Comparison of international height and BMI-for-age growth references and their correlation with adiposity in Brazilian schoolchildren.

This study verified the diagnostic accuracy of the nutritional status classified by the international height and BMI references of the World Health Organization (WHO) (WHO/2007), International Obesity Task Force (IOTF/2012) and MULT (2023). The data pool was composed by 22 737 subjects aged five to 16 years from the Santos and Porto Alegre surveys. A correlation matrix between the z-scores of the BMI references and the skinfold measurements was calculated through the Pearson correlation coefficient (r), and the subject's nutritional status was classified according to the international growth references. The accuracy for diagnosing obesity was performed separately by sex and using the 95th percentile of the triceps and subscapular skinfold sum, while Lin's concordance coefficient, Bland-Altman method and the Cohen's Kappa coefficient (Kappa) were used to verify the concordance and reliability among the BMI references. The correlation matrix showed a high positive correlation among the BMI z-scores (r ≥ 0·99) and among the skinfold measurements (r ≥ 0·86). The prevalence of stunting was higher when applying the MULT reference (3·4 %) compared with the WHO reference (2·3 %). The Bland-Altman plots showed the lowest critical difference (CD) between the height references of WHO and MULT (CD = 0·22). Among the BMI references, the WHO obesity percentile presented lower performance than MULT for boys, presenting a lower +LR value (WHO = 6·99/MULT 18 years = 10·99; 19 years = 8·99; 20 years = 8·09) for the same -LR values (0·04). Therefore, MULT reference holds promise as a valuable tool for diagnosing childhood obesity, particularly when considering sex differences. This enhances its suitability for assessing the nutritional status of Brazilian schoolchildren.

Isolated massive histiocytes renal interstitial infiltration: a case report of an unexpected cause of acute kidney injury in a kidney transplant recipient.

BACKGROUND: Acute kidney injury is a frequent cause of hospital readmission in kidney transplant recipients (KTR), usually associated with infections and graft rejection. Herein, we report a case of an unusual cause of acute kidney injury in a KTR (massive histiocytes renal interstitial infiltration). CASE PRESENTATION: A 40-year-old woman was submitted to a second kidney transplant. One year after surgery, she presented asthenia, myalgia, and fever, haemoglobin 6.1 g/dL; neutrophils: 1.3 × 109/µL; platelets: 143 × 109/µL; blood creatinine 11.8 mg/dL, requiring dialysis. A kidney biopsy revealed diffuse histiocytic infiltration, which was assumed due to dysregulated immunological activation triggered by infections. The patient had multiple infections, including cytomegalovirus infection (CMV), aspergillosis, bacteraemia, and urinary tract infections, which could trigger the immune response. Haemophagocytic lymphohistiocytosis (HLH) was ruled out. The present case highlights the occurrence of isolated massive renal interstitial infiltration of histiocytes that does not meet the criteria for HLH or other related pathologies. CONCLUSIONS: Renal histiocyte activation and infiltration may have been initiated by an immunological mechanism similar to what occurs in HLH and infectious processes. The present case highlights the occurrence of isolated massive renal interstitial infiltration of histiocytes that does not meet the criteria for HLH or other related pathologies.

Validity of the relative fat mass pediatric index (RFMp) for the analysis of body composition in physically active youths at different stages of biological maturation.

BACKGROUND: The paediatric relative fat mass (RFMp) index was valid for analysis of percent body fat (BF%). However, the validation did not consider biological maturation (BM) stages. The present study aimed to verify the validity of the RFMp index in the estimation of BF% in children and adolescents of both sexes at different stages of BM. METHODS: A cross-sectional study was conducted with a sample of 146 young (males: 64.5%. females: 35.5%. age: 13.0 ± 2.2 years) practising sports modalities. We tested the validity of four RFMp equations (1: for boys aged 8-14 years; 2: for girls aged 8-14 years; 3: for both sexes aged 8-14 years; and 4: for both sexes aged 15-19 years) to analyse BF% using dual-energy X-ray absorptiometry as a reference method. BM was analysed by peak height velocity (PHV). Thus, we created subgroups by BM stage (pre-PHV, circum-PHV and post-PHV). RESULTS: Analyses of agreement between methods showed that only the RFMp-3 equation was reliable to analyse BF% in subjects of both sexes aged 8-14 years at the circum-PHV BM stage (proportion bias 95% confidence interval = -0.3 to 0.5, p = 0.7. concordance correlation coefficient = 0.3; validity = 0.9). CONCLUSIONS: The RFMp equation developed for the paediatric population of both sexes aged 8-14 years was valid for predicting BF% in children and adolescents of both sexes at the Circum-PHV stage of the BM.

