17-ß-estradiol affects BLyS serum levels and the nephritogenic autoantibody network accelerating glomerulonephritis in NZB/WF1 mice.

Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects fertile women, suggesting sex hormones are involved in disease pathogenesis. B lymphocyte stimulator (BLyS) has been found to be elevated in SLE patients and to drive a lupus-like syndrome in transgenic mice. Our aim was to evaluate the effects of estrogen administration on BLyS and nephritogenic anti-C1q and anti-dsDNA antibodies in lupus-prone NZB/WF1 mice. We implanted pellets releasing 17-ß-estradiol (18.8 µg/day) on the back side the ear of 10 NZB/WF1 mice (group 1), and compared them with 10 mice intraperitoneally injected with PBS 200 µl twice a week (group 2), as controls. We evaluated BLyS, anti-dsDNA and anti-C1q serum levels starting one week after pellet implantation. We also analyzed time to proteinuria onset, proteinuria-free survival and overall survival. Kidneys, spleen, liver and lungs were harvested for histological analysis. Mice were bred until natural death. BLyS serum levels were higher in group 1 than in group 2 mice at each evaluation. Group 1 mice developed nephritogenic antibodies and proteinuria significantly earlier and at higher levels than controls. Direct correlation between BLyS and anti-C1q (R (2 )= 0.6962, p < 0.0001) or anti-dsDNA (R (2 )= 0.5953, p < 0.0001), and between anti-C1q and anti-dsDNA autoantibodies (R (2 )= 0.5615, p < 0.0001) were found. Proteinuria-free and global survival rates were significantly lower in group 1 than in controls. Histological analyses showed more severe abnormalities in group 1 mice. Estrogen administration is associated with increased levels of BLyS as well as of anti-C1q and anti-dsDNA antibodies, leading to accelerated glomerulonephritis and disease progression in NZB/WF1 mice.

Management of grade III-IV blunt liver traumas: a comparative, observational study.

AIM: The aim of the present study was to assess the impact of angiographic embolization in view of expanding indications for the conservative management of grade III-IV liver injuries. METHODS: Fifty adult patients with grade III-IV hepatic trauma were admitted to our Hepato-Biliary-Pancreatic Surgery and Level II Regional Trauma Center from 1993 to 2010 and retrospectively analyzed. Injury severity, management strategies and outcomes of patients admitted between 1993 and 2005 were analyzed and compared with those admitted between 2005 and 2010. Univariable and multivariable logistic models were fitted to investigate the differences between the two time windows studied, in particular with regard to morbidity, mortality, treatment and outcomes, the use of non-operative management and of angiographic embolization. RESULTS: At univariable analysis the majority of the patients treated after 2005 were more likely to have undergone arterial embolization, and less likely to have incurred morbidity, conversion to surgery, or to be admitted to the Intensive Care Unit after initial treatment (baseline category). At multivariable analysis the patients treated before 2005 were more likely to be older than 25 years to receive angiographic embolization and less likely to undergo conversion to surgery after failure of non-operative management. CONCLUSION: The criteria for the conservative treatment of blunt liver trauma is presently often based on hemodynamic stability in injured patients, but its successful management should, instead, be based also on early CT recognition of arterial bleeding and prompt use of angiographic embolization to control it.

Complications after surgery for colorectal cancer affect quality of life and surgeon-patient relationship.

AIM: This multicentric prospective study aimed to investigate how postoperative complications after surgery for colorectal cancer affect patients' quality of life and satisfaction with care. METHOD: One hundred and sixteen patients operated on for colorectal cancer were enrolled in this study. Patients answered three questionnaires about generic (EORTC QLQ-C30) and disease-specific (EORTC QLQ-CR29) quality of life and treatment satisfaction (EORTC IN-PATSAT32) at the time of admission and at 1 and 6 months after surgery. Non-parametric tests and linear multiple regression models were used for statistical analysis. RESULTS: Twelve patients had complications requiring further surgery (anastomotic leakage, abdominal bleeding, abdominal wall sepsis, wound infection). Patients with complications that required surgery reported a worse score of physical function, emotional function and anxiety than patients without such complications 1 month after surgery. These patients judged their general satisfaction with the quality of care and doctors' interpersonal skills, technical skills, information provision and availability to be worse than in patients without such complications. The presence of postoperative psychiatric complications and anastomotic leakage were independent predictors of quality of life (ß = -0.30, P = 0.004, and ß = -0.42, P < 0.001). CONCLUSION: In patients undergoing surgery for colorectal cancer, complications requiring any kind of surgical management significantly affected patients' perception of all doctor-related items suggesting an impairment of the entire surgeon-patient relationship. Convincing patients that 'zero risk' cannot be achieved in surgical practice is therefore a priority.

