Advanced Interatrial Block across the Spectrum of Renal Function.

Background and Objective: Interatrial block (IAB) is defined as a conduction delay between the right and left atria. No data are available about the prevalence of both partial IAB and advanced IAB among the different stages of chronic kidney disease. The aim of this study was to describe the prevalence and type of advanced IAB across the spectrum of renal function, including patients on dialysis and the clinical characteristics associated with advanced IAB. Materials and Methods: Retrospective, single-center study of 151 patients consecutively admitted to the Nephrology and Ophthalmology Unit for 3 months. The study population was divided into three groups according to stages of chronic kidney disease. We evaluated the prevalence and pattern of IAB among the groups and the clinical characteristics associated with advanced IAB. Results: The prevalence of partial IAB was significantly lower in end-stage kidney disease (ESKD) group compared to control group (36.7% vs. 59.6%; p = 0.02); in contrast the prevalence of advanced IAB was significantly higher in both chronic kidney disease (CKD) (17.8% vs. 5.3%, p = 0.04) and ESKD group (24.5% vs. 5.3%, p = 0.005) compared to control group. The atypical pattern of advanced IAB was more frequent in both the ESKD and CKD group than in the control group (100% and 75% vs. 33.3%; p = 0.02). Overall, among patients that showed advanced IAB, 17 (73.9%) showed an atypical pattern by morphology and 2 (8.7%) showed an atypical pattern by duration of advanced IAB. The ESKD group was younger than the control group (65.7 ± 12.3 years vs. 71.3 ± 9.9 years; p = 0.01) and showed a higher prevalence of beta blockers (42.9% vs. 19.3%; p = 0.009), as in the CKD group (37.8% vs. 19.3%; p= 0.04). Conclusions: The progressive worsening of renal function was associated with an increasing prevalence of advanced IAB. Advanced IAB may be a sign of uremic cardiomyopathy and may suggest further evaluation with long-term follow-up to investigate its prognostic significance in chronic kidney disease.

Impact of Continuous Kidney Replacement Therapy and Hemoadsorption with CytoSorb on Antimicrobial Drug Removal in Critically Ill Children with Septic Shock: A Single-Center Prospective Study on a Pediatric Cohort.

Background: Extracorporeal therapies (ET) are increasingly used in pediatric settings as adjuvant therapeutic strategies for overwhelming inflammatory conditions. Although these treatments seem to be effective for removing inflammatory mediators, their influence on antimicrobials pharmacokinetic should not be neglected. Methods: A prospective observational study of children admitted to the pediatric intensive care unit (PICU) with a diagnosis of sepsis/septic shock. All critically ill children received hemoadsorption treatment with CytoSorb (CS) in combination with CKRT. Therapeutic drug monitoring has been performed on 10 critically ill children, testing four antimicrobial molecules: meropenem, ceftazidime, amikacin and levofloxacin. In order to evaluate the total and isolated CKRT and CS contributions to antibiotic removal, blood samples at each circuit point (post-hemofilter, post-CS and in the effluent line) were performed. Therefore, the clearance and mass Removal (MR) of the hemofilter and CS were calculated. Results: Our preliminary report describes a different impact of CS on these target drugs removal: CS clearance was low for amikacine (6-12%), moderate for ceftazidime (43%) and moderate to high for levofloxacine (52-72%). Higher MR and clearance were observed with CKRT compared to CS. To the best of our knowledge, this is the first report regarding pharmacokinetic dynamics in critically ill children treated with CKRT and CS for septic shock.

Perfluorocarbons in Research and Clinical Practice: A Narrative Review.

Perfluorocarbons (PFCs) are organic liquids derived from hydrocarbons in which some of the hydrogen atoms have been replaced by fluorine atoms. They are chemically and biologically inert substances with a good safety profile. They are stable at room temperature, easy to store, and immiscible in water. Perfluorocarbons have been studied in biomedical research since 1960 for their unique properties as oxygen carriers. In particular, PFCs have been used for liquid ventilation in unusual environments such as deep-sea diving and simulations of zero gravity, and more recently for drug delivery and diagnostic imaging. Additionally, when delivered as emulsions, PFCs have been used as red blood cell substitutes. This narrative review will discuss the multifaceted utilization of PFCs in therapeutics, diagnostics, and research. We will specifically emphasize the potential role of PFCs as red blood cell substitutes, as airway mechanotransducers during artificial placenta procedures, as a means to improve donor organ perfusion during the ex vivo assessment, and as an adjunct in cancer therapies because of their ability to reduce local tissue hypoxia.

