Spontaneous resolution of an intrapericardial thrombus as a complication of pericardiocentesis in a neonate.

We present the case of a premature neonate with pericardial effusion secondary to extravasation of total parenteral nutrition from a mispositioned/migrated umbilical venous catheter. Emergency pericardiocentesis was complicated by an intrapericardial thrombus, which was managed conservatively with spontaneous resolution within 24 hours. This case illustrates that the rare complication of an intrapericardial thrombus after pericardiocentesis can be successfully managed conservatively with close monitoring in haemodynamically stable paediatric patients.

Evaluating student's ability to assess treatment claims: validating a German version of the Claim Evaluation Tools.

BACKGROUND: The Claim Evaluation Tools measure the ability to assess claims about treatment effects. The aim of this study was to adapt the German item sets to the target group of secondary school students (aged 11 to 16 years, grade 6 to 10) and to validate them accordingly. The scale's reliability and validity using Rasch's probabilistic test theory should be determined. METHODS: We conducted a sequential mixed-method study comprising three stages: contextualisation and adaption of the items (stage 1), piloting of the item sets using qualitative interviews (stage 2) and a construct validation by testing the unidimensional Rasch scalability for each item set after data collection in one secondary school in Germany and two secondary schools in Austria. We explored summary and individual fit statistics and performed a distractor analysis (stage 3). RESULTS: Secondary school students (n = 6) and their teachers (n = 5) participated in qualitative interviews in Germany. The qualitative interviews identified the need for minor modifications (e.g. reducing thematic repetitions, changing the order of the items). The data of 598 German and Austrian secondary school students were included to test for Rasch scalability. Rasch analyses showed acceptable overall model fit. Distractor analyses suggested that model fit could be improved by simplifying the text in the scenarios, removing and editing response options of some items. CONCLUSION: After the revision of some items, the questionnaires are suitable to evaluate secondary school students' ability to assess health claims. A future goal is to increase the pool of items being translated and tested.

Roadmap to the Effective Use of Continuous Glucose Monitoring in Primary Care.

Diabetes technology has undergone a remarkable evolution in the past decade, with dramatic improvements in accuracy and ease of use. Continuous glucose monitor (CGM) technology, in particular, has evolved, and coevolved with widely available consumer smartphone technology, to provide a unique opportunity to both improve management and decrease the burden of management for populations across nearly the entire spectrum of people living with diabetes. Capitalizing on that opportunity, however, will require both adoption of and adaptations to the use of CGM technology in the broader world of primary care. This article focuses on mechanisms to expand pathways to optimized glycemic management, thereby creating a robust roadway capable of improving care across broad populations managed in primary care settings. Recent expansions in access to devices combined with improved mechanisms for data access at the time of primary care visits and improved training and evolving systems of support within primary care, hold potential to improve glycemic management in diabetes across the health care spectrum.

Glycaemic profiles of diverse patients with type 2 diabetes using basal insulin: MOBILE study baseline data.

Basal insulin is often prescribed to patients with suboptimally controlled type 2 diabetes (T2D); however, its therapeutic efficacy is inadequate in many. During the MOBILE study's baseline phase, we evaluated 173 participants' continuous glucose monitoring (CGM) data (mean ± SD age 57 ± 9 years; 50% female; HbA1c 9.1% [range 7.1%-11.6%]; 40% using sulphonylureas; 19% using NPH; reported self-monitored blood glucose [SMBG] frequency median 1.0 checks/day) who were using basal, but not prandial insulin. Blinded CGM data were recorded for 10 days prior to randomization. The mean glucose value was 208 ± 47 mg/dL and it was lowest in the early morning. Mean time in the 70-180 mg/dL range was 9.6 ± 6.1 hours/day (40% ± 25%). Hyperglycaemia was extensive with medians of 14.7 (61%) and 5.0 (20.9%) hours/day with glucose greater than 180 and 250 mg/dL, respectively. Hypoglycaemia was infrequent (median [IQR] 0 [0, 4.3] minutes/day [0.0% {0.0%, 0.3%}] with glucose less than 70 mg/dL). Blinded CGM highlights the limitations of infrequent SMBG in basal insulin users with T2D and allows characterization of hyperglycaemia and hypoglycaemia in basal insulin users with suboptimal control. The MOBILE study randomized phase will define the benefits of using real-time CGM compared with SMBG in this population.

