Nutritional management of the patient with pancreatic cancer: from the diagnostic and therapeutic pathway to an integrated hospital-territory approach.

Abstract: Pancreatic cancer is associated to a high risk of malnutrition and neoplastic cachexia even at first diagnosis. Malnutrition is a negative prognostic factor for the outcome of surgery or medical oncology treatments. Despite the good awareness of the problem and the knowledge of the guidelines, the early recognition of malnutrition and its management are still uneven, mainly due to the lack of implementation of standardized and shared protocols and the shortage of dedicated clinical nutritionists and dieticians. An early and appropriate nutritional intervention is mandatory to improve the outcome of patients with pancreatic cancer at any stage of disease. The Mini Nutritional Assessment is useful tool to screen patients malnourished or at risk of malnutrition. The need for the establishment and implementation of an integrated hospital - territorial assistance as well as a home-delivered nutrition service is discussed.

Guideline Application in Real world: multi-Institutional Based survey of Adjuvant and first-Line pancreatic Ductal adenocarcinoma treatment in Italy. Primary analysis of the GARIBALDI survey.

BACKGROUND: Information about the adherence to scientific societies guidelines in the 'real-world' therapeutic management of oncological patients are lacking. This multicenter, prospective survey was aimed to improve the knowledge relative to 2017-2018 recommendations of the Italian Association of Medical Oncology (AIOM). PATIENTS AND METHODS: Treatment-naive adult patients with pancreatic adenocarcinoma were enrolled. Group A received adjuvant therapy, group B received primary chemotherapy, and group C had metastatic disease. The results on patients accrued until 31 October 2019 with a mature follow-up were presented. RESULTS: Since July 2017, 833 eligible patients of 923 (90%) were enrolled in 44 Italian centers. The median age was 69 years (range 36-89 years; 24% >75 years); 48% were female; 93% had Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; group A: 16%, group B: 30%; group C: 54%; 72% Nord, 13% Center, 15% South. In group A, guidelines adherence was 68% [95% confidence interval (CI) 59% to 76%]; 53% of patients received gemcitabine and 15% gemcitabine + capecitabine; median CA19.9 was 29 (range 0-7300; not reported 15%); median survival was 36.4 months (95% CI 27.5-47.3 months). In group B, guidelines adherence was 96% (95% CI 92% to 98%); 55% of patients received nab-paclitaxel + gemcitabine, 27% FOLFIRINOX, 12% gemcitabine, and 3% clinical trial; median CA19.9 was 337 (range 0-20220; not reported 9%); median survival was 18.1 months (95% CI 15.6-19.9 months). In group C, guidelines adherence was 96% (95% CI 94% to 98%); 71% of patients received nab-paclitaxel + gemcitabine, 16% gemcitabine, 8% FOLFIRINOX, and 4% clinical trial; liver and lung metastases were reported in 76% and 23% of patients, respectively; median CA19.9 value was 760 (range 0-1374500; not reported 9%); median survival was 10.0 months (95% CI 9.1-11.1 months). CONCLUSIONS: The GARIBALDI survey shows a very high rate of adherence to guidelines and survival outcome in line with the literature. CA19.9 testing should be enhanced; nutritional and psychological counseling represent an unmet need. Enrollment to assess adherence to updated AIOM guidelines is ongoing.

The Metacognitions about Binge Eating Questionnaire: Investigation of the association between specific metacognitions and Binge Eating Disorder.

