bluuebunny/crossref_metadata_2025 huggingface dataset:
Ran
Authors: Macara Ian G , Brownawell Amy , Welch Katie
Published: November 2023

Ran is a very unusual GTPase. Unlike all other known members of the Ras superfamily of small GTP-binding proteins, Ran is not post-translationally modified. Moreover, its function depends critically on a spatial gradient of the GTP-bound form of Ran. This requirement sets it apart from other small GTPases that act in signal transduction pathways or in vesicle fusion and budding. Ran is concentrated in the nucleoplasm and plays a central role in active nucleocytoplasmic transport through the nuclear pore complex (NPC). It may have additional functions, but these remain to be identified. The vectoriality of transport and the accumulation of cargo in the nuclear or cytoplasmic compartments against a concentration gradient appear to be driven by the Ran-GTP gradient across the NPC. In this limited sense, therefore, nuclear transport behaves like a coupled transmembrane transport system, similar, for example, to the coupling of glucose accumulation to a sodium ion gradient. At a molecular level, however, Ran-mediated transport is unique, and is based on a complex sequence of protein-protein interactions that are controlled by the guanine-nucleotide-bound state of the GTPase. Despite the remarkably rapid progress being made in identifying the players in the nuclear transport machinery, we remain ignorant of many of the fundamental aspects of the transport mechanism.
Nerve terminal membrane trafficking proteins: from discovery to function
Authors: Hazuka Christopher d. , Poletti davide L , Scheller Richard H
Published: November 2023

Release of chemical messengers is the primary means by which neurons communicate with target cells. Chemical neurotransmitters are secreted from the presynaptic nerve terminal, travel across the synaptic cleft, and stimulate receptors on postsynaptic cells in a process termed neurotransmission (1). Initial physiological work demonstrated that neurotransmitter is released in packets or ‘ quanta’, and that each quantum consists of a large number of neurotransmitter molecules (2, 3). Ultrastructural studies indicated that a major feature of the presynaptic nerve terminal is a local concentration of uniformly-sized lipid-bound vesicles, promoting the hypothesis that a quantum of neurotransmitter is stored in a vesicle (4). Subsequently, abundant research demonstrated the primacy of these vesicular structures in neurotransmitter release (5, 6). As each vesicle contains a quantum of neurotransmitter, exquisite control of nervous system communication can result from modulation of the behaviour of synaptic vesicles.
The role of phospholipids in neurosecretion
Authors: Martin Thomas F J
Published: November 2023

As emphasized elsewhere in this volume, the function of the nervous system depends upon chemical communication mediated by extracellular signals such as neurotransmitters, neuropeptides, and neurotrophins. The regulated release of these signals into the extracellular space as well as the responses elicited in cells by these signals depends upon integrated molecular events that are membrane based. Neurotransmitter release requires the fusion of secretory vesicles with the plasma membrane whereas regulation by transmitters is mediated by cell surface transmembrane receptors and associated signal transduction complexes. Research on understanding the molecular mechanisms that underlie these processes has understandably focused on identifying key protein participants that operate within or on membrane bilayers. In contrast, the membrane itself has frequently been regarded as a relatively inert platform upon which protein-protein interactions occur. Research over the last 20 years has, however, progressively revealed a dynamic set of regulatory events that involves membrane phospholipids, in particular the inositol phospholipids. These highly phosphorylated lipids exhibit high rates of turnover, and function both as precursors for intracellular messengers as well as key regulators of protein recruitment to and protein function within the membrane. This chapter provides an overview of the multiple roles of inositol phospholipids in neural cell function.
Functional studies of presynaptic proteins at the squid giant synapse
Authors: Burns Marie E , Augustine George J
Published: November 2023

The work of Katz (1) and colleagues established that synaptic transmission arises from the secretion of quantal packets of neurotransmitter from the presynaptic terminals of neurons. More recent work has revealed that release of neurotransmitters is due to the influx of calcium ions into presynaptic terminals and the subsequent localized elevation of calcium concentration within these terminals (2). This rise in presynaptic calcium concentration triggers the fusion of synaptic vesicles with the presynaptic plasma membrane and results in exocytotic discharge of the neurotransmitters stored within the vesicles (3). Exocytosis is only one reaction in a series of synaptic vesicle trafficking events that leads to the local recycling of vesicle components within the presynaptic terminal (see Chapter 1).
Genetic analysis of neurotranstnitter release in tnice and humans
Authors: Lloyd Thomas E , Bellen Hugo J
Published: November 2023

