bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful nilotinib therapy in a CML affected patient with A380T, P407S and V468A mutations, and a previous suboptimal cytogenetic response to imatinib
Authors: Stagno Fabio , Cupri Alessandra , Stella Stefania , Massimino Michele , Vitale Silvia Rita , Vigneri Paolo
Published: June 2016

Imatinib mesylate (IM) has shown unprecedented effectiveness in the treatment of Chronic Myeloid Leukemia (CML) patients (pts) in the chronic phase of the disease. However, some pts fail to respond or lose their initial response to IM. The European LeukemiaNet (ELN) published recommendations designed to identify patients responding poorly to imatinib. Here we report a case of a suboptimal cytogenetic responder to IM who had a successful response to the second generation tyrosine kinase inhibitor nilotinib (NIL). According to the ELN criteria, CML pts on IM-therapy might show a suboptimal response either because of failure to achieve a CCyR by 12 months of therapy or because of lack of a MMR after 18 months. The prognostic value of these two types of responders might be very different.
Efficacy of nilotinib therapy in patient with CML diagnosed in pre-TKI era and resistant to imatinib
Authors: Pierri Ivana , Bergamaschi Micaela , Cagnetta Antonia , Ghiso Anna , Gobbi Marco
Published: June 2016

Here we report a case of a 32-year-old man, who was diagnosed as having chronic myeloid leukaemia in 1998. After cytoreduction with hydroxyurea, the patient was submitted to high dose chemotherapy with haemopoietic stem cells rescue and reinfusion, and then he started therapy with IFNα without achievement of a cytogenetic response. On November 2000 he took imatinib 400 mg/day and he reached a complete cytogenetic response (CCyR) at 14 months, but not the major molecular response: therefore he was considered a sub-optimal responder according to European LeukemiaNet criteria of 2006. For this reason he increased imatinib dose to 800 mg/day, but after one year he lost CCyR. Considering the patient as a failure, at this time, he switched to second-generation tyrosine kinase inhibitor, nilotinib at the dose of 800 mg/day. After 3 months he reached complete CCyR and after 6 months the major molecular response, maintained until last molecular evaluation.
A complicated case of deep vein thrombosis
Authors: Cerutti Elena , Colagrande Paola , Provera Edoardo , Giusti Massimo
Published: June 2016

We report a case of a patient with deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE) associated to portal vein thrombosis (PVT), complicated by hospital-acquired pneumonia (HAP). The pathogenesis of DVT is multifactorial; among risk factors we can list: transitory situations (surgical interventions, infectious diseases with fever, traumas), acquired conditions (neoplasms, antiphospholipid syndrome) or genetically determined situations (thrombophilia). PVT of the sovrahepatic veins is responsible for 5-10% of portal hypertension cases in adults and can be associated to local or systemic infections. PVT is present in 10% of patients with cirrhosis and often associated to cancers. It can also complicate a surgery abdominal intervention. HAP is defined as pneumonia that appears for the first time within 48 h of hospital admission. In Internal Medicine Departments the incidence is 7-10 cases/1.000 of hospital admissions, with an important impact in terms of both mortality and morbility. An early diagnosis, together with a correct identification of microbiologic agents in cause, allows a suitable antibiotic therapy with consequent improvement of clinical prognosis and a meaningful reduction of mortality. Main risk factors are: age, hospital and department. An important variable to be considered is the onset of pneumonia. The later is the onset of HAP (5 or more days from the admission to hospital), the more often is associated to multidrug resistant (MRD) microorganisms, poorly responsive to antibiotic.
Heart failure and cardiorenal syndrome: a case report
Authors: Zilioli Valentina , Triggiani Marco , Faden Giacomo , Locantore Elisa , Nodari Savina , Faggiano Pompilio , Cas Livio dei
Published: June 2016

Cardio-Renal Syndrome (CRS) is a renal dysfunction occurring in a large percentage of pts hospitalised for congestive heart failure (CHF). It is characterised by an excessive fluid retention inside the body, resistance to conventional medical therapy, worsening renal function (WRF) and higher mortality. The prevalence of CRS is likely increased because of the improved survival of HF patients. WRF occurs frequently among hospitalised HFF and is associated with a significantly worse outcome. Clinical features at admission can be used to identify patients at high risk for developing WRF. The clinical case presented concerns a 70-year-old diabetic man with post-ischemic cardiomyopathy and chronic kidney failure, admitted to our division for acute heart failure. During hospitalisation he showed a progressive WRF and resistance to diuretic treatment. After Ultrafiltration treatment there was a progressive clinical improvement. Many treatments have been investigated in order to improve renal function, but none has been demonstrated to improve clinical outcome. Currently Ultrafiltration is reserved to patients with volume overload when traditional medical therapies fail and/or patients become resistant to diuretics.
Sudden altered mental state in the elderly: nonconvulsive status epilepticus and the role of the Emergency Department
Authors: Galimi Rocco
Published: June 2016

In the elderly, new onset of epilepsy is often associated with vague complaints such as confusion, altered mental status, or memory problems. The absence of clinically apparent convulsions in association with an electroencephalogram showing continuous or recurrent seizure activity has been called nonconvulsive status epilepticus (NCSE). The purpose of this article is to describe the clinical and electroencephalographic features of NCSE in older adults. NCSE is an important, under-recognised and reversible cause of acute prolonged confusion. Although attempts have been made to define and classify this disorder, there is no universally accepted definition or classification yet that encompasses all subtypes or electroclinical scenarios. A urgent electroencephalogram is considered as the method of choice in the diagnostic evaluation of NCSE. Further researches are needed to better define NCSE.
Crossing-over to imatinib 800 mg in a patient with GIST, after progression with standard
dosage: a case report
Authors: Naso Giuseppe , Cortesi Enrico
Published: June 2016

