Main changes in European Clinical Trials Regulation (No 536/2014).

The new Regulation (EU) No. 536/2014 for clinical trials of medicinal products for human is part of a European regulatory framework in which the European Commission has wished to give a strong impetus to scientific research and industrial progress. It is a new regulation that fills a series of regulatory gaps in the Clinical Trials through the creation of a uniform framework for the authorization of clinical trials by all interested Member States with a single assessment of the results. The Regulation thus facilitates cross-border cooperation to make the clinical tests wider and encourage the development of special treatments, for example for rare diseases, but above all streamlines the rules on clinical trials across European Union (EU), introducing simplified rules for experimentation so-called 'low level of intervention', on which much has been discussed and still arouses concern, providing for authorized medicines or used off-label in the presence of scientific evidence published on efficacy and safety and to benefit from they will be mainly the pediatric and oncological therapeutic areas. The applications and any communication will be submitted paperlessly via a new electronic EU portal. The complex processing procedures and shorter time limits are to be stressed in comparison to the previously valid regulations. This is a major challenge for all stakeholders, but on the other hand it should contribute to the future role of the EU in the development of innovative medicines.

Cauda equina syndrome: evaluation of the clinical outcome.

AIM: Cauda equina syndrome is a rare but highly impairing syndrome involving lower limbs as well as urinary, defecatory and sexual function. In the literature the most investigated sphincter dysfunction is the urinary. Bowel and sexual function are often overlooked since they become more relevant after the acute phase. PATIENTS AND METHODS: Eight consecutive male patients affected by cauda equina syndrome with sphincter dysfunction due to herniated disc disease of lumbar spine were treated between 2007 and 2009. Five patients were followed-up for at least two years. Sexual function was evaluated by IIEF-5 questionnaire; bowel function was investigated by means of clinical and instrumental investigation and manometry. RESULTS: Although little clinical improved, patients still complained severe symptoms at first year follow-up while all but one improved significantly in the following year. At two years follow-up only the patient whose cauda equina syndrome was misdiagnosed and surgically treated late respect to the onset of the syndrome, complained a persistent severe sexual and bowel dysfunction. CONCLUSIONS: Our results show that a long-term follow-up is mandatory to evaluate the real outcome of surgical managed cauda equine syndrome because short-term evaluation could be misleading about the residual capacity of late neurologic improving. Despite the relatively low number of cases evaluated, our results confirm that early diagnosing and treating the syndrome are relevant for the final outcome.

Occiput posterior position diagnosis: vaginal examination or intrapartum sonography? A clinical review.

The occiput posterior (OP) position is one of the most frequent malposition during labor. During the first stage of labor, the fetal head may stay in the OP position in 30% of the cases, but of these only 5-7% remains as such at time of delivery. The diagnosis of OP position in the second stage of labor is made difficult by the presence of the caput succedaneum or scalp hair, both of which may give some problem in the identification of fetal head sutures and fontanels and their location in relationship to maternal pelvic landmarks. The capability of diagnosing a fetus in OP position by digital examination has been extremely inaccurate, whereas an ultrasound approach, transabdominal, transperineal and transvaginal, has clearly shown its superior diagnostic accuracy. This is true not only for diagnosis of malpositions, detected in both first and second stage of labor, but also in cases of marked asynclitism.

Suprapubic percutaneous sclero-embolization of symptomatic female pelvic varicocele under local anesthesia.

PURPOSE: To evaluate the safety and feasibility of supra-pubic percutaneous sclero-embolization (SE) in the treatment of symptomatic female pelvic varicocele (FPV), performed under local anesthesia. MATERIALS AND METHODS: The authors selected 28 patients screened by transabdominal and transvaginal ultrasound, with venous Doppler signal. Clinicians performed SE by transfemoral catheterization, under local anesthesia, using of a mix of 2 ml of lauromacrogol 400 (Atossisclerol 3%, Chemische F. Kreussler, Wiesbaden, Germany) and 2 ml of air, in a mixed foam fashion. RESULTS: The total operative time for SE was 7.6 +/- 2.1 min. Intra-surgical blood loss was 40 +/- 14 ml. No migration of sclerosant material occurred and postoperative analgesic request during a 48 hr period occurred in 6 patients. Technical success was 100%. The Authors embolized 8 women bilaterally (28.5%), 18 on the left ovarian vein (OV) (64.2%) and 2 only in the right OV (7.1%): 7 women complained of transitory flank pain (25%), which disappeared in few minutes. The major complications in 10 days after SE were: fever (> 38 degrees C for two days) in 2 patients (7.1%) and pelvic pain for 3 days in eight patients (28.5%). After 30 days only 6 women suffered of FPV lower symptoms which disappeared in 180 days. A substantial reduction in size of pelvic varicosities was noted in all patients. CONCLUSIONS: SE is a safe and feasible procedure. It reduces significantly the mean time of scopies, the intensity of radiation emission, and it is performed under local anaesthesia. This minimally invasive procedure could be proposed to all women with supra-pubic FPV for its reproducibility and feasibility.

Intrapartum sonography head transverse and asynclitic diagnosis with and without epidural analgesia initiated early during the first stage of labor.

