The Development and Pre-Clinical Anti-Inflammatory Efficacy of a New Transdermal Ureasil-Polyether Hybrid Matrix Loaded with Flavonoid-Rich Annona muricata Leaf Extract.

This study aimed to develop a novel ureasil-polyether transdermal hybrid matrix (U-PEO) loaded with Annona muricata concentrated extract (AMCE), which exhibits potent anti-inflammatory activity. The extract was obtained by maceration, a method that allowed for the extraction of a high concentration of flavonoids (39.27 mg/g of extract). In vivo tests demonstrated that 10 mg/kg of AMCE inhibited inflammation for 6 h. The physicochemical characterization of U-PEO with AMCE was conducted via a thermogravimetric analysis (TGA), while its surface was recorded using atomic force microscopy (AFM). The in vitro macroscopic swelling and release tests demonstrated the hydrophilic profile of the material and the percentage of AMCE released. The TGA results demonstrated that the system exhibited physical compatibility due to the thermal stability of U-PEO. Additionally, the AFM analysis revealed a rough and porous surface, with a particular emphasis on the system with AMCE. The release resulted in the liberation of 23.72% of AMCE within 24 h. Finally, the preclinical tests demonstrated that U-PEO with AMCE was also capable of effectively inhibiting inflammation for 6 h, a duration comparable to that of a commercial formulation. The results permit the advancement of the study towards the development of a transdermal system, thereby rendering its application in clinical studies feasible.

"Effectiveness of Different Treatment Modalities in Initial and Chronic Phases of Thyroid Eye Disease: A Systematic Review with Meta-analysis".

BACKGROUND: Thyroid eye disease (TED), a common extra-thyroidal manifestation of Graves' disease, poses significant management challenges due to potential disfigurement, visual impairment, and decreased quality of life. Uncertainties remain about the optimal treatment approach, especially regarding TED duration and its impact on outcomes. OBJECTIVE: This meta-analysis evaluates the effects of various treatments on inflammatory markers and severity endpoints in TED, stratified by disease duration, distinguishing between treatments initiated within the first six months (initial phase) and those initiated thereafter (subacute/chronic phase). METHOD: Following PRISMA guidelines, a systematic search of multiple electronic databases yielded 26 studies meeting predefined inclusion criteria. Methodological quality was assessed, and data were meticulously extracted and analyzed. FINDINGS: In the initial phase, treatments like corticosteroids and teprotumumab showed significant improvements in Clinical Activity Score (CAS), proptosis, and diplopia. In the subacute/chronic phase, the efficacy of methylprednisolone and teprotumumab is reduced. A "critical window" effect was observed, with treatments showing diminished efficacy after six months of TED duration. CONCLUSIONS: This meta-analysis highlights the importance of tailoring treatment strategies based on TED duration, emphasizing early interventions to maximize benefits. The findings guide clinicians in selecting optimal treatments and underscore the need for further research to refine evidence-based approaches, ultimately enhancing patient outcomes and quality of life.

Intelligent Systems Based on Cyclodextrins for the Treatment of Breast Cancer.

The incidence of breast cancer has been increasing over the last four decades, although the mortality rate has decreased. Endocrine therapy and chemotherapy are the most used options for cancer treatment but several obstacles are still attributed to these therapies. Smart materials, such as nanocarriers for targeting, delivery and release of active ingredients, sensitive to intrinsic-stimuli (pH-responsive, redox-responsive, enzyme- responsive, and thermo-responsive) and extrinsic-stimuli (ultrasound-responsive, magnetic-responsive, light-responsive) have been studied as a novel strategy in breast cancer therapy. Cyclodextrins (CDs) are used in the design of these stimuli-responsive drug carrier and delivery systems, either through inclusion complexes with hydrophobic molecules or covalent bonds with large structures to generate new materials. The present work aims to gather and integrate recent data from in vitro and in vivo preclinical studies of CD-based stimuli- responsive systems to contribute to the research in treating breast cancer. All drug carriers showed high in vitro release rates in the presence of a stimulus. The stimuli-responsive nanoplatforms presented biocompatibility and satisfactory results of IC50, inhibition of cell viability and antitumor activity against several breast cancer cell lines. Additionally, these systems led to a significant reduction in drug dosages, which encouraged possible clinical studies for better alternatives to traditional antitumor therapies.

