Use of Receiver Operating Curve Analysis and Machine Learning With an Independent Dose Calculation System Reduces the Number of Physical Dose Measurements Required for Patient-Specific Quality Assurance.

PURPOSE: Our purpose was to assess the use of machine learning methods and Mobius 3D (M3D) dose calculation software to reduce the number of physical ion chamber (IC) dose measurements required for patient-specific quality assurance during corona virus disease 2019. METHODS AND MATERIALS: In this study, 1464 inversely planned treatments using Pinnacle or Raystation treatment planning software (TPS) were delivered using Elekta Versa HD and Varian Truebeam and Truebeam STx linear accelerators between June 2018 and November 2019. For each plan, an independent dose calculation was performed using M3D, and an absolute dose measurement was taken using a Pinpoint IC inside the Mobius phantom. The point dose differences between the TPS and M3D calculation and between TPS and IC measurements were calculated. Agreement between the TPS and IC was used to define the ground truth plan failure. To reduce the on-site personnel during the pandemic, 2 methods of receiver operating characteristic analysis (n = 1464) and machine learning (n = 603) were used to identify patient plans that would require physical dose measurements. RESULTS: In the receiver operating characteristic analysis, a predelivery M3D difference threshold of 3% identified plans that failed an IC measurement at a 4% threshold with 100% sensitivity and 76.3% specificity. This indicates that fewer than 25% of plans required a physical dose measurement. A threshold of 1% on a machine learning model was able to identify plans that failed an IC measurement at a 3% threshold with 100% sensitivity and 54.3% specificity, leading to fewer than 50% of plans that required a physical dose measurement. CONCLUSIONS: It is possible to identify plans that are more likely to fail IC patient-specific quality assurance measurements before delivery. This possibly allows for a reduction of physical measurements taken, freeing up significant clinical resources and reducing the required amount of on-site personnel while maintaining patient safety.

Safety, feasibility and weight loss after transoral gastroplasty: First human multicenter study.

OBJECTIVE: To evaluate the safety and feasibility in human subjects of a new transoral restrictive procedure for the treatment of obesity. METHODS: The protocol was approved by the institutional review boards (IRBs) of both centers involved, and all patients gave informed consent. Patients met established inclusion criteria for bariatric surgery. The TOGa system (Satiety Inc., Palo Alto, CA), a set of transoral endoscopically guided staplers, was used to create a stapled restrictive pouch along the lesser curve of the stomach. Patients were hospitalized overnight for observation and underwent barium upper gastrointestinal (UGI) the next morning. Post procedure, all patients were placed on a liquid diet for 1 month and asked to begin an exercise program. Follow-up was carried out at 1 week and 1, 3, 4, 5, and 6 months. RESULTS: Twenty one patients were enrolled [17 female, age 43.7 (22-57) years, BMI 43.3 (35-53) kg/m(2)]. Device introduction was completed safely in all patients. There were no serious adverse events (AEs). The most commonly reported procedure or device related adverse events were vomiting, pain, nausea, and transient dysphagia. At 6 month endoscopy, all patients had persistent full or partial stapled sleeves. Gaps in the staple line were evident in 13 patients. Patients lost an average 17.6 pounds at 1 month, 24.5 pounds at three months, and 26.5 pounds at 6 months post-treatment [excess weight loss (EWL) of 16.2%, 22.6%, and 24.4%, respectively]. CONCLUSIONS: There is great interest in new procedures for morbid obesity that could offer lower morbidity than current options. Early experience with the TOGa procedure indicates that this transoral approach may be safe and feasible. Further experience with the device and technique should improve anatomic and functional outcomes in the future. Additional studies are underway.

