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Resumen: Introducción: Las metástasis vertebrales son un problema muy frecuente y asocian un deterioro importante de la calidad de vida en los pacientes oncológicos. El objetivo de esta revisión es determinar el encaje de las técnicas quirúrgicas mínimamente invasivas dentro del manejo de esta entidad. Métodos: Se realizó una revisión bibliográfica en las bases de datos Google Scholar, PubMed, Scopus y Cochrane. Se revisaron los artículos publicados en los últimos 10 años que fueran de una relevancia y calidad adecuadas. Resultados: Tras el cribado de los 2.184 trabajos identificados inicialmente en las distintas bases de datos, se incluyeron un total de 24 artículos en esta revisión. Conclusión: La cirugía mínimamente invasiva de columna es especialmente útil en pacientes oncológicos frágiles con metástasis vertebrales por la reducida comorbilidad que presentan las técnicas que se engloban en ella en comparación con la de la cirugía abierta convencional. Los avances en tecnología aplicada a la cirugía, como la navegación y la robótica, mejoran la precisión y reducen las complicaciones de esta técnica. Abstract: Background: Spinal metastases are a very common problem which dramatically affects the quality of life of cancer patients. The objective of this review is to address the issue of how minimally invasive surgery can play an important role in treating this pathology. Methods: A literature review was performed, searching in the Google Scholar, PubMed, Scopus and Cochrane databases. Relevant and quality papers published within the last 10 years were included in the review. Results: After screening the 2184 initially identified registers, a total of 24 articles were included for review. Conclusion: Minimally invasive spine surgery is specially convenient for fragile cancer patients with spinal metastases, because of its reduced comorbidity compared to conventional open surgery. Technological advances in surgery, such as navigation and robotics, improve accuracy and safety in this technique.

Background: Spinal metastases are a very common problem which dramatically affects the quality of life of cancer patients. The objective of this review is to address the issue of how minimally invasive surgery can play an important role in treating this pathology. Methods: A literature review was performed, searching in the Google Scholar, PubMed, Scopus and Cochrane databases. Relevant and quality papers published within the last 10 years were included in the review. Results: After screening the 2184 initially identified registers, a total of 24 articles were included for review. Conclusion: Minimally invasive spine surgery is specially convenient for fragile cancer patients with spinal metastases, because of its reduced comorbidity compared to conventional open surgery. Technological advances in surgery, such as navigation and robotics, improve accuracy and safety in this technique. Resumen: Introducción: Las metástasis vertebrales son un problema muy frecuente y asocian un deterioro importante de la calidad de vida en los pacientes oncológicos. El objetivo de esta revisión es determinar el encaje de las técnicas quirúrgicas mínimamente invasivas dentro del manejo de esta entidad. Métodos: Se realizó una revisión bibliográfica en las bases de datos Google Scholar, PubMed, Scopus y Cochrane. Se revisaron los artículos publicados en los últimos 10 años que fueran de una relevancia y calidad adecuadas. Resultados: Tras el cribado de los 2.184 trabajos identificados inicialmente en las distintas bases de datos, se incluyeron un total de 24 artículos en esta revisión. Conclusión: La cirugía mínimamente invasiva de columna es especialmente útil en pacientes oncológicos frágiles con metástasis vertebrales por la reducida comorbilidad que presentan las técnicas que se engloban en ella en comparación con la de la cirugía abierta convencional. Los avances en tecnología aplicada a la cirugía, como la navegación y la robótica, mejoran la precisión y reducen las complicaciones de esta técnica.

Background: Venous congestion (VC) is a hallmark of symptomatic heart failure (HF) requiring hospitalization; however, its role in the pathogenesis of HF progression remains unclear. We investigated whether peripheral VC exacerbates inflammation, oxidative stress and neurohormonal and endothelial cell (EC) activation in patients with HF with reduced ejection fraction (HFrEF)., Methods and Results: Two matched groups of patients with HFrEF and with no peripheral VC vs without recent HF hospitalization were studied. We modeled peripheral VC by inflating a cuff around the dominant arm, targeting ∼ 30 mmHg increase in venous pressure (venous stress test [VST]). Blood and ECs were sampled before and after 90 minutes of VST. We studied 44 patients (age 53 ± 12 years, 32% female). Circulating endothelin-1, tumor necrosis factor-α, interleukin-6, isoprostane, angiotensin II (ang-2), angiopoietin-2, vascular cell adhesion molecule-1, and CD146 significantly increased after the VST. Enhanced endothelin-1 and angiopoietin-2 responses to the VST were present in patients with vs without recent hospitalization and were prospectively associated with incident HF-related events; 6698 messenger ribonucleic acid (mRNA probe sets were differentially expressed in ECs after VST., Conclusions: Experimental VC exacerbates inflammation, oxidative stress, neurohormonal and EC activation and promotes unfavorable transcriptome remodeling in ECs of patients with HFrEF. A distinct biological sensitivity to VC appears to be associated with high risk for HF progression., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: Infections are common following left ventricular assist device (LVAD) implantation and predict adverse events. Infections are frequent prior to LVAD implantation although their impact on postoperative outcomes remains unknown. Gut and nasal microbial imbalance may predispose to mucosal colonization with pathogens. Herein, we investigated the predictive role of pre-LVAD infections, and explored the association of nasal Staphylococcus aureus (SA) colonization and gut microbiota, on postoperative outcomes., Methods and Results: Overall, 254 LVAD patients were retrospectively categorized based on pre-LVAD infection status: Group 1, bacterial/fungal bloodstream infection (BSI); Group 2, other bacterial/fungal; Group 3, viral; and Group 4, no infection. In a subset of patients, nasal SA colonization (n = 140) and pre-LVAD stool (n = 25) were analysed using 16S rRNA sequencing. A total of 75 (29%) patients had a pre-LVAD infection [Group 1: 22 (29%); Group 2: 41 (55%); Group 3: 12 (16%)]. Pre-LVAD BSIs were independent predictors of 1-year postoperative mortality and infections [Group 1 vs. 4: hazard ratio (HR) 2.70, P = 0.036 vs. HR 1.8, P = 0.046]. In an unadjusted analysis, pre-LVAD infections other than BSIs, INTERMACS profile ≤2, higher serum creatinine, lower serum albumin and nasal SA colonization were also significantly associated with postoperative infections. Patients with early post-LVAD infections exhibited decreased microbial diversity (P < 0.05)., Conclusions: Pre-LVAD infections are common. BSIs independently predict postoperative mortality and infections. Additional studies are needed to confirm our findings that pre-LVAD SA nasal colonization and gut microbial composition can help stratify patients' risk for infectious complications after LVAD implantation., (© 2021 European Society of Cardiology.)

