Publications by authors named "Isabel Pascual"

28 Publications

  • Page 1 of 1

Neoadjuvant treatment for locally advanced unresectable and borderline resectable pancreatic cancer: oncological outcomes at a single academic centre.

ESMO Open 2020 11;5(6):e000929

CIBERONC, Instituto de Salud Carlos III, Madrid, Comunidad de Madrid, Spain; Department of Medical Oncology, University of Valencia, Valencia, Spain. Electronic address:

Introduction: Pancreatic cancer (PC), even in the absence of metastatic disease, has a dismal prognosis. One-third of them are borderline resectable (BRPC) or locally advanced unresectable PC (LAUPC) at diagnosis. There are limited prospective data supporting the best approach on these tumours. Neoadjuvant chemotherapy (ChT) is being increasingly used in this setting.

Methods: This is a retrospective series of consecutive patients staged as BRPC or LAUPC after discussion in the multidisciplinary board (MDB) at an academic centre. All received neoadjuvant ChT, followed by chemoradiation (ChRT) in some cases, and those achieving enough downstaging had a curative-intent surgery. Descriptive data about patient's characteristics, neoadjuvant treatments, toxicities, curative resections, postoperative complications, pathology reports and adjuvant treatment were collected. Overall survival (OS) and progression-free survival was calculated with Kaplan-Meier method and log-rank test.

Results: Between August 2011 and July 2019, 49 patients fulfilled the inclusion criteria, and all of them received neoadjuvant ChT. Fluorouracil+folinic acid, irinotecan and oxaliplatin was the most frequently used scheme (77%). The most prevalent grade 3 or 4 toxicities were neutropenia (26.5%), neurotoxicity (12.2%), diarrhoea (8.2%) and nausea (8.2%). 18 patients (36.7%) received ChRT thereafter. In total, 22 patients (44,9%) became potentially resectable and 19 of them had an R0 or R1 pancreatic resection. One was found to be unresectable at surgery and two refused surgery. A vascular resection was required in 7 (35%). No postoperative deaths were observed. Postoperative ChT was given to 12 (66.7%) of resected patients. Median OS of the whole cohort was 24,9 months (95% CI 14.1 to 35.7), with 30.6 months for resected and 13.1 months for non-resected patients, respectively (p<0.001).

Conclusion: A neoadjuvant approach in BRPC and LAUPC was well tolerated and allowed a curative resection in 38.8% of them with a potential improvement on OS.
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http://dx.doi.org/10.1136/esmoopen-2020-000929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684818PMC
November 2020

Caustic ingestion: development and validation of a prognostic score.

Endoscopy 2021 08 23;53(8):784-791. Epub 2020 Oct 23.

Department of Digestive Medicine, Hospital Clínic Universitari, Universitat de Valencia, Valencia, Spain.

Background: Caustic ingestion is a potentially severe condition and early identification of poor outcome is essential to improve management; however, prediction based on endoscopy alone can overestimate severity. This study aimed to develop and validate a prognostic score.

Methods: A prospective cohort study was designed to include all consecutive patients aged > 15 years who presented with caustic ingestion between 1995 and 2017. Adverse outcome was defined by intensive care unit admission, urgent surgery, or death. The predictive value of clinical, analytical, and endoscopic variables was assessed in the first cohort (derivation cohort) and a prognostic score based on the resulting risk factors was developed by logistic regression. Internal validation (bootstrapping) was performed and then external validation was checked in an independent sample of patients (validation cohort).

Results: 469 cases of caustic ingestion were included, 265 in the derivation cohort and 204 in the validation cohort. Ingestion of acidic substances (odds ratio [OR] 3.13, 95 % confidence interval [CI] 2.33 - 4.21), neutrophil count (OR 1.05, 95 %CI 1.04 - 1.06), metabolic acidosis (bicarbonate value, OR 0.82, 95 %CI 0.78 - 0.85), and endoscopic injury (OR 3.81, 95 %CI 3.35 - 4.34) were independent risk factors for poor outcome. The prognostic score based on these variables provided better accuracy than endoscopy alone ( = 0.04), with high sensitivity, specificity, positive and negative predictive values (93.3 %, 92.7 %, 72.7 %, 98.5 %, respectively), and area under the curve (0.976, 95 %CI 0.973 - 0.979;  < 0.001).

Conclusions: This score allowed a reliable prognosis of caustic ingestion and was more accurate than endoscopy-based evaluation.
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http://dx.doi.org/10.1055/a-1297-0333DOI Listing
August 2021

The development of type-1 autoimmune hepatitis after chronic hepatitis C (HCV) clearance by direct-acting antivirals (DAA).

Rev Esp Enferm Dig 2020 Aug;112(8):664-665

Aparato Digestivo, Hospital Clinico Universitario de Valencia.

We present the case of a 72-year-old female in follow-up for chronic hepatitis due to hepatitis C virus (HCV) genotype 1b, with a liver stiffness measurement estimated by transient elastography in 2015 of 17 Kp and type 2 diabetes mellitus. She was treated daily with ledipasvir 90 mg and sofosbuvir 400 mg for 12 weeks. In March 2016, she achieved a sustained virological response (SVR) after 12 weeks and 24 weeks. She had a positive determination of antinuclear antibodies 7.9 in 2014.
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http://dx.doi.org/10.17235/reed.2020.6785/2019DOI Listing
August 2020

Clinical assessment of risk factors for infection in inflammatory bowel disease patients.

Int J Colorectal Dis 2020 Mar 8;35(3):491-500. Epub 2020 Jan 8.

Digestive Medicine department, Hospital Clínic Universitari de Valencia, Universitat de Valencia, Avda. Blasco Ibañez, 17, 46010, Valencia, Spain.

Purpose: Recognizing patients with inflammatory bowel disease who are prone to infection would enable the adjustment of the type and intensity of immunosuppressive treatment. The aim of this study was to identify a clinical profile of risk for infections in IBD patients, based on the interaction of immunosuppressive treatment with factors inherent to the patient.

Methods: A case-control study was performed among patients older than 18 years. Patients with any significant infection (any kind of severe or recurrent infection according to standard clinical criteria or a critical enough infection according to the patient) were defined as cases. Both cases and controls were randomly selected in a 1:3 ratio. All the period from diagnosis to the end of recruitment (June 2016) was analyzed. Risk factors for infection were identified by logistic regression analysis; the strength of association was reported by odds ratio (OR) with 95% confidence interval (95%CI).