While organisms such as C. elegans, Drosophila, and squid are excellent model systems for studying the fundamental principles of neurotransmitter release in vivo, one of the ultimate goals of these studies is to understand the mechanisms underlying neurotransmitter release in humans. In this respect, the use of invertebrate model systems is validated by the observation that most proteins and processes implicated in synaptic transmission are highly conserved between invertebrates and vertebrates. However, the simplicity of invertebrate model systems does not substitute for the complexity of vertebrate systems, as many sophisticated physiological paradigms and behavioural analyses can only be performed in complex systems such as mice. These studies may provide clues into not only the normal function of genes, but also the role these genes may play in human behaviour and disease. Thus, given the similarities between the mouse and human nervous system, a reverse genetic approach using knock-out technology in mice is at present, and will continue in the foreseeable future, to be one of the most valuable ways to define the function of proteins that are putatively involved in neurotransmitter release in humans.
On the road to destruction: suppression of protein tyrosine kinase signalling by SOCS family proteins
Authors: Rottapel Robert , Ilangumaran Subburaj , De Sepulveda Paulo
Published: November 2023

The complexity of multicellular organisms established during embryogenesis and maintained during adult life relies on the continuous processing of diverse micro environmental signals by various cell types. These environmental signals are often elaborated in the form of membrane-bound or soluble-peptide ligands that bind to cognate cell-surface receptors. One mechanism of transducing signals across the plasma membrane is to couple ligand-induced oligomerization of cell-surface receptors to the activation of protein tyrosine kinases (PTKs). Growth factor peptides such as insulin, epidermal growth factor, and steel factor bind to a class of transmembrane receptors with intrinsic protein tyrosine kinase activity (RTK). On the other hand, cytokines involved in inflammatory, antiviral, or hormonal growth responses bind to a class of receptors which are non-covalently linked to the cytoplasmic, non-receptor protein tyrosine kinases of the Janus kinase (JAK) family. PTK activation provokes intracellular signal amplification and diversification following covalent modification of a wide number of protein targets by tyrosine phosphorylation. Tyrosine phosphorylation modifies enzymatic activity, induces multimeric protein assembly through the recruitment of SH2-containing proteins, and relocalizes signalling molecules to sub cellular compartments where they exert their function. Cytokine receptors activate a complex network of downstream signalling pathways which mediate a diversity of biological responses including cell survival, proliferation, differentiation, and chemo taxis. The initiation and termination of cytokine-induced signalling is tightly regulated. Many mechanisms have evolved to terminate signalling events following receptor activation.
Mechanisms and biology of signalling by serine/threonine kinase receptors for the TGFP superfamily
Authors: Klüoppel Michael , Hoodless Pamela A , Wrana Jeffrey L , attisano Liliana
Published: November 2023

In a multicellular organism, communication between cells and their environment is of fundamental importance for all developmental and physiological processes. This communication relies on the transfer of information from one cell to another through specific signalling molecules. From worms to fruit flies to mammals, the transforming growth factor J3 (TGFJ3) superfamily of growth factors represents a family of signal ling molecules that is of critical importance for a diverse array of biological processes. Here, we will review the current state of knowledge of TGFJ3 signalling, with special emphasis on the recent advances in our understanding of the intracellular mechanisms that transmit TGFJ3-like signals from the cell surface to the nucleus. In addition, we provide an overview of the involvement of TGFJ3 signalling pathways in development and disease.
Folding events in the submillisecond range
Authors: Gruebele Martin
Published: November 2023

Until quite recently, experimental studies of the dynamics of protein folding have been limited to a time resolution of approximately 2 milliseconds. Folding has been induced by stopped-flow mixing (as distinguished from ‘ultra-rapid’ mixing) and the subsequent reactions monitored by a number of traditional spectroscopic probes. A remarkable feature of the folding of many globular proteins observed by stopped flow methods is the presence of submillisecond burst phases (l; Chapter 3). Within this very short timescale, some proteins acquire more than 60% of their secondary structure as measured by CD (Fig. 1). At the same time, ANS binding shows that they can compact to states that may be classified as molten globules, form some well-defined tertiary interactions that can be native or non-native, or remain in a relatively extended conformational ensemble, depending on the folding conditions (2, 3; Chapter 6).
Band T-cell hybridomas
Authors: Bastin Judy m.
Published: November 2023

In 1975, Kohler and Milstein (1) described details of a powerful method in which B cells secreting antibody of one specificity could be fused with a continuously growing plasmacytoma. The fusion product is called a hybridoma, and it will express the immunoglobulin genes from both the normal antibody forming B cell and the plasmacytoma. It will inherit the potential for unlimited growth from the continuously growing plasmacytoma parent and the genetic material determining a given antibody specificity from the antibody secreting parent. The methods used to generate T-cell hybridomas are essentially the same as for B-cell hybridomas, and in 1978 Kontiainen et al. (2) and Taniguchi and Miller (3) isolated the first T-cell hybrid clones. Antigen specific normal T cells are fused to a T-cell tumour line.
Human cytotoxic T-lymphocyte (CTL) studies
Authors: Rowland-jones Sarah L
Published: November 2023