Background: Trimethylamine N-oxide (TMAO)-a gut-derived metabolite-is elevated in heart failure (HF) and linked to poor prognosis. We investigated variations in TMAO in HF, left ventricular assist device (LVAD), and heart transplant (HT) and assessed its relation with inflammation, endotoxemia, oxidative stress, and gut dysbiosis., Methods: We enrolled 341 patients. TMAO, CRP (C-reactive protein), IL (interleukin)-6, TNF-α (tumor necrosis factor alpha), ET-1 (endothelin-1), adiponectin, lipopolysaccharide, soluble CD14, and isoprostane were measured in 611 blood samples in HF (New York Heart Association class I-IV) and at multiple time points post-LVAD and post-HT. Gut microbiota were assessed via 16S rRNA sequencing among 327 stool samples. Multivariable regression models were used to assess the relationship between TMAO and (1) New York Heart Association class; (2) pre- versus post-LVAD or post-HT; (3) biomarkers of inflammation, endotoxemia, oxidative stress, and microbial diversity., Results: ln-TMAO was lower among HF New York Heart Association class I (1.23 [95% CI, 0.52-1.94] µM) versus either class II, III, or IV (1.99 [95% CI, 1.68-2.30], 1.97 [95% CI, 1.71-2.24], and 2.09 [95% CI, 1.83-2.34] µM, respectively; all P <0.05). In comparison to class II-IV, ln-TMAO was lower 1 month post-LVAD (1.58 [95% CI, 1.32-1.83] µM) and 1 week and 1 month post-HT (0.97 [95% CI, 0.60-1.35] and 1.36 [95% CI, 1.01-1.70] µM). ln-TMAO levels in long-term LVAD (>6 months: 1.99 [95% CI, 1.76-2.22] µM) and HT (>6 months: 1.86 [95% CI, 1.66-2.05] µM) were not different from symptomatic HF. After multivariable adjustments, TMAO was not associated with biomarkers of inflammation, endotoxemia, oxidative stress, or microbial diversity., Conclusions: TMAO levels are increased in symptomatic HF patients and remain elevated long term after LVAD and HT. TMAO levels were independent from measures of inflammation, endotoxemia, oxidative stress, and gut dysbiosis.

Introduction: Effective tacrolimus (TAC) dosing is hampered by complex pharmacokinetics and significant patient variability. The gut microbiome, a key mediator of endotoxemia, inflammation and oxidative stress in advanced heart failure (HF) patients, is a possible contributor to interindividual variations in drug efficacy. The effect of alterations in the gut microbiome on TAC dosing requirements after heart transplant (HT) has not been explored., Methods: We enrolled 24 patients (mean age = 55.8 ±2.3 years) within 3 months post-HT. Biomarkers of endotoxemia ((lipopolysaccharide (LPS)), inflammation (tumor necrosis factor-α (TNF-α)) and oxidative stress (8,12-iso-Isoprostane F-2alpha-VI) were measured in 16 blood samples. 22 stool samples were analyzed using 16S rRNA sequencing. TAC dose and serum trough level were measured at the time of stool and blood collection. TAC doses were reported in mg/kg/day and as level-to-dose (L/D) ratio, and categorized as ≤ vs. > median., Results: The median TAC dose was 0.1 mg/kg/day and L/D ratio was 100.01. Above the median daily weight-based TAC dose was associated with higher gut microbial alpha diversity (p = 0.03); similarly, TNF-α and 8,12-iso-Isoprostane F-2alpha-VI levels were lower and LPS levels were higher in the above median TAC group, although these findings were only marginally statistically significant and dependent on BMI adjustment. We observed n = 37 taxa to be significantly enriched among patients with > median TAC dose (all FDR<0.05), several of which are potential short-chain fatty acid producers with anti-inflammatory properties, including taxa from the family Subdoligranulum., Conclusions: Our pilot study observed gut microbial alpha diversity to be increased while inflammation and oxidative stress were reduced among patients requiring higher TAC doses early after HT., Competing Interests: Dr. Colombo Consultant, Abbott, no honoraria. Research Grant, Abbott. Dr. Naka Consultant, Abbott, Hourly base reimbursement. The sum of payment does not exceed $5000/year. Consultant, CryoLife, Hourly base reimbursement. The sum of payment does not exceed $5000/year. The rest of the co-authors have no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Endothelin-1 (ET-1) is a pivotal mediator of vasoconstriction and inflammation in congestive states such as heart failure (HF) and chronic kidney disease (CKD). Whether peripheral venous congestion (VC) increases plasma ET-1 at pressures commonly seen in HF and CKD patients is unknown. We seek to characterize whether peripheral VC promotes time- and dose-dependent increases in plasma ET-1 and whether these changes are sustained after decongestion. We used a randomized, cross-over design in 20 healthy subjects (age 30 ± 7 years). To experimentally model VC, venous pressure was increased to either 15 or 30 mmHg (randomized at first visit) above baseline by inflating a cuff around the subject's dominant arm; the nondominant arm served as a noncongested control. We measured plasma ET-1 at baseline, after 20, 60 and 120 min of VC, and finally at 180 min (60 min after cuff release and decongestion). Plasma ET-1 progressively and significantly increased over 120 min in the congested arm relative to the control arm and to baseline values. This effect was dose-dependent: ET-1 increased by 45% and 100% at VC doses of 15 and 30 mmHg, respectively ( P  <   0.05), and declined after 60 min of decongestion though remaining significantly elevated compared to baseline. In summary, peripheral VC causes time- and dose-dependent increases in plasma ET-1. Of note, the lower dose of 15 mmHg (more clinically relevant to HF and CKD patients) was sufficient to raise ET-1. These findings support the potentially contributory, not merely consequential, role of VC in the pathophysiology of HF and CKD., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Background: Soluble CD146 (sCD146), is an endothelial marker with similar diagnostic power as natriuretic peptides in decompensated heart failure (HF). While natriuretic peptides are released by the failing heart, sCD146 may be released by veins in response to stretch induced by systemic congestion in HF. This study investigated the source, effects of vascular stress on release and prognostic properties of sCD146 in HF., Methods: In a peripheral venous stress study, plasma concentrations of sCD146 and N-terminal probrain natriuretic-peptide (NT-proBNP) were measured in 44 HF patients at baseline and after 90 min of unilateral forearm venous congestion. In addition, sCD146 and NT-proBNP were measured in peripheral vein (PV) and coronary sinus (CS) blood samples of 137 HF patients and the transcardiac gradient was calculated. Those patients were followed for major adverse cardiovascular events (MACE) during 2 years., Results: The induction of venous stress was associated with a pronounced increase in circulating concentrations of sCD146 in the congested arm (+60 μg/L) compared to the control arm (+16 μg/L, P = 0.025), while no difference in NT-proBNP concentrations was seen. In contrast to positive transcardiac gradient for NT-proBNP, median sCD146 concentrations were lower in CS than in PV (396 vs 434, P < 0.001), indicating a predominantly extracardiac source of sCD146. Finally, increased PV concentrations of sCD146 were associated with higher risk of MACE at 2 years., Conclusions: Soluble CD146 is released from the peripheral vasculature in response to venous stretch and may reflect systemic congestion in chronic HF patients., (© 2016 American Association for Clinical Chemistry.)

