A comparison of chemo-free strategy with G-CSF plus plerixafor on demand versus intermediate-dose cyclophosphamide and G-CSF as PBSC mobilization in newly diagnosed multiple myeloma patients: An Italian explorative cost Analysis.

BACKGROUND: Upfront single or tandem ASCT still represents an integral part of treatment for patients with multiple myeloma. The combination of intermediate dose (ID) - cyclophosphamide plus G-CSF, has been considered the standard method as mobilization regimen. No prospective randomized clinical trials have compared efficacy and costs using ID - cyclophosphamide against a chemo-free mobilization strategy with G-CSF and plerixafor on demand. METHODS: A prospective single arm of 20 patients enrolled in three Italian Centers mobilized with G-CSF plus plerixafor on demand was compared with a retrospective historical control arm of 30 patients mobilized with ID - cyclophosphamide (4 g/sqm) and G-CSF. Costs of the prospective arm was compared with the ones of the retrospective control arm with the aim to collect ≥4 × 106/kg CD34 + . The exploratory cost analysis was performed using microcosting specific inputs of G-CSF plus plerixafor on demand versus ID - cyclophosphamide + G-CSF considering pre-apheresis, peri-apheresis and post-apheresis session. RESULTS: Mobilization with ID - cyclophosphamide and G-CSF resulted in a significantly higher CD34+ peak mean on day 1 yield (119 CD34+ µL vs 67.3; p = 0.06) and in total average CD34+ yield (mean collection 10.6 × 106/kg vs 5.8 × 106/kg; p = 0.004) compared to patients mobilized with G-CSF and plerixafor. There was no significant differences (p = 0.36) in the two groups of patients collecting ≥ 4 million CD34+/Kg with ID - cyclophosphamide and G-CSF (93.3 %) vs G-CSF and plerixafor (90.0 %). None of the patients undergoing G-CSF and plerixafor mobilization had febrile neutropenia compared with 7 patients who received ID - cyclophosphamide and G-CSF (0% vs 23 %, p = 0.03) who had a median of 5 days hospitalization (range 4-6). All patients proceeded to ASCT with a mean of 3.6 CD34+/kg infused for G-CSF and plerixafor arm and 4.4 CD34+/kg for the ID - cyclophosphamide + GCSF group (p = 0.37) with a median time to ANC and PLT engraftment not different in the two groups. Total costs of a mobilizing strategy using a combination of G-CSF and plerixafor on demand was 12.690 euros compared to 16.088 euros with ID - cyclophosphamide and G-CSF (p = 0.07); in particular, mobilization cost components were significantly lower for G-CSF and plerixafor vs G-CSF and ID - cyclophosphamide for hospital stay (3080 euros vs 9653 euros; p < 0.001) whereas for mobilizing agent, there was a significative difference with 5470 euros for G-CSF and plerixafor use due to the cost of plerixafor compared with 1140 euros for ID - cyclophosphamide and G-CSF treatment (P = 0.001). CONCLUSIONS: Our data demonstrate that in patients with multiple myeloma eligible for ASCT, a chemo-free mobilization with G-CSF and plerixafor on demand is associated with efficacy in PBSC collection and optimal safety profile with similar average costs when compared to a chemo-mobilization with ID - cyclophosphamide. A prospective randomized multicenter study could address which is the most cost-effective strategy for this setting of patients. CLINICAL TRIAL REGISTRY: Eudract Number EudraCT 2013-004690-27.

Fotemustine plus etoposide, cytarabine and melphalan (FEAM) as a new conditioning regimen for lymphoma patients undergoing auto-SCT: a multicenter feasibility study.