A 69-years-old patient underwent radical surgery to remove a lesion of small bowel with histological diagnosis of malignant primary stromal cancer of the gastro-intestinal wall (GIST). After a disease-free survival of 25 months instrumental evidence of loco-regional recurrence was detected with subsequent resection of the ileum: histology confirmed recurrent high risk GIST. After 34 months, TC scan showed peritoneal and hepatic progression of disease. Treatment with imatinib was started with standard dose of 400 mg/day, obtaining partial response on peritoneum and liver radiological complete response, after 5 months of therapy. Patient continued treatment with the same dose for 20 months. When radiological progression was detected we decided to increase imatinib to 800 mg/day based on the results of two principal phase III studies. Radiological partial response was reached after three months of therapy. Actually patient is still in treatment with imatinib showing stable disease with good tolerance.
Hypereosinophilia and hepatitis C
Authors: Bussolino Carlo , Saracco Valter
Published: June 2016

We report a case of a 59-year-old Italian man with a history of alcoholic abuse and sustained peripheral blood eosinophilia since 2 years. He arrived at our hospital with progressive oedema, palpitations, dyspnea by heart failure. During hospital stay a diagnosis of CEL-NOS, heart failure and hepatitis C was made. Due to the severe hepatopathy and the mild HCV genotype, along with the therapeutic effect of interferon in chronic myeloid disorders, the patient was treated with PEG-interferon alpha-2a 180 μg weekly and ribavirin 1,000 mg daily. At the end of the treatment the patient showed an important decrease of eosinophil count, normalisation of liver enzymes and the absence of circulating HCV-RNA.
Diabetes mellitus and clopidogrel “resistance”
Authors: Massarelli Laura , Musumeci Giuseppe , Bussolino Carlo , Tomaselli Valerio
Published: June 2016

In our Department arrives a 75-year-old patient with hypertension, diabetes mellitus (DM) treated with hypoglycaemic drugs, dyslipidaemia and ischaemic heart disease post-acute myocardial infarction treated with triple coronary artery bypass surgery and subsequent percutaneous transluminal coronary angioplasty (PTCA). After a new PTCA and positioning of medical stent he is discharged with a double antiplatelet therapy. But after one month two thrombotic events occur in this patients almost simultaneously. Antiplatelet therapy such as clopidogrel and aspirin in combination, is the current gold standard for reducing cardiovascular events in patients with DM, providing a synergistic platelet inhibition through different platelet activation pathways, but platelets of DM patients are characterised by disregulation of several signalling pathways which may play a role not only in the higher risk of developing cardiovascular events and the worse outcome, but also in the larger proportion of DM patients with inadequate response to antiplatelet drugs compared to non DM subjects.
A hidden pathology: Crohn disease
Authors: Zoppis Elisabetta
Published: June 2016

A woman suffering from type 2 diabetes mellitus was admitted, in April 2010, to the Internal Medicine Department for hyperpyrexia: then a diagnosis for spondylodiscitis D3-D4 (Staphylococcus aureus) was made. During these last months, we diagnosed sepsis due to Staphylococcus epidermidis and Escherichia coli, lung consolidation and critical respiratory failure of the 1st type, pulmonary infection due to Candida albicans, and anaemia of multifactorial origin. During PET examination the tracer was initially fixed on the dorsal side, after an antibiotic treatment just at the level of the large intestine’s walls. The diagnosis that explained the chronic anaemia, the spondylodiscitis and the recurring sepsis with pneumonia was made thanks to the colonscopy and the calprotectin increase: Crohn disease in relative activity.
Nursing and clinical course on a burned person complicated by polymicrobial infections
Authors: Valentini Gianluca
Published: June 2016

Here we describe the assistential complexity in an Internal Medicine Division via a multidisciplinary approach taking care of a burned woman. She was transferred in our Division after 90 days of hospitalisation in an Intensive Care Unit from an important centre for burned people for the treatment of burns on 35-40% of the body surface area. We analyse the therapeutic strategies and nursing management in a case complicated by polymicrobial infections: Acinetobacter baumanii and Providencia stuartii on burns, Escherichia coli on respiratory system and Clostridium difficile on enteric apparatus.
Medicine as a frontier: the foreign multipathological patient
Authors: Gallo Roberta
Published: June 2016

A Moroccan 66-year-old female patient arrives in the hospital, where the physicians make the diagnosis of hepatic encephalopathy, HBV-related cirrhosis and decompensated diabetes. This article points out the problems and the aims that a good nursing management must face in the case of a multipathological patient who doesn’t speak italian. In this case the difficulty consists also in the understanding and the acceptance of a new life-style by the patient and her family, due to the chronicity of the diseases. The team work, helped by the assistance of the italian-speaking caregiver, taking into account the clinical condition and the culture and religion related needs, let the patient understand the therapeutic schedule to follow at home and obtained a good compliance by the patient and by her family.
Un raro caso di aplasia eritroide pura che occulta un carcinoma squamoso della lingua
Authors: Incagliato Massimo , Daffonchio Antonella , Celesti Lidia , Bottero Amedeo , Balbi Francesco , D’Ulizia Massimo , Ballestrero Emilia , Costanzo Monia , Primon Valeria , Leone Amelia , Gambarotta Giancarlo
Published: June 2016

