Magnetoencephalography reveals differences in brain activations for fast and slow responses to simple multiplications.

Despite decades of studies, it is still an open question on how and where simple multiplications are solved by the brain. This fragmented picture is mostly related to the different tasks employed. While in neuropsychological studies patients are asked to perform and report simple oral calculations, neuroimaging and neurophysiological studies often use verification tasks, in which the result is shown, and the participant must verify the correctness. This MEG study aims to unify the sources of evidence, investigating how brain activation unfolds in time using a single-digit multiplication production task. We compared the participants' brain activity-focusing on the parietal lobes-based on response efficiency, dividing their responses in fast and slow. Results showed higher activation for fast, as compared to slow, responses in the left angular gyrus starting after the first operand, and in the right supramarginal gyrus only after the second operand. A whole-brain analysis showed that fast responses had higher activation in the right dorsolateral prefrontal cortex. We show a timing difference of both hemispheres during simple multiplications. Results suggest that while the left parietal lobe may allow an initial retrieval of several possible solutions, the right one may be engaged later, helping to identify the solution based on magnitude checking.

Intra-operative fluorescence angiography is reproducible and reduces the rate of anastomotic leak after colorectal resection for cancer: a prospective case-matched study.

AIM: Intra-operative fluorescence angiography (IOFA) with indocyanine green provides information on tissue perfusion that may help prevent an anastomotic leak (AL). The aim of this study was to assess the impact of IOFA on outcomes after left-sided colonic or low anterior resection with anastomosis for colorectal cancer. METHODS: All patients with left-sided colonic or rectal cancer, operated between June 2017 and December 2018, were prospectively included. IOFA has been routinely implemented since May 2018. Reproducibility of IOFA, after a 1:1 matching for relevant clinical risk factors of AL, was studied in patients with IOFA (IOFA+) and without IOFA (IOFA-). Outcomes were compared in terms of postoperative events such as clinically relevant AL as the primary end-point. RESULTS: In the IOFA+ group, changing of the initially planned colon transection due to inadequate perfusion occurred in five out of 46 patients (10.9%). Agreement between intra-operative assessment and postoperative blind review of IOFA was deemed strong (Cohen's kappa index 0.893, 95% CI 0.788-0.998, P < 0.001). Among 111 patients, 42 matched patients were included in each group. There was significantly more clinically relevant AL in the IOFA- group compared to the IOFA+ group (16.7% vs 2.4%, P = 0.026) involving significantly more anastomotic dehiscence which required re-intervention (19% vs 2.4%, P = 0.014). Additionally, more descending colon ischaemia/necrosis was observed in the IOFA- group compared with the IOFA+ group (9.5% vs 0%, P = 0.040). CONCLUSION: In this prospective case-matched study, IOFA decreased the occurrence of clinically relevant AL due to necrosis of the descending colon or anastomosis. Upon blind review, perfusion assessment using IOFA was reproducible.

[New immunotherapeutic approaches in oncology and hematology]. / Nouvelles approches d'immunothérapie en onco-hématologie.

Scientific advances in the last decade have demonstrated the critical role of host immune system in the elimination and suppression of cancer cells. Better knowledge of signaling pathways has enabled the development of new cancer immunotherapy. The discovery of negative feedback mechanisms following the lymphocyte activation has promoted the development of new antibodies targeting molecule inhibitors such as PD1, PDL1 or CTLA-4. Dramatic results were obtained with melanoma. Checkpoint inhibitors (pembrolizumab and ipilimumab) have many advantages in terms of rate of objective response and overall survival. Recent studies in translational research aimed to understand and analyze mechanisms of action of anti-PD1/anti-PDL1. Expression of PDL1 in the tumor is associated with a significantly greater objective response rate (immunohistochemistry). Nevertheless, limits with tumor immunohistochemical analysis encourage new biomarkers research. Other immunotherapy approaches, such as cell and gene therapies using engineered T cells call for further advancements to broaden their applicability. However, these therapies are very expensive and their manufacturing process very restrictive, which could lately limit their use in case of inefficiency of checkpoint inhibitors or when lymphocytic infiltration in tumor is absent. In this case, the objective would be to engineer ex vivo the patient's immune system by restoring the ability of T cells to identify and suppress tumor cells. Currently, two gene-reprogramming tools are under development: chimeric antigen receptor and TCR modified T cells.

