The use of radiation therapy for oligoprogressive/oligopersistent oncogene-driven non small cell lung cancer: State of the art.

Oncogene-driven non small cell lung cancer (NSCLC) is a distinct entity in thoracic oncology. The availability of effective target therapies, like EGFR inhibitors or ALK inhibitors, have revolutionized the prognosis of these patients. However, despite an initial response in the majority of patients, drug resistance ultimately occurs. In some cases, this resistance develops in few clonal cells (oligoprogression), so that a local ablation of these resistant deposits could allow to maintain the same systemic therapy and possibly to prolong patients' survival. For these purposes, stereotactic body radiation therapy (SBRT) is an ideal local ablative treatment, because it is effective, non invasive and with limited side effects. In this review, we aim to analyze available clinical data to verify whether SBRT can allow these patients to continue with existing target therapy longer, delay the switch to other systemic therapies and improve their outcome modifying the natural history of the disease.

Calcifilaxis, a propósito de un caso / Calciphylaxis, about a case

Resumen La calcifilaxis es un síndrome caracterizado por la calcificación de la pared media de las arteriolas de pequeño y mediano calibre de dermis y tejido celular subcutáneo, que se caracteriza clínicamente por úlceras necróticas, intensamente dolorosas, que afectan sobre todo miembros inferiores. Existen factores de riesgo para su desarrollo, como insuficiencia renal crónica, hiperparatiroidismo, sexo femenino, raza caucásica, diabetes, uso de anticoagulantes, entre otros. Si bien no existe un protocolo estandarizado para su tratamiento, se ha propuesto el uso del tiosulfato sódico como primera elección. Se presenta el caso de una paciente de sexo femenino de 75 años de edad con diagnóstico de calcifilaxis.

Abstract Calciphylaxis is a syndrome characterized by calciphication of the media of small and medium vessels of dermis and subcutaneous celular tissue, clinically characterized by extremely painful, necrotic ulcers, that affects especially lower limbs. There are risk factors for its development, such as renal failure, hyperparathyroidism, female gender, caucasian race, diabetes, use of anticoagulants, among others. Although there is not a standarized protocol for the treatment, it has been proposed the use of sodium thiosulfate as first line. We report a case of a woman of 75 years old with calciphylaxis.

A MSFD complementary approach for the assessment of pressures, knowledge and data gaps in Southern European Seas: The PERSEUS experience.

PERSEUS project aims to identify the most relevant pressures exerted on the ecosystems of the Southern European Seas (SES), highlighting knowledge and data gaps that endanger the achievement of SES Good Environmental Status (GES) as mandated by the Marine Strategy Framework Directive (MSFD). A complementary approach has been adopted, by a meta-analysis of existing literature on pressure/impact/knowledge gaps summarized in tables related to the MSFD descriptors, discriminating open waters from coastal areas. A comparative assessment of the Initial Assessments (IAs) for five SES countries has been also independently performed. The comparison between meta-analysis results and IAs shows similarities for coastal areas only. Major knowledge gaps have been detected for the biodiversity, marine food web, marine litter and underwater noise descriptors. The meta-analysis also allowed the identification of additional research themes targeting research topics that are requested to the achievement of GES.

The sap from Euphorbia peplus is effective against human nonmelanoma skin cancers.

BACKGROUND: The sap from Euphorbia peplus, commonly known as petty spurge in the U.K. or radium weed in Australia, has been used as a traditional treatment for a number of cancers. OBJECTIVE: To determine the effectiveness of E. peplus sap in a phase I/II clinical study for the topical treatment of basal cell carcinomas (BCC), squamous cell carcinomas (SCC) and intraepidermal carcinomas (IEC). METHODS: Thirty-six patients, who had refused, failed or were unsuitable for conventional treatment, were enrolled in a phase I/II clinical study. A total of 48 skin cancer lesions were treated topically with 100-300 µL of E. peplus sap once daily for 3 days. RESULTS: The complete clinical response rates at 1 month were 82% (n = 28) for BCC, 94% (n = 16) for IEC and 75% (n = 4) for SCC. After a mean follow-up of 15 months these rates were 57%, 75% and 50%, respectively. For superficial lesions < 16 mm, the response rates after follow-up were 100% for IEC (n = 10) and 78% for BCC (n = 9). CONCLUSIONS: The clinical responses for these relatively unfavourable lesions (43% had failed previous treatments, 35% were situated in the head and neck region and 30% were > 2 cm in diameter), are comparable with existing nonsurgical treatments. An active ingredient of E. peplus sap has been identified as ingenol mebutate (PEP005). This clinical study affirms community experience with E. peplus sap, and supports further clinical development of PEP005 for the treatment of BCC, SCC and IEC.

