Lymphopenia in patients affected by SARS-CoV-2 infection is caused by margination of lymphocytes in large bowel: an [18F]FDG PET/CT study.

BACKGROUND: To investigate the cause of lymphopenia in patients with newly diagnosed COVID-19, we measured [18F]FDG uptake in several tissues, including the ileum, right colon, and caecum at diagnosis and after recovery and correlated these measurements with haematological parameters. METHODS: We studied, by [18F]FDG PET/CT, 18 newly diagnosed patients with COVID-19. Regions of interest were drawn over major organs and in the terminal ileum, caecum, and right colon, where the bowel wall was evaluable. Five patients were re-examined after recovery, and three of them also performed a white blood cell scan with 99mTc-HMPAO-WBC on both occasions. Complete blood count was performed on both occasions, and peripheral blood lymphocyte subsets were measured at diagnosis. Data were analysed by a statistician. RESULTS: Patients had moderate severity COVID-19 syndrome. Basal [18F]FDG PET/CT showed focal lung uptake corresponding to hyperdense areas at CT. We also found high spleen, ileal, caecal, and colonic activity as compared to 18 control subjects. At recovery, hypermetabolic tissues tended to normalize, but activity in the caecum remained higher than in controls. Regression analyses showed an inverse correlation between CD4 + lymphocytes and [18F]FDG uptake in the caecum and colon and a direct correlation between CD8 + lymphocytes and [18F]FDG uptake in lungs and bone marrow. WBC scans showed the presence of leukocytes in the caecum and colon that disappeared at recovery. CONCLUSIONS: These findings indicate that lymphopenia in COVID-19 patients is associated with large bowel inflammation supporting the hypothesis that CD4 + lymphocytes migrate to peripheral lymphoid tissues in the bowel.

Discovering the Italian phenotype of cerebral amyloid angiopathy (CAA): the SENECA project.

Cerebral amyloid angiopathy (CAA) is one of the major types of cerebral small vessel disease, and a leading cause of spontaneous intracerebral hemorrhage and cognitive decline in elderly patients. Although increasingly detected, a number of aspects including the pathophysiology, the clinical and neuroradiological phenotype, and the disease course are still under investigation. The incomplete knowledge of the disease limits the implementation of evidence-based guidelines on patient's clinical management and the development of treatments able to prevent or reduce disease progression. The SENECA (SEarchiNg biomarkErs of Cerebral Angiopathy) project is the first Italian multicenter cohort study aimed at better defining the disease natural history and identifying clinical and neuroradiological markers of disease progression. By a multidisciplinary approach and the collection of a large and well-phenotyped series and biorepository of CAA patients, the study is ultimately expected to improve the diagnosis and the knowledge of CAA pathophysiological mechanisms.

Phenome-wide association study of TTR and RBP4 genes in 361,194 individuals reveals novel insights in the genetics of hereditary and wildtype transthyretin amyloidoses.

Transthyretin (TTR) gene has a causal role in a hereditary form of amyloidosis (ATTRm) and is potentially involved in the risk of wild-type transthyretin amyloidosis (ATTRwt). To understand the genetics of ATTRm and ATTRwt, we conducted a phenome-wide association study of TTR gene in 361,194 participants of European descent testing coding and non-coding variants. Among the 382 clinically relevant phenotypes tested, TTR non-coding variants were associated with 26 phenotypic traits after multiple testing correction. These included signs related to both ATTRm and ATTRwt such as chronic ischaemic heart disease (rs140226130, p = 2.00 × 10-6), heart failure (rs73956431, p = 2.74 × 10-6), atrial fibrillation (rs10163755, p = 4.63 × 10-6), dysphagia (rs2949506, p = 3.95 × 10-6), intestine diseases (rs970866, p = 7.14 × 10-6) and anxiety (rs554521234, p = 8.85 × 10-6). Consistent results were observed for TTR disease-causing mutation Val122Ile (rs76992529) with respect to carpal tunnel syndrome (p = 6.41 × 10-6) and mononeuropathies of upper limbs (p = 1.22 × 10-5). Sex differences were also observed in line with ATTRm and ATTRwt epidemiology. Additionally, we explored possible modifier genes related to TTR function, observing convergent associations of RBP4 variants with the clinical phenotypes associated with TTR locus. In conclusion, we provide novel insights regarding the molecular basis of ATTRm and ATTRwt based on large-scale cohort, expanding our understanding of the phenotypic spectrum associated with TTR gene variation.

