Severe Sequelae Research Articles

Tratamientos agudos de recanalización en el ictus arterial isquémico pediátrico posnatal. Código ictus pediátrico

In children, arterial ischemic stroke is a much less understood disease compared to in adults due to its lower frequency and different aetiology. However, it is also a serious disease, with a high incidence of severe and permanent sequelae that exceeds 50% of total cases.The acute management of postnatal arterial ischaemic stroke (MNAIS) has changed drastically in recent years, chiefly on account of recanalization treatments (thrombolysis and endovascular therapies). These treatments, which used to not be recommended in childhood, are increasingly implemented in everyday clinical practice. Although the evidence from studies carried out in children is not of high quality due to their retrospective design and the small number of reported cases, they support the hypothesis that these treatments are as safe and effective as they are in adults as long as appropriate eligibility criteria are applied and they are used within a certain time from the onset of symptoms (therapeutic window).This article reviews the MNAIS based on the current scientific evidence.Since the efficacy of these treatments is highly dependent on their early initiation, a paediatric stroke code needs to be in place as an extension of the stroke code applied to adults. It has started to be introduced in Spain since 2019, although there are still large areas of the country where it has yet to be applied.

Acute recanalization treatments in postnatal paediatric ischaemic arterial stroke. Paediatric stroke code

In children, arterial ischemic stroke is a much less understood disease compared to in adults due to its lower frequency and different aetiology. However, it is also a serious disease, with a high incidence of severe and permanent sequelae that exceeds 50% of total cases.The acute management of postnatal arterial ischaemic stroke (MNAIS) has changed drastically in recent years, chiefly on account of recanalization treatments (thrombolysis and endovascular therapies). These treatments, which used to not be recommended in childhood, are increasingly implemented in everyday clinical practice. Although the evidence from studies carried out in children is not of high quality due to their retrospective design and the small number of reported cases, they support the hypothesis that these treatments are as safe and effective as they are in adults as long as appropriate eligibility criteria are applied and they are used within a certain time from the onset of symptoms (therapeutic window).This article reviews the MNAIS based on the current scientific evidence.Since the efficacy of these treatments is highly dependent on their early initiation, a paediatric stroke code needs to be in place as an extension of the stroke code applied to adults. It has started to be introduced in Spain since 2019, although there are still large areas of the country where it has yet to be applied.

Prevention of Congenital Cytomegalovirus Infection: Review and Case Series of Valaciclovir versus Hyperimmune Globulin Therapy.

Cytomegalovirus (CMV) is the most common cause of congenital infections in developed countries because is capable of infecting the fetus after both primary and recurrent maternal infection, and because the virus may be spread for years through infected children. Moreover, CMV is the most serious congenital infection associated with severe neurological and sensorineural sequelae, which can occur at birth or develop later on. Hygienic measures can prevent CMV transmission, which mainly involve contact with children under 3 years of age and attending a nursery or daycare. In animal and human pregnancies, many observational and controlled studies have shown that CMV-specific hyperimmune globulin (HIG) is safe and can significantly decrease maternal-fetal transmission of CMV infection and, mostly, the occurrence of CMV disease. Recently, valaciclovir at the dosage of 8 g/day was also reported to be capable of decreasing the rates of congenital infection and disease. However, comparing the results of our two recent case series, the infants born to women treated with HIG showed significantly lower rates of CMV DNA positivity in urine (9.7% vs. 75.0%; p < 0.0001) and abnormalities after follow-up (0.0% vs. 41.7%; p < 0.0001). The implementation of CMV screening would enable primary prevention via hygiene counseling, improve the understanding and awareness of congenital CMV infection, and increase the knowledge of the potential efficacy of preventive or therapeutic HIG or antiviral administration.

The Association of the Levels of High-Density Lipoprotein and Apolipoprotein A1 with SARS-CoV-2 Infection and COVID-19 Severity: An Analysis of the N3C Database.

