Molecular Aspects of Regeneration Mechanisms in Holothurians.

Holothurians, or sea cucumbers, belong to the phylum Echinodermata. They show good regenerative abilities. The present review provides an analysis of available data on the molecular aspects of regeneration mechanisms in holothurians. The genes and signaling pathways activated during the asexual reproduction and the formation of the anterior and posterior parts of the body, as well as the molecular mechanisms that provide regeneration of the nervous and digestive systems, are considered here. Damage causes a strong stress response, the signs of which are recorded even at late regeneration stages. In holothurian tissues, the concentrations of reactive oxygen species and antioxidant enzymes increase. Furthermore, the cellular and humoral components of the immune system are activated. Extracellular matrix remodeling and Wnt signaling play a major role in the regeneration in holothurians. All available morphological and molecular data show that the dedifferentiation of specialized cells in the remnant of the organ and the epithelial morphogenesis constitute the basis of regeneration in holothurians. However, depending on the type of damage, the mechanisms of regeneration may differ significantly in the spatial organization of regeneration process, the involvement of different cell types, and the depth of reprogramming of their genome (dedifferentiation or transdifferentiation).

Accuracy of Preoperative MDCT in Patients With Penetrating Abdominal and Pelvic Trauma.

PURPOSE: This study aims to evaluate the overall diagnostic accuracy of preoperative multidetector computed tomography (MDCT) in penetrating abdominal and pelvic injuries (PAPI). METHOD AND MATERIALS: We used our hospitals' trauma registry to retrospectively identify patients with PAPI from January 1, 2006, to December 31, 2016. Only patients who had a 64-MDCT scan at presentation and subsequently underwent laparotomy or laparoscopy were included in our study cohort. Each finding noted on MDCT was rated using a 5-point scale to indicate certainty of injury, with a score of 0 being definitive. Using surgical findings as the gold standard, the accuracy of radiology reports was analyzed in 2 ways. A κ statistic was calculated to evaluate each pair of values for absolute agreement, and ratings for all organ systems were analyzed using a repeated measures analysis of variance (ANOVA) to determine whether radiology and surgical findings were similar enough to be clinically meaningful. Qualitative review of the radiology and surgical reports focused on the gastrointestinal (GI) tract was conducted. RESULTS: Our cohort consisted of 38 males and 4 females with a median age of 29 years and a median injury severity score of 15.6. For this study, 12 different organ groups were categorized and analyzed. Of those organ groups, absolute agreement between MDCT and surgical findings was found only for liver and spleen (κ values ranging from 0.2 to 0.5). Additionally, the ANOVA revealed an interaction between finding type and organ system (F 1, 33 = 7.4, P < .001). The most clinically significant discrepancies between MDCT and surgical findings were for gallbladder, bowel, mesenteric, and diaphragmatic injuries. Qualitative review of the GI tract revealed that radiologists can detect significant findings such as presence of injury, however, localization and extent of injury pose a challenge. CONCLUSION: The detection of clinically significant injuries to solid organs in trauma patients with PAPI on 64-MDCT is adequate. However, detection of injury to the remaining organ groups on MDCT, especially bowel, mesentery, and diaphragm, remains a challenge.

Pneumomediastinum in blunt trauma: If aerodigestive injury is not seen on CT, invasive workup is not indicated.

BACKGROUND: Pneumomediastinum following blunt trauma is often observed on CT imaging, and concern for associated aerodigestive injury often prompts endoscopy and/or fluoroscopy. In recent years, adoption of multi-detector CT technology has resulted in high resolution images that may clearly identify aerodigestive injuries. The purpose of this study was to evaluate the utility of multi-detector CT in the identification of blunt aerodigestive injuries. METHODS: Over five years, patients with pneumomediastinum following blunt trauma were identified from the registry of a level 1 trauma center. All CT imaging of trauma patients during this time period was accomplished with 64-slice scanners. RESULTS: 127 patients with blunt traumatic pneumomediastinum were identified. Five airway injuries were identified, and all injuries were evident on CT imaging. No patient was found to have airway injury by endoscopy that was not evident on CT. No patient had an esophageal injury. CONCLUSION: Multi-detector CT imaging identifies aerodigestive injuries associated with pneumomediastinum following blunt trauma. The absence of a recognizable aerodigestive injury by CT effectively rules out the presence of such injury.

