Robotic Complete ALPPS (rALPPS)-First German Experiences.

BACKGROUND: ALPPS leads to fast and effective liver hypertrophy. This enables the resection of extended tumors. Conventional ALPPS is associated with high morbidity and mortality. MILS reduces morbidity and the robot adds technical features that make complex procedures safe. MATERIAL AND METHODS: The MD-MILS was screened for patients who underwent rALPPS. Demographic and perioperative data were evaluated retrospectively. Ninety days postoperative morbidity was scored according to the CD classification. The findings were compared with the literature. RESULTS: Since November 2021, five patients have been identified. The mean age and BMI of the patients were 50.0 years and 22.7 kg/m2. In four cases, patients suffered from colorectal liver metastases and, in one case, intrahepatic cholangiocarcinoma. Prior to the first operation, the mean liver volume of the residual left liver was 380.9 mL with a FLR-BWR of 0.677%. Prior to the second operation, the mean volume of the residual liver was 529.8 mL with a FLR-BWR of 0.947%. This was an increase of 41.9% of the residual liver volume. The first and second operations were carried out within 17.8 days. The mean time of the first and second operations was 341.2 min and 440.6 min. The mean hospital stay was 27.2 days. Histopathology showed the largest tumor size of 39 mm in diameter with a mean amount of 4.7 tumors. The mean tumor-free margin was 12.3 mm. One complication CD > 3a occurred. No patient died during the 90-day follow up. CONCLUSION: In the first German series, we demonstrated that rALPPS can be carried out safely with reduced morbidity and mortality in selected patients.

Mol* Volumes and Segmentations: visualization and interpretation of cell imaging data alongside macromolecular structure data and biological annotations.

Segmentation helps interpret imaging data in a biological context. With the development of powerful tools for automated segmentation, public repositories for imaging data have added support for sharing and visualizing segmentations, creating the need for interactive web-based visualization of 3D volume segmentations. To address the ongoing challenge of integrating and visualizing multimodal data, we developed Mol* Volumes and Segmentations (Mol*VS), which enables the interactive, web-based visualization of cellular imaging data supported by macromolecular data and biological annotations. Mol*VS is fully integrated into Mol* Viewer, which is already used for visualization by several public repositories. All EMDB and EMPIAR entries with segmentation datasets are accessible via Mol*VS, which supports the visualization of data from a wide range of electron and light microscopy experiments. Additionally, users can run a local instance of Mol*VS to visualize and share custom datasets in generic or application-specific formats including volumes in .ccp4, .mrc, and .map, and segmentations in EMDB-SFF .hff, Amira .am, iMod .mod, and Segger .seg. Mol*VS is open source and freely available at https://molstarvolseg.ncbr.muni.cz/.

MDsrv: visual sharing and analysis of molecular dynamics simulations.

Molecular dynamics simulation is a proven technique for computing and visualizing the time-resolved motion of macromolecules at atomic resolution. The MDsrv is a tool that streams MD trajectories and displays them interactively in web browsers without requiring advanced skills, facilitating interactive exploration and collaborative visual analysis. We have now enhanced the MDsrv to further simplify the upload and sharing of MD trajectories and improve their online viewing and analysis. With the new instance, the MDsrv simplifies the creation of sessions, which allows the exchange of MD trajectories with preset representations and perspectives. An important innovation is that the MDsrv can now access and visualize trajectories from remote datasets, which greatly expands its applicability and use, as the data no longer needs to be accessible on a local server. In addition, initial analyses such as sequence or structure alignments, distance measurements, or RMSD calculations have been implemented, which optionally support visual analysis. Finally, based on Mol*, MDsrv now provides faster and more efficient visualization of even large trajectories compared to its predecessor tool NGL.

Laparoscopic cholecystectomy during the COVID-19 pandemic in a tertiary care hospital in Germany: higher rates of acute and gangrenous cholecystitis in elderly patients.