BEAM is a widely used conditioning regimen for relapsed/refractory lymphoma patients undergoing auto-SCT. We conducted a multicenter study with an alternative regimen (fotemustine plus etoposide, cytarabine and melphalan (FEAM)) in which BCNU was substituted by the chloroethylnitrosourea fotemustine (FTM). Eighty-four patients with relapsed/refractory Hodgkin's (n=20) and non-Hodgkin's lymphoma (n=64) were conditioned with a FEAM regimen (FTM 150 mg/m(2) on days -7, -6, etoposide 200 mg/m(2) and cytarabine 400 mg/m(2) on days -5, -4, -3, -2 and melphalan 140 mg/m(2) on day -1). Patients were evaluated for toxicity and engraftment parameters. Median times to neutrophil (>500 x 10(9)/l) and plt (>20 000 x 10(9)/l) engraftment were 11 and 13 days, respectively. Grade 3 mucositis occurred in 19 patients (23%), while G3 nausea/vomiting and G3 diarrhea were observed in 13 (15%) and 6 (7%) patients, respectively. No severe hepatic, renal or pulmonary toxicity was detected. Seven patients (7%) experienced G4 mucositis, while no other G4 toxicities or unexpected adverse events of any grade were recorded. Transplant-related mortality was 2.4%. We conclude that a FEAM regimen is feasible and safe. Although toxicity and engraftment times compared favorably with BEAM, longer follow-up is needed to evaluate fully its efficacy and long-term safety.

Gemcitabine, ifosfamide, oxaliplatin and rituximab (R-GIFOX), a new effective cytoreductive/mobilizing salvage regimen for relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a pilot study.

BACKGROUND: The prognosis of patients with aggressive non-Hodgkin's lymphoma (NHL) relapsing or progressing after front-line therapy remains poor. Since high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) can cure a proportion of such patients, provided that a substantial tumor shrinkage is achieved, the development of more effective and less toxic salvage regimens remains a major challenge. We evaluated the clinical activity, toxicity and mobilizing capacity of a new salvage regimen, which combines gemcitabine and oxaliplatin with ifosfamide and rituximab (R-GIFOX) in patients with relapsed and refractory CD20(+) NHL. PATIENTS AND METHODS: Patients were scheduled to receive three courses of therapy followed by mobilization and ASCT or three more courses if ineligible for ASCT. R-GIFOX consisted of rituximab (375 mg/m(2) on day 1), gemcitabine (1000 mg/m(2) on day 2), oxaliplatin (130 mg/m(2) on day 3) and ifosfamide (5 g/m(2) on day 3) as a 24-h single infusion in patients aged < or =65 years, or fractionated over 3 days (days 3-5) in patients aged >65 years. Treatment was given every 2 weeks with G-CSF support (5 microg/kg/day or 10 microg/kg/day at the end of the third course for stem cell mobilization). Responses were evaluated by the integrated FDG-PET/IWC criteria after the third course and at the end of the entire program. RESULTS: Fourteen patients (median age 63 years, range 37-78 years) with relapsed (n = 9) or primary progressive (n = 5) aggressive (diffuse large cell, mantle cell, follicular G3), advanced (stage IV 71%), poor risk (IPI 3-5 50%) NHL were accrued in this pilot study. Patients had received a median of two previous treatment lines (range 1-4). The median number of R-GIFOX courses delivered was 4 (range 1-6). Thirteen patients completed at least three courses of therapy and were evaluable for response. The overall response rate assessed after three courses of R-GIFOX was 77%, with seven complete responses and three partial responses. Effective CD34(+) cell mobilization was obtained in four of six eligible patients and two had ASCT. Hematologic and extra-hematologic toxicity was tolerable. Failure-free survival was 79.6% at median follow-up of 6 months (range 2-12). Molecular remissions were documented in two patients with mantle cell NHL. CONCLUSIONS: Based on the results of this pilot study, we conclude that the R-GIFOX regimen is feasible, tolerable, effective and able to mobilize peripheral stem cells in patients with relapsed and refractory aggressive NHL.

Affective temperament in the eating disorders.