ACARPA, a rare case of ALCAPA.

An anomalous circumflex coronary artery arising from the right pulmonary artery is very rare. Clinical presentation varies from absence of symptoms to arrhythmia and sudden cardiac death. Since prevalence is very low, no definite therapy has been delineated yet. A 19-year-old patient, previously treated for a vascular ring and mitral valve stenosis, was diagnosed with this anomaly through echocardiography revealing collateral coronary flow, with confirmation of this coronary anomaly on subsequent computed tomography examination. To alleviate the burden for arrhythmia in this young patient, he was successfully treated with surgical reimplantation followed by an uneventful recovery.

QRS Duration During Follow-Up of Tetralogy of Fallot: How Valuable is it? Analysis of ECG Changes in Relation to Pulmonary Valve Implantation.

Long-term results after tetralogy of Fallot (TOF) repair are determined by the extent of right ventricular remodeling to chronic pulmonary regurgitation entailing progressive RV dysfunction and a risk of developing ventricular arrhythmia. Pulmonary valve replacement (PVR) can alleviate this burden. As a predictor of ventricular arrhythmia, QRS duration remains a strong parameter in this decision. We performed a retrospective analysis of all PVR patients between 2005 and 2018, studying the time evolution of electrocardiographic parameters before and after PVR through linear mixed model analysis. 42 TOF patients underwent PVR. The median timespan between primary repair and PVR was 18 years (IQR 13-30). The indication for PVR was primarily based on the association of exercise intolerance (67%) and significant RV dilation on cMRI (median RVEDVi 161 ml/m2 IQR 133-181). Median QRS length was 155 ms (IQR 138-164), 4 (10%) patients had a QRS > 180 ms. QRS duration increased significantly before PVR, but barely showed regression after PVR. Changes of QRS duration after PVR were independent of RV dilation. In conclusion, when the decision for PVR in TOF patients is primarily based on RV volume and/or function threshold, QRS duration > 180 ms is rarely observed. In contrast with the significant increase of QRS duration before PVR, QRS length regression appears to be independent of the extent of RV dilation or QRS > 160 ms. Considering that the decision for PVR is based on mechanical RV characteristics, the utility of serial follow-up of QRS duration in contemporary operated TOF patients becomes questionable in absence of clinical arguments for ventricular arrhythmia.

Effect of Continuous Glucose Monitoring on Glycemic Control in Patients With Type 2 Diabetes Treated With Basal Insulin: A Randomized Clinical Trial.

Importance: Continuous glucose monitoring (CGM) has been shown to be beneficial for adults with type 2 diabetes using intensive insulin therapy, but its use in type 2 diabetes treated with basal insulin without prandial insulin has not been well studied. Objective: To determine the effectiveness of CGM in adults with type 2 diabetes treated with basal insulin without prandial insulin in primary care practices. Design, Setting, and Participants: This randomized clinical trial was conducted at 15 centers in the US (enrollment from July 30, 2018, to October 30, 2019; follow-up completed July 7, 2020) and included adults with type 2 diabetes receiving their diabetes care from a primary care clinician and treated with 1 or 2 daily injections of long- or intermediate-acting basal insulin without prandial insulin, with or without noninsulin glucose-lowering medications. Interventions: Random assignment 2:1 to CGM (n = 116) or traditional blood glucose meter (BGM) monitoring (n = 59). Main Outcomes and Measures: The primary outcome was hemoglobin A1c (HbA1c) level at 8 months. Key secondary outcomes were CGM-measured time in target glucose range of 70 to 180 mg/dL, time with glucose level at greater than 250 mg/dL, and mean glucose level at 8 months. Results: Among 175 randomized participants (mean [SD] age, 57 [9] years; 88 women [50%]; 92 racial/ethnic minority individuals [53%]; mean [SD] baseline HbA1c level, 9.1% [0.9%]), 165 (94%) completed the trial. Mean HbA1c level decreased from 9.1% at baseline to 8.0% at 8 months in the CGM group and from 9.0% to 8.4% in the BGM group (adjusted difference, -0.4% [95% CI, -0.8% to -0.1%]; P = .02). In the CGM group, compared with the BGM group, the mean percentage of CGM-measured time in the target glucose range of 70 to 180 mg/dL was 59% vs 43% (adjusted difference, 15% [95% CI, 8% to 23%]; P < .001), the mean percentage of time at greater than 250 mg/dL was 11% vs 27% (adjusted difference, -16% [95% CI, -21% to -11%]; P < .001), and the means of the mean glucose values were 179 mg/dL vs 206 mg/dL (adjusted difference, -26 mg/dL [95% CI, -41 to -12]; P < .001). Severe hypoglycemic events occurred in 1 participant (1%) in the CGM group and in 1 (2%) in the BGM group. Conclusions and Relevance: Among adults with poorly controlled type 2 diabetes treated with basal insulin without prandial insulin, continuous glucose monitoring, as compared with blood glucose meter monitoring, resulted in significantly lower HbA1c levels at 8 months. Trial Registration: ClinicalTrials.gov Identifier: NCT03566693.