We report a case of acquired pure red cell aplasia (APRCA) associated with carcinoma of the tongue: the first was considered a rare paraneoplastic syndrome. We point out that there is no case in literature with this association. After surgical operation (subglottic laryngectomy + right lymphadenectomy + laterocervical on the right) the transfusions required, at the beginning very frequent, decreased relevantly. This is a typical case where the paraneoplastic syndrome precedes the diagnosis of the primary carcinoma of the tongue (one year before what happens in bronchogenic carcinoma).
Internal Medicine Investigations in: “The ghost Pheochromocytoma”
Authors: Giordanetti Stefano , Vallese Giancarlo , Bertinieri Giovanni
Published: June 2016

A 58-year-old man presented with uncontrolled hypertension, elevated norepinephrine and dopamine but normal epinephrine levels. Computed tomography revealed a renal mass. The presence of a pheochromocytoma was excluded. Elevated catecholamines were finally diagnosed as due to sympathetic hyperactivity in the setting of obstructive sleep apnoea. Renal mass was treated as benign. The case will be presented as a detective-story, disclosing intriguing similarities between medical and police investigations.
The point-of-care testing in diabetology
Authors: Matteucci Elena , Giampietro Ottavio
Published: June 2016

In diabetic patients glucose, haemoglobin A1c, ketones, lipids, and urinary albumin monitoring allows prevention, early detection, and treatment of diabetes-related acute and chronic complications. The point-of-care testing (PoCT) technology offers convenient aspects, as long as pre-analytical, analytical, and post-analytical errors are minimised. The overview summarises the current state-of-the-art of PoCT in diabetes care.
Nilotinib efficacy and safety in CML patient with Parossistic Sopraventricular Tachycardia (PSVT), after sub-optimal response to imatinib
Authors: Impera Stefana , Consoli Ugo , Uccello Giuseppina , Guglielmo Patrizia
Published: June 2016

Here we describe the case of a 61-year-old woman who developed chronic myeloid leukaemia in chronic phase under treatment with antiaritmic-therapy (amiodarone) for Parossistic Sopraventricular Tachycardia (PSVT). Initially the patient started with imatinib at standard dose of 400 mg/day but after 6 months of treatment she reached only a Minor Cytogenetic Response (“sub-optimal response”, according to European LeukaemiaNet criteria 2006). After 9 months, she was still in a Minor Cytogenetic Response. We therefore performed a mutation screening analysis that highlighted T240S, N322S, T406A, Y435N mutations. The patient switched to nilotinib at the dose of 800 mg day: Complete Cytogenetic Response and Major Molecular Response were reached after 3 months. Nilotinib was safely administered without further QTc prolongation or haematologic and extrahaematologic adverse side effects.
Different response to imatinib and nilotinib in relationship with the time of administration
Authors: Danise Paolo
Published: June 2016

Here we describe a case of a young patient with chronic myeloid leukemia at low risk, according to the Sokal index. After cytoreduction with hydroxyurea, the patient started imatinib at standard dose (400 mg/day) obtaining a minor cytogenetic response (Ph+ 42.5%) after six months of treatment.Considering the low imatinib concentration evaluated with the blood level testing, we increased the dose of imatinib at 600 mg/day. After about 3 months treatment the patient presented a partial cytogenetic response (Ph+ 30%). Therefore he was considered suboptimal responder according to European LeukemiaNet (ELN) recommendations 2006. For this reason he switched to second generation tyrosine kinase inhibitor nilotinib, at dose 800 mg/die. After switching to nilotinib the patient reached complete cytogenic response and major molecular response, maintained until last molecular evaluation.This kind of patient shows a different response for imatinib and nilotinib, whereas nilotinib therapy has shown to be safe and efficacy.
Management of HIV-1 infection in the paediatric age
Authors: Bonaccini Caterina , Piccini Paola , Serranti Daniele , Gervaso Paola , Galli Luisa
Published: June 2016

Introduction of Highly Active Antiretroviral Therapy (HAART) and implementation of preventive strategies during pregnancy have resulted in a dramatic reduction of the mortality rate in HIV-1 infected children by over 80-90% and in a decrease in the risk of mother-to-child transmission (MCTC) of HIV-1 to approximately 1-2%. However the MCTC remains the main source of HIV-1 infection within the paediatric population. The risk of disease progression is inversely correlated with the age of the child, with the youngest children at greatest risk of rapid disease progression, but in the first year of life it is not possible to identify infants at greatest risk; therefore, according to all the international guidelines, it is necessary to start antiretroviral therapy in all infants < 12 months of age. This article provides a summary of the clinical features of the infection and of the methods for diagnosis. Furthermore it offers an overview of antiretroviral therapy in HIV-1 infected children, including a description of the main classes of antiretroviral drugs, the most common side effects and some issues concerning the disclosure of diagnosis. The objectives of this study are to make a set of practical suggestions to paediatricians for the optimum management of the infection and the antiretroviral therapy.
Imatinib as adjuvant therapy for high risk GIST: a case report
Authors: Lista Patrizia , Ponzetti Agostino
Published: June 2016

