Digital droplet PCR-based quantification of ccfHPV-DNA as liquid biopsy in HPV-driven cervical and vulvar cancer.

PURPOSE: More than 99% of cervical cancers and up to 40% of vulvar cancers are human papillomavirus (HPV) related. HPV 16 and 18 are the most relevant subtypes. Novel technologies allow the detection of minimal amounts of circulating cell-free HPV DNA (ccfHPV-DNA). The aim of this study was to evaluate ccfHPV-DNA assessed by droplet digital PCR (ddPCR) as a biomarker for molecular therapy monitoring in early, advanced, relapsed and metastatic HPV-driven cervical and vulvar cancer. METHODS: Inclusion criteria of the study were histologically proven HPV 16/18-driven cervical and vulvar cancer with first diagnosed disease, newly diagnosed recurrence, or progression of disease. Blood samples were taken pre- and post-therapeutically. Circulating cell-free HPV DNA was quantified using ddPCR and the results were correlated with clinical data. RESULTS: The mean copy number of ccfHPV-DNA was 838.6 (± 3089.1) in pretreatment and 2.3 (± 6.4) in post-treatment samples (p < 0.05). The copy number of ccfHPV-DNA increased with higher FIGO stages (p < 0.05), which are commonly used for clinical staging/assessment. Furthermore, we compared the distribution of copy numbers between T-stage 1 versus T-stage 2/3. We could show higher copy number level of ccfHPV-DNA in T-stage 2/3 (p < 0.05). CONCLUSIONS: Therapy monitoring with determination of ccfHPV-DNA by ddPCR with a small amount of plasma reflects response to therapy and appears feasible for patients in advanced cancer stages of cervical and vulvar cancer. This promising tool should be examined as marker of therapy monitoring in particular in novel HPV-directed therapies.

The influence of stereoscopic vision on surgical performance in minimal invasive surgery-a substudy of the IDOSP-Study (Influence of 3D- vs. 4 K-Display Systems on Surgical Performance in minimal invasive surgery).

PURPOSE: This study is a secondary analysis of the IDOSP trial published in the Annals of Surgery 2020. The aim of this study was to examine the influence of stereo acuity on surgical performance in a laparoscopic training parkour with 3D- versus 4 K-2D-display technique. METHODS: The surgical performance of medical students (MS), non-board-certified surgeons (NBC), and board-certified surgeons (BC) was compared using 3D- versus 4 K-2D-display technique at a training parkour in a randomized cross-over trial. Stereo acuity was tested by TNO and Titmus Stereo tests. RESULTS: Eighty-nine participants were included in this sub-trial. The median stereo acuity for all participants, measured with the Titmus test, was 25 s arc, with TNO test 30 s arc. Higher quality stereo vision, measured with the Titmus test, correlated significantly with a reduced parkour time (r = 0.26, p = 0.02) and error (r = 0.21, p = 0.048) with the 3D screen. The TNO test did not correlate significantly with parkour performance. There was no statistically significant correlation between parkour time nor error and stereo acuity using the 4 K system (p > 0.457 respectively). Higher age showed a significant correlation with lower stereo acuity measured with TNO (r = 0.21, p = 0.014), but not with the Titmus test (r = - 0.7, p = 0.39). Seven percent of the group "NBC and BC" showed reduced stereo acuity > 120 s arc with the Titmus test and 3% with the TNO test. CONCLUSION: High-quality stereo vision is of utmost importance for surgical skills using a 3D-display system. This was most obvious for MS and for tasks that place particularly high demands on hand-eye coordination. The Titmus test was more precise than the TNO test to predict the benefit of a 3D monitor system. Experience and fine motor skills could partly compensate for a poorer stereo acuity. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov (trial number: NCT03445429, registered February 26, 2018).

Uterus-preserving management of pyomyoma: Case report of a rare complication after uterine artery embolization.