Hybrid imaging of musculoskeletal infections.

This review article highlights the role of radiological and nuclear medicine techniques in diagnosis of musculoskeletal infections with particular regard to hybrid imaging of osteomyelitis, prosthetic joint infections, sternal infections and spine infections. Authors conclude on the complementary role of the several techniques with indications for an appropriate diagnostic flow chart, in the light of the recent European Association of Nuclear Medicine guidelines on infection.

Population diversity of the genetically determined TTR expression in human tissues and its implications in TTR amyloidosis.

BACKGROUND: Transthyretin (TTR) amyloidosis is a hereditary disease with a complex genotype-phenotype correlation. We conducted a literature survey to define the clinical landscape of TTR amyloidosis across populations worldwide. Then, we investigated whether the genetically determined TTR expression differs among human populations, contributing to the differences observed in patients. Polygenic scores for genetically determined TTR expression in 14 clinically relevant tissues were constructed using data from the GTEx (Genotype-Tissue Expression) project and tested in the samples from the 1,000 Genomes Project. RESULTS: We observed differences among the ancestral groups and, to a lesser extent, among the investigated populations within the ancestry groups. Scandinavian populations differed in their genetically determined TTR expression of skeletal muscle tissue with respect to Southern Europeans (p = 6.79*10-6). This is in line with epidemiological data related to Swedish and Portuguese TTR Val30Met endemic areas. Familial amyloidotic cardiomyopathy (TTR deposits occur primarily in heart tissues) presents clinical variability among human populations, a finding that agrees with the among-ancestry diversity of genetically determined TTR expression in heart tissues (i.e., Atrial Appendage p = 4.55*10-28; Left Ventricle p = 6.54*10-35). CONCLUSIONS: Genetically determined TTR expression varied across human populations. This might contribute to the genotype-phenotype correlation of TTR amyloidosis.

The role of contrast enhanced computed tomography in the diagnosis of necrotizing fasciitis and comparison with the laboratory risk indicator for necrotizing fasciitis (LRINEC).

PURPOSE: To evaluate the diagnostic efficacy of contrast enhanced computed tomography (CECT) in emergency departments for diagnosis of necrotizing fasciitis (NF) and for differential diagnosis of other musculoskeletal infections; to correlate radiological findings with the laboratory risk indicator for necrotizing fasciitis (LRINEC). MATERIALS AND METHODS: 7 radiological parameters to be analysed on CECT scans were established, exams of 36 patients with proven diagnosis of NF (n 12) and other musculoskeletal infections (n 24) were retrospectively reviewed; LRINEC score was calculated. Fisher's test and Spearman's and Kendall's coefficients of rank correlations were performed. RESULTS: Two parameters were found to be strongly associated with the diagnosis of NF: involvement of the fascia (Spearman's ρ of 0.888, p < 0.001) and lack of fascial enhancement (Spearman's ρ of 0.672, p < 0.001). LRINEC score did not show strong association with the presence of fasciitis NF (Spearman's ρ of 0.490, p = 0.0024). CONCLUSION: Computed tomography (CT) parameters, which are significantly associated with the diagnosis of NF, are the involvement of the fascia and its lack of enhancement; LRINEC score could be high (>5) also in other musculoskeletal infections. Final diagnosis of necrosis among the fascia is surgical. Presence of gas is not a specific sign of necrotizing fasciitis being present in other musculoskeletal infections. CT could easily discriminate NF from other musculoskeletal infections, adds an important value to clinical and laboratory tests in diagnosis of NF in an emergency context when magnetic resonance imaging, which is superior to CT in this discernment, could not be performed.

MRI in the evaluation of facial dermal fillers in normal and complicated cases.