Literature suggested that metacognitions are involved in eating problems and may be relevant to the understanding of Binge Eating Disorder (BED). The goal of the current studies was to develop the first self-report instrument on metacognitions about binge eating. In Study 1, a community sample completed the Metacognitions about Binge Eating Questionnaire (MBEQ); an Exploratory Factor Analysis (EFA) was performed. In study 2, a community sample completed the MBEQ and measures assessing severity of binge eating, irrational food beliefs, anxiety, depression, impulsiveness. A Confirmatory Factor Analysis (CFA) was performed. Concurrent and incremental validity were assessed. In study 3, a clinical sample of participants with a diagnosis of BED completed the MBEQ and other measures. Bivariate correlational analysis and hierarchical linear regression were performed. Participants from the general population and participants with a diagnosis of BED were compared. EFA and CFA supported a two-factor solution consisting of positive and negative metacognitions about binge eating. Concurrent and incremental validity were acceptable. The metacognitions factors correlated positively with anxiety, depression, irrational food beliefs, impulsiveness in the community sample, and anxiety, irrational food beliefs, impulsiveness in clinical sample. The metacognitions factors contributed to the prediction of BEDs symptoms, in community and clinical samples, over and above age, gender, impulsiveness, anxiety, depression, irrational food beliefs. The MBEQ possesses good psychometric properties and appears a reliable and valid measure of positive and negative metacognitions about binge eating. Metacognitions about binge eating could be a therapeutic target to reduce the severity of binge eating episodes.

Postpartum Depression-Identifying Risk and Access to Intervention.

PURPOSE OF REVIEW: As maternal mortality climbs in the USA with mental health conditions driving these preventable deaths, the field of reproductive psychiatry must shift towards identification of women and other birthing individuals at risk and facilitating access. This review brings together recent studies regarding risk of perinatal depression and highlights important comorbidities that place individuals at higher vulnerability to poor perinatal outcomes. RECENT FINDINGS: Recent research suggests that identifying risk for perinatal depression including historical diagnoses of depression, anxiety, trauma, and comorbid substance use and intimate partner violence may move the field to focus on preventive care in peripartum populations. Emerging data shows stark health inequities in racial and ethnic minority populations historically marginalized by the health system and in other vulnerable groups such as LGBTQ+ individuals and those with severe mental illness. Innovative models of care using systems-level approaches can provide opportunities for identification and risk analyses of vulnerable peripartum patients and facilitate access to therapeutic or preventive interventions. Utilizing intergenerational approaches and leveraging multidisciplinary teams that thoughtfully target high-risk women and other birthing individuals could promote significant changes to population-level care in maternal health.

Long-term use of carglumic acid in methylmalonic aciduria, propionic aciduria and isovaleric aciduria in Italy: a qualitative survey.

OBJECTIVE: Organic acidurias (OAs) are a group of rare metabolic disorders that disrupt the regular amino acid metabolism. OAs are characterized by recurrent episodes of acidemia, ketonuria and hyperammonemia which can result in brain/liver damage and renal failure, and despite the life-long protein-restricted diet, impaired growth and long-term complications can occur. Consequently, a long-term management of OAs patients is required, aimed principally at reducing the frequency and duration of metabolic decompensation/hyperammonemia episodes. Nevertheless, unlike the acute phase, evidence on the chronic management of OAs patients is less consolidated. SUBJECTS AND METHODS: To expand the knowledge on this field, 13 Italian referral centers for the management of OAs were involved in a survey focused on the long-term use of carglumic acid (Carbaglu®, Recordati Rare Diseases). RESULTS: Participating centers reported a reduction between 69% and 81% in the annual number of metabolic decompensations with the chronic use of carglumic acid and an improvement in protein intake. Most centers reported no difficulty using carglumic acid as a long-term therapy, along with a great compliance. CONCLUSIONS: Taken together, obtained data align with the available literature and support a positive clinical experience with the long-term carglumic acid administration. Additional studies aimed at better defining a proper dosage for the chronic administration of carglumic acid and the clinical and biochemical characteristics of patients treated chronically are needed. In addition, the potential impact of this treatment regimen on the neurological development and growth of patients should be elucidated.

Management of Patients with Gastric or Gastroesophageal Junction Cancer: From Theory to Integrated Clinical Path- ways Implementation in the Real World.

