Trauma patients centralization for the mechanism of trauma: old questions without answers.

INTRODUCTION: Centralization of trauma patients has become the standard of care. Unfortunately, overtriage can overcome the capability of Trauma Centres. This study aims to analyse the association of different mechanisms of injury with severe or major trauma defined as Injury Severity Score (ISS) greater than 15 and an estimation of overtriage upon our Trauma Centre. METHODS: A retrospective review of our prospective database was undertaken from March 2014 to August 2016. Univariate and multivariable logistic regression models were used to estimate the association between covariates (gender, age, and mechanisms of injury) and the risk of major trauma. RESULTS: The trauma team (TT) treated 1575 patients: among the 1359 (86%) were triaged only because of dynamics or mechanism of trauma. Overtriage according to an ISS < 15, was 74.6% on all trauma team activation (TTA) and 83.2% among the TTA prompted by the mechanism of injury. Patients aged 56-70 years had an 87% higher risk of having a major trauma than younger patients (OR 1.87, 95% CI 1.29-2.71) while for patients aged more than 71 years OR was 3.45, 95% CI 2.31-5.15. Car head-on collision (OR 2.50, 95% CI 1.27-4.92), intentional falls (OR 5.61, 95% CI 2.43-12.97), motorbike crash (OR 1.67, 95% CI 1.06-2.65) and pedestrian impact (OR 2.68, 95% CI 1.51-4.74) were significantly associated with a higher risk of major trauma in a multivariate analysis. CONCLUSIONS: Significant association with major trauma was demonstrated in the multivariate analysis of different mechanisms of trauma in patients triaged only for dynamics. A revision of our field triage protocol with a prospective validation is needed to improve overtriage that is above the suggested limits.

Haemodynamically unstable pelvic trauma: initial validation of a dedicated protocol by a retrospective cohort study with historical controls

Background: We present our experience after the introduction of Advanced Trauma Life Support (ATLS)©, Trauma Team (TT) and Preperitoneal Pelvic Packing (PPP) protocols for the treatment of hemodynamically unstable pelvic blunt trauma.Methods: This is a retrospective study with historical controls: before (Control Group, CG) and after (Study Group SG) the introduction of the protocol. A single physician managed the CG and angiography was the emergency manoeuvre. A team with ATLS guidelines and PPP as an emergency manoeuvre managed the SG. Data were collected retrospectively. Patients were divided into two groups: before and after the introduction of protocols.Results: From January 2007 to October 2014, 36 patients were treated at our Centre. We consider patients from January 2007 to August 2011 (19 patients, CG) and from September 2011 to October 2014 (17 patients, SG). Median age was 54 years (43­69) in the CG vs. 47 (40­63) in the SG (p = 0.43), median initial SBP 90 mmHg (85­103) in the CG 94 (69­103) in the SG, (p = 0.60), heart rate was 90 (80­110) in the CG and 110 (95­130) in the SG, (p = 0.09). Median Injury Severity Score was 33 (21­41) in the CG and 34 (26­41) in the SG (p = 0.29). Time from arrival in the Emergency Department to first therapeutic manoeuvre was 132 minutes (109­180) in the CG and 87 minutes (51­204) in the SG (p = 0.4). The difference in mortality was statistically significant: 64.7% (11/17) in the CG and 23.5% (4/17) in the SG (p = 0.02).Conclusions: The introduction of protocols changed our approach in hemodynamically unstable pelvic trauma, achieving a remarkable improvement in early mortality

Laparoscopic ventral incisional hernia repair: evidence-based guidelines of the first Italian Consensus Conference.

