Factors Associated With Increased Risk of Pediatric Orbital Cellulitis-Who Should Be Scanned?

BACKGROUND: Evaluation of a child with POC/OC is complicated due difficulties in physical examination and risks of imaging by computed tomography. METHOD: Retrospective review of children 0-16 years admitted to the pediatric emergency department for POC/OC from 2009 to 2019. RESULTS: Ten years study period, 243 children younger than 16 years presented to the pediatric emergency department with a diagnosis of POC/OC. OC was documented in 51 (20.6%) patients. The mean age was 7.8 years (±4.3 years). Fever (80.4%), upper respiratory tract infection (43%), swelling of both eyelids (96%), proptosis (33.3%), and tenderness on percussion (24.5%) were more common in comparison to POC (P = 0.0001, 0.03, 0.0001, 0.0001, 0.0001 respectively). All children with suspected diagnosis of OC underwent computed tomography scan. POC accounted for 196 patients. Mean age was 4.6 (±4.3) years. Twenty percent of the cases were recorded as local trauma or insect bite in the infected eye.Mean leukocyte count in the OC group had higher mean of 15.2 (109/L) versus 13.4(109/L) (P = 0.05), absolute neutrophil count was significantly higher in the OC 11.3(109/L) versus 7.2(109/L) (P = 0.0001) whereas the lymphocyte count was higher in the POC 4.5(109/L) versus 2.4(109/L) (P = 0.0001), NLR of 0.318 correlates with orbital cellulitis with sensitivity of 75.5% and specificity of 77.4%.Patients with OC had mean C-reactive protein levels of 11.7 (mg/dL) versus 4.9(mg/dL) (P = 0.0001), erythrocyte sedimentation rate was elevated in the OC 53.6 (cm/h) versus 36.4 (cm/h) (P = 0.02).Based on the aforementioned study a risk calculator for OC was formulated with 6 major variables. CONCLUSIONS: Differentiation between POC/OC is cardinal. This study highlights the importance of ancillary laboratory tests especially C-reactive protein in the assessment of infections of the eye.

Tickborne Relapsing Fever, Jerusalem, Israel, 2004-2018.

To compare tickborne relapsing fever (TBRF) in children and adults in Jerusalem, Israel, we collected data from the medical records of all 92 patients with TBRF during 2004-2018. The 30 children with TBRF had more episodes of fever and lower inflammatory markers than adult patients.

Glucosylsphingosine (lyso-Gb1) as a Biomarker for Monitoring Treated and Untreated Children with Gaucher Disease.

The role of glucosylsphingosine (lyso-Gb1), a downstream metabolic product of glucosylceramide, for monitoring treated and untreated children with Gaucher disease (GD) has not yet been studied. We reviewed the clinical charts of 81 children (<18 years), 35 with mild type 1 GD (GD1), 34 with severe GD1 and 12 with type 3 GD (GD3), followed at Shaare Zedek Medical Center between 2014-2018. Disease severity for GD1 was based on genotypes. Forty children (87%) with severe GD1 and GD3 received enzyme replacement therapy (ERT) compared to two children (6%) with mild GD1. Lyso-Gb1 measurements were conducted on dried blood spot samples taken at each clinic visit. Lyso-Gb1 levels were significantly lower in children with mild compared to severe GD1 (p = 0.009). In untreated children, lyso-Gb1 levels were inversely correlated with platelet counts. During follow-up, lyso-Gb1 increased in almost 50% of untreated children, more commonly in younger children. In treated children, lyso-Gb1 levels were inversely correlated with hemoglobin levels. The increase of lyso-Gb1 while receiving ERT, seen in eight children, was partly associated with compliance and weight gain. Lyso-Gb1 seems to be a useful biomarker for monitoring children with GD and should be included in the routine follow-up. Progressive increase in lyso-Gb1 levels in untreated children suggests ERT initiation.

A Feasibility Open-Labeled Clinical Trial Using a Second-Generation Artificial-Intelligence-Based Therapeutic Regimen in Patients with Gaucher Disease Treated with Enzyme Replacement Therapy.

