Uncovering the spread of drug-resistant bacteria through next-generation sequencing based surveillance: transmission of extended-spectrum ß-lactamase-producing Enterobacterales by a contaminated duodenoscope.

Contamination of duodenoscopes is a significant concern due to the transmission of multidrug-resistant organisms (MDROs) among patients who undergo endoscopic retrograde cholangiopancreatography (ERCP), resulting in outbreaks worldwide. In July 2020, it was determined that three different patients, all had undergone ERCP with the same duodenoscope, were infected. Two patients were infected with blaCTX-M-15 encoding Citrobacter freundii, one experiencing a bloodstream infection and the other a urinary tract infection, while another patient had a bloodstream infection caused by blaSHV-12 encoding Klebsiella pneumoniae. Molecular characterization of isolates was available as every ESBL-producing isolate undergoes Next-Generation Sequencing (NGS) for comprehensive genomic analysis in our center. After withdrawing the suspected duodenoscope, we initiated comprehensive epidemiological research, encompassing case investigations, along with a thorough duodenoscope investigation. Screening of patients who had undergone ERCP with the implicated duodenoscope, as well as a selection of hospitalized patients who had ERCP with a different duodenoscope during the outbreak period, led to the discovery of three additional cases of colonization in addition to the three infections initially detected. No microorganisms were detected in eight routine culture samples retrieved from the suspected duodenoscope. Only after destructive dismantling of the duodenoscope, the forceps elevator was found to be positive for blaSHV-12 encoding K. pneumoniae which was identical to the isolates detected in three patients. This study highlights the importance of using NGS to monitor the transmission of MDROs and demonstrates that standard cultures may fail to detect contaminated medical equipment such as duodenoscopes.

Modeling of inflicted head injury by shaking trauma in children: what can we learn? : Update to parts I&II: A systematic review of animal, mathematical and physical models.

Inflicted shaking trauma can cause injury in infants, but exact injury mechanisms remain unclear. Controversy exists, particularly in courts, whether additional causes such as impact are required to produce injuries found in cases of (suspected) shaking. Publication rates of studies on animal and biomechanical models of inflicted head injury by shaking trauma (IHI-ST) in infants continue rising. Dissention on the topic, combined with its legal relevance, makes maintaining an up-to-date, clear and accessible overview of the current knowledge-base on IHI-ST essential. The current work reviews recent (2017-2023) studies using models of IHI-ST, serving as an update to two previously published reviews. A systematic review was conducted in Scopus and PubMed for articles using animal, physical and mathematical models for IHI-ST. Using the PRISMA methodology, two researchers independently screened the publications. Two, five, and ten publications were included on animal, physical, and mathematical models of IHI-ST, respectively. Both animal model studies used rodents. It is unknown to what degree these can accurately represent IHI-ST. Physical models were used mostly to investigate gross head-kinematics during shaking. Most mathematical models were used to study local effects on the eye and the head's internal structures. All injury thresholds and material properties used were based on scaled adult or animal data. Shaking motions used as inputs for animal, physical and mathematical models were mostly greatly simplified. Future research should focus on using more accurate shaking inputs for models, and on developing or and validating accurate injury thresholds applicable for shaking.

Process model analysis of parenchyma sparing laparoscopic liver surgery to recognize surgical steps and predict impact of new technologies.

BACKGROUND: Surgical process model (SPM) analysis is a great means to predict the surgical steps in a procedure as well as to predict the potential impact of new technologies. Especially in complicated and high-volume treatments, such as parenchyma sparing laparoscopic liver resection (LLR), profound process knowledge is essential for enabling improving surgical quality and efficiency. METHODS: Videos of thirteen parenchyma sparing LLR were analyzed to extract the duration and sequence of surgical steps according to the process model. The videos were categorized into three groups, based on the tumor locations. Next, a detailed discrete events simulation model (DESM) of LLR was built, based on the process model and the process data obtained from the endoscopic videos. Furthermore, the impact of using a navigation platform on the total duration of the LLR was studied with the simulation model by assessing three different scenarios: (i) no navigation platform, (ii) conservative positive effect, and (iii) optimistic positive effect. RESULTS: The possible variations of sequences of surgical steps in performing parenchyma sparing depending on the tumor locations were established. The statistically most probable chain of surgical steps was predicted, which could be used to improve parenchyma sparing surgeries. In all three categories (i-iii) the treatment phase covered the major part (~ 40%) of the total procedure duration (bottleneck). The simulation results predict that a navigation platform could decrease the total surgery duration by up to 30%. CONCLUSION: This study showed a DESM based on the analysis of steps during surgical procedures can be used to predict the impact of new technology. SPMs can be used to detect, e.g., the most probable workflow paths which enables predicting next surgical steps, improving surgical training systems, and analyzing surgical performance. Moreover, it provides insight into the points for improvement and bottlenecks in the surgical process.