PURPOSE: The laparoscopic treatment of ventral incisional hernias is the object of constant attention and is becoming increasingly widespread in the international scientific-surgical community; however, there is ample debate on its technical details and indications. In order to establish a common approach on laparoscopic ventral incisional hernia repair, the first Italian Consensus Conference was organized in Naples (Italy) on 14-15 January 2010. METHODS: The format of the Consensus Conference was freely adapted from the standards of the National Institute of Health and the Italian Health Institute. The parties involved included the followings: a Promotional Committee, a Scientific Committee, a group of Experts, the Jury Panel and a Scientific Secretariat. RESULTS: Eleven statements, regarding three large chapters on the indications, the technical details and the management of complications were drafted on the basis of literature references collected by the Scientific Committee, documents developed by the Experts, reports presented and discussed during the Consensus Conference, and discussion among the members of the Jury. CONCLUSIONS: The laparoscopic approach is safe and effective for defects larger than 3 cm in diameter; old age, obesity, previous abdominal operations, recurrence and strangulation are not absolute contraindications. Ensuring an adequate overlap, careful adhesiolysis and correct fixing of the prosthesis are among the technical details recommended. Complications and recurrences are comparable to, and in some cases, less numerous than with the open approach.

Prospective clinical study of laparoscopic treatment of incisional and ventral hernia using a composite mesh: indications, complications and results.

The aim of this study is to establish the indications, safety, efficacy, feasibility and reproducibility of the laparoscopic technique in treating defects in the abdominal wall, including those of large dimensions, to standardise the surgical technique and to confirm the performance of the composite prosthesis used (Parietex, Sofradim). The study encompassed the period from January 2001 to December 2004 and included 178 nonselected patients (108 women and 70 men), with an average age of 56 years (range: 26-77 years) and an average body mass index (BMI) of 30 (range: 26-40). These patients were treated for either abdominal hernia (156 patients; 89.7%) or a primary defect (22 patients; 10.3%). The dimensions of the abdominal hernias treated varied from 4 to 26 cm (average: 12.1 cm). All patients were treated using the laparoscopic technique, and all meshes were placed in the intraperitoneal position. Eleven (7%) postoperative complications arose after an average follow-up period of 29 months (range: 1-48 months): seven seromas (4.4%) lasting for 4 weeks, with one becoming infected after being punctured repeatedly; we removed the infected prosthesis by laparoscopy; three (1.9%) patients with persistent neuralgia, which were resolved after 2 months with a prescription for FANS; one patient with a haematoma at the trocar site. There were also four recurrences (2.5%), all of which occurred between 1 and 3 months postsurgery: one in the 'small' group of abdominal hernias (less than 9 cm) and three in the 'large' group of abdominal hernias. With the exclusion of any primary defects, an adhesiolysis was carried out in 99.3% of the patients. In seven cases (4.4%) we carried out a raphe for speritonealisations of loops in the small intestine; in four patients (2.5%), following tenacious adhesion (one patient) and loops fixed to the previous scar by stitches (three patients), we carried out an intestinal perforation (ileus) which was sutured by laparoscopy. The average operating time was 65.6 min (range: 28-130 min), with an average postoperative period in the hospital of 2.1 days (range: 1-5 days). No conversion was observed, and mortality was zero. The results obtained during the clinical trial demonstrate the safety and efficacy of the laparoscopic technique and of the mesh used as well as the reproducibility of the technique in the intraperitoneal treatment of congenital and postincision defects in the abdominal wall, including those of large dimensions.

Laparoscopic versus open appendectomy in acute appendicitis: a randomized prospective study.

BACKGROUND: Laparoscopic appendectomy is a safe and effective procedure, as both a diagnostic and therapeutic tool. It seems to be more effective than the corresponding open procedure. Aim of this study is to evaluate a group of patients randomly allocated either to laparoscopic appendectomy (LA) or to open appendectomy (OA). METHODS: From January 1998 to December 2002, 252 consecutive and nonselected patients, 155 women and 97 men, were randomized either to LA or OA. Recorded data were operative time, postoperative length, of stay and complications. RESULTS: Mean operative time was 45 min (range 30-120) for OA and 36 min (25-60) for LA, mean postoperative stay was 5.5 days (4-12) for OA and 3.4 days (2-8) for LA. Complication occurred in 20 patients (14.5%) for OA and in four patients (2.6%) for LA. CONCLUSION: We believe that LA is effective in any kind of clinical situation, with low traumatic impact and best comfort for the patient.

