L1 + macrophages and PD-L1 status on prognosis was identified among the various breast cancer subtypes since only TNBC patients experience an improved prognosis compared to patients with luminal A tumors. Conversely, high infiltration by CD163 + cells is associated with worse prognosis only in patients with luminal A but not in TNBC tumors. Multivariate Cox regression analysis in TNBC patients revealed that increased CD8 + [hazard ratio (HR) = 0.542; 95% confidence interval (CI) 0.309-0.950; p = 0.032), CD8 + TCF1 + (HR = 0.280; 95% CI 0.101-0.779; p = 0.015), CD163 + PD-L1 + (HR: 0.312; 95% CI 0.112-0.870; p = 0.026) cells along with PD-L1 status employing two different scoring methods (HR: 0.362; 95% CI 0.162-0.812; p = 0.014 and HR: 0.395; 95% CI 0.176-0.884; p = 0.024) were independently linked with a lower relapse rate. Multivariate analysis in Luminal type A patients revealed that increased CD163 + was independently associated with a higher relapse rate (HR = 2.360; 95% CI 1.077-5.170; p = 0.032). This study demonstrates that the evaluation of the functional status of CD8 + T cells in combination with the analysis of immunosuppressive elements could provide clinically relevant information in different breast cancer subtypes.

Remote assessment of dental records by using intraoral scan-based digital three-dimensional models in an elderly patient population - an exploratory study.

AIM: To assess the agreement rates of dental records derived from intraoral scan-based digital three-dimensional models (3DM) and 3DM + panoramic radiographs (3DM+PAN-X) compared to clinical findings. MATERIALS AND METHODS: Based on the 3DM/3DM+PAN-X of 50 patients undergoing supportive periodontal therapy (SPT), ten remote raters (inexperienced in using IOS or 3DM) assessed for each site of the dental scheme (32 sites) whether a tooth was missing (M), filled (F), restoration- and caries-free (H), replaced by an implant (I) or decayed (D). Remote records were compared to the clinical reference record of each patient at tooth-level. The clinical records were assessed by an experienced dentist who supplemented the clinical findings with information from available radiographs and the patient records to define the clinical reference record. RESULTS: The agreement-rates for 3DM/3DM+PAN-X at tooth-level are: M: 93%/94%, F: 84%/88%, H: 92%/92%, I: 65%/96%, D: 29%/29%. The overall agreement-rate is 88% for the 3DM-based dental records (14093 of 16000 entries true) and 91% for 3DM+PAN-X (14499 of 16000 entries true). Using 3DM for dental record assessment, posterior teeth had higher odds of correct findings compared to anterior teeth (upper jaw OR=2.34, lower jaw OR=1.27). CONCLUSIONS: The remote detection of healthy, missing and filled teeth and implants by raters inexperienced in using IOS or 3DM shows a high agreement-rate with the clinical findings. The additional evaluation of PAN-X increased the agreement-rate significantly for implants. Thus, the remote assessment of dental records using 3DM+PAN-X has a high accuracy when applied in SPT-patients with low caries activity.

Impact of Salvage Surgery on Health-Related Quality of Life in Oral Squamous Cell Carcinoma: A Prospective Multi-Center Study.

BACKGROUND: Patients with recurrent oral squamous cell carcinoma (OSCC) have limited treatment options. Salvage surgery offers potential curative therapy. The need for extensive ablative surgery together with microvascular reconstruction implies invasive and painful treatment with questionable functional outcome. To address the impact of salvage surgery on the health-related quality of life (HRQoL) of patients suffering from recurrent OSCC, a multi-center prospective analysis was initiated. MATERIAL AND METHODS: Patients with recurrent OSCC from 2015 to 2022 at two German cancer centers were included. Interdisciplinary tumor board decisions determined surgery as the only curative treatment modality. HRQoL, was assessed via a EORTC questionnaire (European Organization for Research and Treatment of Cancer-EORTC: QLQ-C30 and QLQ-H&N35) in dependence of the recurrent tumor stage. Patients completed the questionnaires once before surgery (baseline) and then every 3 months during follow-up or up to the end of treatment. RESULTS: In total, 55 patients were included. The mean follow-up period was 26.7 ± 19.3 months. Global health status showed superior mean scores after 12 months (60.83 ± 22.58) compared to baseline (53.33 ± 26.41) in stage 1 and 2 recurrent tumors. In advanced recurrent tumors' mean scores for global health showed only minor positive differences after 12 months (55.13 ± 22.7) compared to baseline (53.2 ± 25.58). In terms of the mouth pain, mean scores were lower after salvage surgery in small recurrent tumors after 12 months (20.37 ± 17.73) compared to baseline (41.67 ± 33.07; Wilcoxon two-sample signed-rank test p = 0.028). In advanced recurrent tumors, a significant reduction in mean scores was detected 3 months after salvage surgery (29.7 ± 22.94) compared to baseline (47.76 ± 25.77; Wilcoxon two-sample signed-rank test p = 0.003). Up to 12 months, swallowing function was evaluated inferior compared to baseline independent of tumor stage (Mean score recurrent stage I/II: 12-months 48.15 ± 27.57, baseline 28.7 ± 22.87; stage III/IV: 12-months 49.36.42 ± 27.53; baseline 30.13 ± 26.25). CONCLUSION: Improved HRQoL could be obtained in advanced recurrent OSCC after salvage surgery despite reduced swallowing function. In small recurrent tumors, overall, HRQoL was superior to baseline. Salvage surgery positively affected pain burden. For advanced recurrent tumors, important pain relieve could be observed as soon as 3 months after surgery.