Contactless Size Reference in Forensic Photography-Design and Verification of the Novel FreeRef-1 System.

In photographs of evidence in forensic investigations, physical size references (e.g., rulers or stickers) are often placed next to a trace to allow us to take measurements from photos. However, this is laborious and introduces contamination risks. The FreeRef-1 system is a contactless size reference system that allows us to take forensic photographs without having to be close to the evidence, and allows photographing under large angles without losing accuracy. The FreeRef-1 system performance was assessed using technical verification tests, inter-observer checks and user tests with forensic professionals. The results show that the measurements taken with photos using the FreeRef-1 system were at least as accurate as those taken using conventional techniques. Furthermore, with the FreeRef-1 system, even photographs taken under strongly oblique angles provided accurate measurements. The results suggest that the FreeRef-1 system will facilitate photographing evidence even in hard-to-reach places, such as under tables and on walls and ceilings, while increasing the accuracy and speed.

Generic surgical process model for minimally invasive liver treatment methods.

Surgical process modelling is an innovative approach that aims to simplify the challenges involved in improving surgeries through quantitative analysis of a well-established model of surgical activities. In this paper, surgical process model strategies are applied for the analysis of different Minimally Invasive Liver Treatments (MILTs), including ablation and surgical resection of the liver lesions. Moreover, a generic surgical process model for these differences in MILTs is introduced. The generic surgical process model was established at three different granularity levels. The generic process model, encompassing thirteen phases, was verified against videos of MILT procedures and interviews with surgeons. The established model covers all the surgical and interventional activities and the connections between them and provides a foundation for extensive quantitative analysis and simulations of MILT procedures for improving computer-assisted surgery systems, surgeon training and evaluation, surgeon guidance and planning systems and evaluation of new technologies.

Lethal smothering with a pillow - How 181 music festival visitors tried to kill a dummy.

PURPOSE: Smothering to death is most often done with a soft cover, such as a pillow. This is one of the hardest to diagnose causes of death. Knowing more about how people perform such an act and whether there is any correlation between perpetrator characteristics and smothering approaches may help in solving criminal cases involving smothering. METHODS: A total of 181 visitors of a music festival were asked to smother a dummy with a pillow. Each participant provided their age, gender, dominant hand, length, weight, alcohol use (last 24h) and drug use (last 24h) in a questionnaire. Forces applied by the participant on the dummy head with the pillow were continuously measured and the smothering modus operandi (described by aspects such as the placement of the hands, feet and body weight) was obtained from video recordings. RESULTS: Participants with high alcohol consumption provided higher smothering forces. Increases were also found for taller participants and those who had used drugs. Smothering seemed most effective when placing both hands on the pillow on the head and when placing the center of mass as much directly above the dummy head as possible. A stable, central stance also benefitted smothering effectiveness. CONCLUSION: Forensic case work may potentially benefit from these results in the future by linking the current results to the location of hand and finger marks on a pillow.

Thresholds for the assessment of inflicted head injury by shaking trauma in infants: a systematic review.