OBJECTIVES: To ascertain by MRI the presence of filler injected into facial soft tissue and characterize complications by contrast enhancement. METHODS: Nineteen volunteers without complications were initially investigated to study the MRI features of facial fillers. We then studied another 26 patients with clinically diagnosed filler-related complications using contrast-enhanced MRI. TSE-T1-weighted, TSE-T2-weighted, fat-saturated TSE-T2-weighted, and TIRM axial and coronal scans were performed in all patients, and contrast-enhanced fat-suppressed TSE-T1-weighted scans were performed in complicated patients, who were then treated with antibiotics. Patients with soft-tissue enhancement and those without enhancement but who did not respond to therapy underwent skin biopsy. Fisher's exact test was used for statistical analysis. RESULTS: MRI identified and quantified the extent of fillers. Contrast enhancement was detected in 9/26 patients, and skin biopsy consistently showed inflammatory granulomatous reaction, whereas in 5/17 patients without contrast enhancement, biopsy showed no granulomas. Fisher's exact test showed significant correlation (p < 0.001) between subcutaneous contrast enhancement and granulomatous reaction. Cervical lymph node enlargement (longitudinal axis >10 mm) was found in 16 complicated patients (65 %; levels IA/IB/IIA/IIB). CONCLUSIONS: MRI is a useful non-invasive tool for anatomical localization of facial dermal filler; IV gadolinium administration is advised in complicated cases for characterization of granulomatous reaction. KEY POINTS: • MRI is a non-invasive tool for facial dermal filler detection and localization. • MRI-criteria to evaluate complicated/non-complicated cases after facial dermal filler injections are defined. • Contrast-enhanced MRI detects subcutaneous inflammatory granulomatous reaction due to dermal filler. • 65 % patients with filler-related complications showed lymph-node enlargement versus 31.5 % without complications. • Lymph node enlargement involved cervical levels (IA/IB/IIA/IIB) that drained treated facial areas.

Diagnosis and management of dermal filler complications in the perioral region.

BACKGROUND: Lip augmentation with injectable materials is a popular aesthetic procedure. When complications occur, patients often ignore which material was implanted, thus making subsequent treatments difficult. This study aims to present the diagnosis and management of dermal filler complications in the perioral region. STUDY DESIGN: The Medical charts of 26 patients with filler complications in the oral region were reviewed. All patients were submitted to High Frequency Ultrasound, often complemented by Magnetic Resonance Imaging (MRI) and White Blood Cell Scintigraphy, to evaluate filler characteristics and complication types. Antibiotic, corticosteroid or surgical treatment was therefore planned. RESULTS: Imaging always identified dermal fillers in the oral region, distinguishing among infections, fibrosis, granulomatous inflammation and product migration. Nine patients received surgery, ten received medical treatments, six received both, and one refused treatment. Eighty percent of the patients presented an improvement after three- year follow-up. CONCLUSIONS: Complications of oral region fillers are similar in clinical presentation but differ in etiology, therefore necessitating different clinical approaches. Imaging techniques add useful information for treatment planning.

CD38 ligation in peripheral blood mononuclear cells of myeloma patients induces release of protumorigenic IL-6 and impaired secretion of IFNγ cytokines and proliferation.

CD38, a surface receptor that controls signals in immunocompetent cells, is densely expressed by cells of multiple myeloma (MM). The immune system of MM patients appears as functionally impaired, with qualitative and quantitative defects in T cell immune responses. This work answers the issue whether CD38 plays a role in the impairment of T lymphocyte response. To this aim, we analyzed the signals implemented by monoclonal antibodies (mAb) ligation in peripheral blood mononuclear cells (PBMC) obtained from MM patients and compared to benign monoclonal gammopathy of undetermined significance (MGUS). PBMC from MM both failed to proliferate and secrete IFNγ induced by CD38 ligation while it retained the ability to respond to TCR/CD3. The impaired CD38-dependent proliferative response likely reflects an arrest in the progression of cell cycle, as indicated by the reduced expression of PCNA. CD38 signaling showed an enhanced ability to induce IL-6 secretion. PBMC from MM patients displays a deregulated response possibly due to defects of CD38 activation pathways and CD38 may be functionally involved in the progression of this pathology via the secretion of high levels of IL-6 that protects neoplastic cells from apoptosis.