Background/aim: Breast lesions that are not palpable on physical examination but considered suspicious for malignancy on mammography or ultrasonography should be marked before surgery. Wire-guided localization (WGL) is the most frequently used method for preoperative marking of nonpalpable breast lesions (NPBLs). An alternative is marking by a radioactive agent (radio-guided occult lesion localization; ROLL). The present study aimed to compare WGL and ROLL for preoperative marking., Materials and Methods: The study included 25 patients marked by ROLL and 11 patients marked by WGL. The groups were compared in terms of patient and lesion characteristics, method-related characteristics, hospital stay duration, complications, cosmetic outcomes, and rate of correct marking., Results: Suspicious lesions were marked with a success rate of 95.6% by ROLL and 100% by WGL. Complications and pain sensation rates were found significantly lower in the ROLL group compared to WGL. Although ROLL was considered more advantageous in terms of hospital stay duration, positive surgical margins, cosmetic outcomes, and excision duration, the differences between the groups were not statistically significant., Conclusion: ROLL, which is a simple, comfortable, and reliable method, could be used as an alternative to the WGL in preoperative marking of NPBLs.

Venous congestion and endothelial and neurohormonal activation are known to occur in acute decompensated heart failure (ADHF), yet the temporal role of these processes in the pathophysiology of decompensation is not fully understood. Conventional wisdom presumes congestion to be a consequence of worsening cardiovascular function; however, the biomechanically driven effects of venous congestion are biologically plausible contributors to ADHF that remain largely unexplored in vivo. Recent experimental evidence from human models suggests that fluid accumulation and venous congestion are not simply consequences of poor cardiovascular function, but rather are fundamental pro-oxidant, pro-inflammatory, and hemodynamic stimuli that contribute to acute decompensation. The latest advances in the monitoring of volume status using implantable devices allow for the detection of venous congestion before symptoms arise. This may ultimately lead to improved treatment strategies including not only diuretics, but also specific, adjuvant interventions to counteract endothelial and neurohormonal activation during early preclinical decompensation.

Aims: Volume overload and venous congestion are typically viewed as a consequence of advanced and of acute heart failure (HF) and renal failure (RF) although it is possible that hypervolaemia itself might be a critical intermediate in the pathophysiology of these diseases. This study aimed at elucidating whether peripheral venous congestion is sufficient to promote changes in inflammatory, neurohormonal, and endothelial phenotype similar to those observed in HF and RF., Methods: To experimentally model peripheral venous congestion, we developed a new method (so-called venous stress test) and applied the methodology on 24 healthy subjects (14 men, age 35 ± 2 years). Venous arm pressure was increased to ∼30 mmHg above the baseline level by inflating a tourniquet cuff around the dominant arm (test arm). Blood and endothelial cells (ECs) were sampled from test and control arm (lacking an inflated cuff) before and after 75 min of venous congestion, using angiocatheters and endovascular wires. Magnetic beads coated with EC-specific antibodies were used for EC separation; amplified mRNA was analysed by Affymetrix HG-U133 Plus 2.0 Microarray., Results: Plasma interleukin-6 (IL-6), endothelin-1 (ET-1), angiotensin II (AII), vascular cell adhesion molecule-1 (VCAM-1), and chemokine (C-X-C motif) ligand 2 (CXCL2) were significantly increased in the congested arm. A total of 3437 mRNA probe sets were differentially expressed (P < 0.05) in venous ECs before vs. after testing, including ET-1, VCAM-1, and CXCL2., Conclusion: Peripheral venous congestion causes release of inflammatory mediators, neurohormones, and activation of ECs. Overall, venous congestion mimicked, notable aspects of the phenotype typical of advanced and of acute HF and RF.