In order to investigate potential causal relations between the shaking of infants and injuries, biomechanical studies compare brain and skull dynamic behavior during shaking to injury thresholds. However, performing shaking tolerance research on infants, either in vivo or ex vivo, is extremely difficult, if not impossible. Therefore, infant injury thresholds are usually estimated by scaling or extrapolating adult or animal data obtained from crash tests or whiplash experiments. However, it is doubtful whether such data accurately matches the biomechanics of shaking in an infant. Hence some thresholds may be inappropriate to be used for the assessment of inflicted head injury by shaking trauma in infants. A systematic literature review was conducted to 1) provide an overview of existing thresholds for head- and neck injuries related to violent shaking, and 2) to identify and discuss which thresholds have been used or could be used for the assessment of inflicted head injury by shaking trauma in infants. Key findings: The majority of studies establishing or proposing injury thresholds were found to be based on loading cycle durations and loading cycle repetitions that did not resemble those occurring during shaking, or had experimental conditions that were insufficiently documented in order to evaluate the applicability of such thresholds. Injury thresholds that were applied in studies aimed at assessing whether an injury could occur under certain shaking conditions were all based on experiments that did not properly replicate the loading characteristics of shaking. Somewhat validated threshold scaling methods only exist for scaling concussive injury thresholds from adult primate to adult human. Scaling methods that have been used for scaling other injuries, or for scaling adult injury thresholds to infants were not validated. There is a clear and urgent need for new injury thresholds established by accurately replicating the loading characteristics of shaking.

Minimizing aerosol bone dust during autopsies.

When sawing bone for medical or medico-legal procedures, fine, airborne dust is produced (aerosols) that can pose a health hazard when inhaled. The aim of this study was to determine the influence of saw blade frequency and contact load, bone condition, test environment, and saw blade type, on the production of aerosol particles. A custom test setup was designed, manufactured and used in 8 bone sawing experiments, using a particle counter to determine the production of aerosol particles while varying the 5 chosen parameters. The number of counted particles was highest with higher saw blade frequencies, lower saw blade contact loads, in dry completely skeletonized bone compared to fresh bone, and using an electrical oscillating saw compared to hand-sawing. Under all conditions, the high amount of aerosol counted posed potential health risks. The ventilation system that we tested was adequate in removing the produced particles, but these high-tech systems are not always available in developing countries or emergency situations. The production of aerosols can be reduced by optimizing the sawing parameters. However, even the lowest number of aerosol particles counted during the current study was high enough to cause potential health risks to practitioners. Safety precautions should be taken, such as external ventilation, proper breathing gear, and adequate protocols, to truly minimize the risk in all bone sawing scenarios.

Independent root-cause analysis of contributing factors, including dismantling of 2 duodenoscopes, to investigate an outbreak of multidrug-resistant Klebsiella pneumoniae.

BACKGROUND AND AIMS: Worldwide, an increasing number of duodenoscope-associated outbreaks are reported. The high prevalence rate of contaminated duodenoscopes puts patients undergoing ERCP at risk of exogenous transmission of microorganisms. The contributing factors of the duodenoscope design to contamination are not well understood. This article reports on the investigation after the outbreak of a multidrug-resistant Klebsiella pneumoniae (MRKP) related to 2 Olympus TJF-Q180V duodenoscopes. METHODS: We conducted a contact patient screening and microbiologic laboratory database search. Reprocessing procedures were audited, and both duodenoscopes were fully dismantled to evaluate all potential contamination factors. Outcomes were reviewed by an experienced independent expert. RESULTS: In total, 102 patients who had undergone an ERCP procedure from January to August 2015 were invited for screening. Cultures were available of 81 patients, yielding 27 MRKP-infected or -colonized patients. Ten patients developed an MRKP-related active infection. The 2 duodenoscopes had attack rates (the number of infected or colonized cases/number of exposed persons) of 35% (17/49) and 29% (7/24), respectively. Identical MRKP isolates were cultured from channel flushes of both duodenoscopes. The review revealed 4 major abnormalities: miscommunication about reprocessing, undetected damaged parts, inadequate repair of duodenoscope damage, and duodenoscope design abnormalities, including the forceps elevator, elevator lever, and instrumentation port sealing. CONCLUSIONS: Outbreaks are associated with a combination of factors, including duodenoscope design issues, repair issues, improper cleaning, and systemic monitoring of contamination. To eliminate future duodenoscope-associated infections, a multipronged approach is required, including clear communication by all parties involved, a reliable servicing market, stringent surveillance measures, and eventually new duodenoscope designs and reprocessing procedures with a larger margin of safety.