Results: A total of 112 cases and 270 controls were included. The independent risk factors for significant infection are the number of immunosuppressants (one drug: OR 1.28, 95% CI 0.53-3.11, two drugs: OR 2.37, 95% CI 1.01-5,56, and three drugs: OR 5.84, 95% CI 1.57-21.72), body mass index (OR 1.08; 95 %CI 1,01-1,16), the degree of comorbidity (OR 1.52; 95% CI 1.04-2.21), and the intensity of inflammatory activity (OR 1.43; 95% CI 1.19-1.71).

Conclusions: Regardless of immunosuppression, several patient factors such as comorbidity, body mass index, or the inflammatory activity of the disease determine the individual risk of infectious complications and should be considered for an adequate risk assessment.
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http://dx.doi.org/10.1007/s00384-019-03501-0DOI Listing
March 2020

The Particularly Vulnerable Situation of Women Living Homeless in Madrid (Spain).

Span J Psychol 2019 Dec 2;22:E52. Epub 2019 Dec 2.

Universidad de Alcalá (Spain).

People in homeless situation are one of the major embodiments of the phenomenon of social exclusion, and women living homeless are considered a particularly vulnerable group. This paper examines different variables that may affect the situation of vulnerability experienced by women living homeless in Madrid (Spain). The study was carried out using data obtained from a representative sample of homeless men in Madrid (n = 158) and a sample of homeless women in Madrid of a similar size (n = 138). The information was gathered using a structured interview in shelters or other facilities for people in a homeless situation, on the street and in other places not initially designed for sleeping. The results show that woman living homeless are highly vulnerable compared to the domiciled population and, in some respects, to homeless men as well, especially in the number of times homeless (χ2 = 10.314; p < .01), in the time working with a contract and/or self-employed (t = 5.754; p < .001), and in the use of sedatives (χ2= 14.741; p < .001). It is however noted that homeless women show in some aspects greater strengths than homeless men. Such strengths could serve as a supporting point for their social inclusion processes. The analysis of issues that differentiate women in a homeless situation from their male counterparts could be useful for developing public policies and care resources adapted to the specific characteristics and needs of women living homeless.
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http://dx.doi.org/10.1017/sjp.2019.58DOI Listing
December 2019

Long-term follow-up of patients treated with aminosalicylates for ulcerative colitis: Predictive factors of response: An observational case-control study.

United European Gastroenterol J 2019 10 29;7(8):1042-1050. Epub 2019 May 29.

Digestive Disease Department, University Clinic Hospital of Valencia, Valencia, Spain.

Background: Knowing patients' ulcerative colitis history is essential to selecting the appropriate therapy according to risk stratification.

Objective: To evaluate and identify predictive factors of non-response to aminosalicylates judged as the need for a step-up approach over time.

Methods: A case-control study of ulcerative colitis patients treated with aminosalicylates after the diagnosis of disease flare included in the ENEIDA single-centre registry from 1997 to 2017. Long-term treatment maintenance with aminosalicylates and higher therapeutic requirements were recorded. The cumulative incidence of treatment escalation was estimated using Kaplan-Meier curves and compared by the log-rank test. Cox regression analysis was performed to identify predictive factors of treatment with immunomodulators, biological agents or surgery.

Results: A total of 457 patients were included, of whom 28% ( = 126) were non-responders to aminosalicylates. The cumulative probability for a step-up approach within 20 years of follow up was 35%, mainly due to steroid-dependent colitis. Risk factors for treatment escalation were age ≤27 years (hazard ratio 2.31, 95% confidence interval 1.36-3.92), extensive colitis (hazard ratio 1.65, 95% confidence interval 1.04-2.60), Mayo endoscopic subscore ≥2 (hazard ratio 1.45, 95% confidence interval 1.02-2.06) and extraintestinal manifestations (hazard ratio 2.04, 95% confidence interval 1.03-4.05).

Conclusions: Aminosalicylates represent an effective maintenance therapy. Younger age, extensive colitis, endoscopic disease severity and extraintestinal manifestations are risk factors for higher therapeutic requirements.
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http://dx.doi.org/10.1177/2050640619854277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6794696PMC
October 2019

Intravitreal dexamethasone implant Ozurdex in the treatment of diabetic macular edema in patients not previously treated with any intravitreal drug: a prospective 12-month follow-up study.

Curr Med Res Opin 2019 12 19;35(12):2111-2116. Epub 2019 Sep 19.

FISABIO-Oftalmología Médica (FOM), Valencia, Spain.

To evaluate the mid-long-term efficacy and safety of the dexamethasone intravitreal (DEX) implant (Ozurdex) in naïve patients with diabetic macular edema (DME). Prospective and single-center study conducted on consecutive patients with a diagnosis of DME, who received a DEX implant and were followed up for at least 12 months. The main outcomes measurements were the mean change in best corrected visual acuity (BCVA) and in foveal thickness (FT) as compared to the baseline values. Of the 84 screened patients 50 were included in the study. The BCVA significantly improved from 52.4 (20.4) letters at baseline to 62.6 (15.6), 61.2 (18.4), 61.6 (18.6), 60.6 (19.0), and 60.6 (18.8) at 2, 4, 6, 12 months and end of follow-up period, respectively (repeated measures ANOVA and the Greenhouse-Geisser correction;  .0008). At the end of the follow-up period, a gain of BCVA of ≥5, ≥10, and ≥15 letters were observed in 26 (52.0%), 18 (36.0%), and 16 (32.0%) patients, respectively. The mean FT was significantly reduced from 446.0 (139.9) µm at baseline to 327.2 (103.6) at the end of follow-up (repeated measures ANOVA and the Greenhouse-Geisser correction;  .0008). During the study follow-up, the patients receive a mean of 3.4 (2.9-3.9) implants. Of the 32 phakic eyes at baseline, 17 (53.1%) either developed new lens opacity or progression of an existing opacity. In eyes with DME not previously treated with intravitreal drugs, DEX implants provide meaningful functional and anatomical benefits, and these results are sustained mid-long-term.
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http://dx.doi.org/10.1080/03007995.2019.1652449DOI Listing
December 2019

Association of elevated serum triglyceride levels with a more severe course of acute pancreatitis: Cohort analysis of 1457 patients.