Purpose: The aim of this study was to assess the changes in biologic markers of breast cancer ER, PR, HER 2 and Ki-67 in locally advanced breast cancer patients after neoadjuvant chemotherapy., Methods: Data from 63 locally advanced breast cancer patients (stage II or III), whose histological diagnosis was made by core biopsies were retrospectively evaluated. The patients were given 4 cyles of 600 mg/m(2) cyclophosphamide, 60 mg/m(2) doxorubicin every 15 days followed by 4 cycles of paclitaxel 175 mg/m(2) every 15 days, and they underwent surgery within two weeks after the last chemotherapy cycle. Expressions in the preoperative and postoperative status of ER, PR, HER 2 and Ki-67 were compared., Results: The patient mean age was 49.2 ±10.7 years and most (57.1%) were premenopausal. Clinical stages of patients ranged between T2N1 and T3N2. The pathological complete response (pCR) rate was 14.9 % (N=9). Two (5.7%) patients who were ER positive prior to treatment showed ER negativity after treatment. In 7 (21.17percnt;) patients PR became negative after neoadjuvant chemotherapy and in 3 (9.0%) patients PR became positive. Changes in ER and PR receptors were not statistically significant (ER p=0.500 and PR p=0.549, respectively), whereas in 2 (5. 8%) patients hormonal status changed significantly when compared to initial biopsies (p=0.003). In addition, median value for PR intensity decreased from 20 to 10% (p=0.003) and Ki-67 values decreased from 10 to 1% (p<0.001) following neoadjuvant therapy. Six (17%) patients exhibited some changes in HER 2 staining. HER 2 expression became 2+ in 3 patients who were HER 2 negative prior to treatment, and HER 2 expression became negative in two patients with HER 2 1+ and 2+ prior to treatment following neoadjuvant chemotherapy., Conclusion: The biological markers ER, PR, HER 2 and Ki- 67 index demonstrated differences after neoadjuvant treatment in breast cancer patients. These changes may affect the treatment decision.

Purpose: To assess the changes of biologic markers estrogen receptors (ER), progesterone receptors (PR), HER 2 and Ki-67 in locally advanced breast cancer patients after neoadjuvant chemotherapy., Methods: Data from 63 locally advanced breast cancer patients (stage II or III), whose histological diagnosis was made by core biopsies were retrospectively evaluated. The patients were given 4 cycles of 600 mg/m(2) cyclophosphamide, 60 mg/m(2) doxorubicin every 15 days, followed by 4 cycles of paclitaxel 175 mg/m(2), followed by mastectomy within 2 weeks after the last chemotherapy cycle. The changes in ER, PR, HER 2 and Ki-67 status of the operated tumor tissue were compared with the material obtained by initial core biopsies., Results: The patient mean age was 49.2±10.7 years. Most (57.1%) were premenopausal. Clinical disease stages ranged between T2N1 and T3N2. Pathological complete response (pCR) rate was 14.9 7 percent; (n=9). Two (5.7%) patients who were ER positive prior to treatment showed ER negativity after treatment. In 7 (21.1%) patients PR became negative and in 3 (9.0%) became positive after neoadjuvant chemotherapy. Changes in ER and PR receptors were not statistically significant (p=0.500 and PR p=0.549, respectively), whereas in 2 (5.8%) patients hormonal status changed significantly when compared to initial biopsies (p=0.003). In addition, the median value of PR intensity decreased from 20 to 10% (p=0.003) and Ki-67 decreased from 10 to 1% (p<0.001) following neoadjuvant therapy. Five (14.1%) patients exhibited some changes in HER 2 expression: HER 2 expression became 2+ in 3 patients previously being HER 2 negative, and in 2 patients HER 2 became negative whilst it was 1+ and 2+ prior to neoadjuvant chemotherapy., Conclusion: It was observed that the biologic markers ER, PR, HER 2 and Ki-67, from the same tumor material demonstrated differences after neoadjuvant treatment in breast cancer patients. These changes may affect the treatment decision.

Background: Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory disease of the breast. It is related to various etiological factors. The treatment of IGM is challenging as there is a lack of consensus in the literature and treatment options vary widely. Conservative treatment with antibiotics, glucocorticoids and immunosuppressive drugs, and surgery are used in the management of the disease. In this article we report our experience with IGM patients receiving immunosuppressive treatment., Patients and Methods: The medical records of patients with IGM receiving systemic therapy at the Hacettepe University Hospital between October 2007 and May 2010 were reviewed. 15 cases of histopathologically proven IGM were identified. The data was examined for risk factors and success of treatment., Results: 14 patients were given prednisolone together with azathioprine, and 1 patient who was pregnant at the time of diagnosis received only prednisolone (30 mg/day). 11 (73%) patients had a complete response to systemic therapy. 2 patients had a relapse, of whom 1 required surgical drainage and 1 was treated with a higher dose of glucocorticoids., Conclusion: Systemic therapy is a safe and effective treatment for IGM. The addition of azathioprine to glucocorticoid therapy permits quick tapering of the steroid doses and increases the treatment success.

Although inflammation is a physiologic response designed to protect us from infection, when unchecked and ongoing it may cause substantial harm. Both chronic heart failure (CHF) and chronic kidney disease (CKD) are known to cause elaboration of several pro-inflammatory mediators that can be detected at high concentrations in the tissues and blood stream. The biologic sources driving this chronic inflammatory state in CHF and CKD are not fully established. Traditional sources of inflammation include the heart and the kidneys which produce a wide range of pro-inflammatory cytokines in response to neurohormones and sympathetic activation. However, growing evidence suggests that non-traditional biomechanical mechanisms such as venous and tissue congestion due to volume overload are also important as they stimulate endotoxin absorption from the bowel and peripheral synthesis and release of pro-inflammatory mediators. Both during the chronic phase and, more rapidly, during acute exacerbations of CHF and CKD, inflammation and congestion appear to amplify each other resulting in a downward spiral of worsening cardiac, vascular, and renal functions that may negatively impact patients' outcome. Anti-inflammatory treatment strategies aimed at attenuating end organ damage and improving clinical prognosis in the cardiorenal syndrome have been disappointing to date. A new therapeutic paradigm may be needed, which involves different anti-inflammatory strategies for individual etiologies and stages of CHF and CKD. It may also include specific (short-term) anti-inflammatory treatments that counteract inflammation during the unsettled phases of clinical decompensation. Finally, it will require greater focus on volume overload as an increasingly significant source of systemic inflammation in the cardiorenal syndrome.