This study analyzed data from the National COVID Cohort Collaborative (N3C) database to investigate whether high-density lipoprotein (HDL) and its major protein component, apolipoprotein A1 (apoA1), are associated with severe COVID-19 sequelae, specifically acute kidney injury (AKI) and severe COVID-19 disease as defined by the infection resulting in hospitalization, extracorporeal membrane oxygenation (ECMO), invasive ventilation, or death. Our study included a total of 1,415,302 subjects with HDL values and 3589 subjects with apoA1 values. Higher levels of both HDL and apoA1 were associated with a lower incidence of infection as well as a lower incidence of severe disease. Higher HDL levels were also associated with a lower incidence of developing AKI. Most comorbidities were negatively correlated with SARS-CoV-2 infection, presumably due to the behavioral changes that occurred as a result of the precautions taken by individuals with underlying comorbidities. The presence of comorbidities, however, was associated with developing severe COVID-19 disease and AKI. African American and Hispanic populations experienced worse outcomes, including a higher incidence of infection and the development of severe disease, as well as AKI. Smoking and being male were associated with a lower incidence of infection, while they were risk factors for the development of severe disease and AKI. The results on cholesterol and diabetes drugs warrant further research, given that the database included multiple drugs in each category impeding for analysis of specific medications. Despite the current limitations in the N3C data, this study is the first to investigate the roles of HDL and apoA1 on the outcomes of COVID-19 using the US population data.

Cytokine Storm Syndrome Triggered by Extracorporeal Membrane Oxygenation in Pediatric Patients.

Cytokine storm syndrome (CSS) is a serious and potentially life-threatening condition caused by severe systemic inflammation, immune activation, and a positive feedback loop of cytokine release. Typically triggered by systemic infection, malignancy, monogenic or rheumatic disease, similar patterns of hyper-inflammation have been seen in patients undergoing cardiopulmonary bypass (CPB) and in patients treated with extracorporeal membrane oxygenation (ECMO). Typical treatments used for the prevention and treatment of CPB/ECMO-induced hyper-inflammation have not been shown to be substantially effective. Two patients suffering from ECMO-related CSS were identified by their severe hyper-inflammatory profile and life-threatening sequelae of vasodilatory shock and respiratory failure. Anakinra, an interleukin-1 receptor antagonist, was employed as specific cytokine-directed therapy for the treatment of CSS in these two patients to good effect, with significant improvement in hyper-inflammation and cardiorespiratory status. The use of cytokine-directed therapies in CPB/ECMO-related CSS has great potential to improve the treatment and outcomes of this serious condition.

Post-traumatic stress disorder and traumatic events in China: a nationally representative cross-sectional epidemiological study

Post-traumatic stress disorder (PTSD) is one of the most severe sequelae of trauma. But a nationally representative epidemiological data for PTSD and trauma events (TEs) was unavailable in China. This article firstly demonstrated detailed epidemiological information on PTSD, TEs, and related comorbidities in the national-wide community-based mental health survey in China. A total of 9,378 participants completed the PTSD-related interview of the CIDI 3.0. Lifetime prevalence and 12-month prevalence of PTSD in total respondents were 0.3% and 0.2%. while the conditional lifetime and 12-month prevalence of PTSD after trauma exposure were 1.8% and 1.1%. The prevalence of exposure to any type of TE was 17.2%. Among individuals with the exposed to TEs, younger, without regular work (being a homemaker or retried), and intimate relationship breakdown (separated/Widowed/Divorced), living rurally were associated with either the lifetime PTSD or the 12-month PTSD, while the count of a specific TE, the unexpected death of loved one, was related to both. Alcohol dependence was the most common comorbidity among male participants with PTSD but major depressive disorder (MDD) for female counterparts. Our study can provide a reliable reference for future identification and intervention for people with PTSD.

Distribution, Consequences, and Determinants of Time to Antibiotics in Children With Community-Onset Severe Bacterial Infection: A Secondary Analysis of a Prospective Population-Based Study.