Drug self-poisoning in adolescents: A report of 267 cases.

Introduction: The current study aims at describing a sample of adolescents admitted to a tertiary referral pediatric hospital for drug self-poisoning and to identify variables that could explain and predict a higher severity of intoxication. Methods: We retrospectively reviewed the cases of drug self-poisoning in adolescents admitted to the Bambino Gesù Children's Hospital between January 2014 and June 2022 requiring consultation by the local Pediatric Poison Control Center (PPCC). We reported the type and class of drug ingested and correlated the clinical characteristics of the patients with their Poison Severity Score. Results: The data of 267 patients were reported. Most patients were female (85.8 %), with a median age of 15.8 years at presentation. Half of the patients were symptomatic at admission (44.2 %), and most had at least one psychiatric comorbidity (71.1 %). Most patients were hospitalized (79.6 %), 16.6 % of cases required antidote administration and a minority required intensive care. Most patients received a PSS score of 0 (59.6 %). The most frequently ingested drug was acetaminophen (28.1 %) followed by ibuprofen (10.1 %) and aripiprazole (10.1 %). Antipsychotics as a class were the most abused drugs (33.1 %). The correlation of clinical variables with the PSS showed that older and male patients were more prone to be severely intoxicated. Conclusions: This single-center study identifies the most commonly ingested drugs in a large sample of adolescents with voluntary drug self-poisoning, also showing that older and male patients are more susceptible to severe intoxication.

Adverse drugs reactions to paracetamol and ibuprofen in children: a 5-year report from a pediatric poison control center in Italy.

BACKGROUND: This study aimed to analyze all the patients who contacted the hospital's pediatric poison control center (PPCC) for exposure to ibuprofen and acetaminophen, in order to assess the incidence of any adverse reactions. METHODS: We retrospectively reported the clinical data of children who accessed the PPCC of the Bambino Gesù Children's Hospital, IRCCS, Rome, from January 1, 2018 to September 30, 2022 due to wrong, accidental or intentional intake of inappropriate doses of acetaminophen and/or ibuprofen. In addition, we compared patients according to the intake of one of the two drugs and reported the trimestral distribution of cases during the study period. RESULTS: A total of 351 patients accessed the PPCC during the study period. The median age was 3.0 years. Most patients were females (57.8%). The most common reason for inappropriate oral intake of paracetamol or ibuprofen was a wrong use or an accidental intake (78.6%), with a fifth of patients taking the drug with suicidal intent (21.1%). According to the PPCC evaluation, most patients were not intoxicated (70.4%). Hospitalization was required for 30.5% of patients. Adverse reactions were reported in 10.5% of cases, with a similar incidence in patients who took paracetamol or ibuprofen. Nausea and vomiting were the most commonly reported adverse reactions. A higher frequency of moderate intoxication was found in patients who took paracetamol compared to ibuprofen (p = 0.001). The likelihood of intoxication was also higher in the paracetamol cohort. A spike of cases was registered at the end of 2021. CONCLUSIONS: We analyze exposures to the two most commonly used pediatric molecules, paracetamol and ibuprofen, to assess the frequency of adverse reactions. We demonstrated that these relatively "safe" drugs may be associated with intoxications and adverse reactions when inappropriately administered.

Pharmacobezoar after overdose of isoniazid and rifampin.

In clinical toxicology, gastric endoscopic decontamination is rarely used, and only a few cases of pharmacobezoar removal after intentional ingestion of slow-release drugs have been described. Our case describes the use of gastric endoscopic decontamination to remove potential pharmacobezoar in an adolescent after ingestion of a lethal dose of isoniazid and rifampin, even long after gastric lavage. This technique allowed the removal of pharmacobezoars still present in the stomach while preventing further deterioration of the patient.