Pediatric lung transplantation: Results of volume reduction in smaller children.

Pediatric LTX is challenged by the scarcity of suitable donor organs. To alleviate the problem of size matching, volume reduction of the donor is a possible option. Previous reports address mostly older teenagers, and data about younger patients are lacking. The purpose of this study was to investigate whether trimming had influence on the morbidity and mortality in slightly younger recipients, operated in a single center. Between 2015 and 2018, 20 patients were transplanted at the GOSH London. The mean age was 11.5 (±4.6) years. Nine patients underwent volume reduction prior to transplantation (T group). The other patients received classical bilateral LTX (NT group). Ischemia times were longer in the T group, but this difference was not statistically significant. We observed no 30-day mortality. Hospital survival in the T group was 78% vs 90% in the NT group. After almost 3 years, mortality in the T group was 22% vs 28% in the NT group. None of these differences was statistically significant. The mean duration of MV, intensive care stay, and hospital stay were 11.5, 19.9, and 44.8 days, respectively. Results were equal in terms of morbidity, defined as respiratory and neurological complications or the need for ECMO. Results show that volume reduction prior to LTX is a feasible option, even in smaller children. While awaiting long-term results, accepting larger donor organs could be a strategy to further reduce waiting list time and subsequently lower the mortality on the waiting list.

Right superior vena cava draining into the left atrium in a patient with sinus venosus defect.

Right superior vena cava draining into the left atrium is an extremely rare anomaly of systemic venous return. It can be isolated or it can be associated with other congenital heart defects, thus clinical presentation may vary. A case of a 9-year-old asymptomatic patient with sinus venous defect and bilateral superior vena cava with the right-sided draining into the left atrium is described.

Deep hypothermic extracorporeal membrane oxygenation cannula exchange in a child with necrotic pneumonia.

Necrotizing pneumonia can lead to respiratory insufficiency in previously healthy children. Extracorporeal membrane oxygenation can be used for hemodynamic salvage and subsequent lung rest awaiting recovery. We present a case of a child initially placed on veno-arterial extracorporeal membrane oxygenation and converted to veno-venous extracorporeal membrane oxygenation. This was done under deep hypothermia in the operating theater.

The role of intracellular trafficking of CdSe/ZnS QDs on their consequent toxicity profile.

