[Epidemiologic analysis of patients afferent to the ICU]. / Studio epidemiologica sull'attività del centro di rianimazione.

BACKGROUND: To understand in- and out-patients flow to and from an ICU during a year (1998). The setting of the study was an 8-beds Intensive Care Unit of a 480-beds General Hospital with an Emergency Department. METHODS: Retrospective analysis by a specific designed software of all patient data extrapolated from the hospital database, in order to: 1) Divide all ICU patients in four groups, according to the first admission Department; 2) Classify all ICU patients into 3 subgroups: a) medical; b) surgical; c) trauma; 3) Evaluate the different needs of ICU resources in these different patient populations. RESULTS: Two hundred and fifty-four patients were admitted to our ICU during the study period (1.2% of all admissions). The mean duration of ICU stay was 10.4 days. Thirty-five per cent of ICU admissions came from the Emergency Department, 61% of ICU patients were discharged to another hospital ward, while the remaining 7% had to be transferred to a different hospital; 2.8% of our patients had ICU re-admissions. The overall mortality rate was 32%. CONCLUSIONS: Compared with previously reported data, a lower re-admission rate (3%), a longer mean stay in the ICU (>10 days) and a higher occupancy rate (91.4%) were observed. These data suggest that a large part of the available resources for the intensive care in our hospital are devoted to the in-hospital patient care. The hypothesis is suggested that this could be mainly due to the lack of sub-critical care areas.

Local application of radiolabeled monoclonal antibodies in the treatment of high grade malignant gliomas: a six-year clinical experience.

BACKGROUND: Infusion of radiolabeled monoclonal antibodies (MAbs) directly into a tumor or into the site of disease after surgery concentrates a high quantity of antibody and radioisotope in the neoplastic tissue. The strong irradiation delivered by this method can result in control of high grade malignant gliomas. METHODS: Antitenascin MAbs BC-2 and BC-4 labeled with 131I (mean dose, 1998 MBq) were injected into 105 patients with malignant glioma by means of an in-dwelling catheter. Multiple courses (up to six) were given. The patients underwent MAb treatment after their tumors were minimized by surgery, radiotherapy, and, in recurrent lesions, a second operation. Data is presented in this article for 62 evaluable patients with high grade malignant gliomas (58 glioblastomas and 4 anaplastic astrocytomas), of which 31 were newly diagnosed tumors and 31 were recurrent lesions. In 40 cases the disease was minimal at the time of MAb injection, and in 22 cases a macroscopic remnant was present. RESULTS: There were very few adverse effects, all of which were minor. The treatment yielded a significant extension of patients' median survival (23 months) and of the disease free time to relapse (12 months). Favorable objective responses were recorded as follows: 9 partial responses, 3 complete responses, and 20 with no evidence of disease. A response rate of 51.6% was calculated for all assessable patients. The most important factor in obtaining beneficial outcomes was limited extension of the neoplasm at the time of therapy. CONCLUSIONS: In selected patients, locoregional radioimmunotherapy can be included in a multimodal strategy to control high grade malignant gliomas and produce favorable results.

Antibody response of Mexican infants to Haemophilus influenzae type b capsular polyribosylribitol phosphate. Differences between natural and vaccine induced (oligosaccharide-CRM197 conjugated vaccine) immunization.

In this study we compared natural vs. induced Haemophilus influenzae type b (Hib) anti-capsular polyribosylribitol phosphate (PRP) antibody response in a low socioeconomic population. One hundred twenty five 2-month-old children received the complete HbOC vaccine immunization scheme and a booster dose at 15 months of age. One hundred twenty five non-immunized children served as the control group. Serum Hib anti-PRP antibody titers were determined by ELISA in all children. We found at the end of the primary immunization scheme an antibody concentration of 27.28 micrograms/ml in the immunized group vs. 7.48 micrograms/ml in the control group. The antibody response was mainly of the IgG1 class in both groups. After the booster dose the antibody concentration was 30.14 g/ml in the vaccinated group vs. 6.06 micrograms/ml in the control group (p < 0.01). Ninety nine percent of immunized and non-immunized infants had titers greater than 1 microgram/ml. These results confirm that immunization with the HbOC vaccine induces an important increase in anti-PRP specific antibody titer, but they also demonstrate that natural exposure induces responses higher than those referred as protective (1 microgram/ml).

Local treatment of malignant gliomas by direct infusion of specific monoclonal antibodies labeled with 131I: comparison of the results obtained in recurrent and newly diagnosed tumors.