Modeling of inflicted head injury by shaking trauma in children: what can we learn? : Part I: A systematic review of animal models.

Inflicted blunt force trauma and/or repetitive acceleration-deceleration trauma in infants can cause brain injury. Yet, the exact pathophysiologic mechanism with its associated thresholds remains unclear. In this systematic review an overview of animal models for shaking trauma and their findings on tissue damage will be provided. A systematic review was performed in MEDLINE and Scopus for articles on the simulation of inflicted head injury in animals. After collection, the studies were independently screened by two researchers for title, abstract, and finally full text and on methodological quality. A total of 12 articles were included after full-text screening. Three articles were based on a single study population of 13 lambs, by one research group. The other 9 articles were separate studies in piglets, all by a single second research group. The lamb articles give some information on tissue damage after inflicted head injury. The piglet studies only provide information on consequences of a single plane rotational movement. Generally, with increasing age and weight, there was a decrease of axonal injury and death. Future studies should focus on every single step in the process of a free movement in all directions, resembling human infant shaking. In part II of this systematic review biomechanical models will be evaluated.

The influence of contact force on forensic trace collection efficiency when sampling textiles with adhesive tape.

PURPOSE: DNA is a highly valuable lead to identify people who were possibly involved in a crime. Even by small contact events, minute amounts of DNA ('trace DNA') can be transferred from a DNA source to an evidentiary item, which can be enough for a successful DNA analysis. The focus of this research is to get more insight in the collection of trace DNA from textiles by 'stubbing', which is a tape-lifting method using double-sided tape placed on a stub. The relation between the 'stubbing force' (the normal force that is applied during stubbing) and the collection efficiency of microspheres is investigated. METHODS: Microspheres (Ø25 µm) were used as mock traces to mimic DNA-containing micro-traces. The particles were applied to textile substrates in a suspension of ethanol that was left to evaporate before sampling. Experiments were performed on three different polyester substrates. Traces were collected by stubbing while using 5 different stubbing forces. The number of microspheres placed on each substrate was counted before sampling and all stub-tapes were analysed after sampling to count how many of the microspheres were picked up, both by using stitched images from a digital light microscope. Custom-made image recognition software was used to automatically count the microspheres. RESULTS: On all tested polyester substrates, the mean efficiency of the collection of microspheres increased with increasing stubbing force in a concave down increasing function. The increase of collection efficiency stagnated around 3-12 N, depending on the substrate material. The theoretical maximum collection efficiencies varied between 38% and 78%, depending on substrate material as well. CONCLUSIONS: Stubbing with a force higher than 12 N does not notably influence the collection efficiency from the variety of textiles that were tested. However, because the theoretical maxima of the collection efficiencies were far from 100%, it is highly likely that stubbing multiple times on the same spot of a substrate increases the total collection efficiency. The gained knowledge will help to standardize and improve the effectiveness of stubbing.

Modeling of inflicted head injury by shaking trauma in children: what can we learn? : Part II: A systematic review of mathematical and physical models.

Various types of complex biomechanical models have been published in the literature to better understand processes related to inflicted head injury by shaking trauma (IHI-ST) in infants. In this systematic review, a comprehensive overview of these models is provided. A systematic review was performed in MEDLINE and Scopus for articles using physical (e.g. dolls) and mathematical (e.g. computer simulations) biomechanical models for IHI-ST. After deduplication, the studies were independently screened by two researchers using PRISMA methodology and data extracted from the papers is represented in a "7-steps description", addressing the different processes occurring during IHI-ST. Eleven papers on physical models and 23 papers on mathematical models were included after the selection process. In both categories, some models focus on describing gross head kinematics during IHI-ST events, while others address the behavior of internal head- and eye structures in various levels of detail. In virtually all physical and mathematical models analyzed, injury thresholds are derived from scaled non-infant data. Studies focusing on head kinematics often use injury thresholds derived from impact studies. It remains unclear to what extent these thresholds reflect the failure thresholds of infant biological material. Future research should therefore focus on investigating failure thresholds of infant biological material as well as on possible alternative injury mechanism and alternative injury criteria for IHI-ST.

Comparison between pulse wave velocities measured using Complior and measured using Biopac.