The Efficacy of Hybrid Vaginal Ovules for Co-Delivery of Curcumin and Miconazole against Candida albicans.

Curcumin (CUR) is a natural compound that can be combined with miconazole (MCZ) to improve vulvovaginal candidiasis (VVC) caused by Candida albicans treatment's efficacy. This study aimed to develop ureasil-polyether (U-PEO) vaginal ovules loaded with CUR and MCZ for the treatment of VVC. Physicochemical characterization was performed by thermogravimetry (TGA), differential thermal analysis (DTA), Fourier transform infrared spectroscopy (FTIR), and in vitro release. Antifungal assays were used to determine minimum inhibitory concentrations (MICs) and synergism between CUR and MCZ, and the activity of U-PEO ovules were performed by microdilution and agar diffusion. TGA results showed high thermal stability of the hybrid ovules. In DTA, the amorphous character of U-PEO and a possible interaction between CUR and MCZ were observed. FTIR showed no chemical incompatibility between the drugs. In vitro release resulted in 80% of CUR and 95% of MCZ released within 144 h. The MICs of CUR and MCZ were 256 and 2.5 µg/mL, respectively. After combining the drugs, the MIC of MCZ decreased four-fold to 0.625 µg/mL, while that of CUR decreased eight-fold to 32 µg/mL. Synergism was confirmed by the fractional inhibitory concentration index (FICI) equal to 0.375. U-PEO alone showed no antifungal activity. U-PEO/MCZ and U-PEO/CUR/MCZ ovules showed the greatest zones of inhibition (≥18 mm). The results highlight the potential of the ovules to be administered at a lower frequency and at reduced doses compared to available formulations.

Sweat conductivity for diagnosing cystic fibrosis after positive newborn screening: prospective, diagnostic test accuracy study.

OBJECTIVE: To assess the accuracy of sweat conductivity among newborns and very young infants. DESIGN: Prospective, population-based, diagnostic test accuracy study. SETTING: Public Statewide Newborn Screening Programme where the incidence rate of cystic fibrosis (CF) is ≈1:11 000. PATIENTS: Newborns and very young infants with positive two-tiered immunoreactive trypsinogen. INTERVENTIONS: Sweat conductivity and sweat chloride were performed simultaneously, on the same day and facility by independent technicians, with the cut-off values of 80 mmol/L and 60 mmol/L, respectively. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values (PPV and NPV), overall accuracy, positive and negative likelihood ratios (+LR, -LR) and post (sweat conductivity (SC)) test probability were calculated to assess SC performance. RESULTS: 1193 participants were included, 68 with and 1108 without CF, and 17 with intermediate values. The mean (SD) age was 48 (19.2) days, ranging from 15 to 90 days. SC yielded sensitivity of 98.5% (95% CI 95.7 to 100), specificity of 99.9% (95% CI 99.7 to 100), PPV of 98.5% (95% CI 95.7 to 100) and NPV of 99.9% (95% CI 99.7 to 100), overall accuracy of 99.8% (95% CI 99.6 to 100), +LR of 1091.7 (95% CI 153.8 to 7744.9) and -LR of 0.01 (95% CI 0.00 to 0.10). After a positive and negative sweat conductivity result, the patient's probability of CF increases around 350 times and drops to virtually zero, respectively. CONCLUSION: Sweat conductivity had excellent accuracy in ruling in or ruling out CF after positive two-tiered immunoreactive trypsinogen among newborns and very young infants.