Cytotoxic T-lymphocytes (CTLs) play a major part in the cellular immune response to viruses and other intracellular infections, and in the control of many tumours. They are able to recognize cells expressing foreign antigens through a specific interaction of their T-cell receptors (TCRs) with surface class-I HLA molecules on the target cells which have bound peptides from the pathogen or tumour antigens. This leads to the release of cytokines such as interferon-gamma (IFN--y) and tumour necrosis factor-alpha (TNF-a), chemokines such as RANTES and MIP-la, and ultimately to the lysis of the target cell. The lytic process is caused both by the release of perforin and through fas-ligand triggering of programmed cell-death in cells expressing fas (reviewed in ref. 1). On first contact with antigen the CTLs, which initially expand, can persist as memory cells: in most studies of human CTLs, the aim is to detect and expand in vitro this memory-cell population from peripheral blood mononuclear cells (PBMCs).
Limiting dilution analysis for the quantitation of antigen-specific T cells
Authors: Carmichael Andrew
Published: November 2023

To quantify the number of lymphocytes that have a defined functional property (e.g. antigen-specific cytotoxicity) within a mixed population of cells, one needs an assay that is capable of detecting the presence of a single responding cell. Because the cytotoxic activity of an individual T cell is too small to be measured accurately with existing methods, it is necessary to amplify the response by stimulating the single responding cell to undergo clonal proliferation in vitro to generate a sufficiently large population of daughter cells for their combined cytotoxic activity to be detected. Such an assay therefore measures the number of functional precursor cells that are capable of undergoing clonal proliferation and differentiation into effector cells; if for any reason the function of the cells is impaired so that they are incapable of clonal expansion in vitro, the presence of such cells will be underestimated.
Biochemical characterization of lymphocyte surface antigens
Authors: symons Antony , Brown marion h.
Published: November 2023

The approach taken by cellular immunologists to characterize a lymphocyte surface antigen usually begins with the antibody. In many cases the antibody has been raised by immunization with whole cells, that is against the native molecule on the cell surface. If, on the other hand, the characterization of a lymphocyte surface antigen is approached from information about its DNA sequence, the antibody will most probably have been raised against a recombinant protein or a synthetic peptide.
Thymic organ culture
Authors: Owen John j. T , Mcloughlin deirdre e. J
Published: November 2023

The maturation of T lymphocytes in the thymus is a complex process involving a number of distinct molecular events. Initially, stem cells migrate from the blood into the epithelial thymic primordium (1). These stem cells then undergo a process of T-cell receptor gene rearrangement resulting in the production of separate populations of αβ and γ δ T cells (reviewed in ref. 2). The development of α β T cells is preceded by expression of the pre T-cell receptor which controls the maturational process (3). In addition, differentiation of α β T cells is accompanied by expression of CD4 and CDS antigens. CD4+ CDS+ thymocytes then undergo a rigorous selection process involving the positive selection of cells with ‘useful’ T-cell receptors capable of recognizing foreign antigens in ‘self’ MHC, but negative selection of cells with ‘harmful’ receptors capable of autoreactivity (4).
lmmunofluorescence of surface markers
Authors: Loken Michael R , Green Cherie L , Wells Denise A
Published: November 2023

The discovery of monoclonal antibodies by Kohler and Milstein in 1975 dramatically enhanced the use of immunofluorescence for identifying cell-surface antigens. When applied in the flow cytometric analysis of heterogeneous populations, these highly specific monoclonal antibodies have broadened our understanding of diseases such as the progression of HIV infection, the origin and nature of leukaemia and lymphoma, and the regulation of haematopoietic cell differentiation and maturation.

The discovery of new fluorescent chromophores has further exploited the power of quantitative cellular analysis. These new dyes can be used in combina tion with the standard fluorescein isothiocyanate (FITC) to examine multiple antigens simultaneously. The orange and red emitting dyes-phycoerythrin (PE), tandem conjugates, and peridinin-chlorophyll (PerCP)-can all be excited by a single laser wavelength with their emission separated by bandpass filters (see Chapter 2).
Electron microscopy of filamentous fungi
Authors: O’Connell Richard J , Carzaniga Raffaella
Published: November 2023

Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) have made major contributions to our understanding of fungal cell biology. With the application of modern cryopreparation techniques, such as freezesubstitution, and advances in instrumentation, such as field-emission SEM, electron microscopy continues to generate a wealth of new information on the structure and organization of fungal cells. In addition, cytochemical techniques such as immunogold labelling provide a link between structure and biological function by localizing cell components with exquisite specificity and precision. Despite the obvious advantages of confocal microscopy, especially for live cell imaging, optical methods can never approach the spatial resolution offered by electron microscopy. Now that complete fungal genomes are being sequenced, electron microscopy is set to play an important role in helping to ascribe functions to the vast number of genes identified, for example by revealing the morphology of gene replacement mutants and the localization of gene products.
Human Cytogenetics: malignancy and acquired Abnormalities
Authors: Rooney D E
Published: November 2023