Extruded urea levels in lamb supplementation in rainy tropical savanna conditions: the triad host-gastrointestinal nematodes-environment.

The objective of this study was to evaluate the influence of increasing levels of extruded urea (EU, Amireia®) in the diet of lambs naturally infected by gastrointestinal nematodes on the interactions in the host-pasture-soil components in edaphoclimatic conditions of the tropical rainy savanna. A total of 60 Texel lambs with a mean initial weight of 20.7 ± 0.87 and mean age of 2.5 ± 0.70 months were distributed in a completely randomized design, in five treatments consisting of different levels of EU supplementation viz., 0, 6, 12, 18, and 24 g 100 kg-1 live weight (LW). The performance of lambs, parasitological variables, gastrointestinal nematodes (NGIs), and larvae recovery in pasture and soil were evaluated. The highest animal performance was observed in animals that received 0 to 18 g kg-1 LW (146.0 g day-1) and the lowest in animals supplemented with 24 g kg-1 LW (81.0 g day-1) of EU. The body condition score (BCS) was similar in the animals (P > 0.05). Parasitic infection did not differ as a function of EU level (P > 0.05). Eggs of Haemonchus spp., Trichostrongylus spp., Cooperia spp., and Oesophagostomum spp. were found. The largest amount of larvae in the L1/L2 and L3 stages was recovered in the pastures occupied by the animals that received supplementation 0 g kg-1 LW of EU (750 larvae), the smallest in those that the animals received 6 g 100 kg-1 LW of EU (54 larvae). The presence of larvae in the L1/L2 stages changed significantly (P < 0.05) in the soil; in the other stages, it did not differ in the soil. Increasing levels of extruded urea do not influence the eggs per gram of feces (EPG) count. The 0 to 18 g 100 kg-1 LW level maintains animal performance, BCS and FAMACHA©. There is less dispersal of NGI larvae in pasture and soil when EU levels increase in the edaphoclimatic conditions of the rainy tropical savannah, which suggests that this supplement can be implemented in the diet of beef lambs, in addition to to be a lower cost nitrogen source.

A transcriptional and post-transcriptional dysregulation of Dishevelled 1 and 2 underlies the Wnt signaling impairment in type I Gaucher disease experimental models.

Bone differentiation defects have been recently tied to Wnt signaling alterations occurring in vitro and in vivo Gaucher disease (GD) models. In this work, we provide evidence that the Wnt signaling multi-domain intracellular transducers Dishevelled 1 and 2 (DVL1 and DVL2) may be potential upstream targets of impaired beta glucosidase (GBA1) activity by showing their misexpression in different type 1 GD in vitro models. We also show that in Gba mutant fish a miR-221 upregulation is associated with reduced dvl2 expression levels and that in type I Gaucher patients single-nucleotide variants in the DVL2 3' untranslated region are related to variable canonical Wnt pathway activity. Thus, we strengthen the recently outlined relation between bone differentiation defects and Wnt/ß-catenin dysregulation in type I GD and further propose novel mechanistic insights of the Wnt pathway impairment caused by glucocerebrosidase loss of function.

Clinical characteristics and thyroid function in complete hydatidiform mole complicated by hyperthyroidism.