Foreign body ingestion in pediatric patients.

PURPOSE OF REVIEW: The purpose of this article is to review clinical manifestations and management of common pediatric foreign body ingestions, with a particular focus on some of the current trends. RECENT FINDINGS: Foreign body ingestion (FBI) is a problem that is frequently encountered by pediatric providers. As new toys and products enter the marketplace, there may also be new dangers from those objects not initially recognized. Some of the recent trends and findings in pediatric FBI include an increase in adolescent injury from ingestion of laundry detergent pods because of a popular game where participants are encouraged to bite or swallow the pods, and injuries associated with ingesting parts of a popular toy known as a 'Fidget Spinner'. SUMMARY: Adverse events resulting from FBI range the entire gamut from nonexistent or minor symptoms to moderate injury and rarely may be fatal. Factors such as age, type of object ingested, anatomic location of the foreign body, and timing from ingestion to receipt of medical attention all determine the risk posed to the child and guide management decisions. Because of the constant development of products, and the potential for the emergence of new and dangerous trends among children, continued surveillance by the medical community is important in monitoring and managing injuries associated with FBI.

Visceral and gastrointestinal complications in robotic urologic surgery. / Complicaciones viscerales y gastrointestinales en la cirugía urológica robótica.

INTRODUCTION: with the widespread use of minimally invasive techniques, robot-assisted urologic surgery has become widely adopted. Despite their infrequency, visceral and gastrointestinal complications could be life-threatening. OBJECTIVES: To identify the main gastrointestinal injuries that occur in a robot-assisted urologic surgery. To know the overall incidence and how is their management. ACQUISITION OF THE EVIDENCE: Search in PubMed of articles related to visceral and gastrointestinal complications in robot-assisted urology surgery, written in English or Spanish. Relevant publications as well literature reviews and chapters from books were reviewed. SYNTHESIS OF THE EVIDENCE: Along with vascular injuries, visceral and gastrointestinal lesions are among most dangerous complications. A complete preoperative study to individualize each patient characteristics and the correct use of imaging could help us to avoid complications in the first place. To know all the risky steps in the different robotic urologic procedures will let us anticipate the damage. Knowledge of main and most dangerous injuries in the different abdominal and pelvic organs is fully recommended. Early diagnosis and evaluation of lesions will let us an acute management during surgery. Recognition delay could change a repairable injury into a life-threatening situation. CONCLUSIONS: Despite the undeniable benefits of robotic approach, there are minor and major gastrointestinal injuries that all urologic surgeons must know. Those related with trocar placement are especially important. Immediate diagnosis and management is mandatory.

General surgeon management of complex hepatopancreatobiliary trauma at a level I trauma center.

BACKGROUND: The impact of general surgeons (GS) taking trauma call on patient outcomes has been debated. Complex hepatopancreatobiliary (HPB) injuries present a particular challenge and often require specialized care. We predicted no difference in the initial management or outcomes of complex HPB trauma between GS and trauma/critical care (TCC) specialists. MATERIALS AND METHODS: A retrospective review of patients who underwent operative intervention for complex HPB trauma from 2008 to 2015 at an ACS-verified level I trauma center was performed. Chart review was used to obtain variables pertaining to demographics, clinical presentation, operative management, and outcomes. Patients were grouped according to whether their index operation was performed by a GS or TCC provider and compared. RESULTS: 180 patients met inclusion criteria. The GS (n = 43) and TCC (n = 137) cohorts had comparable patient demographics and clinical presentations. Most injuries were hepatic (73.3% GS versus 72.6% TCC) and TCC treated more pancreas injuries (15.3% versus GS 13.3%; P = 0.914). No significant differences were found in HPB-directed interventions at the initial operation (41.9% GS versus 56.2% TCC; P = 0.100), damage control laparotomy with temporary abdominal closure (69.8% versus 69.3%; P = 0.861), LOS, septic complications or 30-day mortality (13.9% versus 10.2%; P = 0.497). TCC were more likely to place an intraabdominal drain than GS (52.6% versus 34.9%; P = 0.043). CONCLUSIONS: We found no significant differences between GS and TCC specialists in initial operative management or clinical outcomes of complex HPB trauma. The frequent and proper use of damage control laparotomy likely contribute to these findings.

