Improving clinical practice through patient registries in allergy and immunology.

Patient registries are a mechanism for collecting data on allergic and immunologic diseases that provide important information on epidemiology and outcomes that can ultimately improve patient care. Key criteria for establishing effective registries include the use of a clearly defined purpose, identifying the target population and ensuring consistent data collection. Registries in allergic diseases include those for diseases such as inborn errors of immunity, food allergy, asthma and anaphylaxis, pharmacological interventions in vulnerable populations, and adverse effects of pharmacologic interventions including hypersensitivity reactions to drugs and vaccines. Important insights gained from patient registries in our field include contributions in phenotype and outcomes in inborn errors of immunity, the risk for adverse reactions in food-allergic patients in multiple settings, the benefits and risk of biologic medications for asthma during pregnancy, vaccine safety, and the categorization and genetic determination of risk for severe cutaneous adverse reactions to medications. Impediments to the development of clinically meaningful patient registries include the lack of funding resources for registry establishment and the quality, quantity, and consistency of available data. Despite these drawbacks, high-quality and successful registries are invaluable in informing clinical practice and improving outcomes in patients with allergic and immunological diseases.

Mitochondrially-associated actin waves maintain organelle homeostasis and equitable inheritance.

First identified in dividing cells as revolving clusters of actin filaments, these are now understood as mitochondrially-associated actin waves that are active throughout the cell cycle. These waves are formed from the polymerization of actin onto a subset of mitochondria. Within minutes, this F-actin depolymerizes while newly formed actin filaments assemble onto neighboring mitochondria. In interphase, actin waves locally fragment the mitochondrial network, enhancing mitochondrial content mixing to maintain organelle homeostasis. In dividing cells actin waves spatially mix mitochondria in the mother cell to ensure equitable partitioning of these organelles between daughter cells. Progress has been made in understanding the consequences of actin cycling as well as the underlying molecular mechanisms, but many questions remain, and here we review these elements. Also, we draw parallels between mitochondrially-associated actin cycling and cortical actin waves. These dynamic systems highlight the remarkable plasticity of the actin cytoskeleton.

An interphase actin wave promotes mitochondrial content mixing and organelle homeostasis.

Across the cell cycle, mitochondrial dynamics are regulated by a cycling wave of actin polymerization/depolymerization. In metaphase, this wave induces actin comet tails on mitochondria that propel these organelles to drive spatial mixing, resulting in their equitable inheritance by daughter cells. In contrast, during interphase the cycling actin wave promotes localized mitochondrial fission. Here, we identify the F-actin nucleator/elongator FMNL1 as a positive regulator of the wave. FMNL1-depleted cells exhibit decreased mitochondrial polarization, decreased mitochondrial oxygen consumption, and increased production of reactive oxygen species. Accompanying these changes is a loss of hetero-fusion of wave-fragmented mitochondria. Thus, we propose that the interphase actin wave maintains mitochondrial homeostasis by promoting mitochondrial content mixing. Finally, we investigate the mechanistic basis for the observation that the wave drives mitochondrial motility in metaphase but mitochondrial fission in interphase. Our data indicate that when the force of actin polymerization is resisted by mitochondrial tethering to microtubules, as in interphase, fission results.

Radiologic Manifestations of Mycobacterium chimaera Infection After Open Heart Surgery.

PURPOSE: The objective of this study is to identify and detail the radiologic manifestations of surgical site and disseminated Mycobacterium chimaera (MC) infection. The aim is to facilitate early identification and diagnosis of MC, considering its indolent nature and the challenges involved in clinically and pathologically establishing the diagnosis. PATIENTS AND METHODS: This was a retrospective cohort study reviewing computed tomography (CT), positron emission tomography (PET)/CT, and magnetic resonance imaging examinations in patients over the age of 18 years with a history of open heart surgery and a clinical or pathologic diagnosis of MC. Two radiology residents, a fellowship-trained nuclear medicine radiologist, and a fellowship-trained cardiothoracic radiologist performed consensus reads to determine the imaging findings seen in MC infection. RESULTS: Twenty-five patients were included. Localized, surgical site infection was more common than disseminated disease. Typical CT findings included peristernal soft tissue thickening, sinus tracts often extending to the cutaneous surface, slowly enlarging fluid collections, and sternal osteolysis. PET/CT findings demonstrated hypermetabolic activity in nearly all patients localized to sites of infection. Imaging findings for disseminated infection included hepatosplenomegaly, lymphadenopathy, involvement of the central nervous system, discitis/osteomyelitis, and distant abscesses. CONCLUSIONS: Imaging plays a vital role in suggesting possible surgical sites and disseminated MC infection acquired from open heart surgery. Radiologists must keep a high index of suspicion given the indolent nature and subtle imaging change over time. PET/CT is most useful in diagnosis and helps in differentiating between a sterile postoperative fluid collection or scarring and active MC infection and helps provide a target for debridement.

