Curcumin induced oxidative stress attenuation by N-acetylcysteine co-treatment: a fibroblast and epithelial cell in-vitro study in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a fatal lung disease of unknown etiology with only two federally approved drug options. Given the complex molecular pathogenesis of IPF involving multiple cell types and multiple pathways, we explore the effects of a potential antifibrotic and antioxidant drug combination. Curcumin is a polyphenolic compound derived from turmeric with significant biological activity including a potential antifibrotic capacity. N-acetylcysteine (NAC) is a precursor to the antioxidant glutathione. To advance our understanding of these molecules, and to identify a clinical application, we present a small number of focused experiments that interrogates the effect of curcumin and NAC on pathways relevant to IPF in both fibroblasts and epithelial cells. METHODS: Primary epithelial cell and fibroblasts isolated from patients with IPF were challenged with a combination treatment of NAC and curcumin. Evaluation of the antifibrotic potential and effect on oxidative stress was performed through QPCR gene expression analysis and functional assays including scratch tests, viability assays, and measurement of induced reactive oxygen species. RESULTS: We demonstrate that curcumin alone does have antifibrotic potential, but that effect is accompanied by proapoptotic increases in oxidative stress. Coupled with this, we find that NAC alone can reduce oxidative stress, but that epithelial cell viability is decreased through this treatment. However, co-administration of these two molecules decreases oxidative stress and maintains high cell viability in both cell types. In addition, this co-treatment maintains an antifibrotic potential. CONCLUSIONS: These findings suggest a novel application for these molecules in IPF and encourage further exploration of this potential therapeutic approach.

T1 colon cancer in the era of screening: risk factors and treatment.

BACKGROUND: The aim of this study was to identify risk factors for lymph node positivity in T1 colon cancer and to carry out a surgical quality assurance audit. METHODS: The sample consisted of consecutive patients treated for early-stage colon lesions in 15 colorectal referral centres between 2011 and 2014. The study investigated 38 factors grouped into four categories: demographic information, preoperative data, indications for surgery and post-operative data. A univariate and multivariate logistic regression analysis was performed to analyze the significance of each factor both in terms of lymph node (LN) harvesting and LN metastases. RESULTS: Out of 507 patients enrolled, 394 patients were considered for analysis. Thirty-five (8.91%) patients had positive LN. Statistically significant differences related to total LN harvesting were found in relation to central vessel ligation and segmental resections. Cumulative distribution demonstrated that the rate of positive LN increased starting at 12 LN harvested and reached a plateau at 25 LN. CONCLUSIONS: Some factors associated with an increase in detection of positive LN were identified. However, further studies are needed to identify more sensitive markers and avoid surgical overtreatment. There is a need to raise the minimum LN count and to use the LN count as an indicator of surgical quality.

Hemorrhoid laser procedure for second- and third-degree hemorrhoids: results from a multicenter prospective study.

BACKGROUND: The aim of our study was to assess the outcome of hemorrhoidal dearterialization, achieved by a dedicated laser energy device. METHODS: From November 2012 to December 2014, 51 patients with second- or third-degree hemorrhoids were studied. The primary end point was a reduction in the bleeding rate; secondary end points were: postoperative complications, reduction in pain and prolapse, resolution of symptoms, and degree of patient's perception of improvement. The procedure was carried out as 1-day surgery. A diode laser device was employed to seal the terminal branches of the hemorrhoidal arteries, detected by a Doppler-equipped proctoscope. Follow-up was scheduled at 1 and 4 weeks, 3, 12, and 24 months. The rate and degree of symptoms was assessed with a four-point verbal rating scale. The rate of subjective symptomatic improvement was also evaluated with the Patient Global Improvement (PGI) Scale. RESULTS: Mean bleeding and pain scores at baseline were 2 and 0.57. All the patients were discharged on the day of surgery. Postoperative complications were bleeding (n = 4) and external hemorrhoidal thrombosis (n = 4). Mean bleeding and pain scores at 3, 12, and 24 months were significatively reduced. After 24 months, complete resolution of bleeding was observed in 28/29 patients (96.7 %), resolution of pain in all patients, and resolution of the mucosal prolapse in 15/18 patients (76.9 %). At 12-month follow-up, 86.3 % of patients reported improvement with the PGI Scale. CONCLUSIONS: The hemorrhoid laser procedure was effective in improving bleeding and pain symptoms in patients with grade II and III hemorrhoids.