BACKGROUND: In this study, we investigate the affective temperamental characteristics in a sample of ED (eating disorder) patients. METHODS: 49 ED patients diagnosed by the SCID (Structured Clinical Interview for DSM-IV), were divided into two groups on the basis of the presence or absence of Binge Eating (restricting-anorexia nervosa [R-AN]= 16; Binge Eaters= 33). All patients were administered the TEMPS-I (Temperament Evaluation Memphis Pisa Semistructured - Interview), to assess affective temperament. A third group of controls (N= 1010), derived from a study with the TEMPS-I on normal subjects, was included for comparison. RESULTS: A full affective temperament was not found in patients of the restricting group. By contrast 24% of the binge eating group had a full affective temperament of one of three types. Comparing the three temperaments for the three groups, only cyclothymic temperament proved to be significant, with higher levels in the binge eating group (p<0.01). CONCLUSIONS: In this study, people with R-AN do not show a full affective temperament. However, people with binge eating, had depressive and hyperthymic temperament, and displayed higher level of cyclothymic temperament than the normal population. The findings of this study add to a growing literature on temperament in people with ED; particularly, they add to the view that may be various paths leading to R-AN, and these may differ from those of binge eating.

Axis I comorbidity in bipolar disorder with psychotic features.

BACKGROUND: Axis I comorbidities are prevalent among patients with severe bipolar disorder but the clinical and psychopathological implications are not clear. AIMS: To investigate characteristics of four groups of patients categorised as follows: substance abuse only (group 1), substance abuse associated with other Axis I disorders (group 2), non-substance-abuse Axis I comorbidity (group 3), no psychiatric comorbidity (group 4). METHOD: Consecutive patients with bipolar disorder with psychotic features (n = 125) were assessed using the Structured Clinical Interview for DSM-III-R--patient version, and several psychopathological scales. RESULTS: By comparison with group 4, group 1 had a higher risk of having mood-incongruent delusions, group 2 had an earlier age at onset of mood disorder, a more frequent onset with a mixed state and a higher risk of suicide, and group 3 had more severe anxiety and a better awareness of illness. CONCLUSIONS: Substance abuse, non-substance-abuse Axis I comorbidity and their reciprocal association are associated with different characteristics of bipolar disorder.

Corticospinal tract degeneration in motor neuron disease.

Long-repetition-time spin-echo MR images showed symmetric hyperintensity of the intracerebral corticospinal tracts in two patients with clinical and neurophysiologic diagnosis of primary lateral sclerosis and amyotrophic lateral sclerosis. In both, axial low-flip-angle gradient-echo images of the cervical spine showed hyperintensity of the lateral columns of the cord consistent with antegrade degeneration of the crossed corticospinal tracts.

Balloon occlusion of the carotid artery in the treatment of cavernous giant aneurysms: two cases.

Over recent years, endovascular occlusion of the carotid artery has become a valid alternative to its more traditional surgical ligation in the treatment of cavernous giant aneurysms. The authors report two cases treated with balloon occlusion in two patients with clinical signs of cavernous sinus syndrome. The procedure consisted of occluding the aneurysm and the carotid by means of detachable balloons. This was preceded by a 30-minute clinically monitored occlusion test aimed at evaluating the functioning of Willis' circle. The treatment was carried out under neuroleptoanalgesia, so optimal control of the neurological condition of the patient was possible. Partial symptom regression was obtained in both cases.

Elsberg syndrome: radiculomyelopathy and acute urinary retention in patient with genital herpes.

We describe a case of a sexually active woman who presented acute urinary retention associated with herpes genitalis infection and with few other neurological signs. The outcome of the disease was positive. We stress the utility of a careful CSF examination.

[Anoxic-ischemic encephalopathy and myoclonic status epilepticus]. / Encefalopatia anossico-ischemica e stato di male epilettico mioclonico.

The Authors present a case of post-anoxic coma accompanied by myoclonic status. They describe the clinical picture and instrumental data. The outcome seems to be determined by the serious anoxic-pathological damage rather than the myoclonic jerks. They discuss the problem concerning preventive treatment by use of thiopental sodium (T.P.S.) in such cases.