We here report a case of 42 years old man who experienced sudden abdominal cramps and then underwent explorative laparotomy because of the CT-finding of a 23 cm abdominal mass at the stomach. Frozen specimen analysis indicated a probable gastrointestinal stromal tumor (GIST). Radical excision was performed. Definitive pathological analysis revealed a CD34 and CD 117(c-KIT) positive GIST with a mitotic count of 15/50 HPF. These features indicate a disease with an high risk of recurrence within few years. Molecular analysis found a WK557-558 deletion of c-KIT exon 11, that indicates a poor prognosis in patients with completely resected GIST. In april 2010 he started adjuvant therapy with imatinib at standard dose of 400 mg/day that was well tolerated: he reported only G1 periocular edema and conjunctivitis. Considering the risk of disease recurrence he continued adjuvant therapy beyond the first year.
Efficacy of nilotinib in a patient in non-optimal response after imatinib treatment but in reduced compliance to the new drug
Authors: Sassolini Francesca
Published: June 2016

We report a case of a patient with chronic myeloid leukemia in chronic phase who was treated with imatinib at standard dose from diagnosis to 18 months end point. He rapidly achieved a stable complete cytogenetic response (CCyR), but not a major molecular response (MMolR). According to European LeukemiaNet (ELN) recommendations, he was classified as a suboptimal patient. Since the treatment was fully tolerated by the patient, we tried an imatinib dose escalation in order to improve this result, obtaining only a transitory MMolR: BCR-ABL trascript level waved from 0,23 to 0,3% (BCR-ABL/ABL%). Therefore, we proposed a change of therapy. Due to his optimal compliance to imatinib and his wish of a future pregnancy, he refused the proposal. Unfortunately the pregnancy remained a desire, therefore, after 1 year of stable results (“near” MMolR), the patient switched to nilotinib at 400 mg/BID. After 3 months of treatment he achieved MMolR and after 6 months we could also document a complete molecular response (CMolR).
Efficacy of nilotinib as third-line treatment in a patient with very late Chronic Myeloid
Leukemia and a possibile cardiologic contraindication
Authors: Orlandi Ester Maria , Redaelli Sara
Published: June 2016

We report a case of a patient with chronic myeloid leukemia who was treated with nilotinib after failure to imatinib and dasatinib. The patient, diagnosed in 1998, was cytogenetically resistant to imatinib. She was switched to dasatinib and achieved a major cytogenetic response, but 3 years later a mutant clone emerged responsible for cytogenetic relapse. The mutation we detected was V299L, that is resistant in vitro to dasatinib, while maintaining a good sensitivity to nilotinib. As the patient was not eligible for allotransplat, we decided to switch to nilotinib, despite a ECG abnormality (wandering pace-maker). After one-year treatment, the patient is in complete cytogenetic response with a low BCR-ABL/ABL transcript ratio. On mutational analysis, the V299L mutation has disappeared. Any cardiologic toxicity has not been observed so far. This case proves that ECG abnormalities do not represent an absolute contraindication to nilotinib and that nilotinib can be effective as third-line BCR-ABL inhibitor.
Nilotinib early switch efficacy in non-optimal responder CML patient after first line imatinib
treatment
Authors: Porretto Ferdinando
Published: June 2016

We report a case of a patient with chronic myeloid leukemia in chronic phase who was treated with Imatinib as first line therapy. He showed a suboptimal response by 2006 ELN criteria after six months, for this reason we performed a mutational analysis that showed the mutation F486S. Due to this finding we made an early switch to Nilotinib (Nil); patients started Nil at 300 bid mg/day obtaining at six month a complete cytogenetic response (CCyR) and a MMolR (RQ-PCR ratio BCR-ABL1/ABL1%IS: 0.05). The patient is now on 24 months Nil treatment showing a RQ-PCR ratio BCR-ABL1/ABL1%IS: 0.004.
Early switch to nilotinib in a case of non-optimal response to imatinib
Authors: Iurlo Alessandra , Radice Tommaso , De Philippis Chiara , Zappa Manuela , Pomati Mauro , Cortelezzi Agostino
Published: June 2016

We report a case of excellent response to nilotinib in a 22 years old man with chronic myeloid leukemia in suboptimal response to imatinib. After diagnosis he started cytoreductive therapy with cytarabine and hydroxyurea, then he begun therapy with imatinib 400 mg/day. After 3 months of treatment, he obtained a complete hematologic response (CHR) and a minor cytogenetic response (minor CyR). At 6 months CHR was confirmed, but bone marrow analysis showed increasing number of Ph+ cells (minimal CyR) and non significant reduction of BCR-ABL levels. According to ELN (European LeukemiaNet) guidelines, this is considered a suboptimal response. Clonal evolution, kinase domain mutations and reduced drug intake were excluded, thus we decided to early switch to nilotinib at 400 mg/BID. After 3 months of treatment we obtained a complete cytogenetic response (CCyR) and a strong reduction of BCR-ABL transcript, almost reaching a major molecular response (MMR).
An unusual case of loss of consciousness: when an epileptic brain let the heart slow down
Authors: Assenza Giovanni , Assenza Federica , Pellegrino Giovanni , Tombini Mario
Published: June 2016