Enhanced recovery after surgery (ERAS) pathway vs traditional care in laparoscopic rectal resection: a single-center experience.

BACKGROUND: The aim of this study was to compare the outcome of an enhanced recovery after surgery (ERAS) pathway with traditional perioperative care in laparoscopic rectal resection. METHODS: A retrospective analysis of prospectively collected data was conducted. Single-center consecutive patients who underwent laparoscopic rectal surgery after an ERAS program were compared with patients who received traditional care over an 8-year period. Primary and total length of stay, and readmission, morbidity and mortality rates were analyzed. For ERAS group, the actual adherence to protocol was also evaluated. RESULTS: Two hundred and ninety-seven patients, 162 in the ERAS group and 135 in conventional care, were studied. Median primary and total length of stay were significantly shorter in the ERAS group (9 vs 12 days; p = 0.0001; 10 vs 12 days; p = 0.01; respectively). The ERAS group experienced a faster recovery of bowel function than the traditional care group (p = 0.0001). A similar morbidity rate was observed in the two groups (32.3 % in ERAS vs 36.1 % in traditional care p = 0.41). Readmission rates were 4.9 % in the ERAS versus 1.5 % in the traditional care group (p = 0.19). There was no mortality in either group. Overall mean compliance with the ERAS protocol was 85.7 % (range 54.4-100 %). CONCLUSIONS: The introduction of the ERAS protocol in laparoscopic rectal resection led to a reduction in primary and total length of hospital stay without an increase in morbidity or readmission rates when compared to traditional care.

Eco-friendly synthesis of CuO/Bi2O3 nanocomposite for efficient photocatalytic degradation of rhodamine B dye.

Plant-mediated synthesized materials are receiving more attention than conventional ones due to their wide availability, ease of access, simple preparation methods, environmental benign, and possess superior physicochemical properties. In this work, plant extract-mediated CuO, Bi2O3, and CuO/Bi2O3 nanocomposite samples were successfully synthesized using bamboo leaves extract as a capping agent. These materials were utilized for the photodegradation of Rhodamine B (RhB) dye, which served as a model organic dye pollutant. The physicochemical characterization techniques such as XRD, SEM-EDS, FTIR, and DRS-UV-vis spectrophotometry provide insight into the crystal structure, morphology, surface functional groups, and optical properties. These analyses confirm the effective formation of CuO, Bi2O3, and CuO/Bi2O3 materials. Surprisingly, upon calcination at 450 °C for 4 h, the color of the nanocomposite changed from pale green to gray greenish, providing evidence for the formation of the CuO in CuO/Bi2O3 nanocomposite. The photocatalytic optimization parameters such as pH (4), catalyst load (35 mg), irradiation time (180 min) and concentration of RhB (10 mg L-1) dye were investigated. By coupling CuO with Bi2O3 nanoparticles resulted in an improved photocatalytic property for the degradation of RhB dye under optimal conditions. As a result, CuO/Bi2O3 nanocomposite exhibited a significantly boosted photocatalytic degradation efficiency (95.6%) compared to pure CuO (40.2%) and Bi2O3 (80.5%) photocatalysts, with good reusability. For comparison purpose, the photocatalytic degradation of RhB dye using selected photocatalyst was evaluated under dark and sunlight systems. This eco-friendly approach holds great potential for synthesis new nanocomposite with modified properties, thereby enabling the practical application of high-efficiency photocatalysts. The plausible mechanism of the electrons and holes transfer was proposed.

Protection of intestinal anastomosis with biological glues: an experimental randomized controlled trial.

