Time-Dependent Prediction Models for Individual Prognosis of Chronic Postsurgical Pain following Knee Replacement Based on an Extensive Multivariable Data Set.

(1) Background: Clinically useful prediction models for chronic postsurgical pain (CPSP) in knee replacement (TKA) are lacking. (2) Methods: In our prospective, multicenter study, a wide-ranging set of 91 variables was collected from 933 TKA patients at eight time points up to one year after surgery. Based on this extensive data pool, simple and complex prediction models were calculated for the preoperative time point and for 6 months after surgery, using least absolute shrinkage and selection operator (LASSO) 1se and LASSO min, respectively. (3) Results: Using preoperative data only, LASSO 1se selected age, the Revised Life Orientation Test on pessimism, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-subscore pain and the Timed "Up and Go" Test for prediction, resulting in an area under the curve (AUC) of 0.617 and a Brier score of 0.201, expressing low predictive power only. Using data up to 6 months after surgery, LASSO 1se included preoperative Patient Health Questionnaire-4, Knee Injury and Osteoarthritis Outcome Score (KOOS)-subscore pain (pain) 3 months after surgery (month), WOMAC pain 3 and 6 months, KOOS subscore symptoms 6 months, KOOS subscore sport 6 months and KOOS subscore Quality of Life 6 months. This improved the predictive power to an intermediate one (AUC 0.755, Brier score 0.168). More complex models computed using LASSO min did little to further improve the strength of prediction. (4) Conclusions: Even using multiple variables and complex calculation methods, the possibility of individual prediction of CPSP after TKA remains limited.

A comparative study of cyanoacrylate-based tissue adhesive and surgical sutures on marginal flap stability following coronally advanced flap.

INTRODUCTION: The present study evaluated the biomechanical characteristics of cyanoacrylate-based tissue adhesive (TA) compared to surgical sutures in coronally advanced flap (CAF) procedures using an ex-vivo model. MATERIAL AND METHODS: Thirty-six half-pig mandibles were divided into three groups, n=12 each: (I) CAF fixed with sutures (sling and tag suture technique), (II) CAF fixed with TA, and (III) CAF fixed with sutures and TA. At mandibular premolars, gingival recession defects extending 3 mm apical to the cemento-enamel junction (CEJ) were created. CAF procedures were performed using a split-full-split approach, with coronal advancement of the flap to 1 mm above the marked CEJ and stabilization according to the respective groups I-III. Marginal flap stability against pull-of forces (maximum tensile force) was measured with a universal material testing machine until the CEJ became visible. RESULTS: The comparison between groups I-III demonstrated a significantly increased maximum tensile force for the TA (II) compared to the suture group (I) (p<0.001). A significantly increased maximum tensile force was found for the suture and TA (III) compared to the suture group (I) (p<0.001). There was also a significantly increased maximum tensile force in the suture and TA (III) compared to the TA group (II) (p<0.001). CONCLUSION: The results suggest that cyanoacrylate-based TA can increase marginal flap stability compared to sutures in CAF procedures. CLINICAL RELEVANCE: Cyanoacrylate-based TA can be considered a useful and valuable adjunct to conventional suturing techniques in periodontal plastic surgery, especially in cases where high flap stability is required. The results of this ex-vivo study can only be transferred to the clinical situation with limitations. Clinical long-term follow-up data must be generated.

Optimism and pessimism are antithetically associated with post-operative knee function in patients' undergoing total knee arthroplasty.

