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.

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.

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.

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.

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.

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.

Changing dialysate composition to optimize acid-base therapy.

In response to rapid alkali delivery during hemodialysis, hydrogen ions (H+ ) are mobilized from body buffers and from stimulation of organic acid production in amounts sufficient to convert most of the delivered bicarbonate to CO2 and water. Release of H+ from nonbicarbonate buffers serves to back-titrate them to a more alkaline state, readying them to buffer acids that accumulate in the interval between treatments. By contrast, stimulation of organic acid production only serves to remove added bicarbonate (HCO3 - ) from the body; the organic anions produced by this process are lost into the dialysate, irreversibly acidifying the patient as well as diverting metabolic activity from normal homeostasis. We have developed an analytic tool to quantify these acid-base events, which has shown that almost two-thirds of the H+ mobilized during hemodialysis comes from organic acid production when bath bicarbonate concentration ([HCO3 - ]) is 32 mEq/L or higher. Using data from the hemodialysis patients we studied with our analytical model, we have simulated the effect of changing bath solute on estimated organic acid production. Our simulations demonstrate that reducing bath [HCO3 - ] should decrease organic acid production, a change we propose as beneficial to the patient. They also highlight the differential effects of variations in bath acetate concentration, as compared to [HCO3 - ], on the amount and rate of alkali delivery. Our results suggest that transferring HCO3 - delivery from direct influx to acetate influx and metabolism provides a more stable and predictable rate of HCO3 - addition to the patient receiving bicarbonate-based hemodialysis. Our simulations provide the groundwork for the clinical studies needed to verify these conclusions.

Eltrombopag-Induced Acute Liver Failure in a Pediatric Patient: A Pharmacokinetic and Pharmacogenetic Analysis.

Eltrombopag is an oral thrombopoietin receptor agonist approved for the treatment of patients with chronic idiopathic thrombocytopenic purpura (ITP), who are more than 1 year old, and show poor response to first-line therapy. ITP is a hematological disorder characterized by isolated thrombocytopenia in the absence of secondary causes or disorders. Eltrombopag is generally well tolerated in the pediatric population; therefore, therapeutic drug monitoring (TDM) is not usually performed in clinical practice.We presented the case study of a 3-year-old girl with chronic ITP. She arrived in the pediatric intensive care unit with acute liver failure due to eltrombopag toxicity despite taking the standard drug dosage. A very high eltrombopag plasma concentration, indicating drug toxicity, was found through TDM. The patient also carried the allelic variations that are involved in drug metabolism [CYP2C8 and UDP glucuronosyltransferase (UGT) 1A1 (UGT1A1)] and drug cellular transportation [ABCG2 (ATP-binding cassette G2)]. This observation highlights the importance of using TDM and pharmacogenetic approaches to manage patients' unusual complications associated with standard pharmacological treatment regimens.

Acid-base homeostasis during hemodialysis: New insights into the mystery of bicarbonate disappearance during treatment.

In patients receiving hemodialysis, it has long been recognized that much more bicarbonate is delivered during treatment than ultimately appears in the blood. To gain insight into this mystery, we developed a model that allows a quantitative analysis of the patient's response to rapid alkalinization during hemodialysis. Our model is unique in that it is based on the distribution of bicarbonate in the extracellular fluid and assesses its removal from this compartment by mobilization of protons (H+ ) from buffers and other sources. The model was used to analyze the pattern of rise in blood bicarbonate concentration ([HCO3- ]), calculated from measurements of pH and PCO2 , in patients receiving standard bicarbonate hemodialysis. Model analysis demonstrated two striking findings: (1) 35% of the bicarbonate added during hemodialysis was due to influx and metabolism of acetate, despite its low concentration in the bath solution, because of the rapidly collapsing gradient for bicarbonate influx. (2) Almost 90% of the bicarbonate delivered to the patients was neutralized by H+ generation. Virtually all the new H+ came from intracellular sources and included both buffering and organic acid production. The small amount of added bicarbonate retained in the extracellular fluid increased blood [HCO3- ], on average, by 6 mEq/L in our patients. Almost all this rise occurred during the first 2 hours. Thereafter, blood [HCO3- ] changed minimally and always remained less than bath [HCO3- ]. This lack of equilibrium was due to the continued production of organic acid. Release of H+ from buffers is a reversible physiological response, restoring body alkali stores. By contrast, organic acid production is an irreversible process during hemodialysis and is metabolically inefficient and potentially catabolic. Our analysis underscores the need to develop new approaches for alkali repletion during hemodialysis that minimize organic acid production.