To describe the distribution, consequences and potential determinants of time to antibiotics administration in children with community-onset severe bacterial infections (COSBIs). Secondary analysis of the available data from a prospective population-based study from 2009 to 2014. An administrative area in western France accounting for 13% of the national pediatric population. All children from 1 month to 16 years old admitted to a PICU or who died before admission and had a COSBI. None. The time to antibiotics was divided into patient interval (from first signs of COSBI to the first medical consultation) and medical interval (from the first consultation to appropriate antibiotics administration). The association between the medical interval and child outcome was studied by a multinomial logistic regression model and the potential determinants of the patient and medical intervals were by a Cox proportional-hazards model. Of the 227 children included (median age 2.1 yr), 22 died (9.7%), and 21 (9.3%) had severe sequelae at PICU discharge. Median patient and medical intervals were 7.0 hours (interquartile range [IQR], 2.0-16.5 hr) and 3.3 hours (IQR, 1.1-12.2 hr), respectively. The last quartile of medical interval was not associated with death (adjusted odds ratio [aOR], 3.7; 95% CI, 0.8-17.5) or survival with severe sequelae (aOR, 1.3; 95% CI, 0.4-4.0) versus survival without severe sequelae. Patient interval was shorter in younger children (adjusted hazard ratio [aHR], 0.95; 95% CI, 0.92-0.99), and medical interval was reduced when the first consultation was conducted in a hospital (aHR, 1.5; 95% CI, 1.1-2.0) versus outpatient medicine. For children with COSBI, we found no significant association between medical interval and mortality or severe sequelae. An initial hospital referral could help reduce the time to antibiotics in COSBIs.

The Future of Lymphedema: Potential Therapeutic Targets for Treatment.

This review aims to summarize the current knowledge regarding the pharmacological interventions studied in both experimental and clinical trials for secondary lymphedema. Lymphedema is a progressive disease that results in tissue swelling, pain, and functional disability. The most common cause of secondary lymphedema in developed countries is an iatrogenic injury to the lymphatic system during cancer treatment. Despite its high incidence and severe sequelae, lymphedema is usually treated with palliative options such as compression and physical therapy. However, recent studies on the pathophysiology of lymphedema have explored pharmacological treatments in preclinical and early phase clinical trials. Many potential treatment options for lymphedema have been explored throughout the past two decades including systemic agents and topical approaches to decrease the potential toxicity of systemic treatment. Treatment strategies including lymphangiogenic factors, anti-inflammatory agents, and anti-fibrotic therapies may be used independently or in conjunction with surgical approaches.

Serological screening for cytomegalovirus during pregnancy: A systematic review of clinical practice guidelines and consensus statements.

Congenital cytomegalovirus (cCMV) is the most common congenital infection worldwide. cCMV can lead to severe long-term sequelae, including neurological impairment and developmental delay. We performed a systematic review of clinical practice guidelines containing recommendations concerning serological screening for CMV during pregnancy. We performed a search of MEDLINE, Turning Research into Practice (TRIP) database and the grey literature for clinical practice guidelines or consensus statements published in the English language from Jan 2010 to June 2022. The quality of the included guidelines was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Textual synthesis was used to summarise and compare the recommendations on CMV serological screening in pregnancy. Eleven guidelines and two consensus statements were included. None recommended universal serological screening for CMV in pregnant women; five recommended screening for high-risk women (those with frequent contact with young children). The overall quality of the guidelines varied; most were medium or low. Although clinical practice guidelines do not actively recommend routine serological screening in pregnancy, most did not meet standard processes for development and predated the emerging data on valaciclovir as a potential intervention. Existing recommendations are underpinned by limited, low-level evidence, exposing the lack of robust data in this area of practice. Further high-level evidence and methodologically robust guidelines are needed to guide clinical practice in this rapidly changing field.

Prevention and management of post-thyroidectomy cervical haematoma. Recommendations of the AFCE (Association francophone de chirurgie endocrinienne) with the SFE (Société française d’endocrinologie) and the SFMN (Société française de médecine nucléaire)

Post-thyroidectomy cervical haematoma (PTCH) requiring reoperation occurs in fewer than 5% of patients but can be fatal or leave severe neurological sequelae if compressive. Risk factors besides anticoagulant treatments are discussed. Preoperative prevention complies with the recommendations of the French Society of Anaesthesia and Resuscitation (SFAR) for the management of antiaggregants and anticoagulants before and after the operation. Intraoperative prevention is centred on careful haemostasis, sometimes aided by coagulation tools and haemostatic agents, although there is no firm evidence of their effectiveness against the occurrence of PTCH. Systematic drainage of the thyroid cavity is no longer standard practice for the prevention of PTCH. Postoperatively, maintenance of normal blood pressure is essential to prevent PTCH, together with control of pain, coughing, nausea and vomiting. To reduce the risk of serious complications, medical and paramedical teams must be trained to recognise a haematoma and manage it so that it can be evacuated as a matter of extreme urgency, if necessary bedside, and then treated for its cause in the operating theatre.