The differential diagnosis of an episode of transient loss of consciousness can be sometimes very tricking, in particular when symptoms peculiar of syncope are mixed with focal neurological symptoms. We report the case of a 54-year-old woman who suddenly claimed, during a polygraphic recording (electroencephalography/electrocardiogram), a feeling of fear and tachycardia followed by loss of consciousness and then a tonic posturing of the left limbs. Polygraphic recording showed a critical electroencephalographic pattern starting from left temporo-zygomatic channels followed after few seconds by a sudden slowing of cortical background activity associated with an episode of asystole, as witnessed simultaneously by electrocardiogram. Muscular activity covered electroencephalographic activity of following minutes. This case provides an opportunity to highlight the existence of rare conditions such as ictal arrhythmias which should be considered in the differential diagnosis of episodes of transient loss of consciousness in particular when dysautonomic and neurological symptoms are intermingled. Autonomic symptoms (vomiting, tachycardia, cyanosis, bradycardia and asystole) may be also more frequent in idiopathic (more rarely symptomatic) epilepsies of childhood (Panayiotopoulos syndrome).
An unsolved case of fever
Authors: Guidetti Elena , Cevenini Monica , Cipollini Maria Luigia , Fabbri Maria Camilla , Tomassetti Paola , Corinaldesi Roberto
Published: June 2016

Fever of unknown origin (FUO) is extremely difficult to diagnose. It is defined as an illness lasting more than 3 weeks with a temperature exceeding 38 °C on several occasions and with an uncertain diagnosis after 1 week of intensive investigations in the hospital. The major causes of FUO are infection, neoplasm, and collagen vascular disease, but the percentages of each of these categories are subject to change due to improvements in diagnostic capability. The diagnostic workup of FUO is complex and, to date, there is no consensus published in the literature regarding guidelines as to the correct approach. A number of diagnostic tests and numerous non-invasive and invasive procedures, which however sometimes fail to explain the fever, are often necessary. In about 20% of cases of FUO the diagnosis is never established. In this article the case of a young man with fever of unknown origin is presented, the cause of which remains undiagnosed, in order to illustrate the difficulties of the diagnostic process. A “watch and wait” approach seems to be acceptable in a clinically stable patient for whom no diagnosis can be made after extensive investigation, and the prognosis is likely to be good.
A case of ectopic ACTH secretion
Authors: Cevenini Monica , Guidetti Elena , Fabbri Maria Camilla , Galassi Eleonora , Tomassetti Paola , Corinaldesi Roberto
Published: June 2016

We report the case of a 48-year-old woman, with a rapidly progressing ACTH neuroendocrine tumour of the pancreas (PNET) and multiple liver metastases. The patient had previously suffered from a peptic ulcer which was responsive to PPI inhibitors and hypertension which was poorly controlled by therapy. Admitted to the hospital for severe asthenia and abdominal pain, she was diagnosed with poorly differentiated PNET with liver metastases, which were positive for synaptophysin, cytokeratin 7 and 9 and neuron specific enolase (NSE). Octreoscan scintigraphy was positive for somatostatin receptors in the pancreas and in two liver lesions. A rapidly progressive Cushing’s syndrome developed, presenting with the classical physical symptoms, hypokalemia and Lysteria monocytogenes meningitis. Ectopic ACTH production was confirmed and eventually the patient died from a septic shock within two months. The case reported focuses on the malignity and the rapid progression of an ACTH-producing PNET and calls attention to the possible fatal progression of these cases.
MEN1 syndrome: an anusual case
Authors: Guidetti Elena , Cevenini Monica , Cipollini Maria Luigia , Ferrata Martina , Tomassetti Paola , Corinaldesi Roberto
Published: June 2016

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant endocrine disorder and is characterised by the concurrent appearance of adenomas of the parathyroid glands, neuroendocrine-enteropancreatic tumours, and pituitary adenomas, as well as other types of less frequent tumours, such as adrenal cortical tumours, carcinoid tumours, lipomas, etc. Two different forms, familial and sporadic, have been described. The gene responsible, MEN1, consists of 10 exons encoding a 610-amino acid protein known as menin. The MEN1 syndrome is caused by inactivating mutations in MEN1 tumour suppressor gene. The combination of clinical and genetic investigation helps in the diagnosis. Genetic testing has been advocated to identify MEN1 carriers of the MEN1 families for the purpose of earlier detection of tumours. We present a patient with traditionally described manifestations of MEN1 (a parathyroid hyperplasia associated with a pancreatic neuroendocrine tumour and a gastrinoma), but with a negative genetic test for the MEN1 mutation.
Bevacizumab and temozolomide in secondary gliomatosis from gemistocytic astrocytoma: a case report
Authors: Trevisan Elisa , Magistrello Michela , Rudà Roberta , Soffietti Riccardo
Published: June 2016

Gliomatosis cerebri is a rare diffuse glioma with a growth pattern consisting of exceptionally extensive infiltration of the CNS with involvement of at least three lobes. It may appear de novo (primary gliomatosis) or result from the spreading of a focal glioma (secondary gliomatosis). Bevacizumab is a monoclonal antibody anti-VEGF active against recurrent high grade gliomas after standard therapy. We report the case of a 41-year-old man with a secondary gliomatosis treated with bevacizumab and temozolomide who responded and the response lasted 17 months. Moreover, we focus on the side effects (hypertension, deep vein thrombosis) induced by bevacizumab and their effective treatments.
Cognitive rehabilitation in neuro-oncological patients: three case reports
Authors: Zucchella Chiara , Pace Andrea , Pierelli Francesco , Bartolo Michelangelo
Published: June 2016

