Climate change poses new threats to plant production as environmental stresses increase significantly. Biotic and abiotic stress that have adverse effects on plant growth and crop productivity and can be major constraints on yield. This will particularly affect major food crops, including legumes and cereals. Biotic and abiotic stresses, such as salinity, drought, chemical toxicity, extreme temperatures and oxidative stress are often interrelated and become serious threats to agriculture. These extreme conditions induce cellular damage and disruption of plant growth and development by a series of morphological, physiological, biochemical and molecular changes. For example, these extreme stresses are often leading to oxidative damage and excessive creation of reactive oxygen species (ROS) in plant cells. Usually, plants interact with these extreme conditions by their innate antioxidative defense system that including enzyme and non-enzyme elements . HoweverTherefore, enhancing the productivity of these important crops is important for the food security of growing populations worldwide. High heterozygosity imposes severe limitations on breeding new varieties of major food crops with desired traits. Conventional plant breeding and genetic research have significantly evolved in recent decades. However, to meet the growing human population’s food demand, especially for major staple cereal and legume crops, genetic gain must be enhanced, making it necessary to exploit genetic diversity within cultivated crops and wild relatives. With modern technologies, plant breeders can use these additional resources of diversity to address problems like biotic and abiotic stresses and yield by combining methods from genomics, and advanced analytics in cereal and legume breeding programs on a massive scale. This topic explores how the recent advances in genomics and plant biotechnology approaches are helping researchers to answer questions related to crop improvement. Therefore, we encouraged contributions to this Research Topic to advance and disseminate knowledge across various facets of this critical field. Our goal is to illuminate the molecular mechanisms that underlie biotic and abiotic stress tolerance, enhance comprehension of plant stress biology, with a particular focus on legumes and cereals. This effort ultimately contributes to bolstering sustainable agriculture and global food security. In this topic, recent advances in genomics and stress tolerance studies of cereals and legumes are presented in six publications, contributed by 52 authors.2+), which plays a crucial role in transmitting signals and regulating numerous physiological processes. This is accomplished through Ca2+ sensors and their target proteins, as highlighted by previous research  IQM genes  using genome-wide bioinformatics analysis and molecular biology techniques. They discussed the phylogenetic relationships, gene structure, conserved motifs, chromosome location, evolutionary pattern analysis, yeast two-hybrid analysis, and expression profile in response to abiotic stress and hormones of the soybean IQM family. Their results provide a theoretical basis for subsequent functional analysis of soybean IQM genes and insights into improving soybean resistance to biotic and abiotic stresses. Furthermore, Hu et al. indicated that the multiple members of CDPKs in wheat (Triticum aestivum) have diverse and vital functions in plant growth, development regulation and stress responses. They reported that every TaCDPKs member has a specific function. Their results clearly provide an important foundation for in-depth exploring the function and the signaling pathways of CDPK family members, especially the interactions between TaCDPKs and TaNOXs in wheat.Many complex signaling pathways are involved in the response of plants to biotic and abiotic stresses . For exaresearch . SpecifiXue et al. performed a research toward deep RNA sequencing to depict long non-coding RNAs (lncRNAs) profiles in rice associated with BPH feeding using the resistant Near-Isogenic Line (KW-Bph36-NIL). They elaborated insightful information on the genome-wide differentially expressed genes (DEGs) and differentially expressed lncRNAs (DELs) expression profiles of rice under BPH invasion by high throughput sequencing. They suggested that NILs could be used in BPH resistance breeding programs.Insect pest infestation is a serious threat to cereal crops and causes extensive damage to crop production annually. The brown planthopper (BPH) is a major threat to rice production. Host-plant resistance is a key component of pest management strategies to reduce the damage caused by BPH in rice production worldwide. Maanju et al. to determine the genetic diversity and population structure of corn leaf aphid (CLA) Rhopalosiphum maidis (Fitch) resistance in barley to identify sources of resistance against R. maidis that considered as a common pest of cereals worldwide. In this study, 10 aphid specific simple-sequence repeats (SSR) markers were used to investigate the genetic diversity and population structure of 109 barley genotypes against R. maidis. Cluster analysis from the agro-morphological features grouped all the germplasm in four subpopulations and approximately 87.52% of the 109 barley genotypes shared a common major allele at any locus and finally they identified two genotypes having high resistance against CLA which highlighted their potential for inclusion in the future CLA resistance breeding programs.A study was undertaken by Park et al. analyzed the transcriptome changes associated with the callus formation process in soybean under the influence of wounding signals and phytohormones. They identified key genes associated with transcription factors, biosynthesis, transporters, and signaling pathways related to phytohormones. The obtained results demonstrated the importance of the coordinated interplay of wounding, auxin, cytokinin, and brassinosteroid signaling pathways to activate the genes involved in determining the fate of meristematic cells. This study provides insights into the regulatory network of callus formation in soybean.With the aim of uncovering facts related to the biological mechanism underlying soybean callus induction and developmental process, Wu et al. reported the analysis of the sugar beet WD40 proteins. They identified 177 bvWD40 from sugar beet and analyzed their evolutionary characteristics, protein structure, gene structure, protein interaction network and gene ontology. They concluded that BvWD40-82 gene is a salt-tolerant candidate gene. Transgenic Arabidopsis thaliana seedlings expressing BvWD40-82 showed enhanced tolerance to salt stress by elevating the contents of osmolytes and antioxidant enzyme activates, maintaining intracellular ion homeostasis and increasing the expression of genes related to salt overly sensitive (SOS) and abscisic acid (ABA) pathway. The obtained results hypothesized the importance of BvWD40-82 as a promising candidate gene for improving crop stress resilience.Salinity is a major environmental stress on crop productivity. Understanding the molecular and physiological mechanisms underlying salt stress tolerance will facilitate efforts to improve crop performance under salinity. In line with this aim, Biotic and abiotic stresses will remain major concerns for future food production and sustainability. The use of the most recent technologies in leveraging genomics, phenomics, machine learning approaches and plant biotechnology along with conventional breeding strategies is the most appropriate way to identify multifactorial interactions networks involved in plant defenses against stress conditions towards improving abiotic and biotic stress tolerance in major crops.PL: Writing – review & editing. MH: Writing – review & editing. RT: Writing – review & editing. MR: Writing – review & editing. HS: Writing – review & editing. H-JJ: Writing – review & editing.


Saccharomyces cerevisiae has been studied in hopes of understanding its causes and identifying conserved pathways that also drive aging in multicellular eukaryotes. While the short lifespan and unicellular nature of budding yeast has allowed its aging process to be observed by dissecting mother cells away from daughter cells under a microscope, this technique does not allow continuous, high-resolution, and high-throughput studies to be performed. Here, we present a protocol for constructing microfluidic devices for studying yeast aging that are free from these limitations. Our approach uses multilayer photolithography and soft lithography with polydimethylsiloxane (PDMS) to construct microfluidic devices with distinct single-cell trapping regions as well as channels for supplying media and removing recently born daughter cells. By doing so, aging yeast cells can be imaged at scale for the entirety of their lifespans, and the dynamics of molecular processes within single cells can be simultaneously tracked using fluorescence microscopy.For several decades, aging in Key featuresThis protocol requires access to a photolithography lab in a cleanroom facility.Photolithography process for patterning photoresist on silicon wafers with multiple different feature heights.Soft lithography process for making PDMS microfluidic devices from silicon wafer templates. Saccharomyces cerevisiae, the traditional method of manual microdissection of mother and daughter cells in order to count replicative lifespan has been largely supplanted by the use of microfluidic devices, which efficiently trap individual mother cells in place while removing newly budded daughter cells . As a reference, yeast cells growing in the device can be seen in Paxman et al. (2022). Age-dependent aggregation of ribosomal RNA-binding proteins links deterioration in chromatin stability with challenges to proteostasis. eLife (