PURPOSE: Personality traits, such as dispositional optimism and pessimism, have impact on a variety of health-related problems. Influence on outcome in total knee arthroplasty (TKA) could only be shown for other personality trait concepts, but not for dispositional optimism/pessimism. This study aims to examine the association of dispositional optimism/pessimism with pre-operative joint function and post-operative outcome in TKA. METHODS: Data were acquired in a multicentre, cross-sectoral, prospective study (the PROMISE Trial). Patients were followed for 12 months post-operatively. Dispositional optimism/pessimism was measured pre-operatively via the revised Life Orientation Test (LOT-R), pre- and post-operative function was measured via the 12 Item Knee-osteoarthritis outcome Scores (KOOS-12). Log-linear regression models considering known confounders and t-test were carried out to show the association of LOT-R scores with pre- and post-operative KOOS-12 scores. RESULTS: 740 patients were analyzed. Optimistic LOT-R was significantly positively associated to the mean scores of KOOS-12 pre- and post-operative, while pessimistic LOT-R was significantly associated negatively (pre-operative: optimistic p = 0.001, pessimistic p = 0.001; post-operative optimistic: 3M p = 0.001, 6M p = 0.001, 12M p = 0.001; post-operative pessimistic: 3M p = 0.01, 6M p = 0.004, 12M p = 0.001). CONCLUSION: Optimism was positively associated with pre-operative joint function and, more importantly, post-operative functional outcome in TKA, while pessimism was associated with the opposite. Assessing patients' general personality traits prior to surgery to identify pessimistic patients, hence being at risk for poor outcome in TKA, should be considered to react to the patients' special needs and possible pessimistic expectations, i.e., through a cognitive-behavioral intervention, to potentially increase optimism and hereby post-operative outcome in TKA. LEVEL OF EVIDENCE: Prognostic Level III.

Evaluation of Medication-Related Osteonecrosis of the Jaw (MRONJ) in Terms of Staging and Treatment Strategies by Dental Students at Different Educational Levels.

Background: The role of medication-related osteonecrosis of the jaw (MRONJ) as a dento-maxillo-facial pathology is becoming increasingly important due to its growing prevalence. The success of preventive and therapeutic measures relies mainly on the dentist's ability to correctly diagnose the disease. Methods: The aim of this study was to evaluate the skills of dental students of different educational levels in choosing the correct stage, diagnostics, and treatment option for MRONJ based on clinical and radiographic imaging (panoramic radiograph, CBCT). The study was designed as a cross-sectional cohort study. Twenty dental students were asked to complete a questionnaire in their third and fifth year of studies in which they had to correctly stage the disease, choose the radiological diagnostics and recommend the treatment. The control group contained experienced oral and maxillofacial surgeons. Results: With an overall performance of 59% (third year: 145.2/248 points; fifth year: 145.3/248 points), no statistically significant difference between the educational levels could be observed. The classification based on CBCT imaging was significantly more often correct compared to panoramic radiographs (p < 0.001). Conclusions: This study highlights students' lack of knowledge in staging, diagnostics, and treatment of MRONJ, even though the CBCT positively affected decision-making. No significant increase in knowledge could be confirmed through clinical education. This study highlights the need for students to catch up on MRONJ diagnostics and treatment planning. Further expansion of teaching in this disease's context and X-ray diagnostics is needed.

13 C-Methacetin Breath Test Predicts Survival in Patients With Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

INTRODUCTION: The 13 C-methacetin breath test ( 13 C-MBT) is a dynamic method for assessing liver function. This proof-of-concept study aimed to investigate the association between 13 C-MBT values and outcomes in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). METHODS: A total of 30 patients with HCC were prospectively recruited. Of these, 25 were included in baseline and 20 in longitudinal analysis. 13 C-MBTs were performed before the first and second TACE session. Patients were followed for at least 1 year. RESULTS: At baseline, the median 13 C-MBT value was 261 µg/kg/hr (interquartile range 159-387). 13 C-MBT, albumin-bilirubin, Child-Pugh, and Model for End-Stage Liver Disease scores were associated with overall survival in extended univariable Cox regression ( 13 C-MBT: standardized hazard ratio [sHR] 0.297, 95% confidence interval [CI] 0.111-0.796; albumin-bilirubin score: sHR 4.051, 95% CI 1.813-9.052; Child-Pugh score: sHR 2.616, 95% CI 1.450-4.719; Model for End-Stage Liver Disease score: sHR 2.781, 95% CI 1.356-5.703). Using a cutoff of 140 µg/kg/hr at baseline, 13 C-MBT was associated with prognosis (median overall survival 28.5 months [95% CI 0.0-57.1] vs 3.5 months [95% CI 0.0-8.1], log-rank P < 0.001). Regarding prediction of 90-day mortality after second 13 C-MBT, the relative change in 13 C-MBT values yielded an area under the receiver-operating characteristic curve of 1.000 ( P = 0.007). DISCUSSION: Baseline and longitudinal 13 C-MBT values predict survival of patients with HCC undergoing TACE. The relative change in 13 C-MBT values predicts short-term mortality and may assist in identifying patients who will not benefit from further TACE treatment.

