The evolution of bicontinuous polymeric nanospheres in aqueous solution.

Complex polymeric nanospheres in aqueous solution are desirable for their promising potential in encapsulation and templating applications. Understanding how they evolve in solution enables better control of the final structures. By unifying insights from cryoTEM and small angle X-ray scattering (SAXS), we present a mechanism for the development of bicontinuous polymeric nanospheres (BPNs) in aqueous solution from a semi-crystalline comb-like block copolymer that possesses temperature-responsive functionality. During the initial stages of water addition to THF solutions of the copolymer the aggregates are predominantly vesicles; but above a water content of 53% irregular aggregates of phase separated material appear, often microns in diameter and of indeterminate shape. We also observe a cononsolvency regime for the copolymer in THF-water mixtures from 22 to 36%. The structured large aggregates gradually decrease in size throughout dialysis, and the BPNs only appear upon cooling the fully aqueous dispersions from 35 °C to 5 °C. Thus, the final BPNs are ultimately the result of a reversible temperature-induced morphological transition.

Exerting pulling forces in fluids by directional disassembly of microcrystalline fibres.

Biomolecular polymerization motors are biochemical systems that use supramolecular (de-)polymerization to convert chemical potential into useful mechanical work. With the intent to explore new chemomechanical transduction strategies, here we show a synthetic molecular system that can generate forces via the controlled disassembly of self-organized molecules in a crystal lattice, as they are freely suspended in a fluid. An amphiphilic monomer self-assembles into rigid, high-aspect-ratio microcrystalline fibres. The assembly process is regulated by a coumarin-based pH switching motif. The microfibre crystal morphology determines the monomer reactivity at the interface, resulting in anisotropic etching. This effect exerts a directional pulling force on microscopic beads adsorbed on the crystal surface through weak multivalent interactions. We use optical-tweezers-based force spectroscopy to extract mechanistic insights into this process, quantifying a stall force of 2.3 pN (±0.1 pN) exerted by the ratcheting mechanism produced by the disassembly of the microfibres.

The proposal of an integrated ultrasonographic approach into the ALS algorithm for cardiac arrest: the PEA protocol.

BACKGROUND AND OBJECTIVE: Guidelines on cardiac arrest (CA) recommend the prompt beginning of cardio-pulmonary resuscitation (CPR) and the identification and correction of reversible causes. This article deals with the application of clinical ultrasonography (US) in resuscitation, presenting a simple codified US protocol usable during CPR to recognize reversible causes of CA. EVIDENCE ON US IN CA AND STATE OF THE ART: Emergency US is a bedside, point-of-care, focused diagnostic procedure with aim to complete the physical examination. It is performed by emergency physician everywhere to answer briefly important clinical questions. Several trials recently experimented US employment during advanced life support, demonstrating its feasibility without delaying CPR. PERSPECTIVES: The PEA Protocol: We propose a simplified US protocol for non-shockable rhythms, called "PEA protocol" to remember the applications of the study (CA in Pulseless Electrical Activity, PEA) and the US scan sequence: Pulmonary scans to depict pneumothorax and pleural effusion and to differentiate wet or dry lung; Epigastric for pericardial effusion, left and right ventricular sides and motion, IVC filling; Abdominal and other scans for aortic aneurism and dissection, peritoneal effusion, bowel occlusion or perforation, deep venous thrombosis. The PEA protocol could be performed both during CA in PEA and during periarrest conditions. CONCLUSIONS: Clinical US, using a well codified protocol, could effectively help to identify reversible causes in CA, even improving patients outcome.

Laparoscopic resection of colorectal cancer: matched comparison in elderly and younger patients.

BACKGROUND: Several studies have addressed the issue of the feasibility of laparoscopic colorectal surgery in elderly patients, usually by choosing an arbitrary cut-off age limit, and retrospectively evaluating patient outcomes. The aim of this study was to assess the effects of age on the outcome of laparoscopic colorectal surgery for cancer in a single department, by comparing younger and older patients, matched by ASA score and type of operation. METHODS: The perioperative outcome of patients ≥75 years old who underwent laparoscopic colorectal surgery for cancer between June 2005 and January 2009 were compared with findings in younger patients, matched by ASA score and type of operation. RESULTS: The study included 100 patients, fifty <75 years old (Group A) and fifty ≥75 (Group B) years old. There were 18 right hemicolectomies, 16 left hemicolectomies, 4 anterior resections, 9 low anterior resections, 2 Miles' operations and 1 segmental resection in each group. We observed a significantly higher overall morbidity rate among elderly patients than among younger patients (24 vs. 8%). CONCLUSIONS: Short-term results after laparoscopic colorectal surgery for cancer in patients ≥75 years old reveal that they have higher postoperative risk compared to their younger counterparts, even when matched by ASA score and type of operation. It suggests that although advanced age, per se, is not a contraindication, it is a risk for patients who undergo laparoscopic colorectal surgery for cancer. This surgery in elderly patients should be performed by experienced surgeons in specialized centers to keep postoperative risk to a minimum.