Background: Pyomyoma of the uterus is a rare but severe complication of uterine artery embolization (UAE). This report describes the uterus-preserving management of a case of fast-developing pyomyoma. Screening methods to minimize the risk of this condition are discussed. Case: A 46-year-old woman presented with fever, abdominal pain and blood stream infection on the third day after UAE, which had been performed to treat symptomatic uterine myomatosus. Broad-spectrum antibiotics proved inadequate. Magnetic resonance imaging (MRI) showed a possible superinfection of the necrotic myoma. Vaginal smear showed the same organism, a resistant Escherichia coli, as in the blood culture. Because the patient declined hysterectomy, multiple hysteroscopies with removal of necrotic pyomyoma were performed. In addition, an intrauterine gentamicin chain was placed. To our knowledge, this is the first case of pyomyoma immediately after UAE and the first report of successful hysteroscopic treatment in a septic patient. Conclusion: In order to reduce the risk of pyomyoma, pre- and postinterventional algorithms should be used.

Gender benefit in laparoscopic surgical performance using a 3D-display system: data from a randomized cross-over trial.

BACKGROUND: The use of 3D technique compared to high-resolution 2D-4K-display technique has been shown to optimize spatial orientation and surgical performance in laparoscopic surgery. Since women make up an increasing amount of medical students and surgeons, this study was designed to investigate whether one gender has a greater benefit from using a 3D compared to a 4K-display system. METHODS: In a randomized cross-over trial, the surgical performance of male and female medical students (MS), non-board certified surgeons (NBCS), and board certified surgeons (BCS) was compared using 3D- vs. 4K-display technique at a minimally invasive training parkour with multiple surgical tasks and repetitions. RESULTS: 128 participants (56 women, 72 men) were included. Overall parkour time in seconds was 3D vs. 4K for all women 770.7 ± 31.9 vs. 1068.1 ± 50.0 (p < 0.001) and all men 664.5 ± 19.9 vs. 889.7 ± 31.2 (p < 0.001). Regarding overall mistakes, participants tend to commit less mistakes while using the 3D-vision system, showing 10.2 ± 1.1 vs. 13.3 ± 1.3 (p = 0.005) for all women and 9.6 ± 0.7 vs. 12.2 ± 1.0 (p = 0.001) for all men. The benefit of using a 3D system, measured by the difference in seconds, was for women 297.3 ± 41.8 (27.84%) vs. 225.2 ± 23.3 (25.31%) for men (p = 0.005). This can be confirmed in the MS group with 327.6 ± 65.5 (35.82%) vs. 249.8 ± 33.7 (32.12%), p = 0.041 and in the NBCS group 359 ± 52.4 (28.25%) vs. 198.2 ± 54.2 (18.62%), p = 0.003. There was no significant difference in the BCS group. CONCLUSION: 3D laparoscopic display technique optimizes surgical performance compared to the 2D-4K technique for both women and men. The greatest 3D benefit was found for women with less surgical experience. As a possible result of surgical education, this gender specific difference disappears with higher grade of experience. Using a 3D-vision system could facilitate surgical apprenticeship, especially for women.

3D Versus 4K Display System - Influence of "State-of-the-art"-Display Technique on Surgical Performance (IDOSP-study) in Minimally Invasive Surgery: A Randomized Cross-over Trial.

OBJECTIVE: To evaluate if "state-of-the-art" 3D- versus 4K-display techniques could influence surgical performance. BACKGROUND: High quality minimally invasive surgery is challenging. Therefore excellent vision is crucial. 3D display technique (3D) and 2D-4K technique (4K) are designed to facilitate surgical performance, either due to spatial resolution (3D) or due to very high resolution (4K). METHODS: In randomized cross-over trial the surgical performance of medical students (MS), non-board certified surgeons (NBC), and board certified surgeons (BC) was compared using 3D versus 4K display technique at a minimally invasive training Parkour. RESULTS: One hundred twenty-eight participants were included (February 2018 through October 2019, 49 MS, 39 NBC, 40 BC). The overall Parkour time (s) 3D versus 4K was 712.5 s ± 17.5 s versus 999.5 s ±â€Š25.1 s (P < 0.001) for all levels of experience. It was (3D vs 4K) for MS (30 tasks) 555.4 s ±â€Š28.9 s versus 858.7 s ±â€Š41.6 s, (P < 0.0001), for NBC (42 tasks) 935.9 s ±â€Š31.5 s versus 1274.1 s ±â€Š45.1 s (P =< 0.001) and for BC (42 task) 646.3 s ±â€Š30.9 s versus 865.7 s ±â€Š43.7 s (P < 0.001). The overall number of mistakes was (3D vs 4K) 10.0 ±â€Š0.5 versus 13.3 ±â€Š0.7 (P < 0.001), for MS 8.9 ±â€Š0.9 versus 13.1 ±â€Š1.1 (P < 0.001), for NBC 12.45 ±â€Š1.0 versus 16.7 ±â€Š1.2 (P < 0.001) and for BC 8.8 ±â€Š1.0 versus 10.0 ±â€Š1.2 (P = 0.18). MS, BC, and NBC showed shorter performance time in 100% of the task with 3D (significantly in 6/7 tasks). For number of mistakes the effect was less pronounced for more experienced surgeons. The National Aeronautics and Space Administration-task load index was lower with 3D. CONCLUSION: 3D laparoscopic display technique optimizes surgical performance compared to the 4K technique. Surgeons benefit from the improved visualization regardless of their individual surgical expertise.

