Next generation sequencing in adult patients with glioblastoma in Switzerland: a multi-centre decision analysis.

BACKGROUND: Glioblastoma is the most common malignant primary brain tumour in adults and driven by various genomic alterations. Next generation sequencing (NGS) provides timely information about the genetic landscape of tumours and might detect targetable mutations. To date, differences exist in the application and NGS assays used as it remains unclear to what extent these variants may affect clinical decision making. In this survey-based study, we investigated the use of NGS in adult patients with glioblastoma in Switzerland. METHODS: All eight primary care centres for Neuro-Oncology in Switzerland participated in this survey. The NGS assays used as well as the criteria for the application of NGS in newly diagnosed glioblastoma were investigated. Decision trees were analysed for consensus and discrepancies using the objective consensus methodology. RESULTS: Seven out of eight centres perform NGS in patients with newly diagnosed glioblastoma using custom made or commercially available assays. The criteria most relevant to decision making were age, suitability of standard treatment and fitness. NGS is most often used in fitter patients under the age of 60 years who are not suitable for standard therapy, while it is rarely performed in patients in poor general health. CONCLUSION: NGS is frequently applied in glioblastomas in adults in Neuro-Oncology centres in Switzerland despite seldom changing the course of treatment to date.

Cerebellar infarction in a patient with cerebral vein thrombosis and patent foramen ovale: brain-to-brain embolism?

Although the association between PFO and cryptogenic stroke is well shown in young adults, the causality is still unclear. The pathogenetic mechanism of ischemic stroke related to PFO is not entirely understood. Indeed, besides the well-known paradoxical embolism, formations of thrombi in situ, especially in the presence of ASA, a higher incidence of atrial fibrillation have been often observed. Cerebral sinus venous thrombosis may be due to local inflammation or to acquired or genetic thrombophilia including hyperhomocysteinemia. We report a case of a young man presenting with a cerebellar infarction probably secondary to a paradoxical brain-to-brain embolism, in which the only detectable embolic source was a cerebral vein thrombosis.

BRIT1/MCPH1 expression in chronic myeloid leukemia and its regulation of the G2/M checkpoint.

BRIT1 (BRCT-repeat inhibitor of hTERT expression), also known as microcephalin (MCPH1), is a crucial gene in the complex cellular machine that is devoted to DNA repair and acts as a regulator of both the intra-S and G2/M checkpoints. The most important role of BRIT1/MCPH1 in the regulation of cell cycle progression appears to be the G2/M checkpoint. The K562 and peripheral blood cells of chronic myeloid leukemia (CML) patients at diagnosis were found to downregulate BRIT1/MCPH1. However, we could not find any correlation between bcr/abl activity and the BRIT1/MCPH1 level. In order to study the genomic instability of CML cells, we evaluated the ability of these cells to arrest mitotic division after exposure to hydroxyurea, a known genotoxic agent. We showed that CML cells continue to proliferate without the activation of the G2/M cell cycle checkpoint arrest or of the apoptotic mechanism. This behavior may predispose the cells to accumulate genomic defects. In conclusion, we found that CML cells have a low BRIT1/MCPH1 level and show a defective G2/M arrest, confirming that these cells have a constitutive genomic instability.

Benign Multicystic Peritoneal Mesothelioma (BMPM) as a rare cause of abdominal pain in a young male: case report and review of the literature.

Benign Multicystic Peritoneal Mesothelioma (BMPM) is a rare benign cystic neoplasm that arise from the peritoneum, typically found in young females (83%), with a high incidence of local recurrence after resection (almost 50% of cases). Fewer than 200 cases have been reported worldwide in 2017. Due to its rarity and the lack of a classical clinical presentation, the diagnosis pre-operatively is challenging; moreover a great part of the literature is composed of case reports and small group studies. Nowadays, guidelines are still not available, and treatment is en bloc resection of the lesion. Some authors suggest the use of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) associated with the surgical approach, even if comparative data on recurrence and complications are lacking. We report a case of BMPM diagnosed in a 40-year-old male who underwent an exploratory laparoscopy and complete excision of the neoformation. Pathology confirmed the presence of a BMPM.

