Laparoscopy training of novices with complex curved instruments using 2D- and 3D-visualization.

PURPOSE: Beside many advantages, disadvantages such as reduced degrees of freedom and poorer depth perception are still apparent in laparoscopic surgery. 3D visualization and the development of complex instruments are intended to counteract the disadvantages. We want to find out whether the use of complex instruments and 3D visualization has an influence on the performance of novices. METHODS: 48 medical students with no experience in laparoscopic surgery or simulator-based laparoscopy training were included. They were randomized in four groups according to a stratification assessment. During a structured training period they completed the FLS-Tasks "PEG Transfer", "Pattern Cut" and "Intracorporeal Suture" and a transfer task based on these three. Two groups used conventional laparoscopic instruments with 3D or 2D visualization, two groups used complex curved instruments. The groups were compared in terms of their performance. RESULTS: In 2D laparoscopy there was a better performance with straight instruments vs. curved instruments in PEG Transfer and Intracorporeal Suture. In the transfer task, fewer errors were made with straight instruments. In 2D vs. 3D laparoscopy when using complex curved instruments there was an advantage in Intracorporeal Suture and PEG Transfer for 3D visualization. Regarding the transfer exercise, a better performance was observed and fewer errors were made in 3D group. CONCLUSION: We could show that learning laparoscopic techniques with complex curved instruments is more difficult with standard 2D visualization and can be overcome using 3D optics. The use of curved instruments under 3D vision seems to be advantageous when working on more difficult tasks.

Tracking and evaluating motion skills in laparoscopy with inertial sensors.

BACKGROUND: Analysis of surgical instrument motion is applicable in surgical skill assessment and monitoring of the learning progress in laparoscopy. Current commercial instrument tracking technology (optical or electromagnetic) has specific limitations and is expensive. Therefore, in this study, we apply inexpensive, off-the-shelf inertial sensors to track laparoscopic instruments in a training scenario. METHODS: We calibrated two laparoscopic instruments to the inertial sensor and investigated its accuracy on a 3D-printed phantom. In a user study during a one-week laparoscopy training course with medical students and physicians, we then documented and compared the training effect in laparoscopic tasks on a commercially available laparoscopy trainer (Laparo Analytic, Laparo Medical Simulators, Wilcza, Poland) and the newly developed tracking setup. RESULTS: Eighteen participants (twelve medical students and six physicians) participated in the study. The student subgroup showed significantly poorer results for the count of swings (CS) and count of rotations (CR) at the beginning of the training compared to the physician subgroup (p = 0.012 and p = 0.042). After training, the student subgroup showed significant improvements in the rotatory angle sum, CS, and CR (p = 0.025, p = 0.004 and p = 0.024). After training, there were no significant differences between medical students and physicians. There was a strong correlation between the measured learning success (LS) from the data of our inertial measurement unit system (LSIMU) and the Laparo Analytic (LSLap) (Pearson's r = 0.79). CONCLUSION: In the current study, we observed a good and valid performance of inertial measurement units as a possible tool for instrument tracking and surgical skill assessment. Moreover, we conclude that the sensor can meaningfully examine the learning progress of medical students in an ex-vivo setting.

AR visualizations in laparoscopy: surgeon preferences and depth assessment of vascular anatomy.

Introduction: This study compares five augmented reality (AR) vasculature visualization techniques in a mixed-reality laparoscopy simulator with 50 medical professionals and analyzes their impact on the surgeon. Material and methods: ​​The different visualization techniques' abilities to convey depth were measured using the participant's accuracy in an objective depth sorting task. Demographic data and subjective measures, such as the preference of each AR visualization technique and potential application areas, were collected with questionnaires. Results: Despite measuring differences in objective measurements across the visualization techniques, they were not statistically significant. In the subjective measures, however, 55% of the participants rated visualization technique II, 'Opaque with single-color Fresnel highlights', as their favorite. Participants felt that AR could be useful for various surgeries, especially complex surgeries (100%). Almost all participants agreed that AR could potentially improve surgical parameters, such as patient safety (88%), complication rate (84%), and identifying risk structures (96%). Conclusions: More studies are needed on the effect of different visualizations on task performance, as well as more sophisticated and effective visualization techniques for the operating room. With the findings of this study, we encourage the development of new study setups to advance surgical AR.