Pancreatology 2019 Jul 13;19(5):623-629. Epub 2019 Jun 13.

Department of Gastroenterology, Hospital Clínico Universitario, University of Valencia, Biomedical Research Institute (INCLIVA), Spain.

Background: Previous publications have reported an association between hypertriglyceridemia (HTG) and severity of acute pancreatitis, but this relationship remains somewhat controversial.

Objective: To evaluate the outcome of acute pancreatitis according to serum triglyceride levels on admission.

Methods: Retrospective analysis of prospectively collected data, which included all consecutive cases of acute pancreatitis admitted to a tertiary hospital (January 2002-December 2014). Acute pancreatitis patients were classified into 3 groups based on serum triglyceride levels (mg/dl) measured within 48 h from admission: normal triglycerides-mild HTG (<200); moderate HTG (200-749); severe HTG (≥750). Primary outcomes were the difference in organ failure, pancreatic necrosis, acute peripancreatic collections and mortality among the three groups.

Results: A total of 1,457 cases were included: 1,335 with normal-mild HTG, 77 with moderate HTG and 45 with severe HTG. The rates of organ failure (11.2% in normal-mild HTG group, 15.6% in moderate HTG and 20.0% in severe HTG), persistent multiple organ failure (2.5% vs. 5.2% vs. 6.7%), pancreatic necrosis (9.2% vs. 14.3% vs. 26.7%) and acute collections (21.6% vs. 40.3% vs. 55.6%) increased significantly with hypertriglyceridemia severity grades. On multivariate analysis, triglycerides as a quantitative variable, evaluated in increments of 100 mg/dl, was independently associated with organ failure, pancreatic necrosis, acute collections and mortality (p < 0.05).

Conclusions: Elevated serum triglyceride levels are independently associated with a more severe course of pancreatitis. It must be highlighted the elevated frequency of local complications in patients with HTG that increases proportionally and significantly with HTG severity grades.
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http://dx.doi.org/10.1016/j.pan.2019.06.006DOI Listing
July 2019

Disease severity and treatment requirements in familial inflammatory bowel disease.

Int J Colorectal Dis 2017 Aug 31;32(8):1197-1205. Epub 2017 Mar 31.

Digestive Disease Department, University of Valencia, University Clinic Hospital of Valencia, Blasco Ibañez Av. 17, 46010, Valencia, Spain.

Purpose: Several studies demonstrate an increased prevalence and concordance of inflammatory bowel disease among the relatives of patients. Other studies suggest that genetic influence is over-estimated. The aims of this study are to evaluate the phenotypic expression and the treatment requirements in familial inflammatory bowel disease, to study the relationship between number of relatives and degree of kinship with disease severity and to quantify the impact of family aggregation compared to other environmental factors.

Methods: Observational analytical study of 1211 patients followed in our unit. We analyzed, according to the existence of familial association, number and degree of consanguinity, the phenotypic expression, complications, extraintestinal manifestations, treatment requirements, and mortality. A multivariable analysis considering smoking habits and non-steroidal-anti-inflammatory drugs was performed.

Results: 14.2% of patients had relatives affected. Median age at diagnosis tended to be lower in the familial group, 32 vs 29, p = 0.07. In familial ulcerative colitis, there was a higher proportion of extraintestinal manifestations: peripheral arthropathy (OR = 2.3, p = 0.015) and erythema nodosum (OR = 7.6, p = 0.001). In familial Crohn's disease, there were higher treatment requirements: immunomodulators (OR = 1.8, p = 0.029); biologics (OR = 1.9, p = 0.011); and surgery (OR = 1.7, p = 0.044). The abdominal abscess increased with the number of relatives affected: 5.1% (sporadic), 7.0% (one), and 14.3% (two or more), p=0.039. These associations were maintained in the multivariate analysis.

Conclusions: Familial aggregation is considered a risk factor for more aggressive disease and higher treatment requirements, a tendency for earlier onset, more abdominal abscess, and extraintestinal manifestations, remaining a risk factor analyzing the influence of some environmental factors.
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http://dx.doi.org/10.1007/s00384-017-2791-yDOI Listing
August 2017

Evidence-based Guidelines for the Management of Exocrine Pancreatic Insufficiency After Pancreatic Surgery.

Ann Surg 2016 Dec;264(6):949-958

*Department of Surgery, Hospital Clinico, University of Valencia, Valencia, Spain †Department of Surgery, Complejo Hospitalario Universitario de Vigo, Vigo, Spain ‡Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands §Department of Gastroenterology, Consorci Sanitari de Terrassa, Terrassa, Spain ¶Department of Gastroenterology, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain ||Department of Surgery, Università Vita e Salute, Ospedale San Raffaele IRCCS, Milano, Italy **Department of Surgery, Institut de Malalties Digestives I Metabòliques, Hospital Clínic, IDIBAPS, Barcelona, Spain ††Department of Medicine, Pancreas Center, University of Verona, Verona, Italy ‡‡Department of Endocrinology and Nutrition, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain. §§Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ¶¶Department of Surgery, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain. ||||Department of Surgery, Hospital Universitario de La Princesa, Madrid, Spain ***Department of Gastroenterology, Complejo Hospitalario de Navarra, Pamplona, Spain †††Unidad de Cirugía Hepato-bilio-pancreática y Trasplante, Hospital Universitari i Politecnic. La Fe, Valencia, Spain ‡‡‡NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK §§§Department of Gastroenterology, Hospital Clinico, University of Valencia, Valencia, Spain ¶¶¶Unit of Digestive Disease, Agencia Sanitaria Costa del Sol, Marbella, Málaga ||||||Department Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy ****Department of Surgery, Hospital Universitario de Guadalajara, Guadalajara, Spain ††††Department of HPB Surgery and Liver Transplantation, Hospital Carlos Haya, Malaga, Spain ‡‡‡‡Exocrine Pancreas Research Unit, Hospital Universitari Vall d'Hebron, Institut de Recerca, Universitat Autònoma de Barcelona, CIBEREHD, Barcelona, Spain §§§§Department of Digestive Surgery- Division of HBP Surgery, Hospital Universitario Donostia, San Sebastián, Spain ¶¶¶¶Department of Gastroenterology, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, IDIBAPS, CiberEHD, Barcelona, Spain ||||||||Department of Gastroenterology, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain.

Objective: To provide evidence-based recommendations for the management of exocrine pancreatic insufficiency (EPI) after pancreatic surgery.