BACKGROUND: The COVID-19 pandemic caused a global health crisis in 2020. This pandemic also had a negative impact on standard procedures in general surgery. Surgeons were challenged to find the best treatment plans for patients with acute cholecystitis. The aim of this study is to investigate the impact of the COVID-19 pandemic on the outcomes of laparoscopic cholecystectomies performed in a tertiary care hospital in Germany. PATIENTS AND METHODS: We examined perioperative outcomes of patients who underwent laparoscopic cholecystectomy during the pandemic from March 22, 2020 (first national lockdown in Germany) to December 31, 2020. We then compared these to perioperative outcomes from the same time frame of the previous year. RESULTS: A total of 182 patients who underwent laparoscopic cholecystectomy during the above-mentioned periods were enrolled. The pandemic group consisted of 100 and the control group of 82 patients. Subgroup analysis of elderly patients (> 65 years old) revealed significantly higher rates of acute [5 (17.9%) vs. 20 (58.8%); p = 0.001] and gangrenous cholecystitis [0 (0.0%) vs. 7 (20.6%); p = 0.013] in the "pandemic subgroup". Furthermore, significantly more early cholecystectomies were performed in this subgroup [5 (17.9%) vs. 20 (58.8%); p = 0.001]. There were no significant differences between the groups both in the overall and subgroup analysis regarding the operation time, intraoperative blood loss, length of hospitalization, morbidity and mortality. CONCLUSION: Elderly patients showed particularly higher rates of acute and gangrenous cholecystitis during the pandemic. Laparoscopic cholecystectomy can be performed safely in the COVID-19 era without negative impact on perioperative results. Therefore, we would assume that laparoscopic cholecystectomy can be recommended for any patient with acute cholecystitis, including the elderly.

Determination and optimization of ideal patient candidacy for anterior odontoid screw fixation.

BACKGROUND: Odontoid process fractures are one of the most common spine fractures, especially in patients over age 70. There is still much controversy over the ideal candidate for anterior odontoid screw fixation (AOSF), with outcomes affected by characteristics such as fracture morphology, nonideal body habitus, and osteoporosis. Therefore, this systematic review seeks to discuss the optimal criteria, indications, and adverse postoperative considerations when deciding to pursue AOSF. METHODS: This investigation was conducted from experiential recall and article selection performed using the PubMed electronic bibliographic databases. The search yielded 124 articles that were assessed and filtered for relevance. Following the screening of titles and abstracts, 48 articles were deemed significant for final selection. RESULTS: AOSF is often utilized to treat Type IIB odontoid fractures, which has been shown to preserve atlantoaxial motion, limit soft-tissue injuries/blood loss/vertebral artery injury/reduce operative time, provide adequate osteosynthesis, incur immediate spinal stabilization, and allow motion preservation of C1 and C2. However, this technique is limited by patient characteristics such as fracture morphology, transverse ligament rupture, remote injuries, short neck or inability to extend neck, barrel chested, and severe spinal kyphosis, in addition to adverse postoperative outcomes such as dysphagia and vocal cord paralysis. CONCLUSION: Due to the fact that odontoid fractures have a significant morbidity in elderly population, treatment with AOSF is generally recommended for this population with higher risk for nonoperative fusion. Considerations should be made to achieve fracture stability and fusion, while lowering the risk for operative and postoperative complications.

Clinical manifestations, classification, and surgical management of sacral tumors and the need for personalized approach to sacrectomy.

BACKGROUND: Although comprising 7% of all spinal tumors, sacral tumors present with a litany of issues due to their slow growth and difficulty in detection. As a result, sacral tumors can grow unperturbed for years until a patient presents for an incidental workup of an unassociated minor trauma or an offending primary tumor source that has metastasized to the sacrum; in most cases, this includes primary tumors of the breast, prostate, and lung. The goal of this review is to outline the pathophysiology underlying sacral tumors including the various tissues and structures that can be targeted for treatment, along with a discussion of the surgical approach to sacrectomy. METHODS: An extensive review of the published literature was conducted through PubMed database with articles simultaneously containing both search terms "sacral tumors" and "sacrectomy." No date restrictions were used. RESULTS: The search yielded 245 related articles. Cross-checking of articles was conducted to exclude of duplicate articles. The articles were screened for their full text and English language availability. We finalized those articles pertaining to the topic. CONCLUSION: Once a sacral tumor has reached the point of diagnostic detection, invasive sacrectomy is typically utilized (through an anterior, posterior, or combination approach) to locally isolate and resect the tumor and minimize risk of future tumor growth and additional bone loss. While institutions have varying criteria for surgical approaches, a combination of anterior and posterior approach has traditionally been used in total and high sacrectomies due to the control it provides surgeons toward the rectum and vasculature anterior to the sacrum. A posterior-only approach can be performed for tumors that failed to invade pelvic organs or extend past the lumbosacral junction. Early detection with screenings can help avoid invasive sacrectomy by identifying the onset of tumor formation in the sacrum, particularly for highly metastatic cancers.