Oral health conditions in patients under antiresorptive therapy are comparable to unexposed during supportive periodontal care.

OBJECTIVES: To investigate oral health and oral health-related quality of life (OHRQoL) of patients under antiresorptive therapy (ART) during supportive periodontal care (SPC) considering history of medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: In this cross-sectional study, 100 patients (50 receiving ART (exposed) and 50 without ART (unexposed)) in regular SPC were enrolled for a clinical oral examination and the evaluation of OHRQoL using the OHIP-G14-questionnaire. History of MRONJ was assessed by anamnesis and reviewing patient records. RESULTS: There were no statistically significant group differences in age (exposed: 70.00 ± 9.07 versus unexposed: 71.02 ± 8.22 years), sex, distribution of systemic diseases and duration of SPC (on average 8.61 ± 5.73 years). Number of teeth (21.02 ± 5.84 versus 21.40 ± 5.42), DMFT (18.38 ± 3.85 versus 17.96 ± 4.08), probing pocket depth (2.31 ± 0.20 versus 2.38 ± 0.26), clinical attachment level (3.25 ± 0.76 versus 3.46 ± 0.58) and bleeding on probing (15.07 ± 11.53 versus 15.77 ± 13.08) were also not significantly different. The OHIP-G14 sum-score was significantly higher in exposed participants (6.10 ± 6.76 versus 3.62 ± 5.22, p = 0.043). History of MRONJ was prevalent in 8% of patients under ART. Periodontal/peri-implant-related MRONJ were reported in three participants with cancer (n = 1 before and n = 2 after active periodontal therapy). History of MRONJ due to endodontic/restorative reasons was reported in one patient with osteoporosis. CONCLUSIONS: Patients under ART in SPC demonstrated similar clinical periodontal and dental status but lower OHRQoL compared to unexposed (not statistically significant). Patient awareness of the MRONJ-risk and appropriate preventive measures should be ensured. CLINICAL RELEVANCE: SPC in osteoporotic patients under ART appeared safe regarding MRONJ, but further investigations on the MRONJ-risk in patients with different risk-profiles are necessary. STUDY REGISTRATION: clinicaltrials.gov (#NCT04192188).

Primary Care Disease Management for Venous Leg Ulceration in German Healthcare: Results of the Ulcus Cruris Care Pilot Study.

Despite proven effectiveness, compression therapy is applied in only 20-40% of patients with venous leg ulceration, leading to avoidable chronification and morbidity. The Ulcus Cruris Care project was established to develop a new disease-management concept comparable to existing programs for chronic diseases to support evidence-based treatment of venous leg ulceration. This prospective controlled study assessed its first implementation. Interventional elements comprised online training for general practitioner practices, software support for case management, and educational materials for patients. A total of 20 practices and 40 patients were enrolled in a 1:1 ratio to the intervention and control group. Guideline-conform compression therapy was applied more frequently in the intervention group (19/20 [95%] vs. 11/19 [58%]; p = 0.006). For patients with ulcers existing ≤ 6 months, the healing rate at 12 weeks was 8/11 [73%] (intervention) compared to 4/11 [36%] (control; p = 0.087). Patients after intervention had higher scores for self-help and education in the PACIC-5A questionnaire (42.9 ± 41.6 vs. 11.4 ± 28.8; p = 0.044). Treatment costs were EUR 1.380 ± 1.347 (intervention) and EUR 2.049 ± 2.748 (control; p = 0.342). The results of this study indicate that the Ulcus Cruris Care intervention may lead to a significant improvement in care. Consequently, a broader rollout in German healthcare seems warranted.

Prediction and outcomes of cerebral vasospasm in ischemic stroke patients receiving anterior circulation endovascular stroke treatment.