Induction of the 'ASIA' syndrome in NZB/NZWF1 mice after injection of complete Freund's adjuvant (CFA).

Adjuvants, commonly used in vaccines, may be responsible for inducing autoimmunity and autoimmune diseases, both in humans and mice. The so-called 'ASIA' (Autoimmune/inflammatory Syndrome Induced by Adjuvants) syndrome has been recently described, which is caused by the exposure to a component reproducing the effect of adjuvants. The aim of our study was to evaluate the effect of injection of complete Freund's adjuvant (CFA) in NZB/NZWF1 mice, a lupus-prone murine model. We injected 10 NZB/NZWF1 mice with CFA/PBS and 10 with PBS, three times, 3 weeks apart, and followed-up until natural death. CFA-injected mice developed both anti-double-stranded DNA and proteinuria earlier and at higher levels than the control group. Proteinuria-free survival rate and survival rate were significantly lower in CFA-treated mice than in the control mice (p = 0.002 and p = 0.001, respectively). Histological analyses showed a more severe glomerulonephritis in CFA-injected mice compared with the control mice. In addition, lymphoid hyperplasia in spleen and lungs, myocarditis, and vasculitis were observed in the former, but not in the latter group. In conclusion, the injection of CFA in NZB/NZWF1 mice accelerated autoimmune manifestations resembling 'ASIA' syndrome in humans.

Vaccination of mice for research purpose: alum is as effective as and safer than complete Freund adjuvant.

Systemic lupus erythematosus (SLE) is an autoimmune disease involving many organ systems. Glomerulonephritis (GLN) is one of the major causes of morbidity and mortality in SLE. It has recently been demonstrated that adjuvants of vaccines could cause the so called ASIA syndrome. The study aimed to assess the effects of Complete Freund's Adjuvant (CFA) vs alum injections in NZB/NZWF1 mice. Mice (n=10 each group) were injected with a total volume of 200 µL of: CFA in PBS (group 1), alum in PBS (group 2), PBS (group 3) as controls, PTX3/CFA (group 4), PTX3/alum (group 5), 3 times, 3 weeks apart /given in each injection, three weeks apart from ten weeks of age. Urine samples were collected weekly to evaluate proteinuria. Blood samples were collected before every injection, at 21 weeks of age, and at death to evaluate levels of anti-PTX3 and anti-dsDNA. Proteinuria free survival and survival rates were analyzed by the Kaplan-Meier method using Mantel-Cox's test for comparisons. CFA-treated mice developed both anti-dsDNA antibodies and proteinuria earlier and at higher levels than alumtreated and PBS-injected mice, starting from 13 weeks of age. Proteinuria free survival rates (proteinuria ≥ 300 mg/dL) and survival rates were lower in CFA-treated mice than those treated with alum or injected with PBS (P<0.001 for all). No difference was observed between the alum-treated group and PBS-injected mice. Notably, groups 4 and 5, immunized with PTX3, developed anti-PTX3 antibodies and no significant difference was observed. Alum seems to be as effective as and safer than CFA as adjuvant, since it did not affect disease progression in immunized NZB/NZWF1 mice.

Bleeding control by radiofrequency in penetrating trauma of the liver.

Termocoagulation by radiofrequency (RF) is widely used for ablation of liver neoplasms. Recently, innovative uses of RF were proposed, as to assist liver resection, to help partial splenectomy, or to treat ruptured hepatocellular carcinoma. A 21 years old man was admitted for massive haemorrhage from a right thoraco-abdominal knife wound. Massive haemothorax was drained but arterial bleeding was caused by a deep penetrating wound on liver segment VIII. During operation, considering the difficult exposure of the source of bleeding, it was taught to stop haemorrhage using RF termocoagulation, under ultrasonographic guidance. Termocoagulation of the pedicle of the liver segment VIII was performed. In this patient with haemorrhagic shock the RF method for bleeding control was very easy and effective, and avoided risks of morbidity due to a major procedure.

