Moderate Mocha Coffee Consumption Is Associated with Higher Cognitive and Mood Status in a Non-Demented Elderly Population with Subcortical Ischemic Vascular Disease

To date, interest in the role of coffee intake in the occurrence and course of age-related neurological and neuropsychiatric disorders has provided an inconclusive effect. Moreover, no study has evaluated mocha coffee consumption in subjects with mild vascular cognitive impairment and late-onset depression. We assessed the association between different quantities of mocha coffee intake over the last year and cognitive and mood performance in a homogeneous sample of 300 non-demented elderly Italian subjects with subcortical ischemic vascular disease. Mini Mental State Examination (MMSE), Stroop Colour-Word Interference Test (Stroop T), 17-items Hamilton Depression Rating Scalfe (HDRS), Activities of Daily Living (ADL), and Instrumental ADL were the outcome measures. MMSE, HDRS, and Stroop T were independently and significantly associated with coffee consumption, i.e., better scores with increasing intake. At the post-hoc analyses, it was found that the group with a moderate intake (two cups/day) had similar values compared to the heavy drinkers (≥three cups/day), with the exception of MMSE. Daily mocha coffee intake was associated with higher cognitive and mood status, with a significant dose-response association even with moderate consumption. This might have translational implications for the identification of modifiable factors for vascular dementia and geriatric depression.     

Intracortical and Intercortical Motor Disinhibition to Transcranial Magnetic Stimulation in Newly Diagnosed Celiac Disease Patients

Background: Celiac disease (CD) may present or be complicated by neurological and neuropsychiatric manifestations. Transcranial magnetic stimulation (TMS) probes brain excitability non-invasively, also preclinically. We previously demonstrated an intracortical motor disinhibition and hyperfacilitation in de novo CD patients, which revert back after a long-term gluten-free diet (GFD). In this cross-sectional study, we explored the interhemispheric excitability by transcallosal inhibition, which has never been investigated in CD. Methods: A total of 15 right-handed de novo, neurologically asymptomatic, CD patients and 15 age-matched healthy controls were screened for cognitive and depressive symptoms to the Montreal Cognitive Assessment (MoCA) and the 17-item Hamilton Depression Rating Scale (HDRS), respectively. TMS consisted of resting motor threshold, amplitude, latency, and duration of the motor evoked potentials, duration and latency of the contralateral silent period (cSP). Transcallosal inhibition was evaluated as duration and latency of the ipsilateral silent period (iSP). Results: MoCA and HDRS scored significantly worse in patients. The iSP and cSP were significantly shorter in duration in patients, with a positive correlation between the MoCA and iSP. Conclusions: An intracortical and interhemispheric motor disinhibition was observed in CD, suggesting the involvement of GABA-mediated cortical and callosal circuitries. Further studies correlating clinical, TMS, and neuroimaging data are needed.     

COX-2 expression of ampullary carcinoma: correlation with different histotypes and clinicopathological parameters

Epidemiological studies suggest that regular intake of nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with reduced incidence of gastrointestinal cancer. Several lines of evidence indicate that the antineoplastic effect of NSAIDs is attributable to COX-2 inhibition. The aim of our study was to assess COX-2 expression in a series of primary untreated ampullary carcinomas and its possible correlation with clinicopathological parameters. In the present study, 45 surgical specimens of invasive ampullary carcinomas were histologically classified into pancreaticobiliary, intestinal, and unusual types. COX-2 expression by immunohistochemical method was analyzed. High COX-2 expression was detected in 35 (77.8%) ampullary carcinomas. Among these, 20/21 (95.2%) were classified as intestinal, 9/18 (50%) pancreaticobiliary, and 6/6 (100%) unusual type. A significant statistical difference in terms of COX-2 expression was found between pancreaticobiliary vs intestinal type (P=0.002). Furthermore, a negative significant statistical correlation was found between T factor and COX-2 expression (P=0.047). The different COX-2 expression among histopathological types supports the concept of histogenetical difference of ampullary carcinomas. Furthermore, the high rate of COX-2 expression in the intestinal subtype of ampullary carcinoma may represent the rational for a histotype-tailored therapy targeting COX-2.     