OBJECTIVES: To identify possible clinical factors associated with hyperthyroidism at presentation and to assess post-evacuation thyroid function in women with complete hydatidiform mole (CHM). METHODS: This observational study included women with CHM attending a specialized Brazilian center in 2002-2018. Clinical and laboratory data (serum hCG, TSH, fT4) were collected at presentation. Factors associated with hyperthyroidism were assessed by logistic regression. Receiver-operating characteristic curves were built to determine the hCG cutoff for predicting hyperthyroidism at CHM presentation. Post-molar evacuation follow-up included clinical assessment and close thyroid function monitoring. RESULTS: Of 137 CHM patients, 69 (50.3%) had hyperthyroidism of any type (43.5% subclinical, 56.5% overt) at presentation. Uterine fundal height > 16 cm or > gestational age (GA), and theca lutein cysts >6 cm were significantly associated with both subclinical and overt hyperthyroidism. The optimal hCG cutoff for predicting hyperthyroidism was 430,559 IU/L (sensitivity 85.5%, specificity 83.8%). Post-evacuation hyperthyroidism/transient hypothyroidism conversion was observed in 13% of the women with hyperthyroidism at presentation. Among the patients not showing conversion to hypothyroidism, median time for TSH normalization was 2 and 3 weeks for subclinical and overt hyperthyroidism, respectively. In the women with overt hyperthyroidism, fT4 was normalized at 2 weeks. CONCLUSIONS: Uterine fundal height > 16 cm, uterine fundal height > GA, theca lutein cysts >6 cm, and hCG >400,000 IU/L at presentation are associated with greater risk of hyperthyroidism and its complications. Close monitoring thyroid function during postmolar follow-up showed that, as thyroid hormones are normalized within 2-3 weeks post-evacuation, the use of beta-blockers or antithyroid drugs can be rapidly discontinued.

Body adiposity index to analyze the percentage of fat in young men aged between 7 and 17 years.

BACKGROUND: The body adiposity index (BAI), uses anthropometry to estimate percent body fat (%F). However, previous studies have shown that the BAI has limited accuracy for children and adolescents. OBJECTIVE: We propose to develop and validate an adjusted BAI for use in male children and adolescents from 7 to 17 years of age. METHODS: The sample consisted of 141 physically active male children and adolescents (age: 12.5 ± 2.14). The %F was determined by X-ray dual energy absorptometry equipment (DXA) as the standard method and by BAI, using an equation that uses height and hip circumference. Arithmetic modeling was used to adjust the structure of the BAI mathematical model. RESULTS: The BAI arithmetic adjustment was successful, resulting in the mathematical model named in the present study of adjusted body adiposity index (BAIADJ ). BAI and BAIADJ correlated with DXA (r ≤ .70, p < .001). Regression analyzes indicate that, BAI (CI 95% ß: [1.35; 1.90], p < .0001) and BAIADJ (CI 95% ß: [1.40; 1.90], p < .0001) have the potential to estimate %F. BAI pointed out a difference in relation to DXA (p = .04). While there was no difference between BAIADJ and DXA (p = .1). There was a proportion bias of 13.2% for BAI (p < .05), but not for BAIADJ (p > .05). CONCLUSION: The adjusted model of the body adiposity index proves to be an effective tool for the analysis of the fat percentage in young males. In addition, it demonstrated significant degrees of agreement and validity in relation to DXA.

Calcitriol Reduces the Inflammation, Endothelial Damage and Oxidative Stress in AKI Caused by Cisplatin.

Cisplatin treatment is one of the most commonly used treatments for patients with cancer. However, thirty percent of patients treated with cisplatin develop acute kidney injury (AKI). Several studies have demonstrated the effect of bioactive vitamin D or calcitriol on the inflammatory process and endothelial injury, essential events that contribute to changes in renal function and structure caused by cisplatin (CP). This study explored the effects of calcitriol administration on proximal tubular injury, oxidative stress, inflammation and vascular injury observed in CP-induced AKI. Male Wistar Hannover rats were pretreated with calcitriol (6 ng/day) or vehicle (0.9% NaCl). The treatment started two weeks before i.p. administration of CP or saline and was maintained for another five days after the injections. On the fifth day after the injections, urine, plasma and renal tissue samples were collected to evaluate renal function and structure. The animals of the CP group had increased plasma levels of creatinine and of fractional sodium excretion and decreased glomerular filtration rates. These changes were associated with intense tubular injury, endothelial damage, reductions in antioxidant enzymes and an inflammatory process observed in the renal outer medulla of the animals from this group. These changes were attenuated by treatment with calcitriol, which reduced the inflammation and increased the expression of vascular regeneration markers and antioxidant enzymes.

Effect of Microencapsulation on Chemical Composition and Antimicrobial, Antioxidant and Cytotoxic Properties of Lemongrass (Cymbopogon flexuosus) Essential Oil.