[Laparoscopic transabdominal preperitoneal repair of inguinal hernia: indications, technique, complications and results in 10 years experience]. / Ernioplastica inguinale transaddominale preperitoneale laparoscopica. Indicazioni, tecnica, complicanze dopo 10 anni di esperienza.

AIM: Inguinal hernia play a major role in a general surgical division. In the last 10 years laparoscopy has gained a key role even in the treatment of this disease. This study aims to review a single institution's experience with laparoscopic transabdominal preperitoneal repair of inguinal hernia (TAPP). METHODS: A retrospective study of 715 operations in 500 patients from 1992 to September 2002. Two hundred and eight six (56.6%) of these were monolateral hernias and 214 (43.4%) were bilateral while 215 (30%) were recurrent. RESULTS: Of 214 operations recurrence rate was 0.43 with a mean operating time of 30 min (range 25-50) for monolateral hernias and of 70 min (range 45-120) for bilateral hernias. Mean length of stay was 2 days (range 1-10). Return to work occurred in 6 days while sports were resumed after 10 days. Complications occurred in 40 (8.6%) patients with only 2 (0.4%) major complications. Mean follow up time was 58.3 months. CONCLUSION: According to personal experience, and in agreement with international literature, laparoscopy showed to be effective mostly in treating bilateral and recurrent hernias, particularly for faster recovery and less postoperative pain compared to traditional techniques.

Laparoscopic liver resection with radiofrequency.

BACKGROUND/AIMS: In this report, the feasibility, efficacy and safety of laparoscopic liver resection with radiofrequency has been evaluated in a small series of patients. METHODOLOGY: From January 1993 to May 2002 we carried out 7 laparoscopic liver resections (3 men and 4 women), five of which were for benign pathology and two for metastases from colorectal cancer. In four of the above resections we used an argon coagulator; the last three were accomplished by means of a radiofrequency instrument. RESULTS: We had no perioperative or postoperative complications in this small series of patients. There were no deaths. Perioperative blood loss was of 120 mL (range 80-200) and the procedure took about 90 minutes (range 80-110). Hospitalization was of 4 days and pain was adequately controlled by 2 mL of Toradol twice a day. CONCLUSIONS: We think that the advantages of laparoscopic techniques together with the efficacy of the radiofrequency instrument in hepatic surgery will allow the diffusion of this method and its extension to safe execution of major resections.

Blocking Chk1 expression induces apoptosis and abrogates the G2 checkpoint mechanism.

Checkpoint kinase 1 (Chk1) is a checkpoint gene that is activated after DNA damage. It phosphorylates and inactivates the Cdc2 activating phosphatase Cdc25C. This in turn inactivates Cdc2, which leads to G2/M arrest. We report that blocking Chk1 expression by antisense or ribozymes in mammalian cells induces apoptosis and interferes with the G2/M arrest induced by adriamycin. The Chk1 inhibitor UCN-01 also blocks the G2 arrest after DNA damage and renders cells more susceptible to adriamycin. These results indicate that Chk1 is an essential gene for the checkpoint mechanism during normal cell proliferation as well as in the DNA damage response.

Abrogation of G2 checkpoint specifically sensitize p53 defective cells to cancer chemotherapeutic agents.

BACKGROUND: Chkl is a checkpoint gene that is activated after DNA damage. It phosphorylates and inactivates Cdc25C at the late G2 phase. The inactivation of Cdc25C and consequently, the inactivation of Cdc2, are required for the G2 arrest induced by DNA damage. METHODS: We treated 184B5 cell line and its E6 transformed cell lines with adriamycin in the presence of staurosporine or UCNO1 and examined G2 arrest and cell death. RESULTS: We found that adriamycin induced a p53 and p21 response as well as a G1 arrest in 184B5 cells, but not in its E6 transformed cells. Staurosporine or UCNO1 abrogated the G2 arrest induced by adriamycin in both cell lines. In addition, staurosporine or UCNO1 specifically sensitized p53 incompetent cells to adriamycin. CONCLUSION: G2/M checkpoint abrogators can potentially enhance the cytotoxic effect of conventional chemotherapeutic reagents specifically to tumor cells.