Evaluation of an Integrated Smart Sensor System for Real-Time Characterization and Digitalization of Postoperative Abdominal Drain Output: A Pilot Study.

Background: For centuries, surgeons have relied on surgical drains during postoperative care. Despite all advances in modern medicine and the area of digitalization, as of today, most if not all assessment of abdominal secretions excreted via surgical drains are carried out manually. We here introduce a novel integrated Smart Sensor System (Smart Drain) that allows for real-time characterization and digitalization of postoperative abdominal drain output at the patient's bedside. Methods: A prototype of the Smart Drain was developed using a sophisticated spectrometer for assessment of drain output. The prototype measures 10 × 6 × 6 cm and therefore easily fits at the bedside. At the time of measurement with our Smart Drain, the drain output was additionally sent off to be analyzed in our routine laboratory for typical markers of interest in abdominal surgery such as bilirubin, lipase, amylase, triglycerides, urea, protein, and red blood cells. A total of 45 samples from 19 patients were included. Results: The measurements generated were found to correlate with conventional laboratory measurements for bilirubin (r = .658, P = .000), lipase (r = .490, P = .002), amylase (r = .571, P = .000), triglycerides (r = .803, P = .000), urea (r = .326, P = .033), protein (r = .387, P = .012), and red blood cells (r = .904, P = .000). Conclusions: To our best knowledge, for the first time we describe a device using a sophisticated spectrometer that allows for real-time characterization and digitalization of postoperative abdominal drain output at the patient's bedside.

Intra-arterial versus negative-staining of embryonal resection borders with indocyanine green (ICG) fluorescence for total mesorectal excision in colorectal cancer - an experimental feasibility study in a porcine model.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Laparoscopic lower rectal resections in accordance with the oncological principles are recommended as the gold standard for CRC surgical management. However, the learning curve for adopting these techniques is quite steep and the incomplete resections are predictive of local recurrence. This study was conducted in an attempt to find a way to help surgeons to overcome some of these difficulties and define the right resection margins. MATERIAL AND METHODS: As such, we carried out two laparoscopic lower rectal resections in porcine models. The first resection was performed following the ligation and selective infusion of Indocyanine Green (ICG) into the inferior mesenteric artery (IMA), and the second after the ligation of both inferior mesenteric artery and vein (IMV) and systemic intravenous infusion of ICG. Fluorescence was detected in real time by means of an infrared imaging system. RESULTS: Sharp resection margins were defined after intra-arterial infusion, and all the tissues in the IMA basin were colored in the first case. In the second model every organ and tissue was colored except the rectum, urinary bladder and ductus deferens. CONCLUSIONS: Although systemic intra-venous application of ICG and negative-staining of the rectum including the mesorectum is much easier compared to laparoscopic inter-arterial perfusion through IMA, image results of selevtive IMA-perfusion appear in sharper discrimination of the several layers. Further investigation should focus on simplifying this technique.

Probabilistic Deep Learning to Quantify Uncertainty in Air Quality Forecasting.

Data-driven forecasts of air quality have recently achieved more accurate short-term predictions. However, despite their success, most of the current data-driven solutions lack proper quantifications of model uncertainty that communicate how much to trust the forecasts. Recently, several practical tools to estimate uncertainty have been developed in probabilistic deep learning. However, there have not been empirical applications and extensive comparisons of these tools in the domain of air quality forecasts. Therefore, this work applies state-of-the-art techniques of uncertainty quantification in a real-world setting of air quality forecasts. Through extensive experiments, we describe training probabilistic models and evaluate their predictive uncertainties based on empirical performance, reliability of confidence estimate, and practical applicability. We also propose improving these models using "free" adversarial training and exploiting temporal and spatial correlation inherent in air quality data. Our experiments demonstrate that the proposed models perform better than previous works in quantifying uncertainty in data-driven air quality forecasts. Overall, Bayesian neural networks provide a more reliable uncertainty estimate but can be challenging to implement and scale. Other scalable methods, such as deep ensemble, Monte Carlo (MC) dropout, and stochastic weight averaging-Gaussian (SWAG), can perform well if applied correctly but with different tradeoffs and slight variations in performance metrics. Finally, our results show the practical impact of uncertainty estimation and demonstrate that, indeed, probabilistic models are more suitable for making informed decisions.