[The study of sleep in full term and preterm neonates with EEG polygraphy]. / Lo studio del sonno nel neonato a termine e pretermine con l'EEG-poligrafia.

We accomplished polygraphies in two groups of infants: 1) preterm infants born before 33 weeks CA, and recorded between 33 and 48 weeks CA; 2) full term infants, recorded between 39 and 48 weeks CA. We compared in each group of infants: 1) the development of behavioral states organization; 2) the maturation of cortical bioelectric activities; 3) the development of concordance between behavioral states and EEG pattern; 4) sequences of behavioral states and EEG pattern when the babies fall asleep. In all the aspects considered, we describe some developmental changes, to understand how, through these changes, the newborn sleep-wake ultradian cycle is replaced by 24 hr-cycle, typical of the infantile period. This basic process is expression of maturation of the central nervous system because it is related to CA and not to extrauterine experience. The EEG-polygraph usually used in clinical practice allow us to follow these extraordinary transformations very closely.

[Mitochondrial oculopharyngeal myopathy: description of a case]. / Miopatia oculo-faringea mitocondriale: descrizione di un caso.

We describe a 55 years old man affected by eyelid ptosis, mild ophthalmoplegia externa and severe dysphagia owing to pharyngoesophageal dyskinesia. Skeletal and eyelid constrictor muscles EMG showed myogenic alterations. Muscle histological findings of ragged red fibers and oxidative histochemical alterations, together with ultrastructural investigation clue for mitochondrial myopathy diagnosis. This, considering the unusual clinical aspects of the case, confirms as mitochondrial disease can widely vary in their phenotypical expression.

[Venous angioma associated with cavernous angioma. Presentation of three cases]. / Associazione di angioma venoso ed angioma cavernoso. Presentazione di tre casi.

Cavernous angiomas and venous angiomas may be discovered as associated lesions in the same patient. Most Authors report that Venous angiomas are not true vascular malformation; they should be considered as variant of normal venous drainage, consisting of tortuous medullary veins converging into a dilated draining one. By rule, they are quite asymptomatic, and very rarely bleed. On the other side, cavernous angiomas are true vascular malformations, usually angiographically occult. Their association is relatively rare, but it is important because of the possibility of bleeding, which should be related to the presence of the cavernous malformation. We report the cases of three patients studied by Computed Tomography, Magnetic Resonance and Digital Angiography in our Neuroradiologic Department.

Parkinsonian syndrome in the course of aqueductal stenosis hydrocephalus.

Report of a case of hydrocephalus secondary to stenosis of the aqueduct with associated parkinsonian syndrome. The suggested etiopathogenesis: damage to the striatal system favored by underlying weakness of the basal ganglia.

Problems of treatment in the neurological complications of Vaquez disease.

A critical review of the therapeutic measures available to neurologists in a Vaquez disease emergency in the light of the physiopathology of the disease and its complications.

Gynecomastia in epileptics treated with phenobarbital, phenytoin and fluoresone: two case reports.

Gynecomastia developed in two epileptic patients some months after the addition of oral fluoresone 750 mg daily to the phenobarbital and phenytoin already being administered. The common systemic diseases that may give rise to gynecomastia were excluded. One of the patients presented hyperprolactinemia and a raised estrogen/androgen ratio but the hormone levels were not raised in the other. The onset of symptoms after fluorescence in both cases is highly suggestive, although the pathogenetic mechanism is not clear.

Epileptic seizures precipitated by eating.

The case of a mentally retarded 18-year-old girl who for 2 years has experienced epileptic seizures exclusively during meals is discussed. Polygraphic recordings have defined the electrical and clinical features of these seizures. None of the possible precipitating factors considered in other cases in the literature (chewing, swallowing, conditioned reflex, etc.) seems to be involved in this case. We hypothesize that in our patient the precipitating factor is the complete act of eating a meal, which involves the satisfaction of a basic drive.