Magnetic Foreign Body Ingestions.

Magnets are inherently attractive to young children, but present a risk when ingested. If consumed alone, small, smooth magnetic foreign bodies are likely to pass without significant event; however, ingestion of multiple magnets may have catastrophic consequences, including bowel perforation, obstruction, peritonitis, and death. Increasing reports of morbidity and mortality in recent years from the US National Electronic Injury Surveillance System has led to numerous safety statements from the American Academy of Pediatrics and the Centers for Disease Control and Prevention, as well as several product recalls from the Consumer Product Safety Commission. This article presents the background and mechanism of injury of magnet ingestion, as well as recommended management and potential complications. We also review current legislation and opportunities for further patient advocacy regarding this polarizing problem.

Conservative management of severe caustic injuries during acute phase leads to superior long-term nutritional and quality of life (QoL) outcome.

PURPOSE: Best clinical management of severe caustic injury is still a subject of debate. Most surgical teams consider severe caustic injury as an indication for emergency surgery. But, under certain circumstances, conservative management is feasible, avoids the need for gastrectomy, and has a low mortality rate. Postponed reconstructive surgery is usually performed several months after caustic ingestion to restore intestinal continuity or to treat stricture sequelae. This study aimed to investigate long-term nutritional and quality of life (QoL) outcomes after reconstructive surgery for high-grade esophageal and gastric caustic injury. METHODS: Twenty-one patients were assessed for biological and nutritional parameters, physical findings, and quality of life surveys at least 25 months after reconstructive surgery among patients who have required emergency surgery (n = 10) and patients who did not undergo emergency surgery (n = 11). RESULTS: After median follow-up of 74 months (after caustic ingestion) and 67 months (after reconstructive surgery), patients who avoided emergency surgery experienced faster oral diet resumption (49 vs. 157 days, p = 0.004), less weight loss (0.3 vs. 20 kg, p = 0.002), greater body fat percentage (22 vs. 18 %, p = 0.046), better nutritional and physical status (SF12 PCS 51 vs. 43, p = 0.036), and less trouble eating (EORTC QLQ-OG 25 31 vs. 56, p = 0.01). CONCLUSIONS: Our study is the first to evaluate long-term nutritional and QoL outcomes, following severe caustic injury. It demonstrates better long-term nutritional outcomes and QoL in patients suitable for initial conservative management. These results support full functional recuperation of spared organs, even severely burned. In the absence of clinical or biological signs necessitating immediate surgery, conservative management should be advocated.

Capítulo VI. Sistema digestivo / Chapter VI. Digestive system

Dentro de las importantes modificaciones que recoge la nueva tabla 2.A.1, Baremo médico, Clasificación y valoración de secuelas, nos encontramos con las que corresponden al Sistema digestivo, Capítulo VI, tanto por reordenación como por organización y valoración, mucho más lógicas y funcionales en todos esos aspectos. Desaparecen algunas secuelas raramente traumáticas, se precisan determinados requerimientos para tomar en consideración algunas secuelas, se incrementa el número de las mismas y se mantiene en este apartado las correspondientes a funciones exclusivamente digestivas (AU)

Among the major changes contained in the new table 2.A.1, medical Scale, Classification and valuation of sequels, we find that for the Digestive System, Chapter VI, therefore reorganization as per organization and evaluation, more logical and functional in all these respects. Some rarely traumatic aftermath disappear, certain requirements to take into account some sequels are required, the number thereof is increased and maintained in this section corresponding exclusively to digestive functions (AU)

Pneumomediastinum following blunt trauma: Worth an exhaustive workup?

