Comparison of different agents and doses of anti-vascular endothelial growth factors (aflibercept, bevacizumab, conbercept, ranibizumab) versus laser for retinopathy of prematurity: A network meta-analysis.

Laser photocoagulation (LPC) and/or intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections constitute the current standard treatment for retinopathy of prematurity (ROP). This network meta-analysis focus on whether a ranking of interventions may be established for different dose levels of intravitreal injection of anti-VEGF agents (aflibercept, bevacizumab, conbercept, ranibizumab) as primary treatments for ROP versus laser in terms of retreatment rate as primary outcome, and time to retreatment and refractive error as secondary endpoints, since best anti-VEGF dosage remains under debate. Sixty-eight studies (15 randomized control trials and 53 nonrandomized studies) of 12,356 eyes of 6445 infants were retrieved from databases (2005 Jan. - 2023 June). Studies were evaluated for model fit, risk of bias and confidence of evidence in Network Meta-Analysis (CINeMA). Bayesian NMA showed that anti-VEGF drugs were not inferior to laser in terms of retreatment rate. For intravitreal bevacizumab (IVB), doses half of the conventional infant dose showed a low risk of retreatment rate (risk ratio (RR) of 1.43; 95% credible interval (CrI): 0.508, 4.03). On probability ranking as surface under the cumulative ranking curve (SUCRA) plot, half dose of bevacizumab had a better position than conventional and augmented (1.2-2 times the regular dose) doses. A similar probability trend was observed for half vs. conventional doses of aflibercept and ranibizumab. Conventional infant dose of conbercept showed the lowest risk for retreatment (RR 0.846; 95% CrI: 0.245, 2.91). For secondary endpoints, lower doses of anti-VEGF agents were associated with shorter times to retreatment. The largest changes were noted for the augmented doses of bevacizumab and ranibizumab (0.3 mg) with means of 14.1 weeks (95% CrI: 6.65, 21.6) and 12.8 weeks (95% CrI: 3.19, 20.9), respectively. Finally, NMA demonstrated better refractive profile for anti-VEGF than laser therapy, especially for the conventional infant doses of bevacizumab and ranibizumab which exhibited a significantly better refractive profile than LPC, with mean differences of 1.67 (spherical equivalent - diopters) (95% CrI: 0.705, 2.67) and 2.19 (95% CrI: 0.782, 3.59), respectively. In the SUCRA plots, LPC had a markedly different position with a higher probability for myopia. Further clinical trials comparing different intravitreal doses of anti-VEGF agents are needed, but our findings suggest that low doses of these drugs retain efficacy and may reduce ocular and systemic undesired events.

Intravenous prostaglandin E1 (alprostadil) bolus in ductus arteriosus-dependent CHD: valid or absolutely contraindicated?

The use of prostaglandin E1 is well documented in ductus arteriosus-dependent CHD or in neonatal pulmonary pathologies that cause severe pulmonary hypertension. The intravenous infusion is well established in loading infusion and maintenance with an onset of action of 30 minutes until 2 hours or even more. Our aim is to report three patients with pulmonary atresia that presented hypercyanotic spell due to a ductal spasm during cardiac catheterisation in whom the administration of a bolus of alprostadil reversed the spasm and increased pulmonary flow, immediately stabilising the condition of the patients allowing subsequent successful stent placement with no serious complications or sequelae after the administration of the bolus. More studies are needed to make a recommendation regarding the use of alprostadil in bolus in cases where the ductal spasm might jeopardise the life of the patient.

Giant early post-surgical aneurysm of the aortic arch in an infant.

Ten-day-old neonate who underwent correction of interrupted aortic arch developed a giant early post-surgical aneurysm. To our knowledge, this unusual complication has been only reported as a late complication.