Two murine monoclonal antibodies, BC-2 and BC-4, raised against tenascin and labeled with 131I were infused locally in the site of neoplastic disease by means of a removable (16 patients) or indwelling (34 patients) catheter. Fifty patients bearing a malignant glioma were treated. Twenty-six of these were suffering from recurrent disease; their tumors relapsed within 9 months (median) after treatment. The remaining 24 cases had a newly diagnosed tumor, and local radioimmunotherapy (RIT) was given immediately after surgery and radiochemotherapy. All efforts were made to reduce the tumor before the infusion of the radiopharmaceutical. Therefore, 22 cases with relapsing glioma underwent additional debulking surgery, which led to total or subtotal removal of tumor in 9 of the patients. Altogether, 28 patients had intralesional RIT when the disease was minimal or microscopic. Conversely, 22 cases underwent local RIT with a tumor the diameter of which was > 2 cm. In many cases, the infusions were repeated up to six times to achieve complete destruction of the neoplastic tissue. The local treatment did not give rise to systemic or to cerebral adverse effects. The labeled monoclonal antibodies, given directly in the site of the lesion, concentrated in very high amount in the neoplastic tissue and remained fixed in the target for a long period of time. For these reasons, the radiation dose to the tumor was remarkable (on average > 30,000 cGy/cycle) and consequently led to promising results. The median survival was, in total, 20 months (18 in recurrent tumors and 23 in newly diagnosed lesions). Moreover, median survival was 17 months in patients with bulky tumors (both recurrent and newly diagnosed tumors) and 26 months in patients with minimal or microscopic disease. The median time to progression was 3 months in recurrent and 7 months in newly diagnosed gliomas. Finally, RIT produced 3 CRs (all in recurrent tumors), 6 PRs (4 in recurrent and 2 in newly diagnosed), and 11 stabilizations of disease (4 in recurrent and 7 in newly diagnosed). In 19 cases (13 recurrent and 6 newly diagnosed) the progression of tumor was recorded. Eleven patients (2 recurrent and 9 newly diagnosed) who were treated by RIT when their disease was minimal and nondetectable by radiological methods remained disease-free and were classified as NED. The overall response rate (NED plus CR plus PR) was 40% (34.6% recurrent and 45.8% newly diagnosed).(ABSTRACT TRUNCATED AT 400 WORDS)

Evolving brain lesions in the first 12 hours after head injury: analysis of 37 comatose patients.

From January 1, 1990, to April 30, 1994, 412 patients were admitted to our intensive care unit in coma after head injuries. Our study group consisted of 37 patients who were retrospectively identified as harboring lesions or developing new lesions within a 12-hour period from the time of admission. We defined the evolution of a lesion as an increase or decrease in the size of an already present hematoma or as the appearance of a totally new lesion. There were 25 male and 12 female patients (mean age, 34.9 yr), and the cause of trauma was road traffic accidents in 32 patients. Nine patients presented with shock, and six had evidence of abnormal coagulation at admission. Patients were divided into two different groups. In Group 1, 15 patients harbored lesions that evolved toward reabsorption. In Group 2, 22 patients harbored hematomas that evolved toward lesions requiring surgical removal. Fifteen of these patients had initial diagnoses of diffuse injury that evolved in this manner, whereas the remaining seven patients had already been operated upon and had developed second, noncontiguous, surgical lesions. Patients with lesions that required surgical evacuation had their computed tomographic (CT) scans obtained earlier and had a higher incidence of clinical deterioration. There was a significant difference in the evolution of the different lesions (P < 0.001), with subdural hematomas being more prone to reabsorption and intracerebral and extradural hematomas being more likely to increase in size or to appear as new lesions. Second CT scans were obtained because of clinical deterioration in 10 patients and because of increase in intracranial pressure in 5 patients. Scheduled CT scans were obtained in 13 patients, whereas in the remaining 9 patients, the diagnosis emerged from a combination of scheduled CT scans and intracranial pressure monitoring. There was a trend toward a poorer result among the patients with clinical deterioration, which, however, was not significant. A significant proportion of post-traumatic patients, particularly those who are unconscious, harbor early evolving intracranial lesions. When the first CT scan is performed within 3 hours after injury, a CT scan should be repeated within 12 hours.

Diagnosis and management of minor head injury: a regional multicenter approach in Italy.