Unintentional cannabis intoxication in infants and toddlers presenting with neurological impairment in a Pediatric Emergency Department.

BACKGROUND: Recent data show that the rising consumption of cannabis has increased the rate of acute intoxication in pediatric age. Common patterns of pediatric poisoning consist of exploratory ingestions in younger children. A history of poisoning is often not provided; therefore, it could be advisable to use an objective biological marker. The clinical presentation of occult ingestion can range from asymptomatic to critically ill. Neurological involvement is one of the most described presentations. The goal of our study was to examine the presentation of acute cannabis intoxication in a sample of 13 pediatric patients under 3 years. METHODS: A retrospective epidemiological investigation on acute cannabinoid intoxication was conducted on children under 3 years, recruited between 2016 and 2020. All patients were tested for urine drug screening suspecting poisoning as reason for Emergency Department (ED) admission. RESULTS: Thirteen of forty-eight patients tested (27%) were positive for Tetrahydrocannabinol (THC). Ingestion was the route of intoxication in all of them. Only in five cases the possible accidental intake of cannabinoids was promptly declared. Twelve children accessed on ED due to a neurological symptomatology not attributable to known causes in the medical history. CONCLUSIONS: Differential diagnosis for abuse drugs exposure in young children is broad: the urine drug screening plays a central role for confirmation of the diagnostic suspicion and identification of the specific substance. A positive result combined with a history of potential access to cannabis could prevent unnecessary, invasive, expensive procedures. When identified, the management is predominantly supportive. In this article, we want to emphasize the importance of always considering drug intoxication in children with acute neurological symptoms especially in cases of ambiguous familiar or social context. Further studies will be needed to better characterize the alarm bells for intoxication and to identify a strategy for the prevention of unintentional cannabinoid intoxication.

Replenishing Alkali During Hemodialysis: Physiology-Based Approaches.

The acid-base goal of intermittent hemodialysis is to replenish buffers consumed by endogenous acid production and expansion acidosis in the period between treatments. The amount of bicarbonate needed to achieve this goal has traditionally been determined empirically with a goal of obtaining a reasonable subsequent predialysis blood bicarbonate concentration ([HCO3 - ]). This approach has led to very disparate hemodialysis prescriptions around the world. The bath [HCO3 - ] usually chosen in the United States and Europe causes a rapid increase in blood [HCO3 - ] in the first 1-2 hours of treatment, with little change thereafter. New studies show that this abrupt increase in blood [HCO3 - ] elicits a buffer response that removes more bicarbonate from the extracellular compartment than is added in the second half of treatment, a futile and unnecessary event. We propose that changes in dialysis prescription be studied in an attempt to moderate the initial rate of increase in blood [HCO3 - ] and the magnitude of the body buffer response. These new approaches include either a much lower bath [HCO3 - ] coupled with an increase in the bath acetate concentration or a stepwise increase in the bath [HCO3 - ] during treatment. In a subset of patients with low endogenous acid production, we propose reducing the bath [HCO3 - ] as the sole intervention.

Acquired methemoglobinemia in children presenting to Italian pediatric emergency departments: a multicenter report.

INTRODUCTION: Methemoglobinemia (MetHb) is a rare inherited or acquired cause of cyanosis in children. Owing to its rarity, case reports and case series are mostly available in the current literature. This study reports data on a large sample of children with acquired MetHb. METHODS: Data on patients admitted for acquired MetHb between January 2007 to December 2020 was extracted from the databases of five Italian pediatric emergency departments (EDs). Demographical and clinical characteristics was reported and discussed. RESULTS: Nineteen cases of acquired MetHb were evaluated. Ten patients (52.6%) were male and 9 (47.4%) were female. The median age was 8.23 months. The median time from trigger to symptom onset was 6 hours. Mostly, the intoxication presumptively occurred by home ingestion of contaminated food, mainly badly preserved vegetable broth. All patients were cyanotic at admission, most patients also presented tachycardia and/or tachypnea, and two patients were comatose. Antidotal therapy with methylene blue was given in 14 patients (73.7%). The median hospital stay was 2 days. All patients survived. DISCUSSION: As MetHb leads to the pathognomonic brown blood discoloration, blood gas analysis is mandatory immediately upon hospital arrival of a cyanotic patient. A correct medical history is crucial to identify the trigger and remove it. In our sample, the age onset was much lower than in the previous literature, and MetHb mainly due to ingestion of contaminated vegetable broth. Methylene blue led to a rapid recovery in all patients. Oxygen therapy may well lead to complete recovery when methemoglobin levels do not exceed 30% in asymptomatic and 20% in mildly symptomatic patients. CONCLUSIONS: The diagnosis and management of acquired MetHb in the emergency setting requires acknowledgment of this condition as a cause of cyanosis in the weaning child. Indeed, when promptly recognized and treated, this severe condition rapidly resolves with no significant acute sequelae.