PURPOSE: To investigate if early epidural analgesia can influence fetal head engagement into the pelvis and if it can increase the rate of transverse and asynclitic position during labour. MATERIALS AND METHODS: 195 women with combined spinal-epidural analgesia (CSE) or without neuraxial analgesia were studied. CSE was performed using a mixture of ropivacaine 0.02% with 0.3 microg/ml of sufentanil administered in the spinal space. Maintenance of analgesia was managed with intermittent epidural administration of 10-15 ml of ropivacaine (0.07%-0.10%) mixed with 0.5 microg/ml of sufentanil, based on the stage of labour and the degree of pain. 2D transabdominal ultrasound (US) was used. Serial transabdominal US examinations were performed at 45-90 min intervals to detect transverse and asynclitic positions, using the following signs: squint sign, sunset thalamus and cerebellum signs that best details the fetal head station. After delivery, the complete set of clinical and US data obtained by each examination were recorded and compared in women with and without labour analgesia. Data were examined by independent reviewers. RESULTS: There was no difference in obstetric outcome between women in whom CSE had been used and those who did not request analgesia during labour (p > 0.05). CONCLUSIONS: Epidural analgesia initiated early during labour and using low doses does not increase the rate of dystocic labors. Transverse fetal head positioning with anterior or posterior asynclitism does not seem to be promoted by drug or technique-related mechanisms, but rather should be the consequence of cephalopelvic disproportion.

Bedside burr hole for intracranial pressure monitoring performed by intensive care physicians. A 5-year experience.

OBJECTIVE: To assess the results of a 5-year experience with bedside burr hole for intracranial pressure (ICP) monitoring performed by intensive care physicians. DESIGN: Prospective, observational study in 120 patients. SETTING: A general-neurologic Intensive Care Unit in a University Hospital. PATIENTS: Patients admitted for acute neural lesion requiring ICP monitoring. METHOD: A 2.71 mm burr hole was made with positioning of a subarachnoid screw, through which a miniaturized fiberoptic, tip transducer device (Camino) was advanced and inserted 2 mm in the frontal cortex. MAIN RESULTS: Over a 5-year period 120 patients, mainly with severe head trauma, underwent ICP monitoring. None of the planned patients was excluded because of technical difficulties. No life-threatening complications were reported, and the overall morbidity rate related to the ICP monitor was 3.3%. Complications were infectious in nature, with 2.5% wound infections and 0.8% meningitis. Although seven patients bled when opening the dura, no intracranial hematomas were recorded due to the ICP monitor. The fiberoptic device was left in place for 5 +/- 1.6 (SD) days (range 1-12 days). Five patients (4.1%) required catheter substitution due to breakage of the system components (fiberoptics). CONCLUSIONS: Bedside insertion of a ICP monitor performed by intensive care physicians is a safe procedure, with a complication rate comparable to other series published by neurosurgeons. The overall morbidity rate is comparable to, or even lower than, that caused by central vein catheterization.

Improved equipment for abdominal fetal electrocardiogram recording: description and clinical evaluation.

Reliable computer-based equipment for transabdominal or indirect recording of fetal electrocardiogram (FECG) is described. The proposed equipment allows a real-time displaying of the signals (fetal + maternal ECG) without averaging procedures and it does not require the employment of a shielded room; moreover, it is user-friendly to medical personnel. An elementary form of semi-automatic computation of the fetal heart rate (FHR) was also implemented. The equipment simultaneously acquires three signals from seven electrodes, six placed on the maternal abdomen following the three space axes, and one placed on the left leg as a indifferent electrode. The signals are magnified and analogically filtered before undergoing digital finite impulse response (FIR) filter. Then the signals are displayed on the screen of a personal computer (PC). The PC also provides the possibility of storing the acquired signals for further analysis of elaborations. The quality of the recordings allows the analysis of both the rapid and slow electrical phenomena of the fetal heart, and it is not significantly influenced by the occurrence at the same time of uterine contractions. The performance of this method was assessed in 140 pregnant women with gestation periods of 29-42 weeks. In 131 cases (93.6%) the fetal QRS complex was detected and the FHR was obtained. A reliable evaluation of P and QRS waves and of ST interval, in spite of the interference of the maternal complexes, was possible in 102 cases (72.8%).

Ischaemic pontomedullary transection with incomplete locked-in syndrome. A case report with MRI.

We describe a case of incomplete locked-in syndrome (LIS) due to basilar artery thrombosis, in which MRI showed a complete, sharply demarcated infarct at the pontomedullary junction. This supports experimental data showing that the lower reticular formation is not critical for the maintenance of consciousness. To our knowledge, this is the first reported case of ischaemic pontomedullary transection with LIS.

[Total intravenous anesthesia with propofol-fentanyl. Experience with elective operations in plastic surgery]. / Anestesia endovenosa totale con propofol-fentanyl. Esperienza in interventi di elezione in chirurgia plastica.

The Authors evaluated a total intravenous anesthesia with propofol and fentanyl in patients who underwent elective plastic surgery. Main hemodynamic parameters resulted particularly stable, and the awakening times which resulted brief and independent from the anesthesia duration have been measured.

Free radical-induced lipoperoxidation and severe head injury. A clinical study.

Ten severely head injured patients (GCS less than or equal to 8), aged 17-62 years, were studied in order to investigate the role of lipoperoxidation in secondary brain damage. No patients had intracranial mass lesions, shock, hypoxemia, fever or sepsis. Blood samples were taken from the jugular bulb and from the right atrium, and thiobarbituric acid reacting substances (TBARS) were measured in plasma by spectrophotometry. Arterio-jugular venous oxygen differences (AVDO2) were obtained in seven patients, in order to estimate cerebral blood flow. Jugular TBARS (TBARSj) were always elevated (from To, to 2 h after injury) and correlated in a linear fashion with TBARS of right atrium (TBARSv): r = 0.74, p less than 0.001. TBARSj and AVDO2 are closely correlated, in accordance with an exponential function (R = 0.45, p less than 0.001) which describes how any cerebral perfusion derangement determines high levels of TBARSj, confirming lipoperoxidation as a key factor in the final common pathway of secondary posttraumatic brain damage.