Detectability of simulated apical lesions on mandibular premolars and molars between radiographic intraoral and cone-beam computed tomography images: an ex vivo study.

Adequate endodontic diagnostic is essential when making a therapy decision. Radiographic imagining acquisition methods (IAMs) are fundamental apical lesions of endodontic (ALE) origin diagnose tool. Thus, the aim of this research was to compare the simulated apical lesions (SALs) diagnose potential of digital intraoral radiography (DIR) and cone-beam computed tomography (CBCT), if there is a relationship between the IAMs, SALs-depth and their correct diagnose likelihood in human mandibular specimens' datasets. 1024 SALs were prepared in cancellous and cortical bone with different penetration depths. The SALs-stages were radiographed with CBCT and DIR. The IAMs were randomly evaluated by 16 observers in two trials. Possible SAL findings were analyzed according to a five-point scale. The null hypothesis established that SALs detection accuracy does not differ between CBCT and DIR. Significantly differences (first 0.935 and second trial 0.960) were found for the CBCT area under the curve when compared with the DIR (first 0.859 and second trial 0.862) findings. SALs of smaller size were earlier detected by CBCT. In SALs without cortical involvement the probability of detection increased from 90 to 100%. The SALs-depth had the highest detectability influence on cancellous bone lesions and CBCT SALs detectability was 84.9% higher than with DIR images. The CBCT diagnose reproducibility was higher than the one of DIR (Kappa CBCT 75.7-81.4%; DIR 53.4-57.1%). Our results showed that CBCT has a higher SALs IAM diagnosing accuracy and that SALs detection accuracy incremented as the SALs-size increased.

eHealth Literacy in German Skin Cancer Patients.

The global incidence of skin cancer has steadily increased in recent years, and malignant melanoma still has one of the fastest-growing incidence rates among all malignant tumors in the western world. Thus, newly diagnosed patients have an increased need for health information concerning their disease. Using a standardized questionnaire, our study aims to investigate our patients' primary sources of health-related information as well as their self-proclaimed eHealth literacy. We received 714 questionnaires. Regardless of age, the primary source of information was the treating dermato-oncologist, followed by the treating general practitioner and the Internet. However, with increasing age, the usage of the Internet decreased. Hence, younger participants were better equipped to find health-related information while using the Internet. Additionally, comprehending health-related information and gaining medical knowledge was significantly increased in better-educated participants. Overall, our study shows that with increased use of eHealth services, accessing web-based information increased, correlating with a better eHealth literacy of our patients. eHealth technologies are increasingly becoming more prevalent as a primary source of information in our modern health care system. Thus, it is crucial to educate cancer patients in eHealth literacy to make autonomous, informed decisions and gain more confidence in dealing with their disease.

Quantitative Analysis of Plasma Cell-Free DNA and Its DNA Integrity and Hypomethylation Status as Biomarkers for Tumor Burden and Disease Progression in Patients with Metastatic Neuroendocrine Neoplasias.