The vascular endothelium is the inner lining of blood vessels serving as autocrine and paracrine organ that regulates vascular wall function. Endothelial dysfunction is recognized as initial step in the atherosclerotic process and is well advanced in diabetes, even before the manifestation of end-organ damage. Strategies capable of assessing changes in vascular endothelium at the preclinical stage hold potential to refine cardiovascular risk. In vitro cell culture is useful in understanding the interaction of endothelial cells with various mediators; however, it is often criticized due to the uncertain relevance of results to humans. Although circulating endothelial cells, endothelial microparticles, and progenitor cells opened the way for ex vivo studies, a recently described method for obtaining primary endothelial cells through endovascular biopsy allows direct characterization of endothelial phenotype in humans. In this article, we appraise the use of endothelial cell-based methodologies to study vascular inflammation in diabetes and atherosclerosis.

Despite accumulating clinical evidence supporting a key role for venous congestion in the development of acute decompensated heart failure (ADHF), there remain several gaps in our knowledge of the pathophysiology of ADHF. Specifically, the biomechanically driven effects of venous congestion on the vascular endothelium (the largest endocrine/paracrine organ of the body), on neurohormonal activation, and on renal and cardiac dysfunction remain largely unexplored. We propose that venous congestion is a fundamental, hemodynamic stimulus for vascular inflammation, which plays a key role in the development and possibly the resolution of ADHF through vascular, humoral, renal, and cardiac mechanisms. A better understanding of the role of venous congestion and endothelial activation in the pathophysiology of ADHF may provide a strong rationale for near-future testing of treatment strategies that target biomechanically driven inflammation. Targeting vascular and systemic inflammation before symptoms arise may prevent progression to overt clinical decompensation in the ADHF syndrome.

Background: The venous endothelium is a key regulator of central blood volume, organ perfusion, and hemostasis in heart failure (HF). We previously reported activation of the inflammatory/oxidative program in venous endothelial cells collected from decompensated HF patients. The underlying causes are unknown. We tested the hypothesis that the pro-inflammatory state of HF and vascular strain associated with congestion can activate the endothelial inflammatory/oxidative and hemostatic programs., Methods and Results: We studied 6 normal (NL) dogs (left ventricular ejection fraction [LVEF] >50%, central venous pressure [CVP] = 8 +/- 2 mm Hg) and 6 dogs with HF (LVEF approximately 30%, CVP 8 +/- 2 mm Hg) produced by intracoronary microembolizations. Normal dogs were studied at baseline and 1 hour after fluid load to a target CVP >or=20 mm Hg. Endothelial cells were scraped from jugular veins; mRNA expression was analyzed by reverse transcription polymerase chain reaction. The endothelial inflammatory/oxidative and hemostatic programs were significantly activated in HF dogs compared with NL. In NL dogs, fluid load significantly activated the endothelial inflammatory/oxidative and hemostatic programs, and, concurrently, caused a significant increase in plasma neurohumoral indices to levels that approached those of HF dogs., Conclusions: The pro-inflammatory state of HF and vascular strain associated with congestion can both activate venous endothelial cells in dogs in a manner consistent with that seen in HF patients.

Haemophiliac pseudotumors are usually observed in the diaphysis of long bones. Pseudotumors due to psoas muscle hematoma are rare and surgical management is difficult. Surgical treatment of these lesions is usually associated with high morbidity and mortality rate. Here, we present a case with iliopsoas haemophiliac pseudotumors with bowel fistulization who underwent three abdominal operations and survived. Based on our experiences in this patient, we recommend to wait for the intraabdominal hematoma and adhesions to resolve and organise, so that the dissection can be kept to a minimum, which decreases the chances of iatrogenic injury and surgical bleeding (Fig. 3, Ref. 15). Full Text (Free, PDF) www.bmj.sk.

Background: Indirect evidence implicates endothelial dysfunction in the pathogenesis of vascular diseases associated with obstructive sleep apnea (OSA). We investigated directly whether dysfunction and inflammation occur in vivo in the vascular endothelium of patients with OSA. The effects of continuous positive airway pressure (CPAP) therapy on endothelial function and repair capacity were assessed., Methods and Results: Thirty-two patients with newly diagnosed OSA and 15 control subjects were studied. Proteins that regulate basal endothelial nitric oxide (NO) production (endothelial NO synthase [eNOS] and phosphorylated eNOS) and inflammation (cyclooxygenase-2 and inducible NOS) and markers of oxidative stress (nitrotyrosine) were quantified by immunofluorescence in freshly harvested venous endothelial cells before and after 4 weeks of CPAP therapy. Vascular reactivity was measured by flow-mediated dilation. Circulating endothelial progenitor cell levels were quantified to assess endothelial repair capacity. Baseline endothelial expression of eNOS and phosphorylated eNOS was reduced by 59% and 94%, respectively, in patients with OSA compared with control subjects. Expression of both nitrotyrosine and cyclooxygenase-2 was 5-fold greater in patients with OSA than in control subjects, whereas inducible NOS expression was 56% greater. Expression of eNOS and phosphorylated eNOS significantly increased, whereas expression of nitrotyrosine, cyclooxygenase-2, and inducible NOS significantly decreased in patients who adhered to CPAP > or = 4 hours daily. Baseline flow-mediated dilation and endothelial progenitor cell levels were lower in patients than in control subjects, and both significantly increased in patients who adhered to CPAP > or = 4 hours daily., Conclusions: OSA directly affects the vascular endothelium by promoting inflammation and oxidative stress while decreasing NO availability and repair capacity. Effective CPAP therapy is associated with the reversal of these alterations.