Background: EPI is a common complication after pancreatic surgery but there is certain confusion about its frequency, optimal methods of diagnosis, and when and how to treat these patients.

Methods: Eighteen multidisciplinary reviewers performed a systematic review on 10 predefined questions following the GRADE methodology. Six external expert referees reviewed the retrieved information. Members from Spanish Association of Pancreatology were invited to suggest modifications and voted for the quantification of agreement.

Results: These guidelines analyze the definition of EPI after pancreatic surgery, (one question), its frequency after specific techniques and underlying disease (four questions), its clinical consequences (one question), diagnosis (one question), when and how to treat postsurgical EPI (two questions) and its impact on the quality of life (one question). Eleven statements answering those 10 questions were provided: one (9.1%) was rated as a strong recommendation according to GRADE, three (27.3%) as moderate and seven (63.6%) as weak. All statements had strong agreement.

Conclusions: EPI is a frequent but under-recognized complication of pancreatic surgery. These guidelines provide evidence-based recommendations for the definition, diagnosis, and management of EPI after pancreatic surgery.
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http://dx.doi.org/10.1097/SLA.0000000000001732DOI Listing
December 2016

Diagnosis, treatment and long-term outcomes of autoimmune pancreatitis in Spain based on the International Consensus Diagnostic Criteria: A multi-centre study.

Pancreatology 2016 May-Jun;16(3):382-90. Epub 2016 Feb 22.

Department of Gastroenterology, Hospital Universitari Dr. Peset, University of Valencia, Valencia, Spain.

Objectives: Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis that has been reported worldwide for the last two decades. The aim of this study is to analyse the clinical profile of patients from Spain with AIP, as well as treatments, relapses and long-term outcomes.

Methods: Data from 59 patients with suspected AIP that had been diagnosed in 15 institutions are retrospectively analysed. Subjects are classified according to the International Consensus Diagnostic Criteria (ICDC). Patients with type 1 AIP (AIP1) and type 2 AIP (AIP2) are compared. Kaplan-Meier methodology is used to estimate the overall survival without relapses.

Results: Fifty-two patients met ICDC, 45 patients were AIP1 (86.5%). Common manifestations included abdominal pain (65.4%) and obstructive jaundice (51.9%). Diffuse enlargement of pancreas was present in 51.0%; other organ involvement was present in 61.5%. Serum IgG4 increased in 76.7% of AIP1 patients vs. 20.0% in AIP2 (p = 0.028). Tissue specimens were obtained in 76.9%. Initial successful treatment with steroids or surgery was achieved in 79.8% and 17.3%, respectively. Maintenance treatment was given in 59.6%. Relapses were present in 40.4% of AIP1, with a median of 483 days. Successful long-term remission was achieved in 86.4%.

Conclusions: AIP1 is the most frequent form of AIP in Spain in our dataset. Regularly, ICDC allows AIP diagnosis without the need for surgery. Steroid and chirurgic treatments were effective and safe in most patients with AIP, although maintenance was required many times because of their tendency to relapse. Long-term serious consequences were uncommon.
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http://dx.doi.org/10.1016/j.pan.2016.02.006DOI Listing
March 2017

Surgical versus nonsurgical treatment of infected pancreatic necrosis: more arguments to change the paradigm.

J Gastrointest Surg 2013 Sep 3;17(9):1627-33. Epub 2013 Jul 3.

Department of Gastroenterology, Hospital Clínico, University of Valencia, Avda. Blasco Ibáñez, 17, 46010, Valencia, Spain.

Objectives: This study aimed to compare primary surgical versus nonsurgical treatment in a series of patients with infected pancreatic necrosis (IPN) and to investigate whether the success of nonsurgical approach is related to a less severe disease.

Methods: Thirty-nine consecutive patients with IPN have been included and further subdivided into two groups: primary surgical (n = 21) versus nonsurgical (n = 18). Outcome measures were the differences in mortality, morbidity, and pancreatic function. Comorbidity, organ failure, and other severity indexes were compared between the two groups.

Results: Mortality occurred in 16.7% of cases in the nonsurgical group versus 42.9% in the surgical group. In the primary nonsurgical group, seven were operated on due to failure of initial conservative treatment. In this latter group, mortality was 28.6% and was performed significantly later than in the primary surgical group. The group of primary surgical treatment was associated with a significant higher rate of multiple organ failure (MOF) at IPN diagnosis, new onset or worsening of organ failure, and MOF and nosocomial infection after surgery.

Conclusions: Initial nonsurgical approach in IPN is associated with better results both in cases which respond to this treatment as well as in those who, failing this conservative approach, have to be operated on after a delayed period. Primary surgically treated patients had a more severe disease at the time of IPN.
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http://dx.doi.org/10.1007/s11605-013-2266-6DOI Listing
September 2013

Malondialdehyde in early phase of acute pancreatitis.

Rev Esp Enferm Dig 2011 Nov;103(11):563-9

Department of Gastroenterology, Hospital Clínico Universitario de Valencia, Universitat de València, València, Spain.

Aims: to assess oxidative stress in acute pancreatitis, its evolution over time and its relationship with the severity of the disease.

Methods: during a two-year period, patients with acute pancreatitis with less than 24 hours of pain were evaluated. Serum was obtained the first, second and fourth day from admittance, if complications were detected, and after recovery. Malondialdehyde was determined by high performance liquid chromatography. Twenty healthy volunteers constituted the control group. Malondialdehyde between groups was compared with Mann-Whitney and Kruskal-Wallis tests; malondialdehyde evolution was studied with Wilcoxon test.

Results: one hundred and sixty-nine patients were included (91 women, median age 67 years, range 20-95); 33 suffered a severe episode. Malondialdehyde decreased from first to fourth day (0.600 vs. 0.451 vs. 0.343 M, respectively, p < 0.05). When complications were detected, malondialdehyde level was similar to that of first and second day (0.473 M, p > 0.05). In severe attacks malondialdehyde was higher than in control group at day 2 (severe: 0.514; mild: 0.440; control: 0.347 M, p < 0.05 severe vs. control).

Conclusions: an early oxidative stress is observed in acute pancreatitis. In severe attacks, oxidative stress remains high longer than in mild episodes. The onset of complications is associated with high malondialdehyde concentration.
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http://dx.doi.org/10.4321/s1130-01082011001100002DOI Listing
November 2011

Sacral nerve stimulation for fecal incontinence.

