Pulmonary artery obstruction index, pulmonary artery diameter and right ventricle strain as prognostic CT findings in patient with acute pulmonary embolism.

OBJECTIVE: This study was designed to determine predictors of pulmonary hypertension and signs of right heart dysfunction caused by pulmonary embolism (PE) that may lead to early detection of high-risk patients. So the predictive value of pulmonary artery obstruction index (PAOI), measured by pulmonary CT angiography (PCTA) in the acute setting, in predicting the patients susceptible to PE cardiac complications was evaluated. Also two other PCTA indices, pulmonary artery diameter (PAD), and right ventricle (RV) strain, in these patients were investigated and their predictive value for cardiac complications on follow up echocardiography were demonstrated. MATERIALS AND METHODS: In the study 120 patients with a definite diagnosis of PE were included. The PAOI, PAD and RV strain were measured using PCTA at the time of the initial diagnosis. Transthoracic echocardiography was done 6 months after the diagnosis of PE and RV echocardiographic indices were measured. Pearson correlation was used to investigate correlation between PAOI, PAD, RV strain and signs of right heart dysfunction. RESULTS: PAOI was strongly correlated with systolic pulmonary artery pressure (SPAP) (r=0.83), RV systolic pressure (r=0.78) and RV wall thickness (r=0.61) in long-term follow up echocardiography. A higher rate of RV dysfunction and RV dilation was detected among the patients with higher PAOI (P<0.001). PAOI≥18 was strongly predictive for development of RV dysfunction. Also developments of pulmonary hypertension, RV systolic hypertension, RV dilation, RV dysfunction, and RV hypertrophy were significantly more common among patients with higher PAD and RV strain (P<0.001). CONCLUSIONS: PAOI, PAD and RV strain are sensitive and specific PCTA indices that can predict the development of long-term complications such as pulmonary hypertension and right heart dysfunction, at the time of initial PE diagnosis.

Índice de obstrucción de la arteria pulmonar, diámetro de la arteria pulmonar y strain del ventrículo derecho como hallazgos pronósticos de la tomografía computarizada en el paciente con embolia pulmonar aguda / Pulmonary artery obstruction index, pulmonary artery diameter and right ventricle strain as prognostic CT findings in patient with acute pulmonary embolism

Objetivo: Este estudio fue diseñado para determinar los predictores de la hipertensión pulmonar y los signos de disfunción cardíaca derecha causados por la embolia pulmonar (EP) que pueden conducir a la detección temprana de los pacientes de alto riesgo. Por lo tanto, se evaluó el valor predictivo del índice de obstrucción de la arteria pulmonar (IOAP), medido mediante angiografía pulmonar por TC (APTC) en el contexto agudo, para predecir los pacientes susceptibles de sufrir complicaciones cardíacas por EP. También se investigaron otros dos índices de APTC, el diámetro de la arteria pulmonar (DAP) y el strain del ventrículo derecho (VD), en estos pacientes y se demostró su valor predictivo de las complicaciones cardíacas en la ecocardiografía de seguimiento. Materiales y métodos: En el estudio fueron incluidos 120 pacientes con diagnóstico definitivo de EP. El IOAP, el DAP y el strain del VD se midieron mediante APTC en el momento del diagnóstico inicial. Se realizó una ecocardiografía transtorácica 6 meses después del diagnóstico de EP y se midieron los índices ecocardiográficos del VD. Se utilizó la correlación de Pearson para investigar la correlación entre IOAP, DAP, strain del VD y los signos de disfunción del hemicardio derecho. Resultados: El IOAP estaba fuertemente correlacionado con la presión arterial pulmonar sistólica (PAPS) (r=0,83), la presión sistólica del VD (r=0,78) y el grosor de la pared del VD (r=0,61) en la ecocardiografía de seguimiento a largo plazo. Se detectó una mayor tasa de disfunción del VD y de dilatación del VD entre los pacientes con mayor IOAP (p<0,001). Un IOAP≥18 fue claramente predictivo del desarrollo de la disfunción del VD. También la evolución de la hipertensión pulmonar, la hipertensión sistólica del VD, la dilatación del VD, la disfunción del VD y la hipertrofia del VD fueron significativamente más frecuentes entre los pacientes con mayor DAP y strain del VD (p<0,001)...(AU)