Point of Care Ultrasound Identification and Aspiration of a Neck Lymph Node.

The tissue diagnosis and staging of all types of lung cancer is foundational for prognosis and establishing the optimal treatment plan. In order to appropriately stage lung cancer, the highest stage should be established using the 8th edition TNM criteria, where tumor size (T), nodal involvement (N), and metastasis (M) are all taken into account. Establishing a tissue diagnosis may involve the use of CT guided biopsy, navigational bronchoscopy, endobronchial biopsy, EBUS, percutaneous lymph node biopsy and/or excisional biopsy of supraclavicular nodes. It is recommended to proceed with the method that is considered least invasive and provides the highest staging. We present a case of recurrent lung adenocarcinoma diagnosed with real time ultrasound-guided fine needle aspiration of a neck lymph node.

Invasive fungal disease in children with solid tumors: An Australian multicenter 10-year review.

Invasive fungal disease (IFD) occurs less frequently during treatment for solid compared to hematological malignancies in children, and risk groups are poorly defined. Retrospective national multicenter cohort data (2004-2013) were analyzed to document prevalence, clinical characteristics, and microbiology of IFD. Amongst 2067 children treated for solid malignancy, IFD prevalence was 1.9% overall and 1.4% for proven/probable IFD. Of all IFD episodes, 42.5% occurred in patients with neuroblastoma (prevalence 7.0%). Candida species comprised 54.8% of implicated pathogens in proven/probable IFD. In children with solid tumors, IFD is rare, and predominantly caused by yeasts.Routine prophylaxis may not be warranted.

Nurse-led approach to standardising the management of iron-deficiency anaemia, achieving the 2-week cancer pathway targets and reducing hospital admissions: practicalities and learnings from a success story.

The most significant and common cause of anaemia is iron deficiency, which occurs when iron absorption cannot meet the body's demands due to growth, pregnancy, poor nutrition, malabsorption or blood loss. It is estimated that in the UK 11% of the adult population have iron-deficiency anaemia (IDA) and investigation is essential to exclude significant pathology as the underlying cause. It has been shown that IDA is responsible for 57 000 hospital admissions in the UK, and at least 10% of gastroenterology referrals per annum. IDA is a major red flag symptom for gastrointestinal cancer. At the Royal Liverpool University Hospital, a dedicated nurse-led IDA service was developed in 2005 to help alleviate the clinical pressures created by the two week suspected cancer referral pathway. With the success of this service, investigation and management of IDA has been extended to referrals from accident and emergency, with the aim of reducing hospital admissions and to investigating and optimising iron replacement therapy in preoperative patients. Delivering this as a nurse consultant-led service was proposed by the gastroenterology medical team who felt that, as a clinical problem with well established, published investigative algorithms, IDA would be suitable for management in a dedicated nurse-led clinic. This article will focus on the strategies employed to achieve sufficient resources and clinic capacity to run this service effectively, develop strong nurse education and training, and the development of agreed investigation pathways. A robust results review process, with rapid management of abnormal results, was established with timely discharge for those patients with normal results. Optimisation of iron replacement therapy and verification of sustained haematological response was prioritised as this was identified as being poorly managed across all specialties. A process for ongoing audit of results was included to show the success of the service and highlight areas for redesign. Here, we demonstrate the effectiveness of our nurse-led IDA service and suggest it as the basis for other IDA services in the UK and beyond.

Exploring NK cell receptor dynamics in paediatric leukaemias: implications for immunotherapy and prognosis.