Carcinoma sebáceo, 6 años de experiencia en el Instituto Nacional del Cáncer

Objetivo: El carcinoma sebáceo (CS) es una neoplasia infrecuente, de la cual no existen reportes nacionales, ni guías de manejo en Chile. El Instituto Nacional del Cáncer (INC) es un centro de referencia nacional en el manejo de patologías oncológicas; el objetivo de este trabajo es describir la experiencia y tratamiento del carcinoma sebáceo en nuestro centro. Material y Método: Se realizó una revisión retrospectiva, descriptiva, de fichas clínicas entre marzo de 2016 y marzo de 2022 en el INC, en las cuales la biopsia definitiva fuese confirmatoria de CS. Resultados: Se reclutaron 10 pacientes, 6 hombres (60%) y 4 mujeres. Edad promedio fue de 62,9 años ± 18,7 DS. En el 80% de los casos el tumor se encontró en cabeza y cuello y solo 2 casos fueron CS ocular (20%). 4 pacientes tenían asociación al Síndrome de Muir-Torre (SMT) (40%), en el 100% de la muestra se realizó tratamiento quirúrgico con resección oncológica y control de márgenes intraoperatorio, utilizándose en solo 3 casos la técnica Cirugía Micrográfica de Mohs (MMS). En 4 pacientes (40%) se realizó biopsia de linfonodo centinela (BLNC), de los cuales ninguno resulto positivo para metástasis. Ningún paciente presento recidiva local, después de la cirugía y no hubo casos de mortalidad a causa de CS. Ningún paciente recibió radioterapia, quimioterapia o inmunoterapia adyuvante, solo 1 paciente recibió braquiterapia (BT) adyuvante. Conclusión: El CS es una patología compleja e infrecuente, que requiere un tratamiento multidisciplinario y cuyo pilar es la cirugía.

Objective: Sebaceous carcinoma (SC) is an infrequent neoplasm, without national reports nor management guidelines in Chile. National Cancer Institute (NCI) is a reference center for this kind of disease. The aim of this research is to describe the experience and treatment of the sebaceous carcinoma in our center. Methods: A retrospective, descriptive review of clinical records was performed, between March 2016 and March 2022 at the INC, in which the definitive biopsy was confirmatory of CS. Results: A total of 10 patients were enrolled; 6 male (60%) and 4 women. The mean age was 62.9 years ± 18.7 (SD). 80% of the cases were located at the head or the cervical area and only 2 cases were found in the ocular region (20%). Association with SMT (40%) was found in 4 patients. Surgical treatment with oncological resection and intraoperative assessment of margins was performed in 100% of the cases, using MMS technique. Sentinel lymph node biopsy (BLNC) was performed in 4 patients (40%), of which none had metastasis. No patient presented local recurrence after surgery and there were no cases of mortality due to CS. No patient received radiotherapy, chemotherapy or adjuvant immunotherapy. Just 1 received adjuvant brachytherapy. Conclusion: SC is a complex and infrequent disease, which requires multidisciplinary treatment mainly with surgery.

Distribution of angiotensin-(1-7) and ACE2 in human placentas of normal and pathological pregnancies.

This work was designed to study the expression of the vasodilator peptide angiotensin-(1-7) [Ang-(1-7)] and its generating enzyme (ACE2) in the uteroplacental interface. Placentas were obtained from 11 early pregnancy failures (5 miscarriages and 6 ectopic pregnancies), 15 normotensive, and 10 preeclamptic gestations. In placental villi, the main sites of immunocytochemical expression of Ang-(1-7) and ACE2 were the syncytiotrophoblast, cytotrophoblast, endothelium and vascular smooth muscle of primary and secondary villi. Syncitial Ang-(1-7) expression in samples obtained from miscarriages and ectopic pregnancies was increased compared to normal term pregnancy [2.0 (2.0-2.25 for the 25 and 75% interquartile range) vs 1.3 (1.0-1.9), p<0.01]. In the maternal stroma, Ang-(1-7) and ACE2 were expressed in the invading and intravascular trophoblast and in decidual cells in all 3 groups. Ang-(1-7) and ACE2 staining was also found in arterial and venous endothelium and smooth muscle of the umbilical cord. The expression of Ang-(1-7) and ACE2 was similar in samples obtained from normal term or preeclamptic pregnancies, except for increased expression of ACE2 in umbilical arterial endothelium in preeclampsia [0.5 (0.5-0.8) vs 0.0 (0.0-0.0), p<0.01]. The uteroplacental location of Ang-(1-7) and ACE2 in pregnancy suggests an autocrine function of Ang-(1-7) in the vasoactive regulation that characterizes placentation and established pregnancy.

