Polymeric nanocapsules: A review on design and production methods for pharmaceutical purpose.

Polymeric nanocapsules have extensive application potential in medical, biological, and pharmaceutical fields, and, therefore, much research has been dedicated to their production. Indeed, production protocols and the materials used are decisive for obtaining the desired nanocapsules characteristics and biological performance. In addition to that, several technological strategies have been developed in the last decade to improve processing techniques and form more valuable nanocapsules. This review provides a guide to current methods for developing polymeric nanocapsules, reporting aspects to be considered when choosing appropriate materials, and discussing different ways to produce nanocapsules for superior performances.

Chironomus sancticaroli (Diptera: Chironomidae) in ecotoxicology: laboratory cultures and tests.

Chironomus sancticaroli is a tropical species, easy to grow and to maintain in laboratory cultures. It has a fast reproduction cycle, under adequate conditions, around 30 days, allowing it to have many generations per year, an important criterion for selecting a test organism in ecotoxicology. Its life stages include: eggs, four larval instars (one planktonic and three benthic), pupa and adult (midges) This study aimed to: (1) review the methods for C. sancticaroli cultivation and its use in ecotoxicological tests, (2) establish a laboratory culture of C. sancticaroli, presenting the difficulties and discussing the ways to overcome them. Early 4th instar larvae was the most used in acute studies, while the 1st instar larvae (early 1st instar) was the most used in chronic studies; 96 h and 28 days were the most frequent durations in acute and chronic studies, respectively. The most common endpoints evaluated were organisms' survival and development, and most of the ecotoxicological studies using C. sancticaroli were performed in laboratory. Most of the tested contaminants were pesticides and these had the most adverse effects on organisms. Most mesocosms with environmental contaminated samples did not show adverse effects on C. sancticaroli. Chronic and field studies as well as those testing the effects of the mixture contaminants on C. sancticaroli were still deficient. Keeping the laboratory environment and equipment effectively sanitized was important as well as maintaining stabilized conditions of temperature, photoperiod, physical, chemical and biological water quality in cultures.

Preformulation Studies to Guide the Production of Medicines by Fused Deposition Modeling 3D Printing.

Fused deposition modeling (FDM) 3D printing has demonstrated high potential for the production of personalized medicines. However, the heating at high temperatures inherent to this process causes unknown risks to the drug product's stability. The present study aimed to assess the use of a tailored preformulation protocol involving physicochemical assessments, including the rheological profiles of the samples, to guide the development of medicines by FDM 3D printing. For this, polymers commonly used in FDM printing, i.e., high impact polystyrene (HIPS), polylactic acid (PLA), and polyvinyl alcohol (PVA), and their common plasticizers (mineral oil, triethyl citrate, and glycerol, respectively) were evaluated using the thermolabile model drug isoniazid (INH). Samples were analyzed by chemical and physical assays. The results showed that although the drug could produce polymorphs under thermal processing, the polymeric matrix can be a protective element, and no polymorphic transformation was observed. However, incompatibilities between materials might impact their chemical, thermal, and rheological performances. In fact, ternary mixtures of INH, PLA, and TEC showed a major alteration in their viscoelastic behavior besides the chemical changes. On the other hand, the use of plasticizers for HIPS and PVA exhibited positive consequences in drug solubility and rheologic behavior, probably improving sample printability. Thus, the optimization of the FDM 3D printing based on preformulation studies can assist the choice of compatible components and seek suitable processing conditions to obtain pharmaceutical products.

Light and Laser Modalities in the Treatment of Cutaneous Sarcoidosis: A Systematic Review.