Arterial stiffness is a reliable prognostic parameter for cardiovascular diseases. The effect of change in arterial stiffness can be measured by the change of the pulse wave velocity (PWV). The Complior system is widely used to measure PWV between the carotid and radial arteries by means of piezoelectric clips placed around the neck and the wrist. The Biopac system is an easier to use alternative that uses ECG and simple optical sensors to measure the PWV between the heart and the fingertips, and thus extends a bit more to the peripheral vasculature compared to the Complior system. The goal of this study was to test under various conditions to what extent these systems provide comparable and correlating values. 25 Healthy volunteers, 20-30 years old, were measured in four sequential position: sitting, lying, standing and sitting. The results showed that the Biopac system measured consistently and significantly lower PWV values than the Complior system, for all positions. Correlation values and Bland-Altman plots showed that despite the difference in PWV magnitudes obtained by the two systems the measurements did agree well. Which implies that as long as the differences in PWV magnitudes are taken into account, either system could be used to measure PWV changes over time. However, when basing diagnosis on absolute PWV values, one should be very much aware of how the PWV was measured and with what system.

Aerosol production during autopsies: The risk of sawing in bone.

When sawing during autopsies on human remains, fine dust is produced, which consists of particles of sizes that may fall within the human respirable range, and can act as vectors for pathogens. The goal of this study was to explore the potential effects of saw blade frequency and saw blade contact load on the number and size of airborne bone particles produced. The methodology involved the use of an oscillating saw with variable saw blade frequencies and different saw blade contact loads on dry human femora. Released airborne particles were counted per diameter by a particle counter inside a closed and controlled environment. Results corroborated with the hypotheses: higher frequencies or lower contact loads resulted in higher numbers of aerosol particles produced. However, it was found that even in the best-case scenario tested on dry bone, the number of aerosol particles produced was still high enough to provide a potential health risk to the forensic practitioners. Protective breathing gear such as respirators and biosafety protocols are recommended to be put into practice to protect forensic practitioners from acquiring pathologies, or from other biological hazards when performing autopsies.

Increasing accuracy of pulse transit time measurements by automated elimination of distorted photoplethysmography waves.

Photoplethysmography (PPG) is a widely available non-invasive optical technique to visualize pressure pulse waves (PWs). Pulse transit time (PTT) is a physiological parameter that is often derived from calculations on ECG and PPG signals and is based on tightly defined characteristics of the PW shape. PPG signals are sensitive to artefacts. Coughing or movement of the subject can affect PW shapes that much that the PWs become unsuitable for further analysis. The aim of this study was to develop an algorithm that automatically and objectively eliminates unsuitable PWs. In order to develop a proper algorithm for eliminating unsuitable PWs, a literature study was conducted. Next, a '7Step PW-Filter' algorithm was developed that applies seven criteria to determine whether a PW matches the characteristics required to allow PTT calculation. To validate whether the '7Step PW-Filter' eliminates only and all unsuitable PWs, its elimination results were compared to the outcome of manual elimination of unsuitable PWs. The '7Step PW-Filter' had a sensitivity of 96.3% and a specificity of 99.3%. The overall accuracy of the '7Step PW-Filter' for detection of unsuitable PWs was 99.3%. Compared to manual elimination, using the '7Step PW-Filter' reduces PW elimination times from hours to minutes and helps to increase the validity, reliability and reproducibility of PTT data.

Workflow and intervention times of MR-guided focused ultrasound - Predicting the impact of new techniques.