Plasmodium malaria parasites [P. falciparum and highlight critical future questions to answer.Isoprenoid precursor synthesis is an ancient and fundamental function of plastid organelles and a critical metabolic activity of the apicoplast in arasites –3. Over arasites , due in arasites ,6. In th Malaria parasites retain a non-mevalonate/methylerythritol phosphate (MEP) pathway for isoprenoid precursor synthesis in the apicoplast organelle. This pathway synthesizes two 5-carbon isoprene subunits, isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), whose sequential condensation is critical for making diverse longer-chain isoprenoids required for a variety of key cellular functions that include protein prenylation, dolichol synthesis for protein glycosylation, and biosynthesis of mitochondrial ubiquinone and heme A . Core enPlasmodium therefore requires the apicoplast and the pathways that support and maintain this key organelle.Within the apicoplast, isoprenoid precursor synthesis requires the support of several additional metabolic pathways. The final 2 enzymes in the MEP pathway, IspG and IspH, contain essential Fe-S cluster cofactors that receive electrons from apicoplast-targeted ferredoxin, which also contains an Fe-S cluster. These critical Fe-S cofactors are produced by the apicoplast Suf pathway, which is therefore essential for isoprenoid synthesis –10. One Plasmodium focused almost exclusively on cellular roles for isoprenoids outside of the apicoplast, since exogenous IPP can rescue parasites from loss of the apicoplast and the attendant ablation of endogenous IPP synthesis. Nevertheless, multiple prior papers reported that MEP pathway inhibitors like fosmidomycin (FOS) blocked apicoplast biogenesis and prevented elongation of the organelle in blood-stage parasites . Sev. Sev4]. The foundational discovery that exogenous IPP could rescue parasites from apicoplast-specific dysfunctions and organelle loss enabled many opportunities to probe the functional properties of the apicoplast and its constituent proteins . BecauseP. falciparum [Plasmodium will be required for organelle maintenance due to a critical role in IPP synthesis and/or in other aspects of apicoplast biogenesis apart from IPP synthesis. Future studies of apicoplast functions can test this prediction and extend or revise its validity to different parasite stages in distinct host environments, where additional apicoplast pathways like type II fatty acid synthesis can produce essential outputs [Current knowledge specifies IPP and coenzyme A (CoA) as the only biosynthetic outputs of the apicoplast that are essential for blood-stage lciparum ,19,20. Ulciparum ,19. Base outputs ,22 that Plasmodium, this paradigm of metabolic interdependence does not appear to hold throughout the phylum Apicomplexa. Toxoplasma gondii parasites express 2 PPS homologs but neither appears to localize to the apicoplast [T. gondii, loss of isoprenoid precursor synthesis has no apparent impact on apicoplast biogenesis [Plasmodium and Toxoplasma presumably reflect the differing selective pressures that guided evolution of these parasites over the 600 Myr timeline of their divergence from a common ancestor. Multiple PPS homologs are also retained by other hematozoan parasites  that are more closely related to Plasmodium than Toxoplasma, but a possible role for PPS in apicoplast biogenesis is unexplored in these organisms. Understanding the similarities and differences in isoprenoid metabolism between broader apicomplexan parasites can unveil and unravel the biochemical forces that have spurred evolution of intracellular parasitism along distinct pathways.The MEP pathway for isoprenoid precursor synthesis is a hallmark of apicoplast retention in apicomplexan parasites . Althougicoplast ,23,24. Aogenesis ,25. ThesP. falciparum parasites that we hope will stimulate future studies in these areas.Below, we lay out several key questions at the frontier of our understanding of the apicoplast and isoprenoid metabolism in Why does apicoplast biogenesis require long-chain linear isoprenoids? We hypothesize that these lipids are critical to tune the biophysical properties and flexibility of apicoplast membranes, such that their deficiency impairs membrane expansion during organelle biogenesis. It remains unknown if these isoprenoids are enriched in specific or all apicoplast membranes and/or serve other roles in organelle biogenesis. It may be possible to test our hypothesis with small-molecule dyes whose fluorescence properties are sensitive to variations in membrane fluidity, together with chemical rescue experiments using a homologous series of progressively longer-chain polyprenols to bypass loss of PPS.How are isoprenoids transported into and out of the apicoplast? Isoprenoid precursors synthesized in the apicoplast, including IPP and DMAPP, are required and utilized outside the organelle. Chemical rescue experiments suggest that IPP and longer isoprenoids can enter the apicoplast. Charged metabolites face an unfavorable energetic barrier to diffuse across the 4 hydrophobic membrane bilayers that encircle the apicoplast, but specific protein transporters that enable their passage into and out of the organelle remain undefined.What prenyl synthase supports the biosynthesis of ubiquinone required in the Plasmodium mitochondrion? Ubiquinone, which has a polyprenyl tail, is critical for function of the mitochondrial electron transport chain. A mitochondrial-targeted polyprenyl synthase has been identified in T. gondii [Plasmodium remain obscure and poorly studied. Apicoplast PPS was proposed to play this role in Plasmodium [. gondii , but theasmodium , but theasmodium .Are there additional metabolic uses of isoprenoids by malaria parasites beyond currently defined products? Plasmodium lacks enzyme homologs for terpene and carotenoid biosynthesis, and recent work found no evidence to support IPP incorporation into carotenoids [otenoids ,3,15. Ne


Patients with traumatic brain injury (TBI) or head trauma present challenges for emergency physicians and neurosurgeons. Traumatic brain injury is currently a community health issue. For the best possible care, it is crucial to understand the various helpful therapy techniques in the pre-operative and pre-hospital phases. The initial rapid infusion of large volumes of mannitol and a hypertonic crystalloid solution to restore blood pressure and blood volume is the current standard of care for people with combined hemorrhagic shock (HS) and traumatic brain injury. The selection and administration of fluids to trauma and traumatic brain injury patients may be especially helpful in preventing subsequent ischemic brain damage because of the hemodynamic stabilizing effects of these fluids in hypovolemic shock. Traumatic brain injury is an essential factor that may lead to disability and death in a patient. Traumatic brain damage can develop either as a direct result of the trauma or as a result of the initial harm. Significant neurologic problems, such as cranial nerve damage, dementia, seizures, and Alzheimer's disease, can develop after a traumatic brain injury. The comorbidity of the victims may also be significantly increased by additional psychiatric problems such as psychological diseases and other behavioral and cognitive sequels. We review the history of modern fluid therapy, complications after traumatic brain injury, and the use of fluid treatment for decompressive craniectomy and traumatic brain injury. The term "traumatic brain injury" (TBI) is most often used to describe brain dysfunction brought on by external trauma. Many types of traumatic injuries happen worldwide, and traumatic brain injury is one of the most contentious health issues in modern society . The CenAn essential part of surgical treatment is administering perioperative fluids, although this process is frequently not completely understood and is still primarily empirical. There are lingering concerns regarding its effectiveness and potential consequences ,11. FluiMethodologyWe undertook a search through PubMed, CENTRAL and other government sources in November 2022 using keywords such as "traumatic brain injury", "fluid resuscitation", "brain injury", "brain trauma", and "colloid solutions"((( traumatic brain injury [Title/Abstract]) OR ("traumatic brain injury" [MeSH Terms]), ("fluid resuscitation" [Title/Abstract])) OR ("fluid resuscitation" [MeSH Terms]), (("brain injury" [Title/Abstract]) OR ("brain injury" [MeSH Terms]) AND ("brain trauma" [Title/Abstract]) OR ("brain trauma" [MeSH Terms]). One reviewer independently checked the papers retrieved based on title and abstract against the inclusion criteria before moving on to the full texts. Another reviewer also reviewed 20% of these studies to validate inclusion studies. The selection of studies Figure  dependedThe evolution of modern fluid therapyThe importance of intravenous fluid therapy in treating cholera initially emerged in the 1830s, thanks to William Brooke O'Shaughnessy's findings on the blood observations of his suffering cholera patients ,25. It wCrystalloidsSmall, water-soluble molecules that make up a crystalloid fluid can quickly diffuse across semi-permeable barriers. These solutions' tonicity  and sodium content (which affects how they are distributed throughout the body compartments) together greatly influence their features . They reColloidsColloids are liquids that impose oncotic pressure on semi-permeable membranes because they are composed of larger, more soluble molecules that are difficult to penetrate. Through osmosis, water is retrieved from the interstitial and international classifications of functioning based on their shape, molecular weight, capillary permeability, and ionic charge. They exit the intravascular region and act for a specific time . All colTraumatic brain injury and fluid therapyOedema development is not significantly impacted by clinically appropriate fluid restriction. The first investigation on human fluid therapy showed that decreasing the standard maintenance volume by 50% for neurosurgical patients causes an increase in serum osmolality over about a week . TherefoFluid treatment for decompressive craniectomyBased on experience, it is suggested that decompressive craniectomy in traumatic epidural hematoma patients improves these patients' outcomes . The genPhysiological reactions in the perioperative stageThe effects of surgery alone and the resulting adjustments to the hormonal environment inside the body are exacerbated in critically ill patients by a systemic inflammatory response that leads to capillary leak development. As a result, the interstitium endures losses that are challenging to balance and frequently display oedema. Additionally, nutritional support and actions that alter acid-base homeostasis can actively or inadvertently influence the fluid and electrolyte imbalances that result in severe illness . The effTable Traumatic brain injury (TBI) is a greater community or social health problem that increases mortality and disability. Traumatic brain injuries can result from physical attacks, sports-related injuries, traffic accidents, etc. The development of therapeutic procedures for TBI recovery has been ongoing for many years, even though there is currently no effective treatment for TBI rehabilitation. For the best possible care, it is crucial to understand the various helpful therapy techniques in the pre-operative and pre-hospital phases. There are still questions concerning the benefits and dangers of perioperative fluid therapy. The rapid infusion of large crystalloids to restore blood volume and blood pressure is now the standard treatment for patients with combined traumatic brain injury (TBI) and hemorrhagic shock (HS). Crystalloid fluid therapy is more effective than colloid fluid therapy in patients with TBI. There are no standards of care or evidence-based guidelines for managing fluid treatment in patients having decompressive craniectomy.


Suicide is a major health problem, mostly related to mental health disorders. However psychological autopsies have revealed the presence of unexpected suicide factors such as dietary patterns particularly folate intake. Which is a naturally occurring form of B9 essential for neurogenesis, nucleotide synthesis and methylation of homocysteine.The aim of our study is to identify the link between folate intake and suicidality.Our literature review was based on the PubMed interface and adapted for 2 databases: Science Direct and Google Scholar using the following combination ( suicide [MeSH terms]) AND (folate [MeSH terms]) AND (prevention [MeSH terms]).Stress-induced neuronal dysfunctions interact with genetic and environmental factors, including diet, to precipitate mental health disorders in vulnerable or predisposed individuals especially mood disorders.In one hand, studies showed delayed onset of clinical improvement even treatment resistance in depressive patients treated with fluoxetine associated with low folate levels.In the other hand Folate depletion has been linked to serotoninergic metabolism disturb.Moreover, co-administration of methylfolate, a highly absorbable form of folic acid, has been found to augment the effects of SSRIs .A duration-response analysis (1-mg dosage) revealed a 5% decrease in suicidal events per month of additional treatment.Accumulating data have shown that these nutrients can enhance neurocognitive function, and may have therapeutic benefits for depression and suicidal behaviors . But the pathological mechanism remains unclear that’s why further studies are needed for a better comprehension and efficiency.None Declared


Other distinct clinical features include keratocystic odontogenic tumors, dyskeratotic palmar and plantar pitting, and skeletal abnormalities. Clinicopathological findings of the syndrome are very diverse, and many symptoms manifest during a certain period of life. We present the compelling whole-body bone scan and