The prognostic role of interatrial block among COVID-19 patients hospitalized in medicine wards.

INTRODUCTION: Some abnormal electrocardiographic findings were independently associated with increased mortality in patients admitted for COVID-19; however, no studies have focussed on the prognosis impact of the interatrial block (IAB) in this clinical setting. The aim of our study was to assess the prevalence and clinical implications of IAB, both partial and advanced, in hospitalized COVID-19 patients. MATERIALS: We retrospectively evaluated 300 consecutive COVID-19 patients (63.22 ± 15.16 years; 70% males) admitted to eight Italian Hospitals from February 2020 to April 2020 who underwent twelve lead electrocardiographic recording at admission. The study population has been dichotomized into two groups according to the evidence of IAB at admission, both partial and advanced. The differences in terms of ARDS in need of intubation, in-hospital mortality and thromboembolic events (a composite of myocardial infarction, stroke and transient ischaemic attack) have been evaluated. RESULTS: The presence of IAB was noticed in 64 patients (21%). In the adjusted logistic regression model, the partial interatrial block was found to be an independent predictor of ARDS in need of intubation (HR: 1.92; p: .04) and in-hospital mortality (HR: 2.65; p: .02); moreover, the advanced interatrial block was an independent predictor of thrombotic events (HR: 7.14; p < .001). CONCLUSIONS: Among COVID-19 patients hospitalized in medical wards, the presence of interatrial block is more frequent than in the general population and it might be useful as an early predictor for increased risk of incident thrombotic events, ARDS in need of intubation and in-hospital mortality.

Use of Extracorporeal Membrane Oxygenation in Acutely Poisoned Pediatric Patients in United States: A Retrospective Analysis of the Extracorporeal Life Support Registry From 2003 to 2019.

OBJECTIVES: To describe the use of extracorporeal membrane oxygenation (ECMO) in the management of pediatric poisoning in the United States and to identify predictors of mortality. DESIGN: Retrospective cohort study. SETTING: Data reported to the Extracorporeal Life Support Organization by 76 U.S. ECMO centers from 2003 to 2019. PATIENTS: Pediatric patients (0-18 yr) receiving ECMO for poisoning. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During our study period, 86 cases of acute poisoning were identified and included in the analysis. The median age was 12.0 year and 52.9% were female. The most commonly reported substance exposures were hydrocarbon (n = 17; 19.8%), followed by chemical asphyxiants (n = 14; 16.3%), neuroactive agents (n = 14; 16.3%), opioid/analgesics (n = 13; 15.1%), and cardiovascular agents (n = 12; 14.0%). Single substance exposures were reported in 83.7% of the cases. The intention of the exposure was unknown in 65.1%, self-harm in 20.9% and 10.5% was unintentional exposure. Fifty-six patients (65.1%) survived. Venoarterial ECMO was used more frequently than venovenous ECMO, and its use increased significantly during the study period (p < 0.01). A bimodal distribution of ECMO support was observed among two age groups: less than or equal to 3 years (n = 34) and 13-17 years (n = 41). Hemodynamic and metabolic parameters improved for all patients with ECMO. Persistent systolic hypotension, acidemia/metabolic acidosis, and elevated Pao2) after 24 hours of ECMO support were associated with mortality. Time from PICU admission to ECMO cannulation was not significantly different between survivors (24.0 hr; interquartile range [IQR], 11.0-58.0 hr) and nonsurvivors (30.5 hr; IQR, 10.0-60.2 hr; p = 0.58). ECMO duration and PICU length of stay were significantly longer in survivors than in nonsurvivors (139.5 vs 70.5 hr; p = 0.007 and 25.0 vs 4.0 d; p = 0.002, respectively). CONCLUSIONS: ECMO may improve the hemodynamic and metabolic status of poisoned pediatric patients. Persistent hypotension, acidemia/acidosis, and elevated Pao2 after 24 hours of ECMO were associated with mortality.