A mathematical framework for virtual IMRT QA using machine learning.

PURPOSE: It is common practice to perform patient-specific pretreatment verifications to the clinical delivery of IMRT. This process can be time-consuming and not altogether instructive due to the myriad sources that may produce a failing result. The purpose of this study was to develop an algorithm capable of predicting IMRT QA passing rates a priori. METHODS: From all treatment, 498 IMRT plans sites were planned in eclipse version 11 and delivered using a dynamic sliding window technique on Clinac iX or TrueBeam Linacs. 3%/3 mm local dose/distance-to-agreement (DTA) was recorded using a commercial 2D diode array. Each plan was characterized by 78 metrics that describe different aspects of their complexity that could lead to disagreements between the calculated and measured dose. A Poisson regression with Lasso regularization was trained to learn the relation between the plan characteristics and each passing rate. RESULTS: Passing rates 3%/3 mm local dose/DTA can be predicted with an error smaller than 3% for all plans analyzed. The most important metrics to describe the passing rates were determined to be the MU factor (MU per Gy), small aperture score, irregularity factor, and fraction of the plan delivered at the corners of a 40 × 40 cm field. The higher the value of these metrics, the worse the passing rates. CONCLUSIONS: The Virtual QA process predicts IMRT passing rates with a high likelihood, allows the detection of failures due to setup errors, and it is sensitive enough to detect small differences between matched Linacs.

Influence of the kidney histology at the time of donation on long term kidney function in living kidney donors.

Living donation is the best choice for kidney transplantation, obtaining long-lasting good results for the recipient. Some concern still remains regarding the donor's long-term health. Kidney biopsy was routinely performed in our donor population at the time of donation many years ago. We found the existence of morphological kidney disease in those samples, in spite of normal clinical evaluations before donation. We attempted to correlate those abnormalities with long-term clinical outcomes. Donors were at least 10 years after surgery. A medical interview, including the SF-36 Health Survey, laboratory evaluation, and ambulatory blood pressure monitoring was performed on 27 donors meeting the inclusion criteria. Two donors had died after donation from unrelated causes with no known nephropathy. Histological analysis showed abnormalities in 16 of 29 donors. We found an increased prevalence of hypertension compared to the general population. Interestingly, there was no proteinuria in the donor population, and none developed clinical nephropathy. All subjects felt emotionally rewarded with donation, stating that their lives had no limitations. Our results suggest that kidney biopsy is neither necessary nor useful prior to donation because, although many donors had morphological kidney disease, none developed clinical nephropathy in the long term.

Traqueostomía en pacientes con COVID-19: recomendaciones actuales / Traqueostomy in COVID-19 patients: current recomendations

Resumen El nuevo coronavirus (SARS-CoV-2), causante de la enfermedad COVID-19, es una pandemia con alta morbimortalidad mundial. Uno de los factores más importantes es su alta tasa de transmisibilidad por gotitas, aerosoles y fómites. La tendencia actual es el aumento progresivo de pacientes contagiados en nuestro país y, por consiguiente, de mayor cantidad de enfermos en unidades de cuidados intensivos (UCI) con uso de ventilación mecánica invasiva (VMI). La traqueostomía (TQT) se utiliza en pacientes críticos para facilitar la VMI a largo plazo y el destete de la ventilación. Una TQT temprana, definida como la realizada en los primeros 7 días después de la intubación orotraqueal (IOT), se asocia a una reducción en el tiempo de la VMI, mortalidad y permanencia en UCI. La TQT es una técnica quirúrgica con alta generación de aerosoles la cual implica medidas especiales frente a la realización de ésta en pacientes con COVID-19. Para limitar el contagio del SARS-CoV-2 en los trabajadores de salud es necesario el uso de elementos de protección personal (EPP) adecuados según la intervención a realizar. Es por esta razón que en el presente artículo se propone utilizar el acrónimo C-O-RO-NA para no olvidar elementos y pasos fundamentales al momento de realizar esta técnica, minimizando de esta manera el contagio en los trabajadores de salud.