Objective: This study was designed to determine predictors of pulmonary hypertension and signs of right heart dysfunction caused by pulmonary embolism (PE) that may lead to early detection of high-risk patients. So the predictive value of pulmonary artery obstruction index (PAOI), measured by pulmonary CT angiography (PCTA) in the acute setting, in predicting the patients susceptible to PE cardiac complications was evaluated. Also two other PCTA indices, pulmonary artery diameter (PAD), and right ventricle (RV) strain, in these patients were investigated and their predictive value for cardiac complications on follow up echocardiography were demonstrated. Materials and methods: In the study 120 patients with a definite diagnosis of PE were included. The PAOI, PAD and RV strain were measured using PCTA at the time of the initial diagnosis. Transthoracic echocardiography was done 6 months after the diagnosis of PE and RV echocardiographic indices were measured. Pearson correlation was used to investigate correlation between PAOI, PAD, RV strain and signs of right heart dysfunction. Results: PAOI was strongly correlated with systolic pulmonary artery pressure (SPAP) (r=0.83), RV systolic pressure (r=0.78) and RV wall thickness (r=0.61) in long-term follow up echocardiography. A higher rate of RV dysfunction and RV dilation was detected among the patients with higher PAOI (P<0.001). PAOI≥18 was strongly predictive for development of RV dysfunction. Also developments of pulmonary hypertension, RV systolic hypertension, RV dilation, RV dysfunction, and RV hypertrophy were significantly more common among patients with higher PAD and RV strain (P<0.001). Conclusions: PAOI, PAD and RV strain are sensitive and specific PCTA indices that can predict the development of long-term complications such as pulmonary hypertension and right heart dysfunction, at the time of initial PE diagnosis.(AU)

Association of body mass index with 30-day outcomes following groin hernia repair.

PURPOSE: Although groin hernia repairs are relatively safe, efforts to identify factors associated with greater morbidity and resource utilization following these operations are warranted. An emphasis on obesity has limited studies from a comprehensive evaluation of the association between body mass index (BMI) and outcomes following groin hernia repair. Thus, we aimed to ascertain the association between BMI class with 30-day outcomes following these operations. METHODS: The 2014-2020 National Surgical Quality Improvement Program database was queried to identify adults undergoing non-recurrent groin hernia repair. Patient BMI was used to stratify patients into six groups: underweight, normal, overweight, and obesity classes I-III. Association of BMI with major adverse events (MAE), wound complication, and prolonged length of stay (pLOS) as well as 30-day readmission and reoperation were evaluated using multivariable regressions. RESULTS: Of the 163,373 adults who underwent groin hernia repair, the majority of patients were considered overweight (44.4%). Underweight patients more commonly underwent emergent operations and femoral hernia repair compared to others. After adjustment of intergoup differences, obesity class III was associated with greater odds of an MAE (AOR 1.50), wound complication (AOR 4.30), pLOS (AOR 1.40), and 30-day readmission (AOR 1.50) and reoperation (AOR 1.75, all p < 0.05). Underweight BMI portended greater odds of pLOS and unplanned readmission. CONCLUSION: Consideration of BMI in patients requiring groin hernia repair could help inform perioperative expectations. Preoperative optimization and deployment of a minimally invasive approach when feasible may further reduce morbidity in patients at the extremes of the BMI spectrum.

Pulmonary artery obstruction index, pulmonary artery diameter and right ventricle strain as prognostic CT findings in patient with acute pulmonary embolism. / Índice de obstrucción de la arteria pulmonar, diámetro de la arteria pulmonar y strain del ventrículo derecho como hallazgos pronósticos de la tomografía computarizada en el paciente con embolia pulmonar aguda.

OBJECTIVE: This study was designed to determine predictors of pulmonary hypertension and signs of right heart dysfunction caused by pulmonary embolism (PE) that may lead to early detection of high-risk patients. So the predictive value of pulmonary artery obstruction index (PAOI), measured by pulmonary CT angiography (PCTA) in the acute setting, in predicting the patients susceptible to PE cardiac complications was evaluated. Also two other PCTA indices, pulmonary artery diameter (PAD), and right ventricle (RV) strain, in these patients were investigated and their predictive value for cardiac complications on follow up echocardiography were demonstrated. MATERIALS AND METHODS: In the study 120 patients with a definite diagnosis of PE were included. The PAOI, PAD and RV strain were measured using PCTA at the time of the initial diagnosis. Transthoracic echocardiography was done 6 months after the diagnosis of PE and RV echocardiographic indices were measured. Pearson correlation was used to investigate correlation between PAOI, PAD, RV strain and signs of right heart dysfunction. RESULTS: PAOI was strongly correlated with systolic pulmonary artery pressure (SPAP) (r=0.83), RV systolic pressure (r=0.78) and RV wall thickness (r=0.61) in long-term follow up echocardiography. A higher rate of RV dysfunction and RV dilation was detected among the patients with higher PAOI (P<0.001). PAOI≥18 was strongly predictive for development of RV dysfunction. Also developments of pulmonary hypertension, RV systolic hypertension, RV dilation, RV dysfunction, and RV hypertrophy were significantly more common among patients with higher PAD and RV strain (P<0.001). CONCLUSIONS: PAOI, PAD and RV strain are sensitive and specific PCTA indices that can predict the development of long-term complications such as pulmonary hypertension and right heart dysfunction, at the time of initial PE diagnosis.

Solution structure of 3-oxo-delta5-steroid isomerase.