Introduction: Best care of esophagogastric junction and gastric cancer (EGC) requires a complex, timely interaction between members of a multi-disciplinary team (MDT). An integrated clinical pathway (ICP) is necessary to achieve this goal as well as the implementation of its use in daily practice. The objective of this study was to elaborate on an integrated clinical pathway for the multi-disciplinary management of ECG. Authors also put in act an implementation program to improve adherence to guidelines thought an ICP. Method: This prospective work carried out by a multi-institutional MDT in Italy identified expert panel extracted relevant recommendations and/or statements from published papers and guidelines obtaining a set of crucial interventions employed the Estimate-Talk-Estimate method. A flow-chart diagram was elaborated to elicit the process at a glance. The primary outcome measure was the elaboration of an ICP with a high consensus rate also reported as a snapshot diagram and its implementation in daily clinical practice. An accredited certification body agency validated results, and an implementation process was started in several hospitals known to treat ECG. Results: A methodologist aggregated a multi-disciplinary panel of experts from different institutions. The panel elaborated a flow-chart diagram with crucial intervention highlight and connecting lines, as well as outcome measures. An accredited certification body agency validated the entire process, representing the basis for empowerment and implementation among patients and oncological professionals in various hospitals. Conclusion: The multi-disciplinary and multi-institutional expert panel successfully elaborated on a validated ICP for all stages ECG. An in-hospital implementation program has been programmed.

Psychometric validation of the desire thinking questionnaire in a Turkish adolescent sample: Associations with internet gaming disorder.

BACKGROUND: Desire thinking is a conscious and voluntary cognitive process that consists of perseverative focus on information, memories, and prefiguration of images related to a desired target. The Desire Thinking Questionnaire (DTQ) is acknowledged as a reliable and valid tool to measure desire thinking in both adults and adolescents. The aim of the present study was to examine the psychometric properties of the DTQ in Turkish adolescent sample. METHODS: A convenience sample of 200 adolescents completed the Turkish version of the DTQ (DTQ-T) and an Exploratory Factor Analysis (EFA) was performed. Subsequently, a convenience sample of 701 adolescents completed the DTQ-T and a battery of questionnaires assessing personality traits, affect, boredom, impulsivity, and Internet Gaming Disorder (IGD). A Confirmatory Factor Analysis (CFA) was performed on the DTQ-T and validity was determined by examining correlations with other measures. RESULTS: A 9-item two-factor structure was observed in the EFA. An 8-item two-factor structure was established in the CFA. Results demonstrated that the DTQ-T yields adequate levels of reliability and concurrent validity. Additionally, an examination of incremental validity showed that DTQ-T significantly predicted IGD when controlling for personality traits, affect, boredom, and impulsivity. CONCLUSIONS: The 8-item DTQ-T was found to be a reliable and valid measure of desire thinking among Turkish adolescents. Desire thinking may be a feasible target for mental health workers to alleviate the symptoms of IGD.

Primary Prophylaxis for Gastrointestinal Bleeding in Children With Biliary Atresia and Portal Hypertension Candidates for Liver Transplantation: A Single-Center Experience.

BACKGROUND: Cirrhosis for biliary atresia (BA) is associated with risk of gastrointestinal bleeding (GB) from gastroesophageal varices due to portal hypertension. Primary prophylaxis of GB is controversial in children who are candidates for liver transplantation (LT). The aim of the study was to define the management of gastroesophageal varices and to identify the benefit of primary prophylaxis for GB in BA children waiting for LT. METHODS: A retrospective single-center study including all BA children listed for LT in 2008-2016. Clinical, endoscopical, and biochemical data were analyzed. RESULTS: Of 82 children, 50 (61%) did not receive primary prophylaxis and did not present any episode of bleeding, 16 (19.5%) underwent primary prophylaxis, and 16 (19.5%) presented spontaneous GB and received secondary prophylaxis. Children without primary prophylaxis and GB were younger than patients with primary prophylaxis and those with GB (7.7 years [range, 4.1-37.9 years] vs 11.2 years [range, 5.1-43 years]; P = .03 vs 10.7 years [range, 6.9-39.9 years], respectively; P = .004). Seventy-five percent of GB occurred in children older than 8 months. Fifteen (93.8%) children with GB presented esophageal varices (grade III = 10 [62.5%]) and 10 (62.5%) required endoscopic treatments, consisting mainly of sclerotherapy. Median time to LT was similar for children with or without bleeding (2 months [range, 0-17.7 months] vs 2.2 months [0-17.9 months], respectively; P = .89). After 45.5 months (range, 13.7-105.5 months) of follow-up, the overall patient survival was 97.6%. At the intention-to-treat analysis, the survival rate was 100% for patients without bleeding episode and 87.5% for children with GB (P = .16). CONCLUSIONS: Despite the risk of GB being not clinically predictable in children with BA waiting for LT, our experience suggests that primary prophylaxis of GB might be unnecessary in children younger than 6 months, while it should be considered in older children. Thus, the occurrence of GB does not delay the timing of transplantation.