Dissecting the prognostic role of baseline body mass index (BMI) in early breast cancer (BC): Individual patient-level analysis from five mammella interGruppo (MIG) and gruppo italiano mammella (GIM) randomized clinical trials (RCTs).

12067 Background: Nearly half of patients (pts) are overweight or obese at BC diagnosis (dx). Higher BMI at dx has been associated with cardiometabolic comorbidities, higher risk of severe treatment-related sequelae, and worse quality of life. Previous studies showed inferior survival outcomes among patients with early BC and high BMI, although not consistently. The aim of this study was to explore the prognostic role of BMI at dx using data from five RCTs of adjuvant therapy for early stage BC with long-term follow-up. Methods: Pts with known BMI at dx, randomized in the MIG-1, MIG-5, GIM-2, GIM-3 and GIM-6 phase III RCTs were included. BMI was categorized as lean ( &lt; 25 kg/m2), overweight (25-30 kg/m2) or obese (≥ 30 kg/m2). Outcomes included disease-free survival (DFS), breast cancer free-interval (BCFI) and overall survival (OS). Survival estimates were compared using the Kaplan-Meier method and log-rank test. Multivariable Cox proportional hazard models stratified by trial and relevant prognostic factors assessed associations between BMI and outcomes. Results: Among 7334 pts in the overall population, mean age was 56.4 years (SD 11.2), 67.8% had node-positive disease, 76.9% received chemotherapy and 83.0% endocrine therapy. Most pts were overweight (33.1%) or obese (21.0%) and 45.9% were lean. Higher BMI was associated with older age, larger tumor size, higher nodal status, and HR+/HER2- subtype. At a median follow-up of 10.0 years (IQR 6.1-15.1) there were 2165 DFS, 1674 BCFI and 1354 OS events. Pts with higher BMI had worse DFS and OS (log-rank p = 0.007 and p &lt; .0001, respectively), but similar BCFI (p = 0.48). BMI at dx was an independent risk factor for worse OS, but not for DFS and BCFI (Table). Results in the HR+/HER2- population (n = 4093) were consistent: pts with higher BMI had worse DFS, BCFI, and OS (log-rank p = 0.001, p &lt; .006, and p &lt; .0001, respectively) and BMI at dx was an independent risk factor only for worse OS (aHR [95%CI] 1.06 [0.84-1.32] and 1.31 [1.02-1.67] for overweight and obese vs lean pts, respectively). Conclusions: In this large study of pts with early BC treated in RCTs with long-term follow-up, higher BMI at dx was an independent risk factor for overall mortality but not for BC-specific outcomes. Weight loss interventions may mitigate the detrimental effect of excess body weight on outcomes of BC survivors, including by reducing the burden and risks of associated cardiometabolic comorbidities. [Table: see text]

Two-Year Outcomes of the Reverse Humeral Reconstruction Prosthesis.