Rev Esp Enferm Dig 2011 Jul;103(7):355-9

Hospital Infanta Sofía, Madrid, Spain.

Objective: to analyze short-term outcomes and complications for our first fifty patients with fecal incontinence undergoing sacral root stimulation.

Patients: fifty patients with fecal incontinence receiving sacral neuromodulation in 4 hospitals are reviewed. Discussed variables include: age, sex, incontinence duration, incontinence cause, prior surgery for incontinence, Wexner scale score, anorectal manometry parameters, and endoanal ultrasonographic findings. Following the procedure Wexner scale score, anorectal manometry parameters, and associated complications are reviewed.

Results: mean age of patients is 59.9 years, with females predominating. Most common causes of incontinence include obstetric procedures, idiopathic origin, and prior anal surgery. Mean follow-up is 17.02 months. Follow-up revealed a statistically significant reduction in Wexner scale score and increase in voluntary anal pressure. Technique-derived minor complications included: 2 surgical wound infections that led to stimulator withdrawal; 2 patients with pain who were managed conservatively; 1 case of externalization in a gluteal stimulator; and 1 broken tetrapolar electrode.

Conclusions: sacral nerve stimulation is a simple technique that improves Wexner scores in a statistically significant manner with a low complications rate.
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http://dx.doi.org/10.4321/s1130-01082011000700004DOI Listing
July 2011

Biosutures improve healing of experimental weak colonic anastomoses.

Int J Colorectal Dis 2010 Dec 11;25(12):1447-51. Epub 2010 Jun 11.

Department of General Surgery C, La Paz University Hospital, Paseo de la Castellana 261, 28046, Madrid, Spain.

Purpose: Use of biosutures in animal models of colonic anastomoses is associated with decreased adhesions without affecting anastomotic strength. This study aimed to evaluate the effect of biosutures on colonic anastomoses kept free of adhesions by peritoneal instillation of icodextrin 4%.

Methods: Three types of colonic anastomoses were compared: group 1, anastomoses without icodextrin 4% and control suture; group 2, anastomoses with icodextrin 4% (adhesion-free anastomoses) and control suture; and group 3, anastomoses with icodextrin 4% (adhesion-free anastomoses) and biosutures. Dehiscence, adhesion formation, and anastomotic strength were evaluated on day 4 after the operation.

Results: When peritoneal icodextrin 4% was used in anastomoses with conventional sutures, a decrease in the adhesion index (P = 0.01) and a lower bursting pressure (P = 0.15) were observed. When adhesion-free anastomoses were compared, those performed with biosutures had a higher bursting pressure (P = 0.008) and a similar pattern of adhesion index (P = 0.48).

Conclusions: Biosutures improve the strength of adhesion-free colonic anastomoses.
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http://dx.doi.org/10.1007/s00384-010-0952-3DOI Listing
December 2010

Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial.

Dis Colon Rectum 2009 Jan;52(1):79-86

Department of Surgery and Cell Therapy, La Paz University Hospital, Universidad Autónoma de Madrid, Madrid, Spain.

Purpose: The feasibility and safety of stem cell-based therapy with expanded adipose-derived stem cells (ASCs) has been investigated in a phase I clinical trial. The present study was designed as a phase II multicenter, randomized controlled trial to further investigate the effectiveness and safety of ASCs in the treatment of complex perianal fistulas.

Methods: Patients with complex perianal fistulas (cryptoglandular origin, n = 35; associated with Crohn's disease, n = 14) were randomly assigned to intralesional treatment with fibrin glue or fibrin glue plus 20 million ASCs. Fistula healing and quality of life (SF-12 questionnaire) were evaluated at eight weeks and one year. If healing was not seen at eight weeks, a second dose of fibrin glue or fibrin glue plus 40 million ASCs was administered.

Results: Fistula healing was observed in 17 (71 percent) of 24 patients who received ASCs in addition to fibrin glue compared with 4 (16 percent) of 25 patients who received fibrin glue alone (relative risk for healing, 4.43; confidence interval, 1.74-11.27); P < 0.001). The proportion of patients with healing was similar in Crohn's and non-Crohn's subgroups. ASCs were also more effective than fibrin glue alone in patients with a suprasphincteric fistulous tract (P = 0.001). Quality of life scores were higher in patients who received ASCs than in those who received fibrin glue alone. At one year follow-up, the recurrence rate in patients treated with ASCs was 17.6 percent. Both treatments were well tolerated.

Conclusion: Administration of expanded ASCs (20 to 60 million cells) in combination with fibrin glue is an effective and safe treatment for complex perianal fistula and appears to achieve higher rates of healing than fibrin glue alone.
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http://dx.doi.org/10.1007/DCR.0b013e3181973487DOI Listing
January 2009

[Biliary atresia in the adult].

Cir Esp 2008 Dec;84(6):342-4

Servicio de Cirugía General C. Hospital Universitario La Paz, Madrid, Spain.

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http://dx.doi.org/10.1016/s0009-739x(08)75050-4DOI Listing
December 2008

Treatment of enterocutaneous fistula in Crohn's Disease with adipose-derived stem cells: a comparison of protocols with and without cell expansion.

Int J Colorectal Dis 2009 Jan 12;24(1):27-30. Epub 2008 Aug 12.

Department of Surgery, La Paz University Hospital, Madrid, Spain.

Background: Expanded adipose-derived stem cells (ASC) have been shown to be effective in treating Crohn's patients with enterocutaneous fistulas. It is possible that unexpanded cells corresponding to the stromal vascular fraction (SVF) may also be effective.

Materials And Methods: A subpopulation of patients from a previous proof-of-concept phase I study with enterocutaneous fistulas received autologous expanded ASCs. The same selection criteria for inclusion were applied to patients who underwent SVF implantation to treat enterocutaneous fistulas. After tract curettage, cell suspensions (either SVF cells from lipoaspirate or expanded ASCs) were injected into the tract walls, and the fistulous tract was sealed with fibrin adhesive (with or without cells).

Results: In the series that received ASCs, four fistulas could be evaluated, and cure was achieved in three out of four cases. In the series that received SVF cells, four fistulas were evaluated, with cure achieved in one out of four cases.