Prevalence of Parkinson's disease and other types of parkinsonism in the Aeolian Archipelago, Sicily.

OBJECTIVE: To estimate prevalence of Parkinson's disease (PD) and other types of parkinsonism in the Aeolian Archipelago, Sicily. METHODS: We studied the frequency of PD and other types of parkinsonism in the Aeolian Archipelago (population 13,431). All potential cases were identified from available medical information sources. To ensure the completeness of the case-findings, a screening questionnaire was also mailed to residents aged 40 years and over. Subjects were considered prevalent if they fulfilled the SNES diagnostic criteria for PD, on prevalence day (January 1, 2001). RESULTS: We identified 17 patients with parkinsonism from medical sources, and 4 from mail-survey. Prevalence for all types of parkinsonism was 156.3/100,000 (95% CI 99.4-234.8). Fourteen subjects fulfilled diagnostic criteria for PD giving a crude prevalence of 104.2/100,000 (95% CI 59.4-170.7) and 422.5/100,000 in the population aged 60 years and over. CONCLUSIONS: Prevalence of all types of parkinsonism and PD found in the Aeolian Archipelago is lower than that previously reported in Sicily.

Hymecromone in the treatment of motor disorders of the bile ducts: a multicenter, double-blind, placebo-controlled clinical study.

Biliary dyskinesia is frequently encountered in clinical practice and is characterized by pain during or after meals. The present study was designed to assess the action of hymecromone in patients with motor disorders of the bile ducts. One hundred twenty-three patients (36 men and 87 women) were enrolled in the multicenter double-blind placebo-controlled study. The mean age was 60.3 years +/- 14.2 SD. Diagnosis was dyspepsia in 58 patients, dyskinesia in 59, cholelithiasis in five and hepatopathy in one. The patients were divided into two groups. One group (61 patients) was treated with hymecromone (300 mg tablets at a dosage of 1,200 mg/day, 2 tablets midday and evening) and another group (62 patients) was treated with placebo. Treatment lasted for 14 days. Control of dyspepsia and pain symptoms of biliary origin was more marked and constant with hymecromone than with placebo. By the end of the treatment, patients in the hymecromone group showed a 70.3% reduction in intensity of spontaneous abdominal pain, while the placebo group showed a 43.8% reduction. Hymecromone was well accepted by the patients and judged to be effective by the investigator in 88.5% of patients treated. The possibility of using hymecromone in 300-mg tablets in the treatment of motor disorders of the bile ducts is thus confirmed.

Posatirelin for the treatment of degenerative and vascular dementia: results of explanatory and pragmatic efficacy analyses.

In order to confirm the efficacy and safety of posatirelin (L-pyro-2-aminoadipyl-L-leucyl-L-prolinamide), a synthetic peptide having cholinergic, catecholaminergic and neurotrophic activities, a multicentre, double-blind, controlled study versus placebo was planned in elderly patients suffering from Alzheimer's disease and vascular dementia, according to National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria, respectively. The trial consisted of a 2-week run-in phase with placebo administered once a day orally, followed by a double-blind period of 3 months, with posatirelin or placebo administered once a day intramuscularly. Efficacy was assessed using the Gottfries-Bråne-Steen (GBS) Rating Scale (primary variable) and the Rey Memory Test (secondary variable). Laboratory tests, vital signs and adverse events were monitored. A total of 360 patients were randomized, the intent-to-treat sample (ITT) being made up of 357 patients and the per protocol sample (PP) of 260 patients. Both pragmatic and explanatory analyses showed significant differences between treatment groups in the GBS Rating Scale and the Rey Memory Test, with no difference in the two types of dementia. No difference between treatments was observed in safety variables, the incidence of adverse events in the posatirelin group being 7.3%. The study confirms previous results showing that treatment with posatirelin can improve cognitive and functional abilities of patients suffering from degenerative or vascular dementia.