Correction to: 3D vs. 4 K Display System - Influence of "State-of-the-art"-Display Technique On Surgical Performance (IDOSP-Study) in minimally invasive surgery: protocol for a randomized cross-over trial.

After publication of our article [1] the authors have notified us that one of the names has been incorrectly spelled.

3D vs. 4K Display System - Influence of "State-of-the-art"-Display Technique On Surgical Performance (IDOSP-Study) in minimally invasive surgery: protocol for a randomized cross-over trial.

BACKGROUND: Three-dimensional (3D) stereoscopic vision is crucial to perform any kind of manual task. The reduction from real life 3D to virtual two-dimensional (2D) sight is a major challenge in minimally invasive surgery (MIS). A 3D display technique has been shown to reduce operation time and mistakes and to improve the learning curve. Therefore, the use of a3D display technique seems to optimize surgical performance for novice and experienced surgeons. Inspired by consumer electronics, a 4K display technique was recently introduced to MIS. Due to its high resolution and zoom effect, surgeons should benefit from it. The aim of this study is to evaluate if "state-of-the-art" 3D- vs. 4K-display techniques could influence surgical performance. METHODS: A randomized, cross-over, single-institution, single-blinded trial is designed. It compares the primary outcome parameter "surgical performance", represented by "performance time "and "number of mistakes", using a passive polarizing 3D and a 4K display system (two arms) to perform different tasks in a minimally invasive/laparoscopic training parkour. Secondary outcome parameters are the mental stress load (National Aeronautics and Space Administration (NASA) Task Load Index) and the learning curve. Unexperienced novices (medical students), non-board-certified, and board-certified abdominal surgeons participate in the trial (i.e., level of experience, 3 strata). The parkour consists of seven tasks (for novices, five tasks), which will be repeated three times. The 1st run of the parkour will be performed with the randomized display system, the 2nd run with the other one. After each run, the mental stress load is measured. After completion of the parkour, all participants are evaluated by an ophthalmologist for visual acuity and stereoscopic vision with five tests. Assuming a correlation of 0.5 between measurements per subject, a sample size of 36 per stratum is required to detect a standardized effect of 0.5 (including an additional 5% for a non-parametric approach) with a power of 80% at a two-sided type I error of 5%. Thus, altogether 108 subjects need to be enrolled. DISCUSSION: Complex surgical procedures are performed in a minimally invasive/laparoscopic technique. This study should provide some evidence to decide which display technique a surgeon could choose to optimize his performance. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03445429 . Registered on 7 February 2018.

Interrater reliability of schizoaffective disorder compared with schizophrenia, bipolar disorder, and unipolar depression - A systematic review and meta-analysis.