BACKGROUND: Incidental pneumomediastinum is a common radiologic finding following blunt thoracic injury; however, the clinical significance of pneumomediastinum on screening imaging is poorly defined (Curr Probl Surg. 2004;41(3):211-380; Injury. 2010;41(1):40-43). The purpose of this study was to define the incidence of aerodigestive injuries in patients with pneumomediastinum after blunt thoracic and neck injury. METHODS: After institutional review board approval was obtained, a retrospective review was performed of all patients admitted to Los Angeles County + University of Southern California Medical Center with blunt neck and/or thoracic injuries between January 2007 and December 2012. All patients with pneumomediastinum on radiologic investigation were included. Data accrued included demographics, admission clinical data, injury severity patterns, incidence of aerodigestive injuries, operative findings, morbidity, mortality, as well as intensive care unit and hospital lengths of stay. RESULTS: A total of 9,946 patients were included in the study. The predominant mechanism was motor vehicle collision (49%), disproportionately male (76%). Overall, 258 patients (2.6%) had a pneumomediastinum: 65 (25%) and 193 (75%) were diagnosed on a chest x-ray or on a computed tomography (CT) scan, respectively. A total of 21 patients (8.1%) had an aerodigestive workup with bronchoscopy, esophagram, and/or esophagoscopy. Overall, four aerodigestive lesions (1.6%) were diagnosed. Three tracheobronchial injuries were identified on CT scan, and one esophageal injury was diagnosed on an esophagram. Two tracheobronchial injuries required surgery, while the remaining cases were managed nonoperatively. The overall mortality in this cohort was 10.9%. CONCLUSION: Isolated findings of pneumomediastinum on screening chest x-ray or CT following blunt trauma is a poor predictor of an aerodigestive injury. Highly selective workup in this clinical setting is warranted. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III; therapeutic study, level IV.

A hospital-based epidemiological study of corrosive alimentary injuries with particular reference to the Indian experience.

Corrosive alimentary tract injuries are a source of considerable morbidity all over the world. Despite this, actual data on the epidemiology of this problem are scarce mainly due to the lack of a well-established reporting system for poisoning in most countries. The burden of the disease is naturally more in countries such as India where the condition is common because of poor regulation of sale of corrosive substances. We analyse the available data on epidemiology of corrosive injuries, as well as patterns of involvement of the alimentary tract, with special reference to Indian data, and also provide an overview of the management options and long-term sequelae of this condition.

A profile of abdominal and pelvic injuries in medico-legal autopsy.

Abdomino-pelvic region is vulnerable to injury in various forms of trauma. This study was undertaken with objectives to study the pattern and type of external and internal abdominal and pelvic injuries and to identify the risk organs in abdomen and pelvis susceptible to trauma among the medico-legal autopsies at the mortuary of a referral centre in eastern Nepal during the period of one year (n = 80). Males constituted 80% of the cases and the mean age of the victims was 30.76 years. The cause of trauma was Road Traffic Accident in 82.5%. The manner of death was accidental in 87.5% and homicidal in 11.25% cases. Liver (57.5%) was the most common organ injured followed by spleen in 37.5% cases. Multiple organs injury was seen in 67.5% and absence of any external injuries was noted in 31.25% cases. Autopsy can play a role in establishing the missed injuries and be helpful to widen the knowledge of the medical faculty in early diagnosis and management of such injuries.

Perforations following endoscopic retrograde cholangiopancreatography: a single institution experience and surgical recommendations.

BACKGROUND: Perforation after endoscopic retrograde cholangiopancreatography (ERCP) is uncommon, and its management is dependent on the mechanism and the graded classification of injury. METHODS: Records of patients undergoing ERCP were analyzed over a 16-year period, patterning the types of injuries, diagnosis, management, and patient outcome. Type I injuries damage the medial or lateral duodenal wall before sphincter cannulation. Type II injuries are periampullary and occur as a result of a precut or a papillotomy. Type III injuries occur secondary to guidewire insertion or stone extraction from the common bile duct. Type IV injuries are probably microperforations that are noted on excessive insufflation during and after ERCP withdrawal. RESULTS: Between 1995 and 2011, 27 perforations were identified from 1,638 ERCP procedures (1.6%). Nearly half of the procedures were regarded as difficult by the endoscopist, with 70% of the ERCPs (19 of 27) being for therapeutic indications. There were 5 type I, 12 type II, 5 type III, and 5 type IV perforations, of which 18 cases were diagnosed at the time of ERCP. Delayed diagnosis of type I perforations that were associated with free intraperitoneal air and contrast leakage proved fatal. Most type II perforations required immediate surgery with pyloric exclusion; delayed surgery with simple drainage had a high mortality rate. Most type III and type IV injuries can successfully be managed conservatively without delayed sepsis. CONCLUSIONS: In perforation, the mechanism of injury during ERCP predicts the need for surgical management. Type I and type II injuries require early diagnosis and aggressive surgery, whereas type III and type IV injuries may be managed conservatively.