BACKGROUND: Neuroendocrine neoplasia (NEN) encompasses a diverse group of malignancies marked by histological heterogeneity and highly variable clinical outcomes. Apart from Chromogranin A, specific biomarkers predicting residual tumor disease, tumor burden, and disease progression in NEN are scant. Thus, there is a strong clinical need for new and minimally invasive biomarkers that allow for an evaluation of the prognosis, clinical course, and response to treatment of NEN patients, thereby helping implement individualized treatment decisions in this heterogeneous group of patients. In the current prospective study, we evaluated the role of plasma cell-free DNA concentration and its global hypomethylation and fragmentation as possible diagnostic and prognostic biomarkers in patients with neuroendocrine neoplasias. METHODS: The plasma cfDNA concentration, cfDNA Alu hypomethylation, and LINE-1 cfDNA integrity were evaluated prospectively in 63 NEN patients with presumably cured or advanced metastatic disease. The cfDNA characteristics in NEN patients were compared to the results of a group of 29 healthy controls and correlated with clinical and histopathological data of the patients. RESULTS: Patients with advanced NEN showed a significantly higher cfDNA concentration and percentage of Alu hypomethylation and a reduced LINE-1 cfDNA integrity as compared to the surgically cured NET patients and the healthy control group. The increased hypomethylation and concentration of cfDNA and the reduced cfDNA integrity in NEN patients were strongly associated with tumor burden and poor prognosis, while no correlation with tumor grading, differentiation, localization, or hormonal activity could be found. Multiparametric ROC analysis of plasma cfDNA characteristics was able to distinguish NEN patients with metastatic disease from the control group and the cured NEN patients with AUC values of 0.694 and 0.908, respectively. This was significant even for the group with only a low tumor burden. CONCLUSIONS: The present study, for the first time, demonstrates that the combination of plasma cfDNA concentration, global hypomethylation, and fragment length pattern has the potential to serve as a potent and sensitive prognostic and therapeutic "liquid biopsy" biomarker for tumor burden and disease progression in patients with neuroendocrine neoplasias.

Sonographic assessment of low muscle quantity identifies mortality risk during COVID-19: a prospective single-centre study.

BACKGROUND: Assessment of muscle quantity by sonographic muscle indices could help identify patients at risk for fatal outcome during coronavirus disease-2019 (COVID-19). The aim of this study was to explore sonographic muscle indices as predictors of COVID-19 outcome and to test the feasibility of sonographic muscle measurement in an isolation context. METHODS: Muscle indices, derived from the psoas muscle or thigh muscles, were quantified by sonography in a cohort of patients without COVID-19 to obtain reference values for low muscle quantity. Gender-specific median of different muscle indices were defined as threshold value for low muscle quantity. The prognostic relevance of low muscle quantity, was prospectively explored in two cohorts of hospitalized COVID-19 patients. Optimal muscle index cutoff values predictive for 30 day mortality during COVID-19 were determined by receiver operating characteristic-area under the curve and Youden index calculation. Muscle quantity and known prognostic factors of COVID-19 were analysed by multivariable log-regression. RESULTS: Compared with other muscle indices, the psoas muscle area index (PMAI) showed the most favourable characteristics to predict outcome of COVID-19 disease. Sonographic morphometry of patients without COVID-19 (n = 136) revealed a gender-specific median for PMAI (male: 291.1 mm2 /m2 , female 260.6 mm2 /m2 ) as threshold value of low muscle quantity. Subsequently, COVID-19 patients (Cohort I: n = 58; Cohort II: n = 55) were prospectively assessed by bedside sonography. The studied COVID-19 patients developed a critical course of disease in 22.4% (Cohort I: n = 13/58) and 34.5% (Cohort II: n = 20/55). Mortality rate reached 12.1% (Cohort I: n = 7/58) and 20.0% (Cohort I: n = 11/55) within 30 days of follow up. COVID-19 patients with a PMAI below the gender-specific median showed a higher 30 day mortality in both COVID-19 cohorts (log rank, P < 0.05). The optimal PMAI cutoff value (206 mm2 /m2 ) predicted 30 day mortality of hospitalized COVID-19 patients with a sensitivity of 72% and specificity of 78.5% (receiver operating characteristic-area under the curve: 0.793, 95% confidence interval 0.671-0.914, P = 0.008). Multivariable log-regression analysis of PMAI, age, gender, BMI and comorbidities confirmed an independent association of low PMAI with 30 day mortality of COVID-19 patients (P = 0.018). CONCLUSIONS: Sonographic morphometry provides reliable muscle quantification under hygienic precautions and allows risk stratification of patients with COVID-19.