Cognitive impairment is one of the most common neurological disorders in neuro-oncological patients, linked with morbidity, disability, and poor quality of life. As pharmacologic interventions have not yet proven effective in the treatment of cognitive deficits, cognitive rehabilitation could represent an alternative approach. This paper presents three case studies, describing the cognitive intervention and discussing its effectiveness in the light of current evidence.
Nilotinib therapy after resistance to imatinib
Authors: Porrini Raffaele , Montefusco Enrico
Published: June 2016

In this article we present the case of a 43-year-old man with chronic myeloid leukemia (CML) successfully treated with nilotinib. At presentation we started him on imatinib at standard dose of 400 mg/day but after 36 months of treatment the patient didn’t achieve a molecular response. We switched him on second-generation tyrosine kinase inhibitor (TKI), nilotinib, at the dose of 800 mg/day. After twelve months on nilotinib the patient obtained a complete molecular response. During treatment with nilotinib we did not observe any drug-related toxicity.
Late onset myoclonic epilepsy in Down syndrome and dementia
Authors: Verri Annapia , Vignoli Aglaia , Terzaghi Michele , Destefani Valeria , Nespoli Luigi
Published: June 2016

Specific forms of epilepsy may be found at various ages in Down Syndrome (DS) and a sharp increase in the incidence of epilepsy with age has been documented. A specific type of myoclonic epilepsy associated with cognitive decline has been reported as “senile myoclonic epilepsy” or “late onset myoclonic epilepsy in DS” (LOMEDS). We report a new case of LOMEDS, documented by clinical and neurophysiological evaluation and psychometric assessment (DSDS and DMR). MF, male, affected by DS, was referred in 2004 at 40 years of age; he had no personal or familial history of epilepsy. Since one year, the patient presented cognitive deterioration, characterized by regression of language abilities, loss of memory, and loss of sphincters control. A brain TC showed mild brainstem and sub-cortical atrophy. In 2006, myoclonic jerks involving upper limbs occurred mainly after awakening. EEG showed a low voltage 8 Hz background activity with diffuse slow activity, intermingled with spikes or polyspikes, persisting during NREM sleep. MF was initially treated with clonazepam and after with topiramate, resulting in partial seizures control. MRI (2008) demonstrated diffuse brain atrophy, associated with marked ventricular enlargement. At the psychometric evaluation, onset of dementia was evident late in 2004, with transition to the middle stage in 2006. Last assessment (2009) showed the clinical signs of a late stage of deterioration, with loss of verbal abilities and autonomous ambulation. Using levetiracetam till 2,000 mg/die, myoclonic jerks decreased but are still present every day after awakening. On the EEG slow and poorly organized background activity with bilateral polyspike-wave discharges was recorded. Therefore, we documented a parallel progression of dementia and myoclonic epilepsy in a DS subject.
Cancer of unknown primary origin: a case report
Authors: De Carlo Elisa , Rossetto Ciro , Fasola Gianpiero
Published: June 2016

Carcinoma of unknown primary origin (CUP) accounts for 2-10% of all malignancies. The apparent absence of the primary tumour, the development of early, uncommon systemic metastases and the resistance to therapy and poor prognosis are hallmarks of this heterogeneous clinical entity and are a challenge for physicians. The diagnostic workup of patients with CUP includes a large amount of histopathological examination, as well as the use of imaging techniques that often fail to identify the primary tumour. Therefore, the optimal workup and treatment for these patients remains to be determined. Molecular diagnostic tools, such as DNA microarray analysis, could help in the search for "lost" CUP origin and guide the further treatment approach. We report the case of a 66-year-old man, with mediastinal lymph nodes metastasis of carcinoma and neurological syndrome with diplopia and balance disorders, in which many exams have been performed without finding the primary tumour.
Complete molecular response induced by nilotinib in a patient previously treated with imatinib, nilotinib and dasatinib
Authors: Pietrantuono Giuseppe
Published: June 2016

We reported a case report of a female patient with chronic myeloid leukemia who was treated with nilotinib after failure to imatinib, nilotinib, dasatinib. The patient was diagnosed in 2001 and treated with imatinib, but complete cytogenetic response (CCyR) and complete hematologic response (CHR) were lost four years later. Doubling imatinib dose to 800 mg/die gave no positive results.
The patient was enrolled in clinical trial with nilotinib, but mutational analysis performed after two months showed Y253H point mutation (no nilotinib sensitive). In April 2007 dasatinib was started and CCyR and major molecular response (MMolR) was reached. In May 2011 Bcr-Abl transcript progressively increased and mutational analysis showed a M244V point mutation. Therapy with nilotinib 800 mg/die was started, and after six months the patient obtained a complete molecular response (CMR), surprising with disappearance of both point mutations.
Deep and early molecular response induced by nilotinb in a newly diagnosed patient with chronic myeloid leukemia (CML)
Authors: Rossi Antonella Russo
Published: June 2016

We report a case of a patient with chronic myeloid leukemia diagnosed in January 2012 and treated with nilotinib 600 mg/die as first line therapy. Patient obtained a complete hematologic response (CHR) and improvement of splenomegaly in 2 weeks. In three months the patient obtained complete cytogenetic response (CCR) and an important transcript level reduction (less than 1%). According to the international recommendations, molecular analysis was performed every three months in a LABNET network laboratory. Treatment was never interrupted or reduced due to any adverse event. After 9 months patient achieved a major molecular response (MMR) and during evaluation a MR4 has been documented.
Hyponatremia: a case report of SIAD
Authors: Canu Letizia , Peri Alessandro , Parenti Gabriele
Published: June 2016