Extensive proximal humeral bone loss in the setting of shoulder arthroplasty represents a difficult challenge for the treating surgeon. Achieving adequate fixation with standard humeral prostheses can be problematic. Allograft-prosthetic composites are a viable solution for this problem, however high rates of complications have been reported. Modular proximal humeral replacement systems are another potential solution, but there is a paucity of outcome data on these implants. This study reports the two-year minimum follow-up outcomes and complications of a single system reverse proximal humeral reconstruction prosthesis (RHRP) for patients with extensive proximal humeral bone loss. We retrospectively reviewed all patients with minimum two-year follow-up who underwent implantation of a RHRP for either 1) failed shoulder arthroplasty or 2) proximal humerus fracture with severe bone loss (Pharos 2 and 3) and/or sequelae thereof. Forty-four patients met inclusion criteria (average age 68.3 ± 13.1 years). The average follow-up was 36.2 ± 12.4 months. Demographic information, operative data, and complications were recorded. Pre- and postoperative range of motion (ROM), pain, and outcome scores were assessed and compared to the MCID and SCB for primary rTSA where available. Of the 44 RHRPs evaluated, 93% (n=39) had undergone prior surgery and 70% (n=30) were performed for failed arthroplasty. ROM improved significantly in abduction by 22° (P = .006) and forward elevation by 28° (P = .003). Average pain on a daily basis and pain at worst improved significantly, by 2.0 points (P < .001) and 2.7 points (P < .001), respectively. Mean SST score improved by 3.2 (P < .001), Constant score by 10.9 (P = .030), ASES score by 29.7 (P < .001), UCLA score by 10.6 (P < .001), and SPADI score by 37.4 (P < .001). A majority of patients achieved the MCID for all outcome measures assessed (56-81%). The SCB was exceeded by half of patients for forward elevation and the Constant score (50%), and exceeded by the majority of patients for the ASES score (58%) and UCLA score (58%). The complication rate was 28%; the most common complication was dislocation requiring closed reduction. Notably, there were no occurrences of humeral loosening requiring revision surgery. This data demonstrates that the RHRP resulted in significant improvements in ROM, pain, and PROMs, without the risk of early humeral component loosening. RHRP represents another potential solution for shoulder arthroplasty surgeons when addressing extensive proximal humerus bone loss.

Epidemiology of invasive meningococcal disease and its sequelae: a population-based study in Italian primary care, 2000-2019.

Invasive meningococcal disease (IMD) is a severe infectious disease. Although effective preventive and therapeutical strategies are available, the fatality rate remains high in the general population, with an occurrence of meningococcal-related severe sequelae involving 10-20% of survivors. Given the crucial role of general practitioners in recognizing and preventing IMD and its related sequelae, we aim to assess the burden of these conditions in primary care. Using an Italian primary care database, the incidence rate of IMD was calculated in the period 2000-2019 by capturing the first diagnosis registered during follow-up. As far as meningococcal-related sequelae are concerned, we identified and clinically evaluated each potential sequela during the first 3 months, from 3 to 12 months, and up to 36 months. Among 508 patients diagnosed with IMD, 403 (incidence rate: 0.24 per 10,000 person-years) comprised those diagnosed with IMD in patients aged 15 years or older. We ascertained 104 sequelae (20.4%); 76% of them occurred in those aged 25 or older; 42, 27, and 35 were assessed as short-, medium-, or long-term sequelae, respectively. Overall, 4.7% of IMD patients reported physical sequelae, while 12.2% and 5.7% of patients reported neurological and psychological sequelae, respectively. Our study showed that a substantial proportion of IMD and related sequelae occur in individuals aged over 25, with a non-negligible burden for healthcare systems. As for the paediatric population, effective communication on the relevance of meningococcal vaccination in adults should be proficiently fostered.

THU-402 - Systematic review: patients with pre-existing chronic liver disease are more vulnerable to the severe sequelae of drug induced liver injury

THU-402 - Systematic review: patients with pre-existing chronic liver disease are more vulnerable to the severe sequelae of drug induced liver injury

Acute Encephalopathy Caused by Inherited Metabolic Diseases.

Acute encephalopathy is a critical medical condition that typically affects previously healthy children and young adults and often results in death or severe neurological sequelae. Inherited metabolic diseases that can cause acute encephalopathy include urea cycle disorders, amino acid metabolism disorders, organic acid metabolism disorders, fatty acid metabolism disorders, mutations in the thiamine-transporter gene, and mitochondrial diseases. Although each inherited metabolic disease is rare, its overall incidence is reported as 1 in 800-2500 patients. This narrative review presents the common inherited metabolic diseases that cause acute encephalopathy. Since diagnosing inherited metabolic diseases requires specific testing, early metabolic/metanolic screening tests are required when an inherited metabolic disease is suspected. We also describe the symptoms and history associated with suspected inherited metabolic diseases, the various tests that should be conducted in case of suspicion, and treatment according to the disease group. Recent advancements made in the understanding of some of the inherited metabolic diseases that cause acute encephalopathy are also highlighted. Acute encephalopathy due to inherited metabolic diseases can have numerous different causes, and recognition of the possibility of an inherited metabolic disease as early as possible, obtaining appropriate specimens, and proceeding with testing and treatment in parallel are crucial in the management of these diseases.