Correlation between digestive disease and psychiatric disease: casual or causal implication?

The aim of this study was to evaluate the prevalence of psychiatric disturbances among patients affected with digestive diseases (both organic and functional) and, viceversa, the prevalence of digestive disturbances among patients with psychiatric diseases. We performed a trasversal study on: 100 patients with organic digestive diseases and 100 patients with functional digestive diseases afferent from a Gastroenterologic Ambulatory (gastroenterologic group); 50 patients afferent from a Psychiatry Service (psychiatric group) and 50 patients afferent from a General Medicine Ambulatory affected with a non gastroenterologic active problem (control group). Each patient underwent an anamnestic, laboratory and instrumental evaluation, in order to ascertain or exclude the presence of digestive symptoms and their eventual organic basis; moreover, a semistructured interview was performed aimed at identifying a psychiatric disturbance, according to DSM-IIIr criteria. Our results showed a significantly higher prevalence: 1) of psychiatric disturbances, in the gastroentorologic group versus the control group (p<0.001), especially of somatoform (p<0.05) and anxious (p<0.001) disorders; 2) of psychiatric disturbances among patients affected by functional digestive disorders versus patients affected by organic digestive disorders; 3) of gastroenterologic disorders, in the psychiatric group versus the control group (p<0.001), with a significantly higher prevalence of functional gastroenterologic syndromes in comparison the organic ones (p<0.001). The well-established bidirectional correlation between digestive functional and psychiatric disorders is a necessary but not sufficient condition to state a relationship of direct causality between the two syndromes; however we can hypothesize that the well documented neuro-hormonal alterations may cause, on clinical grounds different symptoms, that are differently interpreted by the different specialists (gastroenterologists or psychiatrists) consulted.

[Neonatal chylous ascites: a case report and review of the literature]. / Ascite chilosa neonatale: descrizione di un caso e revisione della letteratura.

The case of a newborn with asymptomatic chylous ascites operated on because of voluminous inguino-scrotal hernia is reported and a review of the recent literature about aetiology, diagnosis and treatment of neonatal chylous ascites is made.

Palifermin reduces infection rate and hyperfibrinogenemia in patients treated with high-dose chemotherapy based on beam or BU-thiothepa.

We performed a retrospective study in patients who underwent high-dose chemotherapy and auto-SCT because of haematological malignancies. Forty patients were treated with palifermin while 80 were controls selected after being matched for diagnosis and length of neutropenia. Patients treated with BEAM or BU-CY or THIO-CY (BEAM/BUS) displayed, after palifermin, a lower rate of severe oral mucositis (P=0.03). This beneficial effect of palifermin was not evident in the stratum of patients treated with high-dose melphalan (HD-PAM). After palifermin, we observed in the whole treated population a reduced rate of 'fever of unknown origin' (FUO, P=0.02) and of severe infections not related to Gram-positive bacteria (FUO, Gram-negative bacteremia or pneumonia) (P=0.003). This effect of palifermin on infections not related to Gram-positive bacteria was evident only in patients receiving BEAM/BUS (P=0.01) and not in patients treated with HD-PAM (P=0.11). Fibrinogen peak in plasma was found to be reduced after palifermin in the whole population (P=0.01) and in the stratum who received BEAM/BUS (P=0.02) but not in the stratum of HD-PAM. In conclusion, anti-infectious beneficial effects of palifermin are more evident in BEAM/BUS-treated patients and toward some types of infections. Reduction of fibrinogen level after palifermin suggests that this agent reduces not only the rate of infections but also their severity.

Status cataplecticus misdiagnosed as recurrent syncope.