BACKGROUND AND PURPOSE: Vasospasm is a common complication of endovascular therapy (EVT). There is a lack of understanding of risk factors for periprocedural vasospasm. Here, we aimed to identify factors associated with vasospasm in patients with acute ischemic stroke who undergo EVT. METHODS: We conducted a retrospective single-center analysis of patients receiving EVT for anterior circulation vessel occlusion between January 2015 and December 2021. Patients were excluded if they showed signs of intracranial atherosclerotic disease (ICAD) or if they underwent intra-arterial thrombolysis. Study groups were defined as patients developing vasospasm during EVT (V+) and patients who did not (V-). The study groups were compared in univariable analysis. Multivariable regression models were developed to predict the patient's risk for developing vasospasm based on pre-identified potential prognostic factors. The secondary endpoint was clinical outcome defined as the modified Rankin Scale (mRS) difference between pre-stroke mRS and discharge mRS (delta mRS) and likelihood of successful reperfusion (TICI 2b/3). RESULTS: In total, 132/1768 patients (7.5%) developed vasospasm during EVT. Vasospasm was more likely to occur in EVT with multiple thrombectomy attempts and after several stent retriever maneuvers. Factors associated with developing vasospasm were younger age (OR = 0.967, 95% CI = 0.96-0.98) and lower pre-stroke mRS (OR = 0.759, 95% CI = 0.63-0.91). The prediction model incorporating patient age, pre-stroke mRS, stent retriever thrombectomy attempts, and total attempts as prognostic factors was found to predict vasospasm with good accuracy (AUC = 0.714, 95% CI = 0.709-0.720). V+ patients showed higher median (IQR) delta mRS (2 (1-4) vs 2 (1-3); p = 0.014). There was no difference in successful reperfusion (TICI 2b-3) between those with or without vasospasm. CONCLUSION: Vasospasm was a common complication in EVT affecting younger and previously healthy patients. Presence of vasospasm did not reduce the likelihood of successful reperfusion. As independent predictors, patient age, pre-stroke mRS, thrombectomy maneuvers, and stent retriever attempts predict the occurrence of vasospasm during EVT with good accuracy.

Effect of educational interventions on wound healing in patients with venous leg ulceration: A systematic review and meta-analysis.

Educational interventions for patients with venous leg ulceration (VLU) may promote adherence and self-management, however, their effect on wound healing is unclear. A systematic literature search was performed and randomised controlled trials with a focus on educational interventions were included. Wound healing was analysed by assessing wound healing rate, ulcer size, and the PUSH Score. Additional outcomes comprised pain, quality of life, and functional ability. The study protocol for this work is registered at PROSPERO 2020 (ID: CRD42021286152). Nine studies were included in this meta-analysis. The odds ratio for wound healing was 1.91 (95% CI, 0.99-3.67, P = .053) in favour of educational interventions compared to usual care. Ulcer size reduction was higher (MD: -7.22; 95% CI, -11.91 to -2.53, P = .003) in patients following educational interventions. Included studies also showed significant effects on pain, quality of life, and functional analysis, though no quantitative synthesis was feasible. The overall risk of bias showed some concerns. Educational interventions aim to actively involve patients in their treatment, thereby appearing to be able to have a positive impact on wound healing within 12 weeks. Consequently, integrating educational approaches to routine wound care may be a promising strategy to improve treatment of VLU.

Influence of artificial landmarks on the accuracy of complete arch scans in the partially edentulous maxilla: An in vitro study.

STATEMENT OF PROBLEM: Scan path length and the presence of edentulous alveolar ridge sections have a negative influence on scanning accuracy. How different artificial landmarks combined with an adapted scanning method affect accuracy is unclear. PURPOSE: The purpose of this in vitro study was to determine the influence of 2 different artificial landmarks combined with an adapted scanning method on the scanning accuracy of a partially edentulous maxillary model. MATERIAL AND METHODS: The model simulated a maxilla with 6 prepared teeth to accommodate a complete arch fixed partial denture. Five ceramic precision balls (ball center P1-P5), distributed buccally to the dental arch, were used to detect the dimensional and angular changes between the reference model and the intraoral scans. One intraoral scanner (Primescan) was used to make 30 scans each with either the scanning strategy recommended by the manufacturer (M) or with an adapted scanning strategy and the use of a bar (B) or 4 plates (P) as artificial landmarks in the dorsal palate. Data were statistically analyzed using a generalized least squares regression model (α=.05). RESULTS: Scanning with artificial landmarks reduced the maximum absolute distance deviations (M: 249 µm, B: 190 µm, P: 238 µm) and the maximum angle deviations (M: 0.31 degrees, B: 0.28 degrees, P: 0.26 degrees). Vertical distance deviations were improved by 10 to 50% with the use of artificial landmarks. Absolute mean distance deviations were significantly lower for group M (P<.001). In contrast, with artificial landmarks, mean angle (P<.001) and mean vertical distance deviations (P<.014) improved significantly. CONCLUSIONS: Scanning with artificial landmarks in the dorsal palate combined with an adapted scanning method improved the scanning accuracy and reliability of vertical distance deviations.