The advent of molecular technologies has lead to a rapid acceleration in the cytogenetic study of malignancy and acquired abnormalities. As well as having a chapter devoted to molecular technologies (FISH, PRINS, and CGH), molecular methodology is emphasized in all chapters, for example the role of CGH in solid tumour cytogenetics. Classical techniques are not forgotten, with a detailed description of the preparation and analysis of chromosomes from bone marrow and leukaemic blood. This is followed by three chapters on the specific methodology for the cytogenetic study of myeloid leukaemia, acute lymphoblastic leukaemia, and lymphomas and lymphoproliferative disorders. Also covered are chromosome instability syndromes, mutagen-induced chromosome damage in lymphocytes and the role of cytogenetics in the assessment of haematological disorders. This book will be invaluable to any scientists using cytogenetics to study malignancy and along with its sister volume Human Cytogenetics: Constitutional Analysis will be an essential purchase for any cytogenetics laboratory. The volumes are available individually or as a set.
Cellular functions of cytosolic E. coli chaperones
Authors: Mock Axel , Bukau Bernd , Deuerling Elke
Published: November 2023

The folding of newly synthesized polypeptide chains into their unique three dimensional structures is of fundamental importance in biology. Protein folding mechanisms were first studied in vitro using purified, chemically denatured polypeptides as substrates. In 1973 Anfinsen demonstrated the correct (re)folding of RNase upon removal of denaturant, suggesting that all the information needed for proper (re)folding was contained in the primary sequence of the protein (1). However, the concept of spontaneous protein folding cannot be extrapolated to living cells.
The roles of the cytosolic chaperonin, CCT, in normal eukaryotic cell growth
Authors: Willison Keith R , Grantham Julie
Published: November 2023

How do polypeptide chains synthesized on soluble polysomes in eukaryotic cytosol proceed to their native states? Is it reasonable to ask such questions of the folding pathways of tens of thousands of different proteins and expect to derive general answers or rules? We suspect that many proteins have sampled enough folding pathways during evolution to have had selected within their sequences chemical properties that allow them to fold up rapidly and concomitantly with chain elongation. The study of proteins which require the cooperation of molecular chaperones to assist their successful folding has provided major insights into understanding some of the problems which proteins face in proceeding to their native states.
Somite and Axial Development in Vertebrates
Authors: Hofmann Clementine
Published: November 2023

The development of the axial skeleton starts with somitogenesis. This is an example of a segmentation process in vertebrates. An initially unsegmented body progressively becomes segmented, leading to the formation of the vertebral column, the most obviously segmented structure in vertebrates. In the mesoderm of all vertebrate embryos, the underlying fundamental patterning process generates periodic blocks of cells, the somites, which form on either side of the neural tube. Somites have been studied in embryos from many vertebrate classes using a variety of experimental methods. However, the majority of studies have been performed in avian and amphibian species, because their embryos are more amenable for experimental manipulations and microsurgery than mammalian embryos. For quite some time, the analysis of somitogenesis and axis formation in mammalian embryos was not the focus of attention, although mutations in mice affecting somites and vertebrae have long been described (reviewed in ref. 1). In the past few years, the zebrafish has emerged as an additional model system for the analysis of somite and axis formation, since the transparency of the embryos allows resulting morphological defects in mutants to be observed and analysed in vivo. The establishment of in vitro culture systems for postimplantation mammalian embryos (2, 3) has also enabled the study of somitogenesis in mammalian embryos. In addition, targeted mutagenesis in the mouse by embryonic stem-cell technology has led to a rapid further understanding of the underlying molecular processes.
Insights into the Molecular basis of Vertebrate Forelimb and Hindlimb Identity
Authors: Kawakami Yasuhiko , Tsukui Tohru , NG Jennifer K , Izpisúa-belmonte Juan Carlos
Published: November 2023

Whilst recently we have gained insights into the molecular and cellular mechanisms that initiate the outgrowth and patterning of the vertebrate limb (reviewed in refs 1–5), very little is known about the mechanisms that determine differences between forelimbs and hindlimbs. In all vertebrates the hindlimb is morphologically distinct from the forelimb, yet both are composed of the same components such as nerves, muscles, blood vessels, and bone. These distinctions are even more striking among species. Compare, for instance, the forelimb and hindlimb of various vertebrates, such as the human arm and leg, the chick wing and leg, and the fish pectoral and pelvic fins. The recent identification of genes specifically expressed in the developing forelimb (Tbx5) and hindlimb (Pitx1 and Tbx4) in vertebrates, including human, mouse, chick, Xenopus laevis, newt, and zebrafish, has begun to aid our understanding of how limb identity is determined. Furthermore, gain- and loss-of-function studies have unveiled how these molecular cues function in the limb field to mediate the development of distinct structures. This chapter will review knowledge about the morphological and molecular basis of forelimb and hindlimb identity in vertebrates, and discuss the roles of Tbx4, Tbx5, and Pitx1 in limb-type specification.
The 2023 American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine Pediatric and Adult Brain Death/Death by Neurologic Criteria Determination Consensus Guidelines: What the Critical Care Team Needs to Know*
Authors: Kirschen Matthew P. , Lewis Ariane , Greer David M.
Published: November 2023