The new coronavirus (SARS-CoV-2), which causes COVID-19 disease, is a high mortality pandemic illness. One of the most important factors is its high rate of transmissibility by respiratory droplets, aerosols and fomites. The reigning trend of this disease is progressively increasing infected patients in our country, therefore, more patients in intensive care units (ICU) with invasive mechanical ventilation (IMV). Tracheostomy (TQT) is used in critical patients to facilitate long-term IMV and ventilation weaning. An early TQT, defined as performed in the first 7 days after orotracheal intubation (IOT) is associated with a reduction IMV duration, mortality rate and length of stay in ICU. TQT is a surgical procedure which generates a huge amount of aerosols that need special measures to perform in COVID-19 patients. It is necessary to use appropriate personal protection elements (PPE) according to the intervention, limiting the spread of SARS-CoV-2 in health workers. It is for this reason that this article proposes to use the acronym C-O-RO-NA to remember fundamental elements and steps when performing this technique in order to minimize health workers infection.

Urinary kallikrein and plasma renin activity in normal human pregnancy.

Urinary kallikrein excretion (UK), plasma renin activity (PRA), and 24-hour urine volume, sodium, and potassium excretion rates were determined sequentially in 16 normal pregnant women. Throughout gestation, UK was significantly elevated as compared to values obtained in 13 control women (1466 +/- 152 vs 375 +/- 90 U/g creatinine). The highest level was observed in Period 2 of gestation, corresponding to Weeks 17 to 24. PRA was also significantly elevated during pregnancy (11.97 +/- 1,35 vs 1.06 +/- 0.90 ng/ml/hr), with the highest level in Period 2. Mean 24-hour urine volume, sodium, and potassium excretion rates were significantly higher during pregnancy. Nor correlation was found between UK and: PRA, urine volume, and sodium and potassium excretions. These findings indicate a consistent activation of the renal-kallikrein-kinin system during pregnancy. We postulate that this vasodilator system might play a role in the maintenance of normotension in pregnancy, counteracting tha effect of the renin-angiotensin-aldosterone system.

Renin-secreting tumor. Case report.

Renin-secreting tumor, though rare, should be considered in assessing severe hyperreninemic, hypertensive patients. We studied an 18-year-old girl with hypokalemic hyperreninemic hyperaldosteronism. No angiographic lesion could be detected. The plasma renin activity (PRA) of the right/left renal vein was 7.3. With a presumptive diagnosis of renin-secreting tumor (RST), the patient was operated on, and a cortical nodule was found on the right lower pole. Partial nephrectomy was followed by a rapid fall in PRA (half-life, 33-44 min) and normalization of blood pressure (BP). At 3 1/2 months postoperatively, the patient showed normotension, normokalemia, normal aldosterone, and slightly elevated PRA unresponsive to postural changes and furosemide treatment. Tumoral PRA secretion responded to postural stimulus, spironolactone use, and nitroprusside-induced hypotension. Neither the high aldosterone excretion nor hyperreninemia decreased after 3 days of DOCA; this agrees with a previously reported case suggesting the usefulness of this test in the diagnosis of RST.

Interaction of nonsteroidal anti-inflammatory drugs with antihypertensive and diuretic agents. Control of vascular reactivity by endogenous prostanoids.