BACKGROUND: The aim of the study was to compare the degree of healing and air tightness of hand-sewn colonic anastomoses provided by different biological glues. METHODS: Thirty colonic anastomoses were fashioned in ten rabbits, at 5, 10, 15 cm from the ileocecal valve, with 4/0 PDS running sutures. Each suture was randomized to treatment with fibrin sealant (Tissucol®), a synthetic glue (Coseal®), or nothing (control). After 15 days, the rabbits were killed and the anastomoses examined for their integrity and resistance to bursting. The van der Hamm scale was used to evaluate postoperative adhesions. A blind histological evaluation of the newly formed tissue was made (Ehrlich-Hunt scale). RESULTS: Two rabbits developed an intraabdominal abscess, one in the control anastomosis group without glue. Postoperative adhesions were present in all animals. Median anastomosis bursting pressures were 0.9 atm in all three groups: Tissucol, Coseal, and control. Pressure values were 0.9, 1.0, and 0.9 atm in the three different proximodistal sites, respectively. A trend toward an increased resistance was observed in the glued anastomosis, although this was not significant. Lymphocyte infiltration, fibroblast activity, blood vessel density, and collagen deposition were lower in controls. Anastomoses treated with Tissucol had the highest lymphocyte infiltration level. The Coseal group developed the highest rates of fibroblast activity, collagen deposition, and blood vessel neogenesis. CONCLUSION: The use of biological glues did not result in a statistically significantly increased bursting resistance. Histological evaluation demonstrated more intense tissue neoformation in the glue groups, particularly in the Coseal group. The role of biological glues in decreasing the leakage rate of intestinal anastomoses is uncertain, and larger trials using different protective agents are warranted.

Fecal incontinence: up to date on pathophysiology and treatment.

This study analyzes the most recent insight into the pathophysiology of fecal incontinence considering each of the factors contributing to the mechanism of fecal continence both during urgency to defecate and in resting state. In fact different types of incontinence are caused by different damage to one or more of these physiologic factors. The second part of the study focuses on the therapeutic choices of fecal incontinence. The recent introduction of sacral nerve electrostimulation and the progressive broadening of its clinical indications is progressively replacing and challenging other traditional surgical techniques because of their disappointing long-term results and because they are much more invasive. An emerging new treatment based on the injection of anal bulking agents is nowadays even more preferred for the less severe cases of fecal incontinence. An increasing number of materials is now proposed by the industry in order to identify the best biocompatible material to be injected trans-anally. Traditional surgery could be reserved for patients non-responding to these new treatments.

Should pregnancy be considered a risk factor for aortic dissection? Two cases of acute aortic dissection following cesarean section in non-Marfan nor bicuspid aortic valve patients.

Acute aortic dissection in pregnancy is a rare event and rarer still in healthy young women; however, women with a bicuspid aortic valve or the Marfan syndrome are at a higher risk of dissection. The relationship between pregnancy and aortic dissection is still unclear. We describe the cases of two women with no history of cardiovascular disease who developed an acute aortic type A dissection within a few days after term delivery. Surgical repair was performed with ascending aorta replacement and aortic valve sparing. In both cases, the dissection was diagnosed within a few days following cesarean section done neither because of fetal or maternal distress. To date, only one case of type A and two cases of type B aortic dissection following cesarean section have been reported. Compared with spontaneous delivery, scheduled cesarean section, as in our cases, allows for better control of hemodynamic parameters and should protect against aortic dissection. Postoperative screening for inherent connective tissue disorders detected no mutations within the fibrillin and collagen gene chromosome in either patient. Postoperative recovery was uneventful, and the patients were discharged on postoperative days 7 and 8, respectively.

Does the Ventrica magnetic vascular positioner (MVP) for coronary artery bypass grafting significantly alter local fluid dynamics? A numeric study.