Growth phenotypes of very low birth weight infants for prediction of neonatal outcomes from a Brazilian cohort: comparison with INTERGROWTH

Abstract Objective: To assess the predictive value of selected growth phenotypes for neonatal morbidity and mortality in preterm infants < 30 weeks and to compare them with INTERGROWTH-21st (IG21). Methods: Retrospective analysis of data from the Brazilian Neonatal Research Network (BNRN) database for very low birth weight (VLBW) at 20 public tertiary-care university hospitals. Outcome: the composite neonatal morbidity and mortality (CNMM) consisted of in-hospital death, oxygen use at 36 weeks, intraventricular hemorrhage grade 3 or 4, and Bell stage 2 or 3 necrotizing enterocolitis. Selected growth phenotypes: small-for-gestational-age (SGA) defined as being < 3rd (SGA3) or 10th (SGA10) percentiles of BW, and large-for-gestational-age (LGA) as being > 97th percentile of BW. Stunting as being < 3rd percentile of the length and wasting as being < 3rd percentile of BMI. Single and multiple log-binomial regression models were fitted to estimate the relative risks of CNMM, comparing them to IG21. Results: 4,072 infants were included. The adjusted relative risks of CNMM associated with selected growth phenotypes were (BNRN/IG21): 1.45 (0.92-2.31)/1.60 (1.27-2.02) for SGA; 0.90 (0.55-1.47)/1.05 (0.55-1.99) for LGA; 1.65 (1.08-2.51)/1.58 (1.28-1.96) for stunting; and 1.48 (1.02-2.17) for wasting. Agreement between the two references was variable. The growth phenotypes had good specificity (>95%) and positive predictive value (70-90%), with poor sensitivity and low negative predictive value. Conclusion: The BNRN phenotypes at birth differed markedly from the IG21 standard and showed poor accuracy in predicting adverse neonatal outcomes.

Effect of Hyperthyroidism Control During Pregnancy on Maternal and Fetal Outcome: A Systematic Review and Meta-Analysis.

Context: Although the overt hyperthyroidism treatment during pregnancy is mandatory, unfortunately, few studies have evaluated the impact of treatment on reducing maternal and fetal outcomes. Objective: This study aimed to demonstrate whether treatment to control hyperthyroidism manifested during pregnancy can potentially reduce maternal-fetal effects compared with euthyroid pregnancies through a systematic review with meta-analysis. Data Source: MEDLINE (PubMed), Embase, Cochrane Library Central, LILACS/BIREME until May 2021. Study Selection: Studies that compared, during the gestational period, treated women with hyperthyroidism versus euthyroid women. The following outcomes of this comparison were: pre-eclampsia, abruptio placentae, fetal growth retardation, gestational diabetes, postpartum hemorrhage, low birth weight, stillbirth, spontaneous abortions, premature birth. Data Extraction: Two independent reviewers extracted data and performed quality assessments. Dichotomous data were analyzed by calculating risk differences (DR) with fixed and random effect models according to the level of heterogeneity. Data Synthesis: Seven cohort studies were included. The results of the meta-analysis indicated that there was a lower incidence of preeclampsia (p=0.01), low birth weight (p=0.03), spontaneous abortion (p<0.00001) and preterm birth (p=0.001) favouring the euthyroid pregnant group when compared to those who treated hyperthyroidism during pregnancy. However, no statistically significant differences were observed in the outcomes: abruptio placentae, fetal growth retardation, gestational diabetes mellitus, postpartum hemorrhage, and stillbirth. Conclusions: Our findings demonstrated that treating overt hyperthyroidism in pregnancy is mandatory and appears to reduce some potential maternal-fetal complications, despite there still being a residual risk of negative outcomes.

Temporal trends in intraventricular hemorrhage in preterm infants: A Brazilian multicenter cohort.

BACKGROUND: Intraventricular hemorrhage (IVH) is a serious problem in preterm infants. Brazilian national data are unknown. OBJECTIVE: To evaluate the incidence and temporal trend of IVH in very low birth weight (VLBW) preterm infants of 18 centers of the Brazilian Network on Neonatal Research. STUDY DESIGN: National prospective multicenter cohort study including inborn VLBW preterm infants aged 230/7- 336/7 weeks' gestation, admitted between 2013 and 2018. The center with the mean incidence rate was used as reference. We applied two adjustments models using perinatal variables, and perinatal + neonatal diseases. RESULTS: Of 6,420 infants, 1951/30.4% (range 27.1-33.8%) had IVH and the disease showed a significant trend towards an overall increase in incidence over time (p = 0.003), especially in three centers. Severe IVH (grade III or IV) occurred in 32.2% (range 29.2-34.5%) of those affected by IVH, with a stable incidence. After adjustments for perinatal variables, the differences persisted among centers: for global IVH, 7 centers had significantly lower rates (OR ranging from 0.31 to 0.62), and 2 presented rates higher than the reference center (OR ranging from 2.00 to 12.46) for severe HIV. Considering perinatal and neonatal variables, 6 centers had significantly lower rates (OR ranging from 0.36 to 0.60) for global IVH than the reference center and 3 had statistically higher rates (OR 1.72, 1.86 and 11.78) for severe forms. CONCLUSION: The incidence rate of IVH in this Brazilian cohort was high and it revealed an increasing trend towards over time. The severe IVH rate was also worrisome.