Synthetic glucocorticoids (sGCs) are a well-investigated and standard drug therapy for disorders associated with CNS inflammation. Less is known about treating psychiatric disorders associated with neural autoantibodies. Our aim is to elucidate the repositioning of sGCs in psychiatric diseases that co-exist with neural autoantibodies. We used PubMed to identify articles for this narrative review. To our knowledge, no randomized, placebo-controlled trials have yet been conducted on applying sGC to treat neural autoantibody-associated psychiatric disorders. We describe initial results of cohort studies and single cases or case series often associated with autoantibodies against membrane-surface antigens demonstrating a largely beneficial response to sGCs either as monotherapy or polytherapy together with other immunosuppressive agents. However, sGCs may be less efficient in patients with psychiatric diseases associated with autoantibodies directed against intracellular antigens. These results reveal potential benefits of the novel usage of sGCs for the indication of neural autoantibody-associated psychiatric disease. Further large-scale randomized, placebo-controlled trials are needed to discover whether sGCs are safe, well tolerated, and beneficial in subgroups of neural autoantibody-associated psychiatric diseases. The term drug repurposing refers to employing old drugs for a new purpose, as for another disease category. Two additional subconditions of drug repurposing beyond its superordinate concept are distinguished, namely, drug repositioning and drug reformulation. Drug repositioning means employing an old formula for a new indication, whereas drug reformulation requires either the application of a novel dosage or a novel route, or even both. In our review, we focus on the drug repositioning of steroids in psychiatric disease limited to those patients presenting serum and/or CSF neural autoantibodies. In our review article, we refer only to synthetic glucocorticoids  as they are currently applied in treating diseases involving CNS inflammation. sGCs orchestrate various cellular functions, such as inflammation  application. We excluded patients with neurological disorders apart from dementia, internal medicine diseases, such as pancreatitis, autoimmune encephalitis with a mixed neuropsychiatric or no pure psychiatric symptoms, and psychiatric syndromes associated with non-neural antibodies, such as thyroid antibodies. The efficacy of sGCs has been proven in patients with autoimmune encephalitis associated with membrane-surface autoantibodies  antibodies]. Concerning autoimmune encephalitis following the Graus criteria . There is evidence that the origin of neural autoantibody-associated psychiatric disease is organic, as in autoimmune encephalitis  antibodies and partly responsive to polyimmunotherapy, including sGCs  who underwent this therapy for autoimmune dementia  of patients Table , whereasA large recent chart review study by Endres et al.  showed tDifferent sGC mechanisms with a major impact on neural autoantibody-associated psychiatric disease should be mentioned. First, sGCs can enhance emotional memory by increasing hippocampal activity during the encoding of emotional stimuli , our review data point to a new direction in psychiatry that has emerged in recent years and should be pursued further. However, the use of sGCs must be seriously reconsidered when potent alternative immunotherapeutic drugs such as IVIGs and plasmapheresis are available, in case side effects such as exacerbation of psychiatric symptoms should occur. In every case, a critical risk–benefit evaluation should be made especially in cases with isolated psychiatric syndromes and lacking neural autoantibody detection in CSF.


Waiting and stopping are essential and distinct elements of appropriate behavioral control with its dysfunction implicated in various impulsivity related mental disorders. Although rodent and human studies have investigated both phenomena, the role of preparing to stop in waiting impulsivity has rarely been investigated. Furthermore, convergent evidence from multi-modal investigation tools remains a poorly utilized approach in addressing such questions.Here, we conducted two separate, but hierarchical studies, using functional magnetic resonance imaging (fMRI) to map the neural circuit involved in waiting impulsivity and proactive stopping, and subsequently provide mechanistic and causal evidence of disruption of this circuit by transcranial magnetic stimulation (TMS). In the second study, based on our fMRI study data, we attempted to investigate possible causation between the LIFG and waiting impulsivity by modulating LIFG, i.e. non-invasively producing a “virtual lesion” with an inhibitory transcranial magnetic stimulation (TMS) protocol called continuous theta burst stimulationWe recruited 41 healthy volunteers who performed an adapted version (1CSRT) of the well-established 5 choice serial reaction time task to capture waiting impulsivity. We developed a novel task measuring proactive inhibition. We scanned participants while completing these two tasks. Our fMRI data showed a strong association between LIFG activity and waiting impulsivity on the 1CSRT task. We conducted a single-blind, randomized, between-subjects design of cTBS of the LIFG on a sample of 51 healthy volunteers who completed an adapted version of the 1CSRT task (2CSRT task). Our a priori hypothesis was that cTBS would transiently decrease local cortical activity of the LIFG and increase the frequency of premature responses on both fixed and delayed cue-target interval trials on the 2CSRT task.We first show a shared neural network comprising the pre-supplementary motor area and bilateral anterior insula underlying both waiting impulsivity and proactive stopping. We further demonstrate activity in dorsomedial prefrontal cortex and left inferior frontal gyrus (LIFG) negatively correlated with waiting impulsivity in trials with additional target onset delay. We demonstrate active stimulation significantly increased waiting impulsivity.In these two studies, we validated a novel task measuring proactive inhibition. We further validated the significance of task structure for assessing distinct aspects of impulsivity, which is of translational interest. We further established a causal role of lIFG for waiting impulsivity thus highlighting the integrity of LIFG and related neural circuitry required in waiting impulsivity.None Declared


In November 2022, the Centers for Disease Control and Prevention updated a 2016 practice guideline for opioid prescription.The 2022 Centers for Disease Control and Prevention guideline reiterates that clinicians should prescribe opioids at the lowest effective dose for the expected duration of pain warranting opioid use. The guideline also endorses patient-centered approaches to the initiation or taper of opioids. Clinicians should discuss benefits and risks of opioids and consider patient preference. The 2022 guideline further suggests that clinicians “evaluate benefits and risks with patients within 1-4 weeks of starting opioid therapy for subacute or chronic pain or of dosage escalation.” This recommendation is particularly relevant to the chronic management of patients who begin opioids for hidradenitis suppurativa, erosive lichen planus, or chronic ulcerating conditions, or even in the emergency department, where opioids are frequently prescribed for cellulitis and abscess.Postsurgical pain management comprises the majority of opioid prescriptions among dermatologists.An added 2022 recommendation outlines the use of prescription drug monitoring or high-sensitivity screening questions to mitigate opioid prescriptions to patients at higher risk for substance use. This recommendation is accompanied with the caveat that prescription drug monitoring data should be used with “all patients rather than differentially on the basis of assumptions about what [clinicians] will learn about specific patients.” The 2022 guideline also uses five new guiding principles, which emphasize an individualized, flexible, and multidisciplinary approach to opioid prescription. The fifth guiding principle encourages culturally informed communication to promote access to affordable, diversified pain management regimens and recognizes the role of bias in pain management. The 2022 guideline update is an important step toward thoughtful, safe, and patient-centered opioid stewardship. Dermatologists should continue to build on this national policy update and consider more specific opioid appropriateness recommendations for chronic, nonsurgical dermatologic conditions.None disclosed.


N-glycans stabilized the ligand-binding domain dimer via cation/anion binding and modulated receptor gating properties using electrophysiology. Our findings provide vital structural and functional insights into the unique KAR gating mechanisms.Kainate receptors (KARs) belong to the family of ionotropic glutamate receptors (iGluRs) and are tetrameric ligand-gated ion channels that regulate neurotransmitter release and excitatory synaptic transmission in the central nervous system. While KARs share overall architectures with other iGluR subfamilies, their dynamics are significantly different from those of other iGluRs. KARs are activated by both full and partial agonists. While there is less efficacy with partial agonists than with full agonists, the detailed mechanism has remained elusive. Here, we used cryo-electron microscopy to determine the structures of homomeric rat GluK2 KARs in the absence of ligands (apo) and in complex with a partial agonist. Intriguingly, the apo state KARs were captured in desensitized conformation. This structure confirms the KAR desensitization prior to activation. Structures of KARs complexed to the partial agonist domoate populate in domoate bound desensitized and non-active/non-desensitized states. These previously unseen intermediate structures highlight the molecular mechanism of partial agonism in KARs. Additionally, we show how