Objectives: Immunotherapies targeting natural killer (NK) cell receptors have shown promise against leukaemia. Unfortunately, cancer immunosuppressive mechanisms that alter NK cell phenotype prevent such approaches from being successful. The study utilises advanced cytometry to examine how cancer immunosuppressive pathways affect NK cell phenotypic changes in clinical samples. Methods: In this study, we conducted a high-dimensional examination of the cell surface expression of 16 NK cell receptors in paediatric patients with acute myeloid leukaemia and acute lymphoblastic leukaemia, as well as in samples of non-age matched adult peripheral blood (APB) and umbilical cord blood (UCB). An unsupervised analysis was carried out in order to identify NK cell populations present in paediatric leukaemias. Results: We observed that leukaemia NK cells clustered together with UCB NK cells and expressed relatively higher levels of the NKG2A receptor compared to APB NK cells. In addition, CD56dimCD16+CD57- NK cells lacking NKG2A expression were mainly absent in paediatric leukaemia patients. However, CD56br NK cell populations expressing high levels of NKG2A were highly represented in paediatric leukaemia patients. NKG2A expression on leukaemia NK cells was found to be positively correlated with the expression of its ligand, suggesting that the NKG2A-HLA-E interaction may play a role in modifying NK cell responses to leukaemia cells. Conclusion: We provide an in-depth analysis of NK cell populations in paediatric leukaemia patients. These results support the development of immunotherapies targeting immunosuppressive receptors, such as NKG2A, to enhance innate immunity against paediatric leukaemia.

Towards human-centered AI and robotics to reduce hospital falls: finding opportunities to enhance patient-nurse interactions during toileting.

Introduction: Patients who are hospitalized may be at a higher risk for falling, which can result in additional injuries, longer hospitalizations, and extra cost for healthcare organizations. A frequent context for these falls is when a hospitalized patient needs to use the bathroom. While it is possible that "high-tech" tools like robots and AI applications can help, adopting a human-centered approach and engaging users and other affected stakeholders in the design process can help to maximize benefits and avoid unintended consequences. Methods: Here, we detail our findings from a human-centered design research effort to investigate how the process of toileting a patient can be ameliorated through the application of advanced tools like robots and AI. We engaged healthcare professionals in interviews, focus groups, and a co-creation session in order to recognize common barriers in the toileting process and find opportunities for improvement. Results: In our conversations with participants, who were primarily nurses, we learned that toileting is more than a nuisance for technology to remove through automation. Nurses seem keenly aware and responsive to the physical and emotional pains experienced by patients during the toileting process, and did not see technology as a feasible or welcomed substitute. Instead, nurses wanted tools which supported them in providing this care to their patients. Participants envisioned tools which helped them anticipate and understand patient toileting assistance needs so they could plan to assist at convenient times during their existing workflows. Participants also expressed favorability towards mechanical assistive features which were incorporated into existing equipment to ensure ubiquitous availability when needed without adding additional mass to an already cramped and awkward environment. Discussion: We discovered that the act of toileting served more than one function, and can be viewed as a valuable touchpoint in which nurses can assess, support, and encourage their patients to engage in their own recovery process as they perform a necessary and normal function of life. While we found opportunities for technology to make the process safer and less burdensome for patients and clinical staff alike, we believe that designers should preserve and enhance the therapeutic elements of the nurse-patient interaction rather than eliminate it through automation.

Dual plating in the metastatic distal humerus: Benefits may outweigh the risks.

Background: Impending and complete pathologic fractures of the distal humerus are rare complications of metastatic cancer. Surgical treatment aims to quickly restore function and minimize pain. Plate and screw fixation (PSF) is a common method for addressing these lesions, but unlike in orthopaedic trauma, there are no clear guidelines for best management. While dual PSF theoretically provides better support and reduces the chance of reoperation due to tumor progression, single PSF is currently the more common choice. Materials and methods: Between March 2008 and September 2021, 35 consecutive patients who underwent PSF for distal humerus metastasis or multiple myeloma were retrospectively reviewed. The proportion of patients who developed various postoperative complications, including infection, nonunion, deep vein thrombosis, tumor progression, and radial nerve palsy, as well as those requiring reoperation, was calculated. Mann-Whitney U test, Pearson's chi-squared, and Fisher's exact test were used to investigate differences between the single and dual PSF groups with statistical significance defined as p ≤ 0.05. Results: There was no significant difference (p = 0.259) in revision rate, although 3 of 21 (14.3 %) single PSF patients required reoperation compared to 0 of 14 (0.0 %) dual PSF patients. The revisions were performed in one patient due to refracture and in two patients due to tumor progression. Although not statistically significant, a larger percentage of single PSF patients developed a postoperative complication compared to dual PSF patients [odds ratio 0.42 (95 % confidence interval 0.071 to 2.5); p = 0.431]. Single PSF did lead to shorter operative time compared to dual PSF [p < 0.001]. Conclusion: Dual PSF is non-inferior to single PSF and potentially results in fewer reoperations and postoperative complications in distal humerus pathologic lesions, although it leads to longer operative time. The current study is limited by small sample size due to the rarity of distal humerus metastatic lesions.