Brazilian Thoracic Society recommendations for the diagnosis and treatment of chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious and debilitating disease caused by occlusion of the pulmonary arterial bed by hematic emboli and by the resulting fibrous material. Such occlusion increases vascular resistance and, consequently, the pressure in the region of the pulmonary artery, which is the definition of pulmonary hypertension. The increased load imposed on the right ventricle leads to its progressive dysfunction and, finally, to death. However, CTEPH has a highly significant feature that distinguishes it from other forms of pulmonary hypertension: the fact that it can be cured through treatment with pulmonary thromboendarterectomy. Therefore, the primary objective of the management of CTEPH should be the assessment of patient fitness for surgery at a referral center, given that not all patients are good candidates. For the patients who are not good candidates for pulmonary thromboendarterectomy, the viable therapeutic alternatives include pulmonary artery angioplasty and pharmacological treatment. In these recommendations, the pathophysiological bases for the onset of CTEPH, such as acute pulmonary embolism and the clinical condition of the patient, will be discussed, as will the diagnostic algorithm to be followed and the therapeutic alternatives currently available.

Risk Perception and Decision Making about Early-Onset Sepsis among Neonatologists: A National Survey.

OBJECTIVE: Many newborns are investigated and empirically treated for suspected early-onset sepsis (EOS). This study aimed to describe neonatologists' self-identified risk thresholds for investigating and treating EOS and assess the consistency of these thresholds with clinical decisions. STUDY DESIGN: Voluntary online survey, available in two randomized versions, sent to neonatologists from 20 centers of the Brazilian Network on Neonatal Research. The surveys included questions about thresholds for investigating and treating EOS and presented four clinical scenarios with varying calculated risks. In survey version A, only the scenarios were presented, and participants were asked if they would order a blood test or start antibiotics. Survey version B presented the same scenarios and the risk of sepsis. Clinical decisions were compared between survey versions using chi-square tests and agreement between thresholds and clinical decisions were investigated using Kappa coefficients. RESULTS: In total, 293 surveys were completed (145 survey version A and 148 survey version B). The median risk thresholds for blood test and antibiotic treatment were 1:100 and 1:25, respectively. In the high-risk scenario, there was no difference in the proportion choosing antibiotic therapy between the groups. In the moderate-risk scenarios, both tests and antibiotics were chosen more frequently when the calculated risks were included (survey version B). In the low-risk scenario, there was no difference between survey versions. There was poor agreement between the self-described thresholds and clinical decisions. CONCLUSION: Neonatologists overestimate the risk of EOS and underestimate their risk thresholds. Knowledge of calculated risk may increase laboratory investigation and antibiotic use in infants at moderate risk for EOS. KEY POINTS: · Neonatologists overestimate the risk of EOS.. · There is wide variation in diagnostic/treatment thresholds for EOS.. · Clinical decision on EOS is not consistent with risk thresholds.. · Knowledge of risk may increase investigation and treatment of EOS..

Mepolizumab in Hypereosinophilic Syndrome: A Systematic Review and Meta-analysis.