Magnetic resonance imaging (MRI) has several advantages over computerized tomography (CT) in the treatment planning of central nervous system (CNS) malignancies. The adoption of hybrid MRI and linear accelerators (MRLs) has allowed for more effective tumor control and reduced unnecessary neurotoxicity through precise daily adaptations. In this review, we provide a summary of the evidence for MRLs in the management of various CNS tumors. Additionally, we discuss the potential of multiparametric MRI and genomically guided radiotherapy to enhance patient outcomes.Magnetic resonance imaging (MRI) provides excellent visualization of central nervous system (CNS) tumors due to its superior soft tissue contrast. Magnetic resonance-guided radiotherapy (MRgRT) has historically been limited to use in the initial treatment planning stage due to cost and feasibility. MRI-guided linear accelerators (MRLs) allow clinicians to visualize tumors and organs at risk (OARs) directly before and during treatment, a process known as online MRgRT. This novel system permits adaptive treatment planning based on anatomical changes to ensure accurate dose delivery to the tumor while minimizing unnecessary toxicity to healthy tissue. These advancements are critical to treatment adaptation in the brain and spinal cord, where both preliminary MRI and daily CT guidance have typically had limited benefit. In this narrative review, we investigate the application of online MRgRT in the treatment of various CNS malignancies and any relevant ongoing clinical trials. Imaging of glioblastoma patients has shown significant changes in the gross tumor volume over a standard course of chemoradiotherapy. The use of adaptive online MRgRT in these patients demonstrated reduced target volumes with cavity shrinkage and a resulting reduction in radiation dose to uninvolved tissue. Dosimetric feasibility studies have shown MRL-guided stereotactic radiotherapy (SRT) for intracranial and spine tumors to have potential dosimetric advantages and reduced morbidity compared with conventional linear accelerators. Similarly, dosimetric feasibility studies have shown promise in hippocampal avoidance whole brain radiotherapy (HA-WBRT). Next, we explore the potential of MRL-based multiparametric MRI (mpMRI) and genomically informed radiotherapy to treat CNS disease with cutting-edge precision. Lastly, we explore the challenges of treating CNS malignancies and special limitations MRL systems face. Central nervous system (CNS) tumors pose unique and significant challenges for oncologists. As the understanding of CNS tumors continues to improve, innovative approaches and advancements in radiotherapy techniques are needed to take advantage of these insights to improve patient outcomes. The integration of magnetic resonance imaging (MRI) with linear accelerators (MRLs) has allowed for adaptive magnetic resonance-guided radiotherapy (MRgRT), which has emerged as a promising modality for increased personalization in radiation therapy for treating CNS tumors.MRI plays a central role in both the diagnosis and evaluation of CNS tumors due to its excellent soft tissue imaging and ability to visualize the boundaries between the tumor and normal tissues ,2. High-2 fluid-attenuated inversion recovery (FLAIR) sequence and a true fast imaging with steady-state free precession (TRUFI) sequence [The advent of MRLs marked a revolutionary step in the field of MRgRT for CNS tumors ,7. In adsequence  of a heaIn the subsequent sections, we discuss the unique challenges and limitations associated with treating adult patients with CNS tumors using traditional radiotherapy methods and how MRgRT offers a potential solution to address these issues. Specifically, we explore the role of MRgRT in the treatment of glioblastoma (GBM) and the unique ability of MRLs to detect subtle soft tissue changes and plan adaptation to improve tumor targeting and reduce dose to surrounding healthy tissue . FurtherIn accordance with the guidelines established by the Radiation Therapy Oncology Group (RTOG), the postoperative GBM target includes both the surgical cavity and the adjacent edema . This apAlthough conducting MRI scans throughout RT to account for these changes would be ideal, it is not feasible due to limited scanner availability and cost constraints. Unfortunately, CT-guided radiotherapy (CTgRT) does not adequately account for parenchymal changes because of its inadequate soft tissue contrast. MRLs may offer a solution, as they allow for superior soft tissue contrast to detect subtle geometric changes and for online plan adaptation to account for tumor and post-operative bed changes during therapy. The need for geometric plan adaptation is highlighted in a prospective study involving 61 GBM patients who underwent chemoradiotherapy (CRT) and received diagnostic brain MRIs at planning, fraction 10, fraction 20, and one-month post-CRT. Significant anatomical changes were observed throughout therapy . The stup = 0.036) versus 20.6 Gy (p = 0.005), respectively [A recent study investigated the potential benefits of adaptive radiotherapy for GBM patients using an MRL system . The stuectively . MultiplIn summary, treatment of GBMs with MRLs is associated with improvements in dosimetry and treatment planning due to its ability to detect subtle soft tissue changes and facilitate plan adaptation. Additionally, MRLs can account for changes in the tumor and tumor bed throughout treatment to ensure better target coverage while minimizing unnecessary dose to normal brain parenchyma. Future studies are needed to determine if this translates into better disease control durability and if better normal tissue sparing results in quality-of-life improvements for these patients.SRT is an important modality in the management of brain metastases and other intracranial tumors . An MRL Several studies have explored the dosimetric feasibility of MRgRT for intracranial SRT ,18,19,20Another study examined the dosimetric feasibility of direct post-operative MRL-based SRT for resection cavities of brain metastases, concluding that direct post-operative MRL-based SRT is dosimetrically acceptable, with benefits including increased patient comfort and logistics . StreamlCollectively, the above studies indicate that MRgRT using an MRL has the potential to offer dosimetric and logistical advantages over conventional linear accelerators for intracranial SRT treatment. However, further clinical investigations are necessary to evaluate the clinical benefit of this technology.Spine SRT plays a critical role in managing metastatic disease by alleviating pain, preventing pathological fractures, and reducing neurological morbidity. Stereotactic body radiotherapy (SBRT) has been shown to provide improved efficacy compared with conventional radiotherapy methods . For spiMRLs offer several advantages over CTgRT, including MR imaging in treatment position to allow for easier fusion with the planning CT and superior spinal cord delineation during setup compared with cone-beam CT (CBCT) ,23. DosiSeveral clinical trials are currently investigating the use of MRL in spine SRS/SBRT. These studies will provide valuable insights into the feasibility and effectiveness of this technique for spine treatment. For example, a phase I/II trial is examining the use of Stereotactic MR-guided Adaptive Radiotherapy (SMART) for treating various disease sites, including the spine (NCT04115254). Additionally, the Pilot Study of Same-session MR-only Simulation and Treatment with SMART for Oligometastases of the Spine (NCT03878485) focuses specifically on spine treatment.As more clinical data emerge from these studies, the potential benefits of MRL in spine SRT will become clearer. The integration of MRI with linear accelerators for spine treatment may lead to improved tumor targeting, reduced normal tissue exposure, and better patient outcomes. Ultimately, these advancements may help optimize radiotherapy for patients with metastatic spine disease and contribute to the ongoing evolution of spine SRT techniques.HA-WBRT is a promising technique that aims to achieve the local control benefits of whole brain RT for both macro- and micro-metastatic lesions, while reducing neurotoxicity by specifically avoiding the hippocampus . HA-WBRTParticularly for patients with numerous brain metastases of radioresistant histology, HA-WBRT with a simultaneous integrated boost to gross disease may be an effective strategy ,56, one One of the fundamental goals of radiotherapy is maximizing the dose to target tissue while minimizing the dose to surrounding OARs. In a significant first step towards this aim, MRLs have facilitated treatment plan adaptation to observable anatomic changes throughout therapy. MRLs, however, may be able to enable biological plan adaptation by leveraging MRI’s capability to track biological and physiological changes through advanced mpMRI techniques. These techniques may allow radiation oncologists further insight into a tumor’s biology as it responds to RT over the course of treatment.The treatment paradigm of radiotherapy has traditionally been based on empirical large cohort data rather than individual biology, resulting in a one-size-fits-all approach. However, recent advancements in genomics and radiomics have begun to pave the way towards a more personalized approach based upon individual tumor biology. The synergy between genomically informed radiotherapy, treatment of high-risk sub-volumes based on extraction of radiographic data, and daily mpMRI-guided plan adaptation has the potential to usher in a new treatment paradigm in radiation oncology. Pre-treatment genomic and radiomic analyses of the tumor may improve patient selection for MRL-based dose escalation ,57,58. DThe currently active phase II Habitat Escalated Adaptive Therapy (HEAT), With Neoadjuvant Radiation for Soft Tissue Sarcoma (NCT05301283) is an example of a cutting-edge study utilizing genomic and mpMRI radiomic biomarkers to guide the initial treatment and adaptive treatment approach for high-grade soft tissue sarcomas. Utilizing a similar approach for CNS tumors appears to be technically feasible currently. For example, genomic-adjusted radiation therapy (GARD) could be similarly utilized to identify GBM patients who could benefit from higher doses  with MRIMRL is poised to take a central role at the forefront of this paradigm shift to allow for plan adaptation based not only upon geometric shifts but also on a tumor’s evolving treatment response throughout therapy. An ultra-personalized treatment approach like this allows for total dose, dose distribution , and fractionation changes throughout the course of therapy to improve clinical outcomes for patients. Historically, daily MRgRT plan adaptation has been utilized to manage interfractional geometric changes. However, MRI is also capable of assessing biological and physiological information using advanced mpMRI techniques ,67,68,69One such technique is diffusion-weighted imaging (DWI), which enables the detection of water mobility changes . These a1 relaxation time following a bolus injection of gadolinium [1, T2, and ADC [Dynamic contrast-enhanced (DCE) MRI is another functional imaging technique that investigates perfusion by dynamically evaluating changes in the Tdolinium ,83. Thisdolinium . DCE hasdolinium . As a redolinium . DCE has and ADC . While D and ADC .Additional MR-based techniques, such as magnetic resonance spectroscopic imaging (MRSI) , chemicaAlthough none of the CNS-specific trials within Genomics provides another powerful avenue towards personalized radiation treatment, which when combined with the advances in image guidance listed above, may provide an even more sophisticated approach for challenging malignancies such as GBM. Several such signatures have been introduced as a potential means for genomically guided RT ,109,110.In summary, MRL can be leveraged by incorporating genomically guided RT and mpMRI radiomics to enable a biologically adaptive RT paradigm. Various mpMRI techniques, including DWI, DCE, MRSI, and CEST, have the potential to offer valuable insights into tumor biology and physiology, ultimately leading to more personalized and effective treatment strategies. Using these technologies to identify intratumoral heterogeneity and tumoral sub-volumes at risk may allow for focal dose escalation or avoidance, respectively. As research and development continues in this area, we expect significant advancements in the application of these techniques, potentially revolutionizing the management of CNS tumors.MRgRT offers significant advancements for image-guided radiation therapy (IGRT) and personalized oncology in CNS tumor treatment, but there are certain limitations to be considered. These include substantial financial and time investments for training and operation, development of MR-safety protocols, and unique physical challenges related to the concurrent use of MR and external beam radiotherapy ,116,117.Treating CNS tumors on an MRL presents several unique challenges. The complex anatomy of the CNS, with its highly radiosensitive normal tissues, requires precise targeting and dose delivery. The proximity of critical structures, such as the optic nerves, brainstem, and spinal cord, demands meticulous treatment planning and delivery. Furthermore, CNS tumors often exhibit infiltrative growth patterns, making it almost impossible to accurately delineate tumor boundaries.MRL systems suffer the same limitations as diagnostic MRIs. As such, they’re sensitive to the magnetic susceptibility artifacts that arise from air–tissue  and boneGeometric distortion represents one of the most difficult challenges to account for with any MRgRT. Geometric distortion occurs due to imperfections in the magnetic field, gradient nonlinearities, and magnetic susceptibility differences at tissue interfaces . This caTreatment of CNS tumors on MRLs represents a promising direction for the advancement of personalized cancer care. MRLs provide excellent soft tissue visualization, real-time monitoring of targets and normal tissues with gating capabilities, and the ability for daily plan adaptation. These unique advantages hold the potential to improve radiation delivery to patients with intracranial or spine tumors. Clinical trials are currently underway and seek to clarify the role of MRLs in the treatment of CNS malignancies. Future clinical studies are needed to explore the integration of mpMRIs and genomics to develop a biologically adapted radiation therapy paradigm for CNS tumors.