BACKGROUND: Nanoparticle interactions with cellular membranes and the kinetics of their transport and localization are important determinants of their functionality and their biological consequences. Understanding these phenomena is fundamental for the translation of such NPs from in vitro to in vivo systems for bioimaging and medical applications. Two CdSe/ZnS quantum dots (QD) with differing surface functionality (NH2 or COOH moieties) were used here for investigating the intracellular uptake and transport kinetics of these QDs. RESULTS: In water, the COOH- and NH2-QDs were negatively and positively charged, respectively, while in serum-containing medium the NH2-QDs were agglomerated, whereas the COOH-QDs remained dispersed. Though intracellular levels of NH2- and COOH-QDs were very similar after 24 h exposure, COOH-QDs appeared to be continuously internalised and transported by endosomes and lysosomes, while NH2-QDs mainly remained in the lysosomes. The results of (intra)cellular QD trafficking were correlated to their toxicity profiles investigating levels of reactive oxygen species (ROS), mitochondrial ROS, autophagy, changes to cellular morphology and alterations in genes involved in cellular stress, toxicity and cytoskeletal integrity. The continuous flux of COOH-QDs perhaps explains their higher toxicity compared to the NH2-QDs, mainly resulting in mitochondrial ROS and cytoskeletal remodelling which are phenomena that occur early during cellular exposure. CONCLUSIONS: Together, these data reveal that although cellular QD levels were similar after 24 h, differences in the nature and extent of their cellular trafficking resulted in differences in consequent gene alterations and toxicological effects.

Effect of covalent fluorescence labeling of plasmid DNA on its intracellular processing and transfection with lipid-based carriers.

The development of biotechnological pharmaceutics, like macro- and nanocarriers, can benefit greatly from studying their characteristics in situ using advanced fluorescence microscopy methods. While choosing the optimal labeling method for visualizing the carrier or its cargo is crucial, it seldom receives attention. The possibility that high labeling densities alter the intracellular processing of the molecule is considered, but how and at which point this interference happens is not yet studied. The aim of this study was to elucidate the effect of labeling density on the cellular trafficking of labeled pDNA. Due to the drastic effect on expression levels for higher labeling densities, we tried to determine at which steps in the intracellular processing labeled pDNA behaves different than its nonlabeled counterpart. Therefore, different labeling densities, up to the manufacturer's recommended density, were tested. It was found that the cellular uptake remains unaffected, while the affinity for lipids is increased, which affects dissociation from the lipid-based complex and may affect endosomal escape. Also, nuclear injections clearly demonstrated that transcription is affected. The information and methodology, included in this work, could be helpful in determining if the labeling method and density used yields biological relevant results for the intended research question.

Right coronary sinus aneurysm repair.

In this case report, we describe the surgical treatment of a right coronary sinus aneurysm. A 69-year-old male patient was screened because of palpitations. He was finally diagnosed with an aneurysm of the sinus of Valsalva of the right coronary cusp. According to current aortic guidelines, surgical reconstruction was proposed. The patient underwent a cardiac operation through a median sternotomy under routine cardiopulmonary bypass. After aortic cross-clamping, the aorta was opened and the connection between the aorta and the aneurysm was clearly visualized, underneath the ostium of the right coronary artery. After excision of the right coronary button and the remaining right coronary sinus wall, this sinus was reconstructed with a Dacron graft, with subsequent coronary reimplantation. The postoperative course was uneventful. The patient was discharged on postoperative day 7. A complete sinus reconstruction was preferred over local patching of the defect because of the proximity of the aneurysm sac to the right coronary artery and the fragile, thin aortic tissue just underneath the coronary ostium.

A new recumbirostran 'microsaur' from the lower Permian Bromacker locality, Thuringia, Germany, and its fossorial adaptations.

Several recumbirostran 'microsaurs' are known from early Permian sites across Germany, including the Tambach Formation in Thuringia, central Germany. The only 'microsaur' thus far described from the Tambach Formation was the ostodolepid recumbirostran Tambaroter carrolli. However, there is also the documented presence of an undescribed recumbirostran 'microsaur' at the well-known Bromacker locality. The Bromacker locality is highly recognized and best known for its very diverse and extremely well-preserved terrestrial tetrapod assemblage combined with the co-occurrence of an exceptional vertebrate ichnofossil record. Here we describe a second new recumbirostran taxon from the Tambach Formation, which is also the first from the Bromacker locality itself. Phylogenetic analysis indicates that the new taxon, Bromerpeton subcolossus gen. et sp. nov., is a brachystelechid recumbirostran, a group also known elsewhere in Germany. The following features differentiate Bromerpeton from the other members of the clade: the presence of 13 maxillary teeth, narrow postorbitals that do not substantially contribute to the postorbital region of the skull, the frontal does not contribute to the orbital margin, and the presence of five manual digits. This new recumbirostran 'microsaur' further adds to the unique ecosystem that is preserved at the Bromacker locality, granting us a better understanding of what was living underfoot the larger more well-known animals at the locality. Likewise, it expands our understanding of the evolution of recumbirostran 'microsaurs', especially with regards to digit and limb reduction within the clade.