Research background: Lemongrass (Cymbopogon flexuosus) essential oil exhibits antimicrobial and antioxidant properties due to the presence of α-citral and ß-citral. Essential oils are susceptible to volatilization and oxidation when applied to food matrices. Therefore, a barrier is needed to protect this material. The present study aims to produce microparticles containing lemongrass essential oil, with gum arabic and maltodextrin using spray drying technology. Experimental approach: Lemongrass essential oil was extracted by the hydrodistillation method and later microencapsulated with different wall materials. Free and microencapsulated lemongrass essential oil was evaluated for the cytotoxic activity (using Artemia salina as test sample), chemical composition (GC-MS), encapsulation efficiency, antioxidant activity (DPPH, ABTS and FRAP), antimicrobial activity and minimum inhibitory concentration. Results and conclusions: The lethal concentration (LC50) of lemongrass essential oil in the cytotoxic test was 8.43 µg/mL against Artemia salina; a high activity that can be associated with the presence of α-citral (~33%) and ß-citral (~21%) in the samples, since these were the main compounds with bioactive properties. The highest value of microencapsulation efficiency (88.11%) was obtained when only gum arabic was used as wall material. In general, the microparticles showed satisfactory antioxidant activity (expressed as Trolox equivalents, between 348.66 and 2042.30 µmol/100 g) and bactericidal effect in vitro against Gram-positive and Gram-negative microorganisms. In conclusion, the microencapsulated lemongrass essential oil is a promising functional additive in the food and pharmaceutical industries. Novelty and scientific contribution: This study shows that microparticles containing lemongrass essential oil can be prepared using gum arabic and maltodextrin as wall materials by spray drying, resulting in high microencapsulation efficiency. The drying process maintained the antimicrobial and antioxidant properties of the essential oil. Therefore, the microencapsulated lemongrass essential oil is considered a natural, functional and promising additive in the food industry. Its antimicrobial action can increase the shelf life of fresh and semi-fresh products such as cheese, yogurts and meat products. In addition, its antioxidant action can delay the lipid and protein oxidation in food products.

Performance and ruminal and intestinal morphometry of Santa Inês sheep submitted to feed restriction and refeeding.

A study was carried out to evaluate the performance and ruminal and intestinal morphology of Santa Inês sheep subjected to feed restriction followed by refeeding. A total of 40 uncastrated lambs with an approximate age of 120 ± 15 days and mean body weight (BW) of 17.04 ± 1.18 kg were randomly divided into two groups of BW (20 and 25 kg of BW), which were subjected to different levels of feed restriction (0%, 25%, and 40% of feed restriction). For performance variables, six treatments were considered (0, 25%, and 40% of feed restriction for both groups (20 and 25 kg of BW)) and five treatments for morphometric variables (ad libitum, 25% and 40% for both groups (20 and 25 kg of BW)). All animals were slaughtered with 14 weeks of experimentation. During the feed restriction phase, the dry matter intake (DMI), feed efficiency (FE), and average daily gain (ADG) decreased (P < 0.05) as the level of restriction increased. During the refeeding phase, lambs with 20 kg of body weight subjected to restriction presented lower (P < 0.05) DMI in the ad libitum treatment. However, lambs with 25 kg of body weight under feed restriction presented DMI, FE, and ADG similar (P > 0.05) to the group ad libitum. The final body weight of restricted lambs after refeeding (both groups 20 and 25 kg of body weight) was lower (P < 0.05) than lambs feed ad libitum. In relation to morphology, restricted lambs showed greater height ruminal papillae and larger (P < 0.05) area of ruminal absorption and intestinal absorption, especially the lambs under treatment 40% of feed restriction. The feed restriction followed by refeeding in sheep provided partial compensatory gain, in addition, caused morphological changes in the rumen and intestine that allowed greater absorption and possibly compensatory gain in periods of greater refeeding.

Current practice in transvenous lead extraction in Latin America: Latin American Heart Rhythm Association survey.