Two series of patients admitted to the hospital after a minor head injury were collected in two different periods (1985 and 1989) in a regional hospital with a 24-hour computed tomography (CT) service, but without a neurosurgical unit. In 1988, a regional protocol on the management of patients with minor head injury (based on the presence of skull fractures in adults and on clinical parameters in children) was adopted. There was a 21% reduction in hospital admission in adults, and the number of skull x-ray films performed in children decreased significantly (p < 0.01). A more liberal use of CT examinations in asymptomatic patients with skull fractures produced an earlier identification of patients with extradural hematomas who were sent to neurosurgery before clinical deterioration with good results. Detection of cerebral contusions was clinically less important. Based on the availability of CT scanners in our area and on the results of our study, we have proposed new guidelines in management of minor head injury. The CT scans are obtained in patients with a Glasgow Coma Scale score of 13 or less. Skull x-ray films are obtained in patients older than 10 years with a Glasgow Coma Scale score of 14/15. If a fracture is found, the patient is sent to the nearest regional center for CT examinations. Children younger than 10 years are sent to a regional hospital with 24-hour CT availability for clinical observation or other indicated studies.

Post-traumatic acute subdural haematoma of the posterior fossa extending toward the cerebello-pontine region. Report of a case.

The case of a 73 year old lady hit by a truck is presented. The patient after a short lucid interval (2 hours) became deeply comatose. CT scan (performed in the clinical phase of minor head injury) showed a posterior fossa subdural haematoma (PFSH) extending towards the cerebello-pontine angle and the brainstem. Prompt evacuation of the haematoma led to recovery with severe disability. Mechanisms and causes of acute PFSH are discussed. As in other published cases the clinical diagnosis of a PSFH is difficult; mortality and morbidity are extremely high in spite of surgical treatment.

Extradural haematomas: how many deaths can be avoided? Protocol for early detection of haematoma in minor head injuries.

Since 1988 in the referral area of the Neurosurgical Unit of Cesena, Italy, a protocol for prevention of deterioration in minor head injury was adopted. Adult patients admitted to any hospital with a GCS score of 15 and 14 (transient) without neurological deficit are submitted to skull x-ray: if a fracture is present the patient is sent for CT to the nearest regional Center. In children skull x-ray is not routinely performed and the patients are admitted for observation to the nearest regional hospital. To assess the effects of such a protocol on morbidity and mortality of extradural haematoma (EDH), from June 1989 to September 1991 a consecutive series of 95 patients harbouring a significant acute EDH was collected. Mean age was 31 years; in 70% trauma was caused by a road traffic accident. The patients were divided into 3 categories: a) Clinical deterioration: mean GCS at surgery was 7.7; out of 27 patients, 12 had anysocoria and 3 bilaterally fixed pupils; the outcome showed only two deaths, one related to the EDH and the other to cardiac arrythmia. Most of the patients deteriorated either during transport after being recognized as at risk or already in Neurosurgery allowing rapid surgical treatment. b) Impaired consciousness (18 cases) and c) Minor head injury (50 cases) are groups of patients treated without morbidity and mortality. If we compare these results with those of a previous study of our group done in 1980-86, there is a statistically significant difference concerning both mortality and morbidity. Our protocol proved therefore to be adequate in preventing most deaths that occurred following clinical deterioration in an apparently low risk patient.

Intralesional administration of I-131 labelled monoclonal antibodies in the treatment of malignant gliomas.

The authors report their preliminary experience with the use of radiolabelled monoclonal antibodies (MAb) as an adjuvant treatment for 33 malignant gliomas. MAbs employed in this study are raised against Tenascin (TN) which is an antigen of the extracellular matrix of the tumour. It has also been found in neoplastic cells but never in normal brain tissue. This therapy is aimed to give a local high dose radiation (boost) while sparing healthy brain structures. This treatment has always been well tolerated and no adverse reactions at the level of CNS or major extraneural organs has been observed. Significant improvement of median survival has been obtained but this result should be cautiously evaluate since the study is non-randomized. Comparison with other current adjuvant technique is briefly discussed.

Diffuse axonal injury with brainstem localisation: report of a case in a mild head injured patient.

The authors present the case of a 26-yrs-old woman admitted into our hospital after a severe polytrauma with a mild head injury. CT scanning disclosed two small hemorrhages located in her brainstem and mesial temporal lobe. After splenectomy the patient made a full recovery without neurological sequelae. Radiological signs of diffuse axonal injury even in the brainstem may be present in a clinically mild head injury.