Complex strain induced structural changes observed in fibrin assembled in human plasma.

The structure of the core scaffold of blood clots, the interlinked 3-dimensional network of fibrin fibers, is modified by mechanical forces generated by platelet driven clot retraction, wound repair and shear stress through blood flow. Here X-ray diffraction is used to investigate how uniaxial strain, ε (ε = extension/original length), alters fiber structure in highly aligned human plasma clots covalently cross-linked by Factor XIIIa. Three stretch sensitive axially repeating structures are identified. Firstly, the foundation structure with an initial ≈22 nm axial repeat stretches, fades then disappears at ε ≈ 0.40. A second, lengthened transitory structure emerges at the low strains (ε ≈ 0.20) believed to be developed by cells. Finally, a third shortened structure appears after relaxation. Simultaneously as strain progresses an increasing fraction of molecules become axially disordered. Weak off-axis diffraction maxima indicate the presence of lateral ordering up to ε = 0.40 that partially recovers after relaxation. The reappearance of both axial and lateral order on relaxation demonstrates a surprising resilience in structure. In view of the range and importance of fibrin's functions, this structural heterogeneity, triggered in vivo by cell traction or shear stress, is likely to be of clinical significance.

The use of non-invasive ventilation in the treatment of acute cardiogenic pulmonary edema.

The patient with acute heart failure may present with acute cardiogenic pulmonary edema (ACPE), a condition accompanied by severe respiratory distress, with crackles over the lung and orthopnea, and an O2 saturation usually < 90% on room air, prior to treatment. Non-invasive ventilation is the delivery of assisted ventilation without the need for endotracheal intubation and an invasive artificial airway. Two techniques are used for ventilatory support: continuous positive airway pressure (CPAP) and non-invasive positive-pressure ventilation (NPPV). There is a strong consensus that one of these two techniques should be used before endotracheal intubation and mechanical ventilation because non-invasive techniques dramatically reduce the need for mechanical ventilation via endotracheal intubation and its complications. The aim of this review is to evaluate and resume the evidence for the use of non-invasive positive pressure ventilation in the treatment of acute cardiogenic pulmonary edema according recent literature in order to guide physicians in using CPAP and NPPV in patients affected by ACPE in clinical practice. Recent literature showed that CPAP and NPPV both significantly decrease the need for endotracheal intubation, and CPAP significantly decreases mortality when compared to standard medical treatment. These techniques resulted safe and there is no evidence of increased risk of acute myocardial infarction (AMI) with either of them. Although both CPAP and NPPV present similar efficacy, CPAP has been shown to be cheaper and easier to implement in clinical practice and it could be considered the preferred intervention in patients with ACPE especially in the Emergency Department setting.

Proton pump inhibitors and symptomatic hypomagnesemic hypoparathyroidism.

Hypomagnesemia is a common but often overlooked problem in hospitalized patients. Unrecognized hypomagnesemia can cause serious complications. The association of hypokalemia and hypocalcemia is strongly evocative of a magnesium deficiency. Research into the causes of hypomagnesemia is imperative, as it will definitely change the approach, treatment and prognosis. We report the case of a 65-year-old man with chronic hypocalcemia and hypokalemia associated with cerebellar syndrome, a solitary seizure and cerebellar hyperintensities on magnetic resonance imaging. After the detection and treatment of hypomagnesemia with oral supplements of magnesium and the replacement of pantoprazole with ranitidine, we observed immediate relief of the symptoms. In conclusion, in clinical practice, magnesium depletion should be investigated in elderly patients with hypocalcemia treated with proton pump inhibitors for many years, in particular in the presence of neurological disorders.

Single-band mucosectomy for granular cell tumor of the esophagus: safe and easy technique.