BACKGROUND: Transvenous lead extraction (TLE) is standard of care for the management of patients with cardiac implantable electronic device infection or lead-related complications. Currently, objective data on TLE in Latin America is lacking. OBJECTIVE: To describe the current practice standards in Latin American centers performing TLE. METHODS: An online survey was sent through the mailing list of the Latin American Heart Rhythm Society. Online reminders were sent through the mailing list; duplicate answers were discarded. The survey was available for 1 month, after which no more answers were accepted. RESULTS: A total of 48 answers were received, from 44 different institutions (39.6% from Colombia, 27.1% from Brazil), with most respondents (82%) being electrophysiologists. Twenty-nine institutions (66%) performed <10 lead extractions/year, with 7 (16%) institutions not performing lead extraction. Although most institutions in which lead extraction is performed reported using several tools, mechanical rotating sheaths were cited as the main tool (66%) and only 13% reported the use of laser sheaths. Management of infected leads was performed according to current guidelines. CONCLUSION: This survey is the first attempt to provide information on TLE procedures in Latin America and could provide useful information for future prospective registries. According to our results, the number of centers performing high volume lead extraction in Latin America is smaller than that reported in other continents, with most interventions performed using mechanical tools. Future prospective registries assessing acute and long-term success are needed.

Mitochondrial dysfunction interferes with neural crest specification through the FoxD3 transcription factor.

The neural crest is an important group of cells with pluripotency and migratory ability that is crucially involved in tissue and cell specification during development. Craniofacial shaping, sensory neurons, body asymmetry, and pigmentation are linked to neural crest functionality. Despite its prominent role in embryogenesis, neural crest specification as well as the possible part mitochondria play in such a process remains unclarified. Mitochondria are important organelles not only for respiration, but also for regulation of cell proliferation, differentiation and death. Modulation of mitochondrial fitness and depletion of mitochondrial ATP synthesis has been shown to down-regulate Wnt signaling, both in vitro and in vivo. Since Wnt signaling is one of the crucial players during neural crest induction/specification, we hypothesized a signaling cascade connecting mitochondria to embryonic development and neural crest migration and differentiation. Here, by using pharmacological and genetic modulators of mitochondrial function, we provide evidence that a crosstalk between mitochondrial energy homeostasis and Wnt signaling is important in the development of neural crest-derived tissues. Furthermore, our results highlight the possibility to modulate neural crest cell specification by tuning mitochondrial metabolism via FoxD3, an important transcription factor that is regulated by Wnt. FoxD3 ensures the correct embryonic development and contributes to the maintenance of cell stemness and to the induction of epithelial-to-mesenchymal transition. In summary, our work offers new insights into the molecular mechanism of action of FoxD3 and demonstrates that mitochondrial fitness is linked to the regulation of this important transcription factor via Wnt signaling in the context of neural crest specification.

European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections-endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS), International Society for Cardiovascular Infectious Diseases (ISCVID), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS).

Pacemakers, implantable cardiac defibrillators, and cardiac resynchronization therapy devices are potentially lifesaving treatments for a number of cardiac conditions but are not without risk. Most concerning is the risk of a cardiac implantable electronic device (CIED) infection, which is associated with significant morbidity, increased hospitalizations, reduced survival, and increased health care costs. Recommended preventive strategies such as administration of intravenous antibiotics before implantation are well-recognized. Uncertainties have remained about the role of various preventive, diagnostic, and treatment measures such as skin antiseptics, pocket antibiotic solutions, antibacterial envelopes, prolonged antibiotics post-implantation, and others. When compared with previous guidelines or consensus statements, the present consensus document gives guidance on the use of novel device alternatives, novel oral anticoagulants, antibacterial envelopes, prolonged antibiotics post-implantation, as well as definitions on minimum quality requirements for centres and operators and volumes. The recognition that an international consensus document focused on management of CIED infections is lacking, the dissemination of results from new important randomized trials focusing on prevention of CIED infections, and observed divergences in managing device-related infections as found in an European Heart Rhythm Association worldwide survey, provided a strong incentive for a Novel 2019 International State-of-the-art Consensus document on risk assessment, prevention, diagnosis, and treatment of CIED infections.

From Channels to Canonical Wnt Signaling: A Pathological Perspective.

Wnt signaling is an important pathway mainly active during embryonic development and controlling cell proliferation. This regulatory pathway is aberrantly activated in several human diseases. Ion channels are known modulators of several important cellular functions ranging from the tuning of the membrane potential to modulation of intracellular pathways, in particular the influence of ion channels in Wnt signaling regulation has been widely investigated. This review will discuss the known links between ion channels and canonical Wnt signaling, focusing on their possible roles in human metabolic diseases, neurological disorders, and cancer.