Hyponatremia, defined as serum sodium concentration <136 mEq/l, represents one of the most frequently encountered electrolyte disorder in clinical practice. Among hospitalised patients up to 15-30% present mild hyponatremia (130-135 mEq/l), whereas moderate to severe forms are seen in up to 7% of inpatients. Hyponatremia is associated with significant morbidity and mortality especially in patients with underlying diseases. According to volume status hyponatremia can be classified as hypovolemic, hypervolemic or euvolemic. An accurate diagnostic algorithm has to be performed in order to optimize the therapeutic approach. Acute and severe forms are accompanied by neurological symptoms due to cerebral edema and can cause death if not appropriately treated. Moreover, even a too rapid correction can be associated with serious complications, such as the osmotic demyelination syndrome. Hypovolemic forms have to be treated with isotonic saline infusion, whereas eu-hypervolemic forms require hypertonic saline when symptomatic, and fluid restriction or vaptans when asymptomatic. Here, we report the case of a 79-year-old woman with hyponatremia admitted to the Emergency Department of XXX.
Malnutrition, cachexia and nutritional intervention: when much becomes too much
Authors: Rianda Serena , Rossi Fanelli Filippo , Laviano Alessandro
Published: June 2016

Disease-associated malnutrition, also defined as cachexia, is a complex syndrome characterised by the progressive deterioration of nutritional status resulting from the combined effects of reduced appetite and food intake, and profound changes in host metabolism. Cachexia has been repeatedly demonstrated to represent a negative prognostic factor for patients suffering from acute and chronic diseases, including cancer. In oncology patients, early diagnosis of cachexia and timely nutritional intervention have been demonstrated not only to prevent further deterioration of nutritional status, but also to increase quality of life and survival when integrated in a multiprofessional and multidisciplinary approach. However, nutritional therapy is associated to the possible development of complications, which may be fatal. Therefore, nutritional therapy in severely malnourished patients should be cautiously prescribed by experts in the field, who should develop a monitoring program to early detect complications and to maximise the clinical efficacy.Here we describe a cancer patient affected by refeeding syndrome, who was fortunately early diagnosed and properly treated.
Influence of generics in prescribing dynamics of proton pump inhibitors in general practice
Authors: Cammarota Simona , Citarella Anna , Menditto Enrica , De Portu Simona , Napoli Luigi , Laringe Matteo , Sarnelli Giovanni , Arpino Giovanni , Piccinocchi Gaetano , Cuomo Rosario
Published: June 2016

Use of antisecretory drugs has greatly increased in recent years in Italy. After the launching of generic lansoprazole (early 2006), several Italian Regional Health Authorities have introduced measures to favour the prescription of less expensive PPI. The aim of this study is to evaluate general practitioners’ prescription (GPs) of different Proton Pump Inhibitors (PPIs) in the period between 2005 to 2008. Analysis has been performed on a database of 99 medical practitioners that have managed an average of 150,000 inhabitants. We evaluate the PPIs prescriptions from Jan 2005 to Dec 2008. Evaluations performed are the following: 1) PPI prescription (total and separately for lansoprazole, esomeprazole, pantoprazole, rabeprazole, and omeprazole); 2) prevalence of the reimbursement purpose (Gastroprotection – G; Acid-Related Disease – ARD); 3) PPI prescriptions separately for ARD diagnostic codes. Data were expressed as Compound Annual Growth Rate (CAGR). PPI consumption were quantified using Defined Daily Dose system (DDD). The total volume of PPI’s prescribing increased progressively over the 4 years (CAGR +15%). The proportion of defined daily doses accounted for by lansoprazole increased from 12.0% in 2005 to 30.9% in 2008. The prescription of omeprazole decreased from 42.2% to 26.7%, while that of esomeprazole remained costant. The reimbursement purpose was higher for G (CAGR +43%) than for ARD (CAGR +7%). We found an increase of lansoprazole prescriptions especially for heartburn (CAGR +52.4%), gastroesophageal reflux (CAGR 34,5%) and upper abdominal pain (CAGR 37,2%). Generic PPIs has unexpectedly increased the prescription of whole drug class during the period 2005-2008. Our data suggest that the appropriateness of PPI prescription after generic PPI introduction should be carefully monitored to distinguish between cost-effective from cost-ineffective PPI treatment.
Sugammadex in antagonism of neuromuscular block in anesthesia: a clinical and economic profile
Authors: Sacchi Viola , Iannazzo Sergio , Giunta Francesco
Published: June 2016