BACKGROUND: Mucosectomy involves resection of a digestive wall fragment that frequently removes a part or even all of the submucosal mass. The single-band mucosectomy technique was used to remove a granular cell tumor (GCT) of the esophagus. Only 3% of GCTs, which are relatively uncommon neoplasms, arise in the esophagus. Ultrasonography has allowed for more frequent recognition and better definition of this disease. Until recently, surgical resection of the esophagus has been the only treatment alternative to endoscopic surveillance. Endoscopic techniques such as mucosal resection (EMR), laser, and argon plasma have been proposed as safe and effective alternatives to surgery. However, to date, only a few reports of these endoscopic techniques have been published. This study aimed to evaluate the safety and feasibility of single-band mucosectomy for removing a GCT of the esophagus. METHODS: Six patients (1 man and 5 women; mean age, 45 years) with a GCT were studied between January 2000 and May 2004. They underwent EMR after endoscopic ultrasonography. RESULTS: The EMR was performed with a diathermic loop after injection of saline solution into the esophageal wall. Only one session was necessary for removal of the tumor from all 6 patients, and no complication was observed. During a mean clinical endoscopic follow-up period of 36 months, no recurrences, scars, or stenoses were observed. CONCLUSIONS: These findings show EMR to be a safe and effective technique that allows complete removal of GCTs. Furthermore, this technique provides tissue for a definitive pathologic diagnosis, which laser and argon plasma do not provide. We recommend EMR as the treatment of choice for GCTs after an accurate ultrasonographic evaluation.

Can clinical and endoscopic findings accurately predict early-stage adenocarcinoma?

BACKGROUND: The presentation and management of esophageal cancer are changing, as more patients are diagnosed at an earlier stage of the disease in which endoscopic treatment methods may be contemplated. Therefore, we conducted a study to determine whether symptomatic and endoscopic findings can accurately identify node-negative early-stage adenocarcinoma. METHODS: A total of 213 consecutive patients (171 men and 42 women) with resectable esophageal adenocarcinoma seen from 1992 to 2002 were evaluated. None of these patients received neoadjuvant chemotherapy or radiation therapy. Using a multivariable model, model-based probabilities of early-stage disease (T1 im/sm N0) were calculated for each combination of the following three features: no dysphagia as main symptom at presentation, tumor length

Minimally invasive enucleation of esophageal leiomyoma.

BACKGROUND: Leiomyoma accounts for 70% of all benign tumors of the esophagus. Open enucleation via thoracotomy has long been the standard procedure, but thoracoscopic and laparoscopic approaches have recently emerged as interesting alternatives. To date, only case reports or very small series of such techniques have been reported. The authors report their experience over the past decade. METHODS: Between January 1999 and August 2005, 11 patients (6 men and 5 women; median age, 44 years) underwent surgery after presenting with dysphagia, chest pain, or heartburn. The surgical approaches included right video-assisted thoracoscopy (n = 7) for tumors of the middle lower third of the esophagus and laparoscopy (n = 4) for tumors within 4 to 5 cm of the lower esophageal sphincter or located at the gastroesophageal junction (GEJ). Intraoperative endoscopy with air insufflation during enucleation was used to confirm mucosal integrity and safeguard against esophageal perforation. Reapproximation of the muscle layers was performed after tumor enucleation to prevent the development of a pseudodiverticulum. A Nissen or Toupet fundoplication was added for patients undergoing laparoscopic enucleation of the leiomyoma. RESULTS: The median operative time was 150 min. All tumors were benign leiomyomas (median size, 4.5 cm). One leiomyoma located at the gastroesophageal junction required intraoperative mucosal repair with three stitches for an esophageal perforation (preoperative biopsies had been taken). There were no major morbidities, including deaths or postoperative leaks. The median postoperative hospital stay was 6 days. All the patients were free of dysphagia during a median followup period of 27 months. One patient had a small (< 2 cm) asymptomatic pseudodiverticulum at the 6-month follow-up endoscopy. CONCLUSIONS: Video-assisted enucleation of esophageal leiomyoma can be performed effectively and safely with no mortality and low morbidity. Thoracoscopic and laparoscopic techniques for the removal of esophageal leiomyomas may be recommended as the treatment of choice in centers experienced with minimally invasive surgery.

Predictive factors of coexisting cancer in Barrett's high-grade dysplasia.