FGF signaling deregulation is associated with early developmental skeletal defects in animal models for mucopolysaccharidosis type II (MPSII).

Skeletal abnormalities represent a major clinical burden in patients affected by the lysosomal storage disorder mucopolysaccharidosis type II (MPSII, OMIM #309900). While extensive research has emphasized the detrimental role of stored glycosaminoglycans (GAGs) in the bone marrow (BM), a limited understanding of primary cellular mechanisms underlying bone defects in MPSII has hampered the development of bone-targeted therapeutic strategies beyond enzyme replacement therapy (ERT). We here investigated the involvement of key signaling pathways related to the loss of iduronate-2-sulfatase activity in two different MPSII animal models, D. rerio and M. musculus. We found that FGF pathway activity is impaired during early stages of bone development in IDS knockout mice and in a newly generated Ids mutant fish. In both models the FGF signaling deregulation anticipated a slow but progressive defect in bone differentiation, regardless of any extensive GAGs storage. We also show that MPSII patient fibroblasts harboring different mutations spanning the IDS gene exhibit perturbed FGF signaling-related markers expression. Our work opens a new venue to discover possible druggable novel key targets in MPSII.

When mechanical work meets energetics: Obese versus non-obese children walking.

NEW FINDINGS: What is the central question of this study? The aim was to compare the cost of transport and mechanical work between obese and non-obese children at different walking speeds. What is the main finding and its importance? Our data show that the cost of transport, mechanical efficiency and work are similar and directly mass dependent in obese and non-obese children. The optimal walking speed (most economical walking speed) is reduced in obese children. ABSTRACT: Although studies have shown the influence of gait biomechanics on the metabolic economy in obese adults and adolescents, little is known regarding obese children. We compared the metabolic cost of transport, apparent mechanical efficiency and gait biomechanics (assessed by mechanical energy fluctuations) in obese children (n = 12; mean ± SD: 8.6 ± 0.51 years of age, 1.38 ± 0.04 m, 44.6 ± 6.65 kg, 24.1 ± 3.50 kg m-2 ) and age- and sex-matched non-obese children (n = 12, 7.8 ± 0.90 years of age, 1.31 ± 0.08 m, 26.8 ± 2.24 kg, 16.4 ± 1.40 kg m-2 ) while walking at different speeds (from 1 to 5 km h-1 ) on a treadmill. We found that the mechanical efficiency was higher at 3 km h-1 compared with the remaining speeds for both groups (P < 0.05). Although the internal mechanical work has been greater in obese compared with non-obese children at 4 and 5 km h-1 , the external, total mechanical work and the mechanical efficiency remained similar between obese and non-obese children at all speeds. Likewise, the cost of transport was similar in the two groups, although the optimal walking speed was an average of 0.4 km h-1 slower in obese children. Clearly, these results show that the walking economy is associated with the total mechanical work in obese and non-obese children. Finally, the reduced functional mobility in obese children observed in previous studies seems to be associated with a reduction in optimal walking speed in comparison to non-obese children.

European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections-endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS), International Society for Cardiovascular Infectious Diseases (ISCVID) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS).

Pacemakers, implantable cardiac defibrillators, and cardiac resynchronization therapy devices are potentially life-saving treatments for a number of cardiac conditions, but are not without risk. Most concerning is the risk of a cardiac implantable electronic device (CIED) infection, which is associated with significant morbidity, increased hospitalizations, reduced survival, and increased healthcare costs. Recommended preventive strategies such as administration of intravenous antibiotics before implantation are well recognized. Uncertainties have remained about the role of various preventive, diagnostic, and treatment measures such as skin antiseptics, pocket antibiotic solutions, anti-bacterial envelopes, prolonged antibiotics post-implantation, and others. Guidance on whether to use novel device alternatives expected to be less prone to infections and novel oral anticoagulants is also limited, as are definitions on minimum quality requirements for centres and operators and volumes. Moreover, an international consensus document on management of CIED infections is lacking. The recognition of these issues, the dissemination of results from important randomized trials focusing on prevention of CIED infections, and observed divergences in managing device-related infections as found in an European Heart Rhythm Association worldwide survey, provided a strong incentive for a 2019 International State-of-the-art Consensus document on risk assessment, prevention, diagnosis, and treatment of CIED infections.

Upper extremity deep venous thrombosis and pulmonary embolism after transvenous lead replacement or upgrade procedures.