MRI and MR voiding cystourethrography in the evaluation of male primary bladder neck obstruction: preliminary experience.

PURPOSE: Evaluation of male with primary bladder neck obstruction (PBNO) using MRI and MR voiding cystourethrography (MR-VCU) to study both anatomical aspects of bladder neck and urethral lumen. METHODS: In this retrospective study 21 male patients (mean age 33 ± 14) with urodynamic diagnosis of PBNO and 5 healthy volunteers ((mean age 28 ± 2) as control group were enrolled. Both patients and control group underwent 1.5 T MRI. Sagittal and oblique coronal Turbo-Spin-Echo T2-weighted scans were performed. Only patients underwent MR voiding cystourethrography (MR-VCU) performed with T1-weighted spoiled 3D gradient-echo sagittal acquisitions. Bladder lumen was filled with contrast-material-enhanced urine. Blinded test by two radiologists was performed to evaluate causes of bladder outlet obstruction evaluating MR-VCU. Anatomical MRI features of both control group and patients were compared in consensus by senior radiologist and urologist using the analysis of variance (ANOVA) test. RESULTS: MRI allowed evaluation of the bladder neck muscular structures. We found 4 groups of PBNO patients: 52% hypertrophy of posterior lip of bladder sphincter; 20% asymmetry of lateral portion of bladder sphincter; 14% bladder neck cyst; 14% showed normal aspect of bladder neck. Comparison between the control group and first and second PBNO groups was considered statistically significant (p < 0.05) with diagnostic accuracy of 87%. Only 13 patients (61%) were able to perform MR-VCU and radiologists always made the diagnosis of PBNO. CONCLUSION: MRI together with MR-VCU provides useful anatomical and functional information in the study of bladder neck and urethral lumen. These preliminary results suggest that MRI could substitute for standard cystourethrogram in patients with PBNO.

Multi-Modality Imaging Approach in a Challenging Case of Surgically Corrected Partial Anomalous Pulmonary Venous Return and Atrial Tachycardia Treated With Radiofrequency Ablation.

Pulmonary anomalous venous return (PAPVR) is defined as a congenital anomaly in which at least one but not all of the pulmonary veins abnormally drain into a systemic vein or directly into the right atrium. Signs and symptoms related to this condition are due to the hemodynamic abnormalities secondary to left-to-right shunt and the possible presence of other associated cardiac anomalies (e.g., sinus venous atrial septal defect). Therefore, depending on the extent of the shunt, the clinical presentation of PAPVR is variable, ranging from asymptomatic patients to patients affected by severe heart failure with right-sided volume overload. PAPVR with a clinically significant shunt should be referred for surgical correction with different techniques depending on the presence of associated cardiac anomalies. We are presenting a case of partial anomalous venous return (PAPVR) in a 66-year-old man who underwent surgery 26 years ago to correct an anomalous venous connection between the right superior pulmonary vein (RSPV) and the superior vena cava (SVC) through a veno-atrial baffle. The patient was admitted to the emergency department due to atrial tachycardia. Trans-thoracic echocardiography (TTE) showed a dilated right ventricle (RV) with mild RV systolic dysfunction and pulmonary hypertension. Cardiac magnetic resonance (CMR) further confirmed the findings described by TTE and also demonstrated areas of fibrosis replacement in the hinge points. Cardiac computed tomography (CCT) was able to accurately depict and evaluate the surgically created veno-atrial baffle and also showed an anomalous connection between the left superior pulmonary vein (LSPV) and the brachiocephalic vein (BCV) through a vertical vein. The patient was successfully treated with radiofrequency ablation for his arrhythmia.

Ocular Involvement in Hereditary Amyloidosis.

