Trimebutine Maleate Monotherapy for Functional Dyspepsia: A Multicenter, Randomized, Double-Blind Placebo Controlled Prospective Trial.

Background and Objectives: Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders; it has a great impact on patient quality of life and is difficult to treat satisfactorily. This study evaluates the efficacy and safety of trimebutine maleate (TM) in patients with FD. Materials and Methods: Α multicenter, randomized, double-blind, placebo controlled, prospective study was conducted, including 211 patients with FD. Participants were randomized to receive TM 300 mg twice per day (BID, 108 patients) or placebo BID (103 patients) for 4 weeks. The Glasgow Dyspepsia Severity Score (GDSS) was used to evaluate the relief of dyspepsia symptoms. Moreover, as a pilot secondary endpoint, a substudy (eight participants on TM and eight on placebo) was conducted in to evaluate gastric emptying (GE), estimated using a 99mTc-Tin Colloid Semi Solid Meal Scintigraphy test. Results: Of the 211 patients enrolled, 185 (87.7%) (97 (52.4%) in the TM group and 88 (47.6%) in the placebo group) completed the study and were analyzed. The groups did not differ in their demographic and medical history data. Regarding symptom relief, being the primary endpoint, a statistically significant reduction in GDSS for the TM group was revealed between the first (2-week) and final (4-week) visit (p-value = 0.02). The 99 mTc-Tin Colloid Semi Solid Meal Scintigraphy testing showed that TM significantly accelerated GE obtained at 50 min (median emptying 75.5% in the TM group vs. 66.6% in the placebo group, p = 0.036). Adverse effects of low to moderate severity were reported in 12.3% of the patients on TM. Conclusion: TM monotherapy appears to be an effective and safe approach to treating FD, although the findings presented here warrant further confirmation.

Emotional impairment in a patient with amyotrophic lateral sclerosis: a (99m)Tc-HMPAO SPET brain study.

Behavioral abnormalities have been reported in patients with amyotrophic lateral sclerosis (ALS) but their aetiology is not yet clearly defined. We report on the case of a 48 years old woman with long standing bulbar onset ALS referred to our department for brain perfusion scan for the evaluation of behavioral and emotional disorders. The patient's scores on the neuropsychological tests were satisfactory while magnetic resonance imaging showed no structural brain abnormalities. However, cerebral blood flow imaging with single photon emission tomography with technetium-99m-hexamethyl propylamine oxime demonstrated bilateral frontal cortex hypoperfusion, as well as perfusion defects in the left parietal, temporal and occipital lobes. In conclusion, the reduced regional cerebral blood flow in the frontal lobes might be suggestive of underlying cortical disturbance and potentially explain the patient's symptoms.

PSMA PET in Imaging Prostate Cancer.

After prostate malignancy diagnosis, precise determination of disease extent are fundamental steps for tailored made therapy. The earlier the diagnosis of the burden of the disease, the longer the survival in many cases. National and international guidelines are based on "classic" imaging technics combining radiological and nuclear medicine scans like CT, MRI and bone scintigraphy (BS). The most recent nuclear medicine development is the prostate specific membrane antigen (PSMA) PET and is emerging as the most promising tool of medical imaging, gaining ground every day. Nevertheless, the different onset among multiple studies fails to establish a worldwide admission and incorporation of this technique in guidelines and its position in workaday medical algorithms. It seems that the medical community agrees not to utilize PSMA PET for low-risk patients; intense debate and research is ongoing for its utility in intermediate risk patients. Contrariwise, in high-risk patients PSMA PET is confirmed outperforming CT and BS combined. Additionally, irrespectively to their castration status, patients with biochemical failure should be referred for PSMA PET. Even though PSMA PET reveals more extended disease than expected or exonerates equivalent lesions, thus impacting treatment optimization. Studies being in progress and future trials with clarify whether PSMA PET will be the new gold standard technic for specific groups of patients.

Successful treatment with intralesional talimogene laherparepvec in two patients with immune checkpoint inhibitor-refractory, advanced-stage melanoma.

Monoclonal antibodies that block the programmed death-1 (anti-PD-1) or cytotoxic T-lymphocyte antigen-4 (CTLA-4) immune checkpoint receptors (pembrolizumab, nivolumab, ipilimumab, or the combination of nivolumab with ipilimumab) are approved treatment option for patients with advanced melanoma. Over half of all patients are refractory to these immunotherapies and are in need of alternative or complementary treatment options. Talimogene laherparepvec (T-VEC) is a first-in-class intralesionally delivered oncolytic immunotherapy, which has proven efficacy in the treatment of advanced melanoma. A proportion of patients treated with T-VEC will benefit from an abscopal response of noninjected metastases indicative of a systemic antitumor immune response elicited by the intratumoral injections. At present it remains unknown whether the systemic antitumor responses elicited by T-VEC are nonredundant with immune-checkpoint blockade. Recent data on potential synergy between T-VEC and both PD-1 and CTLA-4 blockade suggest that the mechanism of action may be complementary. We report on the successful treatment with intralesional T-VEC of two female patients with locoregionally advanced BRAF V600 wild-type melanoma who previously progressed on anti-PD-1 and anti-CTLA-4 inhibitors.

Failure of Classical ß-Blocker Carvedilol to Deactivate Brown Adipose Tissue in a Patient With Pheochromocytoma.

A 37-year-old woman with pheochromocytoma underwent presurgical FDG PET/CT. Despite her usual antiadrenergic medication consisting in 25 mg of carvedilol, PET/CT demonstrated intense and widespread FDG uptake in brown adipose tissue (BAT). No BAT FDG uptake was detectable on a repeated examination after specific preparation consisting in 40 mg propranolol and 5 mg diazepam. We therefore recommend this propranolol-diazepam preparation in patients with pheochromocytoma referred for PET/CT. Carvedilol-classically prescribed to alleviate effects of adrenergic overstimulation-seems ineffective on BAT. This observation questions the benefit of carvedilol to reduce ß3-adrenoreceptor-mediated effects, not only in BAT, but also in other tissues.

Measurement of glomerular filtration rate with chromium-51 ethylene diamino tetraacetic acid in the presence of gallium-67 citrate: a novel method for the solution of the problem.

Chromium-51 (5¹Cr)-ethylene diamino tetraacetic acid plasma clearance is commonly used in glomerular filtration rate measurements. In the presence of additional radionuclides in plasma samples, glomerular filtration rate may be seriously underestimated and a correction of the crosstalk interference may be necessary. This type of correction is problematic in the case of gallium-67 (67Ga) mainly because of the close vicinity of its 300 keV photopeak with that of the 320 keV photopeak of 5¹Cr. A novel method of calculating and removing the interfering 67Ga counts within the 5¹Cr counting window, based on the different decay rates of the two radionuclides, is presented, requiring two series of sample counting in the 5¹Cr counting window only, separated by a 3-day interval. This method was developed to solve a clinical problem and then it was validated by a controlled 67Ga contamination of plasma samples with known counts from 5¹Cr-ethylene diamino tetraacetic acid.