Sarcoidosis is a systemic non-caseating granulomatous disease of unknown aetiology. Cutaneous manifestations are present in approximately 10-30% of the patients with the systemic form. Therapy is indicated in case of disabling symptoms, organ dysfunction or cosmetically distressing manifestation. Despite different therapeutic possibilities, cutaneous sarcoidosis remains exceptionally difficult to treat. Light and laser therapy may be a promising alternative. In this systematic review, we summarised the available treatments according to the literature concerning light and laser therapy for cutaneous sarcoidosis. Publications written in English and German, published between January 1990 and July 2016 in the database PubMed, MEDLINE, Embase, and Scopus were analysed. Light therapy with intense pulsed light, photodynamic therapy, and ultraviolet A light therapy, as well as laser therapy with pulsed dye laser, YAG laser, and Q-switched ruby laser were described. The results are based on individual case reports and small case series. Randomised controlled studies are lacking.

The role of artificial intelligence and data science in nanoparticles development: a review.

Artificial intelligence has revolutionized many sectors with unparalleled predictive capabilities supported by machine learning (ML). So far, this tool has not been able to provide the same level of development in pharmaceutical nanotechnology. This review discusses the current data science methodologies related to polymeric drug-loaded nanoparticle production from an innovative multidisciplinary perspective while considering the strictest data science practices. Several methodological and data interpretation flaws were identified by analyzing the few qualified ML studies. Most issues lie in following appropriate analysis steps, such as cross-validation, balancing data, or testing alternative models. Thus, better-planned studies following the recommended data science analysis steps along with adequate numbers of experiments would change the current landscape, allowing the exploration of the full potential of ML.

[Box: see text].

Melt crystallization and thermal degradation profile of the antichagasic drug nifurtimox.

Despite nifurtimox (NFX) being a traditional drug for treating Chagas disease, some of its physicochemical properties are still unknown, especially its thermal behavior, which brings important outcomes regarding stability and compatibility. In this work, a comprehensive study of NFX's thermal properties was conducted to assist incremental innovations that can improve the efficacy of this drug in novel pharmaceutical products. For this purpose, thermal analyses associated with spectroscopy and spectrometry techniques were used. DSC analyses revealed that the melt crystallization of the NFX led to its amorphous form with the possible formation of a minor fraction of a different crystalline phase. Coats-Redfern method using TGA results indicated the activation energy of NFX non-isothermal degradation as 348.8 ± 8.2 kJ mol-1, which coincides with the C-NO2 bond dissociation energy of the 2-nitrofuran. Investigation of the isothermal degradation kinetics using FTIR 2D COS showed the possible detachment of radical NO2 and ethylene from the NFX structure, which could affect its mechanism of action. A preliminary mechanism for the thermal degradation of this drug was also proposed. The results enhanced the understanding of NFX's thermal properties, providing valuable insights, especially for developing NFX-based pharmaceutical products that involve thermal processing.

Customizable Three-Dimensional Printed Earring Tap for Treating Affections Caused by Aesthetic Perforations.

This work aimed to develop a three-dimensional (3D) wearable drug-loaded earring tap to treat affections caused by aesthetic perforations. The initial phase involved a combination of polymers to prepare filaments for fused deposition modeling (FDM) 3D printing using a centroid mixture design. Optimized filament compositions were used in the second phase to produce 3D printed earring taps containing the anti-inflammatory naringenin. Next, samples were assessed via physicochemical assays followed by in vitro skin permeation studies with porcine ear skin. Two filament compositions were selected for the study's second phase: one to accelerate drug release and another with slow drug dissolution. Both filaments demonstrated chemical compatibility and amorphous behavior. The use of the polymer blend to enhance printability has been confirmed by rheological analysis. The 3D devices facilitated naringenin skin penetration, improving drug recovery from the skin's most superficial layer (3D device A) or inner layers (3D device B). Furthermore, the devices significantly decreased transdermal drug delivery compared to the control containing the free drug. Thus, the resulting systems are promising for producing 3D printed earring taps with topical drug delivery and reinforcing the feasibility of patient-centered drug administration through wearable devices.

Conformational analysis and spectroscopic properties of antichagasic nifurtimox.