BACKGROUND: Identification of high-grade dysplasia (HGD) in Barrett's esophagus has been considered an indication for esophagectomy because of the high risk for coexisting cancer. However, rigorous endoscopic surveillance programs recently have been recommended, reserving esophagectomy for patients whose cancer is identified on biopsy. This approach risks continued surveillance for patients who already have cancer unless reliable markers for the presence of occult cancer are identified. This study aimed to determine the endoscopic, histologic, and demographic features associated with the presence of occult cancer in patients with HGD. METHODS: Endoscopic, histologic, and demographic findings for 31 patients who underwent esophagectomy for HGD were reviewed. The presence of an ulcer, nodule, stricture, or raised area on preoperative endoscopy was noted. The results of endoscopic biopsies taken before resection every 1 to 2 cm along the Barrett's segment were reviewed. The HGD was categorized as unilevel if the dysplasia was limited to one level of biopsy and as multilevel if more than one level was involved. Patients were divided into two groups according to the presence or absence of cancer in the resected specimens, and these variables were compared. RESULTS: The prevalence of coexisting cancer in patients with HGD was 45% (14/31). Of the 31 patients in this study, 9 had a visible lesion. Cancer was found in the resected specimens from 7 (78%) of 9 patients with a visible lesion and 7 (32%) of 22 patients without a visible lesion (p = 0.019). Of 22 patients without a visible lesion, 10 had multilevel and 12 had unilevel HGD. The findings showed that 6 (60%) of 10 patients with multilevel HGD and 1 (8.3%) of 12 patients with unilevel HGD had cancer in the resected esophagus (p = 0.009). CONCLUSION: For patients with HGD, a lesion visible on endoscopy and/or HGD at multiple biopsy levels is associated with an increased risk for coexisting cancer. These patients should be considered for early esophagectomy.

Bravo capsule induction of esophageal hypercontractility and chest pain.

BACKGROUND: The Bravo catheter-free pH monitoring system uses a capsule attached to the esophageal mucosa to detect acid exposure. Placement of the Bravo capsule is associated with intermittent chest pain in 50% of normal volunteers. The authors hypothesized that chest pain in this setting may be attributable to hypertensive esophageal contractions induced by the Bravo capsule. METHODS: The study population consisted of 40 consecutive patients with reflux symptoms who had stationary esophageal manometry within 1 h after Bravo capsule placement. The control group consisted of 40 patients with symptomatic gastroesophageal reflux disease (GERD) from a population of patients with foregut symptoms who were computer matched to the study group for age, sex, lower esophageal sphincter (LES) pressure, LES length, and 24-h pH composite score. The patients in the control group had manometry before Bravo capsule placement. The occurrence of chest pain was assessed before and during the monitoring period by interview and review of the patient's diary. Mean contraction amplitudes in the distal third of the esophagus after 10 wet swallows were averaged. The prevalence of patients with esophageal contraction amplitudes in the distal third that exceeded the 95th percentile of normal (180 mmHg) and the mean amplitude of distal third esophageal contractions in the study and control populations were compared. In the study group, the incidence of chest pain among the patients with hypercontractility of the esophagus was compared with the incidence among those without hypercontractility. RESULTS: The mean contraction amplitude was higher in the study group (144.7 vs 105.5 mmHg; p = 0.002). The number of patients with a mean distal esophageal contraction amplitude exceeding the 95th percentile of normal also was significantly higher in the study group (13/40 vs 5/40; p = 0.03). A total of 10 patients experienced new onset of chest pain with the Bravo capsule in place, and 6 patients experienced hypertensive esophageal contractions. CONCLUSIONS: The intraesophageal Bravo capsule can cause hypertensive esophageal contractions, which may lead to chest pain.

Approach to respiratory failure in emergency department.

OBJECTIVES AND BACKGROUND: The goal of this review is to provide update recommendations that can be used by emergency physicians who provide primary cares to patients with Acute Respiratory Failure (ARF), from the admission to an emergency department through the first 24 to 48 hours of hospitalization. This work wants to address the diagnosis and emergency medical care of ARF and the management of medical complications. STATE OF THE ART: A lot of statement has been developed for the early management and treatment of ARF; moreover, over the last fifteen years, we have assisted to the rise of a new technique of ventilation, in the Emergency Department: Non Invasive Ventilation. This kind of ventilation was firsthy applied in intensive Care and in Respiratory Care Unit. Randomized controlled clinical trials have showed its usefulness in the early treatment of several forms of ARF, together with medical therapy.

Review of dilated cardiomyopathies. Dilated cardiomyopathies and altered prothrombotic state: a point of view of the literature.

Heart failure is an enormously important clinical problem that, if not faced, may overwhelm health care resources. Primary and secondary cardiomyopathies cause the majority of cases of clinical heart failure, which is thus better approached from the utility point of view of myocardial failure. Furthermore, the risk of thromboembolic complications presenting in such disease may be higher than in ischemic cardiomyopathy. Intracardiac thrombi and mural endocardial plaques (from the organization of thrombi) are present at necropsy in more than 50% of patients with dilated cardiomyopathy (DCM). Several studies have shown that systemic and pulmonary emboli are more frequent in patients with ventricular thrombi or plaques. Dilated cardiomyopathy has been associated with left ventricular thrombosis which leads to substantial morbidity and mortality as a site for peripheral emboli. There are some studies on patients with dilated cardiomyopathy showing altered hemostasis and platelet behavior despite sinus rhythm. Platelet activation, thrombin activation and fibrinolytic activity are increased in patients with DCM compared to normal subjects. However, these markers reflecting coagulation activation in patients with left ventricle thrombus are comparable to those in patients without thrombus in the left ventricle. The pathophysiology and clinical issues concerning the susceptibility to develop left ventricular (LV) thrombosis and its complications like cerebrovascular disease in patients with DCM are summarized and the most recent articles present in the medical literature are reviewed.