The term amyloidosis describes a group of rare diseases caused by protein conformation abnormalities resulting in extracellular deposition and accumulation of insoluble fibrillar aggregates. So far, 36 amyloid precursor proteins have been identified, and each one is responsible for a specific disease entity. Transthyretin amyloidosis (ATTRv) is one of the most common forms of systemic and ocular amyloidosis, due to the deposition of transthyretin (TTR), which is a transport protein mainly synthesized in the liver but also in the retinal pigment epithelial cells. ATTRv amyloidosis may be misdiagnosed with several other conditions, resulting in a significant diagnostic delay. Gelsolin and keratoepithelin are other proteins that, when mutated, are responsible for a systemic amyloid disease with significant ocular manifestations that not infrequently appear before systemic involvement. The main signs of ocular amyloid deposition are in the cornea, irido-corneal angle and vitreous, causing complications related to vasculopathy and neuropathy at the local level. This review aims at describing the main biochemical, histopathological and clinical features of systemic amyloidosis associated with eye involvement, with particular emphasis on the inherited forms. We discuss currently available treatments, focusing on ocular involvement and specific ophthalmologic management and highlighting the importance of a prompt treatment for the potential sight-threatening complications derived from amyloid deposition in ocular tissues.

ATTRv in Lazio-Italy: A High-Prevalence Region in a Non-Endemic Country.

Hereditary transthyretin amyloidosis (ATTRv, v for variant) prevalence in Italy, a non-endemic region, has been established by ATTRv amyloidosis Italian Registry. However, values of prevalence were extremely heterogeneous, considering different regions. To properly establish the prevalence of the disease in the Lazio region, a survey was sent to university regional hospitals and to main regional hospitals, in order to collect all affected patients regularly followed. We identified 100 ATTRv patients and, considering a Lazio population of 5.8/million, we estimated a ATTRv prevalence of 17.2/million. The ATTRv amyloidosis Italian Registry reported a prevalence of 8.0/million in Lazio, while our survey showed a value of double this. Our survey documented a high-prevalence for a non-endemic country. The increased awareness of the disease among general practitioners and medical specialists is a fundamental step to reduce the diagnostic delay and start an effective treatment of this disease.

An Incidental Diagnosis of SARS-CoV-2 Pneumonia With Magnetic Resonance Imaging.

The Coronavirus disease 2019 (COVID-19) is caused by the human severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. The most common clinical findings related to COVID-19 are fever and cough, with the proportion of patients developing interstitial pneumonia. Other symptoms include dyspnea, expectoration, headache, anosmia, ageusia, myalgia and malaise. To date, the diagnostic criteria for COVID-19 include nasopharyngeal and oropharyngeal swabs. Computed tomography (CT) scans of the thorax showing signs of interstitial pneumonia are important in the management of respiratory disease and in the evaluation of lung involvement. In the literature, there are few cases of COVID-19 pneumonia diagnosis made using magnetic resonance imaging (MRI). In our report, we describe a case of accidental detection of findings related to interstitial pneumonia in a patient who underwent abdominal MRI for other clinical reasons. A 71-year-old woman was referred to our department for an MRI scan of the abdomen as her oncological follow-up. She was asymptomatic at the time of the examination and had passed the triage carried out on all the patients prior to diagnostic tests during the COVID-19 pandemic. The images acquired in the upper abdomen showed the presence of areas of altered signal intensity involving asymmetrically both pulmonary lower lobes, with a patchy appearance and a preferential peripheral subpleural distribution. We considered these features as highly suspicious for COVID-19 pneumonia. The nasopharyngeal swab later confirmed the diagnosis of SARS-CoV-2 infection. There are limited reports about MRI features of COVID-19 pneumonia, considering that high-resolution chest CT is the imaging technique of choice to diagnose pneumonia. Nevertheless, this clinical case confirmed that it is possible to detect MRI signs suggestive of COVID-19 pneumonia. The imaging features described could help in the evaluation of the lung parenchyma to assess the presence of signs suggestive of COVID-19 pneumonia, especially in asymptomatic patients during the pandemic phase of the disease.

Hydro-MDCT for Gastric Adenocarcinoma Staging. A Comparative Study With Surgical and Histopathological Findings for Selecting Patients for Echo-endoscopy.