A 76-year-old patient, since the age of 45, presented with frequent attacks often triggered by emotional stimuli and characterised by forward head drop and a fall to the ground without loss of consciousness. Clinically these episodes were misinterpreted as pseudoseizures and treated with clomipramine for more than 20 years. In spite of this chronic therapy, during the last year, the attacks presented with a daily recurrence and, moreover, after arbitrary clomipramine withdrawal, they increased in frequency until they became subcontinuous. Videopolygraphic analysis, multiple sleep latency test (MSLT) and human leukocyte antigen (HLA) association studies were suggestive of narcolepsy and the recurrent episodes, diagnosed as status cataplecticus, recovered after citalopram administration.

Intraperitoneal rupture of an infected urachal cyst: an unusual cause of acute abdomen in children. A case report and review of the literature.

Urachal cysts are rare and usually asymptomatic until they become infected. This is a report of a case of peritonitis due to intraperitoneal rupture of an infected urachal cyst in a 3-month-old girl. A review of the literature found 31 similar cases previously reported, only seven of which were described in children. The diagnosis and treatment of intraperitoneal perforation of an infected urachal cyst in a child are discussed.

Primary non-refluxing megaureters.

Megaureters may be primary or secondary, and the dilatation may be due to obstruction or reflux, or both or neither. The cause of primary obstructed megaureter is the aperistaltic and narrowed pre-vesical portion of the ureter. The inner sheath of the terminal ureter generally shows a reduced amount of longitudinal smooth muscle bundles and an increased amount of collagen. Primary non-refluxing megaureters represent 23% of all prenatal diagnoses of hydronephrosis. They are more common in males and on the left side, and in 25% are bilateral. In older children they may become symptomatic. The diagnostic work up should include an ultrasound, a micturating cystourethrogram and an isotopic renogram. Most primary megaureters regress spontaneously or remain stable without compromising renal function, but 10-25% require surgery because of a progressive reduction in renal function or increasing dilatation, or because they become symptomatic. The basic principles of surgical repair include: resection of the obstructing segment, reduction in size of the dilated ureter, and re-implantation into the bladder using an anti-reflux technique.

Usefulness of ultrasonography in gastric foreign body retention.

Foreign-body ingestion occurs frequently in childhood. The diagnosis of ingestion is usually made by plain film radiography. Ultrasound is not routinely used in the investigation of gastric foreign bodies because of the limitations imposed by intestinal gas. This drawback can be overcome by distending the stomach with an anechoic liquid, which acts as an acoustic window. In a child who had ingested a coin, US performed after drinking tea was diagnostic and showed a hyperechoic image with an acoustic shadow inside the stomach. We believe that US is an appropriate technique for follow-up of gastric foreign bodies.

[A follow-up study in individuals subjected to ileo-cecal resection in infancy and childhood]. / Controlli a distanza di individui sottoposti in età pediatrica a resezioni intestinali interessanti anche la valvola ileo-cecale.

It is stated that the ileocecal valve delays the passage of ileal contents into the cecum and acts as a barrier against reflux and ascension of colonic bacterial flora into the small bowel: its resection may lead to bacterial colonization of the ileum and to abnormalities of intestinal motility, transit and absorption. In this study twenty individuals subjected in pediatric age (1 day to 11 years) to ileocecal resection have been evaluated from 2 to 19 years after surgery. Three patients underwent limited ileocecal resection, in four this was associated with a significant ileal resection, in five with extensive right colon resection and in eight with extensive ileal and right colon resection. Growth, stool habit, hematology and serum biochemistry were examined; all patients also underwent abdominal ultrasonography. In all body weight and height were within normal limits; seven had moderate diarrhea up to 18 months after surgery and two who required extensive intestinal resection (40 and 30 cm of small bowel left) had diarrhea until about 36 months after surgery: now all of them have daily fecal evacuation. Hematological, biochemical, urinary and fecal studies proved normal except in one treated with TPN who presented transaminases slightly increased and in three suffering from mucoviscidosis in whom steatorrhea with moderate alterations of fats and elevation of alkaline phosphatase and transaminases were present. Urinary and gall stones were not seen in anyone. In conclusion from this study it can be postulated that removal of ileocecal valve can be done safely in children.

Migraine stroke: a possible complication of both migraine with and without aura.