Guidelines for brain death/death by neurologic criteria (BD/DNC) determination were revised to provide a consistent and updated approach to BD/DNC evaluation across all ages by the American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine. This article is intended to complement the guidelines and highlight aspects relevant to the critical care community; the actual guidelines should be used to update hospital protocols and dictate clinical practice. Because BD/DNC evaluations are conducted in the ICU, it is essential for members of the critical care community to familiarize themselves with these guidelines. The fundamental concept of BD/DNC has not changed; BD/DNC is permanent loss of function of the brain as a whole, including the brain stem, resulting in coma, brainstem areflexia, and apnea in the setting of an adequate stimulus. The BD/DNC evaluation requires a sufficient observation period to ensure there is no chance of recovery, followed by exclusion of potentially confounding conditions like hypothermia, hypotension, severe metabolic disturbances, or medication effects. Specific guidance is provided for patients who were treated with therapeutic hypothermia or medical or surgical interventions to manage intracranial hypertension. The guidelines outline a structured and meticulous neurologic examination and detail the responses consistent with BD/DNC. A protocol is provided for how to safely perform apnea testing, including modifications needed for patients on extracorporeal membrane oxygenation. Controversial issues such as consent, BD/DNC evaluation in pregnancy, preservation of neuroendocrine function, and primary posterior fossa injuries are addressed. The ultimate goal is to ensure a consistent and accurate approach to BD/DNC evaluation in patients of all ages, fostering public trust in the medical community’s ability to determine death. By adhering to these guidelines, critical care clinicians can confidently navigate the challenging aspects of BD/DNC determination.
Intersections between HIV and obesity in emerging economies
Authors: Levi Jacob , Fairhead Cassandra , Hill Andrew
Published: November 2023

Purpose of review

HIV epidemics are increasing in many emerging economy countries, whilst the very process of ‘economic emergence’ is obesogenic. Annual deaths related to obesity and overweight are now four times more than for HIV globally. We describe the intersections between HIV and obesity in emerging economies, and highlight potential mitigation options, including antiobesity medications (AOMs), which are safe and effective, but inaccessibly priced.

Recent findings

We summarize what is known about weight-change in HIV and review strategies including public health policies and clinical interventions for emerging economy countries to fight obesity. We also illustrate the landscape from a selection of ‘emerging economy’ countries with available data from UNAIDS, World Bank and World Obesity Federation to visualize the developing challenges faced. AOM course prices are high in many countries, but could be manufactured and sold profitably for much less. We present lessons from the early HIV/AIDS movements on how to improve access and pricing for AOMs for people with HIV with obesity in emerging economy countries.

We illustrate the complex intersectional issues that ‘emerging economy countries’ may experience, with a ‘double burden’ of increasing HIV and obesity epidemics, and explore potential mitigation options, focussing on AOM access and pricing.
Surgical Reconstruction for the Triphalangeal Thumb
Authors: Tiourin Ekaterina , Sharpe Frances , Kalina Sharon , Leis Amber R.
Published: November 2023

The triphalangeal thumb poses a complex reconstructive challenge to the congenital hand surgeon due to its rarity and variable anatomy. We discuss the available evidence, reporting clinical characteristics and outcomes of surgical reconstructive procedures of triphalangeal thumb alongside a representative case. The congenital hand surgeon must approach each patient with triphalangeal thumb individually to optimize the use of available tissues to maximize functional and aesthetic outcomes.
A Pediatric Case of Disseminated Bartonella henselae Infection Accompanied by Multiple Intracranial Lesions
Authors: Hirakawa Jun , Kawamura Masaru , Hoshina Takayuki , Taniguchi Madoka , Kondo Hiroyuki , Satake Hiroshi , Nawata Aya , Tsuneoka Hidehiro , Kusuhara Koichi
Published: November 2023

We report a pediatric case of disseminated Bartonella henselae infection accompanied by multiple intracranial lesions. The patient developed multiple intracranial lesions despite treatment with azithromycin and gentamicin. After switching to rifampicin, the clinical symptoms of the patient improved. Given its good penetration into the central nervous system, rifampicin may be recommended for the treatment of B. henselae infection accompanied by intracranial lesions.
An Initiative to Stop Antibiotics Prescribed for Urinary Symptoms When Urine Culture Is Negative
Authors: Kofoed Benjamin , Morris Jacob , Rich Jennifer
Published: November 2023

Urinary symptoms pose frequent diagnostic and management challenges in the emergency department (ED). In our regional health system, we identified the problem of patients started on antibiotics for urinary symptoms in the ED without a process for eventual review or discontinuation if urine culture (UC) later resulted as negative. To address this gap, we implemented a pharmacist-driven follow-up process to discontinue antibiotics after a negative UC. After project implementation, cases reviewed by a pharmacist increased from 0% to 96.7%. Patients contacted to discontinue antibiotics increased from 0% to 40% postintervention. This process improvement is now shared across five rural departments. Our results have broad applicability in any ED environment.
Bleomycin Sclerotherapy Is Laboratory Monitoring Necessary?
Authors: Mack Joana M. , DeHart Austin N. , Verkamp Bethany , Lewis P. Spencer , Crary Shelley E.
Published: November 2023

Objectives:

Bleomycin is a chemotherapeutic agent also used as a sclerosant for the management of vascular malformations. Although effective and with a low complication profile, the safety and monitoring necessary for this indication is still controversial. This study examines routine periprocedural laboratory results on a cohort of patients undergoing bleomycin sclerotherapy.