Indomethacin and some other nonsteroidal anti-inflammatory drugs partially antagonize the blood pressure lowering effect of drugs used to treat hypertension. They can also produce a mild elevation of blood pressure in normotensive individuals. The elevated arterial pressure caused by these agents is associated with increases in the vascular resistance of mainly the renal and splanchnic beds. This may be due to direct inhibition of the synthesis of vasodilator prostanoids, or it may be due to indirect potentiation of the action of the sympathetic nervous system or of angiotensin II. Nonsteroidal anti-inflammatory drugs also cause renal retention of sodium and this probably contributes to their hypertensive effects. In humans, the sodium retention may involve increased reabsorption in the proximal tubule. Although a direct tubular action is possible, these drugs may change proximal sodium reabsorption by their vascular effects. However, the exact mechanism is not understood. These interactions are clinically significant and may complicate the treatment of common diseases.

Maternal plasma volume expansion and hormonal changes in women with idiopathic fetal growth retardation.

OBJECTIVE: To explore the mechanisms underlying the reduced maternal plasma volume associated with idiopathic fetal growth retardation (FGR). METHODS: In 30 normotensive women with growth-retarded fetuses and 26 with normal-size fetuses, plasma volume was measured with a modified Evan's blue method. Plasma levels of atrial natriuretic peptide, plasma renin activity, aldosterone, estradiol, and progesterone, and urinary excretion of kallikrein, prostacyclin, and thromboxane A2 were measured at 34-40 weeks' gestation. RESULTS: Compared with controls, gravidas with growth-retarded fetuses had a reduced plasma volume expansion (P < .01), similar atrial natriuretic peptide and plasma renin activity levels, and lower serum aldosterone (P < .001) and placental steroids (P < .03). These women also had decreased urinary kallikrein activity and prostaglandin excretion (P < .05). When both groups were combined, maternal plasma volume correlated significantly with birth weight (r = 0.53) and placental weight (r = 0.66). CONCLUSION: Normotensive women with idiopathic FGR have reduced plasma volume expansion. Although the exact mechanisms of this change are unknown, we postulate that the lower maternal aldosterone levels and reduced levels of vasodilator substances, such as prostacyclin and kallikrein, may have a causal role.

Potassium supplementation lowers blood pressure and increases urinary kallikrein in essential hypertensives.

In order to eludicate possible mechanism(s) involved in the blood pressure reduction induced by potassium (K) supplementation, we studied the changes of BP and of some of its regulatory systems, including levels of urinary kallikrein (UKal)--an index of renal kallikrein production. Twenty-four untreated essential hypertensives, with a basal BP of 147/96 +/- 13/7 mmHg and normal renal function, received in crossover, double-blind, randomised fashion, 64 mmol KCl or placebo during two periods of 4 weeks each. At the 4th week of potassium supplementation systolic, diastolic and mean BPs decreased by 6.3 +/- 2 (P less than 0.01), 3.0 +/- 2 and 4.1 +/- 2 (P less than 0.05) mmHg respectively for the supine position, and 5.0 +/- 2, 4.0 +/- 2 (P less than 0.05) and 4.0 +/- 1 (P less than 0.05) mmHg for the standing position. Urinary potassium (K) increased from 55 +/- 4 to 123 +/- 6 mmol/24 hours (P less than 0.001) and UKal from 692 +/- 69 to 1052 +/- 141 mU/24 hours (P less than 0.01). Serum K rose from 3.8 +/- 0.1 mEq/l to 4.1 +/- 0.1 mmol/l (P less than 0.001) and PRA from 0.77 +/- 0.12 to 0.99 +/- 0.14 ng/ml/h (P less than 0.05). Correlations were observed between UKal and urinary K (r = 0.44, P less than 0.0001); between differences in UKal and urinary K and in UKal and urinary Na (r = 0.50, P less than 0.0005 and r = 0.48, P less than 0.001 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Recurrence rate after laparoscopic repair of recurrent inguinal hernias: have we improved?