Awake spine surgery: An eye-opening movement.

BACKGROUND: Awake surgery is performed in multiple surgical specialties, but historically, awake surgery in the field of neurosurgery was limited to craniotomies. Over the past two decades, spinal surgeons have pushed for techniques that only require regional anesthesia as they may provide reduced financial burdens on patients, faster recovery times, and better outcomes. The list of awake spine surgeries that have been found in the literature include: laminectomies/discectomies, anterior cervical discectomy and fusions (ACDFs), lumbar fusions, and dorsal column (DC) stimulator placement. METHODS: An extensive review of the published literature was conducted through PubMed database with articles containing the search term "awake spine surgery." No date restrictions were used. RESULTS: The search yielded 293 related articles. Cross-checking of articles was conducted to exclude of duplicate articles. The articles were screened for their full text and English language availability. We finalized those articles pertaining to the topic. Findings have shown that lumbar laminectomies performed with local anesthesia have shown shorter operating time, less postoperative nausea, lower incidence of urinary retention and spinal headache, and shorter hospital stays when compared to those performed under general anesthesia. Lumbar fusions with local anesthesia showed similar outcomes as patients reported better postoperative function and fewer side effects of general anesthesia. DC stimulator placement performed with local anesthesia is advantageous as it allows real time patient feedback for surgeons as they directly test affected nerves. However, spontaneous movement during the placement of DC stimulators is associated with higher failure rates when compared to general anesthesia (29.7% vs. 14.9%). Studies have shown that the use of local anesthesia during ACDFs has no significant differences when compared to general anesthesia, and patient's report better tolerated pain with general anesthesia. CONCLUSION: The use of awake spine surgery is beneficial for those who cannot undergo general anesthesia. However, it is limited to patients who can tolerate prone positioning with no central airway (i.e., normal BMI with a healthy airway), have no pre-existing mental health conditions (e.g., anxiety), and require a minimally invasive procedure with a short operating time. Future studies should focus on long-term efficacies of these procedures that provide further insight on the indications and limitations of awake spine surgery.

Mol* Viewer: modern web app for 3D visualization and analysis of large biomolecular structures.

Large biomolecular structures are being determined experimentally on a daily basis using established techniques such as crystallography and electron microscopy. In addition, emerging integrative or hybrid methods (I/HM) are producing structural models of huge macromolecular machines and assemblies, sometimes containing 100s of millions of non-hydrogen atoms. The performance requirements for visualization and analysis tools delivering these data are increasing rapidly. Significant progress in developing online, web-native three-dimensional (3D) visualization tools was previously accomplished with the introduction of the LiteMol suite and NGL Viewers. Thereafter, Mol* development was jointly initiated by PDBe and RCSB PDB to combine and build on the strengths of LiteMol (developed by PDBe) and NGL (developed by RCSB PDB). The web-native Mol* Viewer enables 3D visualization and streaming of macromolecular coordinate and experimental data, together with capabilities for displaying structure quality, functional, or biological context annotations. High-performance graphics and data management allows users to simultaneously visualise up to hundreds of (superimposed) protein structures, stream molecular dynamics simulation trajectories, render cell-level models, or display huge I/HM structures. It is the primary 3D structure viewer used by PDBe and RCSB PDB. It can be easily integrated into third-party services. Mol* Viewer is open source and freely available at https://molstar.org/.