IgG anti-pentraxin 3 antibodies in systemic lupus erythematosus.

OBJECTIVE: To evaluate the prevalence and correlates of anti-pentraxin 3 (PTX3) antibodies in systemic lupus erythematosus (SLE). METHODS: Serum samples from 130 patients with SLE, 130 age- and sex-matched healthy subjects and 130 patients with other autoimmune rheumatic diseases (oARD) were analysed by home-made ELISAs using as substrate human recombinant PTX3 and two peptides, PTX3_1 and PTX3_2, obtained from the complete protein, identified as potential antigenic sites using the Lasergene DNA program (DNA Star). Inhibition tests were performed to evaluate potential interferences between bovine serum albumin or C-reactive protein and anti-PTX3 or anti-PTX3 peptides, and between antigens and antibodies. Statistical analysis was performed using receiving operating characteristics curves, the Fisher exact test, two-tailed t test and Pearson correlations. RESULTS: Patients with SLE had higher levels and prevalence of anti-PTX3, anti-PTX3_1 and anti-PTX3_2 antibodies than patients with oARD or healthy controls (p<0.001 for all). No differences were observed between patients with oARD and healthy controls. A correlation was found between anti-PTX3 and anti-PTX3_2 antibodies (r=0.615, p<0.001). No association was observed between these antibodies and disease activity. Univariate and multivariate analyses showed that anti-PTX3 and anti-PTX3_2 antibody levels and prevalence were higher in patients without glomerulonephritis and in patients positive for antiphospholipid antibody. All inhibition tests were negative apart from PTX3 against anti-PTX3 antibody or, to a lesser extent, against anti-PTX3_2 antibody, and PTX3_2 against anti-PTX3_2 antibody, all in a dose-dependent manner. CONCLUSIONS: Anti-PTX3 antibodies are significantly prevalent in patients with SLE where they might provide protection from renal involvement. The antigenic properties of PTX3_2 peptide are similar to those of PTX3, suggesting its potential use in further analyses.

A systematic review on advancement flaps for rectovaginal fistula in Crohn's disease: transrectal vs transvaginal approach.

AIM: Despite advances in the treatment of Crohn's disease (CD), the treatment of rectovaginal (RV) fistula remains challenging. Transrectal (RAF) and transvaginal advancement flaps (VAF) represent two possible alternative surgical approaches to this problem. The study aims to review and compare the results of these approaches for RV fistula in CD. METHOD: Medical databases from January 1983 to August 2008 were consulted for potentially relevant publications. All studies dealing with the RV fistula repair in CD with RAF or VAF were included. Two researchers worked independently on the study selection, quality assessment, data extraction and analysis phases of the study. Analyses were performed with Review Manager 2.0 software. RESULTS: Eleven observational studies were included with a total of 219 flap procedures for RV fistula. The primary fistula closure pooled rate was 54.2% (range 33.3-100%) after RAF and 69.4% (range 0-92.9%) after VAF (P = 0.13). Four studies were eligible for direct comparison between the two procedures. No clearly significant difference between RAF compared with VAF in terms of primary fistula closure rate, nor in terms of overall fistula closure rate, was apparent. The risk of recurrence after RAF compared with VAF seemed similar; in this case, only two studies were taken into consideration. CONCLUSIONS: Although limited by a small number of studies of low clinical evidence level, this systematic review suggests that there is no significant difference in terms of outcome between RAF and VAF for RV fistula in CD.

Hepatic cystic lesion in adult: a challenging diagnosis of undifferentiated primary embryonal sarcoma.