Conclusions: Although a comparison of case series cannot be considered firm evidence, a therapeutic protocol that uses expansion prior to implantation does seem to be more effective than one that uses SVF cells directly from a lipoaspirate sample.
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http://dx.doi.org/10.1007/s00384-008-0559-0DOI Listing
January 2009

Morphological and functional evaluation of the pancreatic duct with secretin-stimulated magnetic resonance cholangiopancreatography in alcoholic pancreatitis patients.

Dig Dis Sci 2008 Dec 10;53(12):3234-41. Epub 2008 May 10.

Department of Gastroenterology, University Clinic Hospital of Valencia, University of Valencia, Avda Blasco Ibañez 17, Valencia, 46010, Spain.

Objectives: The aim of this investigation was to evaluate the pancreatographic findings and dynamics of pancreatic duct diameter, as determined by secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP), in patients with acute alcoholic pancreatitis or chronic alcoholic pancreatitis and in a control group.

Methods: S-MRCP was performed in patients with acute alcoholic pancreatitis who did not manifest the functional and radiological (ultrasonography and computed tomography) criteria of chronic pancreatitis (n = 21), in patients with chronic alcoholic pancreatitis (n = 28) and in a control group (n = 16). The diameter of the main pancreatic duct (MPD) was monitored before secretin administration and at 3 and 10 min after secretin administration. Morphological features were also assessed before and after the administration of secretin.

Results: All ductal diameters were significantly larger in chronic alcoholic pancreatitis (P < 0.0001). There were no differences in MPD caliber between patients with acute alcoholic pancreatitis and the control group. The percentage of variation between basal MPD diameter and at 3 min post-secretin administration was lower in patients with chronic (35.5%) pancreatitis than in those with acute alcoholic pancreatitis (52.3%) and the control group (52.5%). There were no significant differences between patients with acute alcoholic pancreatitis and the control group in terms of the frequency of visualization of side branches, ductal narrowing, intraluminal filling defects, and ductal irregularity. One patient with acute alcoholic pancreatitis presented ductal criteria of chronic pancreatitis following the administration of secretin.

Conclusions: The dynamics of MPD visualized on S-MRCP in patients with acute alcoholic pancreatitis is similar to that observed in the control group and different from that observed in patients with chronic alcoholic pancreatitis. There were no significant differences between patients with acute alcoholic pancreatitis and the control group in terms of morphological pancreatographic features.
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http://dx.doi.org/10.1007/s10620-008-0284-0DOI Listing
December 2008

The concentration of deoxyribonucleic acid in plasma from 73 patients with colorectal cancer and apparent clinical correlations.

Cancer Detect Prev 2008 8;32(1):39-44. Epub 2008 Apr 8.

Department of Surgery, "La Paz" University Hospital, Madrid, Spain.

Background: Detection of cell-free plasma DNA has considerable potential as a tool for the diagnosis and assessment of the prognosis of many types of cancer. The aim of the present study was to quantify, by spectrophotometry, the cell-free DNA in plasma samples from patients with colorectal cancer at different stages of the disease and to attempt to correlate the resultant values with the clinical picture.

Methods: We reviewed the medical reports of 73 patients, who had undergone resection of primary colorectal cancer. Samples of blood had been taken from each patient immediately prior to surgery. DNA was extracted from samples of plasma and quantified, by spectrophotometry, after a storage period of no longer than 2 years in 89% of the cases examined.

Results: The mean(+/-S.D.) concentration of DNA in plasma samples was 108+/-156 ng/microl. We found a statistically significant correlation between the concentration of DNA and the presence of metastases (mainly liver metastases).

Conclusion: The detection and quantitation of cell-free DNA in plasma, using this simple technique, might be of clinical value for the surveillance of colon cancer patients and the detection of metastases.
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http://dx.doi.org/10.1016/j.cdp.2008.01.002DOI Listing
June 2008

An assessment of the incidence of fistula-in-ano in four countries of the European Union.

Int J Colorectal Dis 2007 Dec 7;22(12):1459-62. Epub 2007 Jun 7.

Cellerix, S.L., Madrid, Spain.

Background And Aims: In spite of its long history, fistula-in-ano is generally considered to be relatively uncommon. Nevertheless, no comprehensive analysis of its incidence in developed countries is available. Our goal was to determine the actual incidence of fistula-in-ano based on the study of incidence in four countries of the European Union (EU).

Materials And Methods: We performed a search of hospital inpatient databases in five different countries. We obtained valid data from four European countries, namely, England (UK; Hospital Episodes Statistics), Germany (German hospitals' databases), Italy (Scheda di Dimissione Ospedaliera), and Spain (Conjunto Mínimo Básico de Datos by Insalud-Spanish National Health Institute).

Results: The incidence of fistula-in-ano varied among the different populations in the EU. In the four countries examined, it ranged from 1.04 per 10,000/year in Spain to 2.32 per 10,000/year in Italy. A statistical comparison of rates from the different countries studied gives a confidence interval from 1.20 up to 2.80. The population that we studied represents almost 51% of the total population of the EU.

Conclusion: This study attempts to determine the actual incidence of fistula-in-ano in the European Community, which was previously uncertain despite its major negative effects on quality of life and the high cost of treatment. Our findings indicate that the incidence of fistula-in-ano in the four countries of the EU studied is significantly higher than that in the only previously published report of the incidence of fistula-in-ano in Europe. Nevertheless, our findings confirm the general perception that fistula-in-ano is a relatively uncommon disease.
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http://dx.doi.org/10.1007/s00384-007-0334-7DOI Listing
December 2007

Is prophylactic cholecystectomy useful in obese patients undergoing gastric bypass?

Obes Surg 2006 Jul;16(7):883-5

Department of General Surgery, Hospital Universitario La Paz, Madrid, Spain.

Background: Obesity constitutes a clear risk factor for cholelithiasis, especially if it is associated with a rapid weight loss, as is the case of patients following bariatric surgery. Prophylactic cholecystectomy is indicated in biliopancreatic diversions due to the high incidence of postoperative cholelithiasis. However, there is no agreement on gastric bypass. This study was conducted to establish the incidence of cholecystopathy demonstrated by histology and to assess the indication for prophylactic cholecystectomy in a systematic way on patients undergoing gastric bypass.

Methods: The evaluation is based on 100 consecutive morbidly obese patients undergoing open gastric bypass surgery with concomitant prophylactic cholecystectomy. Variables studied were: age, gender, body mass index, preoperative ultrasound and the anatomopathologic analysis of the gallbladder that was removed.