Pediatric extracorporeal cardiopulmonary resuscitation settled in an emergency department for a propafenone intentional intoxication.

The use of drugs in suicide attempts is becoming more and more frequent among adolescents. Intentional intoxication with propafenone is very rare and mainly reported in adults associated with other drugs. The therapeutic approach is symptomatic, since there is no specific antidote for propafenone. We present a pediatric case of intentional ingestion of 1.8 g of propafenone that caused refractory cardiogenic shock. The patient was successfully rescued with extracorporeal cardiopulmonary resuscitation in the emergency department of a secondary level peripheral hospital.

Beyond bicarbonate: complete acid-base assessment in patients receiving intermittent hemodialysis.

Background: Acid-base assessments in hemodialysis patients have been limited almost entirely to measurements of total CO 2 concentration, and assumptions have been made about the presence of acid-base disorders. To gain a fuller understanding of the acid-base status of stable hemodialysis patients, we analyzed measurements of pCO 2 , pH and HCO 3 - obtained in a cohort of chronic stable hemodialysis patients over a 5-year period. Methods: We reviewed acid-base measurements taken pre-dialysis from fistula blood in 53 outpatients receiving hemodialysis thrice weekly between 2008 and 2012. In these patients, pH and pCO 2 were measured using an onsite blood gas analyzer, and HCO 3 - was computed. Relevant clinical and laboratory data were obtained from medical records. Factors affecting serum HCO 3 - were identified. Simple and mixed acid-base disorders were diagnosed using accepted rules. Results: Serum HCO 3 - was affected by age, normalized protein catabolic rate, interdialytic weight gain and length of interval between treatments. As expected, metabolic acidosis was the most common acid-base disorder, but respiratory acid-base disturbances, as simple or complex disorders, were found in 41% of the measurements. Respiratory alkalosis was seen more frequently than respiratory acidosis, but the latter disorder was more commonly associated with serious comorbidities. Conclusions: Respiratory acid-base disorders are an important component of the acid-base abnormalities seen in hemodialysis patients and are not identified by measuring total CO 2 concentration; hence, complete acid-base measurements are needed to determine the components of hemodialysis patients' acid-base status that are contributing to mortality risk.

The First Report of Bayés Syndrome in Hemodialysis Patient.

A chronic hemodialysis patient-known to have advanced interatrial block (IAB)-had reported symptoms suggesting arrhythmias, hence she underwent hemodialysis treatment while on the cardiac monitor. This allowed us to recognize the occurrence of paroxysmal atrial fibrillation and, in turn, disclose the first case of Bayés syndrome. Even though atrial fibrillation and IAB are very frequent in hemodialysis patients, Bayés syndrome, that comprehends both, has never been described, likely because the IAB is often overlooked and undiagnosed. This case could improve the awareness of IAB and of the Bayés syndrome in hemodialysis population.

pCO2 Reveals Arteriovenous Fistula Recirculation in Bicarbonate Hemodialysis (RecirCO2lation Test).

We propose arterial pCO2 as test to discover vascular access recirculation (VAR) in bicarbonate hemodialysis (HD). We selected 30 HD patients with a ascertained well-functioning arteriovenous fistula (Control). In these patients, we artificially created VAR through the reversion of HD lines (Reversed). Results of the arterial gas analysis were collected at the start of HD (baseline) and after 5 min. At baseline, no differences of pH, pCO2 and HCO3 were found between the 2 groups. At 5 min, pCO2 increased from 38.1 ± 3.3 to 47.2 ± 6.3 mm Hg (p < 0.0001) in Reversed, whereas no increase was found in Control (p = 0.052). Areas under curve of pCO2-increase was 0.96 (0.91-1.00) and pCO2 at 5 min 0.92 (0.85-0.98). pCO2-increase >4.5 mm Hg showed sensitivity 86.7% and specificity 100% with positive predictive value (PPV) 100% and negative predictive value (NPV) 89%. A pCO2 value above 43 mm Hg at 5 min showed sensitivity 80%, specificity 90%, PPV 89%, NPV 82%. pCO2 increase >4.5 mm Hg and/or pCO2 at 5 min >43 mm Hg may accurately detect VAR.