Muscle enzyme elevation after elective neurosurgery.

BACKGROUND: Serum creatine kinase and myoglobin elevation has been described involving muscle manipulation after surgery and also after bariatric, urologic and gynaecologic procedures. It encompasses a wide range of severity, reflecting in the worst cases true rhabdomyolysis. We occasionally noted creatine kinase elevations after intracranial neurosurgery, an occurrence that has not yet been described. To assess whether the issue of postoperative muscle enzyme elevation is relevant to neurosurgery, we prospectively measured serum creatine kinase and myoglobin in a series of neurosurgical patients submitted to craniotomy. MATERIALS AND METHODS: We studied 30 patients aged 22-69 yr submitted to craniotomy. Blood samples were taken prior to the procedure, at the end of anaesthesia and on the first, second and third postoperative days. Blood was checked for creatine kinase, myoglobin, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine and serum electrolytes. We recorded the patient's age, sex, height, weight and body mass index. Throughout surgery, we recorded the highest and the lowest body temperature and sampled the mean arterial pressure at 5 min intervals. We performed backwards stepwise logistic regression analysis to identify the elements that best correlate with the development of cell muscle damage. RESULTS: On the first postoperative day creatine kinase peaked from baseline (305 (107-1306) UI L(-1) vs. 59 (42-94) UI L(-1); P < 0.001) while myoglobin rose significantly from baseline to the end of surgery (70 (42-147) ng mL(-1) vs. 36 (3044) ng mL(-1); P = 0.002). Logistic regression showed that length of surgery was the only factor clearly influencing peak creatine kinase (P < 0.001; R2 0.7) and myoglobin (P = 0.011; R2 0.41) concentration. CONCLUSIONS: Creatine kinase and myoglobin elevation may occur after intracranial neurosurgery. In our series, length of surgery was a risk factor.

Temperature-activity relationship for the intestinal Na+-K+-ATPase of Sparus aurata. A role for the phospholipid microenvironment?

The temperature dependence for Na(+)-K(+)-ATPase has been examined in the proximal-distal axis of the intestine of gilthead seabream (Sparus aurata), i.e. pyloric caeca (PC), anterior intestine (AI) and posterior intestine (PI). Data derived from the Arrhenius plots showed differences in terms of temperature discontinuity points ( Td) (13.29 degrees C, 16.39 degrees C and 17.48 degrees C for PC, AI and PI, respectively) and activation energy ratios (Ea(2)/Ea(1)) obtained at both sides of Td (2.38, 1.98 and 1.78, for PC, AI and PI, respectively). The analyses of polar lipids showed differences in the levels of certain fatty acids among intestinal regions. The content of each fatty acid and different fatty acid ratios were correlated with the corresponding Td and Ea(2)/Ea(1) values. Regression analyses revealed the existence of strong negative correlations between docosahexaenoic acid (22:6n-3, DHA) or the DHA/monoenes ratio and Td. No obvious relationships were observed for other polyunsaturated fatty acids (PUFA) nor saturated fatty acids. The results obtained in the present study indicate that the heterogeneous values of Td displayed by the Na(+)-K(+)-ATPase along the intestinal tract could be related to a modulatory role of certain fatty acid within the lipid microenvironment of the enzyme.

Fatal Kikuchi-Fujimoto disease: the lupus connection.

Kikuchi-Fujimoto disease (KFD) is a histiocytic necrotizing lymphadenitis found mainly in young women. Patients typically present with cervical lymphadenopathy and fever and follow almost always a benign course with excellent outcomes. The etiology of KFD remains unknown and controversial although several viruses have been associated with this disease. One theory proposes that KFD may be a self-limiting form of systemic lupus erythematosus (SLE). This theory is strongly supported by the fact that microscopic features of KFD can be very similar to those found in lupus lymphadenitis. Despite its usually benign course, several cases with fatal outcomes have been reported. We report here a case of clinically aggressive KFD, which featured several autoimmune-related events and resulted in a fatal outcome. Autopsy studies showed characteristic findings of SLE, which suggests a remarkable link between SLE and KFD. Early and intensive immunosuppressive treatment may be the only option for patients who develop very aggressive forms of KFD in order to avoid a fatal outcome.