Diseño de material educativo en alimentación usando Intervention Mapping / Using Intervention Mapping protocol to design a nutrition education material

Introducción: Los materiales educativos basados en evidencia y culturalmente aceptables han demostrado ser una herramienta efectiva en el fomento de la alimentación saludable.  Objetivo: Diseñar un material educativo impreso en alimentación saludable usando Intervention Mapping para una Clínica del Estilo de Vida.  Metodología: Se utilizó la metodología de Intervention Mapping con los pasos 1) evaluación de necesidades, 2) Matrices de objetivos, 3) Métodos teóricos y 4) Diseño.  Resultados: Se construyó el Modelo Lógico PRECEDE, la matriz de objetivos de cambio basado en los determinantes conocimiento, identificación, disponibilidad y apoyo y se utilizó el procesamiento de la información como método teórico. Se obtuvo una revista de 22 páginas con contenido, imágenes, texto y redacción basado en los pasos de Intervention Mapping. Conclusiones: El proceso de Intervention Mapping proporcionó insumos basados en evidencia y participativos para el diseño del material educativo de la Clínica del Estilo de Vida en estudio.

Introduction: Evidence-based and culturally acceptable educational materials have been shown to be an effective tool in promoting healthy eating. Objective: To design a printed nutritional education material using Intervention Mapping protocol for a Lifestyle Clinic. Methods: Four of the steps of the Intervention Mapping protocol were used: 1) needs assessment, 2 identification of behavioral outcomes, performance objectives, and change objectives, 3) selection of theory-based methods and strategies and 4) program development. Results: The Logical Model PRECEDE was built, the matrix of change objectives based on the determinants of knowledge, identification, availability, and information processing was used as a theoretical model. A 22-page magazine was obtained with content, images, text and writing based on the Intervention Mapping steps. Conclusion: The Intervention Mapping process provided evidence-based and participatory inputs for the design of the educational material of the Lifestyle Clinic.

JAK2 mediates lung fibrosis, pulmonary vascular remodelling and hypertension in idiopathic pulmonary fibrosis: an experimental study.

BACKGROUND: Pulmonary hypertension (PH) is a common disorder in patients with idiopathic pulmonary fibrosis (IPF) and portends a poor prognosis. Recent studies using vasodilators approved for PH have failed in improving IPF mainly due to ventilation (V)/perfusion (Q) mismatching and oxygen desaturation. Janus kinase type 2 (JAK2) is a non-receptor tyrosine kinase activated by a broad spectrum of profibrotic and vasoactive mediators, but its role in PH associated to PH is unknown. OBJECTIVE: The study of JAK2 as potential target to treat PH in IPF. METHODS AND RESULTS: JAK2 expression was increased in pulmonary arteries (PAs) from IPF (n=10; 1.93-fold; P=0.0011) and IPF+PH (n=9; 2.65-fold; P<0.0001) compared with PA from control subjects (n=10). PA remodelling was evaluated in human pulmonary artery endothelial cells (HPAECs) and human pulmonary artery smooth muscle cells (HPASMCs) from patients with IPF in vitro treated with the JAK2 inhibitor JSI-124 or siRNA-JAK2 and stimulated with transforming growth factor beta. Both JSI-124 and siRNA-JAK2 inhibited the HPAEC to mesenchymal transition and the HPASMCs to myofibroblast transition and proliferation. JAK2 inhibition induced small PA relaxation in precision-cut lung slice experiments. PA relaxation was dependent of the large conductance calcium-activated potassium channel (BKCa). JAK2 inhibition activated BKCa channels and reduced intracellular Ca2+. JSI-124 1 mg/kg/day, reduced bleomycin-induced lung fibrosis, PA remodelling, right ventricular hypertrophy, PA hypertension and V/Q mismatching in rats. The animal studies followed the ARRIVE guidelines. CONCLUSIONS: JAK2 participates in PA remodelling and tension and may be an attractive target to treat IPF associated to PH.

Furan and p-xylene as candidate biomarkers for prostate cancer.