Laparoscopic repair of recurrent inguinal hernias is becoming increasingly accepted in surgical practice, using an extraperitoneal or transabdominal approach for the placement of mesh. Previous literature reflects that efforts to perform open repair of recurrent inguinal hernias often result in further recurrences, testicular damage, or nerve injuries. Our study reflects physical examination of 37 patients over 4 years that underwent laparoscopic repair of recurrent inguinal hernia(s). Early and late complications are presented. The re-recurrence rate at this short follow up to 54 months is quite low at 2.5%. The laparoscopic repair of recurrent hernia reflects a very low likelihood of recurrence, low occurrence of testicular damage, and less likelihood of other such complications as nerve or spermatic cord injury (none of these occurred in this study). Seroma was clinically significant in 3 patients and no infections were noted. Our study and ongoing careful follow-up are the subject of this report.

Excessive sodium retention as a characteristic of salt-sensitive hypertension.

To investigate the possibility that salt-sensitive hypertensives have deficient sodium excretion, the sodium retained by 20 hypertensive patients during a salt load (SL = 3.88 mEq/Kg/day) was calculated for 3 days immediately after 4 days of sodium deprivation (SD = 9 mEq/d). Patients were divided into two groups by arterial pressure responses to SD: responders (N = 10) whose pressures became normal rapidly and averaged less than 140/90 during SD and nonresponders (n = 10) whose pressures were not affected. Sodium retention (mEq/Kg) during SL was calculated as cumulative sodium intake minus cumulative urinary sodium divided by body weight. Responders retained more sodium during SL than nonresponders (3.71 +/- 0.96 [SD] vs. 2.52 +/- 1.05 mEq/Kg, p less than 0.02). This could not be explained by a measurable decrease in filtered sodium load since creatinine clearance was the same in each group. Neither was it associated with differences in plasma renin activity (PRA) or aldosterone excretion rates (AER). Whereas PRA was significantly lower in responders at the end of SD, AER was not different; with SL, group values were equally suppressed. Also sodium excretion was not correlated with arterial pressure except in non-responders on the last day of SL. These data indicate that salt-sensitive hypertensives handle sodium differently than nonsalt-sensitive hypertensives.

Thermal stability of moniliformin at varying temperature, pH, and time in an aqueous environment.

Moniliformin (MON) is a widely occurring mycotoxin, produced mainly by Fusarium proliferatum and Fusarium subglutinans in corn, that has been shown to be acutely toxic for various animal species and is a suspected cause of Keshan disease in China. The effects of temperature (100, 125, and 150 degrees C) and pH (4, 7, and 9) on the stability of MON were determined in aqueous buffer solutions at processing times ranging from 10 to 60 min. The percentage of MON reduction was positively related to increasing temperature and pH. MON was most stable at pH 4. After 60 min at pH 4 and 150 degrees C, MON was reduced by only 5%. Heating at pH 10 caused major reduction of MON. After 60 min at pH 10 and 100, 125, and 150 degrees C, MON was reduced by 56, 72, and 83%, respectively. One trial done at 175 degrees C and pH 10 showed that less than 1% MON remained after 60 min of processing.

Enhanced expression of Ang-(1-7) during pregnancy.