Background: Limited access to endothelial tissue is a major constraint when investigating the cellular mechanisms of vascular inflammation in patients with cardiovascular and metabolic diseases. We introduce venous endothelial sampling coupled to quantitative analysis of gene transcripts by real-time PCR, as a novel approach to study endothelial gene expression in human subjects., Methods: Endothelial cells were collected from a superficial forearm vein using five guide wires sequentially inserted through a 20-gauge angiocatheter in seven patients with history of cardiovascular events related to advanced vascular disease and in 17 healthy subjects. Endothelial cells were purified using magnetic beads coated with endothelial specific antibodies. Endothelial mRNA was amplified using RiboAmp HS RNA Amplification kit (Molecular Devices, Sunnyvale, CA). Amplified RNA was analyzed by real-time PCR., Results: Linearity of RNA amplification was validated by real-time PCR using RNA from 1,000 human umbilical endothelial cells (HUVECs) before and after amplification. In human subjects, vascular disease was associated with significant induction of proatherosclerotic genes: early growth response gene product (Egr-1) and monocyte chemoattractant protein-1 (MCP-1)., Conclusion: Venous endothelial sampling coupled to real-time PCR analysis is a minimally invasive, safe, and reliable technique to monitor vascular inflammation in human subjects. Expression of genes implicated in the atherosclerotic process is increased in the venous endothelium of patients with arterial vascular disease. Venous endothelial sampling and quantitative analysis of gene expression may help develop new vascular-targeted biomarkers to identify and track the impact of disease states and therapeutic interventions in vascular diseases.

Background: Oxidative stress is an important pathophysiologic feature in chronic heart failure (CHF) and may in part result from the inability to counteract acute surges of circulating oxidant products. Oxidized low-density lipoprotein (oxLDL) is an emerging prognostic marker in CHF. Accordingly, we investigated the effect of exercise-induced oxidative stress on circulating levels of oxLDL and its association with clinical outcomes in CHF., Methods and Results: Plasma levels of oxLDL and low-density lipoprotein cholesterol (LDL-c) were measured at rest and after maximal exercise in 48 subjects with CHF and 12 healthy controls. Subjects with CHF had a higher baseline oxLDL (77.7 +/- 3.2 U/L vs 57.9 +/- 5.0 U/L, P = .01) and a higher baseline oxLDL/LDL-c ratio (0.87 +/- 0.04 vs 0.49 +/- 0.04, P < or = .001). Exercise induced an increase in oxLDL in subjects with CHF (77.7 +/- 3.2 U/L to 85.3 +/- 3.0 U/L, P < or = .001) but not in controls (57.9 +/- 5.0 to 61.4 +/- 5.5, P = .17). In 39 subjects for whom follow-up data were available, an increase in oxLDL of more than 11.0 U/L was associated with an increased risk to meet a combined end point of death and need for ventricular assist device or heart transplant during a 19-month follow-up period (hazard ratio 8.6; 95% confidence interval 1.0-73.8, P = .05); this remained significant when adjusted for peak oxygen consumption, left ventricular ejection fraction, New York Heart Association class, sex, and age (hazard ratio 46.6, 95% confidence interval 1.5-1438.1, P = .02)., Conclusion: Plasma oxLDL and the oxLDL/LDL-c ratio are elevated in subjects with CHF. Whether assessment of oxLDL during maximal exercise allows early identification of subjects at highest risk for adverse outcomes should be systematically investigated.

Background: Prescribing information for nesiritide mandates priming of intravenous tubing prior to connecting to the patient's intravenous access because the drug may adsorb to the line. As of this writing, no published study has quantified the binding effect of nesiritide to intravenous tubing., Objective: To investigate whether priming of peripheral intravenous tubing is necessary and whether nesiritide can be reliably delivered through central intravenous lines, including heparin-coated catheters, where priming cannot occur., Methods: A 23.3-mL bolus of nesiritide followed by a 7-mL/h 2-hour infusion were run through (1) polyvinylchloride (PVC) peripheral intravenous tubing primed with nesiritide, (2) non-primed PVC peripheral intravenous tubing, (3) non-primed polyethylene peripheral intravenous tubing, (4) non-primed PVC peripheral intravenous tubing connected to a central intravenous polyurethane catheter, and (5) non-primed PVC peripheral intravenous tubing connected to a heparin-coated pulmonary artery PVC catheter. Nesiritide concentrations were measured in the intravenous bags and in samples collected from the 5 intravenous settings., Results: Priming of intravenous tubing with nesiritide did not increase drug recovery: at least 94% of the bolus dose and 96% of the total drug were recovered from all intravenous sets., Conclusions: Infusion of nesiritide via non-primed peripheral and central intravenous tubing, including heparin-coated pulmonary catheter, is reliable. Changes in nesiritide labeling appear to be warranted.

The incorporation of a taxane into an anthracycline-containing regimen in the adjuvant treatment of breast cancer is a promising approach. In this study, we aimed to evaluate the safety and efficacy of four cycles of FEC (fluorouracil 500 mg/m2, epirubicin 70 mg/m2, cyclophosphamide 500 mg/m2, every 3 weeks) followed by four cycles of paclitaxel (175 mg/m2 every 3 weeks) in the adjuvant treatment of node-positive and other high-risk breast cancer patients. A total of 88 female patients were enrolled. Mean age (+/- SD) of the patients was 47 +/- 10 (min: 24; max: 71). The patients were followed for a median of 48 months (min: 20; max: 64). The most common side effects were nausea-vomiting (grade I-II: 91%; grade III: 2%), as well as hematological toxicity (grade I-II: 70%; grade III: 3%). Although all patients experienced some degree of toxicity, it was severe enough to be classified as grade III or IV in only 10 (11%) of the cases. Of note, six (8%) patients had grade I and only one (1%) had grade II cardiotoxicity. No grade III or IV cardiotoxicity was observed. The full eight cycles of study treatment could be administered to 75 patients (85%). Side effects necessitated the reduction of the doses of FEC and paclitaxel in one (1%) and three patients (3%), respectively. Median overall (OS) and disease-free survival (DFS) have not yet been reached. Five-year OS and DFS have been estimated to be 78% and 61%, respectively. We conclude that FEC followed by paclitaxel is a well-tolerated and feasible regimen in the adjuvant treatment of early breast cancer. Its efficacity is comparable with other commonly used regimens and merits evaluation in a phase III study.