Background/Objectives: Gaucher Disease type 1 (GD1) is a recessively inherited lysosomal storage disorder caused by a deficiency in the enzyme ß-glucocerebrosidase. Enzyme replacement therapy (ERT) has become the standard of care for patients with GD. However, over 10% of patients experience an incomplete response or partial loss of response to ERT, necessitating the exploration of alternative approaches to enhance treatment outcomes. The present feasibility study aimed to determine the feasibility of using a second-generation artificial intelligence (AI) system that introduces variability into dosing regimens for ERT to improve the response to treatment and potentially overcome the partial loss of response to the enzyme. Methods: This was an open-label, prospective, single-center proof-of-concept study. Five patients with GD1 who received ERT were enrolled. The study used the Altus Care™ cellular-phone-based application, which incorporated an algorithm-based approach to offer random dosing regimens within a pre-defined range set by the physician. The app enabled personalized therapeutic regimens with variations in dosages and administration times. Results: The second-generation AI-based personalized regimen was associated with stable responses to ERT in patients with GD1. The SF-36 quality of life scores improved in one patient, and the sense of change in health improved in two; platelet levels increased in two patients, and hemoglobin remained stable. The system demonstrated a high engagement rate among patients and caregivers, showing compliance with the treatment regimen. Conclusions: This feasibility study highlights the potential of using variability-based regimens to enhance ERT effectiveness in GD and calls for further and longer trials to validate these findings.

The Constrained-Disorder Principle Assists in Overcoming Significant Challenges in Digital Health: Moving from "Nice to Have" to Mandatory Systems.

The success of artificial intelligence depends on whether it can penetrate the boundaries of evidence-based medicine, the lack of policies, and the resistance of medical professionals to its use. The failure of digital health to meet expectations requires rethinking some of the challenges faced. We discuss some of the most significant challenges faced by patients, physicians, payers, pharmaceutical companies, and health systems in the digital world. The goal of healthcare systems is to improve outcomes. Assisting in diagnosing, collecting data, and simplifying processes is a "nice to have" tool, but it is not essential. Many of these systems have yet to be shown to improve outcomes. Current outcome-based expectations and economic constraints make "nice to have," "assists," and "ease processes" insufficient. Complex biological systems are defined by their inherent disorder, bounded by dynamic boundaries, as described by the constrained disorder principle (CDP). It provides a platform for correcting systems' malfunctions by regulating their degree of variability. A CDP-based second-generation artificial intelligence system provides solutions to some challenges digital health faces. Therapeutic interventions are held to improve outcomes with these systems. In addition to improving clinically meaningful endpoints, CDP-based second-generation algorithms ensure patient and physician engagement and reduce the health system's costs.

Serious Bacterial Infections in Preterm Infants: Should Their Age Be "Corrected"?

Adjusting the chronological age of preterm infants according to their gestational age is a widely accepted practice in the field of neurodevelopment. It has been suggested for the assessment of preterm infants with suspected infection, but has been poorly validated. Correcting for chronological age is especially critical in infants with a chronological age above 3 months, but a corrected age below 3 months due to the differences in assessment protocols. This study assessed the difference in incidence of serious bacterial infection (SBI) according to chronological and corrected age in preterm infants. A retrospective analysis of pediatric emergency department (PED) presentations was conducted for all 448 preterm infants born in between January 2010 and August 2019. Of the 448 preterm infants, 204 (46%) presented at one of 3 PEDs in Jerusalem, Israel, during their first year of life. Overall, 141 (31.4%) presented with fever and were included in the study. The infants were divided into 3 age groups: 1-corrected age >3 months; 2-chronological age >3 months, but corrected age <3 months; 3-chronological and corrected age <3 months. SBI was diagnosed in 2.6%, 16.7%, and 33.3% of the infants in groups 1, 2 and 3, respectively; (p < 0.01, p = 0.17, p < 0.001). The incidence of SBI in the control group of 300 term infants <3 months presenting to the PED due to fever was 15.3%. Preterm infants with a corrected age <3 months are at increased risk for SBI, similarly to term infants <3 months of age. Age correction should thus be considered for preterm infants presenting with fever.

A second-generation artificial intelligence-based therapeutic regimen improves diuretic resistance in heart failure: Results of a feasibility open-labeled clinical trial.