BACKGROUND/AIM: In local staging of gastric adenocarcinoma CT is the modality of choice. Less frequently used in a few selected patients is echo-endoscopy. Aim of this study was to evaluate the accuracy of hydro-multidetector-computed tomography (hydro-MDCT) in the evaluation of gastric adenocarcinomas with subsequent surgical and histopathological correlation to select cases for echo-endoscopy. PATIENTS AND METHODS: A total of 65 patients with gastric adenocarcinomas, diagnosed by endoscopy and biopsy, underwent contrast-enhanced hydro-MDCT with subsequent tumor, nodes, metastases (TNM) classification. The distension of the gastric lumen was obtained after the oral administration of 500 ml of water. RESULTS: Hydro-MDCT always detected gastric cancer and in 49/65 patients the assessment of T-parameter was identical to the histopathological results (accuracy: 75%). We found overstaging in 12 and understaging in 4 cases. N-parameter with MDCT was in agreement with histo-pathology in 69%of patients; in metastatic disease hydro-MDCT had an accuracy of 99%. Hydro-MDCT has proven to be a reliable diagnostic technique in evaluating gastric cancer T3-T4 stages in comparison to T1 and T2: in defining T2-stage we found the highest number of errors (37%). CONCLUSION: Hydro-MDCT is a reliable technique in the preoperative staging of gastric adenocarcinoma. Echo-endoscopy could be particularly useful in doubtful cases to evaluate the muscularis propria infiltration (T2 vs. T3) and characterize the peri-gastric lymph nodes.

Epigenetic profiling of Italian patients identified methylation sites associated with hereditary transthyretin amyloidosis.

Hereditary transthyretin (TTR) amyloidosis (hATTR) is a rare life-threatening disorder caused by amyloidogenic coding mutations located in TTR gene. To understand the high phenotypic variability observed among carriers of TTR disease-causing mutations, we conducted an epigenome-wide association study (EWAS) assessing more than 700,000 methylation sites and testing epigenetic difference of TTR coding mutation carriers vs. non-carriers. We observed a significant methylation change at cg09097335 site located in Beta-secretase 2 (BACE2) gene (standardized regression coefficient = -0.60, p = 6.26 × 10-8). This gene is involved in a protein interaction network enriched for biological processes and molecular pathways related to amyloid-beta metabolism (Gene Ontology: 0050435, q = 0.007), amyloid fiber formation (Reactome HSA-977225, q = 0.008), and Alzheimer's disease (KEGG hsa05010, q = 2.2 × 10-4). Additionally, TTR and BACE2 share APP (amyloid-beta precursor protein) as a validated protein interactor. Within TTR gene region, we observed that Val30Met disrupts a methylation site, cg13139646, causing a drastic hypomethylation in carriers of this amyloidogenic mutation (standardized regression coefficient = -2.18, p = 3.34 × 10-11). Cg13139646 showed co-methylation with cg19203115 (Pearson's r2 = 0.32), which showed significant epigenetic differences between symptomatic and asymptomatic carriers of amyloidogenic mutations (standardized regression coefficient = -0.56, p = 8.6 × 10-4). In conclusion, we provide novel insights related to the molecular mechanisms involved in the complex heterogeneity of hATTR, highlighting the role of epigenetic regulation in this rare disorder.

Evaluation of Prognostic Factors for Survival in Transverse Colon Cancer.

Background: Although most of the analyses included transverse colon cancers (TCC) among right colon cancer (RCC), it is not completely clear if they present total similarities with RCC or if they have their specific features. Therefore, we present an observational study to evaluate clinicopathological characteristics and survival data of patients with TCC. Methods: We retrospectively reviewed 450 RCC, of whom 97 stages I-IV TCC were included in this multicenter study; clinicopathological and molecular parameters were analyzed to identify prognostic factors for disease-free survival (DFS) and overall survival (OS). Results: Most of TCC cases were male (61%), with ≤70 years old (62%), and good performance status (ECOG PS 0, 68%). According to WHO classification, 41 (49%) and 40 (48%) tumors were classified as well to moderate and poorly/undifferentiated respectively, regardless of mucinous component (30%). About molecular data, 8 (26%), 45 (63%), and 14 (24%) were MSI-H, KRAS wild-type, and BRAF V600E mutant, respectively. With a median follow-up of 34 months, there were 29 and 50 disease recurrences and deaths respectively. Charlson comorbidity index ≥5 was a significant prognostic factor for DFS (HR = 7.67, 95% CI 2.27-25.92). Colon obstruction/perforation (HR = 2.65, 95% CI 1.01-7.01), and BRAF mutant (HR = 3.03, 95% CI 0.97-9.50) cases showed a worst, despite not statistically significant, DFS. Whereas for OS, at the multivariate model, only tumor grade differentiation (HR = 5.26, 95% CI 1.98-14.01) and BRAF mutation status (3.71, 95% CI 1.07-12.89) were independent prognostic factors. Conclusions: Poorly/undifferentiated tumor grade and BRAF V600E mutation are independent prognostic factors for OS in TCC. Further prospective clinical trials are needed to better define TCC treatment in order to improve patient outcome.