Expert Panel Recommendations for a Standardized Ambulatory Glucose Profile Report for Connected Insulin Pens.

Background: Connected insulin pens capture data on insulin dosing/timing and can integrate with continuous glucose monitoring (CGM) devices with essential insulin and glucose metrics combined into a single platform. Standardization of connected insulin pen reports is desirable to enhance clinical utility with a single report. Methods: An international expert panel was convened to develop a standardized connected insulin pen report incorporating insulin and glucose metrics into a single report containing clinically useful information. An extensive literature review and identification of examples of current connected insulin pen reports were performed serving as the basis for creation of a draft of a standardized connected insulin pen report. The expert panel participated in three virtual standardization meetings and online surveys. Results: The Ambulatory Glucose Profile (AGP) Report: Connected Insulin Pen brings all clinically relevant CGM-derived glucose and connected insulin pen metrics into a single simplified two-page report. The first page contains the time in ranges bar, summary of key insulin and glucose metrics, the AGP curve, and detailed basal (long-acting) insulin assessment. The second page contains the bolus (mealtime and correction) insulin assessment periods with information on meal timing, insulin-to-carbohydrate ratio, average bolus insulin dose, and number of days with bolus doses recorded. The report's second page contains daily glucose profiles with an overlay of the timing and amount of basal and bolus insulin administered. Conclusion: The AGP Report: Connected Insulin Pen is a standardized clinically useful report that should be considered by companies developing connected pen technology as part of their system reporting/output.

The european registry for patients with mechanical circulatory support (EUROMACS): fourth paediatric EUROMACS (Paedi-EUROMACS) report.

OBJECTIVES: The use of ventricular assist devices in children is increasing. However, absolute numbers in individual centers and countries remain small. Collaborative efforts such as the Paedi-EUROMACS are therefore essential in order to combine international experience with paediatric ventricular assist devices. In this paper, the results from the fourth Paedi-EUROMACS report are presented. METHODS: All paediatric (<19 years) patients supported by a ventricular assist device from the EUROMACS database were included. Patients are stratified into a congenital heart disease group and a group with a non-congenital aetiology. Endpoints included mortality, transplantation and recovery. Cox proportional hazard models were used to explore associated factors for mortality, cerebrovascular accident, and pump thrombosis. RESULTS: 590 primary implantations were included. The congenital group was significantly younger (2.5 versus 8.0 years respectively, p < 0.001) and were more commonly supported by a pulsatile flow device (73.5% vs 59.9%, p < 0.001). Mortality was significantly higher in the congenital group (30.8 vs 20.4%; p = 0.009) than in the non-congenital group. However, in multivariable analyses, congenital heart disease was not significantly associated with mortality (HR 1.285, CI 0.8111-2.036, p = 0.740). Pump thrombosis was the most frequently reported adverse event (377 events in 132 patients; 0.925 events per patient-year) and was significantly associated with BSA (HR 0.524 CI 0.333-0.823, p = 0.005), congenital heart disease (HR 1.641 CI 1.054-2.555, p = 0.028) and pulsatile flow support (HR 2.345 CI 1.406-3.910, p = 0.001) in multivariable analyses. CONCLUSIONS: This fourth Paedi-EUROMACS report highlights the increasing use of paediatric ventricular assist devices. The patient populations with congenital and non-congenital aetiology exhibit distinct characteristics and clinical outcomes.

Correlation of dual colour single particle trajectories for improved detection and analysis of interactions in living cells.