Direct N-butyl-2-cyanoacrylate injections to the head and neck for percutaneous embolized devascularization.

BACKGROUND: N-butyl-2-cyanoacrylate (NBCA) has been used for vascular malformations since the 1980s; however, few studies have looked at applications, procedural techniques, and outcome throughout many institutions. Herein, we review applications, procedural techniques, previous literature, and outcomes for the use of NBCA specifically through percutaneous technique in treating head and neck vascular pathology. METHODS: An extensive literature review using PubMed database with published literature containing "N-butyl-2-cyanoacrylate embolization," was performed. No date restrictions were used. Cross-checking of articles was conducted to exclude duplicate articles. The articles were screened for their full text and English language availability. We finalized those articles pertaining to the topic. RESULTS: The search yielded 1124 related articles. When comparing surgical resection to embolization with NBCA for cerebral AVMs, complications were similar in both groups and included hemorrhage (15%), residual AVM (6%), and cerebrospinal fluid leak (3%). Their mortality rate was 3% in both groups. Preoperative percutaneous embolization does show improved surgical outcomes. CONCLUSION: NBCA is a fast-acting liquid embolic material used in the treatment of a variety of vascular malformations and lesions of the head and neck. Investigations surrounding the use of NBCA injections as a new alternative embolic agent began in the 1980's. Administration of NBCA has been shown to be useful in minimizing intraoperative blood loss and controlling acute hemorrhage. Performing percutaneous embolization with NBCA provides a successful alternative for surgeons when transcatheter embolization techniques may prove to be too difficult to perform. Embolization using NBCA will continue to play in integral role in the treatment of malignant lesions and vascular malformations. Continued research is warranted to improve safety, outcomes, and further develop clinical applications of NBCA.

Surgical Margin Mapping of Melanoma In Situ Using In Vivo Reflectance Confocal Microscopy Mosaics.

BACKGROUND: Melanoma in situ (MIS) can have poorly defined borders and subclinical extension that makes margin control challenging. Reflectance confocal microscopy (RCM) is a promising noninvasive technique that can be used to assess subclinical spread. OBJECTIVE: To optimize surgical margins of histology-proven MIS using RCM mosaics. MATERIALS AND METHODS: Prospective review of 22 patients with histology-proven MIS who underwent RCM margin mapping prior to staged excision, between August 1, 2018, and August 13, 2020, at the Department of Dermatology, University of New Mexico, School of Medicine. RESULTS: Twenty patients (91%) had tumor clearance on the first stage using a 3-mm surgical margin after confocal margin mapping. CONCLUSION: Reflectance confocal microscopy margin mapping using the mosaic device tends to clear MIS in one stage, and the use of the handheld device may improve the accuracy for difficult anatomic areas. Current Procedural Terminology codes for RCM do not reflect the time required and complexity of the procedure. Reflectance confocal microscopy margin mapping prior to excision has the potential to decrease the number of stages needed for melanoma removal, reduce treatment time, and cost.

A multi-pronged approach targeting SARS-CoV-2 proteins using ultra-large virtual screening.

The unparalleled global effort to combat the continuing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic over the last year has resulted in promising prophylactic measures. However, a need still exists for cheap, effective therapeutics, and targeting multiple points in the viral life cycle could help tackle the current, as well as future, coronaviruses. Here, we leverage our recently developed, ultra-large-scale in silico screening platform, VirtualFlow, to search for inhibitors that target SARS-CoV-2. In this unprecedented structure-based virtual campaign, we screened roughly 1 billion molecules against each of 40 different target sites on 17 different potential viral and host targets. In addition to targeting the active sites of viral enzymes, we also targeted critical auxiliary sites such as functionally important protein-protein interactions.

High-performance macromolecular data delivery and visualization for the web. Corrigendum.

Two citations in the article by Sehnal et al. [(2020), Acta Cryst. D76, 1167-1173] are corrected.

RCSB Protein Data Bank: powerful new tools for exploring 3D structures of biological macromolecules for basic and applied research and education in fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences.