Pregnancy is a physiological condition characterized by a progressive increase of the different components of the renin-angiotensin system (RAS). The physiological consequences of the stimulated RAS in normal pregnancy are incompletely understood, and even less understood is the question of how this system may be altered and contribute to the hypertensive disorders of pregnancy. Findings from our group have provided novel insights into how the RAS may contribute to the physiological condition of pregnancy by showing that pregnancy increases the expression of both the vasodilator heptapeptide of the RAS, angiotensin-(1-7) [Ang-(1-7)], and of a newly cloned angiotensin converting enzyme (ACE) homolog, ACE2, that shows high catalytic efficiency for Ang II metabolism to Ang-(1-7). The discovery of ACE2 adds a new dimension to the complexity of the RAS by providing a new arm that may counter-regulate the activity of the vasoconstrictor component, while amplifying the vasodilator component. The studies reviewed in this article demonstrate that Ang-(1-7) increases in plasma and urine of normal pregnant women. In preeclamptic subjects we showed that plasma Ang-(1-7) was suppressed as compared to the levels found in normal pregnancy. In addition, kidney and urinary levels of Ang-(1-7) were increased in pregnant rats coinciding with the enhanced detection and expression of ACE2. These findings support the concept that in normal pregnancy enhanced ACE2 may counteract the elevation in tissue and circulating Ang II by increasing the rate of conversion to Ang-(1-7). These findings provide a basis for the physiological role of Ang-(1-7) and ACE2 during pregnancy.

[Severe myogenic pain in an unfit subject after intensive and prolonged abdominal muscle exercise]. / Marcata sofferenza miogena in un soggetto non allenato dopo intenso e prolungato esercizio fisico di flesso-estensione dei muscoli addominali.

The authors report the case of an unfit patient who, following intensive and prolonged physical exercise involving the abdominal muscles, presented a massive and diffuse subcutaneous edema (abdomen, scrotum, chest and face) together with abdominal and thoracic pain which increased in response to finger pressure. In addition, this was accompanied by a marked increase in CK, CK-MB and LDH, and TGO and TGP. Chest or heart pathologies were excluded by monitoring ECG and other clinical parameters, like heart rate and blood pressure, and by performing a chest X-ray. Muscular ultrasonography confirmed the massive subcutaneous edema and abdominal MR showed a slight edema in the suprasacral region, as well as confirming the subcutaneous edema. Hematological data gradually reduced and returned to normal after a week. Edema and pain also regressed gradually: the former finally disappeared after one week and the latter after five days. The authors conclude that clinical and laboratory findings were particularly severe because the subject was unfit and subcutaneous edema was larger than the free liquid in the abdominal cavity because the latter was absorbed by the peritoneum which acted as a dialysing membrane.

[Clinical approach in hypertensive elderly patients]. / Considerazioni sull'approccio clinico di pazienti anziani ipertesi.

Hypertension in the elderly represents a cardiovascular risk factor which increases due to ageing and to the raise of blood pressure (BP) values. The occurrence of hypertension depends on an interaction between genes and environment. An available antihypertensive therapy causes a reduction in the incidence of cardiovascular events. An antihypertensive therapy in the elderly must take into account: in these subjects BP might be spontaneously lower over 30 mmHg in 24 hours; people normally have a postprandial BP reduction; sudden raises or falls of pressure cause cerebral hypoperfusion; some adverse vents of hypertensive drugs worsen their quality of life, not reducing myocardial hypertrophy; possible electrolytic troubles might worsen a congestive heart failure; drastic diets cause a raise in the incidence of colorectal tumours; a high heart rate increases the risk of sudden death; a chronic NSAID intake might cause or aggravate a hypertensive state; a reduction of natrium chlorure and lipides in the diet might cause a BP fall. In short, the BP reduction should be gradual in the hypertensive elderly in order to avoid the occurrence of cardiovascular events, diets should be balanced, rich in fibres and vitamins to avoid colorectal tumours. Besides, NSAID must be used by these patients for a short time and all therapeutic interventions should improve their quality of life.

[Allografts in extensive spinal arthrodesis]. / Aloinjertos en artrodesis vertebrales extensas.