Magnetic resonance guided focused ultrasound surgery (MRgFUS) has become an attractive, non-invasive treatment for benign and malignant tumours, and offers specific benefits for poorly accessible locations in the liver. However, the presence of the ribcage and the occurrence of liver motion due to respiration limit the applicability MRgFUS. Several techniques are being developed to address these issues or to decrease treatment times in other ways. However, the potential benefit of such improvements has not been quantified. In this research, the detailed workflow of current MRgFUS procedures was determined qualitatively and quantitatively by using observation studies on uterine MRgFUS interventions, and the bottlenecks in MRgFUS were identified. A validated simulation model based on discrete events simulation was developed to quantitatively predict the effect of new technological developments on the intervention duration of MRgFUS on the liver. During the observation studies, the duration and occurrence frequencies of all actions and decisions in the MRgFUS workflow were registered, as were the occurrence frequencies of motion detections and intervention halts. The observation results show that current MRgFUS uterine interventions take on average 213min. Organ motion was detected on average 2.9 times per intervention, of which on average 1.0 actually caused a need for rework. Nevertheless, these motion occurrences and the actions required to continue after their detection consumed on average 11% and up to 29% of the total intervention duration. The simulation results suggest that, depending on the motion occurrence frequency, the addition of new technology to automate currently manual MRgFUS tasks and motion compensation could potentially reduce the intervention durations by 98.4% (from 256h 5min to 4h 4min) in the case of 90% motion occurrence, and with 24% (from 5h 19min to 4h 2min) in the case of no motion. In conclusion, new tools were developed to predict how intervention durations will be affected by future workflow changes and by the introduction of new technology.

Effect of heat-induced pain stimuli on pulse transit time and pulse wave amplitude in healthy volunteers.

Pain is commonly assessed subjectively by interpretations of patient behaviour and/or reports from patients. When this is impossible the availability of a quantitative objective pain assessment tool based on objective physiological parameters would greatly benefit clinical practice and research beside the standard self-report tests. Vasoconstriction is one of the physiological responses to pain. The aim of this study was to investigate whether pulse transit time (PTT) and pulse wave amplitude (PWA) decrease in response to this vasoconstriction when caused by heat-induced pain. The PTT and PWA were measured in healthy volunteers, on both index fingers using photoplethysmography and electrocardiography. Each subject received 3 heat-induced pain stimuli using a Temperature-Sensory Analyzer thermode block to apply a controlled, increasing temperature from 32.0 °C to 50.0 °C to the skin. After reaching 50.0 °C, the thermode was immediately cooled down to 32.0 °C. The study population was divided into 2 groups with a time-interval between the stimuli 20s or 60s. The results showed a significant (p < 0.05) decrease of both PTT and PWA on the stimulated and contralateral side. Moreover, there was no significant difference between the stimulated and contralateral side. The time-interval of 20s was too short to allow PTT and PWA to return to baseline values and should exceed 40s in future studies. Heat-induced pain causes a decrease of PTT and PWA. Consequently, it is expected that, in the future, PTT and PWA may be applied as objective indicators of pain, either beside the standard self-report test, or when self-report testing is impossible.

Withdrawal of a novel-design duodenoscope ends outbreak of a VIM-2-producing Pseudomonas aeruginosa.

BACKGROUND AND STUDY AIMS: Infections are a recognized risk of endoscopic retrograde cholangiopancreatography (ERCP). This paper reports on a large outbreak of VIM-2-producing Pseudomonas aeruginosa that was linked to the use of a recently introduced duodenoscope with a specific modified design (Olympus TJF-Q180V). METHODS: Epidemiological investigations and molecular typing were executed in order to identify the source of the outbreak. Audits on implementation of infection control measures were performed. Additional infection control strategies were implemented to prevent further transmission. The design and the ability to clean and disinfect the duodenoscope were evaluated, and the distal tip was dismantled. RESULTS: From January to April 2012, 30 patients with a VIM-2-positive P. aeruginosa were identified, of whom 22 had undergone an ERCP using a specific duodenoscope, the TJF-Q180V. This was a significant increase compared with the hospital-wide baseline level of 2 - 3 cases per month. Clonal relatedness of the VIM-2 P. aeruginosa was confirmed for all 22 cases and for the VIM-2 strain isolated from the recess under the forceps elevator of the duodenoscope. An investigational study of the new modified design, including the dismantling of the duodenoscope tip, revealed that the fixed distal cap hampered cleaning and disinfection, and that the O-ring might not seal the forceps elevator axis sufficiently. The high monthly number of cases decreased below the pre-existing baseline level following withdrawal of the TJF-Q180V device from clinical use. CONCLUSIONS: Duodenoscope design modifications may compromise microbiological safety as illustrated by this outbreak. Extensive pre-marketing validation of the reprocessability of any new endoscope design and stringent post-marketing surveillance are therefore mandatory.