Angiomatous lesions are common in infants and children. Hemangioendotheliomas (HE) represent one type of these lesions. Endothelial cell proliferation and the development of vascular/blood cell-filled spaces are inherent in the growth of HE. Therefore, understanding mechanisms that regulate the proliferation of these lesions should provide key insight into mechanisms regulating angiogenesis. A murine model was used to test the significance of monocyte chemoattractant protein (MCP)-1 in HE proliferation. EOMA cells, a cell line derived from a spontaneously arising murine HE, generate these lesions with 100% efficiency when injected subcutaneously into syngeneic mice. MCP-1 produced by EOMA cells recruit macrophages, which were shown to induce angiogenic behavior in EOMA cells by stimulating transwell migration and inducing sprout formation on type I collagen gels. When EOMA cells were injected into MCP-1(-/-) mice, only 50% of the mice developed tumors, presumably because the low levels of MCP-1 expressed by the injected EOMA cells were enough to overcome any host deficits of this chemokine. When EOMA cells were coinjected with a neutralizing antibody to MCP-1, tumors failed to develop in any of the treated mice, including syngeneic 129P3, C57Bl/6 (wild type), and MCP-1(-/-). These results present the first evidence that MCP-1 is required for HE proliferation and may promote the growth of these lesions by stimulating angiogenic behavior of endothelial cells. This study has produced the first in vivo evidence of a complete response for any neoplasm, specifically a vascular proliferative lesion, to anti-MCP-1 therapy in animals with intact immune systems.

Gastrointestinal system anastomoses, especially colonic anastomoses, have significant morbidity and mortality despite recent technical improvements. Besides regulating the circadian rhythm, the pineal gland and its main neurohormone product melatonin have widespread actions in the organism. The purpose of this study was to investigate the effects of pinealectomy on the healing of colonic anastomoses. One hundred male albino Wistar rats were used in this study. The rats were separated into three groups: control, pinealectomy, and sham groups. In the control group, only colonic resection and anastomoses were performed. Following pinealectomy, colonic anastomosis was performed 2 weeks later on one half and 2 months later on the other half of the pinealectomy group. Only craniotomy was performed on the sham group, and the rats were separated and evaluated like the pinealectomy group. Colonic anastomoses were evaluated on postanastomotic day 3 and 7 by measuring the bursting pressure and the hydroxyproline levels in the anastomotic segments. There was no difference in the bursting pressure measurements between the groups on both postoperative day 3 and 7. Although hydroxyproline levels were different between groups on both postanastomotic days 3 and 7, it has been observed that neither normal nor anastomotic hydroxyproline levels influenced the anastomotic bursting pressure measurements. The percent deviation from the normal values was compared in the anastomotic segments, and no differences were found regarding the bursting pressure and hydroxyproline levels. It was concluded that pinealectomy has no effect on the healing of colonic anastomoses.

Gap junction channels maintain cell-cell communication and are essential for the coordination of tissues, playing a pivotal role in embryonal development. Gap junctional intercellular communication (GJIC), studied here in human fetal skin fibroblasts (HFFF2) and in rat liver epithelial cells (WB-F344), was almost doubled upon exposure to thalidomide (10 microM) in the presence of NADH or NADPH (20 microM). Neither in HFFF2 nor in WB-F344 cells did any detectable alteration in GJIC occur with the thalidomide analog EM 16 (10 microM), known as a non-teratogenic compound. The thalidomide analog EM 364 (10 microM) increased GJIC without prior metabolic activation. It is suggested that GJIC modification may be related to the pharmacological and toxicological properties of thalidomide.

Hydatid disease of the liver is still endemic in certain parts of the world. The diagnosis of noncomplicated hydatid cyst of the liver depends on clinical suspicion. Ultrasonography and computed tomography, the most important diagnostic tools, are helpful for determining the complications and planning treatment. The modern treatment of hydatid cyst of the liver varies from surgical intervention to percutaneous drainage or medical therapy. Surgery is still the treatment of choice and can be performed by the conventional or laparoscopic approach. Percutaneous drainage and treatment of the cyst with hypertonic saline or alcohol seems to be a good alternative to surgery in selected cases. Currently, we treat types I and II by ultrasound-guided percutaneous drainage and types IV and V (excluding totally calcified cysts) surgically. Type III cysts can be managed either way depending on the presence of drainable content. We believe that the laparoscopic approach should be limited to noncomplicated cysts.

Background: The adverse effects of elevated intraabdominal pressure (IAP) on abdominal organs are realized, but its influence on anastomotic healing has not been studied. The aim of this study was to evaluate the effect of elevated IAP on healing of colonic anastomoses., Methods: Thirty rats, which all had right colonic anastomoses, were divided into five groups. Group 1 was the control group, and group 2 had fecal peritonitis. IAP was maintained between 4 to 6 mm Hg in group 3, 8 to 12 mm Hg in group 4, and 14 to 18 mm Hg in group 5 until all rats were sacrificed on day 4. Bursting pressures and tissue hydroxyproline concentrations of anastomoses were then analyzed and compared., Results: Mean +/- SEM of bursting pressures were 143+/-2.9 mm Hg in group 1, 72+/-14.4 mm Hg in group 2, 77.3+/-7.9 mm Hg in group 3, 57.5+/-11.2 mm Hg in group 4, and 40.1+/-9.6 mm Hg in group 5 (P<0.0001, one-way analysis of variance [ANOVA]). Mean +/- SEM of tissue hydroxyproline concentrations were 5.3+/-0.3 microg/mg in group 1, 4.7+/-0.5 microg/mg in group 2, 4.6+/-0.6 microg/mg in group 3, 3.6+/-0.5 microg/mg in group 4, and 2.4+/-0.2 microg/mg in group 5 (P = 0.0026, one-way ANOVA). The bursting pressure and hydroxyproline concentrations had good correlation (P<0.001, r = 0.76)., Conclusions: Elevated IAP delays healing of colonic anastomoses and 4 to 6 mm Hg IAP delays healing as much as fecal peritonitis. More elevated IAP delays healing more than fecal peritonitis. These events may be clinically important and may result from local-systemic effects of IAP.