Schizoaffective disorder is a common diagnosis in clinical practice but its nosological status has been subject to debate ever since it was conceptualized. Although it is key that diagnostic reliability is sufficient, schizoaffective disorder has been reported to have low interrater reliability. Evidence based on systematic review and meta-analysis methods, however, is lacking. Using a highly sensitive literature search in Medline, Embase, and PsycInfo we identified studies measuring the interrater reliability of schizoaffective disorder in comparison to schizophrenia, bipolar disorder, and unipolar disorder. Out of 4126 records screened we included 25 studies reporting on 7912 patients diagnosed by different raters. The interrater reliability of schizoaffective disorder was moderate (meta-analytic estimate of Cohen's kappa 0.57 [95% CI: 0.41-0.73]), and substantially lower than that of its main differential diagnoses (difference in kappa between 0.22 and 0.19). Although there was considerable heterogeneity, analyses revealed that the interrater reliability of schizoaffective disorder was consistently lower in the overwhelming majority of studies. The results remained robust in subgroup and sensitivity analyses (e.g., diagnostic manual used) as well as in meta-regressions (e.g., publication year) and analyses of publication bias. Clinically, the results highlight the particular importance of diagnostic re-evaluation in patients diagnosed with schizoaffective disorder. They also quantify a widely held clinical impression of lower interrater reliability and agree with earlier meta-analysis reporting low test-retest reliability.

Diagnostic shift in patients diagnosed with schizoaffective disorder: a systematic review and meta-analysis of rediagnosis studies.

OBJECTIVES: The diagnosis of schizoaffective disorder (SAD) is well established in clinical practice but is heavily disputed on theoretical grounds. We analyzed the extent and direction of diagnostic shift in SAD patients. METHODS: We searched Medline, Embase, and PsycINFO systematically for all studies documenting two diagnostic assessments at different points in time (rediagnosis studies) and used meta-analytic methods to quantify diagnostic shift. Multiple prespecified and post-hoc subgroup analyses (e.g., rater blinding) and meta-regressions (e.g., year of publication) were carried out. RESULTS: We included 31 studies out of 4,415 articles screened: 27 studies on the shift from and 23 studies on the shift to SAD (median time span was two years). A total of 36% of patients with a diagnosis of SAD at first assessment switch, many to schizophrenia (19%), 14% to affective disorders, and 6% to other disorders. Among patients diagnosed with SAD at second assessment, 55% had received a different diagnosis at first assessment, a large portion of whom had been initially diagnosed with affective disorder (24%), schizophrenia (18%), and other disorders (12%). CONCLUSIONS: Diagnostic shift in SAD patients is substantial. Psychiatrists need to reassess the diagnosis during the course of the illness and to adjust treatment. Slightly more diagnoses of SAD are changed to schizophrenia than to affective disorders, and among patients rediagnosed with SAD, fewer have been diagnosed with schizophrenia than with affective disorders. Thus, at the diagnostic level, there seems to be a slight trend toward schizophrenia during the course of functional psychoses.

Test-retest reliability of schizoaffective disorder compared with schizophrenia, bipolar disorder, and unipolar depression--a systematic review and meta-analysis.

OBJECTIVES: Schizoaffective disorder is a frequent diagnosis, and its reliability is subject to ongoing discussion. We compared the diagnostic reliability of schizoaffective disorder with its main differential diagnoses. METHODS: We systematically searched Medline, Embase, and PsycInfo for all studies on the test-retest reliability of the diagnosis of schizoaffective disorder as compared with schizophrenia, bipolar disorder, and unipolar depression. We used meta-analytic methods to describe and compare Cohen's kappa as well as positive and negative agreement. In addition, multiple pre-specified and post hoc subgroup and sensitivity analyses were carried out. RESULTS: Out of 4,415 studies screened, 49 studies were included. Test-retest reliability of schizoaffective disorder was consistently lower than that of schizophrenia (in 39 out of 42 studies), bipolar disorder (27/33), and unipolar depression (29/35). The mean difference in kappa between schizoaffective disorder and the other diagnoses was approximately 0.2, and mean Cohen's kappa for schizoaffective disorder was 0.50 (95% confidence interval: 0.40-0.59). While findings were unequivocal and homogeneous for schizoaffective disorder's diagnostic reliability relative to its three main differential diagnoses (dichotomous: smaller versus larger), heterogeneity was substantial for continuous measures, even after subgroup and sensitivity analyses. CONCLUSIONS: In clinical practice and research, schizoaffective disorder's comparatively low diagnostic reliability should lead to increased efforts to correctly diagnose the disorder.