Design, Optimization, and Study of Small Molecules That Target Tau Pre-mRNA and Affect Splicing.

Approximately 95% of human genes are alternatively spliced, and aberrant splicing events can cause disease. One pre-mRNA that is alternatively spliced and linked to neurodegenerative diseases is tau (microtubule-associated protein tau), which can cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and can contribute to Alzheimer's disease. Here, we describe the design of structure-specific lead small molecules that directly target tau pre-mRNA from sequence. This was followed by hit expansion and analogue synthesis to further improve upon these initial lead molecules. The emergent compounds were assessed for functional activity in a battery of assays, including binding assays and an assay that mimics molecular recognition of tau pre-mRNA by a U1 small nuclear ribonucleoprotein (snRNP) splicing factor. Compounds that emerged from these studies had enhanced potency and selectivity for the target RNA relative to the initial hits, while also having significantly improved drug-like properties. The compounds are shown to directly target tau pre-mRNA in cells, via chemical cross-linking and isolation by pull-down target profiling, and to rescue disease-relevant splicing of tau pre-mRNA in a variety of cellular systems, including primary neurons. More broadly, this study shows that lead, structure-specific compounds can be designed from sequence and then further optimized for their physicochemical properties while at the same time enhancing their activity.

Acetabular defects in revision hip arthroplasty: a therapy-oriented classification.

INTRODUCTION: The treatment of severe acetabular bone loss remains a difficult challenge. No classification system is available that combines intuitive use, structured design and offers a therapeutic recommendation according to the current literature and modern state of the art treatment options. The goal of this study is to introduce an intuitive, reproducible and reliable guideline for the evaluation and treatment of acetabular defects. METHODS: The proposed Acetabular Defect Classification (ADC) is based on the integrity of the acetabular rim and supporting structures. It consists of 4 main types of defects ascending in severity and subdivisions narrowing down-defect location. Type 1 presents an intact acetabular rim, type 2 includes a noncontained defect of the acetabular rim ≤ 10 mm, in type 3 the rim defect exceeds 10 mm and type 4 includes different kinds of pelvic discontinuity. A collective of 207 preoperative radiographs were graded according to ADC and correlated with intraoperative findings. Additionally, a randomized sample of 80 patients was graded according to ADC by 5 observers to account for inter- and intra-rater reliability. RESULTS: We evaluated the agreement of preoperative, radiographic grading and intraoperative findings presenting with a k value of 0.74. Interobserver agreement presented with a k value of 0.62 and intraobserver at a k value of 0.78. CONCLUSION: The ADC offers an intuitive, reliable and reproducible classification system. It guides the surgeon pre- and intraoperatively through a complex field of practice.

Intraarterial indocyanine green (ICG) fluorescence augmentation by marking embryonal resection areas in colorectal surgery: a feasibility study in a porcine model.

Aim: In this pilot animal study we examined whether it is possible to visualize the embryonal resection layers by using intraarterial indocyanine green (ICG) staining when performing total mesorectal excision (TME) for carcinoma of the rectum. Material and methods: We injected ICG into the inferior mesenteric artery (AMI) of four swines to see whether the watershed area of the arterial supply zone can be sufficiently visualized by fluorescence imaging in order to mark the right dissection area along the fascia parietalis before and during resection. Results: We observed a fluorescence signal in all the supplied areas of AMI but not in other parts of the abdominal cavity or other organs. Additionally, the mesorectum also showed a sharp border between colored and non-colored tissue. Conclusion: In this study we present that resection borders may be determined before resection based on ICG-perfusion and we showed that intraoperative exclusive coloring of the rectum including the mesorectum is possible. Visualizing resection borders based on ICG-perfusion before settling the first cut may be a new approach in oncological surgery.