Cystic lesions of the liver are common. Most of these represent benign simple cysts that generally require no intervention. The diagnosis of simple hepatic cysts is straightforward in the face of typical radiographic findings; however, diagnostic uncertainty, based solely on radiographic criteria alone, is not an uncommon clinical dilemma. In this report, we present a case of a 47 old woman with a cystic liver lesion and acute epigastric pain. The patient had no previous history of oral contraceptive assumption or liver disease. A tender mass was palpable on the upper right quadrant of the abdomen. The abdominal ultrasound (US) showed a cystic lesion with a possible hemorrhagic component on right liver lobe. Abdominal computed tomography (CT) and magnetic resonance (MR) revealed a complex cystic lesion with possible intracystic hemorrhage. The patient was submitted to operation and resection; the final histologic diagnosis revealed a primary undifferentiated embryonal sarcoma of the liver. She relapsed 24 months after a new hepatic resection and chemo-embolization, she is alive at 29 months after first surgery.

Neurolupus is associated with anti-ribosomal P protein antibodies: an inception cohort study.

OBJECTIVE: Serum IgG antibodies (Abs) to phosphorylated ribosomal (P ribosomal) proteins have been inconsistently associated with neuropsychiatric manifestations in systemic lupus erythematosus (SLE). Our aim was to assess whether serum IgG Abs to ribosomal P proteins are associated with neuropsychiatric SLE. PATIENTS AND METHODS: We examined an inception cohort of 219 SLE patients. Neuropsychiatric SLE manifestations were characterized using the American College of Rheumatology (ACR) definition. Serum Abs to P ribosomal proteins were searched for by immunoblotting. In a subgroup of patients, Abs were investigated also in cerebrospinal fluid (CSF). RESULTS: Abs to P ribosomal proteins were detected in 45 (21%) patients, 23 of whom (51%) with neuropsychiatric involvement. Abs to P ribosomal protein were present both in serum and CSF. Abs to P ribosomal proteins significantly correlated with psychosis (p=0.017), mononeuropathy multiplex (p=0.040), malar rash (p=0.004), serum anti-Sm Abs (p=0.042), and lupus anticoagulant (p=0.036). SLE onset age was significantly younger in patients with Abs to P ribosomal proteins. Logistic regression analysis confirmed the relationship between Abs to P ribosomal proteins and psychosis, malar rash, SLE onset age and lupus anticoagulant. CONCLUSIONS: Abs to ribosomal P proteins are associated with psychosis and might be associated with peripheral nervous system complications.

Effects of glucocorticoids in ventilated piglets with severe pneumonia.

There is clinical evidence suggesting that glucocorticoids may be useful in severe pneumonia, but the pathogenic mechanisms explaining these beneficial effects are unknown. The aim of the present study was to determine the effects of adding glucocorticoids to antibiotic treatment in an experimental model of severe pneumonia. In total, 15 Lagerwhite-Landrace piglets were ventilated for 96 h. After intubation, a 75 mL solution containing Pseudomonas aeruginosa (10(6) cfu x mL(-1)) was bronchoscopically inoculated. The animals were randomised into three groups 12 h after inoculation: 1) untreated; 2) treated with ciprofloxacin; and 3) treated with ciprofloxacin plus methylprednisolone. Physiological and laboratory parameters were monitored throughout the study. Pro-inflammatory cytokines were measured in serum and bronchoalveolar lavage (BAL). Histopathology of the lungs and cultures from blood, BAL and lungs were performed. At the end of the study, piglets receiving the antibiotic plus glucocorticoids showed: 1) a decrease in the concentration of interleukin-6 in BAL; and 2) a decrease in the global bacterial burden both in BAL and lung tissue. In conclusion, in this experimental model of pneumonia, the association of glucocorticoids with antibiotics attenuates local inflammatory response and decreases bacterial burden in the lung.

Allergic contact dermatitis from 4-chloro-2-[methylthio]pyrimidine-5-carboxylic acid ethyl ester and methyl 4-hydroxy-2-hexynoate in a laboratory chemist.

We report a case of allergic contact dermatitis to 4-chloro-2-[methylthio]pyrimidine-5-carboxylic acid ethyl ester and methyl 4-hydroxy-2-hexynoate in a laboratory chemist.