Surgery of spinal deformities and vertebral tumors often requires extensive arthrodesis, with the difficulty of obtaining sufficient autogenous bone graft (particularly in children and cases of paralytic deformities) and the necessity of a second incision, thus lengthening the operation and eventual increase of the morbidity. We present 52 patients who suffered from vertebral tumours, fractures or spinal deformities and underwent spinal arthrodesis surgery. Femoral head allografts were used as cancellous bone graft to add to the amount obtained from the arthrodesis bed itself (posterior structures). In three occasions, femoral head grafts shaped as a strut were also used as intersomatic bone graft, being implanted via a costotansversectomy. The only complication was the appearance of seromas of spontaneous resorption in the first 15 cases (thereafter repeated cleaning of the bone graft avoided this problem). In our experience, bone grafts facilitate the carrying out of shorter surgical operations but can also avoid having to recourse the further incisions without reducing the possibility of obtaining a successful arthrodesis.

OS059. Blockade of the bradykinin B2 receptor in early pregnancy reduces fetal growth and trophoblast invasion in guinea-pigs.

INTRODUCTION: Research in preeclampsia (PE) is hampered by the difficulty of sampling the placental bed in early pregnancies followed to delivery to be defined as normal or preeclamptic. Thus, animal models contribute to the understanding of its physiopathology. The guinea-pig shares with humans extensive vascular remodelling, a hemomonochorial placenta [1] and a vasodilator and angiogenic utero-placental repertoire [2]. In pregnancy it expresses bradykinin (BK) B1R and B2R receptors in cells related to invasion, angiogenesis and vasodilatation. In addition, in HTR-8/SVneo cells, BK induces a B2R-mediated increase in migration and invasion [3]. OBJECTIVES: To test whether blocking the B2R with a rodent-selective non-peptide antagonist Bradyzide (BDZ) from days 20 to 34 of an ≈65 day gestation - period of maximal trophoblast invasion and placental development - induces PE-like morphological and functional alterations. METHODS: Virgin Pirbright guinea-pigs (Cavia Porcellus) after mating and echographic confirmation of pregnancy, were allocated in gestational day 20 to to subcutaneous implantation of Alzet pumps that delivered for 14 days saline (Control; n=7), BDZ0,875mg/kg/day (BDZ0,87; n=6) and BDZ 1,2mg/kg/day (BDZ1,2; n=7). Systolic pressure was acquired in the right hindlimb with a Power Lab 8 SP and analyzed with Labchart at day 34. On that day dams were sacrificed, vesical urine was extracted for protein determination, the fetuses and corresponding placentas weighed and the cephalo-caudal length measured. The placentas were studied by HE and immunohistochemistry for cytokeratin to identify trophoblasts. Results are expressed as means±SE. Statistical analysis was performed with Graphpad Prism 5.1, using one-way ANOVA, the recommended post hoc tests and χ2 test. RESULTS: Maternal systolic pressure tended to increase in BDZ0,875 and BDZ1,2 versus controls (63±567±6 versus 56±2,mm Hg respectively; NS). Proteinuria was not observed in any group. The number of viable fetuses tended to be reduced in both BZD treated groups (NS). The fetal weight (% maternal weight) was reduced in animals treated with BDZ0,875 and BDZ1,2 (042±002 and 045±001 versus 054±0,04 in controls; p (P<0.01 and 0.05 respectively). The cephalo-caudal length was reduced in BDZ0,875 and BDZ1,2 (373±24 and 371±07 versus 422±21mm in controls; P<0.01). No differences were observed in placental weight. Spiral arteries surrounded by trophoblasts (%) were reduced in BDZ 0875 and BDZ1,2 versus controls (63 and 66.6 versus 100%, P=0.02). Invaded spiral arteries (%) were also reduced in the treated groups (80 and 43 versus 100%; P<0.002) No differences were observed in the depth of trophoblast decidual invasion. CONCLUSION: This study demonstrates that blocking the B2R in early pregnancy impairs fetal growth and transformation of the spiral arteries, and supports the role of the B2R in the local physiological adaptation. Further studies are needed to elucidate whether the early impairment translates to hypertension and proteinuria in the last third of pregnancy; if so, the guinea-pig would provide a model to understand the physiopathology of the syndrome. Study financed by Fondecyt 1080228.