Buccal Bone Thickness in Anterior and Posterior Teeth-A Systematic Review.

(1) Background: Immediate dental implant placement has been a subject of great interest over the last decade. Here, information regarding the anatomy and bone thickness of the jaw prior to dental implant placement is crucial to increase the surgery's success and the patient's safety. The clinical premises for this approach have been controversially discussed. One of those heavily discussed premises is a buccal bone thickness of at least 1 mm thickness. This meta-analysis aims to systematically review buccal bone thickness (BBT) in healthy patients. Thus, the feasibility of immediate dental implant placement in daily practice can be assessed. (2) Methods: A search in the electronic databases was performed to identify articles reporting on BBT that was measured by computed tomography in adults. (3) Results: We were able to find 45 studies, including 4324 patients with 25,452 analyzed teeth. The analysis showed a BBT at the alveolar crest of 0.76 ± 0.49 mm in the maxillary frontal and of 1.42 ± 0.74 mm in the maxillary posterior region. In the mandible, the average measured values were similar to those in the maxilla (front: 0.95 ± 0.58 mm; posterior: 1.20 ± 0.96 mm). In the maxillary frontal region 74.4% and in the mandibular frontal region 61.2% of the crestal buccal bones showed widths <1 mm. (4) Conclusions: In more than 60% of the cases, the BBT at the alveolar crest is <1 mm in maxillary and mandibular frontal regions. This anatomic data supports careful pre-surgical assessment, planning of a buccal graft, and critical selection of indication for immediate implant placement, especially in the maxillary and mandibular frontal and premolar region.

Is Hyperspectral Imaging Suitable for Assessing Collateral Circulation Prior Radial Forearm Free Flap Harvesting? Comparison of Hyperspectral Imaging and Conventional Allen's Test.

(1) Background: This cross-sectional study aims to compare a new and non-invasive approach using hyperspectral imaging (HSI) with the conventional modified Allen's test (MAT) for the assessment of collateral perfusion prior to radial forearm free flap harvest in healthy adults. (2) HSI of the right hand of 114 patients was recorded. Here, three recordings were carried out: (I) basic status (perfusion), (II) after occlusion of ulnar and radial artery (occlusion) and (III) after releasing the ulnar artery (reperfusion). At all recordings, tissue oxygenation/superficial perfusion (StO2 (0-100%); 0-1 mm depth), tissue hemoglobin index (THI (0-100)) and near infrared perfusion index/deep perfusion (NIR (0-100); 0-4 mm depth) were assessed. A modified Allen's test (control) was conducted and compared with the HSI-results. (3) Results: Statistically significant differences between perfusion (I) and artery occlusion (II) and between artery occlusion (II) and reperfusion (III) could be observed within the population with a non-pathological MAT (each <0.001). Significant correlations were observed for the difference between perfusion and reperfusion in THI and the height of the MAT (p < 0.05). Within the population with a MAT >8 s, an impairment in reperfusion was shown (each p < 0.05) and the difference between perfusion and reperfusion exhibited a strong correlation to the height of the MAT (each p < 0.01). (4) Conclusions: The results indicate a reliable differentiation between perfusion and occlusion by HSI. Therefore, HSI could be a useful tool for verification of the correct performance of the MAT as well as to confirm the final diagnosis, as it provides an objective, reproducible method whose results strongly correlate with those obtained by MAT. What is more, it can be easily applied by non-medical personnel.

Pulp sensitivity changes during orthodontic treatment at different time periods: a prospective study.