INTRODUCTION: Diuretics are a mainstay therapy for congestive heart failure (CHF); however, over one-third of patients develop diuretic resistance. Second-generation artificial intelligence (AI) systems introduce variability into treatment regimens to overcome the compensatory mechanisms underlying the loss of effectiveness of diuretics. This open-labeled, proof-of-concept clinical trial sought to investigate the ability to improve diuretic resistance by implementing algorithm-controlled therapeutic regimens. METHODS: Ten CHF patients with diuretic resistance were enrolled in an open-labeled trial where the Altus Care™ app managed diuretics' dosage and administration times. The app provides a personalized therapeutic regimen creating variability in dosages and administration times within pre-defined ranges. Response to therapy was measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) score, 6-minute walk test (SMW), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and renal function. RESULTS: The second-generation, AI-based, personalized regimen alleviated diuretic resistance. All evaluable patients demonstrated clinical improvement within ten weeks of intervention. A dose reduction (based on a three-week average before and last three weeks of intervention) was achieved in 7/10 patients (70 %, p = 0.042). The KCCQ score improved in 9/10 (90 %, p = 0.002), the SMW improved in 9/9 (100 %, p = 0.006), NT-proBNP was decreased in 7/10 (70 %, p = 0.02), and serum creatinine was decreased in 6/10 (60 %, p = 0.05). The intervention was associated with reduced number of emergency room visits and the number of CHF-associated hospitalizations. SUMMARY: The results support that the randomization of diuretic regimens guided by a second-generation personalized AI algorithm improves the response to diuretic therapy. Prospective controlled studies are needed to confirm these findings.

Improving the effectiveness of anti-aging modalities by using the constrained disorder principle-based management algorithms.

Aging is a complex biological process with multifactorial nature underlined by genetic, environmental, and social factors. In the present paper, we review several mechanisms of aging and the pre-clinically and clinically studied anti-aging therapies. Variability characterizes biological processes from the genome to cellular organelles, biochemical processes, and whole organs' function. Aging is associated with alterations in the degrees of variability and complexity of systems. The constrained disorder principle defines living organisms based on their inherent disorder within arbitrary boundaries and defines aging as having a lower variability or moving outside the boundaries of variability. We focus on associations between variability and hallmarks of aging and discuss the roles of disorder and variability of systems in the pathogenesis of aging. The paper presents the concept of implementing the constrained disease principle-based second-generation artificial intelligence systems for improving anti-aging modalities. The platform uses constrained noise to enhance systems' efficiency and slow the aging process. Described is the potential use of second-generation artificial intelligence systems in patients with chronic disease and its implications for the aged population.

Massive Intestinal Bleeding in an Adult with IgA Vasculitis Treated with Intravenous Immunoglobulin.

We report the case of a 29-year-old adult presenting with severe IgA vasculitis, with cutaneous, urologic, and renal manifestations. The late appearance of severe gastrointestinal bleeding dominated the clinical picture, necessitating the administration of tens of units of packed cells and the augmentation of the immunosuppressive protocol. It was not until therapy with intravenous immunoglobulin (IVIG) was introduced that the massive bleeding was controlled. We herein discuss the patient's presentation, the gastrointestinal manifestations of IgA vasculitis, the recommended treatments, and the existent evidence about IVIG therapy.

Establishing a second-generation artificial intelligence-based system for improving diagnosis, treatment, and monitoring of patients with rare diseases.

Patients with rare diseases are a major challenge for healthcare systems. These patients face three major obstacles: late diagnosis and misdiagnosis, lack of proper response to therapies, and absence of valid monitoring tools. We reviewed the relevant literature on first-generation artificial intelligence (AI) algorithms which were designed to improve the management of chronic diseases. The shortage of big data resources and the inability to provide patients with clinical value limit the use of these AI platforms by patients and physicians. In the present study, we reviewed the relevant literature on the obstacles encountered in the management of patients with rare diseases. Examples of currently available AI platforms are presented. The use of second-generation AI-based systems that are patient-tailored is presented. The system provides a means for early diagnosis and a method for improving the response to therapies based on clinically meaningful outcome parameters. The system may offer a patient-tailored monitoring tool that is based on parameters that are relevant to patients and caregivers and provides a clinically meaningful tool for follow-up. The system can provide an inclusive solution for patients with rare diseases and ensures adherence based on clinical responses. It has the potential advantage of not being dependent on large datasets and is a dynamic system that adapts to ongoing changes in patients' disease and response to therapy.

The role of Staphylococcus lugdunensis as a pathogen in children: a multicentre retrospective study.