Clinical and epidemiological features of acute corrosive poisonings.

BACKGROUND: the ingestion of chemical agents, of caustic nature, represents a serious problem for clinical toxicology. If the ingestion doesn't cause death during the acute period, it will most often cause severe side effects in the upper gastrointestinal tract during the chronic phase. AIMS: The purpose of this study is to show the clinical, epidemiological and socio-economical characteristics seen in acute corrosive poisonings such as ingested caustic agents, causes for abuse and most consequential complications. MATERIAL AND METHODS: a ten year medical data was constructed and collected (2000-2009) from patients with acute corrosive poisonings who were hospitalized and treated in the University Clinic of toxicology and urgent internal medicine in Skopje, Republic of Macedonia. The variables included were: age, sex, type of poisonings and percentage of late post-corrosive complications. RESULTS: In the study, 735 patients files were analyzed, collected in a period often years. The mean age of patients is 32.9 +/- 15.6 years. Majority of patients ingested hydrochloric acid (HCl; n = 354; 48,16%). CONCLUSION: Demographic, diagnostic and therapeutic findings in acute corrosive poisonings are found to be similar to the findings observed in the referenced literature. Conclusively, women between 14 and 30 years old represent a high risk group; hydrochloric acid is the most often abused agent; and high percentage of post-corrosive complications are

[Experience of open renal trauma in a urology service]. / Experiencia de traumatismo renal abierto en un servicio de urología.

INTRODUCTION: Opened renal trauma in urban areas reaches 15 to 20% of all renal traumas. It is mainly caused by gunshot wounds or knifes. Gunshot wounds are classified as high energy trauma and are usually associated to other organ injuries. We present our experience in opened renal trauma in the last 24 months. MATERIAL AND METHODS: Retrospective study: patients with thoracic, abdominal and thoraco-abdominal trauma admitted to the emergency room between July 2009 and June 2011 were studied. Fourteen patients were identified with opened renal trauma, with diagnostic confirmation by imaging study or during surgery. RESULTS: Ages ranged from 16 to 37 years, with a mean age of 24.5 years. Thirteen patients were males. The mechanism of injury was produced by gunshot in 71% (10/14) and by knife in 29% (4/14). The opened renal traumas were classified according to the American Association for the Surgery of Trauma. Of these, 3/14 (21%) belonged to grade II, 4/14 (29%) to grade III, 4/14 (29%) to grade IV and 3/14 to grade V (21%). Fall in hematocrit ranged from 1% to 27%, with an average of 13.9%. Expectant management was done in six patients, however, this management did not take into account those surgeries performed due to non-urologic organ injuries. Six patients (42%) required nephrectomy. Thoraco-abdominal injuries were associated in 11 patients (79%). CONCLUSIONS: Despite the low incidence of opened renal trauma, many patients are observed when other national reports are considered, probably due to the socio-cultural characteristics of this hospital.

Esophagogastroduodenoscopy-associated gastrointestinal perforations: a single-center experience.

BACKGROUND: Esophagogastroduodenoscopy (EGD) is commonly used in the diagnosis and treatment of gastrointestinal (GI) disorders. Our aim was to define the risk of perforation associated with EGD and identify patients who required operative intervention. METHODS: We retrospectively reviewed 72 patients from our institution plus 5 transferred patients who sustained EGD-associated perforations from January 1996 through July 2008. Percutaneous endoscopic gastrostomy, endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography, transthoracic echocardiography, and concurrent colonoscopy procedures were excluded. RESULTS: Perforations in 72 of 217,507 EGD procedures were identified (incidence, 0.033%); 124,844 EGDs included an interventional procedure and 92,663 were examination only. The incidence of perforation was similar whether an interventional procedure was performed or not (0.040% vs 0.029%; P = .181). The esophagus was injured most commonly (51%), followed by the duodenum (32%), jejunum (6%), stomach (3%), and common bile duct (3%). Overall mortality after perforation was 17% with a morbidity rate of 40%. Thirty-eight patients (49%) were initially treated nonoperatively, 7 of whom (18%) failed nonoperative management. The only factors we could determine that were associated with failure were free fluid or contrast extravasation on computed tomography (75% vs 23% [P < .005] and 33% vs 0% [P = .047], respectively). The morbidity of failures was equivalent to those who underwent initial operative management (63% vs 61%; P = .917), with mortality seeming to be greater (43% vs 21%; P = .09). CONCLUSION: EGD is safe in the majority of patients; however, iatrogenic perforation is associated with considerable morbidity and mortality. Nonoperative management of GI perforation can be successful if there is no evidence of contrast extravasation or free fluid on radiographic studies. If nonoperative management fails, the outcomes may be worse than those treated initially with operative repair.