Tricofoliculomas múltiples: reporte de un caso / Multiple trichofolliculomas: a case report

Resumen El tricofoliculomaes un tumor benigno infrecuente del folículo piloso, de mayor prevalencia entre la segunda y la sexta década de vida. Suele presentarse como una lesión solitaria en forma de nódulo,pápulas o placas del color de la piel,asintomático, con un poro o cavidad central obstruido con queratina de la que emerge un "penacho de pelos".La localización más frecuente suele ser el rostro, seguido del cuero cabelludo y el cuello.1Las características histopatológicas son diagnósticas. Se reporta el caso clínico de un paciente de 44 años de edad con tricofoliculomas múltiples en rostro.

Abstract Trichofolliculoma is an infrequent benign tumor of the hair follicle, with a higher prevalence between the second and sixth decade of life. It usually presents as a solitary lesion in the form of a nodule, papules or asymptomatic skin-colored plaques with a pore or central cavity obstructed with keratin from which a "tuft of hairs" emerges.The most frequent location is usually the face, followed by the scalp and neck.1 Histopathological characteristics are diagnostic. We report a case of a 44-year-old man with multiple trichofolliculomas on his face.

OxLDL/beta2GPI-anti-oxLDL/beta2GPI complex and atherosclerosis in SLE patients.

It has been demonstrated that atherosclerosis (ATS) is enhanced in autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE). The reason for this accelerated process is still debatable and, although traditional risk factors are more prevalent in SLE patients than in general population, they do not seem to fully explain the enhanced risk. ATS has the characteristics of an autoimmune chronic disease, involving both the innate and the adaptive immunity. Moreover, it satisfies the four criteria defining an autoimmune disease, proposed by Witebsky and Rose. It has been shown that some autoantibodies, including anti-oxLDL, anti-beta(2)GPI, anti-HSP60/65, and more recently anti-oxLDL/beta(2)GPI, play a key role in the pathogenesis of ATS. However the role of these autoantibodies in accelerated ATS in SLE patients is still controversial. In fact, some of them seem to be proatherogenic and other protective; moreover, it has been demonstrated that induced oral tolerance has a protective role against ATS. We have recently observed that the levels of oxLDL/beta(2)GPI antigenic complexes and their antibodies were higher in patients with SLE than in healthy subjects, but we did not find a clear association between oxLDL/beta(2)GPI complexes and IgG or IgM anti-oxLDL/beta(2)GPI autoantibodies and subclinical ATS in SLE patients. Many other studies are required to explain the role of autoantibodies in the pathogenesis of ATS in SLE patients, because the characteristics of SLE seem to mask their effects for atherogenesis.

Liver resection in elderly: comparative study between younger and older than 70 years patients. Outcomes and implications for therapy.

BACKGROUND AND AIM: to identify the factors that could influence the outcome of the old aged patients underwent liver resection for hepatocellular carcinoma (HCC) or colorectal liver metastases (LMCRC). PATIENT AND METHODS: the Authors identified 51 patients older 70 years-old over 12-years period underwent resection for HCC (n 26) or for LMCRC (n 25). This group was compared with a cohort of 93 patients younger than 70 years who underwent resections in the same period. We have evaluated the results in terms of peroperative morbidity and mortality. RESULTS: the mean age of 51 elderly patients was 74 years-old. Thirty-five were treated with anatomical resection. Cirrhosis was present in 26 patients while 27 had co-morbidities. Thirteen patients developed complications and the mean age of these were 76 years compared with 73 of the patients who have not (p= .01). No mortality was registered. The cirrhosis, blood transfusions, anatomical resection and diameter of the lesion did not influence the outcome. CONCLUSIONS: our results indicate the age per se should not be considered a contraindication for surgery, that proved to be safe and curative therapy, but showed that old age, using 75 years as a cut-off, in association with at least one comorbid medical condition could be considered as relevant factor of morbidity.

Should we routinely use DEBTACE for unresectable HCC? cTACE versus DEBTACE: a single-center survival analysis.