Methods:

Retrospective chart review of prospectively collected data was performed on patients who underwent bleomycin sclerotherapy for vascular malformations from 2011 to 2018. Complete blood count and liver function were assessed before and after sclerotherapy.

Results:

Forty-six patients were identified who underwent a total of 71 sclerotherapy sessions with bleomycin. A median dose of 5 U/m2 of bleomycin was used per procedure (8 U total). No difference between preprocedure and postprocedure values was detected for white blood cell count (7.7–7.9; P = .63) or absolute neutrophil count (4009–4414; P = .20). A nominal difference was found in hemoglobin (12.7–13.0; P = .001), hematocrit (37.0–38.6; P = .001), and platelet counts (278–302; P = .001). No patient had absolute neutrophil count levels below 500 cells/μL. On liver function tests, no change was detected for direct bilirubin (0.19–0.17; P = .4). A small decrease in total bilirubin (0.49–0.41; P = .004), aspartate aminotransferase (32.1–26.9; P < .001), and alanine aminotransferase (31.2–24.3; P < .001) was shown.

Conclusion:

This study suggests that laboratory assessment of immune and liver function, as commonly performed in chemotherapy protocols, is not required following intralesional bleomycin sclerotherapy. Clinically relevant abnormalities are unlikely to be detected as demonstrated in this cohort of patients with vascular malformations.
Prognostic significance of preoperative nutritional status for postoperative acute kidney injury in older patients undergoing major abdominal surgery: a retrospective cohort study
Authors: Sun Rao , Zhou Zhiqiang , Li Xinhua , Xu Qiaoqiao , Zhou Biyun , Yu Honghui , Zhang Wanjun , Sun Qi , Zhang Xiang , Luo Xiaoxiao , Li Shiyong , Luo Ailin
Published: November 2023

Background:

The association between malnutrition and postoperative acute kidney injury (AKI) has not been well studied. In this study, we examined the association between preoperative nutritional status and postoperative AKI in older patients who underwent major abdominal surgery, as well as the predictive value of malnutrition for AKI.

Materials and methods:

We retrospectively included patients aged 65 or older who underwent major elective abdominal surgery. The nutritional status of the patient was evaluated using 3 objective nutritional indices, such as the geriatric nutritional risk index (GNRI), the prognostic nutritional index (PNI), and the controlling nutritional status (CONUT). AKI was determined using the KDIGO criteria. We performed logistic regression analysis to investigate the association between preoperative nutritional status and postoperative AKI, as well as the predictive value of nutritional scores for postoperative AKI.

Results:

A total of 2775 patients were included in the study, of which 707 (25.5%), 291 (10.5%), and 517 (18.6%) had moderate to severe malnutrition according to GNRI, PNI, and CONUT calculations. After surgery, 144 (5.2%) patients developed AKI, 86.1% at stage 1, 11.1% at stage 2, and 2.8% at stage 3 as determined by KDIGO criteria. After adjustment for traditional risk factors, worse nutritional scores were associated with a higher AKI risk. In addition to traditional risk factors, these nutritional indices improved the predictive ability of AKI prediction models, as demonstrated by significant improvements in integrated discrimination and net reclassification.

Conclusions:

Poor preoperative nutritional status, as assessed by GNRI, PNI and CONUT scores, was associated with an increased risk of postoperative AKI. Incorporating these scores into AKI prediction models improved their performance. These findings emphasize the need for screening surgical patients for malnutrition risk. Further research is needed to determine whether preoperative malnutrition assessment and intervention can reduce postoperative AKI incidence.
Practical Clinical Guidelines for Natalizumab Treatment in Patients With Relapsing Multiple Sclerosis
Authors: O'Leary Shirley , Brugger Helen T. , Wallentine Dale , Sershon Lisa , Goff Erica , Saldana-King Toni , Beavin Jill , Avila Robin L. , Rutledge Danette , Moore Marie
Published: November 2023

Natalizumab (TYSABRI®) was the first high-efficacy monoclonal antibody disease-modifying therapy (DMT) approved as a monotherapy for the treatment of adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS. Because natalizumab is administered by intravenous infusion, infusion nurses play a key role in the care of natalizumab-treated patients. In the 16 years since approval, substantial data have been gathered on the long-term, real-world effectiveness and safety of natalizumab. This article provides a synopsis of this data, as well as practical information for optimizing patient care. This includes information on strategies to mitigate the risk of progressive multifocal leukoencephalopathy in natalizumab-treated patients, natalizumab use during pregnancy, and use with vaccines. It also includes guidance on the preparation and administration of natalizumab and monitoring of natalizumab-treated patients.
Acceptability, Appropriateness, and Feasibility of an Educational Program to Promote Treatment Adherence in Patients with Chronic Obstructive Pulmonary Disease
Authors: Trieu Nguyen Thi Thu , Upval Michele , Hoai Nguyen Thi Yen , Van Long Tran , Phuong Nguyen Thi Anh
Published: November 2023