BACKGROUND: Prostate cancer (PCa) is the most frequently diagnosed noncutaneous malignant tumor among males in the Western world. Prostate-specific antigen has been considered the most important biomarker for PCa detection; however, it lacks specificity, leading to the search for alternative biomarkers. Volatile organic compounds (VOCs) are released during cell metabolism and can be found in exhaled breath, urine, and other fluids. VOCs have been used in the diagnosis of lung, breast, ovarian, and colorectal cancers, among others. The objective of this study was to identify urinary VOCs that may be sensitive and specific biomarkers for PCa. METHODS: The study included 29 patients with PCa and 21 with benign prostatic hyperplasia. Urine samples were obtained from all participants before and after prostate massage. VOCs were identified by gas chromatography-mass spectrometry. IBM SPSS Statistics v.20 was used for statistical analysis. Sample normality and homogeneity of variances were studied and, according to the distribution normality, ANOVA or the Kruskal-Wallis test was applied to evaluate significant differences between groups. The Pearson test was used to establish correlations. RESULTS: Fifty-seven VOCs were identified. Samples gathered before prostate massage showed significant between-group differences in urinary levels of furan (P≤ 0.001), 2-ethylhexanol (P = 0.032), 3,5-dimethylbenzaldehyde (P = 0.027), santolin triene (P = 0.032), and 2,6-dimethyl-7-octen-2-ol (P = 0.003). Samples gathered after prostate massage showed significant differences in urinary levels of furan (P≤ 0.001), 3- methylphenol (P = 0.014), p-xylene (P = 0.002), phenol (P≤ 0.001), and 2-butanone (P = 0.001). CONCLUSIONS: Significant differences between PCa and BPH patients were found in urinary levels of certain VOCs both before and after prostate massage, supporting the proposal that VOCs may serve as PCa-specific biomarkers.

A terrestrial planet candidate in a temperate orbit around Proxima Centauri.

At a distance of 1.295 parsecs, the red dwarf Proxima Centauri (α Centauri C, GL 551, HIP 70890 or simply Proxima) is the Sun's closest stellar neighbour and one of the best-studied low-mass stars. It has an effective temperature of only around 3,050 kelvin, a luminosity of 0.15 per cent of that of the Sun, a measured radius of 14 per cent of the radius of the Sun and a mass of about 12 per cent of the mass of the Sun. Although Proxima is considered a moderately active star, its rotation period is about 83 days (ref. 3) and its quiescent activity levels and X-ray luminosity are comparable to those of the Sun. Here we report observations that reveal the presence of a small planet with a minimum mass of about 1.3 Earth masses orbiting Proxima with a period of approximately 11.2 days at a semi-major-axis distance of around 0.05 astronomical units. Its equilibrium temperature is within the range where water could be liquid on its surface.

Diagnóstico angiográfico de síndrome de ALCAPA en el adulto / Angiographic diagnosis of ALCAPA syndrome in an adult

El origen anómalo de la arteria coronaria izquierda del tronco de la arteria pulmonar es una alteración coronaria congénita relativamente frecuente. Aunque con alta mortalidad en el primer año de vida, se puede llegar a la adultez. Se presenta el casode una mujer de 28 años con esta enfermedad y su diagnóstico angiográfico(AU)

Técnica de asistencia con balón en anatomía compleja de la vía de acceso transulnar / Balloon-assisted technique in complex anatomy of transulnar access route

Son claras las ventajas de las vías de acceso transradial y transulnar en el cateterismo cardíaco. Sin embargo, variantes anatómicas complejas pueden ser causa de fracaso en la utilización de este procedimiento. Se presenta el caso de un paciente con anatomía arterial compleja en quien se utilizó la técnica de asistencia con balón. Se considera que puede ser útil en casos seleccionados(AU)

Resultados al año del intervencionismo coronario percutáneo multiarterial / One year follow-up outcome in multivessel percutaneous coronary intervention Abstract