Considering the health relevance of Chagas' disease, recent research efforts have focused on developing more efficient drug delivery systems containing nifurtimox (NFX). This paper comprehensively investigates NFX through conformational analysis and spectroscopic characterization. Using a conformer-rotamer ensemble sampling tool (CREST-xtb), five distinct conformers of NFX were sampled within a 3.0 kcal mol-1 relative energy window. Subsequently, such structures were used as inputs for geometry optimization by density functional theory (DFT) at B3LYP-def2-TZVP level of theory. Notably, harmonic vibrational frequencies were calculated to establish an in-depth comparison with experimental results and existing literature for the NFX or similar molecules and functional groups, thereby achieving a widely reasoned assignment of the mid-infrared band absorptions for the first time. Moreover, UV-VIS spectra of NFX were obtained in several solvents, enabling the determination of the molar absorptivity coefficient for the two electronic transitions observed for NFX. Among the aprotic solvents, a bathochromic effect was observed in the function of the dielectric constants. Furthermore, a hypochromic effect was observed when the drug was dissolved in protic solvents. These findings offer crucial support for new drug delivery systems containing NFX while demonstrating the potential of spectrophotometric studies in establishing quality control assays for NFX drug products.

Follicle-Targeted Delivery of Betamethasone and Minoxidil Co-Entrapped in Polymeric and Lipid Nanoparticles for Topical Alopecia Areata Treatment.

Alopecia areata is managed with oral corticosteroids, which has known side effects for patients. Given that a topical application of formulations containing a corticoid and a substance controlling hair loss progression could reduce or eliminate such adverse effects and increase the patient's adherence to the treatment, this study prepares polymeric and lipidic nanoparticles (PNPs and NLCs) to co-entrap minoxidil and betamethasone and compares the follicular drug delivery provided by topical application of these nanoparticles. The prepared PNPs loaded 99.1 ± 13.0% minoxidil and 70.2 ± 12.8% betamethasone, while the NLCs entrapped 99.4 ± 0.1 minoxidil and 80.7 ± 0.1% betamethasone. PNPs and NLCs presented diameters in the same range, varying from 414 ± 10 nm to 567 ± 30 nm. The thermal analysis revealed that the production conditions favor the solubilization of the drugs in the nanoparticles, preserving their stability. In in vitro permeation studies with porcine skin, PNPs provided a 2.6-fold increase in minoxidil penetration into the follicular casts compared to the control and no remarkable difference in terms of betamethasone; in contrast, NLCs provided a significant (specifically, a tenfold) increase in minoxidil penetration into the hair follicles compared to the control, and they delivered higher concentrations of betamethasone in hair follicles than both PNPs and the control. Neither PNPs nor NLCs promoted transdermal permeation of the drugs to the receptor solution, which should favor a topical therapy. Furthermore, both nanoparticles targeted approximately 50% of minoxidil delivery to the follicular casts and NLCs targeted 74% of betamethasone delivery to the hair follicles. In conclusion, PNPs and NLCs are promising drug delivery systems for enhancing follicular targeting of drugs, but NLCs showed superior performance for lipophilic drugs.

Extrusion-based systems for topical and transdermal drug delivery.

INTRODUCTION: Although the administration of drugs on the skin is a safe and noninvasive therapeutic alternative, producing formulations capable of disrupting the cutaneous barriers is still a challenge. In this scenario, extrusion-based techniques have emerged as disruptive technologies to ensure unique drug-excipient interactions that facilitate drug skin diffusion for systemic or local effect and even mean the key to obtain viable industrial products. AREAS COVERED: This article presents a comprehensive overview of extrusion-based techniques in developing pharmaceutical dosage forms for topical or transdermal drug delivery. First, the theoretical basis of how extrusion-based techniques can optimize the permeation of drugs through the skin is examined. Then, the current state-of-the-art of drug products developed by extrusion-based techniques, specifically by hot-melt extrusion (HME) and fused deposition modeling (FDM) 3D printing, are discussed and contrasted with the current pharmaceutical processes. EXPERT OPINION: A wide variety of pharmaceutical products can be obtained using HME and FDM 3D printing, including new dosage forms designed for a perfect anatomical fit. Despite the limitations of pharmaceutical products produced with HME and FDM 3D printing regarding thermal stability and available excipients, the advantages in industrial adaptability and improved bioavailability allied with patient-match devices certainly deserve full attention and investment.