Colorectal cancer in patients with type 2 diabetes mellitus: a single-center experience.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of colorectal cancer (CRC). The aim of the study is to evaluate the prevalence of CRC in a cohort of Caucasian patients with T2DM and the association with other variables previously known to be related with increased risk of CRC. We retrospectively evaluated the data of 741 consecutive Caucasian patients with T2DM who underwent colonoscopic screening in our tertiary referral center. A control cohort of 333 patients with thyroid disease was selected to evaluate the difference in the incidence of CRC. At a median follow-up of 132.5 months (range 33.3-175.7), 67 cases of cancer (prevalence 9%) occurred; among these, 14 cases of CRC were reported (prevalence 1.88%) among the diabetic patients, while only two case (one of these was a CRC) (overall prevalence 0.006%, prevalence of CRC 0.003%) occurred in the control group; the difference between the prevalence of CRC was statistically significant (chi-square 4.21, p=0.04). The median duration of T2DM to CRC diagnosis was 168 months (range 12-768). At the univariate analysis, older age (p=0.001, r 0.138) and diabetes duration (p=0.001, r 0.138) were related to higher risk of cancer, while metformin seems to be protective towards cancer (p=0.07, r -0.098). In the subset of patients with CRC, the age (RR = 2.25; 95% CI: 0.30 - 17.31; p less than 0.001), the diabetes duration (RR = 1.93; 95% CI: 0.25 – 14.77; p = 0.001) and the sulphonylureas treatment (RR = 2.33; 95% CI: 0.78 – 7.38; p = 0.007) were independently correlated with CRC. In our study, the prevalence of CRC in the cohort of patients with T2DM was higher compared to that from the National Tumor Register in 2010 (0.5%). Furthermore, we could speculate that sulphonylureas may play a role in CRC carcinogenesis impairing the physiological insulin secretion.

Exploiting a new strategy to induce immunogenic cell death to improve dendritic cell-based vaccines for lymphoma immunotherapy.

Although promising, the clinical benefit provided by dendritic cell (DC)-based vaccines is still limited and the choice of the optimal antigen formulation is still an unresolved issue. We have developed a new DC-based vaccination protocol for aggressive and/or refractory lymphomas which combines the unique features of interferon-conditioned DC (IFN-DC) with highly immunogenic tumor cell lysates (TCL) obtained from lymphoma cells undergoing immunogenic cell death. We show that treatment of mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) cell lines with 9-cis-retinoic acid and IFNα (RA/IFNα) induces early membrane exposure of Calreticulin, HSP70 and 90 together with CD47 down-regulation and enhanced HMGB1 secretion. Consistently, RA/IFNα-treated apoptotic cells and -TCLs were more efficiently phagocytosed by DCs compared to controls. Notably, cytotoxic T cells (CTLs) generated with autologous DCs pulsed with RA/IFNα-TCLs more efficiently recognized and specifically lysed MCL or DLBCL cells or targets loaded with several HLA-A*0201 cyclin D1 or HLA-B*0801 survivin epitopes. These cultures also showed an expansion of Th1 and Th17 cells and an increased Th17/Treg ratio. Moreover, DCs loaded with RA/IFNα-TCLs showed enhanced functional maturation and activation. NOD/SCID mice reconstituted with human peripheral blood lymphocytes and vaccinated with autologous RA/IFNα-TCL loaded-IFN-DCs showed lymphoma-specific T-cell responses and a significant decrease in tumor growth with respect to mice treated with IFN-DC unpulsed or loaded with untreated TCLs. This study demonstrates the feasibility and efficacy of the use of RA/IFNα to generate a highly immunogenic TCL as a suitable tumor antigen formulation for the development of effective anticancer DC-based vaccines.