Development and application of a minimal-adenoviral vector system for gene therapy of hemophilia A.

To achieve efficient delivery and sustained expression of the human factor VIII cDNA in vivo, a minimal-adenoviral (mini-Ad) vector system was developed. The system is composed of a mini-Ad vector with essential cis-elements (less than 1 kb) of the viral genome, an E1-deleted ancillary Ad with packaging attenuation, and an E1-complementing production cell line. Based on this system, MiniAdFVIII was generated to deliver a 27 kb expression cassette consisting of a full-length human factor VIII cDNA flanked by human albumin promoter and genomic sequences. The MiniAdFVIII vector mediated expression of functional human factor VIII in HepG2 and 293 cells. A single-dose intravenous injection of 10(11) viral particles in hemophilic mice of MiniAdFVIII produced a sustained high-level expression of human factor VIII (at 100-800 ng/ml up to 369 days) which corrected the FVIII-deficient phenotype. Safety studies of MiniAdFVIII showed that there were no significant toxic effects in mice and dogs after single intravessel doses of up to 3 x 10(11) and 6 x 10(12) viral particles, respectively. Studies for developing the MiniAdFVIII vector with a site-specific integration mechanism and progress in the development of a human factor VIII-tolerized mouse model for pre-clinical studies of MiniAdFVIII are reported. Further pre-clinical studies and product development of MiniAdFVIII for clinical trials are also discussed.

Altered dopaminergic modulation of prolactin and aldosterone secretion in pseudohypoparathyroidism.

It has previously been demonstrated in our laboratory that patients with pseudohypoparathyroidism (PsHP) have impaired PRL responses to TRH and chlorpromazine. We have also observed that these patients have low basal plasma renin activity (PRA) and decreased aldosterone responses to upright posture and isometric handgrip exercise. Since inhibitory dopaminergic modulation of PRL and aldosterone is well established, we have examined whether PsHP is associated with altered dopaminergic inhibition of PRL and aldosterone secretion. To investigate this possibility, we compared the plasma PRL, aldosterone, and PRA responses to the dopamine antagonist metoclopramide (MCP; 10 mg iv) in seven normocalcemic PsHP patients and twelve normal controls. These patients were on no medications except calcium and vitamin D for 2 weeks; they were maintained on a diet containing 50 meq of sodium and 80 meq of potassium for 5 days. Although basal PRL levels were similar in the two groups of subjects, the maximal incremental PRL response in PsHP patients (38.7 +/- 12.6 ng/ml) was less (P less than 0.01) than in normal subjects (61.6 +/- 9.6 ng/ml). Basal supine plasma aldosterone was less (P less than 0.01) in PsHP patients (8.0 +/- 1.1 ng/dl) than in normal subjects (13.4 +/- 2.1 ng/dl). Maximum incremental aldosterone response to MCP (8.7 +/- 1.9 ng/dl) in PsHP patients was also less (P less than 0.01) than in normal subjects (13.4 +/- 2.1 ng/dl). Basal supine PRA was lower (P less than 0.05) in PsHP patients (1.3 +/- 0.3 ng/ml.h) than in normal subjects (2.8 +/- 0.4 ng/ml.h). However, the PRA responses to MCP were similar in both groups. Tonic dopaminergic inhibition of PRL and aldosterone secretion, but not renin secretion, appears to be less pronounced in PsHP patients. This is the first disease state in which reduced aldosterone responses to dopamine antoganism have been observed. Decreased PRL and aldosterone responses to MCP may reflect decreased ambient dopamine levels and/or a reduction in dopamine receptor number or binding affinity.