Somatostatin analogs in treatment of non-growth hormone-secreting pituitary adenomas

Besides well-known effects in GH-secreting adenomas, somatostatin analogs such as octreotide and lanreotide have been used in TSH-secreting adenomas and in the so-called clinically nonfunctioning adenomas. The rationale for their use is based on the evidence that both these tumor types express large amounts of somatostatin receptor subtypes 2 and 5, which are preferentially bound by octreotide and lanreotide. However, whether in TSH-secreting adenomas the results are excellent in the nonfunctioning type, the results are controversial. Some preliminary results showing a very rapid recovery of the visual field have not been confirmed subsequently. No evident effect of tumor shrinkage has been reported. At present, the use of somatostatin analogs in clinically nonfunctioning adenomas is questioned.     

A cluster of Geotrichum clavatum (Saprochaete clavata) infection in haematological patients: a first Italian report and review of literature

Invasive fungal infections, usually Aspergillus and Candida, represent a major cause of morbidity and mortality in patients with malignant haematological diseases, but in the last years rare fungal infections have more frequently been reported. Here, we report the clinical history of three patients affected with haematological malignancies who developed an infection caused by Geotrichum (G.) clavatum. Two out of three patients were affected by acute myeloid leukaemia (AML), and one by mantle cell lymphoma (MCL). All patients received cytarabine‐based chemotherapeutic regimens and developed G. clavatum infection within 3 weeks from therapy initiation. In all cases, G. clavatum was isolated from central venous catheter and peripheral blood cultures. In vitro susceptibility test confirmed an intrinsic resistance to echinocandins and, in all cases, visceral localisations (spleen, liver and lung) were documented by total body computed tomography (CT) scan. A prolonged antifungal therapy with high doses liposomal amphotericin‐B was necessary to obtain fever resolution. Only the patient with MCL died while the other two AML recovered, and one of them after received an allogeneic stem cell transplantation. We consecutively reviewed all published cases of infection caused by G. clavatum. Our experience and literature review indicate that G. clavatum can cause invasive infection in haematological patients, mainly in those with acute leukaemia.     

COX-2 localization within plasma membrane caveolae-like structures in human lobular intraepithelial neoplasia of the breast

Cyclooxygenase-2 (COX-2) is highly expressed in human intraepithelial neoplasia of the breast and takes part in the molecular pathway implicated in progression of breast cancer. Recently, we demonstrated that COX-2 protein is mainly located in plasma membrane of lobular intraepithelial neoplasia (LIN) cells suggesting a localization in caveolae-like structures. The aim of the present study is to establish subcellular locations of COX-2 and its colocalization with caveolin-1 (CAV-1) to caveolae structures in LIN. To establish a relationship between COX-2 and CAV-1, 39 LINs were studied by immunohistochemistry and confocal microscopy analysis. COX-2 and CAV-1 expression was observed respectively in 79.5 and in 94.9% of LIN studied. A positive correlation was found between membrane COX-2 staining pattern and CAV-1 expression, while no correlation was found between cytoplasm COX-2 staining pattern and CAV-1. Confocal analysis showed that COX-2 localized to plasma membrane was strictly associated to CAV-1 suggesting that an amount of COX-2 protein is placed in caveolae-like structures. Our results show that COX-2 is localized within caveolae compartment and colocalized with CAV-1 protein in LIN lesions. Because caveolae are rich in signaling molecules, this COX-2 compartment may play an important role in diverse breast cancer carcinogenesis processes.     

Very delayed hyponatremia after surgery and radiotherapy for a pituitary macroadenoma

Severe hyponatremia (118 mmol/l) with natriuresis, consistent with cerebral salt wasting syndrome (CSWS), occurred 38 days after transsphenoidal surgery in a 59-year-old woman affected by a pituitary non-functioning macroadenoma. From the 35th day after surgery, she showed progressive polyuria, hypotension and hyponatremia associated with natriuresis, decreased plasma and increased urinary osmolality. The clinical examination revealed signs of dehydration and gradual decline in the level of consciousness. The anterior pituitary function was normal due to appropriate replacement of thyroid and adrenal axis. The patient was treated with saline administration until normal natremia and water balance were restored and neurological symptoms had completely disappeared. This case focuses on the unusually prolonged time of development of post-surgery hyponatremia, despite delayed symptomatic hyponatremia being reported to commonly occur 7 days after transsphenoidal surgery. Therefore, we would advise not to limit the periodic follow-up of the hydroelectrolytic balance to the first two weeks after surgery, but to prolong it until after discharge from hospital. In fact, an early diagnosis is of great importance to prevent permanent neurological damage or death. Since CSWS and syndrome of inappropriate secretion of ADH, the two disorders alternatively imputed to generate post-surgical hyponatremia, are characterized by different pathogenic mechanisms and require opposing therapeutic approaches, the occurrence of extracellular volume dilution or of increased sodium renal loss should be carefully investigated. The evidences in favor of CSWS, the possible mechanisms behind the syndrome and diagnosis and management of patients with post-transsphenoidal surgery CSWS are discussed.     