Introduction: Staphylococcus lugdunensis (SL), a tube coagulase negative Staphylococcus, is known to be pathogenic in adults, causing mainly skin infections.Gap Statement: Previous studies assessing SL's role in paediatric populations are sparse and are mainly limited to case reports.Aim: Present the clinical characteristics consistent with SL infections and its putative role as a pathogen in the paediatric population.Methodology: A retrospective multicentre study was conducted in four paediatric medical centres in Israel. Patients with isolates of SL presenting between 2009-2019 were included.Results: SL was isolated from 40 patients. Average (±SD) age at presentation was 5.9 (±6.2) years, with 22 (55 %) being female. Skin, soft tissue and musculoskeletal infections were the most common (n=20, 50%) followed by ear infections (n=13, 32.5%). Five cases of urine isolates and two isolates from blood culture samples were also reported. Skin abscess was the most common infection among skin and soft tissue isolates, reported in 17 children (85%) with SL being the only pathogen in 15 (75%). Otitis media was the most common ear infection accounting for 12 (92%) of all cases with SL as the only isolate reported in 6 (46%). Five cases of SL isolates from urine specimens were reported, all of which with poor growth of bacteria and normal urinalysis. Two cases of SL growth in blood culture were found in children presenting with signs and symptoms consistent with invasive blood stream infection.Conclusions: In the paediatric population, studied infections caused by SL are increasingly observed. The results of this study highlight its role as a pathogen in soft tissue infections and its putative role in otitis media and invasive blood stream infections. However, the role of SL as an uropathogen was not established.

Predicting Weight Loss and Comorbidity Improvement 7 Years Following Laparoscopic Sleeve Gastrectomy: Does Early Weight Loss Matter?

BACKGROUND: Predicting the variables that affect the outcomes following laparoscopic sleeve gastrectomy (LSG) would allow focused resource allocation with a view to improving results. Whilst greater early post-operative weight loss following LSG is associated with greater short-term weight loss, the relationship between early results and long-term outcomes has not been described. METHODS: A retrospective cohort analysis was performed on patients who underwent LSG 7 years before a follow-up telephone interview was performed. Multivariate regression analysis was used to explore the relationship between early weight loss at 4 weeks following surgery and weight loss at 7 years. A non-inferiority analysis assessed whether early weight loss was associated with either improvement or resolution of hypertension or type 2 diabetes mellitus (T2DM) at 7 years after surgery. RESULTS: Of the 156 patients identified between April and October 2012, 130 (83.3%) met the inclusion criteria and were included in the analysis. The average preoperative BMI was 42.5 kg/m2 (standard deviation 5.2). The change in BMI was 4.6 kg/m2 (4.0) at 4 weeks and 12.2 kg/m2 (5.4) at 7 years. There was improvement or resolution in 19/31 (61.3%) patients with T2DM and 14/26 (53.8%) patients with hypertension. Whilst younger age was associated with greater weight loss at 7 years follow-up, no such relationship was identified with early post-operative weight loss. Early post-operative weight loss was also not associated with long-term improvement or resolution in hypertension or T2DM. CONCLUSIONS: Early weight loss does not appear to be associated with greater weight loss nor comorbidity improvement 7 years following LSG. TRIAL REGISTRATION: ClinicalTrials.gov (SZMC-95/19).

ß-Cell DNA Damage Response Promotes Islet Inflammation in Type 1 Diabetes.

Type 1 diabetes (T1D) is an autoimmune disease where pancreatic ß-cells are destroyed by islet-infiltrating T cells. Although a role for ß-cell defects has been suspected, ß-cell abnormalities are difficult to demonstrate. We show a ß-cell DNA damage response (DDR), presented by activation of the 53BP1 protein and accumulation of p53, in biopsy and autopsy material from patients with recently diagnosed T1D as well as a rat model of human T1D. The ß-cell DDR is more frequent in islets infiltrated by CD45+ immune cells, suggesting a link to islet inflammation. The ß-cell toxin streptozotocin (STZ) elicits DDR in islets, both in vivo and ex vivo, and causes elevation of the proinflammatory molecules IL-1ß and Cxcl10. ß-Cell-specific inactivation of the master DNA repair gene ataxia telangiectasia mutated (ATM) in STZ-treated mice decreases the expression of proinflammatory cytokines in islets and attenuates the development of hyperglycemia. Together, these data suggest that ß-cell DDR is an early event in T1D, possibly contributing to autoimmunity.