Fungal infections are increasingly associated with critical illness, especially in major burn injury. The risk factors of invasive fungal infections include central venous catheter (CVC) placement, mechanical ventilation, broad-spectrum antibiotics, renal replacement therapy (RRT), and total parental nutrition. Critically ill burn patients have additional risk factors including extensive wounds, impaired immune system, and repeated surgical intervention. Despite significant morbidity and mortality caused by invasive fungal infections, efforts to prevent them with antifungal prophylaxis have not improved outcomes. In patients who develop invasive fungal infection, appropriate empiric antifungal therapy is imperative to reduce morbidity and mortality especially in the setting of delayed culture and sensitivity data. The purpose of this study was to characterize risk factors associated with the development of invasive fungal infection, invasive fungal infection organisms and surgical and pharmacological management.A retrospective chart review was completed of adult patients admitted to the burn ICU found to have an invasive fungal infection . The primary outcome was to identify common fungal organisms. Secondary outcomes included susceptibility pattern of the organism, location of infection, surgical management including debridement and amputation, pharmacological management, median ICU and hospital length of stay, and in hospital mortality.A total of 10 patients of a goal of 100 patients with a median 54% TBSA burns were evaluated at this time. The most common yeast species included candida albicans; mold species included a variety of organisms such as fusarium, zygomycete and paecilomyces. Common risk factors among these patients included CVC access (57%), mechanical ventilation (43%), and RRT (43%). Yeast infections were primarily treated with anidulafungin and fluconazole, while mold infections were managed with systemic amphotericin as backbone in addition to voriconazole or isavuconazole. Patients underwent aggressive surgical debridement for source control. Median ICU stay was 53 days with a median hospital stay of 63 days, and 42% mortality.Fungal infections among critically ill burn patients are associated with the high morbidity and mortality rates. Therefore, mitigation of modifiable risk factors is of utmost importance. This retrospective review of common fungal growth in our unit will inform future empiric antifungal management for patients with concern of invasive fungal infections.Fungal infections present a clinical challenge for burn practitioners, especially in geographically moist areas. Prevention and informed surgical and pharmacological management are key to overcoming this infectious disease threat.