Encefalopatía e infarto del globus pallidum bilateral, secundarios a intoxicación con disulfiram. Reporte de caso pediátrico

El disulfiram (Antabuse®) es un fármaco que se usa ampliamente en pacientes con consumo crónico de alcohol, como parte del tratamiento del alcoholismo, con el fin de producir síntomas desagradables al mezclarse con etanol, por incremento de acetaldehído. Aunque se han descrito casos de intoxicación aun sin ingesta de alcohol con dosis terapéuticas y más comúnmente por sobredosis en adultos, son pocos los casos que se han descrito en niños.&#x0D; Se presenta a continuación el caso de un niño con intoxicación aguda por disulfiram, quien presentó en la fase aguda somnolencia que evolucionó a estupor; concomitantemente presentó crisis convulsivas, vómito, deshidratación, rigidez, temblor distal y diaforesis; al egreso, con secuelas neurológicas severas, caracterizadas por distonía bilateral y signos piramidales como resultado de lesión bilateral de los ganglios basales documentada por imagenología.

Streptococcus cristatus bacteremia in a patient with poor oral hygiene: a case report

BackgroundStreptococcus cristatus is a member of the Mitis streptococcus group. Like other members of this group, it resides on mucosal surfaces of the oral cavity. However, little is known about its ability to cause disease as there are only a handful of cases in the literature. Two of these cases involved infective endocarditis with significant complications. However, these cases involved additional microbes, limiting the inferences about the pathogenicity of Streptococcus cristatus.Case presentationA 59-year-old African American male with end-stage cryptogenic cirrhosis and ascites presented with fatigue and confusion. A paracentesis was negative for spontaneous bacterial peritonitis, but two separate blood cultures grew Streptococcus cristatus. Our patient had a history of dental caries and poor oral hygiene, which were likely the source of the infection. Echocardiograms revealed new aortic regurgitation, indicating “possible endocarditis” per the Modified Duke Criteria. However, since his clinical picture and cardiac function were reassuring, we elected against treatment for infective endocarditis. He was treated for bacteremia with a 2-week course of cephalosporins consisting of 8 days of ceftriaxone, transitioning to cefpodoxime after discharge. Despite having end-stage liver disease, our patient did not experience any significant complications from the infection.ConclusionA patient with end-stage cirrhosis and poor oral hygiene developed bacteremia with an oral bacterium called Streptococcus cristatus. Unlike previous cases in literature, our patient did not meet criteria for a definitive diagnosis of infective endocarditis, and he experienced no other complications from the infection. This suggests coinfectants may have been primarily responsible for the severe cardiac sequelae in prior cases, whereas isolated Streptococcus cristatus infection may be relatively mild.

Chapter 13: TBE as a matter of public health

The incidence of TBE ranges from ‘only single sporadic cases’ to &gt;50/105 per year depending on the region and on the year of analysis; it is usually 1-10/105 in endemic regions in central Europe. This number may be considered as ‘low’ – not only as an individual risk but also from a public health perspective. If an individual does contract TBE, however, the disease may deeply change her/his life due to the need for acute hospital care and due to potentially severe and long-term sequelae. In 1–2% (-20%) of cases, TBE may even result in death. No specific treatments exist for TBE. The severity of the disease and high frequency of long-term sequelae result in high public awareness and concerns about tick bites in endemic areas. Public health officials in TBE-endemic areas need to address these concerns; moreover, they need to address the concerns of travelers at risk. The principal public health measures aim at reducing TBE cases by reduction of exposure and preventive vaccination. Recommendation/reimbursement of TBE vaccination still is under discussion from side of healthcare payer perspective as well as from the individuals perspective considering long term sequelae.