Acute effects of high-intensity resistance training on central blood pressure parameters of elderly hypertensive women: a crossover clinical trial.

OBJECTIVE: Assess the acute effects of a high-intensity resistance training session on central blood pressure (CBP) parameters of elderly hypertensive women. METHODS: Forty physically active hypertensive women were included in resistance training and control protocols. Resistance training exercises were bench press, leg press and lat pull-down. The resistance training protocol consisted of three sets of 10 repetitions to volitional failure with 90 s of rest between sets. No exercise was performed in the control protocol. CBP parameters were measured in four moments: before (PRE), immediately after (T0), 30 min (T30) and 60 min (T60) following both protocols. RESULTS: Resistance training significantly increased central SBP (cSBP) 107.4 ±â€Š16.3 vs. 117.5 ±â€Š16.7), augmentation index ((24.9 ±â€Š12.7 vs. 33.1 ±â€Š12.0), pulse wave velocity (PWV 9.7 ±â€Š1.0 vs. 10.3 ±â€Š1.1), peripheral pulse pressure (pPP 48.5 ±â€Š11.7 vs. 58.9 ±â€Š13.1), central pulse pressure (cPP 38.3 ±â€Š11.6 vs. 46.5 ±â€Š13.1) and amplified pulse pressure (ampPP 10.2 ±â€Š4.2 vs. 12.4 ±â€Š5.6) immediately after exercises. The comparison between groups showed higher values of cSBP (117.5 ±â€Š16.7 vs. 106.3 ±â€Š14.6), augmentation index (20.9 ±â€Š11.0 vs. 33.1 ±â€Š12.0), pPP (46.6 ±â€Š11.0 vs. 58.9 ±â€Š13.1) and cPP (36 ±â€Š10.2 vs. 46.5 ±â€Š13.1) at T0. After 30 min, all variables returned to the baseline values. CONCLUSION: High-intensity resistance training session increased CBP parameters immediately after exercises, but those changes were not sustained after 30 min.

Bacterial endophthalmitis following anti-VEGF intravitreal injections: a retrospective case series.

BACKGROUND: To describe the incidence of endophthalmitis and the treatment outcomes of acute bacterial endophthalmitis following intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in a Brazilian hospital. The analysis was based on the timing of infection after intravitreal injection, culture results, visual acuity, and the presence of epiretinal membrane after a 1-year follow-up period, spanning nine years. METHODS: This retrospective case series, conducted over a 9-year period, aimed to evaluate the treatment outcomes of acute endophthalmitis following intravitreal Bevacizumab injections. The inclusion criteria involved a chart review of 25 patients who presented clinical signs of acute endophthalmitis out of a total of 12,441 injections administered between January 2011 and December 2019. Negative culture results of vitreous samples or incomplete data were excluded. Ultimately, 23 patients were enrolled in the study. Eight patients were treated with intravitreal antibiotic injections (IVAI) using vancomycin 1.0 mg/0.05mL and ceftazidime 2.25 mg/0.05mL, while 15 patients underwent pars plana vitrectomy (PPV) followed by intravitreal antibiotic injections at the end of surgery (IVAIES). The main outcome measures were the efficacy of controlling the infection with IVAI as a standalone therapy compared to early PPV followed by IVAIES. Data collected included pre-infection and one-year post-treatment best corrected visual acuity (BCVA), optical coherence tomography (OCT) abnormalities, and enucleation/evisceration rates. To compare groups, Mann-Whitney and ANOVA tests were employed for statistical analysis. RESULTS: The incidence rate of bacterial endophthalmitis was 0.185% (1/541 anti-VEGF injections), with the highest infection rates observed in 2014 and 2017. Patients presented clinical symptoms between 2 and 7 days after injection. The most common isolated organisms were coagulase-negative Staphylococci and Streptococci spp. Treatment outcomes showed that both IVAI and PPV + IVAIES effectively controlled the infection and prevented globe atrophy. After one year, the PPV group with BCVA better than Light Perception had a significantly better BCVA compared to the IVAI group (p 0.003). However, PPV group had higher incidence of epiretinal membranes formation compared to the IVAI group. (P 0.035) CONCLUSION: Anti-VEGF injections carry a risk of developing acute bacterial endophthalmitis. Isolated antibiotic therapy could be an effective treatment to control the infection, but performing PPV + IVAIES as a primary treatment showed promising results in terms of improving BCVA after one year, despite a higher rate of epiretinal membrane formation. Further studies are needed to confirm these findings.