The importance of thinking styles in predicting binge eating.

Impulsivity, Body Mass Index, negative emotions and irrational food beliefs are often reported as predictors of binge eating. In the current study we explored the role played by two thinking styles, namely food thought suppression and desire thinking, in predicting binge eating among young adults controlling for established predictors of this condition. A total of 338 university students (268 females) participated in this study by completing a battery of questionnaires measuring the study variables. Path analysis revealed that impulsivity was not associated with binge eating, that Body Mass Index and negative emotions predicted binge eating, and that irrational food beliefs only influenced binge eating via food thought suppression and desire thinking. In conclusion, thinking styles appear an important predictor of binge eating and they should be taken into consideration when developing clinical interventions for binge eating.

LOPED study: looking for an early diagnosis in a late-onset Pompe disease high-risk population.

OBJECTIVE: A multicentre observational study was aimed to assess the prevalence of late-onset Pompe disease (LOPD) in a large high-risk population, using the dried blood spot (DBS) as a main screening tool. DESIGN/METHODS: 17 Italian neuromuscular centres were involved in the late-onset Pompe early diagnosis (LOPED) study. Inclusion criteria were: (1) age ≥5 years, (2) persistent hyperCKaemia and (3) muscle weakness at upper and/or lower limbs (limb-girdle muscle weakness, LGMW). Acid α-glucosidase (GAA) activity was measured separately on DBS by fluorometric as well as tandem mass spectrometry methods. A DBS retest was performed in patients resulted positive at first assay. For the final diagnosis, GAA deficiency was confirmed by a biochemical assay in skeletal muscle, whereas genotype was assessed by GAA molecular analysis. RESULTS: In a 14-month period, we studied 1051 cases: 30 positive samples (2.9%) were detected by first DBS screening, whereas, after retesting, 21 samples were still positive. Biochemical and molecular genetic studies finally confirmed LOPD diagnosis in 17 cases (1.6%). The median time from the onset of symptoms/signs to diagnosis was 5 years. Among those patients, 35% showed presymptomatic hyperCKaemia and 59% showed hyperCKaemia+LGMW, whereas 6% manifested with LGMW. CONCLUSIONS: LOPED study suggests that GAA activity should be accurately screened by DBS in all patients referring for isolated hyperCKaemia and/or LGMW. A timely diagnosis was performed in five patients with presymptomatic hyperCKaemia, but two had already manifested with relevant changes on muscle morphology and MRI. Consequently, enzyme replacement therapy was started in 14/17 patients, including the 2 patients still clinically presymptomatic but with a laboratory evidence of disease progression.

Intra-Operative Contrast Cholangiography in Living Donor Liver Transplantation: The ISMETT Experience.

BACKGROUND: We evaluated the clinical impact of donor biliary anatomy discrepancies (DBAD) achieved by comparing pre-operative evaluation obtained with magnetic resonance (MR)/magnetic resonance cholangiopancreatography (MRCP) imaging, with intra-operative cholangiography (IOC) on the living related liver donor (LDLT) and recipient. METHODS: This single-center, retrospective study included 97 consecutive adult-to-adult (A2A) LDLT performed in our hospital in the last 12 years. Donor sex and age, living donors with biliary and/or vascular anomalies, recipient age, sex, primary etiology, re-transplantation, Model of End-Stage Liver Disease score, co-morbidities, arterial and biliary recipient complications assessed on the basis of clinical follow-up were collected and analyzed for significance through the use of a multivariate linear regression model. RESULTS: Biliary complications in the donor (DBC) were detected in 8 (8.2%) cases. Biliary complications in the recipients (RBC) were detected in 38 (39%) cases. DBADs were found in 32 (33%) cases and resulted strictly related to RBC (P = .05). CONCLUSIONS: After adjusting for co-variables, results of the linear regression analysis confirmed that DBAD is an independent predictor of RBC, but it is not significantly associated with vascular complications or patient survival. We showed that RBCs after LDLT were influenced by DBAD.