Sufficient MRI graft structural integrity at 9 months after anterior cruciate ligament reconstruction with hamstring tendon autograft.

PURPOSE: To assess the MRI-measured structural integrity of hamstring autograft at 9 months after anterior cruciate ligament reconstruction (ACLR) surgery. METHODS: A prospective cohort study was conducted including 34 patients (mean age 36.8 ± 11.8 years; 73.5% males) who underwent ACLR with hamstring autograft. In addition, 36 patients (mean age 39.2 ± 10.5 years; 69.4% males) without any ACL injury were also reviewed and served as control group. The primary outcome used for examining graft maturity at 9 months after ACLR was the MRI-based signal-to-noise quotient (SNQ) of reconstructed ACL. SNQ values were stratified into 3 different categories: excellent: < 0.1; good: ≥ 0.1 and ≤ 0.19; fair: ≥ 0.2. The KT-1000 knee arthrometer was used to measure the side-to-side difference in the anterior tibial translation between the ACLR knee and the contralateral healthy knee in the ACLR group. RESULTS: Reconstructed ACLs were found with a mean SNQ of 0.078 ± 0.061, while almost all ACL-reconstructed patients (97%; 33 out of 34) were found with excellent or good SNQ values (< 0.019). The mean KT-1000 in the ACLR group was 0.071 mm ± 0.926 mm, while there were no patients in the ACLR cohort with a KT-1000 value > 3 mm. The mean 9-months MRI-based SNQ of ACLR group was significantly higher compared to the mean MRI-based SNQ of the control group (p < 0.001). Multiple regression analysis showed no correlation between SNQ and age, gender, time from injury to ACLR, graft size, or simultaneous treatment of additional intra-articular knee lesions. CONCLUSIONS: In this cohort of 34 ACL-reconstructed patients, 97% of hamstring tendon autografts demonstrated excellent/good MRI signal intensity and excellent functional results (KT-1000 < 3 mm) at 9 months after surgery. Based on this finding, it is suggested that return to sports after ACLR with hamstring autograft can be considered safe at 9 months post surgery. Furthermore, while structural integrity of the graft has been achieved at this time point, statistical differences found in SNQ values of ACL-reconstructed patients compared to ACLs of healthy individuals highlight the continuing process of graft maturation and remodelling. LEVEL OF EVIDENCE: Level III.

[Impact of dialysis on the acid-base balance].

In patients on hemodialysis, the reduced alkali urinary loss makes metabolic acidosis less severe. Unexpected is the large occurrence of respiratory alkalosis and acidosis. During the therapy, the convective/diffusive inward fluxes of CO2 and bicarbonate and the loss of organic anions affect acid-base homeostasis. In bicarbonate-dialysis, the neutralization of acids by bicarbonate and gain of gaseous CO from the dialysate cause an increase of CO2 content in the body water, which requires an increase in lung ventilation (>10%) to prevent hypercapnia. In on-line hemodiafiltration, the infusate drags additional CO2 into bloodstream, while in acetate - free biofiltration the dialysate is CO2 - free and this prevents any addition of CO2. Bicarbonate and acetate diffuse into extracellular fluid according to their bath-to-blood concentration gradients. The initially large bicarbonate flux decreases rapidly because of the rapid increase in blood concentration. The smallest acetate flux is instead constant with time providing a constant source of alkali. Rapid alkalinization elicits H+ mobilization that consumes most of the bicarbonate added. Some H+ are originated by back-titration of body buffers, but others are originated by new organic acid production, a maladaptive event that wastes metabolic energy. In addition, organic anions diffuse into dialysate causing a substantial increase in net acid production. A novel dialysis protocol prescribes a low initial bath bicarbonate concentration and a stepwise increase during the therapy. Such a staircase protocol ensures a smoother increase of blood bicarbonate concentration avoiding the initial rapid growth and reducing the rate of organic acid production, thus making the treatment more effective.