Introducción: El intervencionismo coronario percutáneo en la enfermedad multivaso constituye una válida opción de revascularización. Objetivo: Evaluar los resultados del intervencionismo coronario percutáneo multiarterial en pacientes con enfermedad multivaso, e identificar variables predictoras de complicaciones cardíacas graves. Método: Estudio de cohorte retrospectivo y de supervivencia a largo plazo en el Hospital Hermanos Ameijeiras. El seguimiento mínimo fue de un año. La función de supervivencia fue estimada por el método de Kaplan-Meier y se aplicaron análisis uni y multivariado para la identificación de los factores predictores de complicaciones cardíacas graves. Resultados: Fueron tratadas 191 lesiones en 87 pacientes, el 11,5 por ciento presentó enfermedad de tres vasos. El procedimiento fue exitoso en el 97,7 por ciento de los casos y el acceso radial fue el más empleado (67,8 por ciento). La arteria descendente anterior resultó la más frecuentemente tratada (41 por ciento) y el 77 por ciento de las lesiones abordadas fueron complejas (B2 y C). El 14,9 por ciento de los casos presentó alguna complicación cardíaca grave; 3,4 por ciento fallecieron por causa cardíaca, 2,3 por ciento padeció un infarto agudo de miocardio no fatal y el 10,3 por ciento requirió nueva revascularización. La tasa de supervivencia libre de sucesos adversos al año de seguimiento fue de 89,16 por ciento. La enfermedad de tres vasos resultó la única variable que predijo, de forma independiente, la aparición de complicaciones cardíacas graves al año [p=0.01, OR 5,03 (1,18-21,3; 95 por ciento IC)]. Conclusiones: El intervencionismo coronario percutáneo multiarterial, en casos adecuadamente seleccionados, deriva en buenos resultados al año de la intervención. La enfermedad de tres vasos se asoció, de forma independiente, a la ocurrencia de complicaciones cardíacas graves durante el seguimiento(AU)

In silico evaluation of a control system and algorithm for automated insulin infusion in the ICU setting.

BACKGROUND: It is known that tight control of glucose in the Intensive Care Unit reduces morbidity and mortality not only in diabetic patients but also in those non-diabetics who become transiently hyperglycemic. Taking advantage of a recently marketed subcutaneous glucose sensor we designed an Automatic Insulin Infusion System (AIIS) for inpatient treatment, and tested its stability under simulated clinical conditions. METHODS: The system included: reference glucose, glucose sensor, insulin and glucose infusion controllers and emergency infusion logic. We carried out computer simulations using Matlab/Simulink, in both common and worst-case conditions. RESULTS: The system was capable of controlling glucose levels without entering in a phase of catastrophic instability, even under severe simulated challenges. Care was taken to include in all simulations the 5-10 minute delay of the subcutaneous glucose signal when compared to the real-time serum glucose signal, a well-known characteristic of all subcutaneous glucose sensors. CONCLUSIONS: When tested in-Silico, a commercially available subcutaneous glucose sensor allowed the stable functioning of a proportional-derivative Automatic Insulin Infusion System, which was able to maintain glucose within acceptable limits when using a well-established glucose response model simulating a patient. Testing of the system in vivo using animal models is now warranted.

Cigarette smoke-induced pulmonary endothelial dysfunction is partially suppressed by sildenafil.

Cigarette smoke mediated oxidative stress and endothelial dysfunction are important processes in the pathogenesis of several lung disorders. In this study we evaluated the effect of PDE5 inhibition on pulmonary artery endothelial dysfunction induced by cigarette smoke in vitro. Human pulmonary artery endothelial cells (HPAEC) were incubated in the absence or presence of PDE5 inhibitor sildenafil (10 nM-1 microM), PKG agonist 8-Br-cGMP (1mM), or the antioxidants dyphenyleneiodonium (DPI 1 microM) and N-acetylcysteine (NAC 1mM) for 30 min. Then, cigarette smoke extract (CSE) was added for 24h. CSE (2.5-10%)-induced ROS generation was suppressed by DPI, and partially reversed by sildenafil and 8-Br-cGMP. Decreases in intracellular levels of cGMP and extracellular NO induced by CSE were reversed by sildenafil and DPI. Furthermore, CSE-induced pg91(phox) and PDE5 mRNA overexpression were suppressed by both sildenafil and DPI. CSE (2.5-10%) induced upregulation of IL-6, IL-8 and Ang-2, and decreased Ang-1 expression in parallel to apoptosis which were partially suppressed by sildenafil, 8-Br-cGMP, DPI and NAC. This study demonstrates that PDE5 inhibition attenuates the oxidant burden and the inflammatory and remodeling effects of CSE in human HPAEC which may contribute to the therapeutic value of PDE5 inhibitors for pulmonary disorders coursing with endothelial dysfunction.

Treatment of ureteric lithiasis with retrograde ureteroscopy and holmium: YAG laser lithotripsy vs extracorporeal lithotripsy.