The Infection Profile and Survival of Children and Adolescents With COVID-19 Undergoing Cancer Treatment: A Cohort Study.

OBJECTIVE: The objective of this study was to evaluate the clinical evolution of coronavirus disease 2019 (COVID-19) in children and adolescents with cancer. METHODS: Cohort involving patients undergoing cancer treatment, 19 years old and under, with the diagnosis of COVID-19 by real-time polymerase chain reaction, in a reference hospital, between March 2020 and November 2021. Data were collected from medical records and interviews with patients and/or guardians. The primary outcomes studied were severe/critical COVID-19 presentation, deaths from any cause and overall survival. The Cox proportional hazards multivariate regression analysis was performed to determine the risk of death. RESULTS: Sixty-two participants were included, most (67.7%) were male, with a median age of 6.8 years. Severe/critical forms of COVID-19, observed in 24.2%, seemed to indicate that the pediatric population undergoing cancer treatment has a higher morbidity rate than the general pediatric population (8-9.2%). During follow-up (4.5-18 months), 20 patients (32.3%) completed their cancer treatment and 18 died (29%)-6 during hospitalization and 12 after discharge. In total 61.1% of deaths occurred within 63 days of a detectable real-time polymerase chain reaction. Patients with a higher risk of death presented with severe/critical COVID-19 [adjusted hazard risk (aHR): 8.51; 95% confidence interval (CI): 2.91-24.80; P < 0.00] solid tumors (aHR: 3.99; 95% CI: 1.43-11.12; P = 0.008) and diarrhea as a symptom of COVID-19 (aHR: 3.9; 95% CI: 1.23-12.73; P = 0.021). CONCLUSIONS: These findings support the impact that severe acute respiratory syndrome-associated coronavirus 2 infection has on the population of children and adolescents with cancer, not only regarding immediate severity but also in their survival rate. Further studies evaluating long-term outcomes of COVID-19 in children and adolescents with cancer should be encouraged.

Compatibility and stability studies involving polymers used in fused deposition modeling 3D printing of medicines.

One of the challenges in developing three-dimensional printed medicines is related to their stability due to the manufacturing conditions involving high temperatures. This work proposed a new protocol for preformulation studies simulating thermal processing and aging of the printed medicines, tested regarding their morphology and thermal, crystallographic, and spectroscopic profiles. Generally, despite the strong drug-polymer interactions observed, the chemical stability of the model drugs was preserved under such conditions. In fact, in the metoprolol and Soluplus® composition, the drug's solubilization in the polymer produced a delay in the drug decomposition, suggesting a protective effect of the matrix. Paracetamol and polyvinyl alcohol mixture, in turn, showed unmistakable signs of thermal instability and chemical decomposition, in addition to physical changes. In the presented context, establishing protocols that simulate processing and storage conditions may be decisive for obtaining stable pharmaceutical dosage forms using three-dimensional printing technology.

Medicated lacquer for application on adornments to treat affections in aesthetic perforations.