Evaluation of Expected Ventilatory Response to Metabolic Acidosis in Severely Ill Patients.

INTRODUCTION: Winters' formula (pCO2 =1.5*HCO3 +8) is used worldwide to predict the ventilatory response to metabolic acidosis, namely to predict the pCO2 value complying with reduction of serum bicarbonate concentration (HCO3 ). This equation was obtained half a century ago in mostly pediatric subjects. Subsequently different and inconsistent rules have been suggested. The study was done to verify the reliability of Winters' formula in severely ill patients with respect of other modern and commonly used formulas. METHODS: We applied Winters' formula and some other formulas to a dataset of arterial gas analysis from 29 severely ill malaria patients (about half of them requiring ICU or hemodialysis). The expected pCO2 value was computed by each formula and the root mean square error (RMSE) was measured. Beyond predicting the expected pCO2 value, expected range of values was also computed (as expected value ± each own error) and agreement with the best fit equation (± its error) was assessed. RESULTS: In this dataset featured by metabolic acidosis of moderate degree (mean pH 7.2, mean HCO3 : 15.3 mmol/l) a strong positive linear relationship between pCO2 and HCO3 was found (R squared =0.97). The best fit linear equation was in form of pCO2 = 1.28*HCO3 +11.55. Winters' formula exhibits the lowest RMSE (1 mmHg) and shows the better agreement (Cohen's kappa=0.7) with the best fit equation Conclusions: Winters' formula can still profitably used to compute the expected pCO2 value and in turn to infer mixed (metabolic plus respiratory) acid-base disorders in severely ill patients.

Acute Exposure to European Viper Bite in Children: Advocating for a Pediatric Approach.

Viper bite is an uncommon but serious cause of envenoming in Europe, especially in children. Our study aim is to better describe and analyze the clinical course and treatment of viper bite envenoming in a pediatric population. We retrospectively reviewed 24 cases of pediatric viper bites that were admitted to the Pediatric Emergency Department and the Pediatric Intensive Care Unit of the Bambino Gesù Children Hospital in Rome between 2000 and 2020. Epidemiological characteristics of the children, localization of the bite, clinical and laboratory findings, and treatment approaches were evaluated. The median age of the patients was 4.2 years, with male predominance. Most cases of viper bite occurred in the late summer. Most patients required admission to the ward for prolonged observation. The most common presenting signs were pain, local oedema, and swelling. Patients with a high severity score also had a significantly higher white blood cell count and an increase of INR, LDH, and CRP levels. No fatality was reported. Viper bite envenomation is a rare pediatric medical emergency in Italy but may sometimes be severe. A new pediatric severity score may be implemented in the screening of children with viper bites to favor a selective and prompt administration of antivenom.

On the CO2 gain in on-line hemodiafiltration.

BACKGROUND: The dialysis bath holds up to 90 mmHg carbon dioxide (CO2 ) in order to keep pH low and salts in their soluble forms. CO2 crosses the dialyzer membrane and diffuses to patients. In post-dilution on-line hemodiafiltration (HDF) many liters of CO2 -containing dialysis bath - in the form of infusate - are delivered directly to patients bypassing the filtering membrane, but the precise amount of CO2 delivered is unknown. METHODS: To gain insights on this issue 18 outpatients undergoing their regular on-line HDF were investigated by means of blood gas analysis. RESULTS: Arterial pre-dialysis samples show slight hypocapnia (35.40 ± 3.22 mmHg) consistent with the secondary compensatory response to metabolic acidosis. In blood coming back to patients (venous line of extracorporeal circuit) pCO2 doubled, amounting to 69 ± 5.5 mmHg (P < .0001 with respect to pre-dialysis values) hence in on-line HDF a CO2 gain does occur. Turning off the infusate flux pump, pCO2 decreased to 63.1 ± 5.8 mmHg (P = .004) meaning that delivery of infusate in post-dilution mode significantly contributes to CO2 gain, albeit by a small amount. CONCLUSION: On-line HDF is featured by CO2 delivery to patients, in part dragged by the infusate.