Interactions between objects inside living cells are often investigated by looking for colocalization between fluorescence microscopy images that are recorded in separate colours corresponding to the fluorescent label of each object. The fundamental limitation of this approach in the case of dynamic objects is that coincidental colocalization cannot be distinguished from true interaction. Instead, correlation between motion trajectories obtained by dual colour single particle tracking provides a much stronger indication of interaction. However, frequently occurring phenomena in living cells, such as immobile phases or transient interactions, can limit the correlation to small parts of the trajectories. The method presented here, developed for the detection of interaction, is based on the correlation inside a window that is scanned along the trajectories, covering different subsets of the positions. This scanning window method was validated by simulations and, as an experimental proof of concept, it was applied to the investigation of the intracellular trafficking of polymeric gene complexes by endosomes in living retinal pigment epithelium cells, which is of interest to ocular gene therapy.

Failure of Tricuspid Annuloplasty for Functional Tricuspid Regurgitation: Impact of Patient's Body Size.

Tricuspid repair is recommended for significant functional tricuspid regurgitation (FTR) or tricuspid annulus (TA) dilation, based on TA >40 mm or >21 mm/m². The concordance between both TA dimensions related to the patient's body size has not been investigated. Patients who underwent rigid ring tricuspid annuloplasty for FTR between 2009 and 2017 were included. Assuming equality between both TA diameter criteria, patients were divided per body surface area (BSA): group 1 = BSA ≤1.9 m² and group 2 = BSA >1.9 m². The primary outcome was TR recurrence at 5 years. Tricuspid annuloplasty was performed in 186 patients (group 1: 130 patients [69.9%]; group 2: 56 patients [30.1%]). Group 1 comprised more female (70.8% to 23.2%, p <0.001) and older patients (77.1 ± 9.3 years; 74.2 ± 8.2 years, p = 0.048). Group 1 had a smaller absolute TA diameter (group 1: 45.3 ± 5.2 mm; group 2: 48.2 ± 5.6 mm, p <0.001), whereas the indexed TA size was inversely higher (group 1: 26.3 ± 3.4 mm/m²; group 2: 24.2 ± 2.7 mm/m², p <0.001). The tenting height was comparable (group 1: 7.8 ± 3.0 mm; group 2: 8.0 ± 2.7 mm, p = 0.714). The median ring size was 30 (interquartile range 28 to 32) and 32 (interquartile range 30 to 34) for groups 1 and 2, respectively (p <0.001). TR recurrence at 5 years was noticed in 20.2% and 6.5% of group 1 and 2 (p = 0.035). Indexed TA diameter (hazard ratio 1.43, 95% confidence interval 1.10 to 1.87, p = 0.008) and tenting height (hazard ratio 5.52, 95% confidence interval 1.87 to 14.57, p = 0.002) were independent predictors of TR recurrence. In conclusion, when the absolute TA diameter is used as the primary criterion, smaller patients are at a higher risk for TR recurrence by having a proportionally larger TA at the time of repair. An individualized approach guided by patient's body size might be more appropriate to indicate FTR correction to adjust for the annuloplasty sizing method.

Anterior and posterior tracheopexy for severe tracheomalacia.

Objectives: Congenital tracheomalacia can be the cause of respiratory failure in young children. Although the indication for surgical treatment has already been discussed vigorously, no clear guidelines about the modality are available. Methods: Through a sternotomy approach, a combination of posterior pexy and anterior tracheopexy using a tailored ringed polytetrafluoroethylene prosthesis is performed. Patient demographic characteristics, as well as operative details and postoperative outcomes, are included in the analysis. Results: Between 2018 and 2022, 9 children underwent the operation under review. All patients showed severe clinical symptoms of tracheomalacia, which was confirmed on bronchoscopy. The median age was 9 months. There was no operative mortality. Eight patients could be weaned from the ventilator. One patient died because of interstitial lung disease with bronchomalacia and concomitant severe cardiac disease. The longest follow-up now is 4 years, and shows overall excellent clinical results, without any reintervention. Conclusions: Surgical treatment of tracheomalacia through a combination of posterior and anterior pexy is feasible, with acceptable short- and midterm results.