Is ChatGPT a trusted source of information for total hip and knee arthroplasty patients?

Aims: While internet search engines have been the primary information source for patients' questions, artificial intelligence large language models like ChatGPT are trending towards becoming the new primary source. The purpose of this study was to determine if ChatGPT can answer patient questions about total hip (THA) and knee arthroplasty (TKA) with consistent accuracy, comprehensiveness, and easy readability. Methods: We posed the 20 most Google-searched questions about THA and TKA, plus ten additional postoperative questions, to ChatGPT. Each question was asked twice to evaluate for consistency in quality. Following each response, we responded with, "Please explain so it is easier to understand," to evaluate ChatGPT's ability to reduce response reading grade level, measured as Flesch-Kincaid Grade Level (FKGL). Five resident physicians rated the 120 responses on 1 to 5 accuracy and comprehensiveness scales. Additionally, they answered a "yes" or "no" question regarding acceptability. Mean scores were calculated for each question, and responses were deemed acceptable if ≥ four raters answered "yes." Results: The mean accuracy and comprehensiveness scores were 4.26 (95% confidence interval (CI) 4.19 to 4.33) and 3.79 (95% CI 3.69 to 3.89), respectively. Out of all the responses, 59.2% (71/120; 95% CI 50.0% to 67.7%) were acceptable. ChatGPT was consistent when asked the same question twice, giving no significant difference in accuracy (t = 0.821; p = 0.415), comprehensiveness (t = 1.387; p = 0.171), acceptability (χ2 = 1.832; p = 0.176), and FKGL (t = 0.264; p = 0.793). There was a significantly lower FKGL (t = 2.204; p = 0.029) for easier responses (11.14; 95% CI 10.57 to 11.71) than original responses (12.15; 95% CI 11.45 to 12.85). Conclusion: ChatGPT answered THA and TKA patient questions with accuracy comparable to previous reports of websites, with adequate comprehensiveness, but with limited acceptability as the sole information source. ChatGPT has potential for answering patient questions about THA and TKA, but needs improvement.

PARC: a phase I/II study evaluating the safety and activity of pegylated recombinant human arginase BCT-100 in relapsed/refractory cancers of children and young adults.

Background: The survival for many children with relapsed/refractory cancers remains poor despite advances in therapies. Arginine metabolism plays a key role in the pathophysiology of a number of pediatric cancers. We report the first in child study of a recombinant human arginase, BCT-100, in children with relapsed/refractory hematological, solid or CNS cancers. Procedure: PARC was a single arm, Phase I/II, international, open label study. BCT-100 was given intravenously over one hour at weekly intervals. The Phase I section utilized a modified 3 + 3 design where escalation/de-escalation was based on both the safety profile and the complete depletion of arginine (defined as adequate arginine depletion; AAD <8µM arginine in the blood after 4 doses of BCT-100). The Phase II section was designed to further evaluate the clinical activity of BCT-100 at the pediatric RP2D determined in the Phase I section, by recruitment of patients with pediatric cancers into 4 individual groups. A primary evaluation of response was conducted at eight weeks with patients continuing to receive treatment until disease progression or unacceptable toxicity. Results: 49 children were recruited globally. The Phase I cohort of the trial established the Recommended Phase II Dose of 1600U/kg iv weekly in children, matching that of adults. BCT-100 was very well tolerated. No responses defined as a CR, CRi or PR were seen in any cohort within the defined 8 week primary evaluation period. However a number of these relapsed/refractory patients experienced prolonged radiological SD. Conclusion: Arginine depletion is a clinically safe and achievable strategy in children with cancer. The RP2D of BCT-100 in children with relapsed/refractory cancers is established at 1600U/kg intravenously weekly and can lead to sustained disease stability in this hard to treat population. Clinical trial registration: EudraCT, 2017-002762-44; ISRCTN, 21727048; and ClinicalTrials.gov, NCT03455140.