We report a case of renal artery stenosis most probably secondary to chronic pancreatitis. The patient had a traumatic pancreatic fistula. This was followed by numerous attacks of pancreatitis in the following years. At a relatively young age, he developed hypertension. Examinations revealed a right renal artery stenosis which was successfully treated by a percutaneous angioplasty. This rare complication should be kept in mind as a possible complication of pancreatitis.

Cell proliferation is a complex and important event in atherosclerosis, aging and cancer, and is under the control of signalling pathways. These signalling pathways in turn are effected by the presence of a number of chemicals. For this purpose, we have checked the effect of two chemicals on the proliferation of skin fibroblasts. alpha-Tocopherol and silibin dihemisuccinate (SDH) negatively regulate proliferation of human skin fibroblasts. To check the cell-cycle time intervals, a [3H]thymidine incorporation assay was performed, showing DNA replication at around 24 h; this indicated the time required for the incubation with the chemicals. When alpha-tocopherol was added to the growth medium at a physiological concentration of 50 microM, cell proliferation was inhibited by 40% in 72 h. A similar inhibitory effect of cell proliferation was achieved when 500 microM SDH was used (39% inhibition in 72 h). From the dose-response curves obtained it was concluded that both duration of treatment and the concentration of the chemicals are important parameters. The actual mechanism of the inhibition of cell proliferation may be due to the anti-oxidative potential of these chemicals as well as another mechanism effecting signal transduction pathways.

Objective: To assess the effects of laparotomy, and insufflation of carbon dioxide and air, on the immune system in rats., Design: Randomised laboratory study., Setting: Teaching hospital, Turkey., Animals: 77 Wistar rats randomly allocated to 2 groups one of which was sensitised with dinitrofluorobenzene (DNFB, n = 43) and one of which was not (n = 34)., Interventions: The DNFB group was sensitised and subdivided into control (n = 8), laparotomy alone (n = 7), and insufflation with carbon dioxide (CO2) for 30 and 60 mins (n = 7 in each) or room air for 30 and 60 mins (n = 7 in each). A week later DNFB was reapplied to the ears. In the group not sensitised with DNFB the animals were subdivided similarly, the corresponding numbers in each group being, 6, 6, 6, 6, 5, and 5., Main Outcome Measures: Delayed type hypersensitivity (DTH) measured by ear swelling in the DNFB group, and peritoneal bactericidal activity, total free peritoneal cell counts (TPC), and cell types in the non-sensitised group., Results: There were significant differences in the degree of ear swelling in the DNFB group between control and laparotomy groups (p = 0.0001) and between control and both insufflations of air (p = 0.002 and p = 0.0003, respectively). In the non-sensitised group peritoneal bactericidal activity was significantly increased after 7 hours in the 60 mins air insufflation group (p = 0.04). At 24 hours there were no differences among the groups. TPC were not affected. The number of peritoneal polymorphonuclear leucocytes (PMN) was significantly higher in the laparotomy alone group than in the control or any of the insufflation groups (p < 0.05)., Conclusions: Laparotomy and air insufflation depressed cell-mediated immunity. Peritoneal bactericidal activity was affected only after 60 minutes of air insufflation.

Background: Depression of fibrinolysis is known to be a major mechanism for postoperative adhesion formation. Because aprotinin inhibits fibrinolysis it may lead to an increase in adhesion formation whereas its anti-inflammatory effects may lead to a decrease in adhesion formation. Our aim is to clarify conflicting results in previous literature., Methods: Basal levels of intestinal hydroxyproline (OHP) content and local fibrinolytic activity (LFA) were determined using naive groups. In the experiment groups, adhesions were created by scraping and creating a transient ischemia of a segment of terminal ileum. Group I and II rats were injected subcutaneous (s.c.) normal saline (NS) for 3 days and single dose intraperitoneal (i.p.) NS, respectively. Group III and IV rats were injected s.c. aprotinin for 3 days and single dose i.p. aprotinin, respectively. Group V rats were injected intramuscular methylprednisolone (MP) for 3 days. LFA and OHP levels were determined on the second and fifth postoperative days. The severity of adhesion formation was graded on the fifth day., Results: Aprotinin decreased both the severity of adhesions and OHP levels whereas MP decreased only the severity of adhesions. There was an early depression of LFA at the second day in both NS and MP groups increasing to basal levels at the fifth day. OHP levels showed significant correlation with adhesion severity., Conclusion: Results showed that aprotinin decreased intra-abdominal adhesion formation probably by preventing early depression of LFA.

The purpose of this study was to investigate the effects of polyglycolic acid (PGA), an absorbable (ABS) mesh, and polypropylene (PP), a nonabsorbable (NA) mesh, on intestinal adhesion formation. Altogether 72 mice were divided into a control group of 24, an ABS mesh group of 23, and an NA mesh group of 25. All three groups were divided into two subgroups for evaluation of adhesion severity at postoperative (po) days 5 and 90. Adhesion severity was measured with adhesion grading and tissue hydroxyproline (OHP) levels. Adhesion degree was minimal (1) in all subjects on day 5. Also there was no difference in tissue OHP levels between three groups on day 5 (p > 0.05). Adhesion degree and tissue OHP levels as determinants of adhesion severity were higher in the PGA mesh group than the control group and the PP mesh group on day 90 (p < 0.001). There was no difference between the control group and the PP mesh groups (p > 0.05). Adhesion degree was higher on day 90 than on day 5 in the control group and the PGA mesh group (p < 0.05), whereas tissue OHP level was higher on day 90 than on day 5 in all three groups (p < 0.001). Also there was linear correlation between adhesion degree and tissue OHP levels (r = 0.86, p < 0.001). The study demonstrates that ABS PGA mesh has higher potential for adhesion formation than the NA PP mesh, probably related to the increased foreign body and inflammatory reactions during the absorption process of the mesh.