ATTRv amyloidosis Italian Registry: clinical and epidemiological data.

INTRODUCTION: ATTRv amyloidosis is worldwide spread with endemic foci in Portugal and Sweden, Japan, Brazil, Maiorca, and Cyprus. A national Registry was developed to characterise the epidemiology and genotype-phenotype correlation of ATTRv amyloidosis in Italy and to allow a better planning of diagnostic and therapeutic services. METHODS: Fifteen Italian referral centres for amyloidosis spread all over the country have contributed to the Registry. RESULTS: Four-hundred-forty-seven subjects were enrolled, 187 asymptomatic carriers and 260 affected patients. Thirty-one different mutations were recorded. The seven most represented genetic variants were significantly different in terms of age at onset, clinical features and geographical distribution. National prevalence is 4.33/million with higher values in Southern Italy. Overall symptoms of polyneuropathy were present at disease onset in about half of the patients, symptoms of cardiomyopathy in a quarter of patients, the rest referring carpal tunnel syndrome, dysautonomia or lumbar spinal stenosis. 52.6% of patients were in FAP stage 1, 20.4% in stage 2 and 13.5% in stage 3, while 13.5% patients had no neuropathy, presenting only cardiological symptoms. CONCLUSIONS: We presented an epidemiological study based on collaboration among referral centres for ATTRv amyloidosis spread in all the Italian territory, using web-based Registry. It provided a detailed map of the regional distribution of the disease. The increased awareness of the disease among general practitioners and medical specialists has contributed to reduce the diagnostic delay and the rate of misdiagnosis. The Registry will allow to collect also future information about clinical and instrumental follow-up.

Clinical Impact of Highly Purified, Whey Proteins in Patients Affected With Colorectal Cancer Undergoing Chemotherapy: Preliminary Results of a Placebo-Controlled Study.

Background and Aims: Sarcopenia, the loss of both lean body and skeletal muscle mass, may interfere in cancer patients outcome. As investigated, whey proteins could prevent the onset of sarcopenia. We have conducted a study to evaluate the effects of whey protein in colorectal cancer patients, undergoing 5-fluorouracil-based chemotherapy. Methods: After written informed consent, patients were blind randomized 1:1 to whey protein (ProLYOtin; arm A) versus placebo (arm B). The patients were assessed both physically and nutritionally before chemotherapy and after 3 (T2) and 6 months (T3) by body impedance assessment, L3-computed tomography scan, Mini Nutritional Assessment (MNA), and Malnutrition Universal Screening Tool (MUST) tests. Results: Forty-seven patients were included in this preliminary analysis. Baseline characteristics were well balanced between the 2 arms. During chemotherapy, 33 patients were reevaluated: anthropometric parameters (lean body mass from 68.5% to 71.2% vs 68.7% to 66.3%, and sarcopenia from 84% to 54% and 83% to 77% from baseline to T2 evaluation in arms A and B, respectively), nutritional status (MNA >24 = 100% [A] vs 73.7% [B]), and toxicity (no adverse effects in 86% [A] vs 29% [B] and 94% [A] vs 29% [B] for hematological and gastrointestinal toxicities, respectively) resulted to be significantly different. At univariate analysis, a condition of malnutrition risk according to MUST (relative risk [RR] = 7.5, P = .02) or MNA (RR = 1.45, P = .02) and ProLYOtin intake (RR = 0.12, P = .01) were found to be significantly predictive of chemotherapy toxicity. Conclusions: At present, our study shows how whey protein could be an important therapeutic option to improve nutritional status, and particularly to prevent severe toxicity during chemotherapy.