The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), the US data center for the global PDB archive and a founding member of the Worldwide Protein Data Bank partnership, serves tens of thousands of data depositors in the Americas and Oceania and makes 3D macromolecular structure data available at no charge and without restrictions to millions of RCSB.org users around the world, including >660 000 educators, students and members of the curious public using PDB101.RCSB.org. PDB data depositors include structural biologists using macromolecular crystallography, nuclear magnetic resonance spectroscopy, 3D electron microscopy and micro-electron diffraction. PDB data consumers accessing our web portals include researchers, educators and students studying fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences. During the past 2 years, the research-focused RCSB PDB web portal (RCSB.org) has undergone a complete redesign, enabling improved searching with full Boolean operator logic and more facile access to PDB data integrated with >40 external biodata resources. New features and resources are described in detail using examples that showcase recently released structures of SARS-CoV-2 proteins and host cell proteins relevant to understanding and addressing the COVID-19 global pandemic.

RCSB Protein Data Bank: Architectural Advances Towards Integrated Searching and Efficient Access to Macromolecular Structure Data from the PDB Archive.

The US Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) serves many millions of unique users worldwide by delivering experimentally-determined 3D structures of biomolecules integrated with >40 external data resources via RCSB.org, application programming interfaces (APIs), and FTP downloads. Herein, we present the architectural redesign of RCSB PDB data delivery services that build on existing PDBx/mmCIF data schemas. New data access APIs (data.rcsb.org) enable efficient delivery of all PDB archive data. A novel GraphQL-based API provides flexible, declarative data retrieval along with a simple-to-use REST API. A powerful new search system (search.rcsb.org) seamlessly integrates heterogeneous types of searches across the PDB archive. Searches may combine text attributes, protein or nucleic acid sequences, small-molecule chemical descriptors, 3D macromolecular shapes, and sequence motifs. The new RCSB.org architecture adheres to the FAIR Principles, empowering users to address a wide array of research problems in fundamental biology, biomedicine, biotechnology, bioengineering, and bioenergy.

Real-time structural motif searching in proteins using an inverted index strategy.

Biochemical and biological functions of proteins are the product of both the overall fold of the polypeptide chain, and, typically, structural motifs made up of smaller numbers of amino acids constituting a catalytic center or a binding site that may be remote from one another in amino acid sequence. Detection of such structural motifs can provide valuable insights into the function(s) of previously uncharacterized proteins. Technically, this remains an extremely challenging problem because of the size of the Protein Data Bank (PDB) archive. Existing methods depend on a clustering by sequence similarity and can be computationally slow. We have developed a new approach that uses an inverted index strategy capable of analyzing >170,000 PDB structures with unmatched speed. The efficiency of the inverted index method depends critically on identifying the small number of structures containing the query motif and ignoring most of the structures that are irrelevant. Our approach (implemented at motif.rcsb.org) enables real-time retrieval and superposition of structural motifs, either extracted from a reference structure or uploaded by the user. Herein, we describe the method and present five case studies that exemplify its efficacy and speed for analyzing 3D structures of both proteins and nucleic acids.

High-performance macromolecular data delivery and visualization for the web.

Biomacromolecular structural data make up a vital and crucial scientific resource that has grown not only in terms of its amount but also in its size and complexity. Furthermore, these data are accompanied by large and increasing amounts of experimental data. Additionally, the macromolecular data are enriched with value-added annotations describing their biological, physicochemical and structural properties. Today, the scientific community requires fast and fully interactive web visualization to exploit this complex structural information. This article provides a survey of the available cutting-edge web services that address this challenge. Specifically, it focuses on data-delivery problems, discusses the visualization of a single structure, including experimental data and annotations, and concludes with a focus on the results of molecular-dynamics simulations and the visualization of structural ensembles.