We describe four migraine patients who developed an ischemic stroke during their typical migraine attacks. Cerebral infarction as a possible complication of migraine without aura is discussed. We propose a review of the migraine stroke definition of the International Headache Society.

[Follow-up study of pulmonary function in individuals subjected to lobectomy in infancy and childhood]. / Valutazione a distanza della funzionalità respiratoria in individui sottoposti a lobectomia polmonare in età pediatrica.

Experimental research in animals have demonstrated that pulmonary development continues after birth. This happens in man as well: alveolar proliferation and enlargement go on until the eighth year of age, furthermore complete pulmonary development is achieved until the 20-22 years of age. It is therefore possible to hypothesise that respiratory deficit following pulmonary exeresis in children would regress with time. In the Pediatric Surgery of IRCCS Policlinico S. Matteo of Pavia eight children, 4 days to 8 years of age, underwent lobectomy for pulmonary hypertensive emphysema (3), lung abscess (2), bronchogenic cysts (2) and hystiocytoma (1). One of them was lost to follow-up; the remainders were controlled from 3 to 25 years after surgery: all of them enjoy a normal active life. Respiratory function was evaluated through blood chemistry, blood gas analysis, basal and after strain ECG, chest X-ray, spirometry, basal and after strain pulmonary scintigraphy. Basal and after strain ECG, chest X-ray, and arterial blood gas were normal in every examined subjects; spirometry, although results are quite variable, did not show serious respiratory deficits; basal after strain pulmonary scintigraphies weren't homogeneous. These results, although they aren't univocally interpretable, positively confirmed that the residual lung after lobectomy has a satisfactory possibility of functional recovery.

Virological and serological response of cattle following field vaccination with bivalent modified-live vaccine against bluetongue virus serotypes 2 and 9.

Following the bluetongue (BT) epidemic in Italy, the government initiated a vaccination campaign involving all domestic ruminants (cattle, sheep and goats) in the affected and adjacent areas to create a resistant population and to reduce virus circulation. Based on the serotypes circulating in the affected areas, monovalent BT virus (BTV) serotype 2 (BTV-2), or bivalent BTV-2 and BTV-9, modified-live vaccines were used. These are manufactured by Onderstepoort Biological Products in South Africa and, because they are recommended for use in sheep only, very little data exists on their use in cattle under field conditions. To evaluate duration and levels of viraemia and the antibody response following vaccination, 30 cattle in various stages of pregnancy were selected and vaccinated with a bivalent BTV-2/BTV-9 vaccine. Blood samples were taken from the animals three times a week for two months and screened using the competitive enzyme-linked immunosorbent assay (c-ELISA) and the virus neutralisation (VN) test. Intravenous egg inoculation, followed by two blind passages in Vero cells, was used to isolate BTV-2 and BTV-9 from ethylene-diaminetetra-acetic acid (EDTA) blood samples, and virus titres determined in viraemic animals. Titres against BTV were detected in 27 animals between days 4 and 35 post vaccination (pv). Viraemia peaked on day 9 pv with average viral titres of 10(4.5)TCID50/ml. From day 9 pv, the c-ELISA detected antibodies in all animals while low VN titres were observed commencing on day 18 pv. Furthermore, VN antibody to BTV-2 was detected in only 17 of the animals vaccinated and to BTV-9 in 27 animals.

Liver resection for hepatocellular carcinoma in cirrhotic patients.

The results of a multicentric retrospective analysis of 265 liver resections for hepatocellular carcinoma in cirrhotic patients have been collected and assessed. Overall operative mortality was 9.1%. The actuarial 3-year survival was 46.5%. Better results were obtained in patients with encapsulated lesions and alphafetoprotein levels less than 400 ng/dl. Tumoral recurrence, which was the main cause of late death, was related to alphafetoprotein higher levels and to the type of surgery performed: tumor resection with short tumour free margin had the highest recurrence rate. Results were significantly better in those centers where intraoperative ultrasonography was systematically employed.