The mortality rate due to chronic obstructive pulmonary disease (COPD) has increased annually, and non-adherence to treatment is one reason for this rise. Developing intervention programs to enhance treatment adherence for people with COPD is essential. The purpose of this mixed-methods study was to determine the acceptability, appropriateness, and feasibility of such a program. We sought the opinions of 15 healthcare managers and 15 practicing nurses from three hospitals across Vietnam and conducted group discussions and interviews with 30 patients with COPD. We then formulated integrated conclusions on the acceptability, appropriateness, and feasibility of the program. The overall average score of 12 items to test the acceptability, appropriateness, and feasibility of the program from both healthcare managers and practicing nurses was high (M = 4.31; SD = 0.11) and (M = 4.37; SD = 0.12), respectively. Thirty COPD outpatients agreed the content and plan of the program were necessary for them to enhance their treatment adherence at home. The document content was appropriate, easy to understand, and the support and education provided by nurses was helpful. The educational intervention program to promote treatment adherence for patients with COPD was acceptable, appropriate, and feasible from the views of healthcare managers, nurses, and patients with COPD.
Does Initiation of Prophylactic Antiseizure Medication Improve Neurological Outcomes in Patients With Acute Intracerebral Hemorrhage?
Authors: Chhabra Nikita , Crepeau Amy Z. , Demaerschalk Bart M. , Knox Molly G. , Freeman William David , Valencia Sanchez Cristina , Marks Lisa A. , O’Carroll Cumara B.
Published: November 2023

Objective:

The objective of this study was to critically assess current evidence regarding the role of prophylactic antiseizure medication in patients presenting with acute intracerebral hemorrhage (ICH).

Methods:

The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included resident neurologists, a medical librarian, and content experts in the fields of epilepsy, stroke neurology, neurohospitalist medicine, and neurocritical care.

Results:

A randomized clinical trial was selected for critical appraisal. The trial assessed whether prophylactic levetiracetam (LEV) use reduced the risk of acute seizures in patients with ICH, as defined by clinical or electrographic seizure, captured by continuous electroencephalogram 72 hours after enrollment. A total of 42 patients were included in the final analysis (19 in the LEV group and 23 in the placebo group). There was a significantly higher occurrence of seizures in the placebo versus LEV group (LEV 16% vs placebo 43%, P = 0.043). There were no differences in functional outcomes between the groups at 3, 6, or 12 months (P > 0.1).

Conclusions:

The role of prophylactic treatment with antiseizure medication in ICH remains unclear.
The Impact of Body Mass Index on Adverse Outcomes Associated with Panniculectomy: A Multimodal Analysis
Authors: Laspro Matteo , Cassidy Michael F. , Brydges Hilliard T. , Barrow Brooke , Stead Thor S. , Tran David L. , Chiu Ernest S.
Published: November 2023

Background:

Overhanging pannus may be detrimental to ambulation, urination, sexual function, and social well-being. Massive weight loss patients often have high residual body mass index (BMI) and comorbidities presenting a unique challenge in panniculectomy patient selection. This study aims to better characterize the role of BMI in postoperative complications following panniculectomy.

Methods:

A meta-analysis attempted to assess the impact of BMI on complications following panniculectomy. Cochrane Q and I
2 test statistics measured study heterogeneity, with subsequent random effects meta-regression investigating these results. After this, all panniculectomy patients in the National Surgical Quality Improvement Program database in the years 2007 to 2019 were analyzed. Univariate and multivariable tests assessed the relative role of BMI on 30-day postoperative complications.

Results:

Thirty-four studies satisfied inclusion criteria, revealing very high heterogeneity (Cochrane Q = 2453.3; I
2 = 99.1%), precluding further meta-analysis results. Receiver operating characteristic curves demonstrated BMI was a significant predictor of both all causes (area under the curve, 0.64; 95% CI, 0.62 to 0.66) and wound complications (area under the curve, 0.66; 95% CI, 0.63 to 0.69). BMI remained significant following multivariable regression analyses. Restricted cubic spines demonstrated marginal increases in complication incidence above 33.2 and 35 kg/m2 for all-cause and wound complications, respectively.

Conclusions:

Reported literature regarding postoperative complications in panniculectomy patients is highly heterogeneous and may limit evidence-based care. Complication incidence positively correlated with BMI, although the receiver operating characteristic curve demonstrated its limitations as the sole predictive variable. Furthermore, restricted cubic splines demonstrated diminishing marginal predictive capacity of BMI for incremental increases in BMIs above 33.2 to 35 kg/m2. These findings support a reevaluation of the role of BMI cutoffs in panniculectomy patient selection.
Pharmacokinetics, Safety, and Tolerability of the Novel Tetrameric, High-Relaxivity, Macrocyclic Gadolinium-Based Contrast Agent Gadoquatrane in Healthy Adults
Authors: Hofmann Birte Maria , Riecke Kai , Klein Stefan , Berse Matthias , Rottmann Antje , Sutter Gabriele , Ebert Wolfgang
Published: November 2023

Objectives

Gadolinium (Gd)–based contrast agents are well established in clinical routine and have been proven safe and effective. However, there is a need for “next-generation” Gd-based contrast agents that would allow lowering the Gd dose used for routine contrast-enhanced magnetic resonance imaging procedures. The objective of this first-in-human study was to investigate the pharmacokinetic profile, safety, and tolerability of gadoquatrane, a novel high-relaxivity Gd-based contrast agent.