Sugammadex is a modified cyclodextrin which acts by encapsulating and inactivating the neuromuscular blocking agents (NMBAs) rocuronium and vecuronium, used to induce relaxation of skeletal muscles during surgery and to facilitate endotracheal intubation. The procedure of reversal of the block at the end of surgery can influence the time to discharge from the operating room and post-operative residual curarization (PORC) incidence, which is related to an increased rate of adverse respiratory events in the post-anaesthesia care unit. Cholinesterase inhibitors are frequently used to reverse neuromuscular block, but their use is associated with potential cardiovascular and respiratory side-effects. The recommended dose-range for sugammadex is 2-16 mg/kg, depending on the level of block: the dose is approximately 2 mg/kg for reversal of moderate blockade, 4 mg/kg for deep blockade and 16 mg/kg for the immediate reversal of a neuromuscular blockade as early as 3 minutes after 1-1.2 mg/kg of rocuronium. Four pivotal, phase III trials studied sugammadex in routine reversal of moderate, deep neuromuscular block and in the immediate reversal of rocuronium-induced block. In all the cases the drug demonstrated of being significantly more efficient than other reversal strategies, providing a faster reversal than the most used anticholinesterase comparator neostigmine. Sugammadex also appeared to have an acceptable safety profile. Acquisition cost of sugammadex is greater than that of neostigmine, but cost-savings related to the reduced theatre time and to the reduced incidence of PORC episodes can offset it. A Budget Impact analysis in the perspective of the hospital has been conducted for the Italian setting resulting in a total cost-save of 7,420 € for one year of activity. In conclusion, sugammadex appears to be a valuable innovation in anesthesiology. This drug represents a safe and effective alternative to anticholinesterase agents.
Management of patients with metastatic colorectal cancer: economic consequences of different treatment programs
Authors: Lopatriello Stefania , Negrini Cristina , Amoroso Domenico , Donati Sara
Published: June 2016

The clinical pattern of Metastatic ColoRectal Cancer patients, receiving first-line infusional 5-FU or oral capecitabine (CAP) chemotherapies, was valorized in the perspective of the Italian NHS. A cost-minimization analysis was implemented on the basis of retrospective data from 5 centers. 202 subjects: 126 receiving 5-FU-association, 10 5-FU-monotherapy; 31 CAP-association, 35 CAP-monotherapy. Therapeutic patterns differed as to chemotherapy administration resources consumption: 5-FU was administered in Day Hospital and CAP in the outpatient setting. Mean total cost/patient was in the range of € 6,841 (monotherapy-5-FU)- € 12,620 (association-5-FU) and € 2,056 (monotherapy-CAP)-€ 9,745 (association-CAP). The infusional administration route of 5-FU was the driver of costs.
The use of corticosteroids in patients with chronic obstructive pulmonary disease: epidemiological and economic aspects
Authors: Katz Pablo M. , Pegoraro Valeria
Published: June 2016

Objective: this study aimed at assessing the level of compliance to GOLD guidelines regarding the use of ICS containing drugs for the treatment of patients with COPD in the GPs setting in Italy and at evaluating the economic consequences that the use of corticosteroids may have, specifically in mild and moderate COPD patients where it is inappropriate. Methods: the retrospective GPs database study has analyzed patients with at least one diagnosis of COPD during the period January 2005 – December 2008 who had a report of VEMS and at least one prescription of a drug from ATC R03 class within two months from the date of spirometric exam, who were 40 years or older and that have been followed for at least 9 months. Patients were classified in four disease severity groups according to GOLD (2008). Compliance to GOLD guidelines regarding the use of corticosteroids was evaluated on the basis of the first treatment prescribed after spirometric exam. The analysis evaluated exacerbations as well, assuming their occurrence when one prescription of either antibiotic, oxygen or systemic corticosteroid was found. The cost of the first prescription of treatments containing ICS in mild and moderate patients was calculated. Then the “Hypothetic cost” was built for those patients in order to estimate the cost that would have been created in case the considered treatments had been ICS free. The difference between these two costs represents inappropriate cost that could have been avoided by using an ICS free treatment, more appropriate according to GOLD. Results: a cohort of 2,103 Italian patients with the diagnosis of COPD, followed by 700 GPs all over Italy was analyzed. An ICS-containing treatment was prescribed to more than 50% of patients within each disease severity group. The percentage of patients who experienced an exacerbation within 6 months from the first prescription was not found to be different among patients prescribed with an ICS-free treatment and those treated with an ICS-containing treatment and was independent of the disease severity. In mild and moderate COPD patients respectively, 53% and 48% of the cost generated by the ICS containing prescriptions represent the inappropriate cost for the Health Care System. Moreover, patients are unnecessarily exposed to the risk of inadequate therapy.
Effectiveness and cost of treatment with maraviroc in HIV infection
Authors: Sacchi Viola , Pradelli Lorenzo
Published: June 2016

Since 1995, life expectancy and quality of life of HIV patients improved significantly due to the use of Highly Active Anti-Retroviral Therapy (HAART), consisting of different combinations of three classes of antiretroviral agents, nucleoside and non-nucleoside reverse transcriptase inhibitors, and protease inhibitors. Recently, new treatment options for individuals developing resistance to these drugs have become available, with the appearance of new drug classes like integrase inhibitors, fusion inhibitors and CCR5 antagonists. Maraviroc is the first antiretroviral agent belonging to the latter drug class approved for clinical use. CCR5 receptor antagonists act by blocking the interaction of the HIV virus with the CCR5 chemokine receptor, a co-receptor essential to the entry process of R5-tropic viruses. The drug is indicated, in combination with other antiretroviral products, for treatment-experienced adult patients infected with only CCR5-tropic HIV-1 detectable virus strains. Results of main phase III clinical trials indicate that maraviroc, in combination with optimized background therapy (OBT), causes significantly greater reductions in viral load and increases in CD4+ cell count, as compared to OBT alone in this kind of patients. In Italy, the monthly cost of maraviroc therapy is about € 780. A number of economic evaluations, performed for different settings, demonstrate that the therapy including maraviroc is cost-effective if compared to OBT alone, determining an ICER generally below the threshold of three times the GDP per capita. In the Italian context, the ICER determined by OBT + maraviroc vs OBT alone is approximately 45,000 €/LYG.