Conventional trans-arterial chemoembolization (cTACE) for intermediate stage hepatocellular carcinoma (HCC) achieves a partial response in up to 72% of patients and improves median survival. Drug-eluting-beads-TACE (DEBTACE) improves treatment efficacy and tolerance as compared to cTACE. Our aim was to retrospectively evaluate our experience in the treatment of intermediate/advanced HCC with cTACE versus DEBTACE. Overall survival (OS) was the first endpoint. We retrospectively considered our department register data between 2006 and 2012. A total of 82 non-surgical patients, who underwent cTACE or DEBTACE, with a minimum of 12 months follow-up, met the inclusion criteria. Patients received a standard chemotherapy dose (50 mg). Radiological response was evaluated by CT after 30 days and re-treatment was considered. Statistical analysis was performed with SPSS software. 54 patients received cTACE and 28 DEBTACE. In the DEBTACE group the median survival times was 22.7 months (CI 11.6-33.8), while in the cTACE group it was 21.8 months (CI 15.7-27.9). The survival analysis at log-rank (p = 0.708) and Wilcoxon (p = 0.661) tests demonstrated no differences between DEBTACE and cTACE. The probability of death in function of time was significantly associated only to the Child-Pugh score. A Child A score was shown to be protective instead of Child B (OR 0.583; IC 95% = 0.344-0.987). DEBTACE for treating HCC is comparable to cTACE in terms of effectiveness, but seems to be better tolerated. Both treatments can be performed in case of tumor recurrence without substantial increase in procedural complications and risk of liver failure. We do confirm that there are no differences between the two techniques in terms of survival and that it is mainly affected by the reserved liver function proper of each patient.

A simple solution to a technical complication in "piggyback" liver transplantation.

"Piggyback" orthotopic liver transplantation is a technical modification of the standard technique that has found favor with a number of surgeons. One possible complication is that of venous outflow obstruction, which presents as an acute Budd-Chiari syndrome. If not rapidly corrected, it is almost inevitable that the newly implanted graft will fail. Additionally, severe portal hypertension and general infradiaphragmatic venous stasis may compound the damage. We find that anastomosing the donor infrahepatic vena cava to the recipient suprarenal vena cava in an end-to-side fashion is an excellent way to correct the problem.

Protein C, factor VII and prothrombin time as early markers of liver function recovery or failure after liver transplantation.

Irreversible initial non-function of the graft liver is a life-threatening early complication of orthotopic liver transplantation (OLT), which needs immediate retransplantation if the patient is to survive. Since protein C (PC) is a vitamin K dependent protein synthesized in the liver and with the same half-life as factor VII (FVII), the behaviour of PC in patients undergoing OLT was studied in comparison with prothrombin time (PT) and FVII. Twelve OLT patients were divided into two groups on the basis of clinical outcome: group A (six cases) in which OLT was successful, and group B (six cases) who developed initial non-function of the graft liver. PT, FVII activity (FVII:act) and antigen (FVII:Ag) and PC activity (PC:act) and antigen (PC:Ag) were carried out on six blood samples collected during the operation. At baseline, coagulation disorders were in agreement with the underlying liver disease, but no differences were seen between the two groups when all tests were considered. Ten minutes, 1, 2 and 3 h after liver reperfusion, mean PT and FVII:act were always significantly increased in good responder patients compared to non-responders. FVII:Ag and PC:Ag were significantly higher in group A than in group B starting 2 h after the liver graft reperfusion; no difference was seen in PC:act levels between the two groups. In addition, PC:Ag mean levels were increased with respect to corresponding PC:act values in non-responder patients, suggesting a qualitative rather than quantitative defect of protein synthesis due to liver damage. In conclusion, PT and FVII:act were more sensitive than PC activity as early prognostic indices of clinical outcome in OLT.

Combined endoscopic and laparoscopic removal of ingested large foreign bodies. Case report and decisional algorithm.

Foreign body ingestion is a rare occurrence, but quite more frequent in children; adults with mental disorders, bulimia, and dentition alterations; and prison inmates. Most foreign bodies pass spontaneously through the first digestive tract and can move along the entire alimentary canal without giving rise to any major damage. On the contrary, when foreign bodies, because of their shape, size or potential for danger, must be removed, endoscopy is the method of choice. In a small percentage of cases, however, it may be necessary to remove the foreign body surgically. In such cases, the laparoscopic technique certainly can prove to be a most valuable tool, and can be recommended as a first approach. We describe a case in which a large foreign body was accidentally ingested. After a brief analysis of the data in the literature, we propose the decision-making algorithm that we follow.