Materials and Methods

This study was conducted in 2018/2019 as a prospective, randomized, single-blind, single-dose, placebo-controlled, escalating-dose study. Healthy volunteers were randomly assigned (6:2) to intravenous administration of gadoquatrane (0.025 to 0.2 mmol Gd/kg body weight) or placebo. Study procedures included collection of blood samples and excreta for pharmacokinetic analyses and safety assessments.

Results

Forty-nine healthy study participants (mean age ± SD, 35 ± 6.3 years; 24 female) were evaluated. The effective half-life of gadoquatrane in plasma was short and similar in all dose groups (1.4–1.7 hours). Plasma concentrations around the lower quantitation limit (0.0318 μmol Gd/L) were reached 15–72 hours after administration. The volume of distribution at steady state was ~0.2 L/kg in all dose groups. The clearance (total and renal) was ~0.1 L/h per kilogram in all groups. Across dose groups, the exposure of gadoquatrane increased dose-proportionally. Metabolite profiling revealed no hint of degradation in vivo or release of free Gd. Seven of 36 participants (19.4%) receiving gadoquatrane and 4 of 13 participants (30.8%) receiving placebo experienced mild or moderate treatment-emergent adverse events. No serious adverse events occurred. The analysis of the Gd concentration-QTc interval relationship indicated no risk of QT/QTc prolongation (>10 milliseconds) with gadoquatrane at clinical dose levels.

Conclusions

Gadoquatrane with its high-relaxivity, pharmacokinetic similarity to established Gd-based contrast agents and high tolerability is a promising “next-generation” contrast agent for magnetic resonance imaging.
Surgical Techniques and Related Perioperative Outcomes After Robot-assisted Minimally Invasive Gastrectomy (RAMIG)
Authors: de Jongh Cas , Cianchi Fabio , Kinoshita Takahiro , Kingma Feike , Piccoli Micaela , Dubecz Attila , Kouwenhoven Ewout , van Det Marc , Mala Tom , Coratti Andrea , Ubiali Paolo , Turner Paul , Kish Pursnani , Borghi Felice , Immanuel Arul , Nilsson Magnus , Rouvelas Ioannis , Hӧlzen Jens P. , Rouanet Philippe , Saint-Marc Olivier , Dussart David , Patriti Alberto , Bazzocchi Francesca , van Etten Boudewijn , Haveman Jan W. , DePrizio Marco , Sabino Flávio , Viola Massimo , Berlth Felix , Grimminger Peter P. , Roviello Franco , van Hillegersberg Richard , Ruurda Jelle ,   UGIRA Collaborative Group
Published: November 2023

Objective:

To gain insight into the global practice of robot-assisted minimally invasive gastrectomy (RAMIG) and evaluate perioperative outcomes using an international registry.

Background:

The techniques and perioperative outcomes of RAMIG for gastric cancer vary substantially in the literature.

Methods:

Prospectively registered RAMIG cases for gastric cancer (≥10 per center) were extracted from 25 centers in Europe, Asia, and South-America. Techniques for resection, reconstruction, anastomosis, and lymphadenectomy were analyzed and related to perioperative surgical and oncological outcomes. Complications were uniformly defined by the Gastrectomy Complications Consensus Group.

Results:

Between 2020 and 2023, 759 patients underwent total (n=272), distal (n=465), or proximal (n=22) gastrectomy (RAMIG). After total gastrectomy with Roux-en-Y-reconstruction, anastomotic leakage rates were 8% with hand-sewn (n=9/111) and 6% with linear stapled anastomoses (n=6/100). After distal gastrectomy with Roux-en-Y (67%) or Billroth-II-reconstruction (31%), anastomotic leakage rates were 3% with linear stapled (n=11/433) and 0% with hand-sewn anastomoses (n=0/26). Extent of lymphadenectomy consisted of D1+ (28%), D2 (59%), or D2+ (12%). Median nodal harvest yielded 31 nodes (interquartile range: 21–47) after total and 34 nodes (interquartile range: 24–47) after distal gastrectomy. R0 resection rates were 93% after total and 96% distal gastrectomy. The hospital stay was 9 days after total and distal gastrectomy, and was median 3 days shorter without perianastomotic drains versus routine drain placement. Postoperative 30-day mortality was 1%.

Conclusions:

This large multicenter study provided a worldwide overview of current RAMIG techniques and their respective perioperative outcomes. These outcomes demonstrated high surgical quality, set a quality standard for RAMIG, and can be considered an international reference for surgical standardization.