Surgical tracheostomy versus percutaneous dilatational tracheostomy. A prospective-randomized study with long-term follow-up.

BACKGROUND: To compare surgical tracheostomy (ST) versus percutaneous dilatational tracheostomy (PDT) in terms of complication rates. In particular we specifically studied the late tracheal complications of both methods by means of endoscopic controls of patients up to 6 months after the procedures. DESIGN: prospective-randomized clinical study. SETTING: University-affiliated tertiary care referral hospital. PATIENTS: 50 consecutive translaryngeally intubated patients with respiratory failure were randomized to undergo either ST (25 patients) or endoscopic guided PDT (25 patients). RESULTS: ST was performed in 41+/-14 min versus 14+/-6 min for PDT (p<0.0001). There was no procedure-related death. In the ST group there were no intraoperative complications. In the PDT group 2 intraoperative complications (minor hemorrhages) were observed. In the ST group 9 early postoperative complications occurred: one minor bleeding, 7 stomal infections and one accidental decannulation. In the PDT group only one early postoperative complication (minor bleeding) occurred. Early postoperative complication rates were 36% for ST and 4% for PDT. In the ST group there were no late tracheal complications. In the PDT group 2 late tracheal complications (one segmental malacia and one stenosis at the level of the stoma) were observed. CONCLUSIONS: This study confirms that PDT is a simpler and quicker procedure than ST and that it has a lower rate of early postoperative complications. Late tracheal complications were more frequent, although the difference was not statistically-significant, in the PDT group. Further investigations of long-term outcome following PDT are therefore necessary.

Segmental heterogeneity in the biochemical properties of the Na+-K+-ATPase along the intestine of the gilthead seabream (Sparus aurata L.).

The activity of the Na+-K+-ATPase along the intestinal mucosa of the gilthead seabream has been examined. Under optimal assay conditions, found at 35 degrees C, pH 7.5, 2-5 mM MgCl2, 5 mM ATP, 10 mM K+ and 200 mM Na+, maximal Na+-K+-ATPase activities were found in the microsomal fraction of pyloric caeca (PC) and anterior intestine (AI), which were more than two-fold the activity measured in the microsomes from the posterior intestine (PI). Na+-K+-ATPase activities from PC, AI and PI displayed similar pH dependence, optimal Mg2+/ATP and Na+/K+ ratios, affinities for Mg2+ and ATP, and inhibition by vanadate. However, considerable differences regarding sensitivity to ouabain, inhibition by calcium and responses to ionic strength were observed between segments. Thus, Na+-K+-ATPase activity from the AI was found to be ten-fold more sensitive to ouabain and calcium than the enzyme from the PC and PI and displayed distinct kinetic behaviours with respect to Na+ and K+, compared to PC and PI. Analysis of the data from the AI revealed the presence of two Na+-K+-ATPase activities endowed with distinguishable biochemical characteristics, suggesting the involvement of two different isozymes. Regional differences in Na+-K+-ATPase activities in the intestine of the gilthead seabream are compared with literature data on Na+-K+-ATPase isozymes and discussed on the basis of the physiological differences between intestinal regions.

Elective coronary stent implantation in cardiogenic shock complicating acute myocardial infarction: in-hospital and six-month clinical and angiographic results.

Effective treatment of patients with acute myocardial infarction and cardiogenic shock depends on restoring persistent patency of the infarct-related artery. Coronary stenting, reducing abrupt or delayed closure related to dissection and suboptimal result, may improve PTCA results in cardiogenic shock. Eighteen patients (14 males and 4 females, mean age 59 +/- 7 years), referred to catheterization laboratory for acute myocardial infarction and shock, had elective stent implantation during 14 primary and 4 rescue PTCA. Time delay between shock onset and PTCA was 4.1 +/- 3 hr (range, 30 min to 12 hr). The IRA was LAD in seven patients (38%), LCx in two (11%), and RCA in eight (45%). One patient (5.%) had distal LMCA occlusion. Stent deployment was successful in 100% of patients and resulted in TIMI 3 flow in 13 (72%) patients. In 13 (72%) cases, cardiogenic shock gradually resolved and the patients were discharged alive. Five patients (28%) died because of irreversible hemodynamic deterioration without evidence of reinfarction. At 6-month follow-up, all the discharged patients were alive and no patient had reinfarction or recurrent angina. Heart transplant was required in one patient 5 months after stenting because of refractory congestive heart failure. Angiography demonstrated patency of all the coronary arteries treated, with TIMI 3 flow in all patients. Stent restenosis rate was 30%, and target lesion revascularization with CABG or re-PTCA was not required in any case. LV function improved from 39% +/- 15% to 51% +/- 15% (P < 0.01). Elective coronary stenting is an effective treatment for acute myocardial infarction complicated by cardiogenic shock and may improve acute and long-term survival.