We aimed to evaluate the efficacy and safety of mepolizumab (MEP) in the management of hypereosinophilic syndrome (HES). A systematic search was performed, and articles published until March 2021 were analyzed. The primary efficacy results evaluated were hospitalization rate related to HES, morbidity (new or worsening), relapses/failure, treatment-related adverse effects, prednisone dosage ≤10 mg/day for ≥8 weeks, and eosinophil count <600/µL for ≥8 weeks. A meta-analysis was conducted, when appropriate. Three randomized controlled trials (RCTs), with a total of 255 patients, were included. The studies contemplated the use of MEP 300 mg/SC or 750 mg/IV. According to the evaluation of the proposed outcomes, when relapse rates/therapeutic failures were assessed, there was a 26% reduction with MEP 300 mg/SC (RD=-0.26; 95% CI: -0.44 to -0.08; p=0.04) and 48% reduction with MEP 750 mg/IV (RD=-0.48; 95% CI: -0.67, -0.30; p<0.00001). For the outcomes, prednisone dosage ≤10 mg/day for ≥8 weeks was 48% (RD=0.48; 95% CI: 0.35 to 0.62; p<0.00001), and the eosinophil count <600/µL for ≥8 weeks was 51% (RD=0.51; 95% CI: 0.38 to 0.63; p<0.00001), both showed a reduction with MEP 300 mg/IV and 750 mg/IV. No statistically significant differences in treatment-related adverse effects outcomes were observed for either dosage (RD=0.09; 95% CI: -0.05 to 0.24; p=0.20; RD=0.09; 95% CI: -0.11 to 0.29; p=0.39). Despite the positive effects observed for the studied outcomes, the exact significance remains unclear.

Hematologic variables of the Arrau turtle (Podocnemis expansa) under the effects of different anticoagulants and cytologic stains.

BACKGROUND: The hematology of turtles of the Amazon, such as the Arrau turtle (Podocnemis expansa), has not been well described in the literature. Referencing how to collect and analyze blood samples is fundamental for the medical practice of these exotic animals. OBJECTIVES: The aim of this study was to evaluate the hematologic parameters of Arrau turtles of the Amazon to determine the best anticoagulant (EDTA, citrate, or sodium heparin) and cytologic stain (Giemsa, Quick Panoptic, or Rosenfeld) for use with this species. METHODS: Blood samples from eight turtles were collected. Three blood smears were made using blood without anticoagulant, and the rest of the sample was distributed in three tubes, containing EDTA, citrate, and sodium heparin, for erythrogram and leukogram analyses. RESULTS: All blood samples anticoagulated with EDTA showed marked hemolysis. Blood collected with citrate showed minimal hemolysis, and blood collected with sodium heparin did not have any hemolysis. Some analyses were not performed on blood containing EDTA because of the intense hemolysis. The erythrocyte variables were obtained and showed better results for blood samples in heparin. Blood smears without anticoagulant were appropriate for differential leukocyte counts with the three stain types, while blood with any of the anticoagulants made it difficult to differentiate leukocytes. CONCLUSIONS: Sodium heparin showed the best results and should be the anticoagulant of choice for hematologic studies in P expansa. All cytologic stains were efficient, allowing adequate identification of distinct cell groups. Leukocyte differentiation was assured and had better contrast using blood smears made from blood without an anticoagulant.

Mepolizumab in hypereosinophilic syndrome: a systematic review and meta-analysis

We aimed to evaluate the efficacy and safety of mepolizumab (MEP) in the management of hypereosinophilic syndrome (HES). A systematic search was performed, and articles published until March 2021 were analyzed. The primary efficacy results evaluated were hospitalization rate related to HES, morbidity (new or worsening), relapses/failure, treatment-related adverse effects, prednisone dosage ≤10 mg/day for ≥8 weeks, and eosinophil count <600/μL for ≥8 weeks. A meta-analysis was conducted, when appropriate. Three randomized controlled trials (RCTs), with a total of 255 patients, were included. The studies contemplated the use of MEP 300 mg/SC or 750 mg/IV. According to the evaluation of the proposed outcomes, when relapse rates/therapeutic failures were assessed, there was a 26% reduction with MEP 300 mg/SC (RD=-0.26; 95% CI: -0.44 to -0.08; p=0.04) and 48% reduction with MEP 750 mg/IV (RD=-0.48; 95% CI: -0.67, -0.30; p<0.00001). For the outcomes, prednisone dosage ≤10 mg/day for ≥8 weeks was 48% (RD=0.48; 95% CI: 0.35 to 0.62; p<0.00001), and the eosinophil count <600/μL for ≥8 weeks was 51% (RD=0.51; 95% CI: 0.38 to 0.63; p<0.00001), both showed a reduction with MEP 300 mg/IV and 750 mg/IV. No statistically significant differences in treatment-related adverse effects outcomes were observed for either dosage (RD=0.09; 95% CI: -0.05 to 0.24; p=0.20; RD=0.09; 95% CI: -0.11 to 0.29; p=0.39). Despite the positive effects observed for the studied outcomes, the exact significance remains unclear.