OBJECTIVE: Automatic devices have been recently introduced to make the anastomosis procedure quick and efficient when creating a coronary bypass on the beating heart. However, the implantation of these devices could modify the graft configuration, consistently affecting the hemodynamics usually found in the traditional anastomosis. As local fluid dynamics could play a significant role in the onset of vessel wall pathologies, in this article a computational approach was designed to investigate flow patterns in the presence of the Ventrica magnetic vascular positioner (Ventrica MVP) device. METHODS: A model of standard hand-sewn anastomosis and of automated magnetic anastomosis were constructed, and the finite volume method was used to simulate in silico realistic graft hemodynamics. Synthetic analytical descriptors -- i.e., time-averaged wall shear stress (TAWSS), oscillating shear index (OSI) and helical flow index (HFI) -- were calculated and compared for quantitative assessment of the anastomosis geometry hemodynamic performance. RESULTS: In this case study, the same most critical region was identified for the 2 models as the one with the lowest TAWSS and the highest OSI (TAWSS=0.229, OSI=0.255 for the hand-sewn anastomosis; TAWSS=0.297, OSI=0.171 for the Ventrica MVP(R)). However, the shape of the Ventrica MVP does not induce more critical wall shear stresses, oscillating flow and damped helicity in the graft fluid dynamics, as compared with conventional anastomosis. CONCLUSIONS: We found that the use of the Ventrica MVP for the case study under investigation was not associated with more critical fluid dynamics than with conventional hand-sewn anastomosis. Thereby, the device could facilitate beating heart and minimally invasive coronary artery bypass grafting without increasing local hemodynamic-related risks of failure.

Malnutrition in Healthy Individuals Results in Increased Mixed Cytokine Profiles, Altered Neutrophil Subsets and Function.

Malnutrition is commonly associated with increased infectious disease susceptibility and severity. Whereas malnutrition might enhance the incidence of disease as well as its severity, active infection can in turn exacerbate malnutrition. Therefore, in a malnourished individual suffering from a severe infection, it is not possible to determine the contribution of the pre-existing malnutrition and/or the infection itself to increased disease severity. In the current study we focussed on two groups of malnourished, but otherwise healthy individuals: moderately malnourished (BMI: 18.4-16.5) and severely malnourished (BMI <16.5) and compared several immune parameters with those of individuals with a normal BMI (≥18.5). Our results show a similar haematological profile in all three groups, as well as a similar ratio of CD4+ and CD8+ T cells. We found significant correlations between low BMI and increased levels of T helper (Th) 1 (Interferon (IFN)-γ, (interleukin (IL)-2, IL-12), Th2 (IL-4, IL-5, IL-13), as well as IL-10, IL-33 and tumor necrosis factor-α, but not IL-8 or C reactive protein. The activities of arginase, an enzyme associated with immunosuppression, were similar in plasma, peripheral blood mononuclear cells (PBMC) and neutrophils from all groups and no differences in the expression levels of CD3ζ, a marker of T cell activation, were observed in CD4+ and CD8+T cells. Furthermore, whereas the capacity of neutrophils from the malnourished groups to phagocytose particles was not impaired, their capacity to produce reactive oxygen species was impaired. Finally we evaluated the frequency of a subpopulation of low-density neutrophils and show that they are significantly increased in the malnourished individuals. These differences were more pronounced in the severely malnourished group. In summary, our results show that even in the absence of apparent infections, healthy malnourished individuals display dysfunctional immune responses that might contribute to increased susceptibility and severity to infectious diseases.

Myocardial revascularization in patients with ischemic cardiomyopathy: functional observations.

OBJECTIVE: A prospective angiographic study was undertaken to investigate, with an objective analysis, the global and regional wall response to myocardial revascularization. METHODS: Thirty-one patients (30 men and 1 woman, mean age, 61 years) with a left ventricular ejection fraction of less than 0.30 were admitted to our institution between 1992 and 1995 for two- or three-vessel coronary artery disease requiring myocardial revascularization. All patients underwent isolated coronary artery bypass grafting and were studied 3 months later with angiography. Preoperative and postoperative wall motion were analyzed using special software that computed a segmental left ventricular ejection fraction, generating a segmental score. Computerized analysis allowed us to distinguish patients with diffuse hypokinesis and a symmetric contraction pattern from patients with akinesis involving at least two segments and an asymmetric contraction pattern. RESULTS: There were no operative deaths and no patient required intraaortic balloon counterpulsation. One patient had postoperative enzymatic evidence of myocardial infarction. Postoperative angiography showed a graft patency rate of 84%. Global analysis showed a small but significant rise in the left ventricular ejection fraction (0.25 +/- 0.51 to 0.31 +/- 0.70, p < 0.001) and a fall in the left ventricular end-diastolic pressure (23.7 +/- 10 to 16.5 +/- 9 mm Hg, p < 0.01). Mean scores always have been lower after the operation than before it, with the best results obtained for the apex and the worst for the anterobasal segment. The group with a symmetric contraction pattern showed a trend toward a better hemodynamic response than the group with an asymmetric contraction pattern. Regression analysis revealed two important predictors of segmental functional improvement: (1) the absence of an echocardiographic scar, and (2) the presence of a collateral circulation. CONCLUSIONS: Coronary artery bypass grafting produced a small but substantial improvement in patients with ischemic cardiomyopathy. The greater benefit occurred in patients with a symmetric contraction pattern. The absence of an echocardiographic scar and the presence of a collateral circulation predicted segmental functional improvement.