Use of a new diagnostic catheter for transradial internal mammary artery angiography early after minimally invasive coronary bypass.

We describe a new diagnostic catheter specifically designed for selective catheterization of the left internal mammary artery via the ipsilateral radial approach. We used this catheter to assess the patency of the distal mammary-left anterior descending coronary artery anastomosis in 30 consecutive patients early after minimally invasive direct coronary artery bypass grafting. The new catheter design allowed easy and fast engagement of the left internal mammary artery leading to optimal vessel opacification in all cases. Angiography revealed graft problems in seven (23.3%) patients, two of whom required anastomosis revision, surgical in one case and with PTCA in the other. No LIMA injury occurred as a result of selective catheterization. Patients with functionally normal anastomosis were discharged on the same day of the diagnostic procedure.

Successful dissolution of occlusive coronary thrombus with local administration of abciximab during PTCA.

Treatment of intracoronary thrombus poses difficult problems and may result in severe complications. We used a local delivery catheter (InfusaSleeve, LocalMed, Palo Alto, CA) to treat an occlusive coronary thrombus that was refractory to systemic thrombolysis and conventional angioplasty. After local administration of 10 mg of abciximab with this catheter there was successful resolution of coronary thrombus and vessel recanalization. Cathet. Cardiovasc. Intervent. 48:211-213, 1999.

[Percutaneous or surgical trachetomy. Prospective, randomized comparison of the incidence of early and late complications]. / Tracheotomia percutanea e chirurgica. Confronto prospettico, randomizzato dell'incidenza di complicanze precoci e tardive.

BACKGROUND: To compare early and late complications after either conventional surgical or percutaneous dilatational tracheostomy. DESIGN: Prospective, randomized study. SETTING: General intensive care unit and neuro-surgical intensive care unit in a university hospital. PATIENTS: 50 consecutive patients, requiring tracheostomy for prolonged mechanical ventilation. INTERVENTIONS AND MEASUREMENTS: Patients were randomly allocated to receive either surgical (surgical group, n = 25) or percutaneous dilatational tracheostomy (percutaneous group, n = 25). Occurrence of perioperative complication were carefully evaluated during ICU stay. Late complications were evaluated with both physical and endoscopic examination at 1, 3 to 6 months after tracheostomy. RESULTS: All surgical and percutaneous tracheostomies were successfully completed and no deaths directly related to the tracheostomy procedures were reported. Completion of the procedure required 41 +/- 14 min in the surgical group and 14 +/- 6 min in the percutaneous one (p < 0.0001). The incidence of early perioperative complications was higher in the surgical group (36%) than in percutaneous one (12%), (p < 0.05). The endoscopic follow-up demonstrated one segmental malacia and one stenosis of the trachea in the percutaneous group only (p = n.s.). Skin repair was better after percutaneous tracheostomy than in the surgical group (p < 0.01). CONCLUSIONS: In experienced hands, percutaneous dilatational tracheostomy is as safe and effective as the conventional surgical tracheostomy. The percutaneous technique is less time-consuming and has a lower rate of early infectious complications with better cosmetic results than the surgical technique.

Seasonal fluctuations of DIN/DIP and DON/DOP ratio in the northern Adriatic Sea.