The three-dimensional structure of the enzyme 3-oxo-delta5-steroid isomerase (E.C. 5.3.3.1), a 28-kilodalton symmetrical dimer, was solved by multidimensional heteronuclear magnetic resonance spectroscopy. The two independently folded monomers pack together by means of extensive hydrophobic and electrostatic interactions. Each monomer comprises three alpha helices and a six-strand mixed beta-pleated sheet arranged to form a deep hydrophobic cavity. Catalytically important residues Tyr14 (general acid) and Asp38 (general base) are located near the bottom of the cavity and positioned as expected from mechanistic hypotheses. An unexpected acid group (Asp99) is also located in the active site adjacent to Tyr14, and kinetic and binding studies of the Asp99 to Ala mutant demonstrate that Asp99 contributes to catalysis by stabilizing the intermediate.

Synthesis and biochemical studies of 7 alpha-substituted androsta-1,4-diene-3,17-diones as enzyme-activated irreversible inhibitors of aromatase.

Several 7 alpha-thiosubstituted derivatives of androstenedione have demonstrated effective inhibition of aromatase, the cytochrome P450 enzyme complex responsible for the biosynthesis of estrogens. Introduction of an additional double bond in the A ring resulted in 7 alpha-(4'-amino)phenylthioandrosta-1,4-diene-3,17-dione (7 alpha-APTADD), a potent inhibitor that inactivated aromatase by an enzyme-catalyzed process. Additional 7 alpha-thiosubstituted androsta-1,4-diene-3,17-dione derivatives were designed to further examine enzyme-catalyzed inactivation. Two halogenated and one unsubstituted 7 alpha-phenylthioandrosta-1,4-diene-3,17-diones were synthesized via an acid-catalyzed conjugate Michael addition of substituted thiophenols with androsta-1,4,6-triene-3,17-dione. Two 7 alpha-naphthylthioandrosta-1,4-diene-3,17-diones were synthesized via either acid-catalyzed or based-catalyzed conjugate Michael addition of substituted thionaphthols with androsta-1,4,6-triene-3,17-dione. These agents were evaluated for aromatase inhibitory activity in the human placental microsomal preparation. Under initial velocity assay conditions of low product formation, the inhibitors demonstrated potent inhibition of aromatase, with apparent Ki's ranging from 12 to 27 nM. Furthermore, these compounds produced time-dependent, first-order inactivation of aromatase in the presence of NADPH, whereas no aromatase inactivation was observed in the absence of NADPH. This enzyme-activated irreversible inhibition, also referred to as mechanism-based inhibition, can be prevented by the substrate androstenedione. Thus, the apparent Ki values for these inhibitors are consistent with earlier studies on 7 alpha-substituted competitive inhibitors that indicate bulky substituents can be accommodated at the 7 alpha-position.(ABSTRACT TRUNCATED AT 250 WORDS)

Steroidal inhibitors as chemical probes of the active site of aromatase.

Androstenedione analogs containing 7 alpha-substituents have proven to be potent inhibitors of aromatase in human placental microsomes, in MCF-7 mammary cell cultures, and in JAr choriocarcinoma cells. Recent investigations have focused on the use of mechanism-based inhibitors, such as 7 alpha-substituted 1,4-androstadienediones, to biochemically probe the active site of aromatase. Inhibition kinetics were determined under initial velocity conditions using purified human placental cytochrome P450arom protein in a reconstituted system. Derivatives of 1,4-androstadiene-3,17-dione and 1,4,6-androstatriene-3,17-dione exhibited high affinity in the purified enzyme system. 7 alpha-(4'-Amino)phenylthio-1,4-androstadiene-3,17-dione, abbreviated 7 alpha-APTADD, demonstrated rapid time-dependent, first-order inactivation of reconstituted aromatase activity only in the presence of NADPH. The apparent Kinact for 7 alpha-APTADD is 11.8 nM, the first-order rate of inactivation is 2.72 x 10(-3) sec-1, and the half-time of inactivation at infinite inhibitor concentration is 4.25 min. The values for the rate constant and half-time of inactivation are similar to those observed in the placental microsomal assay system. Further studies were performed with radioiodinated 7 alpha-(4'-iodo)phenylthio-1,4-androstadienedione, 7 alpha-IPTADD, and the reconstituted aromatase system. Incubations with [125I] 7 alpha-IPTADD were followed by protein precipitation, solvent extraction, and column chromatography. Analysis of the isolated cytochrome P450arom by gel electrophoresis and autoradiography demonstrated the presence of only one radioactive band, which corresponded to the protein staining band for cytochrome P450arom. HPLC radiochromatographic analysis of the isolated cytochrome P450aroM confirmed the presence of only one radioactive peak coeluting with the u.v. peak for cytochrome P450arom. Peptide mapping analysis by reverse-phase HPLC of digested inhibitor-cytochrome P450arom complex demonstrates that the radioactive inhibitor is covalently bound to a lipophilic fragment. In summary, these inhibitors produced enzyme-catalyzed inactivation of reconstituted aromatase activity, and radioiodinated 7 alpha-IP-TADD binds covalently to the cytochrome P450arom.