Obesity has become a global health epidemic with profound implications for various medical specialties, including reproductive medicine. This comprehensive review focuses on the anesthetic evaluation and management of obese patients undergoing in vitro fertilization (IVF) procedures. Obesity, as defined by BMI, is associated with infertility and poses unique challenges for anesthetic care. The review also addresses the timing of anesthesia concerning IVF procedures, the impact of obesity on IVF success rates, and the importance of emotional and psychological support for obese patients undergoing IVF. Challenges and future directions in the field are highlighted, focusing on ongoing research, emerging technologies, and the role of multidisciplinary teams in managing these complex cases. In conclusion, this review underscores the critical role of tailored anesthesia and perioperative care in optimizing outcomes for obese patients undergoing IVF. It provides valuable insights for anesthetic providers, reproductive specialists, and healthcare teams, emphasizing the need for a patient-centered approach to address the unique challenges posed by obesity in the context of assisted reproductive technology. Obesity has emerged as a global health epidemic, affecting millions of individuals worldwide and presenting a significant public health challenge. In 2005, approximately 1.6 billion adults globally were overweight BMI: 25-30 kg/m2), and at least 400 million were obese (BMI: >30 kg/m2). By 2015, these numbers had escalated to 2.3 billion and 700 million, respectively [0 kg/m2, Obesity and IVF: an overviewDefinition of Obesity and Its ClassificationObesity is a complex health condition marked by excessive adipose tissue accumulation in the body. BMI is the most commonly used metric for defining and categorizing obesity, as classified by the WHO in Table Prevalence of Obesity and Its Association With InfertilityThe global prevalence of obesity has witnessed a concerning and continuous rise in recent decades, emerging as a significant public health issue. Research indicates that this surge in obesity rates has far-reaching consequences, including its profound impact on reproductive health, both in men and women. The association between obesity and infertility is a growing concern within the medical community, as it sheds light on the intricate interplay between body weight and reproductive function .In womeImportance of IVF as a Fertility Treatment OptionOvercoming ovulatory disorders: Obesity is often intricately linked with ovulatory disorders, such as PCOS, which can hinder natural conception. IVF is particularly advantageous as it effectively bypasses these ovulatory challenges. Through IVF, eggs are directly harvested from the ovaries, ensuring a steady supply of eggs for fertilization, thereby circumventing the irregular ovulation associated with PCOS .ControlAnesthetic evaluation of obese women patientsPreoperative Assessment and Patient HistoryEvaluation of comorbidities: The preoperative assessment of comorbid conditions is paramount, particularly in obese patients undergoing surgical procedures. Obesity is often accompanied by a higher prevalence of medical comorbidities, necessitating a thorough evaluation to manage patient risks comprehensively. Conditions such as diabetes, hypertension, cardiovascular disease, and obstructive sleep apnea (OSA) are frequently encountered in the obese population and can significantly influence anesthesia management. Assessing these comorbidities' nature, severity, and control is critical in determining the patient's perioperative risk profile. This assessment is a foundation for tailoring anesthetic strategies and optimizing patient safety .MedicatPhysical Examination in Obese PatientsAssessment of airway anatomy: Obese patients often present unique challenges related to their airway anatomy. Limited neck mobility, short and thick necks, and excess tissue in the oropharyngeal and supraglottic areas may characterize their airways. These anatomical variations can complicate airway management significantly during anesthesia induction and intubation. Anesthesiologists must carefully consider these factors and employ suitable airway management strategies, such as specialized equipment or alternative airway approaches, to mitigate potential difficulties and ensure safe ventilation .EvaluatLaboratory Tests and InvestigationsComplete blood count (CBC): Rather than delving into the definition of a CBC, it is pertinent to elucidate the changes observed in CBC counts within the obese population. Such insights can prove invaluable for healthcare professionals, especially physicians, as they navigate the challenges presented by obesity. In this context, the CBC becomes an essential tool that scrutinizes various blood components, including RBCs, WBCs, and platelets. Each component within the CBC bears crucial information for anesthesia providers during the preoperative evaluation process. For instance, the RBC count and hemoglobin levels are pivotal in assessing the patient's oxygen-carrying capacity. Low values may indicate anemia, a condition that, if left unaddressed, can adversely impact tissue oxygenation during surgery. WBC counts offer insights into the patient's immune status. Deviations from the normal range may indicate underlying infections or inflammatory conditions, necessitating preemptive action before surgery. Platelet counts, vital for normal blood clotting, help in assessing bleeding risks and guiding decisions regarding blood transfusions or medications such as anticoagulants. By examining these hematological parameters and understanding their variations within the obese population, anesthesia providers can make informed decisions to mitigate bleeding risks, optimize oxygen delivery, and ensure a safer perioperative experience .CoagulaAnesthetic Risk StratificationFollowing the comprehensive preoperative assessment, anesthetic risk stratification should be performed. This involves categorizing patients into risk groups based on their comorbidities, physical status, and the nature of the surgical procedure. Standard classification systems include the American Society of Anesthesiologists (ASA) Physical Status Classification and the Charlson Comorbidity Index . AnestheAnesthetic management strategiesPreoperative OptimizationWeight loss and lifestyle modification: Preoperative weight loss and lifestyle modification are proactive and potentially transformative strategies for obese patients embarking on elective surgery, including IVF procedures. These initiatives are driven by the recognition that obesity can engender complex health concerns and perioperative challenges. Here, we delve deeper into the multifaceted aspects of preoperative weight loss and lifestyle modification, elucidating their manifold benefits .ImproveGlycemic ControlCrucial for surgical success: Elevated blood glucose levels in patients with diabetes can heighten the risk of surgical complications, including impaired wound healing, increased infection susceptibility, and cardiovascular events. Achieving and maintaining optimal glycemic control before surgery can mitigate these risks, promoting a smoother and safer perioperative experience .ImplicaAnesthetic choicesGeneral Anesthesia vs. Regional AnesthesiaTable Sedation OptionsPatient comorbidities: Comorbid conditions like cardiovascular disease or OSA should be carefully considered when choosing sedation options. Some medications used for sedation may have hemodynamic effects or exacerbate respiratory compromise, necessitating a tailored approach that minimizes these risks. Additionally, anesthetic providers must monitor vital signs and promptly address adverse reactions .Airway Equipment considerationsSpecially Designed Operating Room Tables and EquipmentBariatric operating tables: Bariatric operating tables are designed to support the weight and dimensions of obese patients effectively. They offer enhanced stability and durability, which is essential during surgical procedures. These tables are more comprehensive and feature robust mechanisms for adjusting patient positioning. This ensures that patients are adequately supported, minimizing the risk of complications related to positioning, such as pressure ulcers or nerve injuries .More coAirway management challengesAdvanced Airway Management SkillsAnesthesia providers should possess advanced airway management skills, allowing them to adapt to the anatomical nuances of obese patients. This includes expertise in various intubation techniques and strategies for optimizing ventilation. Providers should be prepared to handle scenarios where conventional intubation methods may prove challenging .Video LaryngoscopesVideo laryngoscopes are invaluable tools in managing obese patients with difficult airways. These devices incorporate a camera at the tip of the laryngoscope blade, offering a clear view of the airway and vocal cords. This visual aid enhances the accuracy of intubation attempts, even in cases where direct laryngoscopy may be challenging due to anatomical factors .Supraglottic Airway DevicesSupraglottic airway devices, such as the laryngeal mask airway (LMA), are crucial in securing the airway in obese patients. These devices are inserted above the vocal cords and are particularly useful in scenarios where endotracheal intubation is challenging. LMAs provide a secure airway for positive pressure ventilation and can be a bridge to definitive airway management if needed .Comprehensive TrainingAnesthesia providers should undergo comprehensive training in advanced airway management tools and techniques, especially when caring for obese patients. Regular simulation exercises and ongoing education help maintain proficiency and ensure readiness to address airway challenges effectively .Medication dosing in obese patientsInduction AgentsAdjusting for altered pharmacokinetics: Obesity is associated with significant drug distribution and metabolism changes. In particular, the increased adipose tissue content and expanded volume of distribution can lead to prolonged drug effects. As a result, dosing of induction agents like propofol and etomidate should be cautiously approached in obese patients .Consideration of ideal body weight or lean body mass: To prevent the risk of overdosing and subsequent prolonged sedation or respiratory depression, anesthesia providers often base dosing on ideal body weight or lean body mass rather than total body weight in obese patients. Ideal body weight is calculated based on a healthy BMI, which allows for a more accurate alignment of drug dosing with the patient's physiological characteristics .Maintenance AgentsCareful titration based on patient response: Maintenance agents, including inhalational anesthetics and intravenous infusions, require precise titration based on the patient's response. Continuous monitoring of the depth of anesthesia is essential throughout the procedure. Technologies like bispectral index (BIS) monitoring provide real-time feedback on the patient's level of consciousness, enabling anesthesia providers to adjust maintenance agent dosages as needed .Balancing anesthesia depth: The primary goal is to achieve a balanced anesthetic state that ensures patient comfort while minimizing the risks associated with excessive or inadequate anesthesia depth. Overly deep anesthesia can result in delayed emergence, whereas insufficient depth may lead to intraoperative awareness .Neuromuscular Blocking AgentsHigher dosing requirements: Due to the increased volume of distribution in obese patients, higher initial doses of neuromuscular blocking agents (NMBAs) like rocuronium or vecuronium may be necessary to achieve the desired level of muscle relaxation for surgical procedures. This adjustment is crucial to ensure the effectiveness of NMBA-induced paralysis .Monitoring neuromuscular blockade: Train-of-four (TOF) monitoring is paramount when administering NMBAs to obese patients. TOF monitoring assesses the depth of neuromuscular blockade, aiding anesthesia providers in precise dose titration. This approach ensures that the degree of paralysis aligns with the requirements of the surgical procedure, preventing both inadequate blockade and excessive paralysis. Continuous monitoring continues throughout the surgery to guide the administration of reversal agents when necessary, facilitating a smooth recovery .AnalgesicsWeight-adjusted dosing: Pain management is crucial for obese patients during and after surgery. The dosing of analgesics, whether opioids or non-opioid alternatives, should be adjusted to account for weight-related factors. This adjustment ensures that analgesic effects are adequate to control pain effectively while minimizing the risk of overdose .Multimodal analgesia: In obese patients, a multimodal analgesic approach is often favored to reduce reliance on opioids and mitigate their associated side effects, including respiratory depression and postoperative nausea and vomiting. This approach may encompass non-opioid analgesics, regional anesthesia techniques, and adjunct medications like non-steroidal anti-inflammatory drugs (NSAIDs). By combining multiple analgesic modalities, anesthesia providers can enhance pain control and improve the overall safety profile of pain management in obese patients .Ventilation strategiesRisk of Hypoventilation and Respiratory ComplicationsIncreased vulnerability: Obese patients have unique anatomical and physiological characteristics that make them more susceptible to hypoventilation, oxygen desaturation, and postoperative respiratory complications. These challenges stem from decreased lung compliance, reduced functional residual capacity, and a propensity for upper airway obstruction .Positive end-expiratory pressure (PEEP): PEEP is often employed to address these concerns. PEEP helps maintain lung volume by preventing alveolar collapse during expiration. This technique aids in improving oxygenation and mitigating atelectasis, which is a common issue in obese individuals during anesthesia and surgery .Monitoring oxygen saturation: Continuous monitoring of oxygen saturation (SpO2) is essential throughout the surgical procedure to promptly detect any declines in oxygen levels. Obese patients may experience rapid desaturation during periods of hypoventilation, making vigilant monitoring crucial for patient safety .Monitoring end-tidal CO2 (ETCO2): Continuous monitoring of end-tidal carbon dioxide (ETCO2) levels, known as capnography, is a fundamental component of anesthesia for obese patients. ETCO2 monitoring provides real-time feedback on ventilation and allows anesthesia providers to detect hypoventilation early. Rising ETCO2 levels can be an early sign of inadequate ventilation, enabling timely intervention to prevent hypercapnia and associated complications .Elevation of the Head of the BedImproved ventilation: During surgery, elevating the head of the bed in obese patients can help improve ventilation. This adjustment assists in reducing the risk of upper airway obstruction, which is more prevalent when patients are supine. Proper positioning is critical to optimize lung mechanics and maintain effective ventilation .Positioning and Pressure Sore PreventionProper patient positioning is crucial to ensure access to the surgical site and prevent pressure sores, especially in obese patients with limited mobility. Pressure-relieving pads and regular position changes should be employed to minimize the risk of skin complications during prolonged procedures. A thorough understanding of these anesthetic management strategies tailored to obese patients is essential for anesthesia providers and healthcare teams to ensure safe and effective care during IVF procedures .Intraoperative and postoperative considerationsHemodynamic MonitoringContinuous surveillance of hemodynamics is paramount in the care of obese patients undergoing IVF procedures. A higher prevalence of cardiovascular comorbidities, such as hypertension, coronary artery disease, and heart failure, often accompanies obesity. As a result, meticulous attention to hemodynamic parameters is essential to detect and manage potential perioperative cardiovascular issues .Blood Pressure MonitoringClose and continuous blood pressure monitoring, including systolic and diastolic measurements, is crucial. Automated non-invasive blood pressure cuffs should be appropriately sized to ensure accurate readings. This ongoing assessment enables anesthesia providers to detect and respond promptly to changes in blood pressure, whether due to surgical manipulation, anesthesia effects, or underlying cardiovascular conditions .Heart Rate MonitoringContinuous heart rate monitoring is vital to detect any arrhythmias or hemodynamic fluctuations promptly. Anesthesia providers must be prepared to address bradycardia or tachycardia as needed during the surgery, ensuring that the patient remains stable throughout the procedure .Cardiac Output AssessmentIn certain high-risk or complex cases, assessing cardiac output may be necessary. This can be achieved through various techniques, including thermodilution or less invasive methods like pulse contour analysis. Monitoring cardiac output provides valuable insights into the patient's circulatory status and helps guide fluid management and vasopressor/inotropic support when indicated .Temperature managementMaintaining normothermia is of paramount importance in the intraoperative care of obese female patients undergoing IVF. These patients present unique considerations due to their larger body surface area and altered thermoregulation. Such factors elevate their susceptibility to perioperative hypothermia, a condition that can have detrimental consequences, including coagulopathy, heightened vulnerability to surgical site infections, and increased cardiovascular stress .To safeguard the well-being of these patients, it is imperative to employ active warming measures specifically tailored to their needs. One widely utilized method involves the use of forced air warming blankets, which deliver warm air directly to the patient's body, helping to counteract the challenges posed by their altered thermoregulation. Furthermore, warmed intravenous fluids can be employed as an effective means to maintain the core body temperature within the desired range for this patient population. Continuous temperature monitoring throughout the IVF procedure is essential, enabling immediate intervention in case of any deviations from the optimal normothermic range .Fluid managementIn fluid management during surgical procedures, particularly for obese patients, two crucial considerations demand attention. Firstly, obese patients are at a heightened risk of overhydration, which can result in severe complications, including pulmonary edema and cardiovascular strain. Therefore, healthcare providers must exercise caution when administering fluids to this patient population. Implementing individualized fluid management strategies tailored to each patient's unique needs is essential. These strategies should be guided by hemodynamic monitoring, and in some cases, invasive measures might be required to ensure precise fluid balance and prevent overhydration .Secondly, preventing complications like pulmonary edema is paramount when caring for obese surgical patients. To achieve this, it is imperative to avoid excessive fluid administration. Instead, the focus should be on optimizing oxygenation levels. Continuous monitoring of oxygen saturation and end-tidal CO2 and a vigilant assessment for early signs of fluid overload, such as crackles during auscultation, must be integral to the surgical team's protocol. By adhering to these meticulous fluid management and monitoring practices, healthcare providers can minimize the risks associated with overhydration and pulmonary edema, ultimately ensuring safer surgical outcomes for obese patients .Postoperative considerationsPostoperative care for obese patients demands a comprehensive and tailored approach to ensure their safety and well-being during recovery. Firstly, transitioning from the operating room to the recovery room necessitates vigilant monitoring. Healthcare providers must closely observe vital signs, oxygen saturation levels, and consciousness levels and remain alert to any signs of postoperative complications, such as respiratory distress or cardiovascular instability. This heightened level of surveillance is crucial in the immediate postoperative phase to promptly address any issues that may arise .Effective pain management is another critical facet of postoperative care for obese patients. Recognizing that they may require higher doses of analgesics due to altered pharmacokinetics, healthcare teams should adopt multimodal analgesic approaches. These approaches should incorporate non-opioid options to minimize the potential for opioid-related side effects while optimizing pain control and ensuring patient comfort .Early mobilization is a cornerstone of postoperative care for obese individuals. Promptly getting patients up and moving helps mitigate the risk of complications associated with immobility, such as atelectasis (lung collapse) and DVT. Collaboration between physical therapists and nursing staff is vital in facilitating early ambulation and encouraging deep breathing exercises, which can significantly contribute to a smoother recovery .Obese patients are particularly susceptible to postoperative complications, notably atelectasis and DVT. Reduced lung compliance and hypercoagulability make them prone to these issues. Therefore, preventive measures should be integrated into the postoperative care plan. This may include using incentive spirometry to promote lung expansion, early ambulation to improve circulation and lung function, and pharmacological thromboprophylaxis to minimize the risk of DVT formation. By implementing these strategies and maintaining a vigilant postoperative care regimen, healthcare providers can help obese patients recover safely and minimize the potential for complications .Special considerations for IVFTiming of Anesthesia and IVF ProceduresThe timing of anesthesia in conjunction with IVF procedures is a critical and intricately coordinated aspect of patient care. Firstly, anesthesia providers must establish a close and seamless collaboration with the IVF team to ensure that anesthesia induction and surgery are perfectly synchronized with the patient's specific IVF protocol. This synchronization is vital to optimize the timing of crucial IVF procedures, including oocyte retrieval, insemination, and embryo transfer, thereby maximizing the chances of a successful outcome .Oocyte retrieval stands out as a pivotal moment within the IVF process. To ensure patient comfort and minimize discomfort during the transvaginal follicular aspiration, anesthesia should be administered before this procedure. The timing and administration of anesthesia at this stage are critical to ease the patient's experience and allow the IVF team to perform the retrieval smoothly and efficiently .Regarding embryo transfer, the anesthesia approach may differ from oocyte retrieval. In many cases, patients may not require general anesthesia for this procedure. Instead, conscious sedation or regional anesthesia techniques may be more appropriate and well-tolerated by patients. The choice of anesthesia should consider the patient's preferences, comfort, and any specific medical considerations. This personalized approach ensures that the patient remains as relaxed as possible during this crucial step of the IVF process, contributing to a positive overall experience .Implications of Obesity on IVF Success RatesReduced oocyte quality: One of the primary consequences of obesity in the context of IVF is the potential for reduced oocyte (egg) quality in obese women. This decline in oocyte quality can manifest as abnormalities, such as irregular chromosome structure and spindle formation. As a result, obese individuals may experience lower fertilization rates and reduced embryo implantation rates during IVF. These challenges can pose significant obstacles to achieving a successful pregnancy .Altered hormonal profiles: Obesity disrupts hormonal profiles in several ways. Notably, it often leads to increased insulin resistance, a condition in which cells become less responsive to the effects of insulin. Additionally, obesity can alter sex hormone levels, causing elevated estrogen and androgen levels while reducing levels of sex hormone-binding globulin (SHBG). These hormonal imbalances can negatively impact ovarian function, potentially leading to irregular menstrual cycles and suboptimal reproductive outcomes .Increased risk of miscarriage: Obese patients undergoing IVF are at an elevated risk of experiencing miscarriages. This heightened risk emphasizes the importance of preoperative health and weight management optimization. Furthermore, during pregnancy, obese individuals require close monitoring to promptly identify and manage any complications that may arise, given the increased risk associated with their condition .Diminished response to medications: Obesity can result in a diminished response to fertility medications used in IVF, particularly gonadotropins. Due to altered pharmacokinetics, obese patients may require higher doses of these medications to stimulate ovarian follicular development effectively. Tailoring medication dosages to individual patient needs is crucial in optimizing IVF outcomes .Increased risk of complications: Obesity is associated with a heightened risk of complications during IVF procedures. Notably, obese individuals may be at an increased risk of developing ovarian hyperstimulation syndrome (OHSS), characterized by enlarged ovaries and fluid accumulation in the abdomen and chest. Additionally, they may face an elevated risk of thromboembolic events, such as blood clots, during the IVF process. Careful management and monitoring are essential to mitigate these risks and ensure the safety and success of IVF procedures in obese patients .Emotional and Psychological Support for Obese Patients Undergoing IVFPatient counseling: Preoperative counseling tailored to IVF's emotional and psychological aspects is essential for obese patients. It's important to create a safe and non-judgmental space where patients can openly discuss their anxieties, body image concerns, and expectations related to fertility treatment. Addressing these issues early can help patients better cope with the emotional rollercoaster often accompanying IVF .Support groups: Obese patients undergoing IVF can benefit immensely from participating in support groups or counseling sessions for individuals facing similar challenges. These groups provide a supportive environment where patients can share their experiences, express their emotions, and receive advice and encouragement from peers who have undergone similar journeys. Connecting with others who understand their unique struggles can be comforting and empowering .Multidisciplinary approach: A holistic approach involving a team of healthcare professionals is crucial. This multidisciplinary team may include psychologists, social workers, dietitians, and reproductive specialists collaborating to provide comprehensive support. Psychologists and social workers can help patients address the emotional impact of infertility and obesity on their mental health, offering coping strategies and emotional resilience tools .Education: Providing patients with accurate and detailed information about the relationship between obesity, IVF, and fertility outcomes is key. Clear and open communication helps patients make informed decisions and manage their expectations realistically. Educating patients about the specific challenges they may face due to obesity and the potential impact on IVF success can help alleviate anxiety and uncertainty .Challenges and future directionsOngoing Research in the FieldObesity-related factors: Researchers are delving into specific obesity-related factors that can influence fertility and IVF outcomes. This includes studying adipokines (hormones produced by fat tissue), inflammatory markers, and genetic predispositions that may impact reproductive health. Understanding the molecular mechanisms underlying these factors can provide insights into potential interventions to improve fertility and IVF success rates in obese patients .Anesthetic techniques: Research in this area evaluates the safety and efficacy of various anesthetic techniques tailored to obese patients undergoing IVF. This may include investigating the benefits and risks of regional anesthesia options, optimizing sedation strategies, and developing drug dosing protocols that account for the altered pharmacokinetics and pharmacodynamics often seen in obese individuals. Finding the safest anesthesia approach can improve patient comfort and procedural outcomes .IVF protocols: Modified IVF protocols designed to address the unique challenges presented by obesity are a critical area of research. Scientists and clinicians are working on optimizing ovarian stimulation regimens to improve oocyte quality and quantity in obese women. Additionally, researchers aim to develop protocols that reduce the risk of complications like ovarian hyperstimulation syndrome (OHSS) in this patient population, ensuring safer and more successful IVF cycles .Long-term outcomes: Research efforts also extend to studying the long-term outcomes of obese patients and their offspring following IVF. This includes assessing the impact of maternal obesity on maternal and neonatal health and investigating potential epigenetic changes that may occur during IVF procedures. Understanding the lasting effects of IVF in obese patients is crucial for providing comprehensive healthcare and counseling to these individuals and their families .Emerging Technologies and TechniquesPrecision medicine: The application of precision medicine in IVF involves tailoring treatment protocols and anesthesia management to each patient's specific genetic and metabolic characteristics. By analyzing an individual's genetic and metabolic profile, healthcare providers can make more informed decisions regarding fertility medications, dosages, and anesthesia techniques. This personalized approach can optimize treatment outcomes and minimize risks for obese patients, who often exhibit unique physiological variations .RoboticThe Role of Multidisciplinary Teams in Managing Obese Patients Undergoing IVFCollaboration: Effective care for obese patients undergoing IVF requires close collaboration among healthcare specialists. This includes anesthesiologists, reproductive endocrinologists, bariatric specialists, nutritionists, psychologists, and other relevant professionals. These experts work together to develop integrated care plans that address both the medical and psychosocial aspects of obesity and fertility treatment. This collaborative effort ensures that all aspects of a patient's health and well-being are considered .TailoreIn conclusion, the anesthetic evaluation and management of obese patients undergoing IVF procedures is multifaceted and demands precision, empathy, and a multidisciplinary approach. This comprehensive review has underscored the significance of addressing obesity's impact on IVF success rates, the importance of tailored anesthesia and perioperative care, and the need for emotional support throughout the IVF journey. Obesity poses unique medical and psychological challenges, necessitating a holistic approach that bridges the realms of anesthesia, reproductive medicine, and patient well-being. As we move forward, ongoing research, emerging technologies, and collaborative efforts among healthcare providers promise to enhance further the care of obese individuals seeking fertility treatments. By refining our practices and understanding, we can empower these patients to achieve the dream of parenthood while ensuring their safety, comfort, and overall success.