Within the frame of PRISMA 1 "Biogeochemical cycles" research project (April 1995-January 1996) the quantities and the compartments of dissolved nitrogen and phosphorus have been studied in the northern Adriatic basin, considering also the organic pools. The research aimed to provide a better understanding of nutrient availability and to investigate the possible factors which promote the phenomenon of mucilage formation. For this purpose, the availability and the ratios between dissolved nitrogen and phosphorus considering both inorganic and organic fractions have been studied in relation to variations of river outflow and of biological activities. The results obtained reveal the large importance of organic nitrogen (annual average 16 microM) and phosphorus (annual average 0.13 microM) in contributing to the total nutrient availability (annual average total dissolved nitrogen: 29 microM and phosphorus: 0.18 microM) and the pronounced seasonal variability mainly ascribable to biological processes of uptake and remineralization. Furthermore, beside the well documented unbalanced ratio between inorganic nitrogen and phosphorus, the results obtained point out, for the first time, the unbalance also in the organic compartment (ratio between organic nitrogen and phosphorus ranges between 50 and 530), whose consequences might be important in relation to the phenomenon of mucilage formation.

[Implantation of the Palmaz-Schatz stent in coronary vessels irrigating and non-irrigating necrotic myocardial areas: comparison of acute results and at mid-term]. / Impianto di stent di Palmaz-Schatz in vasi coronarici tributari e non tributari di aree miocardiche necrotiche: confronto dei risultati acuti e a medio termine.

Recent evidence suggests that higher restenosis rate is observed after coronary angioplasty of an infarct-related artery. Furthermore, angiographic restenosis seems associated with a deterioration of left ventricular function at follow-up. The aim of this study was to assess the acute results and angiographic restenosis following coronary artery stenting of infarct-related (Group 1) and non infarct-related coronary arteries (Group 2). We retrospectively analyzed the results of 381 consecutive patients treated with Palmaz-Schatz coronary stent implantation between May 1992 and January 1996. Stenting of the infarct-related artery was performed in 154 patients (Group 1), while 227 patients (Group 2) received stenting of the non infarct-related artery. Both groups had similar age, gender, clinical conditions and coronary angiographic pattern. There were no significant differences between groups, concerning type of stented coronary vessel (left anterior descending-LAD 52.4% vs non-LAD 47.6%, Group 1, LAD 59.5% vs non-LAD 40.5%, Group 2) and number of stents per patient (1.31 +/- 0.48 in Group 1, 1.18 +/- 0.56 in Group 2) and per coronary vessel (1.17 +/- 0.54 in Group 1, 1.09 +/- 0.46 in Group 2). The procedure was performed using similar maximal inflation pressures in both groups (13.3 +/- 2.9 atm in Group 1, 13.40 +/- 3.17 atm in Group 2). Technical success was achieved in 96.8% of Group 1 and in 96% of Group 2 patients. Acute coronary stenting success and major adverse events (acute myocardial infarction, emergency bypass, death) were similar in both groups of patients. No difference was found in restenosis rate at 6-month angiographic follow-up (Group 1 = 29.8%, Group 2 = 27%). In conclusion, this study indicates that stenting of infarct and non infarct-related coronary arteries has similar success and 6-month restenosis rates.

7.5% hypertonic saline versus 20% mannitol during elective neurosurgical supratentorial procedures.

This prospective randomized clinical study was designed to compare the effects of equal volumes of 7.5% hypertonic saline solution (HS) or 20% mannitol (M) on brain bulk and lumbar cerebrospinal fluid pressure (CSFP) during elective neurosurgical procedures (aneurysm, arteriovenous malformation, or tumor). After informed consent, 50 American Society of Anesthesiologists physical Status I (ASA I) patients were randomly assigned to M (n = 25) or HS (n = 25) groups. Anesthesia protocol was identical for both, and variables monitored included mean arterial blood pressure (MAP), heart rate (HR), central venous pressure (CVP), CSF pressure (CSFP), arterial blood gases (PaCO2 30-35 mm Hg), serum sodium, potassium, and osmolality, and diuresis. The study period started before hypertonic solution administration (T0) and ended at the opening of the dura mater or 60 min after T0. Data were assessed with repeated measures analysis of variance and Student t test with Bonferroni correction (p < or = 0.05). MAP and CVP were the same in the two groups. After treatment, osmolality increased, and the increase at T15 was higher in HS-treated patients [316.6 +/- 9.3 vs. 304.0 +/- 12.0 (SD) mOsmol/kg; p < 0.001]. Sodium decreased after M and increased after HS. During the study, brain bulk was always considered satisfactory. CSFP was not different between M and HS groups and significantly decreased overtime (p = 0.0056) with no difference between treatments. The results of the present study demonstrate that hypertonic saline is as effective as mannitol in reducing the brain bulk and the CSFP during elective neurosurgical procedures under general anesthesia.