Complete remission of Nelson's syndrome after 1-year treatment with cabergoline

In this case report we demonstrated that treatment with the long-acting D2 receptor agonist cabergoline for 1 year induced normalization of plasma ACTH levels and disappearance of the pituitary tumor in a patient with Nelson's syndrome. A young man underwent bilateral adrenalectomy and subsequent pituitary irradiation for Cushing's disease after unsuccessful neurosurgical treatment. Thereafter, he was given cortisone acetate replacement at the dose of 62.5 mg a day. Fifteen months after pituitary irradiation, he developed Nelson's syndrome, having skin hyperpigmentation, high plasma ACTH levels (376 ng/l) and a pituitary microadenoma (5 mm) documented at magnetic resonance imaging (MRI) of the pituitary region. After 6 months of cabergoline treatment, given at the dose of 1 mg a week, plasma ACTH levels were significantly decreased (from 376 to 113 ng/l) but they were not normalized. Cabergoline dose was then increased up to 2 mg a week. Six months later plasma ACTH levels were normalized (22 ng/l) and MRI demonstrated the disappearance of the pituitary adenoma. In order to investigate on the direct effect played by cabergoline treatment on the remission of Nelson's syndrome, the treatment was withdrawn. Plasma ACTH levels significantly increased (119 ng/l) after 3 months of treatment withdrawal. At the last follow-up, during cabergoline treatment at the dose of 2 mg/week plasma ACTH levels were normalized (40.4 ng/l). This case demonstrated that cabergoline treatment is able to induce the remission of Nelson's syndrome and may be a valid therapeutic alternative in this syndrome.     

Increased incidence of cystic fibrosis gene mutations in adults with disseminated bronchiectasis

In order to identify a possible hereditary predisposition tothe development of obstructive pulmonary disease of unknownorigin, we have looked for the presence of Cystic Fibrosis TransmembraneRegu lator (CFTR) gene mutations in unrelated patients withno signs of Cystic Fibrosis (CF). We screened for 70 commonmutations, and also for rare mutations by denaturing gradientgel electrophoresis analysis. In this search, different CFTRgene mutations (R75Q,     

Clinical significance of occult central nervous system disease in adult acute lymphoblastic leukemia: a multicenter report from the Campus ALL Network

In acute lymphoblastic leukemia (ALL), flow cytometry (FCM) detects leukemic cells in patients’ cerebrospinal fluid (CSF) more accurately than conventional cytology (CC). However, the clinical significance of FCM positivity with a negative cytology (i.e., occult central nervous system [CNS] disease) is not clear. In the framework of the national Campus ALL program, we retrospectively evaluated the incidence of occult CNS disease and its impact on outcome in 240 adult patients with newly diagnosed ALL. All CSF samples were investigated by CC and FCM. The presence of ≥10 phenotypically abnormal events, forming a cluster, was considered to be FCM positivity. No CNS involvement was documented in 179 patients, while 18 were positive by modified conventional morphology with CC and 43 were occult CNS disease positive. The relapse rate was significantly lower in CNS disease negative patients and the disease-free and overall survival (OS) were significantly longer in CNS disease negative patients than in those with manifest or occult CNS disease positivity. In multivariate analysis, the status of manifest and occult CNS disease positivity was independently associated with a worse OS. In conclusion, we demonstrate that in adult ALL patients at diagnosis FCM can detect occult CNS disease at high sensitivity and that the status of occult CNS disease positivity is associated with an adverse outcome. (Registered at clinicaltrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03803670","term_id":"NCT03803670"}}NCT03803670).