A Multistep, Consensus-Based Approach to Organ Allocation in Liver Transplantation: Toward a "Blended Principle Model".

Since Italian liver allocation policy was last revised (in 2012), relevant critical issues and conceptual advances have emerged, calling for significant improvements. We report the results of a national consensus conference process, promoted by the Italian College of Liver Transplant Surgeons (for the Italian Society for Organ Transplantation) and the Italian Association for the Study of the Liver, to review the best indicators for orienting organ allocation policies based on principles of urgency, utility, and transplant benefit in the light of current scientific evidence. MELD exceptions and hepatocellular carcinoma were analyzed to construct a transplantation priority algorithm, given the inequity of a purely MELD-based system for governing organ allocation. Working groups of transplant surgeons and hepatologists prepared a list of statements for each topic, scoring their quality of evidence and strength of recommendation using the Centers for Disease Control grading system. A jury of Italian transplant surgeons, hepatologists, intensivists, infectious disease specialists, epidemiologists, representatives of patients' associations and organ-sharing organizations, transplant coordinators, and ethicists voted on and validated the proposed statements. After carefully reviewing the statements, a critical proposal for revising Italy's current liver allocation policy was prepared jointly by transplant surgeons and hepatologists.

Outcome of Transplantation Using Organs From Donors Infected or Colonized With Carbapenem-Resistant Gram-Negative Bacteria.

Donor-derived infections due to multidrug-resistant bacteria are a growing problem in solid organ transplantation, and optimal management options are not clear. In a 2-year period, 30/214 (14%) recipients received an organ from 18/170 (10.5%) deceased donors with infection or colonization caused by a carbapenem-resistant gram-negative bacteria that was unknown at the time of transplantation. Among them, 14/30 recipients (47%) received a transplant from a donor with bacteremia or with infection/colonization of the transplanted organ and were considered at high risk of donor-derived infection transmission. The remaining 16/30 (53%) recipients received an organ from a nonbacteremic donor with colonization of a nontransplanted organ and were considered at low risk of infection transmission. Proven transmission occurred in 4 of the 14 high-risk recipients because donor infection was either not recognized, underestimated, or not communicated. These recipients received late, short or inappropriate posttransplant antibiotic therapy. Transmission did not occur in high-risk recipients who received appropriate and prompt antibiotic therapy for at least 7 days. The safe use of organs from donors with multidrug-resistant bacteria requires intra- and inter-institutional communication to allow appropriate management and prompt treatment of recipients in order to avoid transmission of infection.

A nationwide survey of PMM2-CDG in Italy: high frequency of a mild neurological variant associated with the L32R mutation.