739 A Review of Current Methicillin-Resistant Staphylococcus Aureus Decolonization Practices in a Pediatric Burn Population

Abstract Introduction Methicillin-resistant staphylococcus aureus (MRSA) infections can result in severe sequela including death. Evidence-based practice guidelines exist for the universal decolonization of adult intensive care (ICU) patients. Evidence has not been established in the pediatric population, resulting in a knowledge gap regarding MRSA decolonization in children. Our practice is to test all patients upon admission for MRSA. Regardless of results, due to the immunocompromise of burn patients, all admissions are placed on a decolonization protocol that includes mupirocin ointment intranasally twice daily for five days. The repeated intranasal swabbing causes both discomfort and psychological distress for our pediatric patients. The purpose of this study was to evaluate current practice and the incidence of MRSA bacteremia in our pediatric population. Methods This was a retrospective review of all pediatric patients admitted to our center between January 2018 and August 2022. Patients who had mupirocin ordered for decolonization (YO) were compared to those who did not (NO). Basic descriptive statistics were calculated. Results A total of 508 individual patients had 519 admissions, YO 73% (n=379) NO 27% (n=140). There were no significant differences between groups for age, gender, race, ethnicity, admission diagnosis or mortality. Mupirocin was ordered at admission for 379 (73%) and administered per orders 74% of the time. YO patients were more likely to require ICU care 19% (n=73) vs 11% (n=16) (p=0.036) and mechanical ventilation 12% (n=46) vs 4% (n=6) (p=0.008). Length of stay (LOS) was longer for the YO group, 9.9 vs 5.11 days (p=0.008). The majority, 93% (n= 482) were admitted for burn injury, with a mean TBSA of YO 8.37 vs NO 5.86 (p=0.023). For YO, the mean number of doses to be administered, adjusted for LOS, was 6.71 vs actual doses given 3.8 (p &amp;lt; .0001). Overall incidence of MRSA positive blood cultures was 0.6% in the center but when controlled for setting it rose to 3% in ICU admissions. There were no positive blood cultures in non-ICU patients or the NO group. Three YOs had blood cultures positive for MRSA and had 80-90% of doses administered. Days to positive culture from admission were 6, 7 and 15. Conclusions Our review demonstrated that mupirocin was frequently discontinued before a full course was administered, yet the overall incidence of MRSA bacteremia was low, with all cases occurring in the pediatric ICU setting. These findings indicate that our current protocol does not perform well in this population and needs refinement. Universal decolonization in non-ICU pediatric patients is likely unnecessary. Applicability of Research to Practice An evidence-based protocol for children would improve antimicrobial stewardship in a vulnerable population and decrease psychological distress.

Biomechanical and transcriptional evidence that smooth muscle cell death drives an osteochondrogenic phenotype and severe proximal vascular disease in progeria.

Hutchinson-Gilford Progeria Syndrome results in rapid aging and severe cardiovascular sequelae that accelerate near end-of-life. We found a progressive disease process in proximal elastic arteries that was less evident in distal muscular arteries. Changes in aortic structure and function were then associated with changes in transcriptomics assessed via both bulk and single cell RNA sequencing, which suggested a novel sequence of progressive aortic disease: adverse extracellular matrix remodeling followed by mechanical stress-induced smooth muscle cell death, leading a subset of remnant smooth muscle cells to an osteochondrogenic phenotype that results in an accumulation of proteoglycans that thickens the aortic wall and increases pulse wave velocity, with late calcification exacerbating these effects. Increased central artery pulse wave velocity is known to drive left ventricular diastolic dysfunction, the primary diagnosis in progeria children. It appears that mechanical stresses above ~ 80kPa initiate this progressive aortic disease process, explaining why elastic lamellar structures that are organized early in development under low wall stresses appear to be nearly normal whereas other medial constituents worsen progressively in adulthood. Mitigating early mechanical stress-driven smooth muscle cell loss/phenotypic modulation promises to have important cardiovascular implications in progeria patients.