An unusual case of Y-shaped right renal vein.

Vascular renal anomalies are frequent, multiple and well described and result from errors in vessel embryogenesis between the 6th and 10th week of gestation. Historically, variations are described in anatomic dissection and currently mostly in image interpretation. We report an anatomic variation concerning the right renal vein which, to our knowledge, has never been described in the literature either by dissection or by radiological examination. This variation was discovered during the routine dissection of an embalmed male body. It consists of a Y-shaped right renal vein and is associated with multiple retroperitoneal variations: a bilateral accessory renal artery, a trident ending of the right renal artery and a left testicular vein variation. Venous and arterial renal anatomy and its variations are fundamentally important in renal surgery, especially concerning living donor renal grafts. These variations may be diagnosed thanks to injected tomodensitometry which has a good sensitivity and specificity for anomalies. Preoperative diagnosis of an anatomic vascular renal variation may reduce morbidity during surgery, which is why precise examination of injected tomography should be mandatory.

Activity and safety of RAD001 (everolimus) in patients affected by biliary tract cancer progressing after prior chemotherapy: a phase II ITMO study.

BACKGROUND: Biliary tract cancer (BTC) is a highly lethal disease for which the best available therapy remains undetermined. The mammalian target of rapamycin (mTOR) pathway is up-regulated in several cancers, including BTC, and preclinical evidence indicates that mTOR inhibition may be effective in the treatment of BTC. We sought to evaluate the activity and tolerability of the mTOR inhibitor RAD001-everolimus-in patients with BTC progressing after prior chemotherapy. PATIENTS AND METHODS: This was an open-label, single-arm, phase II study (EUDRACT 2008-007152-94) conducted in eight sites in Italy. Patients with locally advanced, metastatic or recurrent BTC progressing despite previous chemotherapy received a daily oral dose of everolimus 10 mg administered continuously in 28-day cycles. The two primary end points were disease control rate (DCR) and objective response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival (OS) and time-to-progression (TTP). RESULTS: Thirty-nine patients were enrolled. The DCR was 44.7%, and the ORR was 5.1%. One patient showed a partial response at 2 months and one patient showed a complete response sustained up to 8 months. The median (95% confidence interval) PFS was 3.2 (1.8-4.0) months, and the median OS was 7.7 (5.5-13.2) months. The median TTP was 2.0 (1.7-3.7) months. Most common toxicities were asthenia (43.6%), thrombocytopenia (35.9%), pyrexia (30.8%) and erythema, mainly of mild-to-moderate severity. Two patients required dose reduction due to adverse events. CONCLUSION: Everolimus demonstrated a favourable toxicity profile and encouraging anti-tumour activity. Further trials are needed to establish the role of everolimus in the treatment of BTC. EUDRACT 2008-007152-94.

Effects of two different glibenclamide dose-strengths in the fixed combination with metformin in patients with poorly controlled T2DM: a double blind, prospective, randomised, cross-over clinical trial.