BACKGROUND: Venous obstructions are frequent in patients with transvenous leads, although related clinical findings are rarely reported. After lead replacement or upgrade procedures, these lesions are even more frequent, but there is still no evidence to support this observation. AIM: To investigate the incidence and possible risk factors for upper extremity deep venous thrombosis (UEDVT) and pulmonary embolism (PE) after lead replacement or upgrade procedures. METHODS: Prospective cohort carried out between April 2013 and July 2016. Preoperative evaluation included venous ultrasound and pulmonary angiotomography. Diagnostic exams were repeated postoperatively to detect the study outcomes. Multivariate logistic regression models were used to identify prognostic factors. RESULTS: Among the 84 patients included, 44 (52.4%) were female and mean age was 59.3 ± 15.2 years. Lead malfunctioning (75.0%) was the main surgical procedure indication. Lead removal was performed in 44 (52.4%) cases. The rate of postoperative combined events was 32.6%, with 24 (28.6%) cases of UEDVT and six (7.1%) cases of PE. Clinical manifestations of deep venous thrombosis occurred in 10 (11.9%) patients. Independent prognostic factors for UEDVT were severe collateral circulation in the preoperative venography (odds ratio [OR] 4.7; 95% confidence interval [CI] 1.1-19.8; P = .037) and transvenous lead extraction (OR 27.4; 95% CI 5.8-128.8; P < .0001). CONCLUSION: Reoperations involving previously implanted transvenous leads present high rates of thromboembolic complications. Transvenous lead extraction had a significant impact on the development of UEDVT. These results show the need of further studies to evaluate the role of preventive strategies for this subgroup of patients.

Perturbations in cell signaling elicit early cardiac defects in mucopolysaccharidosis type II.

Morphogens release and activity can be negatively affected by an impaired glycosaminoglycans (GAGs) turnover and proteoglycans assembly in the extracellular matrix, leading to altered tissue morphogenesis. In this work, we show that loss of Iduronate-2-sulfatase (IDS) activity, affecting GAGs catabolism and responsible for a life-threatening valvulopathy in mucopolysaccharidosis type II (MPSII), triggers early Sonic Hedgehog (Shh) and Wnt/ß-catenin signaling defects, leading to aberrant heart development and atrioventricular valve formation in a zebrafish model. In addition, we consistently found impaired Shh signaling activity and cardiac electrophysiological abnormalities in IDS knockout mice at postnatal stages before any evident massive GAGs accumulation. These results suggest that IDS activity substantially affect cardiac morphogenesis through impaired Shh signaling and document an unexplored role of the enzyme in the fine-tuning of cell signaling pathways.

Clinical practice and implementation of guidelines for the prevention, diagnosis and management of cardiac implantable electronic device infections: results of a worldwide survey under the auspices of the European Heart Rhythm Association.

AIMS: Cardiac implantable electronic device (CIED) infection rates are increasing. Worldwide compliance and disparities to published guidelines for the prevention, diagnosis and management of these conditions are not well elucidated. The purpose of this survey, therefore, was to clarify these issues through an inquiry to arrhythmia-related associations and societies worldwide. METHODS AND RESULTS: A questionnaire comprising 15 questions related to CIED infections was distributed among members of seven arrhythmia societies worldwide. A total of 234 centres in 62 countries reported implantation rates of which 159 (68.0%) performed more than 200 device implantations per year and 14 (6.0%) performed fewer than 50 implantations per year. The reported rates of CIED infections for 2017 were ≤2% in 78.7% of the centres, while the infection rates exceeded 5% in 7.8% of the centres. Preventive measures for CIED infection differed from published recommendations and varied among different regions mainly in terms of pocket irrigation and administering post-operative antimicrobial therapy the use of which was reported by 39.9% and 44% of the respondents, respectively. Antibacterial envelopes were used by 37.7% of the respondents in selected circumstances. In terms of pocket infection management, 62% of the respondents applied complete system removal as an initial step. Diagnostic pocket needle aspiration and pocket surgical debridement were reported by 15.8% and 11.8% of centres, respectively. CONCLUSION: Clinical practices for prevention and management of CIED do not fully comply with current recommendations and demonstrate considerable regional disparities. Further education and programmes for improved implementation of guidelines are mandatory.