Aesthetic perforations are often associated with health issues, such as itching, inflammation, or microbial infection. Accordingly, this work proposed a lacquer to be applied on the adornment accessory forming a film from which a proper drug is released. For this, lacquers were formulated containing three different permeation enhancers (limonene - LIM, propylene glycol - PG, and oleic acid - AO) combined according to a mixture design with a model anti-inflammatory natural drug (naringenin) and a soluble film-former polymer (polyvinyl alcohol). Formulations were characterized by physicochemical tests and in vitro and in vivo skin permeation studies. The lacquers were stable and provided a vectorized drug release. LIM, combined with one of the other permeation enhancers, showed a synergic effect, enhancing topical skin penetration in vitro by 53% while preventing permeation to the receptor medium. The in vivo evaluation of lacquers in rodent models showed these systems could provide higher levels of drug retention in the ear (166.4 ± 14.9 µg per ear for F4 and 174.9 ± 29.3 µg per ear for F5) compared to the control (109.2 ± 16.3 µg) without allowing its permeation into the bloodstream, confirming the local drug delivery. Moreover, the anti-inflammatory activity was achieved in the animal model developed for lacquer application on the earring, obtaining inhibition of ear swelling up to 40.8% ± 2.3 compared to the untreated ear. Thus, such an innovative lacquer proved a promising vehicle for treating affections caused by adornments, enhancing skin permeation while avoiding a systemic effect.

Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products.

Here, we assessed the feasibility of hot-melt extrusion (HME) to obtain effervescent drug products for the first time. For this, a combined mixture design was employed using paracetamol as a model drug. Extrudates were obtained under reduced torque (up to 0.3 Nm) at 100 °C to preserve the stability of the effervescent salts. Formulations showed vigorous and rapid effervescent disintegration (<3 min), adequate flow characteristics, and complete solubilization of paracetamol instantly after the effervescent reaction. Formulations containing PVPVA in the concentration range of 15-20% m/m were demonstrated to be sensitive to accelerated aging conditions, undergoing marked microstructural changes, since the capture of water led to the agglomeration and loss of their functional characteristics. HPMC matrices, in contrast, proved to be resistant to storage conditions in high relative humidity, showing superior performance to controls, including the commercial product. Moreover, the combined mixture design allowed us to identify significant interactions between the polymeric materials and the disintegrating agents, showing the formulation regions in which the responses are kept within the required levels. In conclusion, this study demonstrates that HME can bring important benefits to the elaboration of effervescent drug products, simplifying the production process and obtaining formulations with improved characteristics, such as faster disintegration, higher drug solubilization, and better stability.

Contact Dermatitis in the Elderly: Predisposing Factors, Diagnosis, and Management.

Increased aging of the general population is a well-known fact with serious effects on health systems worldwide. Skin aging involves various immunological and structural changes that increase the risk of numerous skin diseases such as contact dermatitis. Contact dermatitis is characterized by an inflammation of the skin caused by an interaction between the skin and external agents and is divided into irritant and allergic contact dermatitis. Irritant contact dermatitis occurs on skin areas directly exposed to irritant substances, which results in a stream of pro-inflammatory cytokines mediating the skin injury. Asteatotic and perineal irritant contact dermatitis are the most important subtypes of irritant contact dermatitis in the elderly. Allergic contact dermatitis is a T cell-mediated inflammatory reaction and requires a prior sensitization. The most common allergens responsible for allergic contact dermatitis in the elderly are fragrance mix, nickel, and balsam of Peru. Elderly patients with stasis dermatitis, chronic wounds, and chronic venous insufficiency have an increased prevalence of sensitization due to the frequent exposure to topical treatments. In this review, the most common types of contact dermatitis in the elderly are enumerated in order to assist dermatologists and other physicians to identify contact dermatitis in this distinct group of the population.

[Magnetic resonance imaging of the liver in postpartum stable women with HELLP syndrome]. / Ressonância magnética hepática em puérperas estáveis com síndrome HELLP.