Microscopic anatomy of the digestive system in normal and regenerating specimens of the brittlestar Amphipholis kochii.

The morphology and regeneration of the digestive system of the ophiuroid Amphipholis kochii were investigated. The epithelia of the esophagus and stomach of A. kochii were composed of typical enterocytes and mucous cells. The digestive epithelium of the stomach contained two types of granular secretory cells. After autotomy of the disk, the animals retained the esophagus and a small part of the stomach. The dedifferentiation of enterocytes and mucous cells began on the first day after autotomy. On day 3 the cells formed an anlage of stomach around the mouth opening. Later, the stomach anlage grew as a result of cell proliferation. The opening on the aboral side of the body was closed by day 7. By this time differentiating cells were already observed in the stomach lining. The stomach mesothelium was formed by peritoneocytes and myoepithelial cells, which migrated from other coelomic epithelia of the body. Our study showed that the formation of the digestive system in A. kochii during regeneration depended on cells from the esophagus and the stomach remnant. Both enterocytes and mucous cells were able to dedifferentiate, migrate, and proliferate to give rise to the luminal epithelium. The basic mechanism of stomach formation was epithelial morphogenesis.

La colonoscopia: ¿es un estudio pre-operatorio indispensable para la restitución del tránsito intestinal en pacientes jóvenes: portadores de colostomía por traumatismo abdominal penetrante? / Colonoscopy: is a necessary pre-operatory study for intestinal transit restitution in young patients carrying a colostomy by penetrating abdominal trauma?

Determinar el impacto de la colonoscopia como procedimiento preoperatorio requisito para la restitución del tránsito intestinal en una población portadora de colostomía por un traumatismo abdominal penetrante. Estudio descriptivo, retrospectivo observacional, donde se evalúan informes de endoscopias digestivas inferiores realizadas por el servicio de Gastroenterología del Hospital General del Oeste "Dr. José Gregorio Hernández" de Caracas, como requisito preoperatorio para la restitución del transito intestinal en pacientes portadores de colostomía por traumatismo abdominal penetrante, en el período comprendido entre enero 2004 y diciembre 2008. De una población total de 46 pacientes, se les realizó una colonoscopia a 34 (73,91%). Los 12 restantes (26,08%), no cumplían con los criterios de inclusión. de los 34 pacientes incluidos para evaluación, 22 (64,70%), presentaron colitis y recidivas por deprivación, 7 (20,59%) con estudio normal y 4 (11,76%) presentaron alguna alteración en la endoscopia digestiva inferior. En este estudio no hay evidencia que sugiera que la realización de una colonoscopia preoperatoria en la cirugía electiva de restitución de tránsito intestinal, evite la aparición de complicaciones, ni permita el diagnóstico de patologías de relevancia en la población estudiada, no teniendo ésta la importancia que se le ha otorgado hasta la actualidad.

To determine the impact of the colonoscopy as pre-operating procedure as a requirement in the population carrying of colostomy by abdominal penetrating trauma for the restitution of the intestinal transit. Descriptive, retrospective and observational study, where the inferior digestive endoscopy made by the service of Gastroenterology in Hospital General del Oeste "Dr. José Gregorio Hernández", Caracas, was valued as pre-operating requirement in carrying patients of colostomy by abdominal penetrating trauma for the restitution of the intestinal transit, in the period between January 2004 to December 2008. In a population of 46 patients, only 34 (73.91%) were included to do the colonoscopy, the others 12 (26,08%) didn't fulfill the inclusion criteria. Of the 34 patients included, 22 (64.70%) were displayed colitis and rectitis by deprivation, 7 (20.59%) were normal study and 4 (11.76%) presented others alteration in the inferior digestive endocopy. In this study there is not evidence to suggest that the realization of preoperatory colonoscopy for surgery in the restitution of intestinal transit, avoid complications or permit diagnosis of diseases in the study population, doing less important the evidence exposed until present.