Outcomes of Thumb Metacarpophalangeal Joint Arthrodesis Using the XMCP Intramedullary Interlocking Device.

Purpose: The intramedullary interlocking device for metacarpophalangeal (MCP) joint arthrodesis (XMCP, Extremity Medical, Parsippany, NJ) has been shown to promote union at a precise angle, provide strong fixation without the need for prolonged immobilization, and lower the incidence of hardware irritation and revision surgery. In this study, we evaluated the clinical outcomes of patients undergoing MCP joint arthrodesis with the XMCP system using a retrospective chart review, patient reported outcomes, and radiographic analysis. Methods: A retrospective chart review and phone survey was conducted on 57 patients (58 cases) from a single institution between 2017 and 2022. The primary outcome was patient satisfaction, including pre- and postoperative Numeric Rating Scale (NRS) pain scores, Disabilities of Arm Shoulder and Hand (QuickDASH) outcomes, perceived grip strength, and willingness to undergo the procedure again. Secondary outcomes included the need for revision procedures, successful fusion of arthrodesis, and postoperative complications. Results: Of the 57 patients who underwent MCP joint arthrodesis of the thumb using the XMCP fusion device, a total of 43 (75%) completed the phone survey. The average age of patients was 67 years with an average clinical follow-up of 9 months (range 1-65 months). Patients who participated in the phone survey questionnaire had an average QuickDASH score of 24.7 ± 20.5. Average perceived NRS scores were 6.2 ± 3.5 and 1.2 ± 2.1 before and after surgery, respectively. Average perceived grip strength of patients was 3 ± 1.3 out of 5. When evaluating for concurrent procedures, there was no statistically significant difference in pre- or postoperative NRS scores. In total, 38 (88%) patients were satisfied with the procedure, and 39 (91%) patients would undergo the procedure again. Conclusion: Metacarpophalangeal joint arthrodesis of the thumb with the intramedullary fusion device is reproducible, allows for immediate use without immobilization, has a low number of complications, and provides improved function and pain relief. Level of Evidence: Therapeutic III.

Narrative bias ("spin") is common in randomised trials and systematic reviews of cannabinoids for pain.

ABSTRACT: We define narrative bias as a tendency to interpret information as part of a larger story or pattern, regardless of whether the facts support the full narrative. Narrative bias in title and abstract means that results reported in the title and abstract of an article are done so in a way that could distort their interpretation and mislead readers who had not read the whole article. Narrative bias is often referred to as "spin." It is prevalent in abstracts of scientific papers and is impactful because abstracts are often the only part of an article read. We found no extant narrative bias instrument suitable for exploring both efficacy and safety statements in randomized trials and systematic reviews of pain. We constructed a 6-point instrument with clear instructions and tested it on randomised trials and systematic reviews of cannabinoids and cannabis-based medicines for pain, with updated searches to April 2021. The instrument detected moderate or severe narrative bias in the title and abstract of 24% (8 of 34) of randomised controlled trials and 17% (11 of 64) of systematic reviews; narrative bias for efficacy and safety occurred equally. There was no significant or meaningful association between narrative bias and study characteristics in correlation or cluster analyses. Bias was always in favour of the experimental cannabinoid or cannabis-based medicine. Put simply, reading title and abstract only could give an incorrect impression of efficacy or safety in about 1 in 5 papers reporting on these products.

Motion of VAPB molecules reveals ER-mitochondria contact site subdomains.

To coordinate cellular physiology, eukaryotic cells rely on the rapid exchange of molecules at specialized organelle-organelle contact sites1,2. Endoplasmic reticulum-mitochondrial contact sites (ERMCSs) are particularly vital communication hubs, playing key roles in the exchange of signalling molecules, lipids and metabolites3,4. ERMCSs are maintained by interactions between complementary tethering molecules on the surface of each organelle5,6. However, due to the extreme sensitivity of these membrane interfaces to experimental perturbation7,8, a clear understanding of their nanoscale organization and regulation is still lacking. Here we combine three-dimensional electron microscopy with high-speed molecular tracking of a model organelle tether, Vesicle-associated membrane protein (VAMP)-associated protein B (VAPB), to map the structure and diffusion landscape of ERMCSs. We uncovered dynamic subdomains within VAPB contact sites that correlate with ER membrane curvature and undergo rapid remodelling. We show that VAPB molecules enter and leave ERMCSs within seconds, despite the contact site itself remaining stable over much longer time scales. This metastability allows ERMCSs to remodel with changes in the physiological environment to accommodate metabolic needs of the cell. An amyotrophic lateral sclerosis-associated mutation in VAPB perturbs these subdomains, likely impairing their remodelling capacity and resulting in impaired interorganelle communication. These results establish high-speed single-molecule imaging as a new tool for mapping the structure of contact site interfaces and reveal that the diffusion landscape of VAPB at contact sites is a crucial component of ERMCS homeostasis.