Intralesional radioimmunotherapy of malignant gliomas. An effective treatment in recurrent tumors.

BACKGROUND: Intralesional radioimmunotherapy (RAIT) may improve the management of malignant gliomas whose prognosis is, at present, very poor. Current treatment modalities (e.g., surgery, radiotherapy, and chemotherapy) may prolong survival by a few months but cannot prevent tumor recurrence. METHODS: Following one or more surgical operations, radiotherapy, and chemotherapy, 24 patients with recurrent malignant gliomas (23 brain and 1 spinal cord) underwent RAIT with 2 murine monoclonal antibodies (MoAb), BC-2 and BC-4, raised against tenascin (TN). This antigen is expressed in large amounts in the stroma of glial tumors but not normal brain tissue. The isotope used was iodine-131 (131I). The radiolabelled antibodies were injected directly into the tumor by means of a removable catheter or an indwelling catheter placed in the site of disease at the time of craniotomy. The patients were admitted to the protocol if histochemical analysis of their tumors demonstrated the presence of TN in high abundance. Biodistribution and dosimetry of an intralesional tracer dose (1 mg MoAb and 37 MBq 131I) were studied. RAIT was performed by the administration of escalating doses of radioiodine, ranging from 15 mCi to 57 mCi. In many cases, RAIT was was repeated two, three, or four times (on 8, 3 and 4 patients, respectively). RESULTS: Pharmacokinetic data resulted, on average, as follows: the 24-hour tumor/background ratio was 16.6; the percentage of injected dose concentrated per gram of tumor at 24 hours was 2.4%; and the effective half-life of the MoAb at the tumor was 74.5 hours. The mean radiation dose to the tumor was 36.48 cGy per MBq of 131I injected. Both systemic and brain toxicities were absent, while human anti-mouse antibody production after MoAb administration occurred in only a few cases. At present, 17 patients are assessable, with a median survival time of 16 months. Objective responses consisted of 5 tumor stabilizations (median time, 9 months), 3 partial remissions (11 months), and 3 complete remissions (15 months).

Glioblastoma therapy by direct intralesional administration of I-131 radioiodine labeled antitenascin antibodies.

Thirty patients with recurrent glioblastomas (29 brain, 1 spinal cord) received intralesional radioimmunotherapy aiming to control the progression of the tumor after surgery and radiotherapy. The BC-2 and/or BC-4 murine MAbs (Sorin-Biomedica, Saluggia, Italy) were utilized. They strongly react against tenascin (TN), which is an extracellular antigen expressed in large amounts by the stroma of glioblastoma but not by normal brain. The MAbs were labeled with I-131 and were injected directly into the tumor mass to maximize the antibody concentration in the tumor and to irradiate the neoplastic cells. The dose consisted, on average, of 3 mg antibody and 1100 MBq I-131. In most cases the radioimmunotherapy (RIT) applications were repeated two, three, or four times. No systemic adverse reactions were recorded. The brain tolerance to direct antibodies injection was quite good. The antibody concentration in the tumor was high and the MAb residence time in neoplastic tumor was prolonged. Consequently the mean radiation dose to the tumor was high: > 25,000 cGy/cycle. Of 23 evaluable patients, we recorded 7 tumor stabilization (lasting, on mean, 9.1 mo), 4 partial remission (10 mo), and 4 complete remission (18 mo). The overall response rate was 34.7%.

Radioimmunotherapy of gastrointestinal cancer and glioblastomas.

Two groups of patients with gastro-intestinal (GI) tumours (41) and recurrent glioblastoma (GBM), (17) underwent radioimmunotherapy after the failure of traditional treatments. A number of different MAbs were employed (anti-CEA and anti-Tenascin) which were labelled with I-131. The radiopharmaceuticals were administered by the intraperitoneal and intratumoral routes. As a rule the cycles were repeated to enhance the effectiveness of RIT. No significant early or late adverse effects were recorded. HAMA development was observed in all GI cases but only in a few GBM patients. The cumulative dose delivered to the target tumors was considerable (mean 8,900 cGy) in the GI group, and was much higher in the GBM patients (mean 51,700 cGy) owing to the particular modality of injection. Survival improved in both series of patients. The objective responses to RIT were promising: in the GI group 10 complete remissions (CR) and 6 partial remissions (PR) were observed, while in the GBM group 3 long-lasting CRs and 3 prolonged PRs were documented.