During the COVID-19 pandemic, clinical trials of vaccines received unprecedented publicity; whether this interest might be transferred to vaccine trials generally is unknown. Enrolment in paediatric COVID19 vaccine trials was slower than uptake of adult vaccine trials, and lessons learned are, therefore, of importance for future recruitment and participant experience. Previous studies have investigated motivations for participation in adult vaccine trials , paediatPreviously, we have observed response rates of 2%-4% for similar trials. We therefore hypothesised that prior vaccine trial experience and exposure might modulate the threshold for trial participation, and descriptively studied motivations and barriers to paediatric vaccine trial participation in this context. Ethical approval and feedback from the Oxford Vaccine Centre Public and Patient Involvement (PPI) group was received. Motivations for trial participation were dichotomised by prior trial participation Table ; self-deThis survey has limitations, being an unvalidated survey instrument, the reliance on self-report, and the inability to ascertain motivations among those who declined to participate. Further research including representative sample of the general UK population and better controlling for social desirability bias may shed further light on the nature and magnitude of differences in motivation, providing a basis for targeting adjustments to enrolment—and improve generalisability especially post-pandemic. Parental motivations for enrolling children in clinical trials are understudied and merit detailed exploration to maximise successful recruitment in future trials.Additional file 1: Supplementary Table 1. Baseline characteristics of 81 respondents. P-values are for chi-squared tests.