Sense of time is slower following exhaustive cycling exercise.

Subjective perception of time is altered during vigorous exercise. This could be due in part to the fatigue associated with physical activity at high intensities. The aim of this study was to determine the effect of fatigue, specifically, on subjective time perception. Twenty-six healthy, untrained subjects (17 men/9 women; age = 26.0 ± 4.3 years; V ˙ O 2 peak = 38.13 ± 5.62 mL/kg/min) completed a maximal aerobic exercise test on a cycle ergometer. Time perception was assessed before (PRE) and after (POST) the exercise test using a time production task wherein subjects started a stopwatch and stopped it once they believed a designated time period had passed. This time produced with the stopwatch was the estimate of the target time that was compared to the target time interval. Relative error of the timing task was significantly higher for POST (0.112 ± 0.260) than for PRE (0.028 ± 0.173), p = .032, η2 = .178. Subjects produced ~ 8.4% more time than the target intervals when fatigued, which is indicative of a slower sense of time perception. A shift in attentional focus from timing to the sensations associated with fatigue is a possible factor to explain this result. Future studies which investigate the effects of exercise on time perception should consider the impact of fatigue experienced during exercise.

Incidence and survival for childhood cancer by endorsed non-stage prognostic indicators in Australia.

BACKGROUND: An international expert panel recently recommended 15 'non-stage prognostic indicators' (NSPIs) across eight childhood cancers, classified as essential or additional, for collection in population-based cancer registries. We aimed to describe the incidence distribution and survival of each of these NSPIs. PROCEDURES: Cases were extracted from the Australian Childhood Cancer Registry. The study cohort (n = 4187) comprised all children aged under 15 years diagnosed with an eligible cancer between 2010 and 2018, with follow-up until 31 December 2020. NSPI data were collected directly from each patient's medical records. Differences in 5-year relative survival were assessed using multivariable flexible parametric models, adjusted for sex and age group at diagnosis. RESULTS: The availability of data varied, exceeding 85% for all essential NSPIs apart from histologic subtype for Wilms tumours (69%) and lineage for acute lymphoblastic leukaemia (78%). Information on additional NSPIs tended to be recorded less often, particularly cytogenetic subtype for non-alveolar rhabdomyosarcoma (28%) and astrocytoma (4%). Eight NSPIs exhibited a significant difference in survival, with the largest disparity occurring among children with astrocytoma according to tumour grade (5-year relative survival of 18% for grade IV disease compared with 99% for grade I disease; p < .001). CONCLUSIONS: Our findings demonstrate that most of the recommended NSPIs can be retrieved from medical records in Australia in recent years, allowing the capability of assessing survival within patient subgroups of clinical interest. Reporting of NSPI data has the capability to inform local and global understanding of population-level disparities in childhood cancer survival.

Characterization of Human Engraftment and Hemophagocytic Lymphohistiocytosis in NSG-SGM3 Neonate Mice Engrafted with Purified CD34+ Hematopoietic Stem Cells.

Immunodeficient mice bearing human immune systems, or "humanized" chimeric mice, are widely used in basic research, along with the preclinical stages of drug development. Nonobese diabetic-severe combined immunodeficiency (NOD-SCID) IL2Rγnull (NSG) mice expressing human stem cell factor, granulocyte-macrophage colony stimulating factor, and interleukin-3 (NSG-SGM3) support robust development of human myeloid cells and T cells but have reduced longevity due to the development of fatal hemophagocytic lymphohistiocytosis (HLH). Here, we describe an optimized protocol for development of human immune chimerism in NSG-SGM3 mice. We demonstrate that efficient human CD45+ reconstitution can be achieved and HLH delayed by engraftment of neonatal NSG-SGM3 with low numbers of human umbilical cord-derived CD34+ hematopoietic stem cells in the absence of preconditioning irradiation.