The laparoscopic Heller-Dor operation remains an effective treatment for esophageal achalasia at a minimum 6-year follow-up.

BACKGROUND: The aim of this study was to investigate the long-term clinical outcome of the laparoscopic Heller Dor procedure for esophageal achalasia. METHODS: A total of 71 consecutive patients with a minimum 6 year follow-up were evaluated. These patients were seen at 1 and 6 months after the operation (at which time barium swallow, endoscopy, manometry, and pH monitoring were performed), and annually thereafter. A dedicated symptom score, that combined severity and frequency of symptoms was used. RESULTS: The median symptom score decreased from 22 (range, 9-29) preoperatively to 4 (range, 0-16) at last follow-up, (p < 0.01). During the follow-up period, 13 patients suffered symptom recurrence; seven of them (54%) had already been diagnosed at the 1-year follow-up. All of these patients were treated with complementary pneumatic dilations. Overall, at a minimum of 6- years after the operation, 81.7% of the patients were satisfied with the treatment and were able to eat normally. CONCLUSIONS: The long-term outcome of laparoscopic surgical treatment of esophageal achalasia is only slightly affected by the length of the follow-up and most of the symptomatic failures occur in the early period after the operation.

Brain natriuretic peptide and acute coronary syndrome.

The natriuretic peptide system (atrial natriuretic peptide, brain natriuretic peptide, BNP, and C natriuretic peptide) is an important marker of cardiac failure. These peptides are synthesized in atrial or ventricular myocytes in response to wall tension. In several studies the correlation between high BNP levels and mortality, in patients with acute coronary syndrome and heart failure, has been demonstrated. On the other hand, plasma levels of BNP could be considered as independent predictors of mortality in patients with heart failure. BNP could be used, for instance, as an early diagnostic marker for the differential diagnosis between cardiogenic and non cardiogenic dyspnea. In the Emergency Department its use will be important in the diagnosis of thoracic pain origin since it may help in the diagnostic and therapeutic course of this patient and to define the modality of hospitalization. Moreover, it can be used as a marker of heart failure severity and as an important negative prognostic factor. Some studies have confirmed that plasma BNP reflects the degree of left ventricular dysfunction and the prognostic significance after acute myocardial infarction and chronic heart failure.

How to use the C-reactive protein in cardiac disease?

Inflammation is an important contributor to atherothrombosis. The C-reactive protein (CRP) is not only an excellent biomarker of inflammation, but it is also a direct participant in atherogenesis. CRP consistently predicts new coronary events, including myocardial infarction and death, in patients with ischemic heart disease. The predictive value of CRP is, in the majority of the studies, independent of and additive to that of the troponins and its levels can be modulated by statins. Prospective observational studies show that moderately elevated levels of CRP are associated with an adverse cardiovascular prognosis among healthy individuals. The availability of high sensibility assays for CRP should provide a valuable tool for identifying patients at risk of cardiovascular events in primary prevention in conjunction with lowering LDL cholesterol and may also have utility in the treatment of acute coronary syndromes with percutaneous coronary intervention (PCI) therapy. High CRP levels, associated with a higher risk, should suggest a more aggressive medical therapy in the long term and also an aggressive and invasive therapy in the short term, including the use of GP IIb/IIIa inhibitors, high doses of statins, and when a PCI is necessary, provisional stenting. Finally, CRP will provide a readily accessible marker for further testing of the inflammatory hypothesis in atherosclerosis.

Heart failure and therapy.

The clinical syndrome of heart failure is the final outcome of a number of diseases affecting the heart. Several studies undertaken over the past decade, have led to a significant change in the therapies available and a growing understanding of the physiopathological mechanisms. Increasingly, the current treatment of heart failure, is not just symptomatic but also etiologic and physiopathologic. In this paper we will try to furnish guidelines, as practical as possible, for the treatment of this syndrome, addressing the physiopathologic and experimental principles which underlie it. The present suggestions are based on the updated literature review, they conform to the latest guidelines of the European Society of Cardiology and are in agreement with the classification in grades, proposed by the American Heart Association and the American College of Cardiology.