Results: Of the 100 patients who took part in the trial, 11 had had a previous cholecystectomy. Among the 89 patients remaining, preoperative ultrasound diagnosis of cholelithiasis was 16.8%, and the actual postoperative incidence was 24.7%. Other histologic alterations were: cholesterolosis 46.1%, chronic unspecified cholecystitis 22.5%, and granulomatous cholecystitis 1.1%. The total incidence of cholecystopathy was 93.3%. The morbi-mortality related to cholecystectomy was 0%.

Conclusions: Based on these results and given the absence of morbidity, we believe that prophylactic cholecystectomy is suitable during open gastric bypass.
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http://dx.doi.org/10.1381/096089206777822287DOI Listing
July 2006

A phase I clinical trial of the treatment of Crohn's fistula by adipose mesenchymal stem cell transplantation.

Dis Colon Rectum 2005 Jul;48(7):1416-23

Department of General Surgery, La Paz University Hospital, Madrid, Spain.

Purpose: The effective management of fistulas in patients with Crohn's disease presents an extremely challenging problem. Mesenchymal adult stem cells extracted from certain tissues, such as adipose tissue, can differentiate into various cell types. Therefore, we have tried to use such cells to stimulate healing of Crohn's fistulas.

Methods: We designed a prospective Phase I clinical trial, involving five patients with Crohn's disease, to test the feasibility and safety of autologous stem cells transplantation in the treatment of fistulas. We also studied the expression of various cell markers and the growth rates of the lipoaspirate-derived cells that were used for transplantation.

Results: One patient was excluded because of bacterial contamination of cultured cells. We inoculated nine fistulas in four patients with autologous adipose tissue-derived stem cells at Passage 3 or earlier. Eight inoculated fistulas were followed weekly for at least eight weeks. In six fistulas, the external opening was covered with epithelium at the end of Week 8, and, thus, these fistulas were considered healed (75 percent). In the other two fistulas, there was only incomplete closure of the external opening, with a decrease in output flow (not healed; 25 percent). No adverse effects were observed in any patient at the end of the follow-up period (minimum follow-up,12 months; maximum follow-up, 30 months; follow-up average, 22 months).

Conclusions: To our knowledge, this is the first report of a clinical trial of cell therapy using autologous stem cells obtained from a lipoaspirate. Our results indicate that our protocol is feasible and safe for the treatment of fistulas in Crohn's disease. The number of patients included and the uncontrolled nature of Phase I clinical trials do not allow demonstration of the effectiveness of the treatment. However, the results of the present study encourage to perform further studies in Phase II.
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http://dx.doi.org/10.1007/s10350-005-0052-6DOI Listing
July 2005

Recurrence of acute gallstone pancreatitis and relationship with cholecystectomy or endoscopic sphincterotomy.

Am J Gastroenterol 2004 Dec;99(12):2417-23

Department of Gastroenterology, University Clinic Hospital of Valencia, University of Valencia, 46010 Valencia, Spain.

Objectives: To determine the prevalence of recurrence of gallstone pancreatitis, its clinical features, and the presence of prognostic factors of recurrence.

Methods: From January 1, 2000 to August 31, 2003, 233 patients admitted with acute gallstone pancreatitis (AGP) were prospectively studied. Patients were divided into two groups: recurrent and nonrecurrent group. Clinical, analytical, radiological, prognostic parameters, and severity (Atlanta criteria) were assessed, along with the performance of cholecystectomy or endoscopic sphincterotomy (ES). Clinical features of recurrence were analyzed. Univariate (chi(2), Student's t-test) and multivariate tests were performed. Statistical significance was assumed if p < 0.05.

Results: Two hundred and eighty-six attacks were identified. Forty-two patients (18.2%) recurred, suffering 53 recurrent attacks, which took place within 30 days in 23.3%. Patients who did not undergo surgery after the first attack had 31-fold risk of recurrence (OR = 31.5%, CI = 95%[7.22-137.84], p < 0.001). In patients not operated, recurrence was more frequent if ES was not performed (37.04%vs 0%, p= 0.019). Among patients with surgical risk, none who recurred underwent ES, compared with 27.9% of those who did not recur. Patients in the nonrecurrent group underwent cholecystectomy within the first 30 days or ES more frequently (31.2%vs 7.3%, p= 0.001).

Conclusions: Recurrence of gallstone pancreatitis is a frequent event. Delay of cholecystectomy implies an increased risk of recurrence. ES could be an acceptable option to prevent recurrence in patients who are not candidates for surgery or who do not desire to undergo cholecystectomy.
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http://dx.doi.org/10.1111/j.1572-0241.2004.40896.xDOI Listing
December 2004

A risk score system for identification of patients with upper-GI bleeding suitable for outpatient management.

Gastrointest Endosc 2004 Jun;59(7):772-81

Servicio de Gastroenterología, Hospital Clínico Universitario, Universitat de Valencia, Valencia, Spain.

Background: The aim of this study was to develop a risk score system for identification of patients with upper-GI hemorrhage who are suitable for outpatient management.

Methods: From a prospective cohort of 983 consecutive patients with upper-GI hemorrhage not associated with portal hypertension, 581 cases that did not meet pre-established criteria for admission were selected, and a logistic regression analysis was performed to identify factors associated with two adverse outcomes: recurrent bleeding and/or the need for emergency surgery. The risk score system was developed by using the beta coefficients of the logistic model, and its performance was evaluated. The results of this model were combined with pre-established criteria for admission to build a simplified scoring system for identification of patients who can be managed safely on an outpatient basis.

Results: Chronic alcoholism, active malignancy, prior upper digestive tract surgery, wasting syndrome, hemodynamic compromise, duodenal ulcer as the cause of upper-GI hemorrhage, and hemorrhage of unknown cause were independently associated with a greater risk of unfavorable outcomes in the group that did not meet pre-established criteria for admission. The logistic model showed a high capacity for discrimination (C statistic: 0.87) and good calibration (p value for Hosmer-Lemeshow goodness-of-fit test, 0.62), with a sensitivity of 100% and specificity of 64%. The simplified score had a sensitivity of 100% and specificity of 29% for adverse outcomes, and sensitivity of 78% and specificity of 38% for mortality.