OBJECTIVE: To analyse the efficiency of extracorporeal shockwave lithotripsy (ESWL) vs retrograde ureteroscopy and holmium:YAG laser lithotripsy, as ESWL is successful in 67-90% of cases but endoscopic lithotripsy with pneumatic lithotrites or lasers is successful in 90-96% of distal ureteric calculi, and holmium:YAG lithotripsy is effective in proximal ureteric calculi. PATIENTS AND METHODS: From April 2006 to April 2008 we assessed 164 patients undergoing ureteric lithiasis in two homogeneous groups: group A included 83 treated with retrograde ureteroscopy and holmium:YAG endoscopic lithotripsy, and group B, 81 treated by ESWL. For laser lithotripsy we used 2071 mJ pulses at 3-6 Hz, with a mean of 1105 pulses and 2.5 kJ of total energy. ESWL was carried out using 37.5-87.5 mJ shock waves, a mean of 3650 shock waves and 187.6 J, with a radioscopy time of 1-4 min. The results were assessed after 3 weeks with plain films and ultrasonography, or urography. The efficiency of each procedure was assessed by calculating the relative risk, and results compared using the chi-square or Student's t-test. The efficiency quotient (EQ) was determined for both procedures, and the focal applied energy quotient (FAEQ) used to assess ESWL. RESULTS: The overall success rate for retrograde ureteroscopy and laser lithotripsy was 96.4% (80/83 patients), with an EQ of 0.52; a JJ catheter was placed in 67 patients. The success rate for the first ESWL session was 48%, and after repeat ESWL was 64% (52/81 patients), giving an EQ of 0.39. For successful treatments the FAEQ was 9.22, vs 6.47 for the failures (P < 0.005). There was a significant difference (P < 0.001) favouring laser lithotripsy, with an absolute benefit of 46% (95% confidence interval 33.8-57.9%), and number needed to treat of 2 (2-3), but no significant differences for lumbar ureteric calculi. CONCLUSIONS: Endoscopic lithotripsy with the holmium laser is more effective than ESWL, but for lumbar ureteric calculi ESWL is therapeutically recommended as it is less invasive.

Patrones de flujo transmitral en pacientes con hipertensión arterial esencial / Patterns of transmitral flow in patients with essential arterial hypertension

Se evaluó el comportamiento de la función diastólica mediante el flujo transmitral por ecocardiografía doppler pulsado en pacientes con hipertensión arterial esencial. Se realizó un estudio descriptivo longitudinal a 400 pacientes hipertensos esenciales del sexo masculino en edades de 30 a 60 años y en el período de 1998 al 2000. Los resultados más relevantes fueron en el patrón tipo I, el 73 por ciento de los pacientes pertenecía al grupo normal alta, mientras que el patrón tipo II, el 68 por ciento correspondía a la hipertensión arterial severa. El captopril fue el medicamento más efectivo en todos los tipos de hipertensión arterial. Se llegó a la conclusión de que el estudio de los patrones de flujo transmitral en los pacientes hipertensos esenciales ha resultado ser de gran utilidad y que los pacientes con disfunción diastólica pueden ser tratados para que no desarrollen insuficiencia cardíaca

Patrones de flujo transmitral en pacientes con hipertensión arterial esencial / Patterns of transmitral flow in patients with essential arterial hypertension

Se evaluó el comportamiento de la función diastólica mediante el flujo transmitral por ecocardiografía doppler pulsado en pacientes con hipertensión arterial esencial. Se realizó un estudio descriptivo longitudinal a 400 pacientes hipertensos esenciales del sexo masculino en edades de 30 a 60 años y en el período de 1998 al 2000. Los resultados más relevantes fueron en el patrón tipo I, el 73 por ciento de los pacientes pertenecía al grupo normal alta, mientras que el patrón tipo II, el 68 por ciento correspondía a la hipertensión arterial severa. El captopril fue el medicamento más efectivo en todos los tipos de hipertensión arterial. Se llegó a la conclusión de que el estudio de los patrones de flujo transmitral en los pacientes hipertensos esenciales ha resultado ser de gran utilidad y que los pacientes con disfunción diastólica pueden ser tratados para que no desarrollen insuficiencia cardíaca(AU)