Myocardial revascularization with multiple arterial grafts: comparison between the radial artery and the right internal thoracic artery.

BACKGROUND: Bilateral internal thoracic artery (ITA) harvesting is significantly underused, whereas the radial artery is being used with increasing frequency. We have retrospectively analyzed perioperative and short-term outcomes of patients receiving a radial artery versus those receiving a right ITA as a second arterial graft. METHODS: Between February 1999 and May 2000, 250 patients underwent coronary artery bypass grafting using the radial artery (156 patients) or the right ITA (94 patients) in combination with the left ITA and, when required, the saphenous vein. RESULTS: There was a higher prevalence of risk factors in the radial artery group. More coronary artery bypass graftings (p < 0.001) were performed with the radial artery. Operative mortality was not different (p = not significant). In the right ITA group there was more bleeding (p < 0.001) and a longer hospital stay (p < 0.001). Mean follow-up was 8.1 +/- 3.9 months. The probability of survival was similar (p = not significant). CONCLUSIONS: The radial artery can extend the benefits of multiple arterial grafting to those patients who are usually excluded from bilateral ITA harvesting because of multiple risk factors. Perioperative and short-term results are good.

Isolated atresia of the left main coronary artery in an adult.

A 49-year-old woman with isolated atresia of the left main coronary artery is presented. The patient who suffered from angina underwent myocardial revascularization 14 years after the onset of symptoms. A left internal mammary artery to left anterior descending coronary artery bypass was performed. Twenty months after the operation, the patient is free from angina and leads a normal life. The clinical features, diagnosis and management of the left main coronary atresia in adults are discussed.

Gastroepiploic artery free graft for coronary bypass.

The internal mammary artery (IMA) is the graft of choice for CABG but has a limited number and length. For multivessel coronary disease, saphenous vein grafts have to be added but they show poorer long-term patency. Investigation to provide adjunctive reliable grafts has recently focussed on the right gastroepiploic artery (GEA) and encouraging results have been reported employing this vessel as a pedicled graft to bypass distal coronary vessels. From December 1988 to February 1989, to achieve complete myocardial revascularization with only arterial grafts we used a GEA free graft in combination with the two IMAs in 20 consecutive patients under 70 years of age undergoing elective surgery. Before starting, histological studies were carried out and a significant similarity between IMA and GEA was found. In the 20 patients, 76 coronary anastomoses were performed (3.8 bypasses/patient), the GEA graft revascularized the right coronary artery in 9 patients, the circumflex in 8 patients and the anterior descending and/or diagonal in 3 patients; in 7 patients the GEA graft was used for sequential anastomoses. No perioperative deaths, no myocardial infarctions and no gastroenterological complications occurred. Coronary angiographic postoperative control showed 20/20 patent GEA grafts. After follow-up ranging from 7 to 9 months, all patients are free from angina. The GEA free graft is not difficult to harvest, is easier than the pedicled GEA graft to handle in the pericardium and is suitable for sequential anastomoses. The use of GEA graft however increases the complexity of bypass operations.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary "open" endarterectomy and reconstruction: short- and long-term results of the revascularization with saphenous vein versus IMA-graft.