Management of low-risk head injuries in an entire area: results of an 18-month survey.

All patients admitted following a minor head injury (GCS is without neurological deficits) during an 18 month period in an entire area were submitted to the same diagnostic and therapeutic protocol. Adult patients were x rayed and in the cases with skull fracture (even asymptomatic), a computed tomographic (CT) scan was performed. Children (below the age of 14) did not routinely receive skull X-rays but were admitted to one of the five regional hospitals where a CT scanner was available 24 hours per day. Neuroradiologic investigations (carried out in over 600 patients) showed posttraumatic lesions in 201 cases; 113 of these patients were transferred to the neurosurgical center. There were 49 patients with extradural hematomas, 41 with brain contusions, 17 with depressed skull fractures, and six with subdural hematomas. Of these 113, 40 patients were operated on (mainly extradural hematomas); surgical indications were based on appearance of clinical deterioration, lesion volume, presence of midline shift, and/or compressed third ventricle and basal cisterns. In eight cases there was a clinical deterioration to a GCS of 13 or less; in all of these patients, the CT diagnosis (and transfer to a neurosurgical center, preceded the onset of deterioration. All patients admitted to such a center had a good outcome, but a survey of deaths related to head injury in the area revealed two fatalities following minor head injury. The only avoidable death was a patient with multiple brain contusions who developed sudden brain swelling on day 12 post-trauma. We conclude that, even if management mortality is not zero, our protocol is sufficiently safe for the treatment of minor head injury.

Arachnoid cyst of middle cranial fossa and ipsilateral subdural haematoma: diagnostic and therapeutic implications in three cases.

We describe three cases of arachnoid cyst of the middle cranial fossa with associated intracystic and subdural haematomas. In all of the patients the diagnosis was made before surgical treatment. No bleeding could be attributed to ruptured bridging veins. In two cases the source of bleeding was identified at the interface between the dura mater and the outer membrane at the temporal skull base. We suggest that, even if wide outer membrane membranectomy is probably not indicated, careful coagulation of the membrane at the skull base is necessary to avoid bleeding within the cyst.

Treatment of intracranial human glioblastoma by direct intratumoral administration of 131I-labelled anti-tenascin monoclonal antibody BC-2.

Ten patients with bulky brain glioblastoma, recurring after surgery, radiotherapy or chemotherapy, underwent direct intralesional radioimmunotherapy (RIT) using a monoclonal antibody (MAb), BC-2, raised against tenascin and labelled with 131I. Tenascin, the BC-2-recognized glycoprotein, is an antigen expressed by the stroma of malignant gliomas but not by normal cerebral tissue. Preliminary studies in animals have demonstrated the ability of anti-tenascin radiolabelled MAbs to detect and reduce tumours. A mean MAb dose of 1.93 mg (corresponding to 551.3 MBq of 131I) was injected directly into the tumour by means of a stereotaxic technique. Both systemic and local toxicity were negligible. After 24 hr, average tumour BC-2 uptake was 4.9% per gram and its effective half-life in neoplastic tissue was 66.5 hr: a mean radiation dose to target tissue of 36.48 cGy per MBq of injected 131I was delivered. Normal brain tissue and the major organs were spared. Most patients underwent multiple injections, reaching a cumulative tumour radiation ranging from 7,000 to 41,000 cGy. RIT failed to achieve any result in 4 of the 10 patients; in 3, the disease was stabilized; in the remaining 3, CT scan or NMR revealed 2 partial remission (greater than 50% reduction in tumour volume; PR) and I complete remission (CR). One patient with PR relapsed after II months; the other 2 patients were still maintaining their responses at the time of writing, 17 (CR) and 12 (PR) months after injection.

The distribution of intravenous nicardipine in rat brain after subarachnoid hemorrhage.

The distribution of intravenously injected nicardipine in rat brain was investigated, as well as the influence of subarachnoid hemorrhage on its distribution. Autoradiographic studies demonstrated the accumulation of 3H-nicardipine only in the ventricles and subarachnoid spaces around pial vessels in normal brains. Thirty minutes after subarachnoid hemorrhage, the concentration of 3H-nicardipine was higher in the ventricles and in the subarachnoid space than that found in normal brains. It is concluded that nicardipine penetrates into the subarachnoid spaces and ventricles from pial vessels and/or choroid plexus, and that subarachnoid hemorrhage increases the penetration of nicardipine from vessels into the subarachnoid space.