OBJECTIVE: The purpose of this investigation was to recognize pulp sensitivity changes in teeth receiving orthodontic treatment by means of an electric pulp tester (Vitality Scanner Model 2006; Kerr Corporation, Brea CA, USA). MATERIALS AND METHODS: An electric stimulus response threshold of eight teeth in 22 patients was measured prior to positioning orthodontic attachments, immediately before ligation of a nickel titanium archwire, immediately after ligation of a stainless steel archwire and 9 to 15 months after having achieved the clinical purposes established with the nickel titanium archwires. The first measurement served as baseline. RESULTS: All teeth responded to an electrical stimulus at all times. No statistical differences were observed between the response thresholds obtained at different treatment times. The mean response threshold of the second measurement showed a decreasing response threshold tendency when compared with those of the baseline measurement. The mean response threshold of the third measurement showed an increasing tendency when compared with those of the baseline measurement. The first maxillary incisor and canine showed the lowest decreasing response threshold after the second measurement and the highest increasing response threshold after the third measurement. Less noticeable, but similar decreasing and increasing response threshold tendencies were observed in all other teeth after the second and third measurements, respectively. CONCLUSIONS: The results obtained in this investigation suggest that pulp sensitivity can be monitored during orthodontic treatment by means of an electric pulp tester. CLINICAL RELEVANCE: The importance of monitoring the pulp status during orthodontic treatment.

Impact of non-selective ß-blockers on hepatic encephalopathy in patients with liver cirrhosis.

BACKGROUND: Non-selective ß-blockers (NSBB) are frequently used for the treatment of portal hypertension and gastroesophageal varices in patients with liver cirrhosis; however prospective studies investigating the potential association between NSBB use and hepatic encephalopathy (HE) are still scarce. We investigated the potential association between NSBB use and the presence of covert HE (CHE) as well as the development of overt HE (OHE). METHODS: 224 patients with liver cirrhosis were included into this cohort study at two German centers and followed for a median of 364 days. CHE was diagnosed by pathological results in the PHES. Predictors for the presence of CHE or the development of OHE were analyzed using logistic-regression or cox-regression models. RESULTS: 39% of patients were treated with NSBB and CHE was detected in 34% of patients at study inclusion. In logistic regression analysis, NSBB use, higher MELD score and a history of OHE were independently associated with the presence of CHE. Cumulative incidence of OHE was considerably higher in NSBB users than in non-users (p<0.001). In Cox-regression models NSBB use, presence of CHE, lower albumin and higher MELD score were independently associated with the development of OHE in the whole cohort as well as in the subgroup of patients with decompensated liver cirrhosis. NSBB use was independently associated with higher risk of mortality or need for liver transplantation in decompensated patients but not in the total cohort. CONCLUSION: NSBB use seems to be associated with the presence of CHE as well as the development of OHE in patients with decompensated liver cirrhosis.

Association between diabetes mellitus and hepatic encephalopathy in patients with cirrhosis.

BACKGROUND: Diabetes mellitus may lead to increased serum ammonia and systemic inflammation thereby promoting hepatic encephalopathy (HE). AIM: To investigate the potential association between diabetes mellitus/glycaemic control and the presence of covert HE as well as the development of overt HE in a prospective setting. METHODS: A total of 240 patients with liver cirrhosis were included into this prospective cohort study and followed for a median of 17 months. Covert HE was diagnosed by pathological results in the Portosystemic Hepatic Encephalopathy Score. Predictors for the presence of covert HE or the development of overt HE were analysed using logistic regression or Cox-regression models. RESULTS: At study inclusion, 65 patients (27.1%) presented with diabetes mellitus and covert HE was detected in 33.3%. Patients with diabetes mellitus had a more preserved liver function as compared to patients without diabetes mellitus (MELD 9 vs 10; P = 0.043). In regression analyses after adjustment for confounders, diabetes mellitus was independently associated with the presence of covert HE at study inclusion and the development of overt HE during follow-up. These associations were confirmed in separate propensity-score-weighted regression models. In subgroup analyses, patients with worse glycaemic control (HbA1c >= 6.5%) had a pronounced risk for covert HE (OR 2.264, 95% CI 1.002-5.118) and overt HE (HR 4.116, 95% CI 1.791-9.459). CONCLUSIONS: Diabetes mellitus may associate with higher risk for the presence of covert HE and the development of overt HE in patients with liver cirrhosis. Adequate glycaemic control may be a potential target to attenuate this important complication.