OBJECTIVES: To describe magnetic resonance (MR) findings in the liver of stable patients with HELLP syndrome in the puerpuerium. METHODS: A descriptive study was carried out from August 2005 to July 2006, involving a series of 40 postpartum patients admitted to an obstetric intensive therapy unit in IMIP (Instituto Materno Infantil Prof. Fernando Figueira) with diagnosis of HELLP syndrome (complete and partial). Complete HELLP syndrome was defined when all laboratory parameters were present and incomplete when one or more but not all laboratory findings were present. All patients had stable clinical conditions and were evaluated with magnetic resonance of the liver and the main findings were recorded. RESULTS: Average maternal age was 26.8 +/- 6.4 years and gestational age at delivery was 34 +/- 26.8 weeks. The MR imaging was performed between eight and 96 hours after diagnosis of HELLP syndrome (56 +/- 31 h). The most frequent findings were ascitis in 20% (n = 8), pleural effusion in 17.5% and hepatic steatosis in 7.5%. The periportal intensity signal was normal in all cases. Cases of liver infarction and sub-capsular or parenchymatous hematoma were not observed. CONCLUSION: Findings of magnetic resonance imaging of the liver in stable HELLP syndrome postpartum patients were few and unspecific. Severe liver injuries such as parenchymatous or sub-capsular hematoma, entailing life risk were not found. Results do not corroborate the use of magnetic resonance as routine examination for stable patients with HELLP syndrome.

Coração em Criss-Cross: um relato de caso / Criss-Cross Heart: a case report

Coração em criss-cross (ou coração entrecruzado) foi descrito pela primeira vez em 1974. Trata-se de uma malformação cardíaca congênita, rara, ocorrendo 8 casos a cada 1.000.000 de crianças, e representando somente 0,1% das malformações congênitas. Os métodos diagnósticos de escolha são o ecocardiograma transtorácico, a ressonância magnética cardíaca (RMC), a angiotomografia (TC) e, eventualmente, o cateterismo cardíaco. Neste relato, descreve-se o caso de um recém-nascido com coração em criss-cross somado à dupla via de saída do ventrículo direito (VD), com vasos mal posicionados, além de comunicação interatrial (CIA), comunicação interventricular (CIV), displasia de valva tricúspide e veia cava superior esquerda persistente. Não se sabe a etiologia exata dessa malformação, mas parece ocorrer pela rotação dos ventrículos em seu eixo longitudinal, não acompanhada das rotações atrial e das valvas atrioventriculares (AV). Esse movimento produz uma alteração das vias de entrada dos ventrículos, determinando que o VD se posicione em plano superior e o esquerdo em plano inferior. Apesar de ainda não se saber a exata causa dessa anomalia, acredita-se que uma alteração genética possa estar levando a esses casos: a mutação do gene Cx43. O diagnóstico do caso em questão foi dado pela ecocardiografia transtorácica e da TC de aorta e artérias pulmonares, que mostraram, além do criss-cross, outras alterações, como dupla via de saída do VD, CIA e CIV amplas.(AU)

Criss-cross heart was first described in 1974. It is a rare congenital heart malformation that occurs in 8 cases per 1,000,000 children, and represents only 0.1% of congenital malformations. The diagnostic methods of choice are transthoracic echocardiography, cardiac magnetic resonance (CMR), computed tomography angiography (CT) and, sometimes, cardiac catheterization. This report describes the case of a newborn with a criss-cross heart in addition to double-outlet right ventricle (RV), with poorly positioned vessels, in addition to atrial septal defect (ASD), interventricular septal defect, tricuspid valve dysplasia and persistent left superior vena cava. The exact etiology of this malformation is not known, but it seems to occur due to rotation of the ventricles in their longitudinal axis, not accompanied by rotation of the atrial and atrioventricular (AV) valves. This movement produces abnormal ventricular inlets, determining that the RV be positioned on a superior plane and the left ventricle on an inferior plane. Although the exact cause of this anomaly is still unknown, it is believed that a genetic abnormality may be leading to these cases: mutation of the Cx43 gene. Diagnosis of the case concerned was given by transthoracic echocardiography and computed CT of the aorta and pulmonary arteries, which showed, in addition to the criss-cross heart, other abnormalities, such as double-outlet RV, large ASD and ventricular septal defect (VSD).(AU)