From June 1984 to December 1990, 96 patients underwent "open" coronary endarterectomy and reconstruction. In 50 patients (group 1), a saphenous vein (SV) graft was used to reconstruct and bypass 54 coronary vessels. In 46 patients (group 2), 46 coronary vessels were reconstructed with an SV patch and then bypassed with the internal mammary artery (IMA): Seventy-four LAD coronary arteries (36 in group 1 and 38 in group 2) were treated with these procedures. Operative mortality was 8% in group 1 and 2.1% in group 2. Five patients (10%) in group 1 and 1 patient (2.1%) in group 2 developed perioperative myocardial infarction. The early postoperative patency of the reconstructed vessels was 84.6% in group 1 and 92.5% in group 2. Angiographic controls were performed between 30 and 36 months after operation in 18 patients (72%) of group 1 and in 16 patients (69%) of group 2 with patency rates of 66.7% and 81.5%, respectively. A further angiographic study performed between 54 and 60 months after operation of 9/22 patients of group 1 and 5/9 patients of group 2 did not show any additional closure of the endarterectomized vessels. Three- and 5-year survival analyzed by the Kaplan-Meier method was 79.6% and 69.7%, respectively, in group 1 and 86.8% for both the 3- and 5-year survival in group 2. After a mean follow-up of 51.0 and 35.5 months, 62.8% of the surviving patients of group 1 and 75.6% of group 2 were asymptomatic.(ABSTRACT TRUNCATED AT 250 WORDS)

[Left atrium rupture after non-penetrating injury to the back]. / Rottura di auricola sinistra dopo trauma non penetrante del dorso.

Survival after cardiac rupture associated with blunt thoracic trauma is very uncommon. In these patients successful management demands a high index of suspicion of cardiac injury. A case of a 24-year-old woman who presented unconscious and shocked in the emergency room after motorcycle trauma strictly limited to her back is reported. Rib and sternal fractures were absent; the typical signs of cardiac tamponade were not found. Therefore the suspicion of cardiac chamber rupture was not immediate and the cardiologist was consulted after several diagnostic exams. Transthoracic echocardiography showed a pericardial effusion with clots and initial cardiac tamponade. The patient was transferred to the operating room and a large hemopericardium was disclosed. Two lacerations were noticed: the first pericardial, near the inferior vena cava, and the second one in the posterior wall of the left atrium. It is possible that the associated pericardial tear and pericardial clots could have contributed to survival. After surgical repair, carried out during cardiopulmonary bypass, the recovery was quick and complete. This case report confirms the possibility of heart chamber rupture after blunt chest trauma even in the absence of obvious thoracic lesion and it shows that the presentation could be very insidious without a "classic" clinical picture of cardiac tamponade. In front of an unexplained shock after nonpenetrating thoracic trauma, a rupture of the heart chambers should be suspected and echocardiography is mandatory. In the emergency room environment pericardiocentesis should be performed only with a quickly available cardiac surgery or in the presence of overwhelming hemodynamic failure.

In vitro hemodynamics and valve imaging in passive beating hearts.

Due to their high complexity, surgical approaches to valve repair may benefit from the use of in vitro simulators both for training and for the investigation of those measures which can lead to better clinical results. In vitro tests are intrinsically more effective when all the anatomical substructures of the valvular complexes are preserved. In this work, a mock apparatus able to house an entire explanted porcine heart and subject it to pulsatile fluid-dynamic conditions was developed, in order to enable the hemodynamic analysis of simulated surgical procedures and the imaging of the valvular structures. The mock loop's hydrodynamic design was based on an ad-hoc defined lumped-parameter model. The left ventricle of an entire swine heart was dynamically pressurized by an external computer-controlled pulse duplicator. The ascending aorta was connected to a hydraulic circuit which simulated the input impedance of the systemic circulation; a reservoir passively filled the left atrium. Accesses for endoscopic imaging were located in the apex of the left ventricle and in the aortic root. The experimental pressure and flow tracings were comparable with the typical in vivo curves; a mean flow of 3.5±0.1l pm and a mean arterial pressure of 101±2 mmHg was obtained. High-quality echographic and endoscopic video recordings demonstrated the system's excellent potential in the observation of the cardiac structures dynamics. The proposed mock loop represents a suitable in vitro system for the testing of minimally-invasive cardiovascular devices and surgical procedures for heart valve repair.