Conclusions: The score system developed in this study may be helpful in deciding between hospitalization and outpatient management for patients with upper-GI hemorrhage, but it remains to be validated in patient groups other than those used for its development.
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http://dx.doi.org/10.1016/s0016-5107(04)00362-1DOI Listing
June 2004

Elevated serum eotaxin levels in patients with inflammatory bowel disease.

Am J Gastroenterol 2002 Jun;97(6):1452-7

Department of Allergy and Clinical Immunology, Hospital Clínico Universitario, Universidad de Valencia, Spain.

Objective: Eotaxin is a recently characterized chemokine with potent and selective chemotactic activity for eosinophils. Previous studies indicating that eosinophils accumulate and become activated in inflammatory bowel disease (IBD) led us to hypothesize that eotaxin is potentially involved in the pathophysiology of IBD and, therefore, that eotaxin would be increased in the serum of patients with IBD. The objective of this study was to test those assumptions.

Methods: We investigated 72 patients with IBD, 35 with ulcerative colitis, and 37 with Crohn's disease. A total of 27 patients had active and 45 inactive disease; 26 were receiving corticosteroids. Eotaxin serum levels were determined by solid phase sandwich ELISA. Lymphocytes, monocytes, and granulocyte subpopulations were determined in fresh blood samples with an automated autoanalyzer.

Results: Serum eotaxin levels were significantly higher in patients with Crohn's disease and in those with ulcerative colitis than in the control subjects (p < 0.0001). Patients with inactive Crohn's disease had significantly higher levels of eotaxin than patients with inactive ulcerative colitis (p < 0.05). We did not find significant differences for activity or inactivity of disease, nor for treatment with prednisone. A negative correlation (p < 0.05) was found between eotaxin serum level and eosinophil counts in peripheral blood in patients with Crohn's disease.

Conclusions: There is an increased expression of eotaxin in IBD patients, suggesting that eotaxin may be involved in the pathogenesis of IBD. This increase is more accentuated in Crohn's disease and negatively correlates with the eosinophil number in peripheral blood. Our data support the increasing evidence that eosinophil are functionally involved in the pathophysiology of IBD.
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http://dx.doi.org/10.1111/j.1572-0241.2002.05687.xDOI Listing
June 2002

Quadruply Bonded Dichromium Complexes with Variously Fluorinated Formamidinate Ligands.

Inorg Chem 1999 May;38(9):2182-2187

Laboratory for Molecular Structure and Bonding, Department of Chemistry, P.O. Box 30012, Texas A&M University, College Station, Texas 77842-3012, and Escuela de Química, Universidad de Costa Rica, Ciudad Universitaria, Costa Rica.

Complexes of chromium with various amidinate anions of N,N'-di(biphenyl)formamidine (DbiPhF), N,N'-di(pentafluorophenyl)formamidine (DPh(F)()5F), N,N'-di(p-fluorophenyl)formamidine (DPh(p)(-)(F)F), N,N'-di(o-fluorophenyl)formamidine (DPh(o)(-)(F)F), N,N'-di(3,5-fluorophenyl)formamidine (DPh(3,5)(-)(F)F), and N,N'-di(m-fluorophenyl)formamidine (DPh(m)(-)(F)F) have been synthesized and structurally characterized to study the response of the M-M multiple bond to the donor capacity of the ligand by varying the substituents of the aromatic rings. All six of these dinuclear fluorinated amidinate derivatives of the chromium(II) compounds have the paddlewheel configuration. The synthetic route involves the reaction of CrCl(2) with the corresponding lithium salt of the ligands, LiDArF (where Ar = o-C(6)H(4)F, m-C(6)H(4)F, p-C(6)H(4)F, p-C(6)H(4)C(6)H(5), C(6)F(5), or 3,5-C(6)H(3)F(2)). Compounds [Cr(2)(DPh(p)(-)(F)F)(4)] (1), [Cr(2)(DPh(m)(-)(F)F)(4)] (2), [Cr(2)(DPh(3,5)(-)(F)F)(4)].C(6)H(14) (3.C(6)H(14)), and [Cr(2)(DbiPhF)(4)].0.7CH(2)Cl(2) (4.0.7CH(2)Cl(2)) show no variation in the Cr-Cr quadruple bond length, even though the ligands have very different basicities. In the solid state, [Cr(2)(DPh(F)()5F)(4)] (5) shows close axial contacts between the o-F atoms and the chromium metal centers. The (19)F NMR show an unresolved and broad signal for all o-F atoms that cannot be resolved even at very low temperature. To assess the efficiency of the contacts, [Cr(2)(DPh(o)(-)(F)F)(4)] (6) was prepared.( )()The crystal structure shows the same kind of Cr.F interactions as in 5, and an elongation of the Cr-Cr quadruple bond, compared with the values for the complexes 1, 2, 3, and 4. These new complexes reveal that the electronic contribution of the ligand basicity to the M-M bond is smaller and less important than the axial interactions of the chromium centers. Crystal data: for 1, orthorhombic, space group Fddd with a = 25.25(7) Å, b = 26.752(12) Å, c = 28.57(4) Å, alpha = beta = gamma = 90 degrees, and Z = 16; for 2, triclinic, space group P&onemacr; with a = 9.606(12) Å, b = 9.727(10) Å, c = 13.249(11) Å, alpha = 69.24(1) degrees, beta = 73.84(2) degrees, gamma = 84.24(2) degrees, and Z = 1; for 3.C(6)H(14), triclinic, P&onemacr; with a = 10.8274(10) Å, b = 13.739(2) Å, c = 18.152(4) Å, alpha = 83.25(1) degrees, beta = 75.61(2) degrees, gamma = 70.246(10) degrees, and Z = 2; for 4.0.7CH(2)Cl(2), triclinic P1 with a = 9.689(2) Å, b = 13.7088(3) Å, c = 16.844(3) Å, alpha = 69.90(3) degrees, beta = 87.10(3) degrees, gamma = 70.13(3) degrees, and Z = 1; for 5, monoclinic, C2/c with a = 19.114(3) Å, b = 18.957(3) Å, c = 29.923(6) Å, beta = 97.27(1) degrees, and Z = 4; for 6, triclinic, P&onemacr; with a =10.225(2) Å, b = 11.312(2) Å, c = 11.797(3) Å, alpha = 117.08(1) degrees, beta = 96.432(2) degrees, gamma = 107.52(2) degrees, and Z = 1.
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http://dx.doi.org/10.1021/ic990007lDOI Listing
May 1999
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