Who profits from three-dimensional optics in endoscopic surgery? Analysis of manual tasks under two-dimensional/three-dimensional optic vision using a pelvic trainer model.

Background: In endoscopic operations, direct binocular view, tissue sensation and depth perception get lost. It is still unclear whether the novel three-dimensional (3D) high-definition (HD) cameras are able to compensate the limited senses and how this affects the skill set of users with different endoscopic experience. This study aimed first to evaluate if the 3D technology improves depth perception, precision and space orientation as compared to conventional two-dimensional (2D) HD technology. The second aim was to determine the 3D influence on participants with different endoscopic experience. Methods: A total of 24 participants of different experience levels performed three different tasks on a pelvic trainer using the same thoracoscopic unit in 2D and 3D modes. Results were statistically analysed using Student's t-test and Pearson's product-moment correlation. Results: Across all the participants, we found that 3D optic vision significantly reduced the needed time to perform a defined difficult task in comparison to 2D. This difference was less pronounced in participants with higher experience level. Participants with eyeglasses performed slower in both 2D and 3D in comparison to participants with normal vision. Only participants with normal vision could significantly improve their completion times with 3D optic vision. Conclusions: By testing the novel generation of 3D HD cameras, we could demonstrate that the 3D optic of these systems improves depth perception and space orientation for novices and experienced users and especially inexperienced users benefit from 3D optic.

Sucrose and Ethylene Signaling Interact to Modulate the Circadian Clock.

Circadian clocks drive rhythmic physiology and metabolism to optimize plant growth and performance under daily environmental fluctuations caused by the rotation of the planet. Photosynthesis is a key metabolic process that must be appropriately timed to the light-dark cycle. The circadian clock contributes to the regulation of photosynthesis, and in turn the daily accumulation of sugars from photosynthesis also feeds back to regulate the circadian oscillator. We have previously shown that GIGANTEA (GI) is required to sustain Suc-dependent circadian rhythms in darkness. The mechanism by which Suc affects the circadian oscillator in a GI-dependent manner was unknown. Here, we identify that Suc sustains rhythms in the dark by stabilizing GI protein, dependent on the F-box protein ZEITLUPE, and implicate CONSTITUTIVE TRIPLE RESPONSE1 (CTR1), a negative regulator of ethylene signaling. Our identification of a role for CTR1 in the response to Suc prompted a reinvestigation of the effects of ethylene on the circadian oscillator. We demonstrate that ethylene shortens the circadian period, conditional on the effects of Suc and requiring GI These findings reveal that Suc affects the stability of circadian oscillator proteins and can mask the effects of ethylene on the circadian system, identifying novel molecular pathways for input of sugar to the Arabidopsis (Arabidopsis thaliana) circadian network.

5-Hydroxymethylcytosine is a nuclear biomarker to assess biological potential in histologically ambiguous heavily pigmented melanocytic neoplasms.

BACKGROUND: 5-Hydroxymethylcytosine (5-hmC) is an epigenetic marker detectable through immunohistochemistry (IHC) that has been shown to distinguish benign nevi from melanoma with high sensitivity and specificity. The purpose of the study was to explore its diagnostic utility in a subset of histologically challenging, heavily pigmented cutaneous melanocytic neoplasms. METHODS: 5-hmC IHC was performed on 54 heavily pigmented melanocytic tumors. Semi-quantitative analysis of immunoreactivity was correlated with clinical, pathologic and follow-up data. RESULTS: Benign melanocytic neoplasms (4 of 4 blue nevi with epithelioid change; 12 of 12 combined nevi; 5 of 5 deep penetrating nevi, DPN) exhibited strong 5-hmC nuclear reactivity. Eight heavily pigmented blue nevus-like melanomas and 7 of 8 pigmented epithelioid melanocytomas (PEM) showed significant 5-hmC loss. Five of 7 atypical DPN cases and 8 of 10 melanocytic tumors of uncertain malignant potential (MELTUMP) showed low to intermediate 5-hmC immunoreactivity. These differences were statistically significant (P-value <.0001). CONCLUSIONS: Loss of 5-hmC may be helpful in differentiating benign, diagnostically challenging, heavily pigmented melanocytic tumors from those with malignant potential. The intermediate to low 5-hmC immunoreactivity in atypical DPNs, PEMs and so-called MELTUMP categories further underscores the need to consider these neoplasms as having some potential for lethal biological behavior.