A Multi-Pronged Approach Targeting SARS-CoV-2 Proteins Using Ultra-Large Virtual Screening.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously known as 2019 novel coronavirus (2019-nCoV), has spread rapidly across the globe, creating an unparalleled global health burden and spurring a deepening economic crisis. As of July 7th, 2020, almost seven months into the outbreak, there are no approved vaccines and few treatments available. Developing drugs that target multiple points in the viral life cycle could serve as a strategy to tackle the current as well as future coronavirus pandemics. Here we leverage the power of our recently developed in silico screening platform, VirtualFlow, to identify inhibitors that target SARS-CoV-2. VirtualFlow is able to efficiently harness the power of computing clusters and cloud-based computing platforms to carry out ultra-large scale virtual screens. In this unprecedented structure-based multi-target virtual screening campaign, we have used VirtualFlow to screen an average of approximately 1 billion molecules against each of 40 different target sites on 17 different potential viral and host targets in the cloud. In addition to targeting the active sites of viral enzymes, we also target critical auxiliary sites such as functionally important protein-protein interaction interfaces. This multi-target approach not only increases the likelihood of finding a potent inhibitor, but could also help identify a collection of anti-coronavirus drugs that would retain efficacy in the face of viral mutation. Drugs belonging to different regimen classes could be combined to develop possible combination therapies, and top hits that bind at highly conserved sites would be potential candidates for further development as coronavirus drugs. Here, we present the top 200 in silico hits for each target site. While in-house experimental validation of some of these compounds is currently underway, we want to make this array of potential inhibitor candidates available to researchers worldwide in consideration of the pressing need for fast-tracked drug development.

BinaryCIF and CIFTools-Lightweight, efficient and extensible macromolecular data management.

3D macromolecular structural data is growing ever more complex and plentiful in the wake of substantive advances in experimental and computational structure determination methods including macromolecular crystallography, cryo-electron microscopy, and integrative methods. Efficient means of working with 3D macromolecular structural data for archiving, analyses, and visualization are central to facilitating interoperability and reusability in compliance with the FAIR Principles. We address two challenges posed by growth in data size and complexity. First, data size is reduced by bespoke compression techniques. Second, complexity is managed through improved software tooling and fully leveraging available data dictionary schemas. To this end, we introduce BinaryCIF, a serialization of Crystallographic Information File (CIF) format files that maintains full compatibility to related data schemas, such as PDBx/mmCIF, while reducing file sizes by more than a factor of two versus gzip compressed CIF files. Moreover, for the largest structures, BinaryCIF provides even better compression-factor ten and four versus CIF files and gzipped CIF files, respectively. Herein, we describe CIFTools, a set of libraries in Java and TypeScript for generic and typed handling of CIF and BinaryCIF files. Together, BinaryCIF and CIFTools enable lightweight, efficient, and extensible handling of 3D macromolecular structural data.

Coexistence of three specialist predators of the hemlock woolly adelgid in the Pacific Northwest USA.

The hemlock woolly adelgid (Hemiptera: Adelgidae: Adelges tsugae Annand) is an invasive insect, introduced from Japan to eastern North America, where it causes decline and death of hemlock trees. There is a closely related lineage of A. tsugae native to western North America. To inform classical biological control of A. tsugae in the eastern USA, the density and phenology of three native western adelgid specialist predators, Leucopis argenticollis (Zetterstedt), Le. piniperda (Malloch) (Diptera: Chamaemyiidae), and Laricobius nigrinus Fender (Coleoptera: Derodontidae), were quantified in the Pacific Northwest. Infested branches were collected from western hemlock (Pinaceae: Tsuga heterophylla (Raf.) Sarg.) at four sites around the Puget Sound, Washington and three sites in Oregon. Immature Leucopis were identified to species using DNA barcodes. Leucopis argenticollis was roughly twice as abundant as Le. piniperda. Laricobius nigrinus larvae were more abundant than the two species of Leucopis during the egg stage of the first adelgid generation, but Leucopis were present as feeding larvae during the second adelgid generation when La. nigrinus was aestivating in the soil, resulting in Leucopis being more abundant than La. nigrinus across the entire sampling period. Adelges tsugae and La. nigrinus densities were not correlated, while A. tsugae and Leucopis spp. densities were positively correlated. Leucopis spp. and La. nigrinus densities were negatively correlated. These results support the complementary use of La. nigrinus and the two Leucopis species for biological control of A. tsugae in the eastern USA, and point to the need for further investigation of spatial and temporal niche partitioning among the three predator species.