Carbon Dioxide and Acetate-Free Biofiltration: A Relationship to be Investigated.

As the name reveals, acetate-free biofiltration (AFB) is featured by lack of acetate and this would seem to allow better hemodynamic stability. However, AFB also has a unique characteristic of carbon dioxide (CO2 )-free dialysate, whereas all other modern dialysis techniques imply an overload of CO2 from dialysate to the patient. This notwithstanding the role of CO2 in tolerance to dialysis treatment, both AFB and all other dialysis techniques seem not investigated in due depth. Specifically, the amount of CO2 coming back to the patient's bloodstream during AFB and bicarbonate dialysis (BD) is unknown. We measured partial pressure of CO2 (pCO2 ) in blood samples withdrawn from the venous line of the extracorporeal circuit during BD and subsequently during AFB in 22 stable chronic hemodialysis outpatients. The amount of CO2 coming back to the patient's bloodstream is higher in BD (59.1 ± 4.0 mmol/L) than in AFB (42.8 ± 4.5 mmol/L, P < 0.0001). Such difference exceeds 30%. Moreover, shifting from BD to AFB shows, notably for each patient, the reduction of pCO2 toward physiological values. BD implies CO2 overload from dialysate, whereas AFB does not. Further studies are required to evaluate if AFB would be the most appropriate dialysis technique in patients affected by chronic, but especially acute, lung diseases.

Ultrasound-guided left brachiocephalic vein cannulation in children with underlying bleeding disorders: a retrospective analysis.

OBJECTIVES: To evaluate the safety and effectiveness of ultrasound-guided left brachiocephalic vein cannulation in infants and children with underlying bleeding conditions. DESIGN: Retrospective cohort. SETTING: PICU of a tertiary pediatric hospital. PATIENTS: Thirty-four patients requiring central venous catheterization from January 2011 to January 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two pediatric intensivists, experienced in ultrasound-guided vessel cannulation, performed the ultrasound catheterization of the left brachiocephalic vein. Ultrasound equipment consisted of a standard ultrasound monitor with a linear 6-13 MHz probe. The ultrasound monitor was set on a resolution with a depth of 1.8 cm for infants and 2.2 cm for children. The "in-plane" technique was used for all patients. Thirty-four catheterizations were performed. Patient median age was 12.5 months (5.75-63.5 mo) and median weight was 9.25 kg (7-16.25 kg). The population of infants and children analyzed was composed of 25 patients with hematologic disorder (73%) treated with hematopoietic stem cell transplantation, five patients (15%) supported with extracorporeal membrane oxygenation for viral pneumonias, and four patients (12%) with uremic hemolytic syndrome. A 4F catheter was used in 79% of cases. Left brachiocephalic vein cannulation was successful in all 34 patients. Median time needed for cannulation was 350 seconds (277.5-450 s). The overall complication rate was 9% (3 of 34) and consisted of difficulty in advancing the guidewire after having pierced the vein. The time required for catheter positioning and complications was not associated with both lower body weight and body surface area of the patients (p > 0.05). Mean central venous catheter duration was 32 ± 4 days. CONCLUSIONS: Data reported in this retrospective study confirm the safety and effectiveness of ultrasound-guided left brachiocephalic vein catheterization in infants and children with underlying bleeding disorders.

Factors affecting bone strength other than osteoporosis.

Osteoporosis is the most common cause of bone fragility, especially in post-menopausal women. Bone strength may be compromised by several other medical conditions and medications, which must be ruled out in the clinical management of patients affected by fragility fractures. Indeed, 20-30% of women and up to 50% of men affected by bone fragility are diagnosed with other conditions affecting bone strength other than osteoporosis. These conditions include disorders of bone homeostasis, impaired bone remodeling, collagen disorders, and medications qualitatively and quantitatively affecting bone strength. Proper diagnosis allows correct treatment to prevent the occurrence of fragility fractures.

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.