Autoimmune encephalitis (AIE).

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Autoimmune encephalitis (AIE)

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Transpiration and growth of young African mahogany plants subject to different water regimes.

Timber production has been prominent in the Brazil scenario to minimize deforestation. Thus, technical information is necessary to define the productive process of the African mahogany in the Midwest region of Brazil, especially with regard to its hydric parameters. Recent studies, reported in the literature, have shown that irrigation improves the performance of young African mahogany plants in the field. Sap flow measurement can be used to estimate transpiration of perennial plants and to determine their water demand. This study evaluated the influence of two water regimes on the transpiration and growth of an African mahogany forest after irrigation has ceased. Moreover, this study also characterizes the seasonal patterns of transpiration and growth of African mahogany under these conditions. African mahogany plants with 2.5 years of age were cultivated in Bonfinopolis-GO and evaluated for 2 years. Treatments were IT-irrigated until 2 years of age-and NIT-non-irrigated. Plant height (PH), breast height diameter (DBH), trunk volume (TRV), leaf area (LA), leaf dry matter (LDM), and transpiration (T) were monitored by heat dissipation probe (HDP) between Oct/2014 and Oct/2015. Higher growth in LA, DBH, and LDM were observed in IT. However, increase in PH and TRV was similar in both treatments. The mean annual T was similar between treatments (15.0 L m-2 month-1). The highest T was recorded in October/2014 (IT = 33.0 L m-2 month-1) and July/2015 (NIT = 20.5 L m-2 month-1). The greater LA and water deficit blades DEF > 30 mm promoted lower transpiration in the irrigated plants. Irrigation maintained plant growth in PH, DBH, and LA in the third year, even after irrigation has ceased. However, non-irrigated plants were similar in TRV (0.065 m3) and transpiration rates (≈ 15 L m-2 month-1). Winter transpiration (11.3 L m-2 month-1) was lower than in summer (18.8 L m-2 month-1) for irrigated plants and similar for non-irrigated plants (≈ 14 L m-2 month-1). Based on that, in order to maintain the homogeneity of the plants, the irrigation in the first 2 years of cultivation is recommended, and also, the sap flow measures presented satisfactory results regarding the determinations of the water needs of African mahogany.

Brazilian Thoracic Society recommendations for the diagnosis and treatment of chronic thromboembolic pulmonary hypertension / Recomendações para o diagnóstico e tratamento da hipertensão pulmonar tromboembólica crônica da Sociedade Brasileira de Pneumologia e Tisiologia

ABSTRACT Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious and debilitating disease caused by occlusion of the pulmonary arterial bed by hematic emboli and by the resulting fibrous material. Such occlusion increases vascular resistance and, consequently, the pressure in the region of the pulmonary artery, which is the definition of pulmonary hypertension. The increased load imposed on the right ventricle leads to its progressive dysfunction and, finally, to death. However, CTEPH has a highly significant feature that distinguishes it from other forms of pulmonary hypertension: the fact that it can be cured through treatment with pulmonary thromboendarterectomy. Therefore, the primary objective of the management of CTEPH should be the assessment of patient fitness for surgery at a referral center, given that not all patients are good candidates. For the patients who are not good candidates for pulmonary thromboendarterectomy, the viable therapeutic alternatives include pulmonary artery angioplasty and pharmacological treatment. In these recommendations, the pathophysiological bases for the onset of CTEPH, such as acute pulmonary embolism and the clinical condition of the patient, will be discussed, as will the diagnostic algorithm to be followed and the therapeutic alternatives currently available.