Connectivity between surface and deep waters determines prokaryotic diversity in the North Atlantic Deep Water.

To decipher the influence of depth stratification and surface provincialism on the dark ocean prokaryotic community composition, we sampled the major deep-water masses in the eastern North Atlantic covering three biogeographic provinces. Their diversity was evaluated using ordination and canonical analysis of 454 pyrotag sequences. Variance partitioning suggested that 16% of the variation in the bacterial community composition was based on depth stratification while 9% of the variation was due to geographic location. General linear mixed effect models showed that the community of the subsurface waters was connected to the dark ocean prokaryotic communities in different biogeographic provinces. Cluster analysis indicated that some prokaryotic taxa are specific to distinct regions in bathypelagic water masses. Taken together, our data suggest that the dark ocean prokaryotic community composition of the eastern North Atlantic is primed by the formation and the horizontal transport of water masses.

Single-incision laparoscopic cholecystectomy with curved versus linear instruments assessed by systematic review and network meta-analysis of randomized trials.

BACKGROUND: Single-incision laparoscopic surgery poses significant ergonomic limitations. Curved instruments have been developed in order to address the issue of lack of triangulation. Direct comparison between single-incision laparoscopic surgeries with conventional linear and curved instruments has not been performed to date. METHODS: MEDLINE, CENTRAL and OpenGrey were searched to identify relevant randomized trials. A network meta-analysis was applied to compare operative risks, conversion, duration of surgery and the need for placement of an adjunct trocar in single-incision laparoscopic cholecystectomy with linear and curved instruments. The random-effects model was applied for two sets of comparisons, with conventional laparoscopic cholecystectomy as the reference treatment. Odds ratios, mean differences and 95% confidence intervals were calculated. RESULTS: Twenty-three randomized trials encompassing 1737 patients were included. The use of curved instruments was associated with increased operative time (mean difference 32.53 min, 95% CI 24.23-40.83) and higher odds for the use of an adjunct trocar (odds ratio 22.81, 95% CI 16.69-28.94) compared to the use of linear instruments. Perioperative risks could not be comparatively assessed due to the low number of events. CONCLUSION: Single-incision laparoscopic cholecystectomy with curved instruments may be associated with an increased level of operative difficulty, as reflected by the need for auxiliary measures for exposure and increased operative time as compared to the use of linear instruments. Current instrumentation requires further improvement, tailored to the features of single-incision laparoscopic surgery (CRD42015015721).

Laparoscopic colorectal surgery confers lower mortality in the elderly: a systematic review and meta-analysis of 66,483 patients.

BACKGROUND: Increasing life expectancy requires specific attention on geriatric patients. Data support a potential reduction of surgical morbidity for patients undergoing laparoscopic surgery as compared to conventional surgery. The aim of this study was to investigate the comparative effect of laparoscopic and open colorectal surgery on geriatric patients. METHODS: A systematic review of electronic information sources was undertaken. Studies that provided outcome data on patients aged 65 years or older, subjected to laparoscopic or open colorectal surgery, were considered. Mortality, morbidity, cardiac and pulmonary complications were the outcome measures of treatment effect. The methodological quality of selected studies was independently appraised by two reviewers. Random effects model was applied to synthesize outcome data. RESULTS: Twenty-seven articles providing data for 66,592 patients were included in the analysis. Patients undergoing laparoscopic surgery had a decreased risk for mortality (2.2 vs. 5.4 %; OR 0.55, 95 % CI 0.44-0.67), overall morbidity (19.3 vs. 26.7 %; OR 0.54, 95 % CI 0.46-0.63), cardiac (4.7 vs. 7.7 %; OR 0.60, 95 % CI 0.39-0.92) and respiratory complications (3.9 vs. 6.3 %; OR 0.67, 95 % CI 0.47-0.95). Sensitivity analysis including reports with similar age, American Society of Anesthesiologists score and/or similar prevalence of cardiopulmonary morbidity between the laparoscopic and the open treatment arm validated the outcome estimates of the primary analysis. CONCLUSIONS: This analysis supports a substantial benefit for elderly patients undergoing laparoscopic in comparison with open colorectal surgery. The comparative effect of either approach on geriatric patients with pulmonary and cardiac comorbidities is a subject of further investigation.