A double-blind, prospective, randomised, cross-over clinical trial was performed comparing a glibenclamide (G) 5.0 mg/metformin (M) 400 mg combination with a G 2.5 mg/M 400 mg formulation to evaluate whether a higher dose of glibenclamide was able to improve glycaemia in poorly controlled Type 2 diabetic patients. One hundred and ninety-eight patients with poorly controlled Type 2 diabetes mellitus were randomised to receive one of the two trial drugs for a first 3-month period, and were then assigned to the alternative combination for further 3 months. The starting dose (2 tablets/day, 30 min before breakfast and dinner) was to be up-titrated to 3 tablets/day when required. A standard dietary regimen was kept constant for the total trial duration. Fasting plasma glucose, HbA1c, C-peptide, insulin and lactate levels, haematology and blood chemistry were measured at the start/end of each cycle. Patients' self-assessment of the glycaemic profile (at fasting and 2 hr after the main meals) was performed weekly. Patients were constantly monitored for adverse events and episodes of hypoglycaemia, and all events were recorded. Decrease of mean fasting glucose levels measured in the first cycle was more pronounced in the group treated with G 5.0 mg/M 400 (p<0.01) compared to baseline, although the difference was not significant--no changes were observed in the second 3-month period. Results of patients' self-assessment of the glycaemic profile in the overall 6-month period show that the two trial drugs produced similar effects on fasting glucose, but the decrease of post-prandial glycaemic levels was markedly higher with G 5 mg/M 400 mg than with G 2.5 mg/M 400 mg at both main meals. A similar significant decrease (p<0.01) of HbA1c was observed in both sequence groups at the end of the first 3-month treatment period, and mean levels remained unchanged at 6 months. Drug-related adverse events were observed in 2 patients during treatment with G 2.5 mg/M 400 mg and in 5 with G 5 mg/M 400 mg, while 14 and 22 episodes of hypoglycaemia occurred with the two trial drugs, respectively (p=NS between treatments). Metformin-induced increases of lactate levels were similar in the two sequence groups. No differences between groups were found either in the number of up-titrated patients or in all the other laboratory parameters. In conclusion, the new combination containing 5-mg glibenclamide produced a greater improvement in post-prandial glycaemic control compared with the standard fixed doses, and resulted equally safe and well tolerated.

Combined immunodeficiency phenotype associated with inappropriate spontaneous and activation-induced apoptosis.

Programmed death of T cells has been proposed as one of the mechanisms by which HIV induces a decline in the number and functions of T cells in advanced AIDS. In this study we report on a patient affected by a congenital form of combined immunodeficiency presenting as a profound T cell activation deficiency. Subsequently, a gradual loss of T cells occurred, eventually resulting in a classical form of severe combined immunodeficiency (SCID). In this patient a sizeable fraction of apoptotic cells was documented in the first phase of the disease by either propidium iodide staining or DNA fragmentation analysis. The presence of anergic T cells of maternal origin and engrafted in the child was excluded by analysis of DNA polymorphic regions. At 4 years of age the patient died of disseminated interstitial pneumopathy, while still awaiting an HLA-matched bone marrow transplantation. On the occasion of a new pregnancy in the mother, the prenatal immunological evaluation of the female fetus revealed a T B+ SCID phenotype. This is the first observation of a primary immunodeficiency associated with inappropriate apoptosis.

[Benign tumors of the mandible. The experience of reconstruction using immediate bone grafts]. / I tumori benigni della mandibola. Esperienza di ricostruzione mediante innesti ossei immediati.

The numerous benign pathologies of the mandible are considered, attention being focused on the large neoplasms that require full demolition and appropriate reconstructive surgery. Among the most frequent mandibular tumours, a clear-cut prevalence was noted for odontogenic tumours; on the subject of reconstructive therapy, on the other hand, stress is laid on the need for increasingly frequent use of immediate bone grafts for which the iliac bone provides the most available bone tissue both in terms of quantity and ease of access, modellability and tolerance.

[Osteoma of the frontal sinus. Remarks on a clinical case]. / Osteoma del seno frontale. Considerazioni su di un caso clinico.

A case of frontal osteoma observed at the Maxillofacial Surgery and Odontostomatology Division of the Miulli di Acquaviva delle Fonti (Ba) Regional Hospital, treated surgically by the creation of a bone passage in correspondence with the anterior wall of the sinus which is then reset and osteosynthesized, is reported. The technique adopted thus makes possible full visualisation of the neoformation and valid morphological and aesthetic recovery.

[Fracture of the orbito-maxillo-zygomatic complex. Follow-up study]. / Fratture del complesso orbito-maxillo-zigomatico. Controlli a distanza.

The cases are examined of 82 patients out of 126 surgically treated for OMZ fractures who were followed up years later. The assessment of certain parameters reveals that many patients especially those suffering extensive OMZ injuries continued to complain of problems with the sensitivity of the orbital nerve.