Catatonia is a complex psychomotor syndrome that often goes unrecognized and, consequently, untreated. Prompt and correct identification of catatonia allows for highly effective treatment and prevention of possible complications. Benzodiazepines and electroconvulsive therapy (ECT) are the most widely studied treatment methods. However, no uniform treatment method has yet been brought forward and no previous attempts to treat catatonia on a patient suffering concomitant major depressive disorder (MDD) with NMDA receptor antagonists have been documented so far.To describe the unknown and novel management of catatonia and MDD with intranasal esketamine, a NMDA receptor antagonist.A 55-year-old woman with a diagnosis of long-standing recurrent major depressive disorder who was admitted to the psychiatric inpatient unit of UniversityHospital Marqués de Valdecilla  suffering a complex catatonic, mutative state framed on a severe MDD. Different ineffective therapeutic interventions were deployed during the course of her illness. After failing to improve under conventional pharmacological treatment and ECT, and given the complexity of peripheral venous access on this patient (which disabled the option for iv ketamine use), we decided to initiate compassionate treatment with intranasal esketamine.Intranasal esketamine was effective in the resolution of patient’s complex catatonic state. Clinical response from catatonia was observed after 6 intranasal esketamine administrations (2-week follow-up), reaching full catatonia and MDD remission after 12 sessions in absence of significant adverse eventsEsketamine showed promising effectiveness for the treatment of catatonia in the context of MDD, although further research on this topic is needed.None Declared


Cardiac fibrosis is a pathological response characterized by excessive deposition of fibrous connective tissue within the heart. It typically occurs following cardiac injuries or diseases. However, the lack of suitable models for disease modeling and high-throughput drug discovery has hindered the establishment of an effective treatments for cardiac fibrosis. The emergence and rapid progress of stem-cell and lineage reprogramming technology offer an unprecedented opportunity to develop an improved humanized and patient-specific model for studying cardiac fibrosis, providing a platform for screening potential drugs and synchronously elucidating the underlying molecular mechanisms. Furthermore, reprogramming cardiac fibroblasts into cardiomyocyte-like cells to reduce scar volume and induce myocardial tissue regeneration is a promising approach in treating cardiac fibrosis. In this review, we summarize the current advancements in stem cell technologies applied to study cardiac fibrosis and provide insights for future investigations into its mechanisms, drug discovery as well as therapy method. Cardiac fibrosis is a prevalent pathological alteration observed in the advanced stages of most cardiovascular diseases (CVDs). This debilitating condition is frequently associated with various cardiac disorders, resulting in impaired heart function and potentially life-threatening complications such as heart failure  plays a pivotal role in initiating cardiac fibrogenesis in response to mechanical stress  Leask , mitogenFollowing myocardial damage, a plethora of signaling molecules such as chemokines, cytokines and growth factors are released, triggering the activation of cardiac fibroblasts through diverse pathways. The RAAS is activated during the process of cardiac fibrosis and interacts with pathways that contribute to fibrosis , including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), have substantially expanded the availability of human cells for modeling cardiac fibrosis and discovering drugs due to their ability to unlimitedly self-renew and differentiate into types of cells within the body  (about 40%) derived from hESCs better mimics the pathological process of cardiac fibrosis . The transplantation of hPSC-CMs holds the potential to directly enhance cardiac function in individuals with reduced fibrosis and increased vascular density. Additionally, hPSC-CMs can enhance cardiac tissue regeneration and repair processes by secreting growth factors, cytokines, and other signaling molecules . This feature illustrates the potential to obtain abundant cardiomyocytes for transplantation   in the implantation of hPSC-CMs in a subacute myocardial infarction pig model , mesoderm posterior bHLH transcription factor 1 (MESP1), myocardin (MYOCD), and zinc finger protein, multitype 2 (ZEPM2) to convert human fibroblasts into human induced cardiomyocyte-like cells (hiCMs)  from mouse and human fibroblasts, which possess multipotency to differentiate into various types of cardiovascular cells using a transgene-free reprogramming approach involving six small molecules: CHIR99021, A83-01, GSK126, Forskolin (an adenylyl cyclase activator), CTPB (a P300 histone acetyltransferase activator), and AM580 (a RARα activator) (Wang et al. Despite the considerable potential of stem cell therapy in addressing cardiac fibrosis, there are still several obstacles need to be overcome. These challenges encompass the selection of appropriate stem cells sources, concerns regarding biosafety during cell transplantation, and the necessity to improve cell survival and retention rates, among other factors. The advantages and disadvantages of stem cell transplantation and cell reprogramming for cardiac fibrosis therapy are summarized in Table In summary, stem cell therapy for cardiac fibrosis is an advancing field with promising prospects for the future. Ongoing research and technological advancements are propelling these therapeutic approaches towards potential success. However, several challenges persist in current stem cell treatments. Further investigation is required to address issues such as the selection of appropriate stem cell sources, biosafety concerns, and the feasibility to monitor treatment efficacy. Moreover, ensuring the successful engraftment and survival of transplanted stem cells into the heart remains to be tackled. Many transplanted cells do not exhibit long-term viability or fail to differentiate into functional cardiac cells, thereby impeding the overall effectiveness of this therapy. To ensure the safety and efficient implementation of these stem cell-based approaches, rigorous clinical studies and repeated validation are indispensable. Efforts are underway to establish a high-throughput drug screening platform for the development of novel therapies. Striking a balance between complexity and user-friendliness is pivotal for this platform. Through comprehensive research and validation, we can surmount these challenges and unlock the full potential of stem cell therapy for cardiac fibrosis in the future.


Long-term success of peritoneal dialysis as a kidney replacement therapy requires a well-functioning peritoneal dialysis catheter. With ongoing reductions in infectious complications, there is an increased emphasis on the impact of catheter-related and mechanical complications. There is currently a marked variation in the utilization of various types of catheters , methods of catheter insertion , timing of catheter insertion, location of catheter placement  and peri-operative practices. Specialized approaches to catheter placement in clinical practice include use of extended catheters and embedded catheters. Marked variations in patient lifestyle preferences and comorbidities, specifically in high acuity patient populations  necessitate individualized approaches to catheter placement and care. Current consensus guidelines recommend local procedural expertise, consideration of patient characteristics and appropriate resources to support catheter placement and long-term functioning. This review focuses on an overview of approaches to catheter placement with emphasis on a patient-centered approach. It is reported that approximately 424,000 patients worldwide utilize peritoneal dialysis (PD) as a method of kidney replacement therapy . A well-Knowledge of best practices in catheter insertion can minimize the risk of catheter complications leading to early PD failure. Guideline committees under the sponsorship of the International Society for Peritoneal Dialysis (ISPD) recommend optimal PD catheter implantation be based on individualized patient factors, facility resources and operator expertise . Currentvia trocar and blind insertion via Seldinger technique  at the time of catheter placement , 22. EarAnother strategy for timely initiation of PD is the embedded catheter technique, with the external limb of catheter embedded in subcutaneous tissue until the need for dialysis initiation. This allows for early patient commitment to PD, more predictable operating room scheduling, and immediate utilization of the catheter after exteriorization. However, there is a risk of non-usage of catheters, in addition to catheter dysfunction rates secondary to fibrin accumulation –28.No specific catheter placement approach has been proven to produce superior outcomes. Comparison of percutaneous placement, open surgical dissection and basic surgical laparoscopy have shown equivalent patient outcomes , 29–31. The goals of PD catheter placement involve a balance between pelvic position of catheter tip to facilitate inflow and outflow of dialysate along with an easily visible and accessible exit site. Operator expertise and experience necessitates selection of appropriate available catheter type suited to patient specific conditions. Placement includes the consideration of body habitus, belt-line, skin creases, prior scars, stomas, gastrostomy tubes, recreational habits and occupation. An ideal exit site is either above or below the beltline, with a lateral and inferior directed exit site . In the via a 2- piece extended catheter system, with a long subcutaneous section, while maintaining optimal catheter tip position. Alternatively, single piece catheters with long intercuff segments are also utilized in certain centers  necessitate a specialized approach for successfully conducting PD as a dialysis modality. This includes not only optimal exit site and catheter tip position, but utilization of focused interventions to ensure ideal long term function. Patients with obesity require creation of an easily visible upper abdomen/presternal exit site requiring an extended catheter approach. The catheter should be allowed to heal completely for several weeks prior to PD initiation. Ideally, a laparoscopic approach is recommended, utilizing selective omentopexy along with resection of epiploic appendices of sigmoid colon if needed. The upper abdominal and chest exit sites are located in areas with relatively thin subcutaneous layer, minimizing tubing stresses from mobility of the subcutaneous fat layer with postural changes. Data suggests longer time to first exit site infections in patients with extended catheters . MoreovePatients with autosomal dominant polycystic kidney disease (ADPKD) present a unique set of concerns regarding limited peritoneal space, peritonitis risk and hernias. Several studies have reported the feasibility of PD in ADPKD patients –40. WithPatients with cirrhosis present their own unique challenges with regards to potential bacterial peritonitis, nutritional challenges, and concerns for leaks –49. SeveSafe and effective placement of PD access is critical to the ultimate outcomes of PD as a home dialysis modality. SK and MR were responsible for preparation, writing and editing of this manuscript. Both authors contributed to the article and approved the submitted version.