Laparoscopic versus open obesity surgery: a meta-analysis of pulmonary complications.

The clinical effects of laparoscopy in the pulmonary function of obese patients have been poorly investigated in the past. A systematic review was undertaken, with the objective to identify published evidence on pulmonary complications in laparoscopic surgery in the obese. Outcome measures included pulmonary morbidity, pulmonary infection and mortality. The random effects model was used to calculate combined overall effect sizes of pooled data. Data are presented as the odds ratio (OR) with 95% confidence interval (CI). A total of 6 randomized and 14 observational studies were included, which reported data on 185,328 patients. Pulmonary complications occurred in 1.6% of laparoscopic and in 3.6% of open procedures (OR 0.45, 95% CI 0.34-0.60). Pneumonia was reported in 0.5% and in 1.1%, respectively (OR 0.45, 95% CI 0.40-0.51). Available evidence suggests lower pulmonary morbidity for laparoscopic surgery in obese patients; further quality studies are however necessary to consolidate these findings.

A systematic review and analysis of factors associated with methodological quality in laparoscopic randomized controlled trials.

Several methods for assessment of methodological quality in randomized controlled trials (RCTs) have been developed during the past few years. Factors associated with quality in laparoscopic surgery have not been defined till date. The aim of this study was to investigate the relationship between bibliometric and the methodological quality of laparoscopic RCTs. The PubMed search engine was queried to identify RCTs on minimally invasive surgery published in 2012 in the 10 highest impact factor surgery journals and the 5 highest impact factor laparoscopic journals. Eligible studies were blindly assessed by two independent investigators using the Scottish Intercollegiate Guidelines Network (SIGN) tool for RCTs. Univariate and multivariate analyses were performed to identify potential associations with methodological quality. A total of 114 relevant RCTs were identified. More than half of the trials were of high or acceptable quality. Half of the reports provided information on comparative demo graphic data and only 21% performed intention-to-treat analysis. RCTs with sample size of at least 60 patients presented higher methodological quality (p = 0.025). Upon multiple regression, reporting on preoperative care and the experience level of surgeons were independent factors of quality.

Laparoscopic augmentation of the diaphragmatic hiatus with biologic mesh versus suture repair: a systematic review and meta-analysis.

PURPOSE: Laparoscopic repair of large hiatal hernias is associated with high recurrence rates. Erosion and mesh migration are rare but devastating complications of synthetic mesh repair, whereas reoperation is accompanied by significant operative morbidity. The aim of this study was to estimate the comparative risk of hernia recurrence following primary suture or biologic mesh repair. METHODS: A systematic literature search of the MEDLINE database was performed and comparative data of relevant studies were combined using the Mantel-Haenszel meta-analysis model. The odds ratio (OR) for hernia recurrence with 95 % confidence interval (CI) was calculated. RESULTS: Five relevant studies (two randomized controlled trials and three case-control studies) and one follow-up report of a randomized trial, encompassing 295 patients, were identified. Small intestine submucosa and human acellular cadaveric dermis were used as mesh grafts. Short-term recurrence rates were 16.6 and 3.5 % for suture repair and biologic mesh repair, respectively (OR 3.74, 95 % CI 1.55-8.98, p = 0.003). Long-term recurrence based on data provided by one trial only was 51.3 and 42.4 %, respectively (OR 1.43, 95 % CI 0.56-3.63, p = 0.45). Sensitivity analysis of the two randomized trials at short-term follow up demonstrated no significant difference (OR 2.54, 95 % CI 0.92-7.02, p = 0.07). CONCLUSIONS: Biologic mesh repair of large hiatal hernias may confer short-term benefits in terms of hernia recurrence; however, the limited available information does not allow us to make conclusions about the long-term efficacy of biologic mesh in this setting. Individual biologic mesh grafts require further clinical assessment.