RESUMO A hipertensão pulmonar tromboembólica crônica (HPTEC) é uma doença grave e debilitante, causada pela oclusão do leito arterial pulmonar por êmbolos hemáticos e por material fibroso induzido pela presença desses êmbolos. Essa oclusão eleva a resistência vascular e, por consequência, a pressão do território arterial pulmonar, caracterizando a presença de hipertensão pulmonar. Esse aumento da carga imposta ao ventrículo direito leva a progressiva insuficiência do mesmo e, finalmente, ao óbito. No entanto, ao contrário das outras formas de hipertensão pulmonar, a HPTEC possui uma particularidade muito significativa: a existência de tratamento potencialmente curativo através da tromboendarterectomia pulmonar. Dessa forma, o objetivo primordial do manejo deve ser a avaliação do potencial cirúrgico do paciente em um centro de referência em HPTEC. Entretanto, nem todos os pacientes podem ser submetidos à cirurgia. Para esses pacientes outras alternativas terapêuticas viáveis são a angioplastia de artérias pulmonares e o tratamento farmacológico. Nestas recomendações, discutir-se-ão as bases fisiopatológicas para o surgimento de HPTEC, a partir da embolia pulmonar aguda, bem como o quadro clínico apresentado pelo paciente, o algoritmo diagnóstico a ser seguido e as alternativas terapêuticas disponíveis.

Pulmonary Hypertension in General Cardiology Practice.

The finding of pulmonary hypertension (PH) by echocardiography is common and of concern. However, echocardiography is just a suggestive and non-diagnostic assessment of PH. When direct involvement of pulmonary circulation is suspected, invasive hemodynamic monitoring is recommended to establish the diagnosis. This assessent provides, in addition to the diagnostic confirmation, the correct identification of the vascular territory predominantly involved (arterial pulmonary or postcapillary). Treatment with specific medication for PH (phosphodiesterase type 5 inhibitors, endothelin receptor antagonists and prostacyclin analogues) has been proven effective in patients with pulmonary arterial hypertension, but its use in patients with PH due to left heart disease can even be damaging. In this review, we discuss the diagnosis criteria, how etiological investigation should be carried out, the clinical classification and, finally, the therapeutic recommendations for PH.

Pulmonary Hypertension in General Cardiology Practice / Hipertensão Pulmonar na Prática do Cardiologista

Abstract The finding of pulmonary hypertension (PH) by echocardiography is common and of concern. However, echocardiography is just a suggestive and non-diagnostic assessment of PH. When direct involvement of pulmonary circulation is suspected, invasive hemodynamic monitoring is recommended to establish the diagnosis. This assessent provides, in addition to the diagnostic confirmation, the correct identification of the vascular territory predominantly involved (arterial pulmonary or postcapillary). Treatment with specific medication for PH (phosphodiesterase type 5 inhibitors, endothelin receptor antagonists and prostacyclin analogues) has been proven effective in patients with pulmonary arterial hypertension, but its use in patients with PH due to left heart disease can even be damaging. In this review, we discuss the diagnosis criteria, how etiological investigation should be carried out, the clinical classification and, finally, the therapeutic recommendations for PH.

Resumo O achado de hipertensão pulmonar (HP) em avaliação ecocardiográfica é frequente e preocupante. No entanto, o ecocardiograma é apenas um exame sugestivo e não diagnóstico de HP. Quando se suspeita de acometimento direto da circulação pulmonar, está indicada medida hemodinâmica invasiva para estabelecer o diagnóstico. Essa avaliação permite, além da confirmação diagnóstica, a correta identificação do território vascular predominantemente acometido (arterial pulmonar ou pós-capilar). O tratamento com as medicações específicas de HP (inibidores da fosfodiestarese 5, antagonistas do receptor de endotelina, análogos da prostaciclina e estimulador da guanilil ciclase solúvel) é comprovadamente eficaz para pacientes com hipertensão arterial pulmonar, mas seu uso em pacientes com HP decorrente de doença cardíaca de câmaras esquerdas pode até mesmo ser prejudicial. Discutiremos nesta revisão o critério diagnóstico, a maneira de proceder a investigação etiológica, a classificação clínica e, finalmente, as recomendações terapêuticas na HP.