PMM2-CDG (PMM2 gene mutations) is the most common congenital disorder of N-glycosylation. We conducted a nationwide survey to characterize the frequency, clinical features, glycosylation and genetic correlates in Italian patients with PMM2-CDG. Clinical information was obtained through a questionnaire filled in by the referral physicians including demographics, neurological and systemic features, neuroimaging data and genotype. Glycosylation analyses of serum transferrin were complemented by MALDI-Mass Spectrometry (MALDI-MS). Between 1996 and 2012, data on 37 Italian patients with PMM2-CDG were collected. All the patients with a severe phenotype were unable to walk unaided, 84 % had severe intellectual disability and 81 % microcephaly. Conversely, among 17 mildly affected patients 82 % had independent ambulation, 64 % had borderline to mild intellectual disability and 35 % microcephaly. Epilepsy and stroke-like events did not occur among patients with the mild phenotype. The rate and extent of systemic involvement were more pronounced in severely affected patients. The L32R misfolding mutation of the PMM2 gene occurred in 70 % of the patients with the mild phenotype and was associated with a less severe underglycosylation of serum Tf at MALDI-MS analyses. Despite their different disease severity, all patients had progressive (olivo)ponto-cerebellar atrophy that was the hallmark clinical feature for the diagnosis. A mild neurological phenotype of PMM2-CDG marked by preserved ambulatory ability and autonomy and associated with L32R mutation is particularly frequent in Italy. PMM2-CDG should be considered in patients with even mild developmental disability and/or unexplained progressive cerebellar atrophy.

Evolution of surgical technique in conventional open hepatectomy for living liver donation over a 12-year period in a single center.

We report details of the experience from the largest Italian program with hepatic living donation, focusing particularly on the use of intraoperative ultrasound in liver transplantation and living donation. During a 12-year period we changed our surgical technique in the conventional open procedures thanks to the experience gained into the laparoscopic setting. Intraoperative ultrasound has been implemented during these delicate procedures for ensuring a fast and safer detection of the accessory veins and final severing of the vascular stumps during liver transection.

Liver transplantation in defects of cholesterol biosynthesis: the case of lathosterolosis.

We report the outcome of liver transplantation (LT) in the only surviving patient with lathosterolosis, a defect of cholesterol biosynthesis characterized by high lathosterol levels associated with progressive cholestasis, multiple congenital anomalies and mental retardation. From her diagnosis at age 2 she had shown autistic behavior, was unable to walk unaided and her sight was impaired by cataracts. By age 7 she developed end-stage liver disease. After a soul-searching discussion within the transplantation team, she was treated with LT as this represented her only lifesaving option. At 1-year follow-up, her lathosterol levels had returned to normal (0.61 mg/dL from 13.04 ± 2.65) and her nutrition improved. She began exploring her environment and walking by holding onto an adult's hand and then independently. Her brain magnetic resonance imaging (MRI) had shown a normal picture at age 1, whereas a volume reduction of white matter with ex vacuo ventricular dilatation and defective myelinization were observed before transplant. At 5-year follow-up, a complete biochemical recovery, an arrest of mental deterioration and a stable MRI picture were achieved, with a return to her every day life albeit with limitations. Timely liver transplant in defects of cholesterol biosynthesis might arrest the progression of neurological damage.

Hyperammonemic coma in a patient with late-onset OTC deficiency.

Urea Cycle Disorders ( UCD ) are among the most common genetic diseases of the metabolism and ornithine transcarbamylase deficiency (OTC), an X-linked defect is the most frequent among them. It is responsible for hyperammonemia that can lead to chronic neurological illness and potentially to death in case of delayed diagnosis and treatment. With regards to the OTC deficiency there is great clinical heterogeneity with early-onset phenotypes with mostly poor prognosis and late-onset phenotypes with a better one. In the article it is reported the case of a 8 years old patient with diagnosis of OTC deficit with late-onset phenotype. The kid was brought to our hospital because of continuous vomiting and gastro- intestinal disorders, associated with irritability and lethargy later resulted into coma. Measurement of plasma ammonia concentration, followed by measurement of plasma amino acid and urine orotic acid levels allowed to diagnose the OTC deficit, lately confirmed by molecular genetic studies. The patient has been promptly treated with Sodium Phenylbutyrate, Arginine and discontinuing the protein intake. Gradually the ammonemia value decreased, and general and neurological conditions improved with resolution of the coma. To conclude, for patients presenting unexplained neurological symptoms, confusion and decreased level of consciousness, up to coma, urea cycle disorders and in particularly OTC deficiency should be considered in the differential diagnosis and an urgent ammonia level determined. In case of hyperammonemia, the treatment should be started immediately , even without a precise ethiologic diagnosis.